Default network connectivity during a working memory task.

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task-related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task-related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task-positive networks at rest.

Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity.

UNLABELLED: Working memory processing and resting-state connectivity in the default mode network are altered in patients with posttraumatic stress disorder (PTSD). Because the ability to effortlessly switch between concentration on a task and an idling state during rest is implicated in both these alterations, we undertook a functional magnetic resonance imaging study with a block design to analyze task-induced modulations in connectivity. METHODS: We performed a working memory task and psychophysiologic interaction analyses with the posterior cingulate cortex and the medial prefrontal cortex as seed regions during fixation in 12 patients with severe, chronic PTSD and 12 healthy controls. RESULTS: During the working memory task, the control group showed significantly stronger connectivity with areas implicated in the salience and executive networks, including the right inferior frontal gyrus and the right inferior parietal lobule. The PTSD group showed stronger connectivity with areas implicated in the default mode network, namely enhanced connectivity between the posterior cingulate cortex and the right superior frontal gyrus and between the medial prefrontal cortex and the left parahippocampal gyrus. LIMITATIONS: Because we were studying alterations in patients with severe, chronic PTSD, we could not exclude patients taking medication. The small sample size may have limited the power of our analyses. To avoid multiple testing in a small sample, we only used 2 seed regions for our analyses. CONCLUSION: The different patterns of connectivity imply significant group differences with task-induced switches (i.e., engaging and disengaging the default mode network and the central-executive network).

Cognitive and electroencephalographic disturbances in children with attention-deficit/hyperactivity disorder and sleep problems: new insights.

There is overlap between the behavioural symptoms and disturbances associated with Attention-Deficit/Hyperactivity Disorder (AD/HD) and sleep problems. The aim of this study was to examine the extent of overlap in cognitive and electrophysiological disturbances identified in children experiencing sleep problems and children with AD/HD or both. Four groups (aged 7-18) were compared: children with combined AD/HD and sleep problems (n=32), children with AD/HD (n=52) or sleep problems (n=36) only, and children with neither disorder (n=119). Electrophysiological and cognitive function measures included: absolute EEG power during eyes open and eyes closed, event-related potential (ERP) components indexing attention and working memory processes (P3), and a number of standard neuropsychological tests. Children with symptoms of both AD/HD and sleep problems had a different profile from those of children with either AD/HD or sleep problems only. These findings suggest it is unlikely that disturbances in brain and cognitive functioning associated with sleep problems also give rise to AD/HD symptomatology and consequent diagnosis. Furthermore, findings suggest that children with symptoms of both AD/HD and sleep problems may have a different underlying aetiology than children with AD/HD-only or sleep problems-only, perhaps requiring unique treatment interventions.

Evidence-based medicine evaluation of electrophysiological studies of the anxiety disorders.

We provide a systematic, evidence-based medicine (EBM) review of the field of electrophysiology in the anxiety disorders. Presently, electrophysiological studies of anxiety focus primarily on etiological aspects of brain dysfunction. The review highlights many functional similarities across studies, but also identifies patterns that clearly differentiate disorder classifications. Such measures offer clinical utility as reliable and objective indicators of brain dysfunction in individuals and indicate potential as biomarkers for the improvement of diagnostic specificity and for informing treatment decisions and prognostic assessments. Common to most of the anxiety disorders is basal instability in cortical arousal, as reflected in measures of quantitative electroencephalography (qEEG). Resting electroencephalographic (EEG) measures tend to correlate with symptom sub-patterns and be exacerbated by condition-specific stimulation. Also common to most of the anxiety disorders are condition-specific difficulties with sensory gating and the allocation and deployment of attention. These are clearly evident from evoked potential (EP) and event-related potential (ERP) electrical measures of information processing in obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder (PD), generalized anxiety disorder (GAD) and the phobias. Other'ERP measures clearly differentiate the disorders. However, there is considerable variation across studies, with inclusion and exclusion criteria, medication status and control group selection not standardized within condition or across studies. Study numbers generally preclude analysis for confound removal or for the derivation of diagnostic biomarker patterns at this time. The current trend towards development of databases of brain and cognitive function is likely to obviate these difficulties. In particular, electrophysiological measures of function are likely to play a significant role in the development and subsequent adaptations of DSM-V and assist critically in securing improvements in nosological and treatment specificity.

