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Violent behavior is associated with antisocial personality disorder and to a lesser extent with schizophrenia. Neuroimaging studies have suggested that several biological systems are disturbed in schizophrenia, and structural changes in frontal and temporal lobe regions are reported in both antisocial personality disorder and schizophrenia. The neural substrates that underlie violent behavior specifically and their structural analogs, however, remain poorly understood. Nor is it known whether a common biological basis exists for aggressive, impulsive, and violent behavior across these clinical populations. To explore the correlates of violence with brain structure in antisocial personality disorder and schizophrenia, the authors used magnetic resonance imaging data to investigate for the first time, to the authors' knowledge, regional differences in cortical thickness in violent and nonviolent individuals with schizophrenia and/ or antisocial personality disorder and in healthy comparison subjects. Subject groups included right-handed men closely matched for demographic variables (total number of subjects=56). Violence was associated with cortical thinning in the medial inferior frontal and lateral sensory motor cortex, particularly in the right hemisphere, and surrounding association areas (Brodmann's areas 10, 11, 12, and 32). Only violent subjects with antisocial personality disorder exhibited cortical thinning in inferior mesial frontal cortices. The biological underpinnings of violent behavior may therefore vary between these two violent subject groups in which the medial frontal cortex is compromised in antisocial personality disorder exclusively, but laminar abnormalities in sensorimotor cortices may relate to violent behavior in both antisocial personality disorder and schizophrenia.

Personality is known to influence cognitive and affective functioning as well as the risk of psychiatric disorders. Exploration of the neurobiological correlates of personality traits has the potential to enhance understanding of their significance in development of related psychopathological states. The authors examined the association between individual differences in neuroticism and brain activity in response to threat of electric shocks. Fourteen right-handed healthy men underwent functional MRI during a 5-min experiment that involved repeated presentations of two 30-s alternating conditions. In 1 of these conditions, subjects were told to expect mild but painful electric shocks; there was no possibility of receiving shocks in the other condition. The results revealed that neuroticism correlated positively with the ratings of fear of shock and negatively (indicating suppression) with brain activity from safe to shock conditions in the anterior and posterior cingulate, superior/middle temporal gyrus extending to the hippocampus, precuneus, putamen, thalamus, and middle occipital gyrus. The observations support recent psychophysiological research that has demonstrated reduced processing of pain in subjects with higher levels of neuroticism, especially the anxiety component of this trait. Keywords: individual differences, neuroticism, anxiety, fMRI, brain

Sexually dimorphic cognitive performance in men (n = 42) and women (n = 42) was related to testosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin, measured in 10-ml blood samples collected between 0900 and 1030 and. among women, during the follicular phase of the menstrual cycle. Significant sex differences favored men on spatial tasks (Mental Rotation and Judgment of Line Orientation) and on an inhibition task and favored women on a verbal task (category fluency). However, there were no significant relationships between any of the hormones and cognitive performance, suggesting that there are few, if any, consistent, substantial relationships between endogenous, nonfluctuating levels of gonadal hormones or gonadotropins and these cognitive abilities in men or women.

Objective: The authors investigated the structural brain correlates of antisaccade performance. Method: Magnetic resonance imaging was used to measure the volumes of the prefrontal, premotor, sensorimotor, and occipitoparietal cortices as well as the caudate, thalamus, cerebellar vermis, and cerebrum in 20 first-episode psychosis patients and 18 healthy comparison subjects. Antisaccades were recorded by using infrared oculography. Results: Groups significantly differed in terms of antisaccade error rate and amplitude gain and tended to differ in terms of latency but not brain region volumes. Premotor cortex volume predicted antisaccade error rate among comparison subjects. In the patient group, caudate volume was related to latency and amplitude gain. Negative symptoms, independent of structural volumes, predicted error rate. Conclusions: These findings point to altered structure-function relationships in first-episode psychosis.

Objective: The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis. Method: Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniforrn disorder (N-167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment. Results: An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine. Conclusions: Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.

