Darren L. Weber

Abnormal stimulus processing in posttraumatic stress disorder

This study investigated event-related potential (ERP) indices of information processing in sufferers of posttraumatic stress disorder (PTSD). ERPs were obtained from 18 PTSD patients and 20 controls while they performed a target discrimination task requiring the detection of infrequent target tones from a background sequence of frequent and infrequent distractor tones. A delayed N2 and an attenuated P3 that failed to differentiate target from distractor tones indicated that patients had abnormal difficulty distinguishing task stimuli of differing relevance. It is proposed that this difficulty is reflected behaviorally in the slowed reaction time by patients to target stimuli and may underlie the disturbed concentration and memory impairments found in PTSD. It may also be related to dysfunction in central noradrenaline function, which has been shown to be both crucial in selective attention and abnormal in PTSD.

Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study.

BACKGROUND This study examined cerebral function in posttraumatic stress disorder (PTSD) during the updating of working memory to trauma-neutral, verbal information. METHODS Ten PTSD and matched control subjects completed a visuoverbal target detection task involving continuous updating (Variable target condition) or no updating (Fixed target condition) of target identity, with updating activity estimated by condition comparison. RESULTS Normal updating activity using this paradigm involved bilateral activation of the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe. The PTSD group lacked this activation in the left hemisphere and was significantly different from control subjects in this regard, but showed additional activation in the superior parietal lobe, bilaterally. CONCLUSIONS The pattern of parietal activation suggests a dependence on visuospatial coding for working memory representation of trauma-neutral, verbal information. Group differences in the relative involvement of the DLPFC indicate less dependence in PTSD on the executive role normally attributed to the left DLPFC for monitoring and manipulation of working memory content in posterior regions of the brain.

Relationships between changes in symptom ratings, neuropsychological test performance and quality of life in schizophrenic patients treated with clozapine

This study examined the correlations between reduction in symptoms, changes in neuropsychological test performance and improved quality of life in 19 schizophrenic outpatients treated with clozapine. Reduction in both negative symptoms and general psychopathology was associated with a better quality of life. Some improvement in neuropsychological test performance was found, with a variable pattern of association with change in psychopathology. Improved verbal fluency was associated with reduction in negative symptoms, while improved verbal concept formation was associated with reduction in positive symptoms.

Updating working memory for words: A PET activation study

A PET study of 10 normal individuals was carried out to investigate the cerebral regions involved in the controlled updating of verbal working memory. Subjects viewed single concrete words on a computer monitor and detected occasional target words in an attended color. In the activating condition, a target was defined as a word that was identical to the previous word presented in the attended color. In the control condition, the target was a predesignated word. The same word lists, target probabilities, and target response demands were used for both conditions, with interword intervals constrained to ensure equivalence in the demand for target rehearsal. A comparison of the conditions found bilateral activation of dorsolateral prefrontal (middle frontal gyrus; MFG) and inferior parietal (supramarginal gyrus; SMG) cortical regions. Activation of the MFG is taken to reflect executive control by prefrontal regions over the working memory updating process linking posterior representations of the anticipated target stimulus to anterior representations of the planned response. It is proposed that the updating of the stimulus link is mediated via connections between the MFG and SMG. The role of the SMG as an amodal region binding the various modal representations in posterior association cortex of the word being retained in working memory is considered and reviewed. It is suggested that the combined activation of these regions is related to the executive control of goal‐setting in planned behavior. Hum. Brain Mapping 9:42–54, 2000.

Working memory in posttraumatic stress disorder—an event‐related potential study

This study examined ERP topography during the updating and the utilization of working memory in subjects with PTSD. Event-related potentials of 18 participants with PTSD and 18 controls were recorded from 32 scalp electrodes during an auditory target detection task requiring the constant updating of target identity. Midline N2 and P3 abnormalities previously noted in PTSD during target detection were replicated. Scalp topographic data revealed sustained reduction in activity over the right hemisphere during working memory updating. Executive processes were associated with brief but widespread right hemisphere reductions during the P3, followed by sustained, bilateral reduction frontally. This study identifies an abnormal pattern of cortical network function during both the updating and use of working memory in PTSD.

