Cogprints: No conditions. Results ordered -Date, Title. 2018-01-17T14:26:19ZEPrintshttp://cogprints.org/images/sitelogo.gifhttp://cogprints.org/2014-08-24T21:07:30Z2015-04-20T11:40:47Zhttp://cogprints.org/id/eprint/9756This item is in the repository with the URL: http://cogprints.org/id/eprint/97562014-08-24T21:07:30ZCo-Variations among Cognition, Cerebellar
Disorders and Cortical Areas With
Regional Glucose-Metabolic Activities in a
Homogeneous Sample with Uner Tan Syndrome:
Holistic Functioning of the Human BrainPatients with Uner Tan syndrome (UTS) exhibit habitual quadrupedal locomotion (QL), intellectual disability, dysarthric speech and truncal ataxia. Examination of cognitive ability in this syndrome has not yet been demonstrated in the scientific literature. Aims: (i) To analyze the cognitive abilities of the siblings with UTS; (ii) to assess the grade of their ataxia in relation to cerebellar disorders; (iii) to measure the metabolic activities of various cerebral regions in comparison with healthy individuals; (iv) to detect the interrelationships among all of the measured variables (IQ test scores, ataxia scores, cerebro-cerebellar areas and their metabolic activity levels) to reveal the holistic activity of the
brain. The Minimental State Examination (MMSE) and Wechsler Adult Intelligence Scale (WAIS-R) were applied to the affected cases and healthy subjects. Cerebellar disorders were assessed by the International Cooperative Ataxia Rating Scale (ICARS). Brain MRI scans were performed and cerebro-cerebellar areas were measured on MRI scans, including their metabolic activities (SUV), measured by positron emission tomography (PET) scanning. MMSE and WAIS-R scores both correlated with cerebro-cerebellar areas. Cerebello-vermial areas and their metabolic activities were significantly smaller in patients than in normal controls; areas of the remaining structures were not significantly different between patients and healthy subjects. Brain areas significantly inter-correlated: ICARS negatively correlated with WAIS-R,MMSE scores, SUV, and cerebro-cerebellar areas, which significantly correlated with each other. The results suggested (i) ICARS may not only be a test for cerebellar disorders, but also may be related to global functioning of all of the
cerebro-cerebellar regions; (ii) ICARS, WAIS-R and MMSE may be measures of emergent properties of the holistic
activity of the brain; (iii) the psychomotor disorders in UTS may be related to decreased brain metabolism.Prof. Dr. Uner Tanunertan37@yahoo.com2011-12-16T00:08:33Z2011-12-16T00:08:33Zhttp://cogprints.org/id/eprint/7748This item is in the repository with the URL: http://cogprints.org/id/eprint/77482011-12-16T00:08:33ZToward molecular neuroeconomics of obesity.Because obesity is a risk factor for many serious illnesses such as diabetes, better
understandings of obesity and eating disorders have been attracting attention in
neurobiology, psychiatry, and neuroeconomics. This paper presents future study
directions by unifying (i) economic theory of addiction and obesity (Becker and Murphy,
1988; Levy 2002; Dragone 2009), and (ii) recent empirical findings in neuroeconomics
and neurobiology of obesity and addiction. It is suggested that neurobiological
substrates such as adiponectin, dopamine (D2 receptors), endocannabinoids, ghrelin,
leptin, nesfatin-1, norepinephrine, orexin, oxytocin, serotonin, vasopressin, CCK,
GLP-1, MCH, PYY, and stress hormones (e.g., CRF) in the brain (e.g., OFC, VTA,
NAcc, and the hypothalamus) may determine parameters in the economic theory of
obesity. Also, the importance of introducing time-inconsistent and
gain/loss-asymmetrical temporal discounting (intertemporal choice) models based on
Tsallis’ statistics and incorporating time-perception parameters into the neuroeconomic
theory is emphasized. Future directions in the application of the theory to studies in
neuroeconomics and neuropsychiatry of obesity at the molecular level, which may help
medical/psychopharmacological treatments of obesity (e.g., with sibutramine), are
discussed.Taiki Takahashitaikitakahashi@gmail.com2010-09-13T03:59:01Z2011-03-11T08:57:40Zhttp://cogprints.org/id/eprint/6939This item is in the repository with the URL: http://cogprints.org/id/eprint/69392010-09-13T03:59:01ZUner Tan Syndrome: History, Clinical Evaluations, Genetics, and the
Dynamics of Human QuadrupedalismAbstract: This review includes for the first time a dynamical systems analysis of human quadrupedalism in Uner Tan syndrome, which is characterized by habitual quadrupedalism, impaired intelligence, and rudimentary speech. The first family was discovered in a small village near Iskenderun, and families were later found in Adana and two other small villages near Gaziantep and Canakkale. In all the affected individuals dynamic balance was impaired during upright walking,and they habitually preferred walking on all four extremities. MRI scans showed inferior cerebellovermian hypoplasia with slightly simplified cerebral gyri in three of the families, but appeared normal in the fourth. PET scans showed a decreased glucose metabolic activity in the cerebellum, vermis and, to a lesser extent the cerebral cortex, except for one patient,
whose MRI scan also appeared to be normal. All four families had consanguineous marriages in their pedigrees,
suggesting autosomal recessive transmission. The syndrome was genetically heterogeneous. Since the initial discoveries
more cases have been found, and these exhibit facultative quadrupedal locomotion, and in one case, late childhood onset. It has been suggested that the human quadrupedalism may, at least, be a phenotypic example of reverse evolution. From the viewpoint of dynamic systems theory, it was concluded there may not be a single factor that predetermines human quadrupedalism in Uner Tan syndrome, but that it may involve self-organization, brain plasticity, and rewiring, from the many decentralized and local interactions among neuronal, genetic, and environmental subsystems.Prof. Dr. Uner Tanunertan37@yahoo.com2010-09-13T03:56:39Z2011-03-11T08:57:40Zhttp://cogprints.org/id/eprint/6949This item is in the repository with the URL: http://cogprints.org/id/eprint/69492010-09-13T03:56:39ZAntipsychotics and Sexual Dysfunction :Sexual Dysfunction - Part III Satisfying sexual experience is an essential part of a healthy and enjoyable life for most people. Antipsychotic drugs are among the various factors that affect optimal sexual functioning. Both conventional and novel antipsychotics are associated with significant sexual side effects. This review has presented various studies comparing different antipsychotic drugs. Dopamine antagonism, increased serum prolactin, serotonergic, adrenergic and cholinergic mechanisms are all proposed to be the mechanisms for sexual dysfunction. Drug treatment for this has not given satisfactory long-term results. Knowledge of the receptor pharmacology of an individual antipsychotic will help to determine whether it is more or less likely to cause sexual side effects and its management.AKM Nagarajnagarajakm24@gmail.comNB PaiS Rao2010-04-01T11:36:18Z2011-03-11T08:57:36Zhttp://cogprints.org/id/eprint/6817This item is in the repository with the URL: http://cogprints.org/id/eprint/68172010-04-01T11:36:18ZThe complexity of theory of mindThere is no abstract for this paper.Livia ColleFrancesca M. BoscoMaurizio Tirassamaurizio.tirassa@unito.it2010-04-01T11:36:29Z2011-03-11T08:57:36Zhttp://cogprints.org/id/eprint/6816This item is in the repository with the URL: http://cogprints.org/id/eprint/68162010-04-01T11:36:29ZTh.o.m.a.s.: An exploratory assessment of Theory of Mind in schizophrenic subjectsA large body of literature agrees that persons with schizophrenia suffer from a Theory of Mind (ToM) deficit. However, most empirical studies have focused on third-person, egocentric ToM, underestimating other facets of this complex cognitive skill. Aim of this research is to examine the ToM of schizophrenic persons considering its various aspects (first vs. second order, first vs. third person, egocentric vs. allocentric, beliefs vs. desires vs. positive emotions vs. negative emotions and how each of these mental state types may be dealt with), to determine whether some components are more impaired than others. We developed a Theory of Mind Assessment Scale (Th.o.m.a.s.) and administered it to 22 persons with a DSM-IV diagnosis of schizophrenia and a matching control group. Th.o.m.a.s. is a semi-structured interview which allows a multi-component measurement of ToM. Both groups were also administered a few existing ToM tasks and the schizophrenic subjects were administered the Positive and Negative Symptoms Scale and the WAIS-R. The schizophrenic persons performed worse than control at all the ToM measurements; however, these deficits appeared to be differently distributed among different components of ToM. Our conclusion is that ToM deficits are not unitary in schizophrenia, which also testifies to the importance of a complete and articulated investigation of ToM.Francesca M. BoscoLivia ColleSilvia De FazioAdele BonoSaverio RubertiMaurizio Tirassa2008-08-24T10:57:20Z2011-03-11T08:57:10Zhttp://cogprints.org/id/eprint/6172This item is in the repository with the URL: http://cogprints.org/id/eprint/61722008-08-24T10:57:20ZNeuroethical Considerations Regarding Transcranial Magnetic StimulationAlong with advances in brain technologies comes the ability to enhance the cognitive and affective states of normal people. In this essay, I examine a relatively young technology used in cognitive neuroscience called transcranial magnetic stimulation (TMS). I explain what it is, how it works and what some of its applications are. I suggest that a potential source of reservation one might have regarding brain-altering enhancement is the threat it seemingly poses to the subjective importance of mental states. I then consider the possibility of its being used as an enhancement device and question the authenticity of abilities of individuals that are enhanced by use of TMS. I conclude that judgments regarding the appropriateness of such neurocognitive enhancements should be considered on a case by case basis.Chuck Stiegstie0076@umn.edu2009-02-13T01:14:04Z2011-03-11T08:57:18Zhttp://cogprints.org/id/eprint/6344This item is in the repository with the URL: http://cogprints.org/id/eprint/63442009-02-13T01:14:04ZTorture, Culture, War Zone Exposure and Posttraumatic Stress Disorder: Criterion A's Bracket CreepTHIS IS A COMMENTARY/LETTER TO THE EDITOR, THUS THERE IS NO ABSTRACTDr. H. Stefan Brachah.bracha@va.govDr. Kentaro Hayashi2007-12-10T21:45:54Z2011-03-11T08:57:01Zhttp://cogprints.org/id/eprint/5858This item is in the repository with the URL: http://cogprints.org/id/eprint/58582007-12-10T21:45:54ZUNERTAN SYNDROME: A CASE SERIES DEMONSTRATING HUMAN DEVOLUTIONA large family with six individuals exhibiting the Unertan syndrome (UTS)was identified residing in southern Turkey. All of the individuals had mental impairments and walked on all four extremities. The practice of intra-familial
marriages suggested that theUTS may be an autosomal recessive disorder, similar to previously described cases. The inferior portions of the cerebellum and vermis were
absent as evidenced by MRI and CT scans. The height and head circumference of those affected were within normal ranges. Barany’s test suggested normal vestibular
system function. The subjects could not name objects or their close relatives. The males (n = 4) could understand simple questions and commands, but answered questions with only one or two sounds. The females (n = 2) were superior to
the males with respect to language skills and walking, suggesting an association between walking and speaking abilities. One male exhibited three walking patterns
at the same time: quadripedal, tiptoe, and scissor walking. Another male used two walking styles: quadripedal and toe-walking. It is emphasized that there are important differences between the UTS and the disequilibrium syndrome. It is suggested that the inability to walk upright in those affected with the UTS may be
best explained by a disturbance in lateral-balance mechanisms,without being related to the cerebello-vestibular system.An interruption of locomotor development during the transition from quadripedality to bipedality may result in habitual walking on all four extremities and is normal in some children. Because quadripedal
gait is an ancestral trait, individuals with the UTS, exhibiting a manifestation of reverse evolution in humans, may be considered an experiment of nature, useful
in understanding the mechanisms underlying the transition from quadripedality to bipedality during human evolution. The proposed mutant gene or gene pool playing
a role in human quadrupedality may also be responsible for human bipedality at the same time. Herein there is no intent to insult or injure; rather, this report is an
endeavor to better understand human beings. Supplementary materials are available for this article. Go to the publisher’s online edition of International Journal of
Neuroscience for the following free supplemental resource(s): video clips.Prof. Dr. Uner Tanunertan37@yahoo.comDr. Sibel Karacasibelemre2003@yahoo.comDr. Meliha TanMeliha_Tan@yahoo.com2006-12-03Z2011-03-11T08:56:42Zhttp://cogprints.org/id/eprint/5267This item is in the repository with the URL: http://cogprints.org/id/eprint/52672006-12-03ZNeuropsychological Generation of Source Amnesia: An Episodic Memory Disorder of the Frontal BrainSource amnesia is an explicit memory (declarative) disorder, particularly episodic, where source or contextual information concerning facts is severely distorted and/or unable to be recalled. This paper reviews the literature on source amnesia, including memory distrust syndrome, and its accepted correlation with the medial diencephalic system and the temporal lobes, and the suggested linkage between the frontal lobes, including special interest with the prefrontal cortex. Posthypnotic induction was the first presentation of source amnesia identified in the literature. The Wisconsin Cart Sorting Test (WCST), Positron Emission Topography (PET), Phonemic Verbal Fluency Test, Stroop Color Word Interference Test, and explicit and implicit memory tests are defined and linked to empirical research on amnesiacs.Shaheen Emmanuel Lakhanslakhan2006-10-05Z2011-03-11T08:56:35Zhttp://cogprints.org/id/eprint/5125This item is in the repository with the URL: http://cogprints.org/id/eprint/51252006-10-05ZThe primary function of REM sleepIn this paper, the physiological features associated with the different stages of REM sleep and with what information processing researchers have called “effort” and “arousal” are compared. It is suggested that tonic REM sleep and effort involve an increase in the metabolism of cerebral glycogen, and phasic REM sleep and arousal involve the transfer of glucose from the body to the brain. Both stages of REM sleep seem to elevate cerebral glucose levels and likely result in increased ATP generation in some part(s) of the brain. It is noted that the functioning of the hippocampus depends heavily on ATP, and that this part of the brain becomes especially active during REM sleep. From this, although many details remain to be clarified, it seems clear that the primary function of REM sleep is to re-energize the brain.Mr. Andrew E. Bernhard2006-07-23Z2011-03-11T08:56:32Zhttp://cogprints.org/id/eprint/5011This item is in the repository with the URL: http://cogprints.org/id/eprint/50112006-07-23ZEVIDENCE FOR "UNERTAN SYNDROME" AND THE EVOLUTION OF THE HUMAN MINDA new family exhibiting “Unertan Sydnrome” was discovered. The pedigree analysis showed marriages between relatives. This family was similar to the first one (see Tan, 2006a), providing a firm evidence for the new syndrome. The affected children showed habitual quadrupedal walking gait, that is, they walked on wrists and feet with straight legs and arms. Their heads and bodies were mildly flexed; they exhibited mild cerebellar signs, and severe mental retardation. The pedigree demonstrated a typical autosomal-recessive inheritance. The genetic nature of