•A detail review on regular clocking schemes in Quantum dot Cellular Automata (QCA) are discussed.•Various regular clocking scheme in QCA are compared and establish a relation based on their performance.•This paper shows why QCA clocking should be symmetric and regular.

Objective: The authors investigated the modulating effects of biological sex and age on regional decreases in cortical gray matter and increases in subarachnoid CSF in 25 patients with chronic schizophrenia and 28 group-matched healthy comparison subjects. Method: Computational cortical pattern-matching methods were employed to measure the local proportions of gray matter and subarachnoid CSF at thousands of homologous cortical surface locations in each subject using high-resolution magnetic resonance images. Principal-component analysis reduced tissue proportion values obtained at each cortical surface point into component scores for each subject. Principal-component analysis scores were used as dependent variables in statistical analyses that included diagnosis, age, and sex as predictor variables. To reveal more regional changes in tissue proportions, statistical differences in gray matter and CSF were compared at each cortical surface location and mapped in three dimensions. Results: Principal-component analyses revealed main effects of diagnosis, sex, and age for the CSF increases seen in the schizophrenia patients, in male subjects, and in association with age. Significant diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-sex-by-age interactions were also observed, revealing CSF increases in male patients at younger ages. Statistical maps showed regional increases in subarachnoid CSF in association with the above effects. For cortical gray matter measurements, only main effects of age were observed. Conclusions: Regionally specific increases in sulcal and subarachnoid CSF occur during adulthood and appear prematurely in male schizophrenia patients. Cortical gray matter reductions show aging effects but are below the threshold of significance in schizophrenia.

Objective: Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. Method: Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. Results: Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%). Conclusions: As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.

Objective: The inferior parietal Iobule is a heteromodal association cortical region that has been implicated in the pathophysiology of schizophrenia. Inferior parietal Iobule gray matter volumes have been shown to differ between healthy male and female subjects, with male subjects having larger left volumes. The authors sought to determine whether these volumetric sex differences also exist in patients with schizophrenia. Method: The authors used magnetic resonance imaging to measure inferior parietal Iobule volumes of 15 pairs of male and female schizophrenic subjects who were individually matched to each other and to 15 pairs of healthy male and female subjects. Results: Male schizophrenic patients exhibited a reversal of the normal left-greater-than-right male asymmetry in this region and had left inferior parietal Iobule gray matter volumes that were significantly smaller than those of healthy male subjects. Female schizophrenic patients did not differ significantly from healthy female subjects in left or right inferior parietal Iobule volume or in asymmetry. Conclusions: This study provides further evidence of brain morphology sex differences in schizophrenia that possibly contribute to the differential clinical disease expression in men and women.

Objective: The authors tested the hypothesis that the use of an atypical drug, clozapine, for patients with schizophrenia is related to less impairment in information processing deficits (assessed by prepulse inhibition of the startle response) than is the use of typical antipsychotics. Method: Two groups of schizophrenic patients - receiving either clozapine or a range of typical antipsychotics - were tested for prepulse inhibition (a reduction in response to a startling stimulus, if preceded briefly by a weak, nonstartling stimulus; measured at prepulse-to-pulse intervals of 30 msec, 60 msec, and 120 msec) of the acoustic startle response and compared with a group of healthy volunteers. Results: Patients receiving typical antipsychotics showed less prepulse inhibition with 30-msec and 60-msec prepulse trials than did comparison subjects. Clozapine-treated patients showed normal levels of prepulse inhibition. Conclusions: Clozapine is superior to typical antipsychotics in normalizing prepulse inhibition, presumably because of its pharmacological effects on prefrontal regions of the brain or its effects on a broader range of neuroreceptors.

