The Brain Dynamics Centre - Convenor of BRAINnet

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.

Voxel-based morphometry (VBM) studies have provided valuable data on the nature and distribution of gray and white matter abnormalities in schizophrenia relative to the whole brain. Most VBM studies have focused on chronic patients, but there are accumulating studies of first-episode schizophrenia and other high-risk groups such as first-degree relatives. This review outlines the evidence from VBM studies of both chronic and first-episode/high-risk groups. The most consistent reduction revealed in chronic patients is in the superior temporal cortex, and in first-episode/high-risk individuals, in frontal brain regions. These findings are reviewed in relation to complementary evidence for neurodevelopmental deviation, and functional associations with both neuroimaging and behavioral measures of general and social cognition.

The limit cycles of brain activity are studied using a compact continuum model that reproduces the main features of electroencephalographic signals, including bifurcations of fixed points and limit cycles in seizures. Frequencies and amplitudes are predicted analytically and related to physiology. Gaussian stimuli yield two distinct evoked responses in the linearly stable zone, consistent with experiment. Limit cycles can be initiated or suppressed by control signals or stimuli.

We show that observed spatial- and frequency-domain signatures of intense solar-wind Langmuir waves can be described as eigenmodes trapped in a parabolic density well. Measured solar-wind electric field spectra and waveforms are compared with 1D linear solutions and, in many cases, can be represented by 1-3 low-order eigenstates. To our knowledge, this report is the first observational confirmation of Langmuir eigenmodes in space. These results suggest that linear eigenmodes may be the starting point of the nonlinear evolution, critical for producing solar type II and type III radio bursts.

Elevated body mass index (BMI) is associated with adverse neurocognitive outcome in adults, including reduced neuropsychological test performance. It is unknown whether this relationship also exists in children and adolescents. A total of 478 children and adolescents (age 6-19) without significant medical or psychiatric history provided demographic information and completed a computerized cognitive test battery. Participants were categorized using clinical criteria into underweight, normal weight, at risk for overweight and overweight groups based on age and gender. Partial correlation and MANCOVA analyses adjusting for age and intellectual function found no relationship between BMI and cognitive test performance in the full sample. However, analyses performed separately by gender showed that underweight females exhibited poorer memory performance than other female BMI groups. These findings suggest that elevated BMI is not associated with cognitive function in healthy children and adolescents, though underweight might be a risk factor for reduced memory performance in females. Further work is needed to clarify the inconsistent findings between adults and minors.

A successful physiologically based continuum model of the corticothalamic system is applied to determine the relative contributions of axonal and intrinsic cellular delays to the waveforms of absence seizures. The predicted period of the absence seizure depends linearly on model parameters describing thalamocortical, corticothalamic, intracortical, and synaptodendritic delays, and these dependences are linked to the seizure mechanism by showing how time intervals between peaks in the waveforms depend on the parameters. Counterintuitively, it is found that a peak in the local field potential recorded in the thalamic relay nuclei can precede the peak in the cortical field that drove it, without violating causality, but rendering naive interpretation of time intervals between peaks invalid. We argue that a thalamocortical loop mechanism for absence seizures is consistent with intrathalamic cellular properties being the leading determinant of the frequency of spike-wave discharges in rat genetic models, with the combination of network and cellular properties providing a natural explanation for the lower frequency of human absence seizures. Finally, our results imply that the seizure frequency is not determined by the fastest thalamocortical and corticothalamic fibers, but rather depends on an effective weighted conduction velocity of all pathways present.

The valence-arousal (W. Heller, 1993) and approach-withdrawal (R. J. Davidson, 1998a) models hypothesize that particular patterns of hemispheric brain activity are associated with specific motivational tendencies and psychopathologies. We tested several of these predictions in two groups-a posttraumatic stress disorder (PTSD) and a "supercontrol" group, selected to be maximally different from those with PTSD. Contrary to almost all hypotheses, individuals with PTSD did not differ from controls on resting electroencephalogram (EEG) asymmetry. Particular aspects of PTSD were also not related to EEG hemisphere differences. Our null findings are consistent with the few studies that have examined resting EEG asymmetries in PTSD and suggest that PTSD may be associated with different processes than psychopathologies previously examined in studies of hemispheric brain activity (e.g., major depressive disorder, panic disorder).

