NFTsim: Theory and Simulation of Multiscale Neural Field Dynamics.

A user ready, portable, documented software package, NFTsim, is presented to facilitate numerical simulations of a wide range of brain systems using continuum neural field modeling. NFTsim enables users to simulate key aspects of brain activity at multiple scales. At the microscopic scale, it incorporates characteristics of local interactions between cells, neurotransmitter effects, synaptodendritic delays and feedbacks. At the mesoscopic scale, it incorporates information about medium to large scale axonal ranges of fibers, which are essential to model dissipative wave transmission and to produce synchronous oscillations and associated cross-correlation patterns as observed in local field potential recordings of active tissue. At the scale of the whole brain, NFTsim allows for the inclusion of long range pathways, such as thalamocortical projections, when generating macroscopic activity fields. The multiscale nature of the neural activity produced by NFTsim has the potential to enable the modeling of resulting quantities measurable via various neuroimaging techniques. In this work, we give a comprehensive description of the design and implementation of the software. Due to its modularity and flexibility, NFTsim enables the systematic study of an unlimited number of neural systems with multiple neural populations under a unified framework and allows for direct comparison with analytic and experimental predictions. The code is written in C++ and bundled with Matlab routines for a rapid quantitative analysis and visualization of the outputs. The output of NFTsim is stored in plain text file enabling users to select from a broad range of tools for offline analysis. This software enables a wide and convenient use of powerful physiologically-based neural field approaches to brain modeling. NFTsim is distributed under the Apache 2.0 license.

The impact of melancholia versus non-melancholia on resting-state, EEG alpha asymmetry: electrophysiological evidence for depression heterogeneity.

While depression has been associated with relatively greater right than left frontal cortical activity - a neurophysiological marker reflecting greater activation of the withdrawal system - contradictory findings have been reported. It was hypothesised that melancholia would be associated with relative right frontal activation, in comparison to non-melancholia and controls. We collected 2-min of resting-state, eyes closed, electroencephalographic activity from a total of 237 participants including 117 patients with major depressive disorder (57 with melancholia, 60 with non-melancholia) and 120 healthy controls. In contrast to hypotheses, patients with non-melancholia displayed relative left frontal activation in comparison to controls and those with melancholia. These findings were associated with a small to moderate effect size (Cohen's d=0.30-0.34). Critically, patients with melancholic subtype did not differ from controls despite increased severity - relative to those with non-melancholia - on clinical measures. These results may reflect an increase in approach tendencies in patients with non-melancholia including reassurance seeking, anger or irritable aggression. Findings highlight the need for further research on the heterogeneity MDD.

Comparison of ictal electroencephalogram between ultrabrief- and brief-pulse right unilateral electroconvulsive therapy: a multitaper jackknife analysis.

OBJECTIVE: Characterization of the ictal electroencephalogram (EEG) generated during ultrabrief pulse electroconvulsive therapy (ECT) is important to progress its use in routine ECT practice particularly in indicating treatment efficacy. The study compared 2- to 5-Hz and 5.2- to 13-Hz bands of the ictal EEG signal between brief- and ultrabrief-pulse ECT. METHODS: Twenty-five patients with major depression were randomized to brief- (1 millisecond [ms]) and ultrabrief-pulse (0.3 ms) right unilateral ECT. In sessions 2 to 8, when patients in either group received 6 times threshold ECT, right and left frontal ictal EEG between ultrabrief (n = 60) and brief pulse (n = 63) were compared. Electroencephalographic spectra from 2- to 5-Hz and 5.2- to 13-Hz bands in the mid and postictal phases were subjected to multitaper jackknife analysis of spectral power density (µV/Hz) and its SD or "regularity" (µV/Hz), peak spectral frequency (Hz), and its standard deviation (SD) or regularity (Hz). Linear mixed-effect models were used to compare the outcomes. RESULTS: In ultrabrief ECT, spectral power density and its SD were significantly smaller within the mid seizure of both bands, whereas peak frequency and its SD were similar. Postseizure suppression of spectral power density of both bands was similar in either treatments. CONCLUSION: Lower spectral power densities were noted with ultrabrief-pulse ECT vis-a-vis brief-pulse ECT. However, in ultrabrief pulse ECT, regularity measures and postseizure suppression were comparable to brief-pulse ECT.