this syndrome suggests a backward stage in human evolution (devolution), which would be consistent with theories of punctuated evolution. The results reflected a
new theory on the evolution of human beings. That is, the evolution of humans would in fact be the evolution of the extensor motor system, responsible for upright posture, against the gravitational forces. This would be coupled with the emergence of the human mind, which can be considered a reflexion of the human motor system, in accord with the psychomotor theory (see Tan, 2005a). The
most important characteristic of the newly emerged human mind was the resistance against gravitational forces. This was the resistive mind, the origins of human creativity.Prof. Dr. Uner Tan2006-01-21Z2011-03-11T08:56:20Zhttp://cogprints.org/id/eprint/4710This item is in the repository with the URL: http://cogprints.org/id/eprint/47102006-01-21ZDelusional Belief induced by clomiphene treatmentWe report the case of a 35 year old women who developed a complex paranoid delusion during the course of clomiphene treatment für ovulation. The psychopathology was remarkable, because after a short hypomanic period the patient was without severe cognitive disturbance but struggled with a complex monothematic delusion. The delusion vanished in the course of a combination treatment with olanzapine a cognitive behavioral therapy. We could not entirely rule out the possibility of an endogenous psychiatric disease but nevertheless we encountered an unusual monothematic delusion which showed a strong temporal correlation with the intake of clomiphene. We provide some speculation about underlying neurobiological mechanisms on the basis of the dopamine theory of delusion.Dr. Oliver GrimmDr. Petra Hubrich2006-09-01Z2011-03-11T08:56:35Zhttp://cogprints.org/id/eprint/5095This item is in the repository with the URL: http://cogprints.org/id/eprint/50952006-09-01ZDelusional Belief induced by clomiphene treatmentWe report the case of a 35 year old women who developed a complex paranoid delusion during the course of clomiphene treatment für ovulation. The psychopathology was remarkable, because after a short hypomanic period the patient was without severe cognitive disturbance but struggled with a complex monothematic delusion. The delusion vanished in the course of a combination treatment with olanzapine a cognitive behavioral therapy. We could not entirely rule out the possibility of an endogenous psychiatric disease but nevertheless we encountered an unusual monothematic delusion which showed a strong temporal correlation with the intake of clomiphene. We provide some speculation about underlying neurobiological mechanisms on the basis of the dopamine theory of delusion.Dr. Oliver GrimmDr. Petra Hubrich2006-08-01Z2011-03-11T08:56:32Zhttp://cogprints.org/id/eprint/5028This item is in the repository with the URL: http://cogprints.org/id/eprint/50282006-08-01ZDietary-Free Glutamate: Implications for Research on Fear-Overconsolidation and PTSDn/aDr. Stefan BrachaDr. Edward Chronicle2006-08-01Z2011-03-11T08:56:33Zhttp://cogprints.org/id/eprint/5033This item is in the repository with the URL: http://cogprints.org/id/eprint/50332006-08-01ZCombat and Warfare in the Early Paleolithic and Medically Unexplained Musculo-Facial Pain in the 21st Century War Veterns and Active-Duty Military PersonnelIn a series of recent articles, we
suggest that family dentists, military
dentists and psychiatrists with expertise
in posttraumatic stress disorder (especially in the Veterans Health Administration) are likely to see an increased
number of patients with symptomatic
jaw-clenching and early stages of tooth-
grinding (Bracha et al., 2005). Returning
warfighters and other returnees from
military deployment may be especially
at risk for high rates of clenching-
induced masticatory muscle disorders
at early stages of incisor grinding. The
literature we have recently reviewed
strongly supports the conclusion that
clenching and grinding may primarily
be a manifestation of experiencing
extreme fear or severe chronic distress
(respectively). We have recently
reviewed the clinical and paleoanthropological literature and have noted that
ancestral warfare and ancestral combat,
in the early Paleolithic Environment of
Evolutionary Adaptedness (EEA) may
be a neglected factor explaining the
conservation of the archaic trait of
bite-muscle strengthening. We have
hypothesized that among ancestral
warriors, jaw clenching may have
rapidly strengthened the two primary
muscles involved in biting, the masseter
muscles and the much larger temporalis muscles. The strengthening of
these muscles may have served the
purpose of enabling a stronger, deeper,
and therefore more lethal, defensive
bite for early Paleolithic humans. The
neuroevolutionary perspective presented here may be novel to many dentists. However, it may be useful in
patient education and in preventing
progression from jaw-clenching to
chronic facial pain. Dr. Stefan BrachaDr., COL, MC Donald A. PersonDr. David M. BernsteinDr. Norman A. FlaxmanNicole K. Masukawa2006-09-25Z2011-03-11T08:56:34Zhttp://cogprints.org/id/eprint/5084This item is in the repository with the URL: http://cogprints.org/id/eprint/50842006-09-25ZCombat and Warfare in the Early Paleolithic and Medically Unexplained Musculo-Facial Pain in the 21st Century War Veterns and Active-Duty Military PersonnelIn a series of recent articles, we
suggest that family dentists, military
dentists and psychiatrists with expertise
in posttraumatic stress disorder (especially in the Veterans Health Administration) are likely to see an increased
number of patients with symptomatic
jaw-clenching and early stages of tooth-
grinding (Bracha et al., 2005). Returning
warfighters and other returnees from
military deployment may be especially
at risk for high rates of clenching-
induced masticatory muscle disorders
at early stages of incisor grinding. The
literature we have recently reviewed
strongly supports the conclusion that
clenching and grinding may primarily
be a manifestation of experiencing
extreme fear or severe chronic distress
(respectively). We have recently
reviewed the clinical and paleoanthropological literature and have noted that
ancestral warfare and ancestral combat,
in the early Paleolithic Environment of
Evolutionary Adaptedness (EEA) may
be a neglected factor explaining the
conservation of the archaic trait of
bite-muscle strengthening. We have
hypothesized that among ancestral
warriors, jaw clenching may have
rapidly strengthened the two primary
muscles involved in biting, the masseter
muscles and the much larger temporalis muscles. The strengthening of
these muscles may have served the
purpose of enabling a stronger, deeper,
and therefore more lethal, defensive
bite for early Paleolithic humans. The
neuroevolutionary perspective presented here may be novel to many dentists. However, it may be useful in
patient education and in preventing
progression from jaw-clenching to
chronic facial pain. Dr. Stefan BrachaDr., COL, MC Donald A. PersonDr. David M. BernsteinDr. Norman A. FlaxmanNicole K. Masukawa2005-11-12Z2011-03-11T08:56:12Zhttp://cogprints.org/id/eprint/4591This item is in the repository with the URL: http://cogprints.org/id/eprint/45912005-11-12ZDimensional approaches to experimental psychopathology of schizophrenia: shift learning and report of psychotic-like experiences in college students
Adopting a dimensional approach to experimental psychopathology, and taking into account inconsistencies in the previous literature, we examined whether reports of psychotic-like experiences in undergraduate students were associated with shift-learning deficits, akin to those seen in schizophrenia. The participants (N=72) were tested on a new compound stimulus discrimination task (CSDT) before and after a target shift, and were administered a multi-dimensional schizotypy inventory (O-LIFE). Performance impairment following a target shift was associated with the negative (Introvertive Anhedonia) and the impulsive (Impulsive Non-conformity) dimension of schizotypy, but not with the positive (Unusual Experiences), nor the disorganised (Cognitive Disorganisation) dimension. None of the schizotypy measures were associated with performance on discrimination learning before the target shift. The obtained results are in line with past evidence that shift learning is associated with the severity of the negative symptomatology of schizophrenia. The possibility that psychotic-like features may contribute differentially to performance deficits across successive stages of learning is considered. Elias TsakanikosPhil Reed2005-11-12Z2011-03-11T08:56:12Zhttp://cogprints.org/id/eprint/4590This item is in the repository with the URL: http://cogprints.org/id/eprint/45902005-11-12ZSeeing words that are not there: Detection biases in schizotypyObjective. The present studies introduced a novel word-detection paradigm to examine detection biases as a function of different schizotypy dimensions in a sample of undergraduate students.
Method. The participants (N = 80) were asked to detect fast moving (8 frames/sec) words among simultaneously moving non-words.
Results. Positive schizotypy was associated with a tendency to report words that never appeared in the trials. This effect was independent of task order, impulsivity and social desirability. None of the schizotypy measures was associated with correct words (detection accuracy).
Conclusions. It is inferred that a bias to report events in the absence of corresponding events may constitute a cross-modal mechanism responsible for translating internally generated experiences into perceptual experiences.
Tsakanikos EliasReed Phil2005-04-14Z2011-03-11T08:55:54Zhttp://cogprints.org/id/eprint/4187This item is in the repository with the URL: http://cogprints.org/id/eprint/41872005-04-14ZA case of ciprofloxacin-induced acute polymorphic psychosis with a distinct deficit of the executive functionsWe present the case of a 45-year-old female patient who developed an acute polymorphic psychosis after treatment with the antibiotic ciprofloxacin. The patient showed a distinct neuropsychological deficit of the executive
function. Comparing the psychopharmacological features of ketamine and ciprofloxacine we hypothesize that ciprofloxacine leads to psychosis similar to a ketamine induced psychosis. Our case report is unique not only because fluorquinolone induced psychosis has a very low incidence, but although because we were the first in obtaining a detailed neuropsychological testing.Dr. Oliver GrimmDr. Barbara Alm2005-06-19Z2011-03-11T08:56:04Zhttp://cogprints.org/id/eprint/4387This item is in the repository with the URL: http://cogprints.org/id/eprint/43872005-06-19ZCognitive Performance and Liver Function among Recently Abstinent Alcohol AbusersIt has frequently been suggested that some of the enduring subtle cognitive impairments seen in sober alcohol-dependent persons may be a result of sub-clinical liver dysfunction. Cognitive performance and liver function among 85 recently abstinent alcohol-dependent persons were assessed by means of a neuropsychological examination and the GGT test of liver function. Unlike some previous studies, no relationships were found between the two areas of functioning. It is argued that lack of statistical power did not account for the failure to find an association between the two domains. The proposition that residual cognitive impairment in abstinent alcoholic persons is (partly) mediated by earlier liver dysfunction rests on slight empirical foundations and remains speculative.Dr John F O'Mahony2005-12-19Z2011-03-11T08:56:14Zhttp://cogprints.org/id/eprint/4652This item is in the repository with the URL: http://cogprints.org/id/eprint/46522005-12-19ZEpilepsy – A Brief OverviewEpilepsy is a neurological condition in which an individual experiences chronic abnormal bursts of electrical discharge in the brain. These seizures can cause a variety symptoms depending on the areas of the brain affected. Symptoms can vary from mild to severe and can include complete or partial loss of consciousness, loss of speech, uncontrollable motor behavior, and/or unusual sensory experiences. From various studies worldwide6, approximately 0.5% of the population is reported to be affected by active epilepsy.Alain Koyama2006-09-25Z2011-03-11T08:56:36Zhttp://cogprints.org/id/eprint/5164This item is in the repository with the URL: http://cogprints.org/id/eprint/51642006-09-25ZEpilepsy – A Brief OverviewEpilepsy is a neurological condition in which an individual experiences chronic abnormal bursts of electrical discharge in the brain. These seizures can cause a variety symptoms depending on the areas of the brain affected. Symptoms can vary from mild to severe and can include complete or partial loss of consciousness, loss of speech, uncontrollable motor behavior, and/or unusual sensory experiences. From various studies worldwide6, approximately 0.5% of the population is reported to be affected by active epilepsy.Alain Koyama2006-11-16Z2011-03-11T08:56:42Zhttp://cogprints.org/id/eprint/5255This item is in the repository with the URL: http://cogprints.org/id/eprint/52552006-11-16ZEvolution of the human fear-circuitry and acute sociogenic pseudoneurological symptoms: The Neolithic balanced-polymorphism hypothesis
In light of the increasing threat of large-scale massacres such as terrorism against non-combatants (civilians), more attention is warranted not only to posttraumatic stress disorder (PTSD) but also to acute sociogenic pseudoneurological ("conversion") symptoms, especially epidemic sociogenic symptoms. We posit that conversion disorders are etiologically related to specific evolutionary pressures (inescapable threats to life) in the late stage of the human environment of evolutionary adaptedness (EEA). Bracha et al. have recently argued that from the neuroevolutionary perspective, medically unexplained efferent vasovagal syncope and medically unexplained craniofacial musculoskeletal pain in young otherwise healthy individuals, may be taxonomized as stress and fear-circuitry disorders. In the present article, we extend neuroevolutionary perspectives to acute pseudoneurological sociogenic ("conversive") symptoms: psychogenic non-epileptic attacks ("pseudoseizures"), epidemic sociogenic disorders (DSM-IV-TR Epidemic "Hysteria"), conversive motor deficits (pseudo-paralysis and pseudo-cerebellar symptoms), and psychogenic blindness. We hypothesize that these perplexing pseudoneurological stress-triggered symptoms, which constitute psychopathology in extant humans, are traceable to allele-variant polymorphisms which spread during the Neolithic EEA. During Neolithic warfare, conversive symptoms may have increased the survival odds for some non-combatants by visually (i.e., "non-verbally") signaling to predatory conspecifics that one does not present a danger. This is consistent with the age and sex pattern of conversive disorders. Testable and falsifiable predictions are presented; e.g., at the genome-transcriptome interface, one of the major oligogenic loci involved in conversive spectrum disorders may carry a developmentally sensitive allele in a stable polymorphism (balanced polymorphism) in which the gene expression mechanism is gradually suppressed by pleiotropic androgens especially dehydroxyepiandrosterone sulfate (DHEA-S). Taxonomic implications for the much-needed rapprochement between the forthcoming Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-V) and the International Classification of Diseases (ICD) are discussed.