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.

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.

BACKGROUND: Although cognitive behaviour therapy (CBT) is the treatment of choice for post-traumatic stress disorder (PTSD), approximately half of patients do not respond to CBT. No studies have investigated the capacity for neural responses during fear processing to predict treatment response in PTSD.MethodFunctional magnetic resonance imaging (fMRI) responses of the brain were examined in individuals with PTSD (n=14). fMRI was examined in response to fearful and neutral facial expressions presented rapidly in a backwards masking paradigm adapted for a 1.5 T scanner. Patients then received eight sessions of CBT that comprised education, imaginal and in vivo exposure, and cognitive therapy. Treatment response was assessed 6 months after therapy completion. RESULTS: Seven patients were treatment responders (defined as a reduction of 50% of pretreatment scores) and seven were non-responders. Poor improvement after treatment was associated with greater bilateral amygdala and ventral anterior cingulate activation in response to masked fearful faces. CONCLUSIONS: Excessive fear responses in response to fear-eliciting stimuli may be a key factor in limiting responses to CBT for PTSD. This excessive amygdala response to fear may reflect difficulty in managing anxiety reactions elicited during CBT, and this factor may limit optimal response to therapy.

Evoked potentials are the transient electrical responses caused by changes in the brain following stimuli. This work uses a physiology-based continuum model of neuronal activity in the human brain to calculate theoretical cortical auditory evoked potentials (CAEPs) from the model's linearized response. These are fitted to experimental data, allowing the fitted parameters to be related to brain physiology. This approach yields excellent fits to CAEP data, which can then be compared to fits of EEG spectra. It is shown that the differences between resting eyes-open EEG and standard CAEPs can be explained by changes in the physiology of populations of neurons in corticothalamic pathways, with notable similarities to certain aspects of slow-wave sleep. This pilot study demonstrates the ability of our model-based fitting method to provide information on the underlying physiology of the brain that is not available using standard methods.

A method of obtaining rate equations from conductance-based equations is developed and applied to fast-spiking and bursting neocortical neurons. It involves splitting systems of conductance-based equations into fast and slow subsystems, and averaging the effects of fast terms that drive the slowly varying quantities by showing that their average is closely proportional to the firing rate. The dependence of the firing rate on the injected current is then approximated in the analysis. The resulting behavior of the slow variables is then substituted back into the fast equations, with the further approximation of replacing the fast voltages in these terms by effective values. For bursting neurons the method yields two coupled limit-cycle oscillators: a self-exciting oscillator for the slow variables that commences limit-cycle oscillations at a critical current and modulates a fast spike-generating oscillator, thereby leading to slowly modulated bursts with a group of spikes in each burst. The dynamics of these coupled oscillators are then verified against those of the conductance-based equations. Finally, it is shown how to place the results in a form suitable for use in mean-field equations for neural population dynamics.

OBJECTIVE: To index the extent to which treatment response in posttraumatic stress disorder (PTSD) is predicted by rostral anterior cingulate cortex (rACC) volume. METHOD: We used structural magnetic resonance imaging in a 1.5 T scanner to examine subjects with PTSD (n = 13), traumatized control subjects (n = 13) and nontraumatized control subjects (n = 13). Subjects with PTSD then participated in 8 sessions of cognitive-behavioural therapy, after which we reassessed them for PTSD. RESULTS: According to voxel-based morphometry, treatment responders had larger rACC volume than nonresponders. Further, symptom reduction was associated with larger rACC volume. CONCLUSION: Consistent with evidence for the neural bases of extinction learning, PTSD patients with larger rACC volume may be better able to regulate fear during cognitive-behavioural therapy and thus achieve greater treatment gains.