Working memory function in post-traumatic stress disorder: an event-related potential study.

OBJECTIVE: Previous studies using event-related potentials (ERPs) in post-traumatic stress disorder (PTSD) have demonstrated reduced P3 amplitude during target detection and working memory (WM) processes. This study investigated effects of psychotropic medication (primarily antidepressants) on these ERP components. METHODS: ERPs were recorded from 26 scalp sites in 34 PTSD patients (20 unmedicated, 14 medicated) with age- and gender-matched controls during a WM paradigm that involved detection of target letters on a visual display. RESULTS: As expected, PTSD patients showed a reduced amplitude P3wm component during WM updating and a reduced and delayed target P3 component. Contrary to expectation, these ERP effects were most apparent in the medicated subgroup of PTSD patients. The medicated PTSD subgroup showed a trend towards reduced P3wm amplitude compared with controls and a significant amplitude reduction and delay of target P3 component, while there was little difference between the non-medicated PTSD subgroup and controls. Neither ERP nor behavioural measures were related to Clinician Administered PTSD Scale (CAPS) symptom severity measures. CONCLUSIONS: These results are consistent with research that suggests antidepressant medication may impair working memory performance. SIGNIFICANCE: The present study illustrates the importance of monitoring medication effects on cognitive performance during clinical efficacy studies.

Functional connectivity reveals inefficient working memory systems in post-traumatic stress disorder.

We applied a covariance-based multivariate analysis to functional magnetic resonance imaging (fMRI) data to investigate abnormalities in working memory (WM) systems in patients with post-traumatic stress disorder (PTSD). Patients (n=13) and matched controls (n=12) were scanned with fMRI while updating or maintaining trauma-neutral verbal stimuli in WM. A multivariate statistical analysis was used to investigate large-scale brain networks associated with these experimental tasks. For the control group, the first network reflected brain activity associated with WM updating and principally involved bilateral prefrontal and bilateral parietal cortex. Controls' second network was associated with WM maintenance and involved regions typically activated during storage and rehearsal of verbal material, including lateral premotor and inferior parietal cortex. In contrast, PTSD patients appeared to activate a single fronto-parietal network for both updating and maintenance tasks. This is indicative of abnormally elevated activity during WM maintenance and suggests inefficient allocation of resources for differential task demands. A second network in PTSD, which was not activated in controls, showed regions differentially activated between WM tasks, including the anterior cingulate, medial prefrontal cortex, fusiform and supplementary motor area. These activations may be linked to hyperarousal and abnormal reactivity, which are characteristic of PTSD.

Abnormal recruitment of working memory updating networks during maintenance of trauma-neutral information in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is characterised by disturbances in concentration and memory, symptoms which are a source of further distress for patients. Related to this, abnormalities in underlying working memory (WM) systems have been identified [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M.E., Marcina, J., Tochon-Danguy, H.J., Egan, G.F., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481.], indicating dysfunction in left hemisphere brain regions. In this study, we performed functional magnetic resonance imaging (fMRI) in 13 patients with severe PTSD and matched non-traumatized Controls, during performance of visuo-verbal tasks that involved either maintenance or continual updating of word stimuli in WM. The PTSD group failed to show differential activation during WM updating, and instead appeared to show abnormal recruitment of WM updating network regions during WM maintenance. These regions included the bilateral dorsolateral prefrontal cortex (DLPFC) and the inferior parietal lobe (IPL). Several other regions were significantly more activated in Controls than in PTSD during WM updating, including the hippocampus, the anterior cingulate (AC), and the brainstem pons, key regions that are consistently implicated in the neurobiology of PTSD. These findings suggest compensatory recruitment of networks in PTSD normally only deployed during updating of WM and may reflect PTSD patients' difficulty engaging with their day-to-day environment.

