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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.

Introduction: Depression is characterized by disturbances in affect, cognition, brain and body function, yet studies have tended to focus on single domains of dysfunction. An integrated approach may provide a more complete profile of the range of deficits characterized by depressed individuals, but it is unclear whether this approach is able to predict depression severity over and above that predicted by single tasks or domains of function. In this study, we examined the value of combining multiple domains of function in predicting depression severity. Methods: Participants contained in the International Brain Database, () had completed three testing components including a web-based questionnaire of Personal History, the Brain Resource Cognition battery of Neuropsychological tests, Personality assessment and Psychophysiological testing. Two hundred and sixty six of these participants were able to be classified as either non-depressed, mild-moderately or severely (non-clinically) depressed, based on a depression screening questionnaire. Analysis of variance identified variables on which the categorized participants differed. Significant variables were then entered into a series of stepwise regressions to examine their ability to predict depression scores. Results: An integrated model including measures of affect (increased Neuroticism; decreased Emotional Intelligence), cognition (increased variability of reaction time during a working memory task; decreased "name the word component score" in the verbal interference task), brain (decreased left-lateralized P150 ERP component during a working memory task) and body function (increased negative skin conductance level gradient) were found to predict more of the variation in depression severity than any single domain of function. Discussion: On the basis of behavioral as well as Psychophysiological findings reported in this study, it was suggested that deficits in subclinically depressed individuals are more pronounced during automatic stages of stimulus processing, and that performance in these individuals may improve (to the level displayed by controls) when task demands are increased. Findings also suggest that it is important to consider disturbances across different domains of function in order to elucidate depression severity. Each domain may contribute unique explanatory information consistent with an integrative model of depression, taking into account the role of both behavior and underlying neural changes.

Obstructive sleep apnea (OSA) is expected to impair vigilance and executive functioning, owing to the sensitivity of the prefrontal cortex to the effects of sleep fragmentation and intermittent hypoxia. Studies examining the pattern of cognitive dysfunction show variable results, with the heterogeneity in part due to small sample sizes in current studies and little consistency of the tests used. We examined a group of fifty subjects from the Brain Resource International Database (BRID), predicted to have OSA on the basis of the Multivariable Apnea Prediction Index, and compared them with 200 matched controls. On electrophysiological tests, the OSA group showed reduced eyes closed alpha power, increased auditory oddball N100 and P200 amplitude, but reduced N200 and P300 amplitude. The latency to P300 was not significantly different between groups, but latencies to N200 and P200 were prolonged in the OSA group. Performance testing of the executive function found that verbal interference and the switching of attention were impaired in the OSA group. We have demonstrated that a diagnostic algorithm based on apnea symptoms and demographic factors can be used to select a group with likely OSA manifesting deficits in information processing and executive function.

Early Life Stress (ELS) has been associated with a range of adverse outcomes in adults, including abnormalities in electrical brain activity [1], personality dimensions [40], increased vulnerability to substance abuse and depression [14]. The present study seeks to quantify these proposed effects in a large sample of non-clinical subjects. Data for the study was obtained from The Brain Resource International Database (six laboratories: two in USA, two in Europe, two in Australia). This study analyzed scalp electrophysiological data (EEG eyes open, closed and target auditory oddball data) and personality (NEO-FFI), history of addictive substance use and ELS) data that was acquired from 740 healthy volunteers. The ELS measures were collected via a self-report measure and covered a broad range of events from childhood sexual and physical abuse, to first-hand experience of traumatizing accidents and sustained domestic conflict [41]. Analysis of covariance, controlling for age and gender, compared EEG data from subjects exposed to ELS with those who were unexposed. ELS was associated with significantly decreased power across the EEG spectrum. The between group differences were strongest in the eyes closed paradigm, where subjects who experienced ELS showed significantly reduced beta (F1,405=12.37, p=.000), theta (F1,405=20.48, p=.000), alpha (F1,405=9.65, p=.002) and delta power (F1,450=36.22, p=.000). ELS exposed subjects also showed a significantly higher alpha peak frequency (F1,405=6.39, p=.012) in the eyes closed paradigm. Analysis of covariance on ERP components revealed that subjects who experienced ELS had significantly decreased N2 amplitude (F1,405=7.73, p=.006). Analyses of variance conducted on measures of personality revealed that subjects who experienced ELS had significantly higher levels of neuroticism (F1,264=13.39, p=.000) and openness (F1,264=17.11, p=.000), but lower levels of conscientiousness, than controls (F1,264=4.08, p=.044). The number of ELS events experienced was shown to be a significant predictor of scores on the DASS questionnaire [27], which rates subjects on symptoms of depression (F3,688=16.44, p=.000, R2=.07), anxiety (F3,688=14.32, p=.000, R2=.06) and stress (F3,688=20.02, p=.000, R2=.08). Each additional early life stressor was associated with an increase in these scores independent of age, gender and the type of stressor. Furthermore, the number of ELS experiences among smokers was also found to be a positive predictor of the nicotine dependency score (Faegstrom Test For Nicotine Dependence, [19]) (F3,104=10.99, p=.000, R2=.24), independent of age, gender and type of stressor. In conclusion, we highlight the impact of a history of ELS showed significant effects on brain function (EEG and ERP activity), personality dimensions and nicotine dependence.