Autonomic and cortical reactivity in acute and chronic posttraumatic stress.

This study investigated attention (P300 amplitude) and orienting (skin conductance amplitude) to auditory tones in a standard oddball task in early trauma-exposed groups (Acute Stress Disorder: ASD) (n=12) or no ASD (n=13), compared to individuals with chronic posttraumatic stress disorder (PTSD) (n=17) and non-trauma-exposed controls (n=17). Individuals with ASD displayed significantly higher SCR and P3 amplitudes to target tones than individuals with PTSD, non-traumatized controls, and traumatized controls. These findings suggest that attention and orienting responses are greater to neutral, task-relevant target tones in ASD than PTSD and traumatized and non-traumatized controls.

Eye tracking and physiological reactivity to threatening stimuli in posttraumatic stress disorder.

This study tested the vigilance-avoidance model of anxiety and attention bias in posttraumatic stress disorder (PTSD). This study used eye tracking technology to record initial fixations, pupil dilation, fixation time and concurrent skin conductance response to examine initial orienting towards threat stimuli and subsequent fixations. Twenty-one traumatized participants (11 diagnosed with PTSD and 10 trauma-exposed participants without PTSD) viewed 32 stimuli (with four words in each quadrant). Sixteen trials contained a trauma-relevant word in one quadrant and 16 had four neutral words. PTSD patients reported significantly greater number of initial fixations to trauma words, and a greater number of skin conductance responses to initial threat fixations. There were no significant differences in subsequent fixations to trauma words between groups. Although this study provides evidence of attentional bias towards threat that is accompanied by specific autonomic arousal, it does not indicate subsequent avoidance of threat stimuli in PTSD.

Anterior cingulate activity to salient stimuli is modulated by autonomic arousal in posttraumatic stress disorder.

Reduced ventral anterior cingulate (vACC) activity to threat is thought to reflect an impairment in regulating arousal networks in posttraumatic stress disorder (PTSD). Concurrent functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) recording were used to examine neural functioning when arousal networks are engaged. Eleven participants with PTSD and 11 age- and sex-matched non-traumatized controls performed an oddball task that required responding to salient, non-trauma-related auditory target tones embedded in lower frequency background tones. Averaged target-background analyses revealed significantly greater dorsal ACC, supramarginal gyrus, and hippocampal activity in PTSD relative to control participants.With-SCR target responses resulted in increased vACC activity in controls, and dorsal ACC activity in PTSD. PTSD participants had reduced vACC activity relative to controls to target tones when SCR responses were present. This reduction in vACC in PTSD relative to controls was not apparent in without-SCR responses. These findings suggest that a reduction in vACC in PTSD occurs specifically when arousal networks are engaged.

Integrating objective gene-brain-behavior markers of psychiatric disorders.

There is little consensus about which objective markers should be used to assess major psychiatric disorders, and predict/evaluate treatment response for these disorders. Clinical practice relies instead on subjective signs and symptoms, such that there is a "translational gap" between research findings and clinical practice. This gap arises from: a) a lack of integrative theoretical models which provide a basis for understanding links between gene-brain-behavior mechanisms and clinical entities; b) the reliance on studying one measure at a time so that linkages between markers are their specificity are not established; and c) the lack of a definitive understanding of what constitutes normative function. Here, we draw on a standardized methodology for acquiring multiple sources of genomic, brain and behavioral data in the same subjects, to propose candidate markers of selected psychiatric disorders: depression, post-traumatic stress disorder, schizophrenia, attention-deficit/hyperactivity disorder and dementia disorders. This methodology has been used to establish a standardized international database which provides a comprehensive framework and the basis for testing hypotheses derived from an integrative theoretical model of the brain. Using this normative base, we present preliminary findings for a number of disorders in relation to the proposed markers. Establishing these objective markers will be the first step towards determining their sensitivity, specificity and treatment prediction in individual patients.