Dr. H. Stefan Bracha1Dawn T. YoshiokaNicole K, MasukawaDeborah J.J. Stockman2005-12-19Z2011-03-11T08:56:14Zhttp://cogprints.org/id/eprint/4653This item is in the repository with the URL: http://cogprints.org/id/eprint/46532005-12-19ZA Review on the Cognitive Neuroscience of AutismWith increased recognition in the media, heightened prevalence, and advances in research technologies, investigation into the causes of autism has broadened in recent years. Studies at the molecular, structural, and behavioral levels have resulted in significant findings, linking autism to qualitative differences in neurological function and an alteration of early development. Familial aggregation of autism demonstrate a strong genetic factor, although genetics can not completely account for its pathogenesis. Studies show autism having one of the most complex pathologies among neurodevelopmental disorders. Future studies applying sophisticated methodologies in new areas may shed light on current mysteries surrounding the disorder.Alain Koyama2006-10-05Z2011-03-11T08:56:38Zhttp://cogprints.org/id/eprint/5208This item is in the repository with the URL: http://cogprints.org/id/eprint/52082006-10-05ZA Review on the Cognitive Neuroscience of AutismWith increased recognition in the media, heightened prevalence, and advances in research technologies, investigation into the causes of autism has broadened in recent years. Studies at the molecular, structural, and behavioral levels have resulted in significant findings, linking autism to qualitative differences in neurological function and an alteration of early development. Familial aggregation of autism demonstrate a strong genetic factor, although genetics can not completely account for its pathogenesis. Studies show autism having one of the most complex pathologies among neurodevelopmental disorders. Future studies applying sophisticated methodologies in new areas may shed light on current mysteries surrounding the disorder.Alain Koyama2004-10-06Z2011-03-11T08:55:41Zhttp://cogprints.org/id/eprint/3817This item is in the repository with the URL: http://cogprints.org/id/eprint/38172004-10-06ZLess words, more words: psychometric schizotypy and verbal fluency
Positive and negative symptoms of schizophrenia have been differentially associated with irregularities in verbal production, suggesting the involvement of different underlying mechanisms in psychotic symptomatology. In view of that, the present investigation examined whether the amount of verbal production would be also differentially associated with negative and positive symptoms of psychometric schizotypy in a sample of college students (N=190). The participants were tested on a typical verbal fluency test and completed the O-LIFE schizotypy scales. The analyses revealed that decreased verbal fluency was associated with increased levels of negative schizotypy in participants who scored one standard deviation above the mean on the ‘Introvertive Anhedonia’ scale. In contrast, increased verbal fluency was associated with increased levels of positive schizotypy in participants who scored one standard deviation above the mean on the ‘Unusual Experiences’ scale. The obtained results are discussed in terms of the proposal that psychotic-like unusual experiences, like hallucinations, may be the product of a higher automatic spreading activation among stored lexical units, a mechanism which seems to account for the previously reported link between positive schizotypy and creativity. Dr Elias TsakanikosProfessor Gordon Claridge2012-11-09T19:34:57Z2012-11-09T19:34:57Zhttp://cogprints.org/id/eprint/8082This item is in the repository with the URL: http://cogprints.org/id/eprint/80822012-11-09T19:34:57ZDopaminergic Regulation of Neuronal Circuits in Prefrontal CortexNeuromodulators, like dopamine, have considerable influence on the
processing capabilities of neural networks.
This has for instance been shown in the working memory functions
of prefrontal cortex, which may be regulated by altering the
dopamine level. Experimental work provides evidence on the biochemical
and electrophysiological actions of dopamine receptors, but there are few
theories concerning their significance for computational properties
(ServanPrintzCohen90,Hasselmo94).
We point to experimental data on neuromodulatory regulation of
temporal properties of excitatory neurons and depolarization of inhibitory
neurons, and suggest computational models employing these effects.
Changes in membrane potential may be modelled by the firing threshold,
and temporal properties by a parameterization of neuronal responsiveness
according to the preceding spike interval.
We apply these concepts to two examples using spiking neural networks.
In the first case, there is a change in the input synchronization of
neuronal groups, which leads to
changes in the formation of synchronized neuronal ensembles.
In the second case, the threshold
of interneurons influences lateral inhibition, and the switch from a
winner-take-all network to a parallel feedforward mode of processing.
Both concepts are interesting for the modeling of cognitive functions and may
have explanatory power for behavioral changes associated with dopamine
regulation.Gabriele Schelergscheler@gmail.com2002-01-29Z2011-03-11T08:54:53Zhttp://cogprints.org/id/eprint/2051This item is in the repository with the URL: http://cogprints.org/id/eprint/20512002-01-29ZConditioned blocking and schizophrenia: a replication and study of the role of symptoms, age, onset-age of psychosis and illness-durationIntroduction:
Measures of selective attention processing like latent inhibition (LI) and conditioned blocking (CB) are disturbed in some patients with schizophrenia. (LI is the delay in learning about the associations of a stimulus that has been associated with no event [vs. de novo learning]; CB is the delay in learning the associations of a stimulus-component when the other component has already started to acquire these associations.) We proposed, -
a) to replicate the reported decreases of CB in patients without paranoid-hallucinatory symptoms,
b) to see if CB depends on the age of illness-onset and its duration, as reported for LI.
Methods:
We studied 101 young and old, acute and chronically ill patients with schizophrenia, of whom 62 learned a modified 'mouse-in-house' CB task, and compared them with 62 healthy controls matched for age, education and socio-economic background.
Results:
1/ CB was more evident in patients with a diagnosis of paranoid schizophrenia than other subtypes.
2/ An unusual persistence of high CB scores through testing was associated with productive symptoms (including positive thought disorder).
3/ Reduced CB related to the increased expression of a) Schneider's first rank symptoms of ideas-of-reference and b) to negative symptoms like poor rapport and poor attention.
4/ CB was less evident in the older patients (age range 9.5-63.3y) and those with an earlier illness-onset (range 8.5-45.8y).
Conclusions:
In contrast to the similar LI test of selective attention CB is found in patients with paranoid schizophrenia and, unlike LI, the expression of CB by patients with schizophrenia is not related closely to illness-duration.
Reduced CB tended to be found in those with an earlier onset, a group often noted for more severe cognitive problems. These results imply that CB and LI reflect the activity of different underlying processes.
We suggest that reduced CB on the first few test-trials in nonparanoid schizophrenia reflects the unusual persistence of controlled information processing strategies that would normally become automatic during conditioning. In contrast continued CB during testing in patients with positive (paranoid) symptoms reflects an unusual persistence of automatic processing strategies.
Bender Müller Oades Sartory2002-01-11Z2011-03-11T08:54:52Zhttp://cogprints.org/id/eprint/2018This item is in the repository with the URL: http://cogprints.org/id/eprint/20182002-01-11ZDehydroepiandrosterone sulphate and corticotropin levels are high in young male patients with conduct disorder: comparisons with growth factors, thyroid and gonadal hormonesIntroduction: The biological concomitants of childhood conduct disorder (CD) have seldom been considered separate from those of hyperkinesis with which CD is often comorbid. CD predicts an increased likelihood of developing a personality disorder and is often associated with an antisocial outcome. Childhood CD may originate in a stressful upbringing in a dysfunctional family environment, and has been reported to be associated with unusual physical or sexual development and thyroid dysfunction.
Methods: We therefore explored circulating levels of hormones from adrenal, gonadal and growth-hormone axes associated with stress, aggression and development in 28 CD patients and 13 age-matched healthy children (10-18 years old).
Results:
1/ The CD group had higher levels of dehydroepiandrosterone sulphate (DHEA-S) and corticotropin (ACTH) and for those under 14 years of age there was more free triiodothyronine (fT3) in the circulation.
2/ There were no differences for gonadal hormones, and neither the levels of steroid hormones nor the ratings of maturity (early/late) were associated with aggression, as has been reported elsewhere. 3/ Smaller physical measures in CD children correlated with DHEA-S and growth factors (e.g. IGF-I): 4/ increased ACTH and fT3 correlated with restless-impulsive ratings, and DHEA-S with 'disruptive behaviour'.
Conclusions: Imbalances in the adrenal and growth axes may indeed have neurotrophic repercussions in growth and development.
Dmitrieva Oades Hauffa Eggers2002-11-19Z2011-03-11T08:55:06Zhttp://cogprints.org/id/eprint/2613This item is in the repository with the URL: http://cogprints.org/id/eprint/26132002-11-19ZImitation, mirror neurons and autismVarious deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and ‘theory of mind’ abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.Justin H.G. WilliamsAndrew WhitenThomas SuddendorfDavid I. Perrett2002-01-11Z2011-03-11T08:54:52Zhttp://cogprints.org/id/eprint/2015This item is in the repository with the URL: http://cogprints.org/id/eprint/20152002-01-11ZNeuropsychological indicators of heteromodal cortex (dys)function relevant to conditioned blocking measures of attention in schizophreniaBackground.
Learning a predictive relationship between two events can block learning about an added event (conditioned blocking, CB). Patients with nonparanoid schizophrenia can show reduced CB and learn about the similar consequences of the added event. What parts of the brain are involved in the functions required in learning the CB task and actually showing 'blocking' - a part of normal selective attention processes? As a first approximation, we ask if neuropsychological test performance sensitive to specific cortical regions is associated with these two functions.
Methods.
This study reports on the relationship of associative learning and CB measures of attention obtained with a visuospatial maze-like task to signs of heteromodal cortex function provided by performance on a battery of 10 neuropsychological tasks. These tasks were sensitive to frontal, parietal and temporal lobe function of the left and right hemisphere. Acquisition criteria for the task were achieved by 62 patients with schizophrenia and 62 matched controls but not by 39 other people with schizophrenia.
Results.
First right-hemisphere, visuo-spatial abilities were generally associated with faster task-learning (e.g. visual reproduction, immediate and delayed, picture-completion), and patients that could not learn the task were poorer on tests emphasising set-switching and problem-solving abilities associated with left frontal lobe function (e.g. trail-making, block-design).
Second CB expression depended on Stroop- and Mooney-faces-task performance that are reported to require cingulate and parietal lobe function.
Conclusions.
As would be predicted right hemisphere function was implicated in performing a visuospatial learning task. The additional CB requirement incurred additional anterior cingulate and right parietal involvement. Functionally this probably reflected effortful attentional processes, and illustrates the problems of patients with schizophrenia in switching between automatic and controlled processing strategies. The results are astonishingly consistent with imaging studies implicating brain regions such as the cingulate and intra-parietal sulcus in attention (Mesulam, 1999).
R.D. Oades Bender Müller Sartory2002-01-29Z2011-03-11T08:54:53Zhttp://cogprints.org/id/eprint/2050This item is in the repository with the URL: http://cogprints.org/id/eprint/20502002-01-29ZNovelty-elicited mismatch negativity in patients with schizophrenia on admission and dischargeIntroduction:
MMN, an electrophysiological measure of auditory working memory, is usually recorded as the difference in the event-related potential (ERP) elicited by a rare deviant and a common standard sound. The amplitude is usually reduced in patients with schizophrenia (refs below). Here we looked at the response in the extreme and most simple case of the deviant being always a novel, different tone on every presentation. We compared the novelty-MMN with clinical symptoms expressed - both measures being made soon after admission and again 2-3 months later just before discharge.
Methods:
We compared 20 patients (mean age 26y) with a first, second or third episode of schizophrenia on admission with 21 healthy controls (mean age 26y) and were able to repeat the measures with 12 patients at discharge and with 15 controls. An early MMN component (80-140 ms), a later component (140-300 ms) and the P3a were recorded and topography examined after min-max norming from 19 sites. Symptoms were assessed with the positive and negative syndrome scale (PANSS).
Results:
a) Novelty-elicited MMN was not significantly reduced on admission.
b) The early component remained unaltered, but the amplitude of the later component decreased significantly during inpatient treatment. While the decrease appeared significant over the left hemisphere in the raw data, the lateral difference was lost after normalizing the data.
c) Improved positive symptom ratings were associated with increases of the early component latency, but decreases of the late component latency.
d) P3a at Fz showed an increased latency between sessions in the patients but there were no group differences in amplitude.
Conclusions:
Our results are partially consistent with two other studies using a conventional MMN that showed a lack of MMN normalization where symptoms improved (Schall et al., 1998; Umbricht et al., 1998) - in the present study MMN deteriorated. While trait features have been attributed to conventional MMN reductions in schizophrenia, our results suggest that if novelty responses are impaired in patients with schizophrenia then the differences may be sensitive to state.
Grzella Müller Oades Bender Schall Zerbin Wolstein Sartory2000-12-19Z2011-03-11T08:54:27Zhttp://cogprints.org/id/eprint/1129This item is in the repository with the URL: http://cogprints.org/id/eprint/11292000-12-19ZWHAT CATATONIA CAN TELL US ABOUT "TOP-DOWN MODULATION": A NEUROPSYCHIATRIC HYPOTHESISDifferentialdiagnosis of motor symptoms, as for example akinesia, may be difficult since they may be either of neurologic, as for example Parkinsons, or psychiatric, as for example catatonia, origin leading to a so-called conflict of paradigms. Despite different origins such symptoms may clinically be more or less similar which may reflect functional brain organisation in general and cortical-subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinsons as a motor disorder and catatonia as a psychomotor disorder may be accounted for by functional differences between top-down modulation and bottom-up modulation between prefrontal/frontal cortex and basal ganglia implying double dissociation between both diseases with regard to underlying pathophysiology.
