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Bursting has been observed in many sensory neurons, and is thought to be important in neural signaling, sleep, and some disorders of the brain. Bursting neurons have been studied via various types of conductance-based models at the single-neuron level. Important features of bursting have been reproduced by this type of model, but it is not certain how well the behavior of populations of bursting neurons can be represented solely by that of individual neurons. To study bursting neurons at the population level, a conductance-based model is incorporated into a mean-field model to yield a mean-field bursting model. The responses of the model to sinusoidal inputs are studied, showing that neurons with various different initial states are capable of phase-locked or intermittent firing, depending on their baseline voltage. Furthermore, depending on this voltage, the bursting frequency either slaves to the original unperturbed bursting frequency or approaches a steady value when the external driving frequency increases. Finally, use of white noise perturbations shows that the bursting frequency of the neurons remains the same even under a more general external stimulus.

Efforts to identify genetic factors that confer an increased risk for the expression of psychiatric symptoms have focused on polymorphisms in variety of candidate genes, including the catechol-O-methyltransferase (COMT) gene. Results from previous studies that have examined associations between the functional COMT polymorphism (Val158Met) and mental health have been mixed. In the present study, we examined the relationships between COMT, early life stress, and personality in a healthy adult sample. Consistent with previous studies, we hypothesized that individuals with the low-activity genotype would have higher neuroticism and lower extraversion and that this effect would be more pronounced in females. In addition, we extended the previous literature by investigating the potential influence of early life stress. A total of 486 healthy adults underwent genetic testing and personality assessment. Results revealed that individuals homozygous for the COMT low enzyme activity allele had lower extraversion on the NEO-FFI and demonstrated a trend toward greater neuroticism. These relationships were not influenced by sex or the presence of reported early life stress. The finding that COMT genotype was associated with extraversion, and more weakly with neuroticism, is consistent with previous studies. Future research to clarify the influence of sex and gene-environmental interactions is warranted.

OBJECTIVE:: To determine the nature and severity of cognitive functioning impairment in adolescent anorexia nervosa (AN) when underweight and following weight gain. METHOD:: In 37 first admission adolescent (12-18 years) AN patients and 45 matched controls, general cognitive functions were assessed at baseline and follow-up using the IntegNeuro-computerized battery. AN participants were tested between days 3 and 10 of their admission when underweight, with retesting conducted after weight restoration. RESULTS:: When underweight, AN participants performed more poorly than controls on sensori-motor speed tasks and exhibited a susceptibility to interference, but had superior working memory. Once the weight is restored, individuals significantly improved relative to their own performance. Relative to controls, they were significantly faster on attention and executive function tasks, exhibited superior verbal fluency, working memory, and a significantly superior ability to inhibit well-learnt responses. DISCUSSION:: Cognitive impairments in adolescent AN appear to normalize with refeeding and weight gain. (c) 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009.

Both general and social cognition are important in providing endophenotypic markers and predicting real-world functional outcomes of clinical psychiatric disorders. However, to date, focus has been on general cognition, rather than on core domains of social/emotional cognition. This study sought to determine core domains of emotion processing for both explicit identification and implicit recognition and their relationships with core domains of general cognition. Age effects and sex differences were also investigated. A sample of 1,000 healthy individuals (6 to 91 years, 53.5% female) undertook the WebNeuro tests of emotion identification and recognition and tests of general cognitive function. Factor analysis revealed seven core domains of emotion processing: speed of explicit emotion identification, speed of implicit emotion recognition, implicit emotion recognition accuracy, "threat" processing, sadness-disgust identification, "positive emotion" processing, and general "face perception." Seven corresponding core domains of general cognition were identified: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. Factors of emotion processing generally showed positive associations with those of general cognitive function, suggesting commonality in processing speed in particular. Moreover, age had a consistent nonlinear impact on both emotion processing and general cognitive factors, while sex differences were more specific. These findings contribute to a normative and standardized structure for assessment of emotional and general cognition in clinical groups.

