ABSTRACT
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.
Subject(s)
Brain/physiopathology , Magnetic Resonance Imaging , Memory, Short-Term , Nerve Net/physiopathology , Stress Disorders, Post-Traumatic/physiopathology , Stress Disorders, Post-Traumatic/psychology , Adult , Case-Control Studies , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Motor Cortex/physiopathology , Multivariate Analysis , Parietal Lobe/physiopathology , Prefrontal Cortex/physiopathology , Stress Disorders, Post-Traumatic/diagnosis , Verbal LearningABSTRACT
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.
Subject(s)
Attention/physiology , Brain/physiopathology , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Memory, Short-Term/physiology , Nerve Net/physiopathology , Positron-Emission Tomography , Stress Disorders, Post-Traumatic/physiopathology , Verbal Learning/physiology , Adult , Brain Mapping , Dominance, Cerebral/physiology , Female , Gyrus Cinguli/physiopathology , Hippocampus/physiopathology , Humans , Male , Middle Aged , Parietal Lobe/physiology , Parietal Lobe/physiopathology , Pons/physiopathology , Prefrontal Cortex/physiopathology , Psychomotor Performance/physiology , Recruitment, Neurophysiological/physiology , Semantics , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/psychologyABSTRACT
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.