Catatonia can be characterized by concomittant motor, emotional, and behavioral symptoms which may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity as a form of horizontal i.e. cortico-cortical modulation. Furthermore alteration in top-down modulation of caudate and other basal ganglia by gaba-ergic mediated orbitofrontal cortical deficits may account for motor symptoms in catatonia. Parkinsons in contrast can be characterized by predominant motor symptoms which may be accounted for by altered bottom-up modulation between dopaminergic mediated deficits in striatum and premotor/motor cortex. Due to connectional asymmetry i.e. unidirectionality in prefronto-premotor/motor cortical connections, there is no further dysregulation in other prefrontal cortical areas in Parkinsons as it is reflected in absence of major psychiatric symptoms in such patients.
It is concluded that comparison between Parkinsons and catatonia may reveal the nature of both top-down modulation and bottom-up modulation in further detail. Furthermore difference between Parkinsons as a motor and catatonia as a psychomotor disorder may be accounted for by pecularities in horizontal i.e. cortico-cortical modulation which, unlike top-down and bottom-up modulation as forms of vertical modulation, may be unidirectional and thus asymmetric not allowing for direct modulation of prefrontal cortical areas by premotor/motor cortex.
Key-words: Catatonia - Parkinsons - Top-down modulation - Bottom-up modulation - Horizontal modulation
Differentialdiagnosis of motor symptoms, as for example akinesia, may be difficult since they may be either of neurologic, as for example Parkinsons, or psychiatric, as for example catatonia, origin leading to a so-called conflict of paradigms. Despite different origins such symptoms may clinically be more or less similar which may reflect functional brain organisation in general and cortical-subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinsons as a motor disorder and catatonia as a psychomotor disorder may be accounted for by functional differences between top-down modulation and bottom-up modulation between prefrontal/frontal cortex and basal ganglia implying double dissociation between both diseases with regard to underlying pathophysiology.
It is concluded that comparison between Parkinsons and catatonia may reveal the nature of both top-down modulation and bottom-up modulation in further detail. Furthermore difference between Parkinsons as a motor and catatonia as a psychomotor disorder may be accounted for by pecularities in horizontal i.e. cortico-cortical modulation which, unlike top-down and bottom-up modulation as forms of vertical modulation, may be unidirectional and thus asymmetric not allowing for direct modulation of prefrontal cortical areas by premotor/motor cortex.
Georg Northoff2000-06-14Z2011-03-11T08:53:42Zhttp://cogprints.org/id/eprint/149This item is in the repository with the URL: http://cogprints.org/id/eprint/1492000-06-14ZTHE MIND AND BRAIN SCHOLAR AS A HITCH-HIKER IN POST-GUTENBERG GALAXY: PUBLISHING AT 2000 AND BEYONDElectronic journal (e-journal) publishing has started to change the ways we think about publish-ing. However, many scholars and scientists in the mind and brain sciences are still ignorant of the new possibilities and on-going debates. This paper will provide a summary of the issues in-volved, give an update of the current discussion, and supply practical information on issues re-lated to e- journal publishing and self-archiving relevant for the mind and brain sciences. Issues such as differences between traditional and e-journal publishing, open archive initiatives, world-wide conventions, quality control, costs involved in e-journal publishing, and copyright questions will be addressed. Practical hints on how to self-archive, how to submit to the e-journal Psycolo-quy, how to create an open research archive, and where to find information relevant to e-publishing will be supplied.Brigitte StemmerMarianne CorreYves Joanette2000-05-13Z2011-03-11T08:53:42Zhttp://cogprints.org/id/eprint/147This item is in the repository with the URL: http://cogprints.org/id/eprint/1472000-05-13ZThe study of the regenesis of mind in the 21st centuryThe enigma of consciousness and the brain-mind relationship will - most likely - be unveiled in the 21st century through the new technologies developed at the end of the 20th century and new technologies yet to come. The new technologies will be used to tackle the problem from evolu-tionary, developmental, normal and pathological brain functioning. A major contribution, how-ever, will surface when investigating a particular perspective of pathological brain functioning - a perspective that has not received any attention in the past: the investigation of the re-emergence of mind out of prolonged coma and coma like states.Paul Walter SchönleBrigitte Stemmer2001-10-27Z2011-03-11T08:54:48Zhttp://cogprints.org/id/eprint/1841This item is in the repository with the URL: http://cogprints.org/id/eprint/18412001-10-27ZDifferential measures of 'sustained attention' in children with attention-deficit/hyperactivity or tic disorders: relations to monoamine metabolismIntroduction: Controversy exists on whether the constructs related to sustained attention and tested by paper/pencil tasks and computerized continuous-performance-tests (CPT) are similar, and whether the deficits recorded in children with attention-deficit/hyperactivity symptoms (ADHD) using these different forms of testing information processing are comparable.
Methods: Signal-detection measures (d-prime and beta-criterion) and type of error were recorded on four such tests of 'sustained attention', with increasing working-memory requirements (respond to 'x', respond to 'x' only after 'a') in healthy children (n = 14, mean 10 years of age), and those with ADHD (n = 14, mean 10 years of age) or a tic syndrome (TS, n = 11, mean 11 years of age). Clinical associations were sought from 24h-urinary measures of monoamine activity (parent amines and metabolites), - dopamine (DA), HVA, noradrenaline (NA), MHPG, serotonin (5-HT), 5-HIAA.
Results:
The cancellation paper/pencil test revealed no group differences for errors or signal detection measures. In contrast, on the CPTx ADHD children made more omission and commission errors than controls, but TS children made mostly omissions. This reflected the poor perceptual sensitivity (d-prime, d') for ADHD and conservative response criteria (beta) for TS children.
This group difference extended to the CPT ax which was shown on a regression analysis to test for putative working-memory-related abilities as well as concentration. In all children immediate response-feedback (vs. feedback at the end of the test) reduced omissions, and modestly improved d'. CPT ax performance related negatively to dopamine metabolism in controls and to serotonin metabolism in the ADHD group. But comparisons between the metabolites in the ADHD group suggest that increased serotonin- and decreased noradrenaline- with respect to dopamine-metabolism may detract from CPT performance in terms of d-prime.
Conclusions: CPT tasks demonstrated a perceptual-based impairment in ADHD and response conservatism in TS patients independent of difficulty. Catecholamine activity was implicated in the promotion of perceptual processing in normal and ADHD children, but serotonin activity may contribute to poor CPTax performance (emphasis on working-memory function) in ADHD patients.
Robert D. Oades2001-10-27Z2011-03-11T08:54:48Zhttp://cogprints.org/id/eprint/1843This item is in the repository with the URL: http://cogprints.org/id/eprint/18432001-10-27ZNeuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancyIntroduction:
Patients with schizophrenia are widely reported to show impairments of attention and neuropsychological performance, but the extent to which this is attributable to medication and dopamine (DA) function remains largely unexplored.
Methods:
We describe here the putative influence of 1) the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), 2) the antipsychotic serum concentration (neuroleptic units in terms of butyrophenone displacement from animal neostriatum) and 3) the approximated DA D2-receptor occupancy in the brain (based on regression curves from 11 studies published for 5 neuroleptics) - - on conditioned blocking (CB) measures of attention and performance on a neuropsycholog-ical battery. We studied 108 patients with schizophrenia with 62 healthy controls.
Results:
1) Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid vs. non-paranoid diagnosis, and in female vs. male patients (independent of symptom severity).
2) Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB measures of selective attention in nonparanoid patients.
3) Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance on the trail-making and picture completion tests (negative) and the block-design test (positive) showed the functional importance of DA-related activity.
4) High estimates of D2-occupancy were related to impaired verbal fluency - but - were associated with improved recall of stories, especially in paranoid patients.
5) Non-dopaminergic aspects of medication (i.e. CPZ-dependent but not D2-occupancy-associated) impaired verbal recall in males (left-hemisphere function) and non-verbal performance in females (reflecting right hemisphere function).
Conclusions:
This first study of its kind tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB and verbal fluency) and temporal lobe functions (verbal recall), as well as in some non-verbal abilities mediated more in the right hemisphere of patients with schizophrenia
R.D. OadesM.L. RaoS. BenderG. SartoryB.W. Müller2000-02-28Z2011-03-11T08:53:41Zhttp://cogprints.org/id/eprint/141This item is in the repository with the URL: http://cogprints.org/id/eprint/1412000-02-28ZRegional differentiation of neuron morphology in human left and right hippocampus: Comparing normal to schizophreniaRegional differentiation based on size, form, and orientation angle of the soma of individual neurons in human post-mortem hippocampus was determined through correlations between pairs of hippocampal subfields in each side separately. The neurons were previously measured on a computer. In the normal cases, a left-right asymmetrical pattern of regional differentiation based on soma size emerged, while for form and orientation angle, the patterns appeared symmetrical. In schizophrenia, regional soma size, form, and orientation variability were expressed largely symmetrically. Regional correlations based on neuronal density revealed an asymmetrical hemispheric pattern in the normal cases versus a nearly symmetrical pattern in schizophrenia. Taken together, the inter-regional correlations favor a hippocampal landscape that deviates in each side from connectivity based on the canonical trisynaptic hippocampal circuitry. It is proposed that during morphogenesis, rudimentary inter-regional networks are formed through specific interactions between regional neurons; these networks are present in the adult hippocampus and may be vulnerable in brain diseases.D. W. Zaidel1999-07-14Z2011-03-11T08:53:40Zhttp://cogprints.org/id/eprint/106This item is in the repository with the URL: http://cogprints.org/id/eprint/1061999-07-14ZThe Future of Research on Electroreception and Electrocommunication.Besides the rounding out of presently active areas, six are selected for predictions of marked advance. (1) Most discoveries will be in cellular componentry and molecular mechanisms for one or another class of receptors or central pathways. (2) More major taxa will be found with electroreceptive species, possibly birds, reptiles or invertebrates, representing independent evolutionary "inventions". (3) Electric organs with weak and episodic electric discharges will be found in new taxa; first, among siluriforms. (4) New examples are expected, like lampreys, where synchronized muscle action potentials add up to voltages in the range of weakly electric fish. Some of these will look like intermediates in the evolution of electric organs. (5) Ethological significance will be found for a variety of known physiological features. Exs.: uranoscopids, skates and weakly electric catfish with episodic electric discharges of unknown role; electroreceptive ability of some of the diverse group having Lorenzinian-type ampullae (besides elasmobranchs) including lampreys, chimaeras, lungfish, sturgeons, paddlefish, and salamanders; gymnotiform and mormyrid detection of capacitive component of impedance. (6) The organization of some higher functions in the cerebellum and forebrain will gradually come to light.Theodore H. Bullock1999-12-15Z2011-03-11T08:53:41Zhttp://cogprints.org/id/eprint/125This item is in the repository with the URL: http://cogprints.org/id/eprint/1251999-12-15ZIntroductionThe introduction to the special issue briefly discusses the origins and development of the word "pragmatics", pragmatic theory and its application to neurolinguistics. The special issue covers a total of 11 articles investigating pragmatic and neuropragmatic issues from different theoretical, experimental and clinical perspectives.Brigitte Stemmer2001-03-30Z2011-03-11T08:54:36Zhttp://cogprints.org/id/eprint/1420This item is in the repository with the URL: http://cogprints.org/id/eprint/14202001-03-30ZFrontal, temporal and lateralized brain function in children with attention-defiocit hyperactivity disorder: a psychophysiological and neuropsychological viewpoint on developmentIntroduction: This review considers deficits in the selective aspects of perception (i.e. attention) underlying symptoms of impaired attention and impulsivity in children with attention-deficit hyperactivity syndrome (ADHD) in terms of frontal and temporal lobe function and cerebral asymmetry.
Review: Tomographic studies suggest a disturbance of fronto-striatal function, but have neglected limbic contributions under activating conditions and are contradictory or equivocal on the nature of apparent lateralised differences of structure.
Functional neuropsychological (e.g. go/no-go and covert orienting of attention tasks) and psychophysiological studies (e.g. event-related potentials and mismatch negativity [1]) suggest that early and late stages of information processing are affected in both the frontal and temporal lobes.
Performance differences in young ADHD patients imply an impairment in the inter-cortical dialogue. Given the evidence for a normal specialisation in global processing in the right and the processing of details in the left hemisphere, the lateralised impairment may progress from situational ADHD (resulting in impaired selective aspects of perception on the right) to pervasive ADHD (inducing an additional impairment in decision making on the left: compare risk taking).
Conclusions: Accordingly a proportion of ADHD children may experience an early negative neurodevelopmental influence that only appears as the brain region matures (especially around 8-12 years of age) while others show an independent, longer term, delayed development of CNS function.
R.D. Oades2001-03-30Z2011-03-11T08:54:36Zhttp://cogprints.org/id/eprint/1418This item is in the repository with the URL: http://cogprints.org/id/eprint/14182001-03-30ZPlasma neuropeptide-Y levels, monoamine metabolism, electrolyte excretion and drinking behavior in children with attention-deficit hyperactivity disorderIntroduction: This study was conducted against a background of the following four points: a) increased drinking behavior in children with attention-deficit hyperactivity disorder (ADHD), b) the parallel between some behaviours associated with ADHD and with hypertension, c) the use of the spontaneously hypertensive rat as a model for ADHD, and d) similarities in the changes of neuropeptide-Y (NPY) and catecholamine in the studies of hypertension and drinking,
Methods: Measures of NPY, catecholamines and electrolyte balance were compared in the plasma and urine of healthy children and those with ADHD. Drinking was monitored during three hours of neuropsychological tests over two days in 14 ADHD (mean 9.8 years-of-age) and 9 healthy children (10.6 years-of-age).
Results:
Patients drank 4 times more water and showed twice the levels of NPY in controls. In controls there were positive and in patients there were negative relationships for NPY with drinking and restless behavior.
Patients' plasma levels of norepinephrine (NE) and epinephrine were slightly elevated, but urinary levels of NE and the serotonin metabolite were markedly increased. Urinary excretion rates for sodium (not potassium), phosphate and, especially calcium were decreased in patients. NPY levels were inversely related to calcium excretion and drinking inversely to sodium circulating (but positively with potassium and phosphate excretion).
Conclusions: Increases of drinking and increased levels of circulating NPY in ADHD children and decreased electrolyte excretion may reflect a common disturbance in the homeostatic control of metabolism.This may contribute to the impairments of attentional and behavioural control typical of ADHD children.