Objective: Down's syndrome is associated with structural brain abnormalities and language deficits. The aim of this study was to investigate whether the superior temporal gyrus and the planum temporale, both parts of the anatomic substrate for language, are abnormal in Down's syndrome. Method: The authors examined volumetric magnetic resonance imaging (MRI) measures of the superior temporal gyrus and the planum temporale for 17 community-dwelling patients with Down's syndrome and 17 matched healthy comparison subjects. For the subjects with Down's syndrome, the correlations of the superior temporal gyrus and planum temporale volumes with performance on tests of language function were examined. Results: The planum temporale volume of the patients with Down's syndrome was smaller than that of the healthy subjects, even after differences in whole brain volume were controlled for. The volume of the superior temporal gyrus in the Down's syndrome patients was proportionally similar to that of the comparison group. For the subjects with Down's syndrome, neither superior temporal gyrus nor planum temporale volume was significantly correlated with performance on language tests after total brain volume was controlled for. Conclusions: In Down's syndrome, planum temporale volume may be selectively smaller than normal, although the effect of this volume deficit on language is not clear.

Objective: The nature and time course of temporal lobe abnormalities in psychotic illness remain controversial. Confounds include disease chronicity, gender, and handedness. The present study investigated temporal substructures in right handed male patients experiencing their first episode of psychotic illness. Method: Magnetic resonance imaging scans were obtained for 25 minimally treated patients experiencing their first psychotic episode and 16 healthy comparison subjects. Group differences in volumes of the hippocampus, amygdala, planum temporale, and Heschl's gyrus were tested. Results: The patients had smaller bilateral hippocampal and left planum temporale volumes than the comparison subjects. Paranoid and nonparanoid patients differed in left amygdala volume. Conclusions: The authors conclude that bilateral hippocampal and left planum temporale abnormalities are present near the onset of psychosis. (Am J Psychiatry 2002; 159:1232-1234)

Over the last decade, the concept of 'recovery' has become a common thread in behavioral health care; providers are expected to routinely include recovery as a component of their treatment [...]

Patients entering treatment for mental illness and substance use disorders often experience deficits in at least one domain of cognitive functioning (e.g., attention, memory, verbal fluency, cognitive flexibility). Significant gray [...]

Ethanol’s complete miscibility in water makes it a widely used solvent in various applications, such as organic compound synthesis, paint manufacture, chromatography, and cosmetics preservation. Studies suggest that ethanol’s concentration at interfaces can be higher than in the bulk due to its amphiphilic nature, especially at lower concentrations, making it a surface-active agent. Accordingly, ethanol plays a crucial role in controlling the emulsion stability, foam formation, heat transfer, and coating adhesion. However, the precise concentration ranges up to which ethanol’s surface activity dominates its interfacial properties, and the underlying molecular mechanism is not fully understood in the literature. In this context, our foamability experiments, coupled with film stability experiments conducted via ethanol drop impact on varying concentration ethanol–water mixture pools, indicate that the surface-active nature of ethanol is observed up to a maximum of 10% molar ethanol concentration in water. We next employ all-atom molecular dynamics simulations to reveal that the surface tension and other interfacial properties are most significantly affected only up to the molar concentration in the range of 0–10% of ethanol in water. This observation is further supported by free energy analyses, indicating that the stabilization free energy of an ethanol molecule at the interface becomes comparable to that in the bulk region beyond this concentration range. The transition from surface-active to a behavior resembling a homogeneous solution occurs when the molar concentration of ethanol in water exceeds 10%. This transition is attributed to distinctive alterations in the number and strength of ethanol–water hydrogen bonds. These findings provide valuable insights into the interfacial molecular structure, which can be suitably exploited to modulate interfacial properties and dynamic behavior in a wide array of industrial and scientific applications.

A paradigm shift needs to occur in the way that we view and treat behavioral health conditions so that we can improve clinical outcomes and recovery of patients seeking mental [...]

We are well into the second decade of the 21st century. On almost a weekly basis, new discoveries gleaned from advanced neuroimaging techniques, rigorous clinical trial outcomes data, and the [...]

