Nicholas R. Cooper

Integrative Neuroscience: The Role of a Standardized Database

Most brain related databases bring together specialized information, with a growing number that include neuroimaging measures. This article outlines the potential use and insights from the first entirely standardized and centralized database, which integrates information from neuroimaging measures (EEG, event related potential (ERP), structural/functional MRI), arousal (skin conductance responses (SCR)s, heart rate, respiration), neuropsychological and personality tests, genomics and demographics: The Brain Resource International Database. It comprises data from over 2,000 “normative” subjects and a growing number of patients with neurological and psychiatric illnesses, acquired from over 50 laboratories (in the USA, United Kingdom, Holland, South Africa, Israel and Australia), all with identical equipment and experimental procedures. Three primary goals of this database are to quantify individual differences in normative brain function, to compare an individuals performance to their database peers, and to provide a robust normative framework for clinical assessment and treatment prediction. We present three example demonstrations in relation to these goals. First, we show how consistent age differences may be quantified when large subject numbers are available, using EEG and ERP data from nearly 2,000 stringently screened normative subjects. Second, the use of a normalization technique provides a means to compare clinical subjects (50 ADHD subjects in this study) to the normative database with the effects of age and gender taken into account. Third, we show how a profile of EEG/ERP and autonomic measures potentially provides a means to predict treatment response in ADHD subjects. The example data consists of EEG under eyes open and eyes closed and ERP data for auditory oddball, working memory and Go-NoGo paradigms. Autonomic measures of skin conductance (tonic skin conductance level, SCL, and phasic skin conductance responses, SCRs) were acquired simultaneously with central EEG/ERP measures. The findings show that the power of large samples, tested using standardized protocols, allows for the quantification of individual differences that can subsequently be used to control such variation and to enhance the sensitivity and specificity of comparisons between normative and clinical groups. In terms of broader significance, the combination of size and multidimensional measures tapping the brains core cognitive competencies, may provide a normative and evidence-based framework for individually-based assessments in “Personalized Medicine.”

Development and validation of a World-Wide-Web-based neurocognitive assessment battery: WebNeuro

Assessment of neurocognitive functioning is a critical task in many clinical, educational, service, and industrial settings. We report on descriptive and validation data of a new, World-Wide-Web-based, comprehensive battery of neurocognitive functioning, WebNeuro, that can be used in both applied and research contexts. Fifty healthy control participants completed both WebNeuro, and an established non-Internet-based computerized cognitive assessment battery, IntegNeuro, that uses a touchscreen platform. Results indicated comparability across the two batteries, in terms of critical single test scores, factor analysis derived indices, overall performance scores, and sex differences. These results support the validity of WebNeuro as a neurocognitive assessment measure. Advantages of its use in applied and research settings are discussed.

Explicit identification and implicit recognition of facial emotions: II. Core domains and relationships with general cognition

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.

CROSS-CULTURAL ASSESSMENT OF NEUROPSYCHOLOGICAL PERFORMANCE AND ELECTRICAL BRAIN FUNCTION MEASURES: ADDITIONAL VALIDATION OF AN INTERNATIONAL BRAIN DATABASE

Previous studies haverevealed significant differences in performance on nonlanguage dependent cognitive tests across international settings among younger individuals, with less pronounced differences evident among older individuals (>54 years of age). The present study examined a broad range of cognitive performance as well as electrophysiological indices of brain function in a multisite and international context. A total of 200 individuals in the United States, 233 individuals in Europe, and 829 individuals in Australia were administered a standardized computerized neuropsychological battery, and complementary electroencephalogram (EEG) recordings were completed. Results revealed no significant differences in cognitive function or electrophysiology across the three continents. Similarly, although there was a main effect for age, the interaction between age and continent was not significant in any of the omnibus analyses. These findings indicate a high degree of similarity in neurocognitive and electrophysiological function among individuals residing in developed Western cultures, consistent with a traitlike status and the high heritability of the EEG.

EEG alpha asymmetry in schizophrenia, depression, PTSD, panic disorder, ADHD and conduct disorder.

Models of laterality infer distinct aspects of EEG alpha asymmetry in clinical disorders, which has been replicated for over three decades. This biomarker now requires a more fine-grained assessment of its clinical utility as a diagnostic and treatment predictive marker. Here, within the same study we assessed resting brain laterality across six clinical disorders, for which deviant laterality has been implicated as core dysfunction. These disorders were evaluated in comparison to a large normative dataset (∼1,900) from the Brain Resource International Database. EEG alpha asymmetry was assessed in the frontocentral region, for resting Eyes Closed and Eyes Open conditions. Schizophrenia was characterized by significantly greater left lateralized alpha power than controls, indicating a deficit in left frontal activity at rest, which may relate to “disconnections” across wider fronto-temporal networks. The depression group showed a trend-level tendency towards the opposite pattern of greater right-lateralized activity than controls. The remaining anxiety and behavioral disorders did not show any significant deviance in alpha asymmetry from the normative control group. However, at a non-significant level laterality for these groups was generally consistent with expected directions, suggesting a propensity towards a particular lateralization but still remaining within the normative range. Overall, the results of the current study indicate that EEG alpha asymmetry may show the most clinical utility as a biomarker for schizophrenia and depression in comparison to other clinical disorders.

Cortical inhibition in motor and non-motor regions: a combined TMS-EEG study.

