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The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS−). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS−. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.
Dopaminergic genes are likely candidates for heritable influences on cigarette smoking. In an accompanying article, Lerman et al. (1999) report associations between allele 9 of a dopamine transporter gene polymorphism (SLC6A3-9) and lack of smoking, late initiation of smoking, and length of quitting attempts. The present investigation extended their study by examining both smoking behavior and personality traits in a diverse population of nonsmokers, current smokers, and former smokers (N = 1,107). A significant association between SLC6A3-9 and smoking status was confirmed and was due to an effect on cessation rather than initiation. The SLC6A3-9 polymorphism was also associated with low scores for novelty seeking, which was the most significant personality correlate of smoking cessation. It is hypothesized that individuals carrying the SLC6A3-9 polymorphism have altered dopamine transmission, which reduces their need for novelty and reward by external stimuli, including cigarettes.
Assesses the psychological risk associated with temporal lobe epilepsy and epilepsy in general and identifies other variables associated with an increased risk of psychopathology in epilepsy by reviewing 64 studies published since 1962. Methodological problems include the definition of epilepsy and the interictal state, sample selections, and the need for appropriate controls; until these problems are overcome, the behavioral ramifications of limbic system dysfunction in epilepsy will remain controversial. Greater methodological rigor in the field of epilepsy/psychopathology research will help assess whether animal studies of kindling of limbic structures with subsequent behavior changes have any validity for human psychopathology. There is a growing interest in the behavioral ramifications of neurological disease; however many factors outside of those that are biologically indigenous to the disorder play significant roles in the determination of psychopathology. A conceptual model (brain-, non-brain-, and treatment-related factors) is offered to help explain different proportions of variance for different behavior disorders. (6 p ref)
A pathology of brain serotonergic (5-HT) systems has been found in psychiatric disturbances, normal aging and in neurodegenerative disorders including Alzheimer's and Parkinson's disease. Despite the clinical importance of 5-HT, little is known about the endogenous factors that have neurotrophic influences upon 5-HT neurons. The present study examined whether chronic pain parenchymal administration of the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or NGF could prevent the severe degenerative loss of serotonergic axons normally caused by the selective 5-HT neurotoxin p-chloroamphetamine (PCA). The neurotrophins (5–12 micrograms/d) or the control substances (cytochrome c or PBS vehicle) were continuously infused into the rat frontoparietal cortex using an osmotic minipump. One week later, rats were subcutaneously administered PCA (10 mg/kg) or vehicle, and the 5-HT innervation was evaluated after two more weeks of neurotrophin infusion. As revealed with 5-HT immunocytochemistry, BDNF infusions into the neocortex of intact (non-PCA-lesioned) rats caused a substantial increase in 5-HT axon density in a 3 mm diameter region surrounding the cannula tip. In PCA-lesioned rats, intracortical infusions of BDNF completely prevented the severe neurotoxin-induced loss of 5-HT axons near the infusion cannula. In contrast, cortical infusions of vehicle or the control protein cytochrome c did not alter the density of serotonergic axons in intact animals, nor did control infusions prevent the loss of 5-HT axons in PCA-treated rats. NT-3 caused only a modest sparing of the 5-HT innervation in PCA-treated rats, and NGF failed to prevent the loss of 5-HT axon density. The immunocytochemical data were supported by neurochemical evaluations which showed that BDNF attenuated the PCA-induced loss of 5-HT and 5- HIAA contents and 3H-5-HT uptake near the infusion cannula. Thus, BDNF can promote the sprouting of mature, uninjured serotonergic axons and dramatically enhance the survival or sprouting of 5-HT axons normally damaged by the serotonergic neurotoxin PCA.