The present study combined neuropsychological and electrophysiological measures to obtain a comprehensive profile of the everyday attentional and memory dysfunction reported in PTSD. The event-related potential (ERP) literature has consistently found abnormalities in late components (N2, P3) reflecting working memory (WM) function. However, the neuropsychological profile reported in the literature has considerable variation. The present study examined ERP activity in 33 PTSD participants and matched controls during a standard two-tone auditory oddball task. Neuropsychological assessment was carried out using a task battery assessing a wide range of cognitive functions. Consistent with previous work, the PTSD group showed delayed N2 latency and reduced P3 target amplitude, together with slower and less accurate target detection. Scalp topography provided evidence of widespread abnormality during WM function, but with strongest effects broadly over the left hemisphere. Neuropsychological testing found concomitant difficulties on factorial measures of verbal memory retention/access and sustained attention but enhanced performance on measures of immediate recall. This integrative pattern of effects reflects a specific impairment in the operation of working memory systems that guide ongoing, planned behavior and that facilitate the acquisition and retention of new memories.

Over the last decade, an increasing number of research studies have focused on the construct of Emotional Intelligence (EI), which may be broadly defined as the capacity to perceive and regulate emotions in oneself as well as those of others. Researchers have generally adopted an organizational or management focus to the study of EI, however studies which adopt a more integrated perspective by combining psychological with biological measures, may help in further elucidating this relatively abstract construct. The first objective of this paper was to report on the psychometric properties of a brief, self-report measure of EI (Brain Resource Inventory for Emotional intelligence Factors or BRIEF), comprising internal emotional capacity (IEC), external emotional capacity (EEC) and self concept (SELF). Second, we further explored the validity of the measure by assessing the relationships between the BRIEF and variables considered relevant to the understanding of EI (including gender, age, personality, cognitive intelligence and resting state electroencephalography, EEG). The BRIEF possessed sound psychometric properties (internal consistency, r=0.68-0.81; test-retest reliability, r=0.92; construct validity with the Self Report Emotional Intelligence Test, r=0.70). As hypothesized, females were found to score higher than males on EI. EI was associated more with personality than with cognitive ability, and EEG was found to explain a significant portion of the variance in EI scores. The finding that low EI is related to underarousal of the left-frontal cortex (increased theta EEG) is consistent with research on patients with depression, as well as attention deficit hyperactivity disorder. Although EI did not display age-related increases, this might relate to the exclusion of adolescents from our sample. In conclusion, examination of the way in which EI measures relate to a complementary range of psychological and biological measures may help to further elucidate this construct.

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 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.

Aims: To examine how general (e.g., memory, attention) and social (emotional and interpersonal processes) cognition relate to measures of brain function and structure. Methods: PCA was used to identify general and social cognitive factors from the Brain Resource International Database in 1,316 subjects. The identified factors were correlated with each subject's corresponding brain structure (MRI) and function (EEG/ERP) data. Results: Seven core cognitive factors were identified for general and three for social. General cognition was correlated with global grey matter, while social cognition was negatively correlated with grey matter in fronto-temporal-somatosensory regions. Executive function, information processing speed and verbal memory performance were correlated with delta-theta qEEG, while most general cognitive factors negatively correlated with beta qEEG. Faster information processing speed was correlated with alpha qEEG. Executive function and information processing speed was correlated with negative-going ERP amplitude and slower ERP latency at frontal sites, but at posterior sites negative correlations were found. Discussion: In contrast to general cognition, social cognition is identified by different functional (automated) activity and more localized neural structures. Only general cognition, requiring more effortful, controlled processing is related to brain function measures, particularly in frontal cortices. Integrative Significance: Recording measures from multiple modalities including MRI, EEG/ERP, social and general cognition within the same subject provides a method of brain profiling for use in cognitive-neurotherapy and pharmacological studies.