A number of studies using paired pulse transcranial magnetic stimulation (TMS) have demonstrated that cortical inhibition (CI) of the motor cortex can be recorded and also gauged through surface electromyography. However, recording CI from other brain regions that are more directly related with the pathophysiology of some neurologic and psychiatric disorders (e.g., dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously fraught with technical difficulties. This study was therefore designed to examine, through a combination of TMS with EEG, whether CI could be measured directly from the motor cortex, DLPFC, and another non-motor region. To index CI, long interval cortical inhibition (LICI; a TMS paradigm) was used in the motor cortex and DLPFC in 14 healthy subjects, and in the parietal lobe in 5 of those subjects. In the motor cortex, LICI resulted in a significant suppression in mean cortical evoked activity on EEG (37.31 ± 47.51 %). In the DLPFC, LICI resulted in a significant suppression (32.45 ± 47.86 %) in mean cortical evoked activity and did not correlate with LICI in the motor cortex although they did not significantly differ. In the parietal lobe, LICI resulted in significant suppression (47.76 ± 44.70 %) in mean cortical evoked activity. In conclusion, CI in the dorsolateral prefrontal cortex, motor cortex and parietal cortex were similar at 120% of motor threshold. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurologic and psychiatric disorders.

Individualized Alpha Activity and Frontal Asymmetry in Major Depression

Lateralized differences in frontal alpha power in individuals with major depressive disorder (MDD) are thought to reflect an aberrant affective processing style. However research into anterior alpha asymmetry and MDD has often produced conflicting results. The current study aimed to investigate whether individualized alpha bandwidths provide a more sensitive measure of anterior alpha asymmetry in MDD than the traditional fixed 8–13 Hz alpha band. Resting EEG was recorded from 34 right-handed female participants (18 controls, 16 MDD). Each participants Individual Alpha Frequency was used to delineate a broad individualized alpha band and three individualized narrow alpha sub-bands: lower alpha1, lower alpha 2 and upper alpha. Activity within the broad and narrow individualized bandwidths and within the traditional fixed alpha band were used to compare a) controls and acutely depressed individuals and b) medicated and unmedicated MDD participants. Individualizing and subdividing the alpha bandwidth did not add appreciably to the sensitivity of anterior alpha asymmetry in MDD as no significant differences in lateralized alpha power between controls and MDD participants were observed in any alpha bandwidth. This finding was consistent under two reference schemes and across multiple scalp locations. Within the MDD group, antidepressant use was associated with significantly greater right than left hemispheric power in the lower alpha 1 band. The relevance of this finding is discussed in relation to the electrophysiological correlates of antidepressant medication use, lateralized differences in affective processing and treatment resistant MDD.

EEG MARKERS FOR COGNITIVE DECLINE IN ELDERLY SUBJECTS WITH SUBJECTIVE MEMORY COMPLAINTS

New treatments for Alzheimers disease require early detection of cognitive decline. Most studies seeking to identify markers of early cognitive decline have focused on a limited number of measures. We sought to establish the profile of brain function measures which best define early neuropsychological decline. We compared subjects with subjective memory complaints to normative controls on a wide range of EEG derived measures, including a new measure of event-related spatio-temporal waves and biophysical modeling, which derives anatomical and physiological parameters based on subjects EEG measurements. Measures that distinguished the groups were then related to cognitive performance on a variety of learning and executive function tasks. The EEG measures include standard power measures, peak alpha frequency, EEG desynchronization to eyes-opening, and global phase synchrony. The most prominent differences in subjective memory complaint subjects were elevated alpha power and an increased number of spatio-temporal wave events. Higher alpha power and changes in wave activity related most strongly to a decline in verbal memory performance in subjects with subjective memory complaints, and also declines in maze performance and working memory reaction time. Interestingly, higher alpha power and wave activity were correlated with improved performance in reverse digit span in the subjective memory complaint group. The modeling results suggest that differences in the subjective memory complaint subjects were due to a decrease in cortical and thalamic inhibitory gains and slowed dendritic time-constants. The complementary profile that emerges from the variety of measures and analyses points to a nonlinear progression in electrophysiological changes from early neuropsychological decline to late-stage dementia, and electrophysiological changes in subjective memory complaint that vary in their relationships to a range of memory-related tasks.

Reduced cortico-motor facilitation in a normal sample with high traits of autism

Recent research in social neuroscience proposes a link between mirror neuron system (MNS) and social cognition. The MNS has been proposed to be the neural mechanism underlying action recognition and intention understanding and more broadly social cognition. Pre-motor MNS has been suggested to modulate the motor cortex during action observation. This modulation results in an enhanced cortico-motor excitability reflected in increased motor evoked potentials (MEPs) at the muscle of interest during action observation. Anomalous MNS activity has been reported in the autistic population whose social skills are notably impaired. It is still an open question whether traits of autism in the normal population are linked to the MNS functioning. We measured TMS-induced MEPs in normal individuals with high and low traits of autism as measured by the autistic quotient (AQ), while observing videos of hand or mouth actions, static images of a hand or mouth or a blank screen. No differences were observed between the two while they observed a blank screen. However participants with low traits of autism showed significantly greater MEP amplitudes during observation of hand/mouth actions relative to static hand/mouth stimuli. In contrast, participants with high traits of autism did not show such a MEP amplitude difference between observation of actions and static stimuli. These results are discussed with reference to MNS functioning.

Brain structure and function correlates of general and social cognition

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 Brain Resource International Database in 1,316 subjects. The identified factors were correlated with each subjects 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.