Objective: People with schizophrenia exhibit abnormalities in brain structure, often in the left hemisphere. Disturbed structural lateralization is controversial, however, and effects appear mediated by gender. The authors mapped differences between schizophrenic and normal subjects in gyral asymmetries, complexity, and variability across the entire cortex. Method: Asymmetry and shape profiles for 25 schizophrenic patients (15 men) and 28 demographically similar normal subjects (15 men) were obtained for 38 gyral regions, including the sylvian fissure and temporal and postcentral gyri, by using magnetic resonance data and a novel surface-based mesh-modeling approach. Cortical complexity was examined for sex and diagnosis effects in lobar regions. Intragroup variability was quantified and visualized to assess regional group abnormalities at the cortical surface. Results: The patients showed greater variability in frontal areas than the comparison subjects. They also had significant deviations in gyral complexity asymmetry in the superior frontal cortex. In temporoparietal regions, significant gyral asymmetries were present in both groups. Sex differences were apparent in superior temporal gyral measures, and cortical complexity in inferior frontal regions was significantly greater in men. Conclusions: Cortical variability and complexity show regional abnormalities in the frontal cortex potentially specific to schizophrenia. The results indicate highly significant temporoparietal gyral asymmetries in both diagnostic groups, contrary to reports of less lateralization in schizophrenia. Substantially larger study groups are necessary to isolate smaller deviations in surface asymmetries, if present in schizophrenia, suggesting their diagnostic value is minimal. (Am J Psychiatry 2001; 158:244-255)

Objective: There is some evidence of thalamic abnormalities in schizophrenia. This study investigated thalamic volumes in patients experiencing their first episode of psychosis and non-psychotic comparison subjects. Method: Magnetic resonance imaging scans were obtained for 38 patients and 29 comparison subjects. Patients' symptoms were rated by research psychiatrists using the Positive and Negative Syndrome Scale. Results: Thalamic volumes were smaller in patients than in comparison subjects. There were no significant correlations between thalamic volumes and symptom scores. Conclusions: Thalamic abnormalities are present close to the onset of psychosis. (Am J Psychiatry 2001; 158:116-118)

Objective: Evidence suggests that patients with schizophrenia have a deficit in 'theory of mind,' i.e., interpretation of the mental state of others. The authors used functional magnetic resonance imaging (MRI) to investigate the hypothesis that patients with schizophrenia have a dysfunction in brain regions responsible for mental state attribution. Method: Mean brain activation in five male patients with schizophrenia was compared to that in seven comparison subjects during performance of a task involving attribution of mental state. Results: During performance of the mental state attribution task, the patients made more errors and showed less blood-oxygen-level-dependent signal in the left inferior frontal gyrus. Conclusions: To the authors' knowledge, this is the first functional MRI study to show a deficit in the left prefrontal cortex in schizophrenia during a socioemotional task. (Am J Psychiatry 2000; 157:2040-2042)

Objective: Structural magnetic reasonance imaging (MRI) studies that focus on first-episode psychosis avoid some common confounds, such as chronicity of illness, treatment effects, and long-term substance abuse. However, such studies may select subjects with poor short-term treatment response or outcome. In this study, the authors focus on structural brain abnormalities in never or minimally treated patients who underwent MRI scanning early in their first episode of psychosis. Method: The authors examined 37 patients (13 medication naive, 24 previously treated) who were experiencing their first episode of psychosis; the mean duration of symptoms was short (31 weeks). These patients were comparable in age, gender, handedness, ethnicity, and parental socioeconomic status to a group of 25 healthy comparison subjects. A three-dimensional, inversion recovery prepared, fast spoiled gradient/recall in the steady state scan of the whole brain that used 1.5-mm contiguous sections was performed to acquire a [T.sub.1]-weighted data set. Human ratings of volumetric measurement of brain structures were performed with stereological techniques on three-dimensional reconstructed MRIs. Results: The patient group had significant deficits in cortical gray matter, temporal lobe gray matter, and whole brain volume as well as significant enlargement of the lateral and third ventricles. Structural deviations were found in both treatment-naive and minimally treated subjects. No relationships were found between any brain matter volumes and positive or negative symptoms. Conclusions: Structural brain abnormalities were distributed throughout the cortex with particular decrement evident in gray matter. This feature is consistent with altered cell structure and disturbed neuronal connectivity, which accounts for the functional abnormality of psychosis.

The ability of functional magnetic resonance imaging to provide high quality imaging of brain function without the need for radioactive tracers is rapidly making it the technique of choice for [...]