A number of psychiatric and neurological disorders are characterized by impairments in facial emotion recognition. Recognition of individual emotions has implicated limbic, basal ganglionic, and frontal brain regions. Since these regions are also implicated in age-related decline and sex differences in emotion processing, an understanding of normative variation is important for assessing deficits in clinical groups. An internet-based test ("WebNeuro") was administered to 1,000 healthy participants (6 to 91 years, 53% female) to assess explicit identification of basic expressions of emotion (happiness, sadness, fear, anger, disgust, neutral). A subsequent implicit recognition condition was based on a priming protocol, in which explicit identification provided the "study" phase. Responses were most accurate for happiness and slowest for fear in the explicit condition, but least accurate for happiness and fastest for fear in the implicit condition. The effects of age, by contrast, showed a similar pattern for both explicit and implicit conditions, following a nonlinear distribution in which performance improved from childhood through adolescence and early adulthood and declined in later adulthood. Females were better than males at explicit identification of fear in particular. These findings are consistent with the priority of threat-related signals, but indicate opposing biases depending on whether emotion processing is conscious or nonconscious. The lifespan trends in emotion processing over 10 decades point to an interaction of brain-based (maturation, stability, and then atrophy of cortical and subcortical systems) and experiential contributing factors. These findings provide a robust normative platform for assessing clinical groups.

This paper demonstrates a method for analyzing target evoked potentials in an auditory oddball task, using Wiener deconvolution to separate the brain's task-dependent properties from its task-invariant response. It is shown that a target response can be deconvolved, and the result contains two delta-like peaks separated by approximately 100 ms, implying that targets resemble a superposition of two standard responses. The latencies and areas of these delta-like peaks give quantitative measures of the evoked potential, providing a method of analysis that is simpler and more physiologically meaningful than peak scoring. This deconvolution method is applied to both synthetic and experimental evoked potential data, and is demonstrated to be applicable even when normal evoked potential features are not clearly visible.

Altered hippocampal volume, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and neuroticism have each been implicated in the etiology of psychiatric disorders, especially depression. However, the relationship between these variables is not well understood. Here, we determined the effects of the BDNF Val66met polymorphism on the five-factor personality dimensions (assessed using the NEO-FFI), trait depression (assessed with the DASS-21) in a cross-sectional cohort of 467 healthy volunteers. A large matched subset of this cohort was also assessed for grey matter volume of the hippocampus and contiguous temporal cortical regions using magnetic resonance imaging. In Met carriers, elevations in neuroticism and trait depression and stress were associated with lower mean hippocampal volume, but there were no such associations in Val homozygotes. Trait depression, in particular, was found to moderate the effects of BDNF genotypes on hippocampal volume. Met carriers with high trait depression showed a reduction in grey matter volume of the mean hippocampus compared with Val homozygotes. These findings suggest that even in otherwise healthy subjects, trait depression may contribute to the susceptibility of Met carriers to hippocampal grey matter loss.

Affective impairment is observed in children and adolescents with attention-deficit hyperactivity disorder (ADHD). Low levels of long-chain polyunsaturated fatty acids (LC-PUFA), specifically omega-3 (omega-3) fatty acids in blood measures have been linked to a range of behavioural and mood disorders including ADHD. However, nothing is known about the relationship between omega-3 and brain function in children with ADHD. In the current study, 20 adolescent boys with ADHD were assessed for total lipid fractions in red blood cells and their event-related potential (ERP) response to the presentation of facial expressions of happiness, sadness and fearfulness. The results supported the hypothesis of a positive association between eicosapentaenoic acid (EPA) and a cognitive bias in orientation to overt expressions of happiness over both sad and fearful faces as indexed by midline frontal P300 amplitude. Additional exploratory analyses revealed a positive association between levels of docosahexaenoic acid (DHA) and the right temporal N170 amplitude in response to covert expressions of fear. The arachidonic (AA)/DHA ratio was negatively associated with the right temporal N170 amplitude also to covert expressions of fear. These findings indicate that EPA and DHA may be involved in distinct aspects of affect processing in ADHD and have implications for understanding currently inconsistent findings in the literature on EFA supplementation in ADHD and depression.