A recent continuum model of the large scale electrical activity of the cerebral cortex is generalized to include cholinergic modulation. In this model, dynamic modulation of synaptic strength acts over the time scales of nicotinic and muscarinic receptor action. The cortical model is analyzed to determine the effect of acetylcholine (ACh) on its steady states, linear stability, spectrum, and temporal responses to changes in subcortical input. ACh increases the firing rate in steady states of the system. Changing ACh concentration does not introduce oscillatory behavior into the system, but increases the overall spectral power. Model responses to pulses in subcortical input are affected by the tonic level of ACh concentration, with higher levels of ACh increasing the magnitude firing rate response of excitatory cortical neurons to pulses of subcortical input. Numerical simulations are used to explore the temporal dynamics of the model in response to changes in ACh concentration. Evidence is seen of a transition from a state in which intracortical inputs are emphasized to a state where thalamic afferents have enhanced influence. Perturbations in ACh concentration cause changes in the firing rate of cortical neurons, with rapid responses due to fast acting facilitatory effects of nicotinic receptors on subcortical afferents, and slower responses due to muscarinic suppression of intracortical connections. Together, these numerical simulations demonstrate that the actions of ACh could be a significant factor modulating early components of evoked response potentials.

OBJECTIVE: This study explored the concurrent courses of the neuroanatomical and neuropsychological changes that occurred over the first 2-3 years of illness in patients with first-episode schizophrenia (FES). METHODS: Fifty-two patients with FES underwent neuropsychological testing and a structural magnetic resonance imaging (sMRI) scan within three months of their first presentation to mental health services with psychotic symptoms (time1). Patients' cognitive performance was evaluated via an extensive neuropsychological test battery, which assessed 9 cognitive domains. Of the 52 patients at time1, 32 returned 2-3 years later (time2) for follow-up neuropsychological testing, and 20 of these also underwent follow-up sMRI. MR images were preprocessed in SPM99. Grey matter volumes of patients' whole-brain, frontal lobes and temporal lobes were calculated by convolving the preprocessed images with manually-drawn binary masks. RESULTS: Patients exhibited longitudinal improvements in full-scale IQ, performance IQ and visual memory. In contrast, concurrent reductions in grey matter were observed for the whole-brain (3% reduction) and the frontal lobe (3.65% reduction). Furthermore, the extent of patients' whole-brain and frontal-lobe grey matter changes were positively correlated with longitudinal changes in verbal learning and memory. DISCUSSION: The results of this study suggest that while the early stages of schizophrenia are associated with a mild improvement in patients' overall cognitive functioning, they are also associated with progressive grey matter atrophy.

INTRODUCTION: Anomalies on probabilistic reasoning, theory of mind (ToM) tasks, and attributional biases have been found in delusional people. Delusions are also effectively modified by cognitive behavioural therapy (CBT). We sought to examine whether CBT reduces delusional conviction by changing such general reasoning anomalies. METHOD: Sixteen patients commenced an 8-11 week CBT programme that targeted their delusions. Probabilistic reasoning, attributional biases, and ToM were assessed pre- and post-treatment. Delusional conviction, preoccupation, and distress were rated at each session. Pretreatment task performances were compared to norms. Repeated measures analyses compared pre- and posttreatment task performances and ratings of delusions. Correlational analyses were used to identify factors associated with reduced delusional conviction. RESULTS: At baseline, 11 patients showed some form of abnormal probabilistic reasoning, 13 excessive attributional biases, and 13 defective ToM compared to norms. Fourteen patients completed the CBT programme and showed significant reductions in delusional conviction and preoccupation. Despite some inconsistent evidence of improvement in verbal ToM tasks, reasoning styles in these 14 patients were largely unchanged by CBT. CONCLUSION: Reasoning anomalies associated with delusions in this sample mark a vulnerability that persists and is independent of the effectiveness of CBT.

The identification of alpha rhythm in the human electroencephalogram (EEG) is generally a laborious task involving visual inspection of the spectrum. Moreover the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to automate the process of identifying alpha peaks and quantifying their frequency, amplitude and width as a function of position on the scalp. Experimental EEG was fitted with parameterized spectra spanning the alpha range, with results categorized by multi-site criteria into three distinct classes: no distinguishable alpha peak, a single alpha peak, and two alpha peaks. The technique avoids visual bias, integrates spatial information, and is automated. We show that multiple alpha peaks are a common feature of many spectra.