The hippocampus of the rat loses neurons with age, a loss which may eventuate in some of the functional impairments typical of senescence. Cumulative exposure to corticosterone (CORT) over the lifespan may be a cause of this neuronal loss, as it is prevented by adrenalectomy at mid- age. In this study, we demonstrate that prolonged exposure to CORT accelerates the process of cell loss. Rats were injected daily with sufficient CORT to produce prolonged elevations of circulating titers within the high physiological range. Animals treated for 3 months (chronic subjects) resembled aged rats in a number of ways. First, both groups had extensive and persistent depletions of CORT receptors in the hippocampus; in the case of chronic rats, no recovery of receptor concentrations occurred 4 months after the end of steroid treatment. Second, autoradiographic analysis revealed that the receptor depletion was due, in part, to a loss of CORT-concentrating cells, especially in the CA3 cell field. Remaining cells bound significantly less [3H]corticosterone than did those of control rats. Finally, analysis of size distributions of hippocampal cell bodies indicated that chronic subjects lost neurons of the same size as those lost in the aged hippocampus. Furthermore, chronic subjects also had increased numbers of small, darkly staining cells of CA3; these corresponded in size to the dark glia whose numbers increase in the aged hippocampus, and which are thought to infiltrate in response to neuronal damage or destruction. Thus, this study supports the hypothesis that cumulative exposure to CORT over the lifespan may contribute to age-related loss of neurons in the hippocampus, and that prolonged stress or exposure to CORT accelerates this process.
This book describes the application of single photon emission tomography (SPET) to neuroactivation imaging in particular and neuroimaging in general. Protocols for SPET, neuroactivation and neuroimaging are described in detail and results are given and discussed on the basis of clinical material and case histories. Normal functional anatomy is correlated with data from MRI. High resolution cerebral blood flow (CBF) imaging is described with the use of SPET technology. Split dose CBF imaging is also mentioned, for activation studies in a variety of normal and diseased states which include the dementias (AIDS, Alzheimer's disease and multi-infarction dementia), cerebrovascular disease, depression, schizophrenia, obsessive compulsive disorders, movement disorders (Parkinson's disease, Gilles de la Tourette syndrome, Huntingdon's chorea, Sydenham's chorea), epilepsy and tumours. Examples of motor, frontal and visual activation studies are also given.
Forced normalisation is a paradoxical relationship between seizure activity and behavioural problems. A 20-year-old man with recurrent refractory tonic-clonic epilepsy experienced forced normalisation while on medication with multiple anti- epileptic drugs (valproate sodium, carbamazepine and topiramate). A reduction in the seizure burden correlated with sudden behavioural changes manifesting with aggressive outbursts and violence. The case may help clarify the mechanism of forced normalisation while providing some helpful hints regarding the diagnosis and treatment of symptoms observed in recurrent refractory seizures.
Introduction:
Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible alternative to electroconvulsive therapy for the treatment of selected patients with depression, bipolar affective disorder and schizophrenia. The aim of this study was to evaluate the evidence for the effectiveness of rTMS in mood disorders and schizophrenia.
Methods:
Studies were identified using MEDLINE (1966 to January 2000), EMBASE/Excerpta Medica (1980 to January 2000), Biological Abstracts and Index to Scientific and Technical Proceedings. A number of biomedical and TMS related websites were also searched. We estimated the number needed to treat to show beneficial effect of rTMS when compared with the placebo controlled group.
Results:
Seven controlled trials of rTMS depression were identified. Five of these were suitable for meta-analysis and show a beneficial effect of rTMS compared to placebo, with a number needed to treat of 2-3 with a 95 % confidence interval 1.6 to 4.0, total; 81 patients. A single trial of rTMS has also been performed in mania, which shows a beneficial effect of right hemisphere stimulation when compared with left hemisphere stimulation. A controlled trial in schizophrenia failed to show any benefit of rTMS.
Discussion:
rTMS has demonstrable beneficial effects in depression. The extent and the duration of the anti-depressant effect of rTMS has yet to be defined. There now needs to be randomized controlled trials to compare rTMS directly with standardized electroconvulsive therapy in order to take this subject forward. With regard to the treatment of other mood disorders and schizophrenia, we are at an early stage in the assessment of further studies that are needed to examine any potential role for rTMS.
Michael Trimble and Bettina Schmitz have assembled a multi-national team of experts to review the most recent findings and explore the interface between epilepsy and behaviour disorders. They begin by looking at the classifications available and examine how adequate they are for defining the subtleties of behavioural changes in patients with neurological disorders. Coverage is broad-ranging, from related cognitive problems, the biological underpinnings and pseudoseizures, to clinical aspects and treatment issues. There has been a great deal of research in this area over recent years, but limited published reviews. This timely book covers the practical implications of ongoing research, and offers both a diagnostic and management perspective. It will be essential reading for all professionals engaged in the treatment of epileptic patients.