Recent research has revealed significant relationships between the vermian regions of the cerebellum and cognitive functions typically associated with prefrontal lobe function. These relationships are believed to be supported by anatomical connections between the distant brain regions. Recent evidence also suggests that age-related reductions in the posterior vermis are associated with age-related decline in frontal lobe cognitive functions, but these studies did not consider concomitant age-related atrophy of the prefrontal lobes. In the present study we addressed this issue by examining cognitive and structural MRI data obtained from 251 adults ranging in age from 18 to 79. Cognition was examined with a computerized cognitive battery and volumes of the cerebellar vermian regions and the prefrontal lobes were determined using quantitative morphometry. Results of the study revealed that both prefrontal and vermian volumes were smaller in older adults compared to younger adults, and both volumes correlated with cognitive performances in the older individuals. However, after controlling for prefrontal volume, the relationships between cognitive function and vermian volumes were eliminated, whereas prefrontal lobe volume remained significantly related to cognitive function after controlling for vermian volumes. These results suggest that while a reduction in cerebellar vermian volume does not significantly relate to normal age-related cognitive decline, prefrontal volume is significantly related to cognitive aging. Our results are consistent with the frontal aging hypothesis.

Although it has been established that acute stress disorder (ASD) and posttraumatic stress disorder occur after mild traumatic brain injury (MTBI) the qualitative differences in symptom presentation between injury survivors with and without a MTBI have not been explored in depth. This study aimed to compare the ASD and posttraumatic stress disorder symptom presentation of injury survivors with and without MTBI. One thousand one hundred sixteen participants between the ages of 17 to 65 years (mean age: 38.97 years, SD: 14.23) were assessed in the acute hospital after a traumatic injury. Four hundred seventy-five individuals met the criteria for MTBI. Results showed a trend toward higher levels of ASD in the MTBI group compared with the non-MTBI group. Those with a MTBI and ASD had longer hospital admissions and higher levels of distress associated with their symptoms. Although many of the ASD symptoms that the MTBI group scored significantly higher were also part of a postconcussive syndrome, higher levels of avoidance symptoms may suggest that this group is at risk for longer term poor psychological adjustment. Mild TBI patients may represent a injury group at risk for poor psychological adjustment after traumatic injury.

In this study, we examined whether the Met allele of the BDNF Val66Met polymorphism is associated with selective disruptions to task-relevant information processing. In 475 non-clinical participants for whom BDNF genotype status was determined we used the 'IntegNeuro' computerized battery of neuropsychological tests to assess cognitive performance, an auditory oddball task to elicit the P300 event-related potential (ERP) and, in smaller subsets of these subjects, high resolution structural MRI imaging to quantify fronto-hippocampal grey matter (n=161), and functional magnetic resonance imaging to assess fronto-hippocampal BOLD activation (n=37). Met/Met (MM) homozygotes had higher verbal recall errors, in the absence of differences in attention, executive function, verbal ability or sensori-motor function. Further, MM homozygotes demonstrated a slowed P300 ERP during the oddball task, with corresponding alterations in hippocampal and lateral prefrontal activation, and a localized reduction in hippocampal grey matter. These results are consistent with a subtle impact of the Met allele on fronto-hippocampal systems involved in selective information processing of stimulus context and memory updating within the normal population. The findings also indicate that heritable endophenotypes such as the P300 have value in elucidating genotype-phenotype relationships.

Attentional impairment in depression is a cardinal feature of depression and has been proposed as a candidate endophenotype for major depressive disorder. Event-related potentials (ERPs) elicited by oddball signal detection tasks provide objective markers of selective stimulus processing, and are pertinent endophenotypic markers for depression. While previous studies have sought to determine objective markers for attentional impairment in depression, evidence is inconsistent and may involve heterogeneity in relatively small samples. Here, we brought together oddball ERP recording with source localization of neural correlates of selective attention in outpatients with major depressive disorder (MDD; n = 78) and participants with depressed mood (PDM; n = 127) relative to healthy controls (CTL; n = 116). The key finding was a dimensional exaggeration of the P200 (140-270 ms) to both target (signal) and non-target (noise) stimuli, most pronounced in MDD, followed by PDM, relative to CTL. This exaggeration was coupled with slower and more variable response times, suggesting that neural systems are attempting to compensate for a difficulty in discriminating signal from noise. P200 alterations were localised to limbic (hippocampal), temporal and ventral prefrontal regions, key components of the signal detection network. A subsequent reduction and delay in the P300 was also revealed for MDD indicating that the pronounced lack of discrimination in clinical depression may also lead to impaired stimulus evaluation. This P200 increase in depression could provide a potential mechanism for the attentional impairment frequently observed in depression and consequent alterations in the P300 may differentiate clinically significant depression.