Integrating "brain" and "body" measures: correlations between EEG and metabolic changes over the human lifespan.

AIMS: This study investigated the relationship between electroencephalograph (EEG) power and basal metabolic rate (BMR) over the human lifespan, to better understand the mechanisms involved in the decline of neural activity with age. METHODS: Eyes-open EEG power was calculated in standard frequency bands and averaged across recording sites in 1831 healthy subjects aged 6 to 86 years, from the Brain Resource International Database. In a subset of 175 subjects, structural MRI scans were also undertaken to determine the role of grey matter. Cerebral metabolic rate (CMR) was estimated using two models of EEG power, based on: (1) normalization of BMR by total body mass, and (2) scaling by cortical grey matter. RESULTS: Regression analysis revealed a linear relationship between the CMR estimates and EEG power under both models. In the full sample, CMR explained 65% of the variance in delta power, and 53% of the variance in theta power over the age span. DISCUSSION: The results demonstrate that the large EEG signals in early childhood are associated with a higher BMR during that age. INTEGRATIVE SIGNIFICANCE: The use of cross-modal measurements in this study highlights the utility of capturing data in an integrative framework to reveal fundamental physiological relationships.

Mapping frontal-limbic correlates of orienting to change detection.

Orienting responses are elicited by salient stimuli, and may be indexed by skin conductance responses. Concurrent functional magnetic resonance imaging and skin conductance response recording was used to identify neural correlates of orienting to abrupt sensory change (infrequent high pitch oddball 'target' tones embedded in frequent lower pitch 'standard' tones) in 16 healthy participants. 'With skin conductance response' responses to targets were distinguished by preferentially greater activity in the amygdala and ventral medial and lateral frontal cortical regions. By contrast, 'without skin conductance response' responses elicited distinctive activity in the dorsal lateral frontal cortex and supramarginal gyrus. These findings suggest that orienting to unexpected sensory change elicits a network for appraising salience and novelty, whereas, in the absence of orienting, a parallel network for sensory and context evaluation is preferentially engaged.

Neural networks of information processing in posttraumatic stress disorder: a functional magnetic resonance imaging study.

BACKGROUND: Neuroimaging studies report reduced medial prefrontal cortical (particularly anterior cingulate) but enhanced amygdala response to fear signals in posttraumatic Stress Disorder (PTSD). We investigated whether anterior cingulate-amygdala dysregulation in PTSD would generalize to salient, but nonthreat related signals. METHODS: Individuals with PTSD (n = 14) and age and sex-matched nontraumatized controls (n = 14) completed an auditory oddball paradigm adapted to functional magnetic resonance imaging at a 1.5-T field strength. RESULTS: Controls displayed bilateral activation in ventral anterior cingulate and amygdala networks, and PTSD subjects showed bilateral dorsal anterior cingulate and amygdala activation to targets relative to nontargets. Compared to controls, PTSD subjects showed enhanced responses to targets in the dorsal and rostral anterior cingulate, and left amygdala. Whole-brain analyses confirmed the expected pattern of distributed prefrontal-parietal responses to targets in the oddball task. Greater activity in posterior parietal somatosensory regions was observed in PTSD. CONCLUSIONS: Our findings of enhanced anterior cingulate responses in PTSD contrast with reports of reduced activity for threat stimuli, suggesting that the latter may be specific to processing of threat-related content. Activation in rostral and dorsal anterior cingulate, left amygdala and posterior parietal networks in response to salient, nonthreatening stimuli may reflect generalized hypervigilance.