Compared with many other cognitive functions, relatively little is known about time representation in the brain. Recent work shows disrupted timing and time estimation in older adults, although it is unclear whether these effects are the result of normal aging or disease-related processes. The present study examined time estimation in persons across the adult lifespan who were free from significant medical or psychiatric history. Results showed older adults exhibited greater variability in time estimation, but no evidence for systematic acceleration or slowing emerged. This variability was correlated with performance on a variety of cognitive tests including attention, working memory and executive function. Although no relationship emerged between time estimation and EEG indices from central regions, multiple MRI indices were significantly correlated with time estimation. Stepwise regression showed volume of the supplementary motor area predicted variability in time estimation. These results indicate that healthy aging is associated with altered time estimation and suggest that changes in frontal brain regions mediate these effects.

Posttraumatic Stress Disorder (PTSD) is characterized by symptoms of hyperarousal, avoidance and intrusive trauma-related memories and deficits in everyday memory and attention. Separate studies in PTSD have found abnormalities in electroencephalogram EEG, in event-related potential (ERP) and behavioral measures of working memory and attention. The present study seeks to determine whether these abnormalities are related and the extent to which they share this relationship with clinical symptoms. EEG data were collected during an eyes-open paradigm and a one-back working memory task. Behavioral and clinical data (CAPS) were also collected. The PTSD group showed signs of altered cortical arousal as indexed by reduced alpha power and an increased theta/alpha ratio, and clinical and physiological measures of arousal were found to be related. The normal relationship between theta power and ERP indices of working memory was not affected in PTSD, with both sets of measures reduced in the disordered group. Medication appeared to underpin a number of abnormal parameters, including P3 amplitude to targets and the accuracy, though not speed, of target detection. The present study helps to overcome a limitation of earlier studies that assess such parameters independently in different groups of patients that vary in factors such as comorbidity, medication status, gender and symptom profile. The present study begins to shed light on the relationship between these measures and suggests that abnormalities in brain working memory may be linked to underlying abnormalities in brain stability.

The current study aimed to investigate whether children and adolescents diagnosed with Attention Deficit/Hyperactivity Disorder Predominantly Inattentive (AD/HD-in; Child n = 24, Adolescent n = 33) and Combined (AD/HD-com; Child n = 30, Adolescent n = 42) subtypes were more distractible than controls (Child n = 54; Adolescents n = 75), by assessing event-related potential (ERP), performance and peripheral arousal measures. All AD/HD groups displayed smaller amplitudes and/or shorter latencies of the P3a ERP component — thought to reflect involuntary attention switching — following task-deviant novel stimuli (checkerboard patterns) embedded in a Working Memory (WM) task. The P3a results suggested that both AD/HD-in and AD/HD-com subtypes ineffectively evaluate deviant stimuli and are hence more "distractible". These abnormalities were most pronounced over the central areas. AD/HD groups did not display any abnormalities in averaged heart rate over the WM task, a measure of peripheral arousal. They did display abnormalities in performance measures from the task, but these were unrelated to P3a abnormalities. AD/HD groups also displayed a number of deficits on Switching of Attention and Verbal Memory tasks, however, the pattern of abnormality mostly reflected general cognitive deficits rather than resulting from distraction.

There have been significant advances in understanding the neurobiology of Attention-Deficit/Hyperactivity Disorder (ADHD) and it is timely to examine the ability of biological and psychological markers to predict medication response in this disorder. We evaluated prediction of medication response in adolescent ADHD using neuropsychological testing and psychophysiological measures of central and autonomic function. Fifty ADHD adolescents participated in pre- and post-stimulant medication testing. Separately ranked performance in auditory oddball and visual Working Memory (WM) tasks determined 20 "responders" and 20 "non-responders" with 10 "neutrals" excluded from the discriminant function analyses (DFA). For both oddball and WM performance rankings, the two groups did not differ in age, sex, or handedness. However, responders did have higher levels of symptomatology than non-responders at baseline. Pre-stimulant medication psychophysiology variables were used as predictors in each DFA. Oddball performance correctly classified 85.0% of responders and 95.0% of non-responders. Better response was associated with increased resting beta power (left posteriorly), delayed oddball target N1 (frontally), decreased oddball target P2 (left posteriorly) and decreased WM distractor P3 (right frontally). Working memory performance classified 80.0% of responders and 90.0% of non-responders, with a broadly similar profile of psychophysiological predictors. These finding indicate the value of integrating neuropsychological and psychophysiological data in predicting medication response in ADHD.