R.D. OadesR. DanielsW. Rascher2000-12-04Z2011-03-11T08:54:27Zhttp://cogprints.org/id/eprint/1120This item is in the repository with the URL: http://cogprints.org/id/eprint/11202000-12-04ZThe development of conditioned blocking and monoamine metabolism in children with attention-deficit-hyperactivity disorder or complex tics and healthy controls: an exploratory analysisIntroduction:
Conditioned blocking (CB) measures the transient suppression of learning that a new stimulus, added during learning, has the same consequences as the conditioned stimulus already present. Normal CB increases from puberty across adolescence, between the age of 8 and 20 years (Oades et al., 1996). Is there a delay in the development of selective attention abilities in children with a primary diagnosis of attention-deficit/hyperactivity disorder (ADHD) and does this differ from children with Tourette syndrome who also express some symptoms of attention deficit?
Methods:
CB development was compared between 13 healthy children (CN: mean age 11.0 years), 13 with attention-deficit/hyperactivity disorder (ADHD: mean 10.5y) and 11 with complex tic or Tourette syndrome who also showed some attention-deficit symptoms (TS: mean 11.8y). The ADHD group were medication naive, but 3 TS were receiving tiapride, and two pimozide. The 'mouse-in-house' task form was used.
Results:
1. All children required fewer trials to learn the task with increasing age: (the ADHD group was slightly slower).
2. However, only healthy controls improved CB with increasing age (figure 1, left).
3. TS patients under 11y tended to show impaired CB, and over 11y they were significantly worse than controls.
4. While ADHD children over 11y showed less CB than controls, under 11y they tended to show more CB.
5. A correlational analysis of the status of monoamine metabolism in 24h urine samples showed a positive relationship for CB with dopamine (DA) metabolism in normal and TS children, but a negative relationship in ADHD patients (figure 1, right).
6. In contrast, increases of serotonin (5-HT) metabolism were negatively related to CB in TS, but positively related to CB in ADHD children (figure 1, right).
7. Both ADHD and TS groups showed a depressed NA turnover compared to normal children: but the ADHD showed a marked suppression of the ratio of DA and 5HT metabolites (i.e. HVA/5HIAA) that reflected their higher 5-HIAA levels. [The TS group showed increased DA turnover possibly reflecting medication.] see figure 2.
Conclusions:
When selective information processing abilities reflected by CB start to develop at the onset of puberty, there is a relative worsening in ADHD patients. In contrast TS patients show an impairment independent of age. Changes in the balance between dopamine and serotonin systems may contribute to normal and to abnormal cognitive development.
R.D. OadesB. Müller2000-12-18Z2011-03-11T08:54:27Zhttp://cogprints.org/id/eprint/1155This item is in the repository with the URL: http://cogprints.org/id/eprint/11552000-12-18ZImpaired attention-dependent augmentation of MMN in nonparanoid vs paranoid schizophrenic patients: a comparison with obsessive-compulsive disorder and healthy subjectsIntroduction: Mismatch negativity (MMN), in the deviant-minus-standard event-related potential (ERP) difference-waveform, may represent a working memory trace for tone differences (a deviant among a sequence of standards). Most, but not all studies find MMN reduced in patients with schizophrenia.
Aims: This report investigates if differences may be attributable to experimental condition (diffuse vs focused attention), component identification (N1-like vs N2-like), topographic distribution and clinical condition (with / without paranoid -hallucinatory symptoms, PH/NP). Comparisons were made for 12 PH and 12 NP schizophrenic patients with 13 obsessive compulsive and 25 normal control subjects.
Results: Frontal MMN reduction in schizophrenics largely resulted from an absence of an increase in focused attention conditions as in comparison groups. But there was marked activity recorded from sites over the temporal lobe in NP patients. These features were not reflected in other components except for a visible but nonsignifiant N1-like temporal locus in NP patients. Further, schizophrenic patients did not show an increase in late positivity with focused attention like the comparison groups.
Conclusions: The results show that so-called automatic processing deficits in schizophrenia (amount and locus of MMN) are best seen in situations requiring the activation of controlled attentional processes. It is suggested that impaired processing of irrelevant stimuli and reduced frontal MMN in NP patients may reflect reduced dopaminergic responsivity.
Robert D. OADESAlexandra DITTMANN-BALCARDieter ZERBINIna GRZELLA2000-12-18Z2011-03-11T08:54:27Zhttp://cogprints.org/id/eprint/1156This item is in the repository with the URL: http://cogprints.org/id/eprint/11562000-12-18ZA left temporal lobe impairment of auditory information processing in schizophrenia: an event-related potential studyIntroduction: A measure of auditory prepulse inhibition (PPI) or sensory gating is the reduction of the scalp-recorded P1 event-related potential (ERP) after a sound that is preceded by 100-300 ms by a click as prepulse. This measure of sensory gating was adapted to study the effect of a prepulse on processing tones that were part of a "Go/no-go" discrimination.
Methods: ERPs were recorded at right and left frontal and temporal sites on the scalp of groups of patients with schizophrenia (SCH, 8), obsessive compulsive disorder (OCD, 10) and healthy controls (CON, 19).
Results:
a) Both patient groups responded slower and showed more errors of omission than controls.
b) A prepulse presented 100 ms (but not at 500 ms) before either tone reduced the P1 or P50 ERP amplitude on healthy controls, but showed a right temporal shift in the SCH patients.
c) If the tone was the 'no-go' stimulus in the tone discrimination the prepulse reduced the N1 amplitude in both normal controls and SCH patients. This N100 amplitude was similar in records from over the left and right hemisphere of controls but was shifted to right temporal sites in the SCH group.
d) OCD patients showed a relative predominance of the left hemisphere in the gating of frontal P1, N100 and P300 components, but early gating was not significantly impaired in this group.
Conclusions: These results show a reduction of a PPI-like effect on early processing (e.g. P50/P1) that is more marked in the left hemisphere of SCH patients, and may affect channel selection for processing information about task-relevant sounds (e.g. N100)
U. SchallA. SchönD. ZerbinS. BenderC. EggersR. D. Oades2000-12-04Z2011-03-11T08:54:27Zhttp://cogprints.org/id/eprint/1138This item is in the repository with the URL: http://cogprints.org/id/eprint/11382000-12-04ZStimulus dimension shifts in patients with schizophrenia, with and without paranoid hallucinatory symptoms, or obsessive compulsive disorder: strategies, blocking and monoamine statusIntroduction: Reversal and intra-dimensional (ID) and extra-dimensional (ED) non-reversal shifts in task discrimination learning were compared. The aim was to see if "learned inattention" to the irrelevant dimension differentially influenced the efficacy of learning and of the stimulus choice strategy. (An overall indicator of monoamine metabolism was measured for potential congruence between switches of attention and dopamine activity: see Oades, Neurosci. Biobehav. Rev., , 9, 261-283, 1985).
Methods: Performance on pattern-discrimination discrimination shifts was compared with conditioned blocking (CB: another test of "learned inattention") and related to the status of monoamine neurotransmitter metabolism reflected in 24h-urine samples between tests. Results are reported for 29 healthy subjects (mean age 18.0y), 13 patients with obsessive compulsive disorder (OCD: mean age16.3y), and 28 with schizophrenia, including 14 paranoid hallucinatory (PH: 19.6y) and 14 nonparanoid patients (NP: 17.5y).
Results:
1. PH and NP patients improved learning with practice but showed an impaired shift on each task.
2. Unlike PH and control subjects, the NP shift impairment was non-specific and related to their problems on simple reversal of the discrimination.
3. The length of the stimulus-response sequences showed that all subjects were able to acquire a set for colour.
4. An analysis of choice on sequential pairs of stimuli showed that while all patients showed fewer win-stay sequences, only PH patients perseverated with lose-stay sequences. This type of error in PH patients contrast with the increase of win-shift errors in NP patients (figure 1).
5. Learning about the added stimulus on the CB task related to the efficiency of intra-dimensional shift in NP patients.
6. An impairment with OCD patients was restricted to the ED-shift (not reversal or ID-shift).
7. Increases of dopamine activity related to slower initial learning, but to more switches (and rapid learning) on all shift tasks: (positive correlations with win/lose-shift, negative with win-stay). NA activity in PH and NP patients related to increased win-stay and decreased lose-shift decisions (figure 1).
8. Increased serotonin activity correlated with faster learning in controls, OCD and PH patients. But the opposite relationships for dopamine and serotonin activity held for NP patients (figure 2).
Conclusions:
The different tasks of the "learned inattention" paradigm have different if related requirements and correlates. The monoamine data are consistent with the postulated function of noradrenaline in tuning and dopamine in switching operations. The behavioural data are consistent with the automatization of endogenous information processing, while NP patients use exogenous attentional strategies fir selecting information and PH patients show inefficient endogenous control of attention.
Robert D. OADES2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5312This item is in the repository with the URL: http://cogprints.org/id/eprint/53122006-12-22ZPrenatal growth markers in schizophrenia: a monozygotic co-twin control study.
OBJECTIVE: This co-twin study investigated monozygotic twins who were discordant for schizophrenia for evidence of prenatal growth differences between the affected and well co-twins. METHOD: Four dermatoglyphic markers of prenatal growth were obtained by established procedures from 26 monozygotic twin pairs discordant for schizophrenia, 13 monozygotic twin pairs concordant for schizophrenia, and several normal monozygotic twin samples. RESULTS: The a-b ridge count differences between the affected and well co-twins were greater than those found for concordant and normal monozygotic pairs. In comparison with their well co-twins, the affected twins, in discordant pairs, had developed fewer epidermal ridges in the a-b interdigital area of their right palms. In contrast, no significant differences were found between the affected twins and their well co-twins on markers associated with fetal development before 13 or after 15 weeks estimated gestational age. CONCLUSIONS: Because the a-b ridges are known to complete development between 13 and 15 weeks estimated gestational age, the results provide physical evidence suggesting that the schizophrenia-affected monozygotic twins alone experienced a time-specific and time-limited dysgenesis during this time. Commonalities in the ontogeny of epidermal and neurological structures are discussed.JO DavisHS Bracha2000-12-28Z2011-03-11T08:54:28Zhttp://cogprints.org/id/eprint/1167This item is in the repository with the URL: http://cogprints.org/id/eprint/11672000-12-28ZAuditory event-related potential (ERP) and difference-wave topography in schizophrenic patients with/without active hallucinations and deluisions: a comparison with young obsessive-compulsive disorder (OCD) and healthy subjectsIntroduction:
Event-related potentials (ERPs) in schizophrenics have been reported to show a reduced P3 on the left and less frontal mismatch negativity. But the specificity of such findings to component, its locus, the type of eliciting event and patient group remains uncertain. Hence, we examined ERP topography for P3, N2 and 3 precursor peaks according to stimulus (3-tone oddball), attention condition (diffuse/focused) and four types of difference-waves (Mismatch negativity, Processing negativity, Negative difference (Nd) and the 'Goodin-Waveform').
Method:
We contrasted ERPs in a 3-tone oddball task-form in 24 healthy (mean 18.5y of age) and 13 OCD (mean age 16.3 y) subjects with schizophrenic patients with high versus low ratings of active delusions and hallucinations (12 paranoid-hallucinatory, PH [mean age 18.5y]; 12 nonparanoid, NP [mean age 18.9y])
Results:
1. P3 peaks were delayed and reduced in NP and PH groups. Peaks in the midline were usual in the focused attention condition, but a right bias in diffuse attention (passive presentation).
2. P3 responses to irrelevant non-targets remained lateralised in NP, and small in OCD patients. All showed a small left and anterior bias in the P3-like peak recorded after subtraction in the difference waves.
3. Mismatch negativity (MMN) peaks shifted to the right in OCD, laterally to both sides in PH and more posteriorly in NP patients.
4. Frontal processing negativity was biased to the left (early) in NP and to the right (late) in PH groups.
5. Early peak topography in the difference waveforms reflected some of these later changes (e.g., for PH and NP groups the normal right bias in the P1-like peak was absent; the N1-like peak was reduced and widely distributed: for the NP group, the P2-like peak appeared smaller on the left).
6. In OCD patients, the peak latencies were topographically undifferentiated for P1 and P2, or delayed in the case of the N2 component.
Conclusions:
A) The OCD group showed an unusual regional allocation of processing effort.
B) Before 200 ms, fronto-central activity was more widespread in both the PH and NP groups.
C) NP patients, in particular, treated irrelevant stimuli anomalously.
D) Lateralisation of negativity in target- and nontarget-derived difference waves may reflect differential disruption of the frontal-temporal dialogue in registering important vs. unimportant features. Indeed, the apparent left/right differences of negative difference (Nd) or processing negativity amplitude may not so much reflect amplitude differences as a delayed latency over left frontal areas in PH and over the right frontal areas in NP patients with schizophrenia.
Robert D. OADESD. ZERBINA. DITTMANN-BALCARC. EGGERS2000-12-28Z2011-03-11T08:54:28Zhttp://cogprints.org/id/eprint/1168This item is in the repository with the URL: http://cogprints.org/id/eprint/11682000-12-28ZAuditory event-related potentials (ERPs) and mismatch negativity (MMN) in healthy children and those with attention-deficit or Tourette/tic symptomsIntroduction: This study compared 5 auditory, event-related potential (ERP) components (from P1 to P3, 50 to 500 ms post stimulus) after 3 tones differing in pitch and in rarity presented to three groups of children. The mismatch negativity (MMN), the ERP trace of auditory working memory for deviant stimuli was also studied.
Methods: Topographic recordings were derived from 19 electrodes over the scalp of 12 children with attention-deficit/hyperactivity disorder (ADHD): mean 10.2 years-of age), 12 healthy controls matched for age, and 10 with chronic complex Tic- or Tourette syndrome (TS), who also showed symptoms of attention-deficit.
Results:
Four major effects are reported:
a) Shorter ERP latencies were evident in ADHD children as early as 100 ms after the stimulus;
b) Both ADHD and TS children showed larger P2 component amplitudes than the controls with their maxima shifted more anteriorly;
c) Frontal MMN was not significantly different between ADHD and healthy controls, but the normalised data showed a left-sided distribution in the ADHD group and a right-sided distribution in the normal children. Maxima for TS children was unusually more posterior. (In adults the distribution is normally frontal and bilateral.)
d) ADHD patients did not show the usual right-biased P3 asymmetric distribution (nor a frontal vs. parietal latency difference).
