Biomedical subjects

Robert J Thoma

Publications and source records attributed to Robert J Thoma.

14 recordsLinked to original sources

PubMed2006

Impairment on the hippocampal-dependent virtual Morris water task in schizophrenia.

Traditional neuropsychological tests of visual and verbal memory have been used to evaluate memory deficits in schizophrenia. However, these tests cannot be used in non-human animal research, which is important for the discovery of treatments that will improve cognition and for study of the etiology of schizophrenia. To help bridge the gap between human and non-human animal research on hippocampal function in schizophrenia, this study sought to characterize the behavioral performance exhibited by patients using the Morris water task (MWT). The MWT has been shown in human and non-human animal studies to be hippocampus-dependent. In the virtual MWT, human subjects navigate a computer-generated on-screen environment to escape from the "water" by locating a platform. Patients with schizophrenia and controls performed two versions of the virtual MWT: a hippocampal-dependent hidden-platform version, relying on allocentric navigational abilities, and a non-hippocampal-dependent visible-platform version, relying on cued-navigational abilities. Patients traveled further and took longer to find the hidden platform over training blocks and spent less time in the correct quadrant during a probe trial. There was no deficit in the visible-platform condition. These findings identify a behavioral impairment on a hippocampal-dependent task in schizophrenia and support using the MWT in testing animal models of schizophrenia.

Adult↗

PubMed2006

Developmental instability and the neural dynamics of the speed-intelligence relationship.

Two of the most securely established findings in the biology of intelligence are the relationship between reaction time (RT) and intelligence, and the heritability of intelligence. To investigate why RT may related to intelligence, researchers have used a variety of techniques to subdivide RT into cognitive and motor components. In the current study, magnetoencephalographic (MEG) dipole latencies were used to examine the speed and timing of specific brain processing stages engaged during visually cued simple and choice reaction time tasks. Simple and choice reaction time and timing of MEG sources were considered in relation to fluid intelligence (as measured by the Raven's Advanced Progressive Matrices, RAPM). To address heritability of intelligence, developmental instability (DI) was assessed, measured here as fluctuating asymmetry. DI represents the degree to which an organism is susceptible to developmental stress arising from both environmental and genomic sources. Analyses showed that choice, but not simple reaction time was negatively correlated with RAPM score. MEG revealed a set of complex relationships between the timing of regional brain activations and psychometric intelligence. The neural component associated with integration of sensory and motor information was most associated with RAPM compared to other components. Higher values of fluctuating asymmetry predicted reduced psychometric intelligence, a result suggesting that some part of the variance of the heritability of intelligence reflects DI. Fluctuating asymmetry was significantly and negatively correlated with timing during all components of task completion. These observations suggest that fluid intelligence is primarily related to speed during processing associated with decision time, while fluctuating asymmetry predicted slower processing across all stages of information processing.

Adolescent↗

PubMed2006

Neuropsychological and sensory gating deficits related to remote alcohol abuse history in schizophrenia.

Recent evidence suggests that changes in brain structure associated with alcohol abuse are compounded in individuals dually diagnosed with alcohol abuse and schizophrenia. To investigate the separate, and possibly interacting, effects of these diagnoses, an event-related brain potential (ERP) measure of auditory information processing (P50 sensory gating paradigm) and neuropsychological measures were administered to healthy control participants with either (1a) no history of alcohol abuse/dependence, or (1b) a remote history of alcohol abuse/dependence, and patients with schizophrenia with either (2a) no history of alcohol abuse/dependence, or (2b) a remote history of alcohol abuse/dependence. Schizophrenia was associated with impaired P50 sensory gating and poorer performance across neuropsychological scores compared to measurements in healthy control participants. Those with a positive alcohol history had impaired gating ratios in contrast to those with a negative alcohol history. There were additive effects of schizophrenia diagnosis and alcohol history for P50 sensory gating and for neuropsychological scores: attention, working memory, and behavioral inhibition. For executive attention and general memory there was an interaction, suggesting that the combination of schizophrenia and history of alcohol abuse results in greater impairment than that predicted by the presence of either diagnosis alone.