A disturbance in the interactions between distributed cortical regions may underlie the cognitive and perceptual dysfunction associated with schizophrenia. In this article, nonlinear measures of cortical interactions and graph-theoretical metrics of network topography are combined to investigate this schizophrenia "disconnection hypothesis." This is achieved by analyzing the spatiotemporal structure of resting state scalp EEG data previously acquired from 40 young subjects with a recent first episode of schizophrenia and 40 healthy matched controls. In each subject, a method of mapping the topography of nonlinear interactions between cortical regions was applied to a widely distributed array of these data. The resulting nonlinear correlation matrices were converted to weighted graphs. The path length (a measure of large-scale network integration), clustering coefficient (a measure of "cliquishness"), and hub structure of these graphs were used as metrics of the underlying brain network activity. The graphs of both groups exhibited high levels of local clustering combined with comparatively short path lengths--features consistent with a "small-world" topology--as well as the presence of strong, central hubs. The graphs in the schizophrenia group displayed lower clustering and shorter path lengths in comparison to the healthy group. Whilst still "small-world," these effects are consistent with a subtle randomization in the underlying network architecture--likely associated with a greater number of links connecting disparate clusters. This randomization may underlie the cognitive disturbances characteristic of schizophrenia.

BACKGROUND: Although schizophrenia has been characterized by disruptions to neural synchrony, it remains unknown whether these disturbances are related to symptoms and loss of grey matter. We examined relations between 40 Hz Gamma band synchrony and grey matter in patients with schizophrenia at first episode and after 2.5 years. METHODS: From an initial recruitment of 35 medicated patients with a first episode of schizophrenia, 25 patients completed clinical and oddball task-elicited Gamma synchrony within 3 months of health service contact and again after 2.5 years, 23 completed magnetic resonance imaging (MRI) at these time points, and 13 completed all sessions. We compared patients with 35 matched healthy controls. We identified early (0-150 ms) and late (250-500 ms) peaks in Gamma synchrony locked to oddball targets, and we analyzed MRI data using voxel-based morphometry. We evaluated group and test-retest differences using repeated-measures analyses of variance. RESULTS: Compared with controls, at first contact, patients with a first episode of schizophrenia showed a disruption to the laterality of early Gamma synchrony and global reduction in late Gamma synchrony, with a corresponding loss of fronto-temporal-parietal grey matter. Gamma synchrony was increased at follow-up among patients with a first episode of schizophrenia. It related negatively to further loss of grey matter, but positively to improvement in reality distortion symptoms. These relations could not be explained by medication dose. LIMITATIONS: Our study did not include unmedicated patients or normative follow-up testing. CONCLUSION: Gamma synchrony may track the progression of schizophrenia from first episode. An increase in Gamma synchrony over time might reflect an attempt to adapt to a progressive loss of cortical grey matter and associated changes in cognitive and emotional function.

Antidepressants are important in the treatment of depression, and selective serotonin reuptake inhibitors are first-line pharmacologic options. However, only 50% to 70% of patients respond to first treatment and <40% remit. Since depression is associated with substantial morbidity, mortality, and family burden, it is unfortunate and demanding on health resources that patients must remain on their prescribed medications for at least 4 weeks without knowing whether the particular antidepressant will be effective. Studies have suggested a number of predictors of treatment response, including clinical, psychophysiological, neuroimaging, and genetics, each with varying degrees of success and nearly all with poor prognostic sensitivity and specificity. Studies are yet to be conducted that use multiple measures from these different domains to determine whether sensitivity and specificity can be improved to predict individual treatment response. It is proposed that a focus on standardized testing methodologies across multiple testing modalities and their integration will be crucial for translation of research findings into clinical practice.