Conclusions: These results suggest that ADHD children process information faster from the early N1 (c. 100 ms) stage. Both groups of children with attention-deficit symptoms showed a marked enhancement of the inhibitory phase of processing in the auditory cortex marked by P2. That this is shown even after a standard stimulus indicates an increased likelihood of unimportant stimuli being further processed and coming to control behaviour, while stimuli competing for attention are suppressed. Later indices of processing (N2-P3) showed a frontal impairment (TS), especially in the right hemisphere (ADHD) that are suggested to be indicative of anomalous timing in the development of frontal function.
Robert D. OADESAlexandra DITTMANN-BALCARRenate SCHEPKERChristian EGGERSDieter ZERBIN2000-12-21Z2011-03-11T08:54:28Zhttp://cogprints.org/id/eprint/1166This item is in the repository with the URL: http://cogprints.org/id/eprint/11662000-12-21ZConditioned blocking in patients with paranoid, non-paranoid psychosis or obsessive compulsive disorder: associations with symptoms, personality and monoamine metabolismIntroduction: Conditioned blocking (CB) refers to a delay in learning that a new stimulus, added during learning, has the same consequences as the conditioned stimulus already present. In animals such "learned inattention" depends on monoaminergic and limbic function and, thus, CB performance should be informative on selective information processing impairments found in subgroups of psychotic patients. Attenuated CB in acute schizophrenia has been reported to normalize rapidly.
Method: This study examines in young patients the specificity of CB performance to illness, and its associations with symptoms, personality traits and monoaminergic metabolic status.
Results: Performance: CB was attenuated in psychotic patients with nonparanoid symptoms (NP: n=12, mean age 17 years) with respect to obsessive compulsive (OCD: n=13, mean age 16 years) and healthy subjects (CON; n=29, mean age 18 years), but only a transient attenuation was observed in paranoid hallucinatory patients (PH: n=14, mean age 19 years). The severity of negative symptoms in psychosis and specific negative/positive symptoms in the NP/PH groups were associated with reduced CB. Outgoing personality traits in CON and OCD subjects correlated with CB. In NP patients attenuated CB was associated with increasing neurotic lability. In PH patients CB correlated positively with "manic" but negatively with psychotic or neurotic scores. Monoamines: Increased dopamine activity (24h urine samples) correlated positively with CB, but relative increases of noradrenaline metabolism in NP and serotonin metabolism in OCD patients interfered.
Conclusions: Marked psychotic or neurotic traits and some negative symptom states were associated with reduced CB. The particular selective processing problems of NP patients may reflect inappropriate NA activity.
R. D. OADESB. ZIMMERMANNC. EGGERS2001-01-05Z2011-03-11T08:54:28Zhttp://cogprints.org/id/eprint/1181This item is in the repository with the URL: http://cogprints.org/id/eprint/11812001-01-05ZEvent-related potentials during an auditory discrimination with prepulse inhibition in patients with schizophrenia, obsessive-compulsive disorder and healthy subjectsIntroduction: Prepulse inhibition (PPI) is a measure of the influence of a stimulus (S1) on the response elicited by a second stimulus (S2) occurring shortly afterwards. Most S1/S2 measures of gating have used behavioral startle and the P50 event-related potential (ERP) amplitudes to detect PPI in a simple paired stimulus paradigm.
Aims: Here we report on two behavioral (EOG and reaction time, RT) and 5 ERP measures of PPI where S2 was the target or standard in an oddball discrimination. Subjects were 21 healthy controls (CON), 11 obsessive-compulsive (OCD) and 9 schizophrenic patients (SCH).
Results: The prepulse 100ms before S2 induced fewer omission errors and longer RTs compared to a 500ms S1-S2 interval in all subjects. PPI was also evident in EOG, P50, N1, P3 but not P2 or N2 amplitudes of CON subjects. SCH patients showed attenuation of PPI on the same measures. OCD patients were characterized only by their slow RT and a marginal attenuation of EOG-PPI.
Discussion: A correlational analysis implied separate relationships of ERP indices of PPI to the cognitive and psychomotor consequences of the prepulse on behavioral and discrimination responses. However SCH patients showed a general rather than a specific impairment of these indices.
Ulrich SchallAnja SchoenDieter ZerbinChristian EggersRobert D. Oades2000-01-24Z2011-03-11T08:53:41Zhttp://cogprints.org/id/eprint/130This item is in the repository with the URL: http://cogprints.org/id/eprint/1302000-01-24ZTheodore Holmes BullockThey tell me I was born on a sunny Sunday in May in Nanking, China, in 1915. I was the second of four children of Presbyterian missionary parents, Amasa Archibald Bullock and Ruth Beckwith, who had come to China in 1909, honeymooning on the way for six months in Europe and India. Several years before, father had answered a call for western teachers, published by the Empress; he spent a contract year in Chengtu, in western Szechuan, teaching chemistry, his major subject at U.C. Berkeley. He fell in love with the people, their eagerness to listen, and their respect for learning. Seeing a niche that called him, in the scattered experiments with western style education, especially teacher training, he returned to the states to take a master's degree in education at Chicago and then advanced work in psychology with Thorndike at Columbia. His college roommate's sister was preparing to be a missionary in Hartford Theological Seminary and they had corresponded but not met before he came to visit and in four days secured her assent to return with him and spend a life in China. He joined the faculty of the University of Nanking to start its normal school and, among other activities, its program in agriculture. The still extant guest book of our home shows the signatures of Sun Yat Sun, then President of China, and several members of his cabinet.T.H. Bullock2001-01-10Z2011-03-11T08:54:28Zhttp://cogprints.org/id/eprint/1198This item is in the repository with the URL: http://cogprints.org/id/eprint/11982001-01-10ZConnections between studies of the neurobiology of attention, psychotic processes and event-related potentialsAttention: the selective aspect of perception, requires wakefulness (organism), activation (behavior) and inhibition (neuronal systems). It may be observed momentarily (concentration), over time (vigilance) and in the selection between channels (e.g. the rejection of irrelevance in focussed and divided conditions).
Anatomical Organisation: Information ascending through the thalamus not only alerts the sensory cortices, but thalamic projections to association areas receive direct feedback allowing gating and preparation of sensory areas for further analysis. A frontal organizational role is subserved by descending pathways allowing for valuation (orbitofrontal cortex, amygdala), association (hippocampal complex) and response possibilities (basal forebrain). Interactions between the latter allow for automatic processes, but with the former limbic connections bring the possibility of conscious control.
Neurotransmitters: Additional involvement of brainstem mechanisms allows for volume-control (serotonin, 5HT), tuning (noradrenaline, NA) and switching (dopamine, DA) mechanisms in determining priority in selective mechanisms. Failures of brainstem mechanisms can impair the modulation of several systems ranging from affect (e.g. 5HT, hostility) to the assessment of information relevance (DA, perseveration, switching). Such non-specific features of psychotic processes can be incurred by unusual amino-acid transmission (e.g. Glu, Asp, GABA) from the neo- and archicortices.
Psychopathology: The locus of supra- or sub-liminal damage may provide specificity to the symptom and speculatively the schizophrenic syndromes of poverty, disorganization and reality distortion. Useful "attentional" paradigms for the study of the nature and distribution of these processes include sustained attention, the influence of irrelevant stimuli (learned inattention -"blocking"), the covert orienting of attention (cost/benefits of cueing), dichotic and multidiscrimination (allocation), prepulse inhibition and masking (sensory gating) and concept formation.
Psychophysiology: Our own work shows, for example, that mismatch negativity is severely reduced in young patients with schizophrenia with or without reality distortion (by 50% and again by 50%, respectively). But only the non-paranoid patients show an abnormal loosening of selection processes, reflected in reduced conditioned blocking (that in turn reflects switching between relevant and irrelevant stimuli and learning about both). This latter result proved to be related to changes of daily DA utilization (measured in 24h-urine samples) consistent with a DA role in switching.
Robert D. Oades1999-07-22Z2011-03-11T08:53:40Zhttp://cogprints.org/id/eprint/110This item is in the repository with the URL: http://cogprints.org/id/eprint/1101999-07-22ZNeural Integration at the Mesoscopic Level: the Advent of some Ideas in the Last Half CenturyHistory seen by a professional historian, based only on the documented record, always incomplete and liable to bias, can be unreliable. Modern history seen by a protagonist must surely be among the most unreliable. My only excuse for this effort is that I was invited by the relevant Society committee. My reason for accepting is that I feel even the fragmentary part of neuroscience I can speak about is a human drama, romantic and exciting, and a flood on which we are floating, unable to dump the baggage of past biases. Our points of view, priorities, and positions on all the controversial issues and even the well established, noncontroversial ones, are not as rational as we would like to think but are strongly conditioned by where we came from. I will depend mainly on selected vignettes of the way things looked when I was a student, a young postdoctoral fellow and an Assistant Professor, to compare with the way they look to me or to others now, in each of half a dozen mesoscopic domains. I mean by mesoscopic domains the middle levels - those in between the most basic subcellular or molecular and the higher levels of learning and cognition. The half dozen domains constitute of course, anything but a representative fraction of neuroscience. I believe, however, that they add up to a nontrivial segment of the big picture with respect to the integrative aspects of our science. Most of the fronts that grew into today's popular branches of our science are not represented but a small set of particular interest and probability of further surprises.Theodore H. Bullock2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5314This item is in the repository with the URL: http://cogprints.org/id/eprint/53142006-12-22ZPrenatal development of monozygotic twins and concordance for schizophreniaWhile twin concordances for schizophrenia have been used to estimate heritability and to develop genetic models, concordances in subtypes of monozygotic (MZ) twins can also be used to investigate the influence of prenatal development in the etiology of mental illness. We used within-pair variability and mirroring of fingerprints to estimate retrospectively the placentation status of concordant and discordant MZ twins. The results indicate that concordant MZ pairs were more likely to have been monochorionic (MC) and to have shared a single placenta, whereas discordant MZ pairs appear more likely to have been dichorionic (DC) with separate placentas. Pairwise concordances for MZ twins without MC markers averaged 10.7 percent. In contrast, concordances for MZ twins with one or more MC markers averaged 60 percent. This suggests that simple MZ concordance rates may overestimate schizophrenia heritability and that prenatal development may also be important in the etiology of schizophrenia. Because MC (but not DC) twins usually share fetal blood circulation and hence are likely to share infections, these results are consistent with the hypothesis that fetal infections may be a significant etiological factor in schizophrenia.
JO DavisJA PhelpsHS Bracha2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5300This item is in the repository with the URL: http://cogprints.org/id/eprint/53002006-12-22ZSubclinical microcrania, subclinical macrocrarnia, and fifth-month fetal markers (of growth retardation or edema) in schizophrenia: a co-twin control study of discordant monozygotic twins.Summary: We tested the hypothesis that gestational injuries in some patients with schozophrenia would leave their mark as a subtle reduction in head circumference (subclinical microcrania).
Conclusions: The head circumferences of all subjects were in the normal range. Decreased head circumference in affected MZ co-twins (relative to unaffected MZ co-twin) characteriazes discordant MZ pairs with larger finger-ridge-count differences (i.e., second-trimester fetal-size differences). This study using ideal genetic controls suggests that, while present only in some patients with schizophrenia, the decrease in head circumference is most likely a consequence of in-utero nonshared environmental deleterious events manifesting as groth retardation or as fetal edema and occurring around the fifth prenatal month. HS BrachaP GilB LangeJ GilderEF TorreyII GottesmanDS McCray2001-02-02Z2011-03-11T08:54:29Zhttp://cogprints.org/id/eprint/1269This item is in the repository with the URL: http://cogprints.org/id/eprint/12692001-02-02ZChildhood autism: an appeal for an integrative and psychobiological approachIntroduction: Childhood autism, overtly expressed as social indifference and repetitive motor patterns, in fact involves a range of problems covering sensory, attentional, cognitive, emotional, language as well as motor areas of function - 25 symptoms can be listed. Although a reduced verbal IQ and language difficulties are frequent, a major intervening variable may be problems with the development of a "theory-of-mind" ....the ability to comprehend the mental states of others. Prevalence rates per 10,000 of the population range from 2 to 16 in different countries, rising to 50 if one includes spectrum autistic disorder. A number of sometimes related organic associations and potentially separate aetiologies are described.
Biology: Evidence for delayed neurotransmission (evoked potentials) and a lack of flexibility in physiological responses (signal detection, cross-modal integration) may underlie the attenuation of monitoring processes that lead to withdrawal and stereotypies. Neuropsychological task performance provides limited and qualified evidence for impaired frontal function, although this could explain event-related potential (ERP) evidence for more of a deficit with controlled attention (Nd) than in automatic processing (MMN). [ERPs also underline the difficulties in generating differential responses to relevant and irrelevant stimuli.] Imaging studies show some structural abnormalities in half the patients (e.g. ventricle volume increases), but indices of activation, though in the normal range do not appear situation-appropriate.
Pharmacology:
a) A significant proportion of autistic subjects show increased peripheral measures of serotonin and quite often raised dopamine metabolism - that in some high-functioning cases has been claimed to be beneficial. It is plausible that changes in monoaminergic transmission are inadequately compensated by changes in the other transmitter systems.
b) With serotonin and dopamine responsible for inhibition/volume-control and for switching/flexibility we propose an imbalance of these systems that results in a stop-go form of neuronal communication that inevitably leads to anomalous responses at the whole organism level.
c) At least 20 forms of pharmocotherapy have been attempted, the best with improvement limited to a few patients improving particular symptoms only. The best have proved to be dopamine or opioid antagonists, but at best - these have a limited and modest role to play in clinical care
Conclusions: The impairment of children with autism manifests itself at many levels - treatment concepts must attempt to integrate these, with emphasis on the particular abilities and difficulties of the individual. The need is to synthesize the different levels of analysis for a psychobiological approach to be integrated into the wide-ranging remedial programmes currently practised..