The effects of methylphenidate (MPH) on 32 healthy human male volunteers (aged 18 to 25 years, mean age = 22.26) were examined using a within-subject design. Each participant attended six testing periods, held once per week. Within each testing period, three repeat testing sessions were undertaken: pre-medication, on-medication and two hours post-medication. In these sessions, dose was manipulated (placebo, 5 mg, 15 mg or 45 mg) according a double-blind placebo design. In this report, we focus on behavioral, autonomic arousal (heart rate, skin conductance) and psychophysiological (ERP) data acquired during the working memory task. We found increased autonomic arousal (heart rate, skin conductance and blood pressure) with MPH. A linear reduction in reaction time, omission errors and target P3 latency, and a corresponding increase in background P3 amplitude was observed with increased MPH dose. The relationship between these measures supported an increase in performance and underlying brain function with MPH. To our knowledge, this is the first paper to use behavioral, arousal and electrophysiological measures in an integrative approach to study the effects of MPH on healthy adults.

Clinical depression is one of the most common psychiatric disorders in adults, yet non-clinical depression in the community may go unnoticed, despite high prevalence rates and significant psychosocial impairment. The aim of the current study was to classify 1,226 individuals from a community sample on the basis of depression scores (using the Depression Anxiety Stress Scales, DASS) and to determine whether depression in a non-clinical sample differed significantly from healthy controls on a profile of multimodal measures. The data analyzed in this study included personality, emotional intelligence, cognition and psychophysiology. It was predicted that non-clinically depressed participants would differ from healthy controls on measures of personality (increased neuroticism; decreased extraversion), emotional intelligence (decreased), cognition (impairments in executive dysfunction and memory impairment), psychophysiology (increased resting-state, right-frontal activation; diminished skin conductance) after controlling for gender, age, handedness and years of education. Findings provide support for the majority of hypotheses, though no evidence was found for memory impairment or frontal hemispheric asymmetry. Longitudinal studies are needed to determine the extent to which of these findings will have utility for the prediction of depression onset and treatment response/non-response.

Coherent cognition requires activity to be brought together across diverse brain networks. Synchronous, in-phase oscillations in the high-frequency (40 Hz) Gamma range are thought to be one mechanism underlying the functional integration of brain networks. While sex differences have been observed across a range of cognitive functions, their role in normal cortical synchronization has not been elucidated. We recorded Gamma phase synchrony in 500 male and 500 female subjects during an auditory oddball task, which taps discrimination of task-relevant signals. Results revealed a marked sex-linked dissociation in the spatio-temporal pattern of cortical synchronization. Females showed increased Gamma synchrony in the frontal brain, while males showed enhanced synchrony in the parieto-occipital region. These differences were not accounted for by sex differences in whole brain MRI volume. However, there were positive associations between Gamma synchrony and gray matter for females, while these relationships were negative for males. Sex differences in the profile of cortical synchronization may reflect distinct aspects of evolutionary advantage.

Decline in cognitive function is well recognized, yet few neurophysiological correlates of age-related cognitive decline have been identified. In this study we examined the impact of age on neurocognitive function and Gamma phase synchrony among 550 normal subjects (aged 11-70). Gamma phase synchrony was acquired to targets in the auditory oddball paradigm. The two tasks of executive function were switching of attention and an electronic maze. Subjects were divided into four age groups, which were balanced for sex. We hypothesized that reduced cognitive performance among older healthy individuals would be associated with age-related changes in gamma phase synchrony. Results showed a significant decrease in executive function in the oldest (51-70 years) age group. ANOVAs of age-by-frontal Gamma synchrony also showed a significant effect of age on Gamma phase synchrony in the left frontal region that corresponded modestly to the age effect found on executive task performance, with reduced performance associated with increased gamma synchrony. The results indicate that age-related changes in cognitive function evident among elderly individuals may in part be related to decreased ability to integrate information and this may be reflected as a compensatory increase in gamma synchrony in frontal regions of the brain.

A recently developed quantitative model of cortical activity is used that permits data comparison with experiment using a quantitative and standardized means. The model incorporates properties of neurophysiology including axonal transmission delays, synaptodendritic rates, range-dependent connectivities, excitatory and inhibitory neural populations, and intrathalamic, intracortical, corticocortical and corticothalamic pathways. This study tests the ability of the model to determine unique physiological properties in a number of different data sets varying in mean age and pathology. The model is used to fit individual electroencephalographic (EEG) spectra from post-traumatic stress disorder (PTSD), schizophrenia, first episode schizophrenia (FESz), attention deficit hyperactivity disorder (ADHD), and their age/sex matched controls. The results demonstrate that the model is able to distinguish each group in terms of a unique cluster of abnormal parameter deviations. The abnormal physiology inferred from these parameters is also consistent with known theoretical and experimental findings from each disorder. The model is also found to be sensitive to the effects of medication in the schizophrenia and FESz group, further supporting the validity of the model.