Separate dimensions of schizotypy have been differentially associated with electrophysiological measures of brain function, and further shown to be modified by sex/gender. We investigated event-related potential (ERP) correlates of two subdimensions of positive schizotypy, paranormal ideation (PI) and unusual experiences (UEs). Seventy-two individuals with no psychiatric diagnosis (men=36) completed self-report measures of UE and PI and performed an auditory oddball task. Average scores for N100, N200 and P300 amplitudes were calculated for left and right anterior, central and posterior electrode sites. Multiple linear regression was used to examine the relationships between the measures of schizotypy and ERPs across the entire sample, as well as separately according to sex. PI was inversely associated with P300 amplitude at left-central sites across the entire sample, and at right-anterior electrodes in women only. Right-anterior P300 and right-posterior N100 amplitudes were negatively associated with UE in women only. Across the entire sample, UE was negatively associated with left-central N100 amplitude, and positively associated with left-anterior N200 amplitude. These results provide support from electrophysiological measures for the fractionation of the positive dimension of schizotypy into subdimensions of PI and UE, and lend indirect support to dimensional or quasidimensional conceptions of psychosis. More specifically, they suggest that PI may be associated with alteration in contextual updating processes, and that UE may reflect altered sensory/early-attention (N100) mechanisms. The sex differences observed are consistent with those previously observed in individuals with schizophrenia.

BACKGROUND: Dissociative reactions in post-traumatic stress disorder (PTSD) have been regarded as strategic responses that limit arousal. Neuroimaging studies suggest distinct prefrontal responses in individuals displaying dissociative and hyperarousal responses to threat in PTSD. Increased prefrontal activity may reflect enhanced regulation of limbic arousal networks in dissociation. If dissociation is a higher-order regulatory response to threat, there may be differential responses to conscious and automatic processing of threat stimuli. This study addresses this question by examining the impact of dissociation on fear processing at different levels of awareness. METHOD: Functional magnetic resonance imaging (fMRI) with a 1.5-T scanner was used to examine activation to fearful (versus neutral) facial expressions during consciously attended and non-conscious (using backward masking) conditions in 23 individuals with PTSD. Activation in 11 individuals displaying non-dissociative reactions was compared to activation in 12 displaying dissociative reactions to consciously and non-consciously perceived fear stimuli. RESULTS: Dissociative PTSD was associated with enhanced activation in the ventral prefrontal cortex for conscious fear, and in the bilateral amygdala, insula and left thalamus for non-conscious fear compared to non-dissociative PTSD. Comparatively reduced activation in the dissociative group was apparent in dorsomedial prefrontal regions for conscious fear faces. CONCLUSIONS: These findings confirm our hypotheses of enhanced prefrontal activity to conscious fear and enhanced activity in limbic networks to non-conscious fear in dissociative PTSD. This supports the theory that dissociation is a regulatory strategy invoked to cope with extreme arousal in PTSD, but this strategy appears to function only during conscious processing of threat.

The aim of the paper is to describe a standardized "Integrative Neuroscience" Platform that can be applied to elucidate brain-body mechanisms. This infrastructure includes a theoretical integration (the INTEGRATE Model). To demonstrate this infrastructure, hypotheses from the INTEGRATE Model are applied in an example investigation of the cognitive, brain and body markers of individual differences in the trait characteristic of Negativity Bias (the tendency to see oneself and one's world as negative). A sample of 270 healthy participants (18-65 years old) were grouped into equal sized matched subsets of high "Negativity Bias" and high "Positivity Bias" (n = 135 in each group). Participants were assessed using a standardized battery of psychological traits, cognition and brain and body (autonomic) activity. Greater "Negativity Bias" relative to "Positivity Bias" was characterized by greater autonomic reactivity and early neural excitation to signals of potential danger, at the timescale of Emotion (< 200 ms). Concomitantly, there was a relatively lower level of "Thinking", reflected in cognitive dimensions and associated electrical brain measures of working memory and EEG Theta power. By contrast, Negativity and Positivity Bias did not differ in levels of emotional resilience and social skills at the longer time scale of Self Regulation. This paper provides a demonstration of how an Integrative Neuroscience infrastructure can be used to elucidate the brain-body basis of trait characteristics, such as Negativity Bias, that are key indicators of risk for poor well-being and psychopathology.