Surfactants are amphiphilic additives primarily used to reduce the surface tension of water and manipulate its wettability on various surfaces. Recent reports suggest that volatile surfactants, such as aroma molecules, diffuse more quickly to the interface from the vapor-phase than conventional surfactants typically used in the aqueous phase. The ability to adsorb from the vapor phase, in addition to their use as cosurfactants, expands the potential applications of volatile surfactants, particularly in situations where adding surfactants from the liquid phase is difficult. Here, we present a molecular level understanding of the adsorption kinetics of linalool, a common aroma molecule, on the water interface using molecular dynamics simulations. We note that the value of surface tension while adsorption from vapor and liquid phases is dependent only on the surface coverage. A minimum surface tension of 32 ± 1.8 mN/m is obtained in both cases at a maximum surface coverage of 4.88 μmol/m2at 300 K. We observe the extent of decrease of the H-bonds between linalool–water and linalool–linalool molecules at various surface coverages to explain the mechanism of surface tension reduction. We solve Gibb’s adsorption equation to establish a correlation between the surface coverage of linalool and the corresponding bulk concentration in experiments. We investigate the free energy profile of linalool’s adsorption behavior at different surface coverages and temperatures. Our report suggests that linalool adsorption onto the water interface is an enthalpy-driven process primarily dependent on the strength of the interaction between the hydroxyl group of linalool and water molecules. These insights are crucial for selecting a suitable aroma molecule for various applications that target the vapor-phase adsorption mechanism.

A survey of in-patients and staff at an acute psychiatric hospital revealed that as far as the patients are concerned having visitors was the most important aspect of hospital care. This was followed by walking in the grounds and spending a day or a weekend at home. The nurses rated speaking to the nurses and drug treatment as the most important aspects, with a weekend at home in third place.

This study assessed the neural correlates of the effects of rivastigmine, a CNS-selective cholinesterase inhibitor, given as an add-on therapy to antipsychotics-treated patients with schizophrenia who displayed moderate cognitive impairments, using functional magnetic resonance imaging (fMRI) during a sustained attention task. The study used a placebo-controlled, randomized, double-blind longitudinal design. Twenty patients stable on antipsychotics, 11 assigned to receive rivastigmine and 9 to receive placebo, underwent fMRI and clinical assessments at baseline and after 12 weeks. The fMRI task used a periodic block design and involved 3 conditions rest, detecting a nonzero number ("nonzero" condition), and detecting a specific number ("specific number" condition) among a series of 6-digit numbers. Online data (via button presses) were acquired on both occasions. Behavioral results showed a trend (P= 0.075) for the rivastigmine-treated patients to have more correct responses and the placebo group to have fewer correct responses at 12 weeks compared with baseline in the "nonzero" condition. There was also an increase in regional brain activity in the cerebellum in the rivastigmine group at 12 weeks in both conditions, which was only partially explained by change in behavioral measures; no change was observed in the placebo group. Our results showed that rivastigmine treatment increased cerebellar activity and influenced attentional processes.

The first episode of schizophrenia represents a transition from a premorbid to a morbid state. Studying the first episode of schizophrenia is useful since it is devoid of the confounds of chronicity and long-term medication. It is also likely to direct us to the core deficits of the illness. Studies on first-episode schizophrenia suggest a generalized neuropsychologic impairment, but that memory, attention and executive function are more severely impaired. Support for a neurodevelopmental model of neuropsychologic impairment in schizophrenia is derived from the findings that much of the neuropsychologic impairment is present by illness onset, that neuropsychologic impairment remains stable over time and that there is a weak relation between duration of untreated psychosis and neuropsychologic impairment. However, neuropsychologic impairment is moderated by neuroleptic treatment, with some evidence that atypical antipsychotics may have some beneficial effects over conventional antipsychotics. The causal mechanisms of brain abnormality in the temporal and frontal lobes appear to be different to that of neuropsychologic impairment in schizophrenia. The observation that there is a brain volume decrement over time and that the rate of change is higher during the first 5 years would be consistent with a neurodegenerative model of schizophrenia. At the same time, the basal ganglia are vulnerable to volumetric increase secondary to neuroleptic medication. Understanding the roles of the neurodevelopmental and neurodegenerative models of schizophrenia is important in deciding intervention strategies.