Michael Trimble and Bettina Schmitz have assembled a multi-national team of experts to review the most recent findings and explore the interface between epilepsy and behaviour disorders. They begin by looking at the classifications available and examine how adequate they are for defining the subtleties of behavioural changes in patients with neurological disorders. Coverage is broad-ranging, from related cognitive problems, the biological underpinnings and pseudoseizures, to clinical aspects and treatment issues. There has been a great deal of research in this area over recent years, but limited published reviews. This timely book covers the practical implications of ongoing research, and offers both a diagnostic and management perspective. It will be essential reading for all professionals engaged in the treatment of epileptic patients.
A comprehensive review of current research on synaptic plasticity.
The traditional model of synapses as fixed structures has been replaced by a dynamic one in which synapses are constantly being deleted and replaced. This book, written by a leading researcher on the neurochemistry of schizophrenia, integrates material from neuroscience and cell biology to provide a comprehensive account of our current knowledge of the neurochemical basis of synaptic plasticity.
The book presents the evidence for synaptic plasticity, an account of the dendritic spine and the glutamate synapse with a focus on redox mechanisms, and the biochemical basis of the Hebbian synapse. It discusses the role of endocytosis, special proteins, and local protein synthesis. Additional topics include volume transmission, arachidonic acid signaling, hormonal modulation, and psychological stress. Finally, the book considers pharmacological and clinical implications of current research, particularly with reference to schizophrenia and Alzheimer's disease.
Bradford Books imprint
Objective: Decreases in prefrontal electroencephalogram (EEG) cordance that are detectable as early as 48 hours after the start of medication have been related to clinical outcome in treatment trials for major depressive disorder. The relationship between brain changes during the placebo lead-in phase and medication treatment outcome is unknown. The authors hypothesized that decreases in prefrontal cordance during the placebo lead-in phase would be associated with better clinical outcome in subjects treated with antidepressants. Method: Data were pooled examining 51 adults with major depressive disorder from two independent double-blind placebo-controlled trials. A 1-week single-blind placebo lead-in phase preceded 8 weeks of randomized treatment with medication (fluoxetine 20 mg or venlafaxine 150 mg) or placebo. The authors obtained quantitative EEG cordance measures at baseline and at the end of the placebo lead-in period. Relationships between regional cordance changes at the end of the placebo lead-in period and clinical outcome (the final 17-item Hamilton Rating Scale for Depression scores) were examined using multiple linear regression analysis. Results: As hypothesized, decreases in prefrontal cordance during the placebo lead-in period were associated with lower final Hamilton depression scale scores in subjects randomly assigned to medication. Prefrontal changes explained 19% of the variance in final Hamilton depression scale scores. Conclusions: Neurophysiological changes during a placebo lead-in period may serve as nonpharmacodynamic biomarkers of eventual treatment outcomes in clinical trials for major depressive disorder.
This book presents the anatomical systems that take part in the scientific and clinical study of emotional functions and neuropsychiatric disorders. It discusses the limbic system (the cortical and subcortical structures in the human brain involved in emotion, motivation, and emotional association with memory) at length and how this is no longer a useful guide to the study of psychiatric disorders. The book provides an understanding of brain anatomy, with an emphasis on the new anatomical framework which has emerged during the last quarter century. The goal is to provide the reader will develop an understanding of the gross anatomical organisation of the human forebrain. 1) The book provides an understanding of brain anatomy, with an emphasis on the new anatomical framework which has emerged during the last quarter century 2) The reader will develop an understanding of the gross anatomical organisation of the human forebrain 3) The origin and meaning of terms such as ventral stiatum, ventral pallidum and cortico-subcorticalreentrant circuits, which are increasingly familiar terms in basic and clinical neuroscience, are discussed 4) The extended amygdala and its place in the functional-anatomical organisation of the brain, is discussed 5) The greater limbic lobe and its particular relevance in neuropsyciatric disorders, is presented 6) The role of functional neurosurgery in the treatment of neuropsychiatric disorders is presented 7) The challenges that lie ahead in the field of deep brain stimulation are discussed 8) The book included 2 dvd's of brain dissection, particularly useful for the course instructor.