This study demonstrates that the EEG phenotypes as described by Johnstone, Gunkelman & Lunt are identifiable EEG patterns with good inter-rater reliability. Furthermore, it was also demonstrated that these EEG phenotypes occurred in both ADHD subjects as well as healthy control subjects. The Frontal Slow and Slowed Alpha Peak Frequency and the Low Voltage EEG phenotype discriminated ADHD subjects best from controls (however the difference was not significant). The Frontal Slow group responded to a stimulant with a clinically relevant decreased number of false negative errors on the CPT. The Frontal Slow and Slowed Alpha Peak Frequency phenotypes have different etiologies as evidenced by the treatment response to stimulants. In previous research Slowed Alpha Peak Frequency has most likely erroneously shown up as a frontal theta sub-group. This implies that future research employing EEG measures in ADHD should avoid using traditional frequency bands, but dissociate Slowed Alpha Peak Frequency from frontal theta by taking the individual alpha peak frequency into account. Furthermore, the divergence from normal of the frequency bands pertaining to the various phenotypes is greater in the clinical group than in the controls. Investigating EEG phenotypes provides a promising new way to approach EEG data, explaining much of the variance in EEGs and thereby potentially leading to more specific prospective treatment outcomes.

There is a growing evidence that elevated body mass index (BMI) is associated with adverse neurocognitive outcome, though no study has examined whether morphometric differences are found in persons across the adult life span. We compared 201 healthy individuals in normal weight, overweight, and obese groups (aged 17-79). After correcting for demographic differences, obese individuals showed smaller whole brain and total gray matter volume than normal weight and overweight individuals. These findings support an independent relationship between BMI and brain structure and demonstrate that these differences are not limited to older adults.

A functional polymorphism of the brain-derived neurotrophic factor, BDNF Val66Met, is associated with risk for major depression alongside impairments in memory and selective attention. This study aims to identify the mediating neural mechanisms in links between BDNF and depression using highly heritable electroencephalographic (EEG) recordings. In 305 healthy subjects, BDNF Val66Met genotypes were compared in terms of trait depression, neural function (EEG during a resting state) and cognitive performance. The mediating effects of the EEG brain imaging endophenotypes were also examined using structural equation (path) modeling. A genotype-endophenotype-phenotype path model showed that Met homozygosity predicted elevated working memory commission errors and altered EEG activity; that is elevated relative theta and delta power coupled with reduced alpha power. In turn, reduced EEG alpha activity mediated the relationship between the Met/Met genotype and trait depression. These findings demonstrate the utility of an integrative endophenotype approach. They suggest that the BDNF Met/Met homozygote has a direct impact on memory systems, but impacts trait depression via the secondary effects of neural changes.

OBJECTIVES: Recent studies have explored a model of the disconnection hypothesis of schizophrenia through the demonstration of abnormal stimulus induced gamma phase synchrony (GPS). These studies have principally examined synchrony in the 40 Hz band elicited in post-stimulus time periods, relative to a pre-stimulus baseline. In this study we examined the absolute magnitude of GPS elicited by a selective attention task, in first-episode psychosis (FEP). We hypothesized that FEP would be associated with abnormalities in absolute GPS, particularly when required to selectively attend to task-relevant stimuli. METHODS: Fifty-five first-episode psychosis (FEP) subjects and one hundred and ten matched healthy control subjects underwent an auditory oddball selective attention task during EEG recording. The absolute magnitude of GPS was extracted for the range 35-45 Hz, and time-locked to stimulus onset. GPS averaged were computed for oddball 'target' (task-relevant) and 'non-target' (task-irrelevant) stimuli, for each subject. RESULTS: FEP subjects showed a significant elevation in absolute GPS relative to controls, apparent across the 35-45 Hz range. This elevation was most marked in the left centro-temporal region, across the 800 ms post-stimulus period. In FEP subjects, the elevation in GPS was also greater for target compared to non-target stimuli, while healthy controls did not show a stimulus effect. CONCLUSION: These findings complement previous evidence for reductions in peak gamma synchrony, calculated relative to a pre-stimulus baseline, in schizophrenia. The results an excess of absolute GPS in schizophrenia may contribute to an inability to effectively integrate task-relevant information, which underlie psychotic symptoms.