Adult↗

PubMed2006

Efficacy of olanzapine and risperidone in schizophrenia: a randomized double-blind crossover design.

This article compares the efficacy of olanzapine and risperidone for positive and negative symptoms using an 18-week, randomized, double-blind, crossover design. The hypotheses were that olanzapine would be more efficacious for treating negative symptoms, and that risperidone would be superior in treating positive symptoms. Positive and negative symptoms scores improved throughout treatment, regardless of medication type. Differences between the medications were found for negative and general psychopathology rating scales. Overall, olanzapine led to greater improvements in negative symptoms than did risperidone. When each scale was analyzed individually, greater improvements were found for olanzapine on Positive and Negative Symptoms Scale (PANSS) General,PANSS total, and Scale for the Assessment of Negative Symptoms (SANS)attention. A nearly significant trend favoring olanzapine was found for the Calgary Depression Scale. Several negative symptom subscales followed a nonsignificant trend toward olanzapine being more efficacious than risperidone.Thus, there was a very consistent pattern of greater efficacy for olanzapine, particularly for negative symptoms. Despite the small number of subjects, this study shows the potential of a within-subject design to elucidate differences in efficacy.

Adult↗

PubMed2005

A parietal-frontal network studied by somatosensory oddball MEG responses, and its cross-modal consistency.

Previous studies using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) of the brain have found that a distributed parietal-frontal neuronal network is activated in normals during both auditory and visual oddball tasks. The common cortical regions in this network are inferior parietal lobule (IPL)/supramarginal gyrus (SMG), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). It is not clear whether the same network is activated by oddball tasks during somatosensory stimulation. The present study addressed this question by testing healthy adults as they performed a novel median-nerve oddball paradigm while undergoing magnetoencephalography (MEG). An automated multiple dipole analysis technique, the Multi-Start Spatio-Temporal (MSST) algorithm, localized multiple neuronal generators, and identified their time-courses. IPL/SMG, ACC, and DLPFC were reliably localized in the MEG median-nerve oddball responses, with IPL/SMG activation significantly preceding ACC and DLPFC activation. Thus, the same parietal-frontal neuronal network that shows activation during auditory and visual oddball tests is activated in a median-nerve oddball paradigm. Regions uniquely related to somatosensory oddball responses (e.g., primary and secondary somatosensory, dorsal premotor, primary motor, and supplementary motor areas) were also localized. Since the parietal-frontal network supports attentional allocation during performance of the task, this study may provide a novel method, as well as normative baseline data, for examining attention-related deficits in the somatosensory system of patients with neurological or psychiatric disorders.

Adult↗

PubMed2005

M50 sensory gating predicts negative symptoms in schizophrenia.

Impaired auditory sensory gating is considered characteristic of schizophrenia and a marker of the information processing deficit inherent to that disorder. Predominance of negative symptoms also reflects the degree of deficit in schizophrenia and is associated with poorer pre-morbid functioning, lower IQ, and poorer outcomes. However, a consistent relationship between auditory sensory gating and negative symptoms in schizophrenia has yet to be demonstrated. The absence of such a finding is surprising, since both impaired auditory gating and negative symptoms have been linked with impaired fronto-temporal cortical function. The present study measured auditory gating using the P50 event related potential (ERP) in a paired-click paradigm and capitalized on the relative localization advantage of magnetoencephalography (MEG) to assess auditory sensory gating in terms of the event related field (ERF) M50 source dipoles on bilateral superior temporal gyrus (STG). The primary hypothesis was that there would be a positive correlation between lateralized M50 auditory sensory gating measures and negative symptoms in patients with schizophrenia. A standard paired-click paradigm was used during simultaneous EEG and MEG data collection to determine S2/S1 sensory gating ratios in a group of 20 patients for both neuroimaging techniques. Participants were administered the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale (PANSS), and the Calgary Depression Scale for Schizophrenia. Consistent with previous reports, there was no relationship between ERP P50 sensory gating and negative symptoms. However, right (not left) hemisphere ERF M50 sensory gating ratio was significantly and positively correlated with negative symptoms. This finding is compatible with information processing theories of negative symptoms and with more recent findings of fronto-temporal abnormality in patients with predominantly negative symptoms.