Depression is a frequent psychiatric symptom in epilepsy and has been related to epilepsy of temporal origin, especially of left-sided foci. No study differentiated the precise localization of the epileptogenic lesion within the temporal lobe. Regarding this issue, we evaluated depression assessed by the Beck Depression Inventory in 60 patients with temporal lobe epilepsy, with particular consideration of morphological abnormalities within the temporal lobe (mesial temporal sclerosis (MTS) versus neocortical lesions) and lateralization of the lesion. Multivariate analyses indicated significant higher depression scores in MTS independent of the lateralization of the lesion. Depression was a good indicator for MTS but not vice versa. Hence, MTS can be discussed as a predisposing factor for the development of mood disorders in focal epilepsy.
This study characterizes the rate of current Axis I DSM-IV disorders using a brief standardized psychiatric interview procedure, the Mini International Neuropsychiatric Interview (v5.0) (MINI), and determined the validity of MINI diagnoses of current depressive episodes to the research standard (Structured Clinical Interview for DSM-IV Disorders [SCID]). One hundred seventy-four patients with chronic epilepsy from five tertiary medical centers were interviewed using the MINI and the mood disorders module of the SCID. Current Axis I disorders were evident in one-half the sample (49%), with prevalent anxiety (30.4%) and mood (21.8%) disorders. Major depressive episode was the most common individual diagnosis (17.2%). Concordance was high between the MINI and SCID for diagnoses of current depression, especially for major depression. Of those with current major depression, less than one-half were treated with antidepressant medications. Current Axis I DSM-IV diagnoses can be effectively and accurately identified in clinical settings using shorter standardized psychiatric interview techniques. Issues regarding recognition and treatment of psychiatric morbidity in epilepsy are discussed.
The monoamine theory has implicated abnormalities in serotonin and norepinephrine in the pathophysiology of major depression and bipolar illness and contributed greatly to our understanding of mood disorders and their treatment. Nevertheless, some limitations of this model still exist that require researchers and clinicians to seek further explanation and develop novel interventions that reach beyond the confines of the monoaminergic systems. Recent studies have provided strong evidence that glutamate and other amino acid neurotransmitters are involved in the pathophysiology and treatment of mood disorders. Studies employing in vivo magnetic resonance spectroscopy have revealed altered cortical glutamate levels in depressed subjects. Consistent with a model of excessive glutamate-induced excitation in mood disorders, several antiglutamatergic agents, such as riluzole and lamotrigine, have demonstrated potential antidepressant efficacy. Glial cell abnormalities commonly associated with mood disorders may at least partly account for the impairment in glutamate action since glial cells play a primary role in synaptic glutamate removal. A hypothetical model of altered glutamatergic function in mood disorders is proposed in conjunction with potential antidepressant mechanisms of antiglutamatergic agents. Further studies elucidating the role of the glutamatergic system in the pathophysiology of mood and anxiety disorders and studies exploring the efficacy and mechanism of action of antiglutamatergic agents in these disorders, are likely to provide new targets for the development of novel antidepressant agents.
Part One * Consciousness and the Scientific Observer * Proposals and Disclaimers Part Two * Neural Darwinism * Reentrant Signaling * Perceptual Experience and Consciousness Part Three * Memory as Recategorization * Time and Space: Cortical Appendages and Organs of Succession * Concepts and Presyntax Part Four * A Model of Primary Consciousness * Language * Higher-Order Consciousness * The Conscious and the Unconscious * Diseases of Consciousness Part Five * Physics, Evolution, and Consciousness: A Summary * Philosophical Issues: Qualified Realism * Epilogue
We provide a comprehensive review of the neurobiological basis of attention-deficit/hyperactivity disorder. This summary was accomplished by a review of research in three areas: neuroimaging, genetics, and neurochemistry. Additionally, we also discuss a newer conceptualization of the disorder. Although none of the current findings present a unified picture of the pathophysiology of the disorder, the vast array of studies reviewed do highlight CNS abnormalities that, when taken together, present a convincing argument that the cause clearly resides within the realm of developing brain.