This study was undertaken using the INTEGRATE Model of brain organization, which is based on a temporal continuum of emotion, thinking and self regulation. In this model, the key organizing principle of self adaption is the motivation to minimize danger and maximize reward. This principle drives brain organization across a temporal continuum spanning milliseconds to seconds, minutes and hours. The INTEGRATE Model comprises three distinct processes across this continuum. Emotion is defined by automatic action tendencies triggered by signals that are significant due to their relevance to minimizing danger-maximizing reward (such as abrupt, high contrast stimuli). Thinking represents cognitive functions and feelings that rely on brain and body feedback emerging from around 200 ms post-stimulus onwards. Self regulation is the modulation of emotion, thinking and feeling over time, according to more abstract adaptions to minimize danger-maximize reward. Here, we examined the impact of dispositional factors, age and genetic variation, on this temporal continuum. Brain Resource methodology provided a standardized platform for acquiring genetic, brain and behavioral data in the same 1000 healthy subjects. Results showed a "paradox" of declining function in the "thinking" time scale over the lifespan (6 to 80+ years), but a corresponding preservation or even increase in automatic functions of "emotion" and "self regulation". This paradox was paralleled by a greater loss of grey matter in cortical association areas (assessed using MRI) over age, but a relative preservation of subcortical grey matter. Genetic polymorphisms associated with both healthy function and susceptibility to disorder (including the BDNFVal(66)Met, COMTVal(158/108)Met, MAOA and DRD4 tandem repeat and 5HTT-LPR polymorphisms) made specific contributions to emotion, thinking and self regulatory functions, which also varied according to age.

The present study sought to determine a profile of integrated behavioral, brain and autonomic alterations in PTSD. Previous findings suggest that PTSD is associated with changes across electrophysiological (EEG and ERP), autonomic and cognitive/behavioral measures. In particular, PTSD has been associated with reduced cognitive performance, altered cortical arousal (measured by EEG), diminished late ERP component to oddball task targets (reduced P3 amplitude) and increased autonomic arousal relative to healthy controls. The present study examined measures of cognitive function, auditory oddball ERP components, autonomic function (heart rate and skin conductance) and EEG during resting conditions in 44 individuals with PTSD and 44 non-trauma-exposed controls, and predicted that an integrated profile of changes across a number of these measures would show a high level of sensitivity and specificity in discriminating PTSD from controls. Nine variables showing strongly significant (p < 0.002) between-group differences were entered into a discriminant function analysis. Four of these measures successfully discriminated the PTSD and non-PTSD groups: change in tonic arousal, duration of attention switching, working memory reaction time and errors of commission during visuospatial maze learning. Tonic arousal change contributed the most variance in predicting group membership. These results extend previous findings and provide an integrated biomarker profile that characterizes both PTSD and non-PTSD groups with a high degree of sensitivity and specificity. This outcome provides a platform for future studies to test how this profile of disturbances in autonomic and information processing may be unique to PTSD or may occur generically across clinical and/or other anxiety disorders.

OBJECTIVE: Posttraumatic stress disorder (PTSD) involves deficits in information processing that may reflect hypervigilence and deficient inhibitory control. To date, however, no PTSD neuroimaging study has directly examined PTSD-related changes in executive inhibition. Our objective was to investigate the hypothesis that executive inhibitory control networks are compromised in PTSD. METHODS: Functional magnetic resonance imaging (fMRI) was used during a Go/No-Go inhibition task completed by a sample of patients with PTSD (n = 23), a matched sample of healthy (i.e. without trauma exposure) control participants (n = 23) and a sample of control participants with trauma exposure who did not meet criteria for PTSD (n = 17). RESULTS: Participants with PTSD showed more inhibition-related errors than did individuals without trauma exposure. During inhibition, control participants activated a right-lateralized cortical inhibitory network, whereas patients with PTSD activated only the left lateral frontal cortex. PTSD was associated with a reduction in right cortical activation and increased activation of striatal and somatosensory regions. CONCLUSION: The increased inhibitory error and reduced right frontal cortical activation are consistent with compromised inhibitory control in PTSD, while the increased activation of brain regions associated with sensory processing and a greater demand on inhibitory control may reflect enhanced stimulus processing in PTSD, which may undermine cortical control mechanisms.