Enlarged frontal P300 to stimulus change in panic disorder

This study investigated event-related potential (ERP) indices of information processing in sufferers of panic disorder (PD). ERPs were recorded from 14 PD patients and 15 controls during an auditory target detection task. The task required subjects to discriminate infrequent target tones (p = .14; 2000 Hz) from frequent (p = .72; 1000 Hz) and infrequent (p = .14; 500 Hz) distractor tones. A frontal P300 (P3a) identified in the PD group was characteristic of activity that would be expected to novel, task-irrelevant stimuli and is consistent with junctional pathology involving the prefrontal-limbic pathways. This study provides psychophysiological evidence of an abnormality in PD of the brains processing of physical changes in the stimulus field that occurs even under conditions of low stimulus load. It may assist in helping to understand the breakdown in information processing that occurs in PD under high load conditions such as crowds and supermarkets.

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 subjects 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. Hum. Brain Mapping 18:53–77, 2002.

The effect of clozapine on the speed and accuracy of information processing in schizophrenia.

1. The study aimed to investigate the effects of clozapine on the speed and accuracy of information processing in patients with schizophrenia. Data are reported from 13 subjects with schizophrenia, treated with clozapine for 6.8 (+/- 1.8) months. 2. Reaction time and accuracy of target detection on a tone detection task were measured before and during clozapine treatment, and these results were compared with a matched control group. 3. Symptom severity and performance on three timed tests of cognitive function were also measured prior to clozapine treatment in the schizophrenia group, and these measures were repeated during treatment with clozapine. 4. Treatment with clozapine was found to significantly improve reaction time and the accuracy of target detection in patients with schizophrenia. Despite this improvement their performance remained significantly inferior to that of a matched control group. Both positive and negative symptoms improved with clozapine treatment, as did performance on the WAIS-R digit symbol substitution test. 5. Improved performance on the WAIS-R digit symbol substitution test correlated with reduction in negative symptoms, and faster reaction time showed some correlation with reduction in positive symptoms. 6. The results of this pilot study indicate that treatment with clozapine can produce limited improvement in cognitive function in schizophrenia.

Cortical network dynamics during verbal working memory function

This study is an exploratory investigation of the regional timing of cortical activity associated with verbal working memory function. ERP activity was obtained from a single subject using a 124-channel sensor array during a task requiring the monitoring of imageable words for occasional targets. Distributed cortical activity was estimated every 2.5 ms with high spatial resolution using real head, boundary element modelling of non-target activity. High-resolution structural MRI was used for segmentation of tissue boundaries and co-registration to the scalp electrode array. The inverse solution was constrained to the cortical surface. Cortical activity was observed in regions commonly associated with verbal working memory function. This included: the occipital pole (early visual processing); the superior temporal and inferior parietal gyrus bilaterally and the left angular gyrus (visual and phonological word processing); the dorsal lateral occipital gyrus (spatial processing); and aspects of the bilateral superior parietal lobe (imagery and episodic verbal memory). Activity was also observed in lateral and superior prefrontal regions associated with working memory control of sensorimotor processes. The pattern of cortical activity was relatively stable over time, with variations in the extent and amplitude of contributing local source activations. By contrast, the pattern of concomitant scalp topography varied considerably over time, reflecting the linear summation effects of volume conduction that often confound dipolar source modelling.

Cocktails and brainwaves-experiments with complex and subliminal auditory stimuli

The paper deals with the problem of processing acoustic signals originating from multiple sources in a potentially noisy environment. Previous research in speech processing and cognitive modelling has tended to concentrate on single sources and relatively noise free signals. Separating out different signals from a multitude of sources is a significant part of human auditory processing. In speech processing research, the problem we are dealing with is known as the cocktail party syndrome. The processing of polyphonic music involves similar challenges, and auditory scene analysis (ASA) has been proposed as a means of separating out component signals and identifying their sources. In subliminal auditory processing, a speech signal which is masked from conscious awareness by a music signal provides an extreme form of the multiple source problem and permits exploration of the boundary between conscious and unconscious auditory processing. The research presented employs machine learning and associative models to characterize and track individual signals, and uses electroencephalographic (EEG) analysis to more precisely characterize human processing of multimodal signals.