OBJECTIVE: It is increasingly recognized that cognitive assessments, unlike symptom ratings, provide a reliable predictor of functional outcome in schizophrenia. This study evaluated the utility of the 'IntegNeuro' computerized test battery for assessing cognition in first episode schizophrenia. We determined the presence of separable factors of general and social cognition, their equivalence to the consensus domains identified by the NIMH MATRICS project, and their effectiveness in predicting real world functional outcomes. METHOD: Fifty six first episode schizophrenia (FES) patients and 112 matched healthy controls were assessed on the touchscreen-based 'IntegNeuro' cognitive test battery and FES patients for social functioning (SOFAS) and quality of life (WHOQOL-BREF). RESULTS: Principal components analysis identified i) six factors corresponding to MATRICS domains of general cognition ('Information Processing Speed', 'Verbal Recall', 'Working Memory Capacity', 'Sustained Attention/Vigilance', 'Verbal Processing', 'Executive Function'), ii) an 'Emotional Intelligence' factor corresponding to the MATRICS social cognition domain, and iii) an additional 'Sensori-Motor Function' factor of general cognition and 'Negativity' factor of social cognition. Patients showed impairments relative to controls across all factors, but especially for Working Memory Capacity, followed by Verbal Memory, Sustained Attention/Vigilance and Negativity. These factors strongly predicted poorer social functioning in FES, along with poorer quality of life in psychological, social, and health satisfaction facets. CONCLUSION: The IntegNeuro battery has utility for assessing separable domains of general and social cognition in FES, which are predictive of real world outcomes. Thus, it may be appropriate for clinical application, including in multi-center trials targeting new treatments for cognition in schizophrenia.

The first laboratory confirmation of stochastic growth theory is reported. Floating potential fluctuations are measured in a vacuum arc centrifuge using a Langmuir probe. Statistical analysis of the energy density reveals a lognormal distribution over roughly 2 orders of magnitude, with a high-field nonlinear cutoff whose spatial dependence is consistent with the predicted eigenmode profile. These results are consistent with stochastic growth and nonlinear saturation of a spatially extended eigenmode, the first evidence for stochastic growth of an extended structure.

When two conditioned stimuli (CSs) are presented in compound, the response is typically stronger than to the individual CSs, implying that their associative strengths combine. However, to identify exactly how associative strengths combine requires an accurate description of the relationship between associative strength and responding. The authors have used the delta rule (Rescorla & Wagner, 1972) to constrain the predicted growth of associative strength (V) to identify the relationship between V and responding across the course of Pavlovian conditioning of two CSs (one auditory, one visual). Responding to the compound was best predicted as 0.6xV(CS1)+0.6xV(CS2), suggesting that only 60% of the associative strength of each CS generalized to the compound. A second experiment confirmed this result and additionally showed that summation of responding between two same-modality CSs (both auditory or both visual) declined across training. A third experiment applied the procedure to compound conditioning, showing that responding to the compound was equal to the sum of the response rates to the individual CSs. The results are discussed in terms of configural and elemental models of Pavlovian conditioning.

OBJECTIVE: This study examines the utility of new measures of event-related spatio-temporal waves in the EEG as a marker of ADHD, previously shown to be closely related to the P3 ERP in an adult sample. METHODS: Wave activity in the EEG was assessed during both an auditory Oddball and a visual continuous performance task (CPT) for an ADHD group ranging in age from 6 to 18 years and comprising mostly Combined and Inattentive subtypes, and for an age and gender matched control group. RESULTS: The ADHD subjects had less wave activity at low frequencies ( approximately 1 Hz) during both tasks. For auditory Oddball targets, this effect was shown to be related to smaller P3 ERP amplitudes. During CPT, the approximately 1 Hz wave activity in the ADHD subjects was inversely related to clinical and behavioral measures of hyperactivity and impulsivity. CPT wave activity at approximately 1 Hz was seen to "normalise" following treatment with stimulant medication. CONCLUSIONS: The results identify a deficit in low frequency wave activity as a new marker for ADHD associated with levels of hyperactivity and impulsivity. SIGNIFICANCE: The marker is evident across a range of tasks and may be specific to ADHD. While lower approximately 1 Hz activity partly accounts for reduced P3 ERPs in ADHD, the effect also arises for tasks that do not elicit a P3. Deficits in behavioral inhibition are hypothesized to arise from underlying dysregulation of cortical inhibition.