ABSTRACTResearch has shown that many of the long-term deficits that are observable in schizophrenia populations are present prior to the emergence of psychotic symptoms. Recent research suggests schizophrenia has a “prodromal” period, whereby significant changes from premorbid functioning can be observed. Accurate classification of this period could have far-reaching implications for schizophrenia prevention. This article aims to provide an indepth evaluation of the perceived benefits of vulnerability marker research in this unique phase. It is hoped that identification of such markers may improve the predictive potency of prodromal criteria, and perhaps pave the way for future screening and primary prevention strategies.

AbstractThe study of social cognition in psychiatric disorders has become increasingly popular in recent years. This is due to the its proposed link to social functioning and the inability of general neurocognitive skills to explain the spectrum of impairments observed in patients. This article reviews research into two of the processes thought to underlie social cognition (emotion perception and theory of mind) in schizophrenia and autism. This is followed by a look at neuroimaging studies and their efforts to localize the neural correlates of emotion perception and theory of mind in the two disorders. We concluded that while a specific impairment in emotion perception and theory of mind skills cannot be generalized to all individuals with autism and schizophrenia, there are subpopulations that have lingering deficits of social cognition tasks. Neuroimaging work consistently points to the involvement of the fusiform gyrus and amygdala in emotion processing, while the medial prefrontal and frontal cortex are implicated in tasks invoking theory of mind. We propose that deficits of social cognition may benefit from cognitive remediation therapy and pharmacological cognitive enhancers.

The aim of this study was to investigate the neural correlates of affect processing in depressed anhedonic patients and healthy controls. Whole brain functional magnetic resonance imaging scans were obtained from seven females with a diagnosis of chronic unipolar major depression and high levels of anhedonia, and seven healthy females, while they were presented with positive valence and neutral images. Patients, compared to controls, showed decreased activation in medial frontal cortex, and increased activation in inferior frontal cortex, anterior cingulate, thalamus, putamen and insula. Reduced activation in medial frontal cortex may underlie abnormal positive affect processing in patients. Increases in neural activation in putamen and thalamus, previously found in transient sadness, and anterior cingulate could point to an involvement of these structures in anhedonia.

Incidents of aggression and violence in severe mental disorders like psychosis, personality disorders and substance misuse disorders are higher than in the general population. Recent advances in neuroimaging techniques may help to predict violent behaviour in mentally ill individuals and to identify anomalies in brain functioning that may be amenable to treatment.

Structural brain abnormalities are consistently reported in schizophrenic subjects but the etiology of these abnormalities remains unclear. We tested the contribution of genetic predisposition and obstetric complications to the structural brain abnormalities found in schizophrenic probands and their relatives. MRI scans were carried out on 35 schizophrenic probands from families multiply affected with the disorder, and 63 of their unaffected relatives, including 10 parents who appeared to transmit genetic risk to their children; as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives; and finally 68 controls. Volumetric measurements of whole brain, lateral ventricles, third ventricle, cerebellum, and temporal lobes were completed for each subject. The impact of obstetric complications on brain structure was assessed across the gradient of presumed genetic predisposition. Both groups of schizophrenic probands displayed enlargement of the lateral and third ventricles, and there was a gradient of ventricular enlargement amongst the unaffected relatives in proportion to their likelihood of carrying schizophrenic genes. Ventricular enlargement was largely confined to males in both probands and unaffected relatives. Obstetric complications were associated with ventricular enlargement only in the familial probands. Non-familial probands displayed reduced volume of the temporal lobes bilaterally. In families with several schizophrenic members, ventricular enlargement is a marker for genetic liability, particularly in males. Individuals inheriting the susceptibility to schizophrenia appear particularly prone to develop ventricular enlargement in response to obstetric complications. © 2002 Wiley-Liss, Inc.