Sustained sleep problems such as insomnia have been shown to be detrimental to health. This study examines the less understood, finer grained effects of a single bad night's sleep on mood, cognitive, autonomic and electrophysiological functions. We assessed 338 individuals who had no symptoms of a clinical sleep disorder. Of these, 226 individuals had six or more hours sleep and 112 individuals had less than six hours sleep prior to an assessment of mood, cognition, autonomic and electrophysiological functioning. Individuals in the relatively "bad night" sleep group had higher depression, anxiety, and stress scores and reported significantly poorer overall wellbeing. They made more errors on simple cognitive tasks while more complex task components were unaffected. They also had an increase in heart rate and EEG alpha and beta power at rest. Participants in this study had no symptoms of a clinical sleep disorder, however the effects of a poor night sleep on measures of mood, cognition, autonomic and electrophysiological function were similar, but less severe than those reported in insomnia patients. The integrative profile of measures reported here point to an increase in physiological arousal and sub-optimal cognition, following a poor night's sleep.

The approach-withdrawal and valence-arousal models both predict that depressive and anxious profiles will be associated with relatively reduced left frontal and increased right frontal activity respectively, while the valence-arousal model also proposes a dissociation by lower and higher right parietotemporal activity, respectively. Recent work further suggests that subtypes of anxiety disorders may be characterized by distinctive patterns of activity depending on their type of arousal (anxious arousal/apprehension). The aim of this study was to investigate the relationships among nonclinical depression/anxiety and lateralized frontal/parietotemporal activity by categorizing participants (N=428) on the basis of both negative mood and alpha EEG. Key findings include: (i) greater right frontal lateralization in anxious participants, symmetrical frontal activity in depressed/comorbid, and left frontal lateralization in healthy controls; (ii) right frontal lateralization in anxious arousal participants, left frontal and right parietotemporal lateralization in anxious apprehension; (iii) bilateral increase in frontal and increased right parietotemporal activity in depressed/comorbid participants. Findings support predictions for frontal but not posterior regions. Grouping on the basis of EEG may not be reciprocally predictive of negative mood groupings, suggesting involvement of additional factors.

BACKGROUND: In addition to cognitive impairment, there are disruptions to mood and emotion processing in attention-deficit/hyperactivity disorder (ADHD) but little is known about their neural basis. We examined ADHD disturbances in mood and emotion recognition and underlying neural systems before and after treatment with stimulant medication. METHODS: Participants were 51 unmedicated ADHD adolescents and 51 matched healthy control subjects rated for depressed and anxious mood and accuracy for identifying facial expressions of basic emotion. Brain function was recorded using event-related potentials (ERPs) while subjects viewed these expressions. ADHD subjects were retested after 4 weeks, following treatment with methylphenidate (MPH). RESULTS: ADHD subjects showed a profile of emotion-related impairment: higher depression and anxiety, deficits in identifying threat-related emotional expressions in particular, and alterations in ERPs. There was a pronounced reduction in occipital activity during the early perceptual analysis of emotional expression (within 120 msec), followed by an exaggeration of activity associated with structural encoding (120-220 msec) and subsequent reduction and slowing of temporal brain activity subserving context processing (300-400 msec). Methylphenidate normalized neural activity and produced some improvement of emotion recognition but had no impact on negative mood. Improvements in neural activity with MPH were consistent predictors of improvement in clinical features of emotional lability and hyperactivity. CONCLUSIONS: Objective behavioral and brain function measures of emotion processing may provide a valuable addition to the clinical armamentarium for assessing emotional disturbances in ADHD and the efficacy of stimulants for treating these disturbances.

Biological models of posttraumatic stress disorder (PTSD) suggest that patients will display heightened amygdala but decreased medial prefrontal activity during processing of fear stimuli. However, a rapid and automatic alerting mechanism for responding to nonconscious signals of fear suggests that PTSD may display heightened rather than decreased MPFC under nonconscious processing of fear stimuli. This study used functional magnetic resonance imaging to examine blood oxygenation level-dependent signal changes during nonconscious presentation (16.7 ms, masked) of fearful and neutral faces in 15 participants with PTSD and 15 age and sex-matched healthy control participants. Results indicate that PTSD participants display increased amygdala and MPFC activity during nonconscious processing of fearful faces. These data extend existing models by suggesting that the impaired MPFC activation in PTSD may be limited to conscious fear processing. Hum Brain Mapp, 2008. (c) 2007 Wiley-Liss, Inc.