This study investigated whether children and adolescents diagnosed with the predominantly inattentive and combined subtypes of attention deficit/hyperactivity disorder (AD/HD-in and AD/HD-com, respectively) differed on psychophysiological indices of working memory updating off- and on-stimulant medication, as compared with control subjects and each other. ERPs were recorded in AD/HD and control participants during a one-back working memory task. The N100 (discrimination), P150 (selection), N300 (memory retrieval), and P450wm (updating) components after nontarget stimuli, which served to update working memory with target identity, were assessed. Premedication abnormalities were obtained for the N300 component, delayed in the child AD/HD-com group, and attenuated in the adolescent AD/HD-in group and P450wm component for all AD/HD groups, expressed as either delayed latency and/or attenuated amplitude. ERP abnormalities were predominantly ameliorated after stimulant medication. There were no psychophysiological differences between the subtypes. A general feature of the disorder relates to a deficit in the conscious updating of working memory systems with newly relevant information (P450wm), which varies with age and subtype. Children with AD/HD-com and adolescents with AD/HD-in also exhibit abnormalities in the retrieval of relevant prior memories (N300). This study indicates that AD/HD is related to abnormalities in the capacity to modulate the content of working memory stores.

The study aimed to identify brain functional indicators of working memory systems development between 6 and 18 years. Event-related potentials (ERPs) were recorded from 251 normally developing children to stimuli requiring the updating of working memory. Cluster analysis of event-related potential componentry divided the sample into three clusters (mean ages 9, 12 and 16 years), with ascending cluster membership independently associated with improved task performance. The clusters correspond to periods of grey matter loss and white matter increase observed in developing children, supporting the view that the clusters delineate three key qualitative stages in advancing cognitive capability during the maturation of higher brain systems function. This outcome identifies a biomarker with the potential for assessing abnormalities in the rate of brain development.

Although biases toward signals of fear may be an evolutionary adaptation necessary for survival, heightened biases may be maladaptive and associated with anxiety or depression. In this study, event-related potentials (ERPs) were used to examine the time course of neural responses to facial fear stimuli (versus neutral) presented overtly (for 500 msec with conscious attention) and covertly (for 10 msec with immediate masking to preclude conscious awareness) in 257 nonclinical subjects. We also examined the impact of trait anxiety and depression, assessed using psychometric ratings, on the time course of ERPs. In the total subject group, controlled biases to overtly processed fear were reflected in an enhancement of ERPs associated with structural encoding (120-220 msec) and sustained evaluation persisting from 250 msec and beyond, following a temporo-occipital to frontal topography. By contrast, covert fear processing elicited automatic biases, reflected in an enhancement of ERPs prior to structural encoding (80-180 msec) and again in the period associated with automatic orienting and emotion encoding (230-330 msec), which followed the reverse frontal to temporo-occipital topography. Higher levels of trait anxiety (in the clinical range) were distinguished by a heightened bias to covert fear (speeding of early ERPs), compared to higher depression which was associated with an opposing bias to overt fear (slowing of later ERPs). Anxiety also heightened early responses to covert fear, and depression to overt fear, with subsequent deficits in emotion encoding in each case. These findings are consistent with neural biases to signals of fear which operate automatically and during controlled processing, feasibly supported by parallel networks. Heightened automatic biases in anxiety may contribute to a cycle of hypervigilance and anxious thoughts, whereas depression may represent a "burnt out" emotional state in which evaluation of fear stimuli is prolonged only when conscious attention is allocated.

Hopfield's Lyapunov function is used to view the stability and topology of equilibria in neuronal networks for visual rivalry and pattern formation. For two neural populations with reciprocal inhibition and slow adaptation, the dynamics of neural activity is found to include a pair of limit cycles: one for oscillations between states where one population has high activity and the other has low activity, as in rivalry, and one for oscillations between states where both populations have the same activity. Hopfield's Lyapunov function is used to find the dynamical mechanism for oscillations and the basin of attraction of each limit cycle. For a spatially continuous population with lateral inhibition, stable equilibria are found for local regions of high activity (solitons) and for bound states of two or more solitons. Bound states become stable when moving two solitons together minimizes the Lyapunov function, a result of decreasing activity in regions between peaks of high activity when the firing rate is described by a sigmoid function. Lowering the barrier to soliton formation leads to a pattern-forming instability, and a nonlinear solution to the dynamical equations is found to be given by a soliton lattice, which is completely characterized by the soliton width and the spacing between neighboring solitons. Fluctuations due to noise create lattice vacancies analogous to point defects in crystals, leading to activity which is spatially inhomogeneous.