Alzheimer's disease is common in the elderly and causes tremendous distress to patients and their carers. With the advent of newer pharmacological treatments, significant improvement in the early diagnosis of Alzheimer's disease is required. This article examines the usefulness of neuroimaging techniques to predict Alzheimer's disease in prediagnosis individuals.

According to the World Development Report 1993 one third of people with a mental illness suffer from a depressive disorder. There is a need for early diagnosis and effective treatment in order to limit the impact on patients' lives. Knowledge gained from brain imaging research may help to improve our understanding and treatment of depression.

Schizophrenia is a serious mental illness that affects 1% of the population. It is beset with problems of diagnosis and difficulties in assessing treatment. Neuroimaging has long contributed to our understanding of schizophrenia but recent developments suggest it may ultimately play a practical role in its early detection and management.

Conjunctionanalysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a go-stimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared “inhibitory” neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices. Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices. Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices. On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflectinga left frontoparietal specialization for response selection.

We used multislice functional magnetic resonance imaging (fMRI) to investigate the association between behavioral and neurophysiological measures of working memory task performance in 20 right-handed male healthy volunteers. Images were acquired over a 5-min period at 1.5 Tesla. We used a periodic design, alternating 30-s blocks of the “n-back” working memory task with 30-s blocks of a sensorimotor control task to activate verbal working memory systems. The power of functional response to the task was estimated by sinusoidal regression at each voxel. The relationship between power of fMRI response and mean reaction time over all 11 working memory trials was explored by multiple regression, with age and mean reaction time to the control task as covariates, at voxel and regional levels of analysis. All subjects were able to perform the n-back task accurately. A spatially distributed network was activated, including dorsolateral prefrontal cortex, inferior frontal gyrus, lateral premotor cortex, and supplementary motor area (SMA) in the frontal lobes. More posteriorly, there were major foci of activation in parietal and occipitoparietal cortex, precuneus, lingual, and fusiform gyri of the ventral occipital lobe, inferior temporal gyrus, and cerebellum. The power of functional response was positively correlated with reaction time in bilateral posterior parietal cortex (Talairach coordinates in x, y, z (mm) 35, −44, 37 and −32, −56, 42), indicating that subjects who found the task difficult, and responded with a slower reaction time, tended to activate these regions more powerfully. One interpretation of this regionally specific relationship between prolonged reaction time and increased power of posterior parietal activation is consistent with prior studies identifying similar areas of parietal cortex as the site of the phonological storage function in verbal working memory.

This paper is concerned with the problem of evaluating goodness-of-fit of a path analytic model to an interregional correlation matrix derived from functional magnetic resonance imaging (fMRI) data. We argue that model evaluation based on testing the null hypothesis that the correlation matrix predicted by the model equals the population correlation matrix is problematic because P values are conditional on asymptotic distributional results (which may not be valid for fMRI data acquired in less than 10 min), as well as arbitrary specification of residual variances and effective degrees of freedom in each regional fMRI time series. We introduce an alternative approach based on an algorithm for automatic identification of the best fitting model that can be found to account for the data. The algorithm starts from the null model, in which all path coefficients are zero, and iteratively unconstrains the coefficient which has the largest Lagrangian multiplier at each step until a model is identified which has maximum goodness by a parsimonious fit index. Repeating this process after bootstrapping the data generates a confidence interval for goodness-of-fit of the best model. If the goodness of the theoretically preferred model is within this confidence interval we can empirically say that the theoretical model could be the best model. This relativistic and data-based strategy for model evaluation is illustrated by analysis of functional MR images acquired from 20 normal volunteers during periodic performance (for 5 min) of a task demanding semantic decision and subvocal rehearsal. A model including unidirectional connections from frontal to parietal cortex, designed to represent sequential engagement of rehearsal and monitoring components of the articulatory loop, is found to be irrefutable by hypothesis-testing and within confidence limits for the best model that could be fitted to the data.