Adolescent↗

PubMed2005

A specific test of hippocampal deficit in schizophrenia.

Despite numerous studies in which hippocampal abnormalities were found, schizophrenia patients' hippocampal neural activity has not been systematically evaluated on a specific hippocampal-dependent task. The transverse-patterning task (TP) is sensitive to the relational mnemonic capabilities of the hippocampus. Ten schizophrenia patients and 10 controls performed TP and control tasks that are not hippocampal dependent. As predicted, patients displayed a behavioral impairment in TP and not in control tasks. Magnetoencephalography showed controls activating right hippocampus during TP performance. Patients showed more bilateral or left hippocampal activation during TP, and greater left lateralization was associated with better performance on TP. Patients' abnormal hippocampal lateralization may play a role in the hippocampal-dependent behavioral deficit.

Adult↗

PubMed2005

Cross-modal generality of the gating deficit.

Auditory P50/M50 paired-click studies have established an association between schizophrenia and impaired sensory gating in the auditory modality. However, the presumed cross-modal generality of the gating deficit has received little study. The present study examined gating in area 3b of primary somatosensory cortex to evaluate patients' somatosensory gating at this first stage of cortical processing. One hundred twenty-two channels of magnetoencephalography (MEG) data were collected from 27 subjects with chronic schizophrenia and 21 controls during a somatosensory paired-pulse paradigm with a 75- or 500-ms interstimulus interval. M20 somatosensory responses were localized using magnetic source imaging, and a gating ratio was calculated. In a subset of these subjects, MEG was also done for the standard auditory paradigm to assess M50 gating. Patients showed abnormal auditory M50 gating but normal somatosensory M20 gating. Results argue against a cross-modal gating deficit in primary somatosensory cortex.

Acoustic Stimulation↗

PubMed2005

Distinct M50 and M100 auditory gating deficits in schizophrenia.

The time course of the schizophrenia auditory gating deficit may provide clues to mechanisms of impaired cognition. Magnetoencephalography was recorded during a standard paired-click paradigm. Using source strength of the M50 and M100 components for each click, calculated from dipole locations identified as underlying each component for the first click, a ratio of the second divided by the first was used to measure gating. Patients showed a left-hemisphere gating deficit in M50 and a bilateral gating deficit in M100. Hypothesizing that an early deficit may affect later processing, hierarchical regression was used to examine variance shared between the components. A left-hemisphere M100 gating deficit was coupled with the left M50 gating deficit. In contrast, a right-hemisphere M100 gating deficit was unrelated to M50 gating in either hemisphere. Investigations of interhemisphere gating relations may clarify group differences in regional connectivity and their role in gating.

Adult↗

PubMed2003

A non-invasive method for observing hippocampal function.

A non-invasive method for observing the functioning of the hippocampus could be invaluable in understanding the role of hippocampal abnormalities in many brain disorders. Transverse patterning, a hippocampal-dependent memory task, was used in an attempt to study the functioning hippocampus. Subjects performed transverse patterning while whole-head MEG data were collected. The MEG data were analyzed using a spatial-temporal multiple-dipole approach. Controls showed right hippocampal activation. Patients with unilateral hippocampal damage showed activation in undamaged hippocampus. MEG during transverse patterning performance is a promising, non-invasive tool for assessing hippocampal function.

Adult↗

PubMed2003

Visual processing of facial affect.

To evaluate the role of the fusiform gyrus in identifying and processing facial emotional expression in humans, MEG data were collected while six healthy subjects judged whether photographs of faces displayed emotion (happiness or disgust) compared to neutral faces and equiluminant scrambled faces. For all six subjects, a magnetic source localizing to right fusiform gyrus was evident approximately 150 ms following presentation of face stimuli, but not following non-face stimuli. MEG source strength for this component was greatest for happy, intermediate for disgust, and lowest for neutral facial expressions, suggesting that activity in fusiform gyrus is sensitive to both face-specific stimuli and to the affective content of the face. These findings are considered in the context of a specialized neural face-dependent information system.

Adult↗

PubMed2003

Lateralization of auditory sensory gating and neuropsychological dysfunction in schizophrenia.