Robert D. OadesC. Eggers2001-03-16Z2011-03-11T08:54:36Zhttp://cogprints.org/id/eprint/1373This item is in the repository with the URL: http://cogprints.org/id/eprint/13732001-03-16ZDoes Schizophrenia have a substantial genetic component?Aims:
A side by side comparison of two articles : -
Genetic studies [ Is schizophrenia inherited ? ] E.R.Straube & R.D. Oades
Schizophrenia: The clash of determinisms R.C. Lewontin, S. Rose, L.J. Kamin
with an
Introduction to the Controversy, Discussion, Questions to stimulate discussion and Suggestions for further reading
from S.O. Lilienfeld
Straube and Oades review the evidence from twin adoption studies of schizophrenia and conclude that schizophrenia is substantially influenced by genetic factors. Lewontin, Rose and Kamin find the evidence for the heritability of schizophrenia to be unconvincing and argue that greater attention should be focused on social and cultural factors in the genesis of schizophrenia.
E.R. StraubeR.D. OadesR.C. LewontinS. RoseL.J. KaminS.O. Lilienfeld1999-11-16Z2011-03-11T08:53:41Zhttp://cogprints.org/id/eprint/124This item is in the repository with the URL: http://cogprints.org/id/eprint/1241999-11-16ZDynamics of event-related potentials to trains of light and dark flashes: responses to missing and extra stimuli in elasmobranch fish.To characterize the dependencies of ERPs in lower vertebrates and brain levels upon recent history and sequences of stimuli, trains of flashes were delivered at various frequencies to unanesthetized rays while recording in optic tectum and telencephalon. ERPs to repetitive stimuli cannot be understood in terms of simple refractoriness and recovery. Processes must be invoked such as simultaneous excitation and suppression, facilitation and its opposite, rebound and induced rhythms, each with development and decay times and nonlinearities. Some of these processes are uncovered by omitting a stimulus from a train. Omitted stimulus potentials (OSPs) act as though the brain expects a stimulus within 5-7 ms of the interstimulus interval (ISI) of the train. Very few ISIs suffice. The effect upon VEP form and duration of the number of stimuli in short trains, before the steady state response (SSR) is established, is complex. Alternation of the amplitude of successive VEPs (1 large every 2 VEPs, 1 in 3, 1 in 4) is one indication of complexities in the SSR. OSPs also alternate. A single extra stimulus interpolated into a regular train causes distinct effects according to its position. Sharp discontinuities in these effects appear with <5 ms shifts. Total power of the SSR decreases with stimulation frequency but there is a large peak of increased power at 7 Hz and another at 12 Hz. Induced rhythms are a labile, late phase of OSPs as well as of rested VEPs and of the OFF response to a long light pulse. Jittered ISI experiments show that the apparent expectation of the OSP is little affected and that the intervals in the last few hundred milliseconds are most influential. The OSP studied here (ISI <0.5 s)is quite different from that so far studied in human subjects (ISI >1s). We predict further similarities when each taxon is tested in the other ISI range. A major category of response characteristics, besides sensitivity, receptive fields and recovery times, is dependence upon recent history of iterative events, including intervals, delays, omissions and perhaps multiple facilitating and forgetting time constants. The variables examined parametrically in this study are only some of those available. Such dynamical characteristics are important neglected properties of afferent systems at each level.Sacit KaramürselT.H. Bullock2001-01-15Z2011-03-11T08:54:29Zhttp://cogprints.org/id/eprint/1227This item is in the repository with the URL: http://cogprints.org/id/eprint/12272001-01-15ZMonoamine activity reflected in urine of young patients with obsessive compulsive disorder, psychosis with and without reality distortion and healthy subjects: an explorative analysisIntroduction: Positive psychotic symptoms are reported to be associated with high dopamine (DA), negative symptoms with low DA activity and serotonin (5-HT) activity may be altered in obsessive-compulsive disorder (OCD).
Method: We analysed 24h urine samples in groups of patients with OCD, paranoid and non-paranoid schizophrenia and in healthy controls for supportive evidence.
Results: Young unmedicated OCD subjects excreted more adrenaline (AD) and homovanillic acid (HVA) and showed a higher HVA/MHPG metabolite ratio and metabolic rate than healthy controls. Independent of general metabolic rate OCD patients showed higher HVA concentrations which suggests that the relative activity of catecholamine systems in OCD (HVA/MHPG) is due more to high DA than to low noradrenergic (NA) activity. Concentrations of 5-HT were also high in OCD patients. In psychotic patients low levels of DA, HVA, NA and MHPG probably resulted from neuroleptic medication.
Conclusions: 1. Patients diagnosed with paranoid psychosis showed higher DA utilization than controls and those with few paranoid symptoms showed high 5-HT utilization. 2. These results support studies suggesting that paranoid psychosis is associated more with increased DA activity (discussed in the context of neuroleptic reactivity), that non-paranoid forms are associated more with increased 5-HT activity and that OCD patients are unusually aroused with high levels of Adrenaline, 5-HT and HVA.
R. D. Oades Röpcke Eggers2001-01-15Z2011-03-11T08:54:29Zhttp://cogprints.org/id/eprint/1229This item is in the repository with the URL: http://cogprints.org/id/eprint/12292001-01-15ZSerum gonadal steroid hormones in young schizophrenic patientsPsychosis is reported to show a later age of onset in women than in men and its nature and course in women may also differ.
Our aim was to see if levels of four steroid hormones at the start of early-onset psychosis differ from other groups of young people and if predicted low levels of estrogen (E2) are a feature of female psychosis. [We would predict that female schizophrenia patients on a child and adoelscent psychiatry ward would show low levels of E2 with its putative neuroleptic like protective properties.]
Methods: Two blood samples from 22 young psychotic patients were analysed by radioimmunoassay for E2, progesterone (PROG), testosterone (TE) and dehydroepiandrosterone sulphate (DHEAS).
Results: Female psychotic patients showed E2 levels lower than matched healthy cycling controls but higher than those on a contraceptive pill: they also showed higher TE levels than controls.
Male psychotic patients had higher DHEAS levels than healthy or obsessive compulsive disorder subjects.
Conclusions: We suggest that illness-related changes of steroids can be measured superimposed on medication - induced changes and that lower E2 levels in psychotic women may increase their vulnerability to psychosis. Changes of TE in female and DHEAS in male psychotics may be more a consequence of the illness. However we postulate that increased DHEAS levels could interfere with normal neurodevelopmental neuronal pruning processes (cf. increased DHEAS levels in male adolescents with conduct disorder, Dmitrieva et al., 1999, 2001)
Oades Schepker2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5315This item is in the repository with the URL: http://cogprints.org/id/eprint/53152006-12-22ZCorrelation of severity of psychiatric patients' delusions with right hemispatial inattention (left-turning behavior)
Studies associate psychotic disorders with various forms of subtle inattention to the right hemispace (left-turning behavior). The authors examined the correlation between this dopamine-related sign and severity of delusions (presumably dopaminergic symptoms) in 20 psychotic patients. Delusions were significantly correlated with severity of left-turning bias, and this neurological sign accounted for 33% of the variance in severity of delusions.HS BrachaRL LivingstonJ ClothierBB LiningtonCN Karson1999-10-21Z2011-03-11T08:53:41Zhttp://cogprints.org/id/eprint/121This item is in the repository with the URL: http://cogprints.org/id/eprint/1211999-10-21ZInterval-specific event related potentials to omitted stimuli in the electrosensory pathway in elasmobranchs: an elementary form of expectationMultiunit activity and slow local field potentials show Omitted Stimulus Potentials (OSP) in the electrosensory system in rays after a missing stimulus in a 3 to >20 Hz train of microvolt pulses in the bath, at levels from the primary medullary nucleus to the telencephalon. A precursor can be seen in the afferent nerve. The OSP follows the due-time of the first omitted stimulus with a, usually, constant main peak latency, 30-50 ms in medullary dorsal nucleus, 60-100 ms in midbrain, 120-190 ms in telencephalon - as though the brain has an expectation specific to the interstimulus interval (ISI). The latency, form and components vary between nerve, medulla, midbrain and forebrain. They include early fast waves, later slow waves and labile induced rhythms. Responsive loci are quite local. Besides ISI, which exerts a strong influence, many factors affect the OSP slightly, including train parameters and intensity, duration and polarity of the single stimulus pulses. Jitter of ISI does not reduce the OSP substantially, if the last interval equals the mean; the mean and the last interval have the main effect on both amplitude and latency. Taken together with our recent findings on visually evoked OSPs, we conclude that OSPs do not require higher brain levels or even the complexities of the retina. They appear in primary sensory nuclei and are then modified at midbrain and telencephalic levels. We propose that the initial processes are partly in the receptors and partly in the first central relay including a rapid increase of some depressing influence contributed by each stimulus. This influence comes to an ISI-specific equilibrium with the excitatory influence; withholding a stimulus and hence its depressing influence causes a rebound excitation with a specific latency.T.H. BullockSacit KaramürselMichael H. Hofmann2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5316This item is in the repository with the URL: http://cogprints.org/id/eprint/53162006-12-22ZSecond-trimester markers of fetal size in schizophrenia: a study of monozygotic twinsOBJECTIVE: Since the second prenatal trimester is the critical period of massive neural cell migration to the cortex, and fingertip dermal cells migrate to form ridges during this same period, the authors sought to determine whether there are differences in fingertip ridge count in pairs of monozygotic twins discordant for schizophrenia, possibly indicating that a prenatal anatomical insult affected the twins differently. METHOD: The fingertip dermal ridges of 30 pairs of monozygotic twins (23 pairs in which the twins were discordant for schizophrenia and seven pairs in which both twins were normal) were counted by two persons trained in anthropometric research. Intrapair differences in the counts were then measured, and the differences among the pairs of normal twins were compared with the differences among the pairs discordant for schizophrenia. RESULTS: The twins discordant for schizophrenia had significantly greater absolute intrapair differences in total finger ridge count and significantly greater percent intrapair differences than the normal twins; i.e., their fingerprints were significantly less "twin-like." CONCLUSIONS: The study suggests that various second-trimester prenatal disturbances in the epigenesis of one twin in a pair discordant for schizophrenia may be related to the fact that only one of the twins expresses his or her genetic predisposition toward schizophrenia. This is consistent with a "two-strike" etiology of schizophrenia: a genetic diathesis plus a second-trimester environmental stressor.HS BrachaEF TorreyII GottesmanLB BigelowC Cunniff2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5317This item is in the repository with the URL: http://cogprints.org/id/eprint/53172006-12-22ZA monozygotic mirror-image twin pair with discordant psychiatric illnesses: a neuropsychiatric and neurodevelopmental evaluationOne piece of genetic evidence for the biological distinctness of schizophrenia and bipolar illness is the rarity of monozygotic twin pairs in which one twin suffers from schizophrenia and the other from bipolar disorder. The authors describe a pair of monozygotic mirror-image twins with discordant diagnoses, schizophrenia in one twin and bipolar or schizoaffective disorder in the other.LB LohrHS Bracha2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5318This item is in the repository with the URL: http://cogprints.org/id/eprint/53182006-12-22ZSubtle signs of prenatal maldevelopment of the hand ectoderm in schizophrenia: a preliminary monozygotic twin studyGenes that predispose to psychosis may act by making individuals more vulnerable to the disruptive effects of various prenatal insults. Fetal organogenesis is mostly completed in the first prenatal trimester. The second trimester is a critical period of massive neuronal migration from the periventricular germinal matrix to the cortex. A peripheral appendage developing simultaneously with this neural migration to the cortex is the distal upper limb. The ectodermal cells of the fetal upper limb migrate to form the hand skin during the fourth and fifth months of gestation (first two-thirds of the second prenatal trimester). Discrepancies in hand morphology between two identical (monozygotic [MZ]) co-twins may be temporal markers, that is, the "fossilized" evidence of various ischemic and other nongenetic insults that may have affected one fetus more than his MZ co-twin during that early part of the second trimester. In twins, prenatal insults (e.g., ischemia) frequently do not affect both co-twins to the same extent, so we examined seven putative markers of prenatal injury to the hand in 24 MZ twin pairs discordant for schizophrenia or delusional disorder. Compared with well co-twins, the affected co-twins had significantly higher total scores of fourth- and fifth-month dysmorphological hand anomalies.
HS BrachaEF TorreyLB BigelowJB LohrBB Linington2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5303This item is in the repository with the URL: http://cogprints.org/id/eprint/53032006-12-22ZEtiology of structural brain asymmetry in schizophrenia, an alternative hypothesisDuring normal development of the fetal brain, the left hemisphere lags behind the right hemisphere in intrauterine growth, causing the left hemisphere to be smaller than the right hemisphere throughout the early and mid-prenatal period. By the end of the second trimester, the right hemisphere has achieved almost full-term size; thus second-trimester injuries affecting neurons, that is, anoxic, ischemic, toxic, or infectious insults that are systemic and bilateral, will affect the left hemisphere more than the right hemisphere. While other explanations for brain asymmetries in schizophrenia have been proposed, the embryological literature is consistent with the hypothesis that a prenatal injury may be one etiological factor in producing the structural brain asymmetries seen in psychotic adult patients.
HS Bracha2001-03-09Z2011-03-11T08:54:35Zhttp://cogprints.org/id/eprint/1354This item is in the repository with the URL: http://cogprints.org/id/eprint/13542001-03-09ZA controlled crossover trial of fendluramine in autismIntroduction: Against a background of variable results achieved by the treatment of childhood autism with dopaminergic agonists or antagonists, and opiate antagonists and mild behavioural improvements achieved following treatment with fenfluramine (Geller et al., 1982; Ritvo et al., 1984 among others) a 12 month double-blind crossover trial of fenfluramine was undertaken. [the d-isomer releases serotonin, the l-isomer modestly blocks dopamine receptors.]
Methods: Six female and 14 male children and adolescents with autism were enrolled (median 9y; range 5-17 years of age) in a trial run over a 1 month baseline, 5 months of treatment, 2 months placebo, and 5 months of treatment. Parent diaries were kept. Various tests and rating scales for development, verbal and noverbal abilities along with measures of blood serotonin, urinary catecholamines and auditory event-related potentials (ERPs) were measured at 6-month intervals.