Traumatic memories: bridging the gap between functional neuroimaging and psychotherapy.

OBJECTIVE: Neuroimaging studies have highlighted important issues related to structural and functional brain changes found in sufferers of psychological trauma that may influence their ability to synthesize, categorize, and integrate traumatic memories. METHODS: Literature review and critical analysis and synthesis. RESULTS: Traumatic memories are diagnostic symptoms of post-traumatic stress disorder (PTSD), and the dual representation theory posits separate memory systems subserving vivid re-experiencing (non-hippocampally dependent) versus declarative autobiographical memories of trauma (hippocampally dependent). But the psychopathological signs of trauma are not static over time, nor is the expression of traumatic memories. Multiple memory systems are activated simultaneously and in parallel on various occasions. Neural circuitry interaction is a crucial aspect in the development of a psychotherapeutic approach that may favour an integrative translation of the sensory fragments of the traumatic memory into a declarative memory system. CONCLUSION: The relationship between neuroimaging findings and psychological approaches is discussed for greater efficacy in the treatment of psychologically traumatized patients.

Abnormal frontal and parietal activity during working memory updating in post-traumatic stress disorder.

This study used event-related potentials (ERPs) to investigate the timing and scalp topography of working memory in post-traumatic stress disorder (PTSD). This study was designed to investigate ERPs associated with a specific working memory updating process. ERPs were recorded from 10 patients and 10 controls during two visual tasks where (a) targets were a specific word or (b) targets were consecutive matching words. In the first task, nontarget words are not retained in working memory. In the second task, as in delay-match-to-sample tasks, a non-target word defines a new target identity, so these words are retained in working memory. This working memory updating process was related to large positive ERPs over frontal and parietal areas at 400-800 ms, which were smaller in PTSD. Estimation of cortical source activity indicated abnormal patterns of frontal and parietal activity in PTSD, which were also observed in regional cerebral blood flow [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M., Marcina, J., Tochon-Danguy, H., Egan, G., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481]. Frontal and parietal cortex are known to be involved in distributed networks for working memory processes, interacting with medial temporal areas during episodic memory processes. Abnormal function in these brain networks helps to explain everyday concentration and memory difficulties in PTSD.

Investigating the generators of the scalp recorded visuo-verbal P300 using cortically constrained source localization.

Considerable ambiguity exists about the generators of the scalp recorded P300, despite a vast body of research employing a diverse range of methodologies. Previous investigations employing source localization techniques have been limited largely to equivalent current dipole models, with most studies identifying medial temporal and/or hippocampal sources, but providing little information about the contribution of other cortical regions to the generation of the scalp recorded P3. Event-related potentials (ERPs) were recorded from 5 subjects using a 124-channel sensor array during the performance of a visuo-verbal Oddball task. Cortically constrained, MRI-guided boundary element modeling was used to identify the cortical generators of this target P3 in individual subjects. Cortical generators of the P3 were localized principally to the intraparietal sulcus (IPS) and surrounding superior parietal lobes (SPL) bilaterally in all subjects, though with some variability across subjects. Two subjects also showed activity in the lingual/inferior occipital gyrus and mid-fusiform gyrus. A group cortical surface was calculated by non-linear warping of each subject's segmented cortex followed by averaging and creation of a group mesh. Source activity identified across the group reflected the individual subject activations in the IPS and SPL bilaterally and in the lingual/inferior occipital gyrus primarily on the left. Activation of IPS and SPL is interpreted to reflect the role of this region in working memory and related attention processes and visuo-motor integration. The activity in left lingual/inferior occipital gyrus is taken to reflect activation of regions associated with modality-specific analysis of visual word forms.