OBJECTIVE: Sensory gating assessed via EEG in a paired-click paradigm has often served as a neurophysiological metric of attentional function in schizophrenia. However, the standard EEG measure of sensory gating using the P50 component at electrode Cz does not foster differential assessment of left and right hemisphere contributions. Magnetoencephalography (MEG) is complementary to EEG, and its analogous M50 component may be better suited for localization and analysis of such lateralized cortical generators. The authors hypothesized that 1) auditory gating would be evident in M50 sources in superior temporal gyrus, demonstrating ratios similar to P50; 2) M50 would resemble P50 in distinguishing gating in comparison subjects and patients with schizophrenia, but M50 would show lateralization of the gating deficit; and 3) P50 and M50 sensory gating ratios would predict neuropsychological measures in patients and comparison subjects, with the MEG identification of left and right hemisphere sources allowing for the evaluation of lateralization in brain-behavior relationships. METHOD: Event-related EEG and MEG recordings were simultaneously obtained from 20 patients with schizophrenia and 15 comparison subjects. P50 amplitudes, M50 dipole source strengths, and P50 and M50 gating ratios were compared and assessed with respect to scores on neuropsychological performance measures. RESULTS: M50 dipoles localizing to superior temporal gyrus demonstrated gating similar to that of P50. As expected, patients demonstrated less P50 gating than did comparison subjects. Left (but not right) hemisphere M50 gating 1) correlated with EEG gating, 2) differentiated patients and comparison subjects, and 3) correlated with neuropsychological measures of sustained attention and working memory. CONCLUSIONS: Converging evidence from EEG, MEG, and neuropsychological measures points to left hemisphere dysfunction as strongly related to the well-established sensory gating deficit in schizophrenia.

Acoustic Stimulation↗

PubMed2002

Fluctuating asymmetry and the human brain.

Adaptive development requires the organism to resist genetic and environmental stresses that disrupt the genetic plan for growth, a buffering capacity termed developmental stability. Developmental instability is revealed by fluctuating asymmetry (FA), which has been demonstrated in many species to reflect phenotypic and genetic quality. We report (1) that a measure of developmental instability based on body FA predicts deviation from typical brain asymmetry, (2) that a combined measure of atypical brain asymmetry and body FA correlated negatively with the area of the corpus callosum, especially the portion connecting the left and right planum temporale, and (3) that this combined measure also predicted atypical asymmetry of the size of the somatosensory representation of the two hands, as determined from magnetic source imaging.

Journal Article↗

PubMed2002

Abnormal stimulus-response intensity functions in posttraumatic stress disorder: an electrophysiological investigation.

OBJECTIVE: The purpose of this study was to explore the relationship between combat-related posttraumatic stress disorder (PTSD) and specific augmentation versus reduction patterns for the N100 and P200 components of auditory event-related potentials evoked by tones of increasing intensity. METHOD: Event-related potentials of subjects with PTSD (N=36), subjects with no psychopathology (N=20), subjects with major depression but no PTSD (N=10), and subjects with a history of chronic alcohol abuse but no PTSD (N=8) were recorded. Brain responses were evoked by a 2000-Hz tone presented in intensity blocks of 65, 72.5, 80, 87.5, and 95 dB (SPL). RESULTS: Evoked data from five PTSD subjects were of poor quality and excluded from further analyses. For all but one subject with no psychopathology and for all subjects with a history of alcohol abuse or major depression (but no PTSD), the Cz amplitude of the P200 response component showed augmentation as a nearly linear function of tone intensity. As a group, subjects with PTSD showed no such increase in P200 response magnitude. Examination of the data from individual subjects with PTSD showed that 42% exhibited augmentation patterns similar to those seen for subjects in the comparison groups. However, 58% showed evidence of P200 reduction, with the response to the loudest tone being smaller than responses to tones of intermediate intensity. CONCLUSIONS: The data suggest that there is a significant subgroup of patients with combat-related PTSD who enter into a state of protective inhibition at relatively low stimulus intensities. It is hypothesized that this is an appropriate adaptive mechanism for these subjects rather than an indication of a core neurobiological abnormality.

Acoustic Stimulation↗