Results:
a) With fenfluramine treatment children lost weight, blood serotonin decreased by 60% and urinary catecholamine levels fell (25-45%, but dopamine utilization (HVA/DA) increased 2-4-fold.
b) Under fenfluramine some autistic subjects improved on measures of cognitive and language function. Two mute subjects began to speak, but for the group overall the improvements did not prove significant. [British Ability Scale, Reynell developmental language and Vineland social maturity scale improvements were significant.]
c) Treatment improved early stages of information processing, but impaired later stages as measured in the ERP (i.e. early negative going excitatory vs. later positive going inhibitory response, respectively in 7 patients). The early negativity changes (especially over the right hemisphere) correlated inversely with HVA/DA actvivity.
d) Side effects reported included lethargy and irritability..
Conclusions: While individuals showed marked reductions of stereotypies, hyperactivity, and improvements on develepmental and cognitive measures, the absence of clear group-wide effects suggests that fenfluramine would have but a limited place in the management of some patients with autism.
L.M. SternM.K. WalkerM.G. SawyerR.D. OadesN.R. BadcockJ.G. Spence2001-01-24Z2011-03-11T08:54:29Zhttp://cogprints.org/id/eprint/1256This item is in the repository with the URL: http://cogprints.org/id/eprint/12562001-01-24ZEvent-related potentials and monoamines in autistic children on a clinical trial of fenfluramineIntroduction: As autistic persons have problems with selecting and encoding meaningful stimuli and multi-centre studies (Ritvo et al., 1983, 1986) had reported mild behavioural improvements following treatment with fenfluramine, event-related potential (ERP) stages of information processing were studied in childhood autism as part of a double blind crossover study of the efficacy of dl fenfluramine. .
Methods: Acceptable recordings were derived from midline and 4 lateral sites on the scalp of 7 from 14 young persons with autism who understood the task (6 male, 1 female 5.8-17.7 years-of-age). A three-tone oddball paradigm was presented in a passive and active-task form (72% at 1 kHz, 14% at 0.5 kHz and 14% at 2.0 kHz) under placebo and drug conditions (where each condition lasted 5 months). Eleven patients provided blood and urine samples for monoamine analyses in both conditions.
Results:
a) With fenfluramine treatment blood serotonin decreased and urinary catecholamine levels fell (25-45%, but dopamine utilization (HVA/DA) increased 2-4-fold.
b) Under fenfluramine autistic subjects responded non-significantly faster, with fewer errors of omission and improved /decreased beta criterion (signal detection). [IQ measures increased 7.5 points.]
c) N1 amplitudes (Fz) decreased and latencies increased in the fenfluramine condition.
Early negativity (especially on the right) correlated inversely with HVA/DA actvivity.
Subtraction of the ERPs in nontarget from target conditions showed that the Negative difference (Nd) increased during fenfluramine treatment.
d) P3 amplitudes (especially after the deviants) increased with fenfluramine treatment. But in the difference waveform (active-minus-passive condition) the P3 amplitude was halved. The distribution of the P3 component moved rostrally with treatment.
Conclusions: N1 and P3 components of the ERP were responsive to fenfluramine treament. Treatment appears to have mildly improved early stimulus processing at stages represented by the early negative components, but to have mildly impaired processing at the P3-stage. The N1 / Nd - related improvement seems to be related to increased dopamine activity (cf. neuroleptic-like properties of racemate fenfluramine).
R.D. OadesL.M. SternM.K. WalkerC.R. ClarkV. Kapoor2001-03-09Z2011-03-11T08:54:35Zhttp://cogprints.org/id/eprint/1353This item is in the repository with the URL: http://cogprints.org/id/eprint/13532001-03-09ZAttention deficit disorder and hyperkinetic syndrome: biological perspectivesThe condition, biological indicators and animal models of the symptoms and the disorder are briefly reviewed.
Condition: No single symptom is indispensable to diagnosis. But measures of the condition include motor activity, attention, motivation and psychostimulant responsiveness.Caveat: In the study of the condition, measuring biological correlates of unusual function may prove useful for management of the condition, but could mislead in the search for causes.
Biological indicators: Investigation of attention-related function and associated regional cerebral activity would be improved by the careful application of the results of neuropsychological and psychophysiological study. A more extensive use of within subject protocols would greatly assist interpretation of the relevance of physiological states and the contribution of activity in different transmitter systems.Why are MHPG levels low, and lower in stimulant responders: HVA/MHPG ratios high in responders and nonresponders alike? However, the author sees the paradox to lie less with the induced (sic) metabolic changes as with the inability to mimic the changes with other catecholaminergic agents. Attention is drawn to the trophic effects of the monoamines. Attention is also drawn to the colocalisation of neuropeptide Y in NA neurons and the possibility that alterations in this relationship could underlie other ADHD characteristics such as thirst (1).
Models: Symptom-models attempt to investigate the determinants a single feature of the illness. Examples have been recent demonstrations that where NA activity is low or depleted selective attention may be impaired (e.g. latent inhibition). An interesting observation here is that where NA activity is low, learning in a variety of situations occurs at normal rates to a modest criterion, but then slows severely before eventually reaching good stringent criteria. It is suggested that this is consistent with an NA role in "tuning" (2).Discussion of the various roles of DA must make mention of the specific improvement seen after amphetamine treatment in those children who only achieve a low response criterion: in contrast in animals amphetamine promotes the impulsive response lowering beta-criterion. The resolution oif the enigma may well lie in a better understanding of the interactions of the mesolimbic with the mesocortical DA system. Mesocortical activity can suppress mesolimbic activity, impairment of frontal function releases the mesolimbic system - a change that can be countered by psychostimulant treatment.
Disorder-models are concerned with mimicking a whole cluster of symptoms if not the syndrome itself. Claims of the usefulness of depleting catecholamines with 6-hydroxydopamine (on the one hand) and modifying the environment in which young animals are brought up (rich andsocial contexts for development) are elaborated elsewhere in this book. The similarity of some of the features of hypertensive patients and those of youngsters with ADHD initiates interest in the "spontaneously hypertensive rat" (SHR). Encouraging the use of the SHR as a model are similarities in the DA and NA activity and reactivity. Further, there are similarities in between the responses of the SHR and children on learning schedules requiring the delay of response, - the delay of gratification that is characteristic of many ADHD children, and leads to impulsive responding in the SHR.
Lastly one should not overlook the possible lessons to be learned in the comparative approach, - namely to look at syndromes with more or fewer comorbid symptoms such as Tourette, Conduct-Disorder, Autism, Lesch.Nyhan and Phenylketonuria (3).
R.D. Oades2001-01-24Z2011-03-11T08:54:29Zhttp://cogprints.org/id/eprint/1255This item is in the repository with the URL: http://cogprints.org/id/eprint/12552001-01-24ZEvent-related potentials in autistic and healthy children on an auditory choice reaction time taskIntroduction: Childhood autism can occur in 5 out of 10,000 of the population. The condition covers problems of sensory modulation, comprehension and communication as it relates to both objects and people. Of the stages of information processing recorded in auditory event-related potentials (ERPs), reductions of N1 and P3 amplitude have been reported in many situations, but an increased P3 response to non-targets may represent difficulties in attributing differentially significance to some but not all stimuli..
Methods: Recordings were derived from midline and 4 lateral sites on the scalp of 7 children with autism and 7/13 healthy control children matched for age (median 139 vs. 135 months). A three-tone oddball paradigm was presented in a passive and active-task form (72% at 1 kHz, 14% at 0.5 kHz and 14% at 2.0 kHz)
Results:
a) Autistic subjects showed twice as many errors of omission and a higher beta criterion (signal detection) for targets.
b) For autistic subjects N1 latencies were shorter and N1 amplitude larger to deviants (especially nontargets).
c) However, subtraction of the ERPs in nontarget from target conditions showed that the processing negativity (PN) and especially the Negative difference (Nd) was smaller in autistic subjects.
d) In contrast the P3 amplitude (especially after the target) was smaller in autistic subjects.
e) Within autistic subjects the topography showed more early negativity after deviants at left frontal sites and more target induced late positivity at right parietal sites.
Conclusions: The ERPs of autistic children were more responsive to stimulus features (high frequency or deviance) and less responsive to the stimulus associations (target features). The ERPs also provide conflicting signs of neurodevelopment, -- precocious in the right-hemispheric emphasis for P3, but delayed in that P3 was not maximal at parietal sites.
R.D. OadesM.K. WalkerL.B. GeffenL.M. Stern2006-12-22Z2011-03-11T08:56:44Zhttp://cogprints.org/id/eprint/5302This item is in the repository with the URL: http://cogprints.org/id/eprint/53022006-12-22ZAssymetric rotational (circling) behavior, a dopamine-related asymmetry, preliminary findings in unmedicated and never-medicated schizophrenic patientsCircling behavior is one of the best understood behaviors in animals. It is, for the most part, dopaminergically mediated and related to asymmetry in dopaminergic activity between the left and right basal ganglia or left and right frontal cortex. As a rule, animals rotate toward the hemisphere with lower striatal dopaminergic activity. A direct technique to find human analogs of circling behavior was not available. We have developed an automated rotometer with which we can apply the circling rodent model to humans. Left-prone circling behavior (neglect of right-sided turning) was found in 10 unmedicated schizophrenic patients, whereas 85 normal controls demonstrated almost equal right and left turning. These preliminary results may suggest the presence of a dopaminergic asymmetry in some unmedicated schizophrenic patients; that is, right anterior subcortical or cortical structures of the brain may manifest a relative dopaminergic overactivity compared to left anterior structures in at least some unmedicated patients with schizophrenia.HS Bracha2001-04-25Z2011-03-11T08:54:37Zhttp://cogprints.org/id/eprint/1461This item is in the repository with the URL: http://cogprints.org/id/eprint/14612001-04-25ZAttention deficit disorder with hyperactivity (ADDH): the contribution of catecholaminergic activityIntroduction:
An attention deficit disorder with hyperactivity in children (ADDH, later known as ADHD) is now recognized in most countries, although diagnostic practices differ. Evidence is presented to show that the two cardinal symptoms of poor attentional performance and a high degree of motor activity may be functionally and causally separate.
Psychobiology:
Both attentional and motor-activity alterations are temporarily relieved in a proportion of subjects that respond to psychostimulants. Beneficial treatment decreases noradrenergic (NA) metabolism and normalizes variable levels of dopaminergic (DA) metabolism.
Clinical and animal models:
Parallels are drawn with other clinical syndromes arising from changed catecholaminergic activity (cf. Phenylketonuria, Tourette's syndrome, Lesch-Nyhan syndrome) and with behavioral interpretations of the result of damage to the dorsal noradrenergic bundle and dopaminergic VTA A10 nucleus (an animal model).
Biopsychological research directions:
Prognosis of ADDH subjects after treatment remains relatively poor. There may be a further defect of neurotransmitter metabolism in the ADDH syndrome. Research strategies are suggested based on the neurobiological correlates of the cognitive style of ADDH subjects and limbic/septal function in the animal model of the spontaneously hypertensive rat (SHR)
Topics:
1 . Psychostimulant response ... Catecholamines / Serotonin,
2 . Electrophysiological and behavioral indices
3 . Responses to monoaminergic agents ... Precursors, L-DOPA, amino acids, monoamine oxidase and others:
4 . Clinical comparisons ... Phenylketonuria, Tourette's syndrome, Lesch-Nyhan syndrome:
5 . Models ... spontaneously hypertensive rat, neurobiology of hypertension Noradrenaline (NA), Glutamate (Glu), Neuropeptide Y (NPY) & Angiotensin, Serotonin (5-HT), Dopamine (DA):
6 . Link between behavior and cognition ... the septum and conditioned blocking measures of selective attention.
R. D. Oades2001-05-29Z2011-03-11T08:54:39Zhttp://cogprints.org/id/eprint/1521This item is in the repository with the URL: http://cogprints.org/id/eprint/15212001-05-29ZThe development of food search behavior by rats: the effects of hippocampal damage and haloperidolIntroduction:
The aim of the study was to see if some of the effects of hippocampal brain damage on attention-related function may be mediated perhaps trans-synaptically in the dopamine (DA) system.
Methods:
A food search task in a 16-hole board was developed (based on search studies used to investigate the avian hippocampus (Oades 1976), but suitable for rodents). Food-deprived rats were required to locate 4 pellets located in 4 of 16 holes in an enclosed arena.
Three groups of animals were studied in 11 test sessions : - rats with bilateral hippocampal aspiration lesions, bilateral neocortical damage (overlying the hippocampus), and an unoperated group. Half of each group received haloperidol (DA D2 antagonist) and half saline before sessions 4 through 10. No injections were administered on the first three or the last test session.
Results:
1/ Animals with hippocampal damage visited more non-food holes (errors) than the controls, AND did not develop consistent sequences of food-hole visits as the other animals did.
2/ In unoperated controls haloperidol reduced the number of preferred sequences of food-hole visits, WITHOUT affecting the efficiency of performance as measured by the number of non-food-holes visited (i.e., the number of errors did not increase).
3/ Haloperidol treatment of those with hippocampal damage
reduced the number of non-food-hole visits (i.e. reduced the number of errors made in comparison to the saline treated animals with hippocampal damage).
Conclusions:
It is likely that hippocampal damage incurs increased DA activity elsewhere that for the search task is not adaptive and brings about an increase in the number of errors made. This contrasts with the normal development of a consistent sequence of food-hole visits (individually specific) - one form of working memory aid - that is disrupted by haloperidol and by hippocampal damage. Neuroleptic treatment of the hippocampal animals did not reinstate this preferred sequence but by dampening DA activity (reducing switching between alternatives, Oades 1985) improved attention-related search performance by decreasing the number of erros made.
This result may be seen post-hoc as a model for some of the functions disturbed in schizophrenia - where there is evidence for impaired medial temporal lobe function (hippoicampus, parahippocampal gyrus) and often hyper-active DA systems, sometimes ameliorated through neuroleptic treatment (see further studies by Lipska and Weinberger: e.g. Lipska et al. 1992; 1993, 1994, 1995; Sams-Dodd et al., 1997; Wood et al., 1997).
Oades Isaacson