Comparatively reduced blood flow to frontal brain regions in patients with schizophrenia (hypofrontality) has been frequently observed in the last 25 years. However, there is an inconstant quality to hypofrontality, suggesting either confounded observation of a static (trait‐like) abnormality, or that it is a genuinely dynamic (state‐like) phenomenon. Possible confounds in functional magnetic resonance imaging (fMRI) studies of hypofrontality are classified. Methods for assessment and correction of stimulus correlated motion (an extracerebral confound) are reviewed in the context of fMRI data acquired from five schizophrenic patients and five comparison subjects during performance of a verbal fluency task. Factorial analysis of these and other data, acquired from the same subjects during a semantic decision task, is used to exclude a number of possible intracerebral confounds. By analogy to the historical controversy concerning the appearance of the planet Saturn viewed through early telescopes, understanding the inconstancy of hypofrontality in schizophrenia is likely to progress more by theoretically driven experiments that exploit the repeatability of fMRI than by further technological development alone. Hum. Brain Mapping 8:86–91, 1999. © 1999 Wiley‐Liss, Inc.

In the past year, molecular geneticists have continued to exclude the involvement of particular candidate genes and chromosomal regions in schizophrenia. A Norwegian twin study has confirmed that non-paranoid schizophrenia appears 'more genetic' than paranoid schizophrenia, and a US family study suggests that the highest familial risk is to the relatives of female schizophrenics born between February and May. The prenatal viral hypothesis continues to provoke controversy. Two epidemiological studies suggest that those born or brought up in cities have a higher risk of schizophrenia than their rural counterparts.

Due to the finite spatial resolution of digital magnetic resonance images of the brain, and the complexity of anatomical interfaces between brain regions of different tissue type, it is inevitable that some voxels will represent a mixture of two or three different tissue types. Outright assignment of such "bipartial" or "tripartial" voxels to one class or another is more problematic and less reliable than assignment of "full-volume" voxels, wholly representative of a single tissue type. We have developed a computerized system for brain tissue classification of dual echo MR data, which uses a polychotomous logistic model for discriminant analysis, combined with a Bayes allocation rule incorporating differential prior probabilities, and spatial connectivity tests, to assign each voxel in the image to one of four possible classes: gray matter, white matter, cerebrospinal fluid, or unclassified. The system supports automated volumetric analysis of segmented images, has low operational overheads, and compares favorably with previous multivariate or "multispectral" approaches to brain MR image segmentation in terms of both validity (bootstrap misclassification rate = 3.3%) and interoperator reliability (intra-class correlation coefficients for all three tissue classes >0.9). We argue that these improvements in performance stem from better methodological management of the related problems of non-Normality of MR signal intensity values and partial volume artifact. Copyright 1995, 1999 Academic Press

Cognitive dysfunction, a symptom of schizophrenia, has been recently identified as an important measure of outcome in the treatment of this disorder. Drugmediated symptom improvement, the traditional measure of treatment success for schizophrenia, typically fails to associate with modifications of cognitive dysfunction, resulting in a failure of the patient to reintegrate into society. A paradigm shift is now required in the conceptualization of treatment success away from symptom decrement and towards treatments that improve cognitive function. Clozapine treatment has been shown to provide a significantly greater improvement in several domains of cognitive function, especially attention and verbal fluency, compared with conventional neuroleptics, whereas risperidone appears to have a beneficial effect on working memory. These results may be because of the normalization of dopamine function by clozapine and antagonism of 5HT2receptors.

This case history reports on the sustained clinical efficacy of quetiapine in a 34-year-old man with chronic paranoid schizophrenia, who was a partial responder to traditional therapy. Quetiapine was found to be effective against both positive and negative symptoms of schizophrenia, and had an excellent safety profile. The patient, who had also suffered from alcohol dependency, decreased his alcohol consumption as a result of responding to therapy, and successfully became re-integrated into society.

From a research perspective, it is easy to become excited by the kinds of findings that neuroimaging has delivered in psychiatry; by allowing us to view the undisturbed living brain, we now have a better picture of neurobiological characteristics of different conditions. But what does it add to the clinical management of psychiatric illnesses?