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Probing thalamic integrity in schizophrenia using concurrent transcranial magnetic stimulation and functional magnetic resonance imaging.

ABSTRACT: Schizophrenia is a devastating illness with an indeterminate pathophysiology. Several lines of evidence implicate dysfunction in the thalamus, a key node in the distributed neural networks underlying perception, emotion, and cognition. Existing evidence of aberrant thalamic function is based on indirect measures of thalamic activity, but dysfunction has not yet been demonstrated with a causal method.To test the hypothesis that direct physiological stimulation of the cortex will produce an abnormal thalamic response in individuals with schizophrenia.We stimulated the precentral gyrus with single-pulse transcranial magnetic stimulation (spTMS) and measured the response to this pulse in synaptically connected regions (thalamus, medial superior frontal cortex, insula) using concurrent functional magnetic resonance imaging. The mean hemodynamic response from these regions was fit with the sum of 2 gamma functions, and response parameters were compared across groups.Academic research laboratory.Patients with schizophrenia and sex- and age-matched psychiatrically healthy subjects were recruited from the community.Peak amplitude of the thalamic hemodynamic response to spTMS of the precentral gyrus.The spTMS-evoked responses did not differ between groups at the cortical stimulation site. Compared with healthy subjects, patients with schizophrenia showed a reduced response to spTMS in the thalamus (P=1.86 × 10(-9)) and medial superior frontal cortex (P=.02). Similar results were observed in the insula. Sham TMS indicated that these results could not be attributed to indirect effects of TMS coil discharge. Functional connectivity analyses revealed weaker thalamus-medial superior frontal cortex and thalamus-insula connectivity in patients with schizophrenia compared with control subjects.Individuals with schizophrenia showed reduced thalamic activation in response to direct perturbation delivered to the cortex. These results extend prior work implicating the thalamus in the pathophysiology of schizophrenia and suggest that the thalamus contributes to the patterns of aberrant connectivity characteristic of this disease.

SUBMITTER: Guller Y

PROVIDER: S-EPMC3411883 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Probing thalamic integrity in schizophrenia using concurrent transcranial magnetic stimulation and functional magnetic resonance imaging.

Guller Yelena Y Ferrarelli Fabio F Shackman Alexander J AJ Sarasso Simone S Peterson Michael J MJ Langheim Frederick J FJ Meyerand Mary E ME Tononi Giulio G Postle Bradley R BR

Archives of general psychiatry 20120701 7

<h4>Context</h4>Schizophrenia is a devastating illness with an indeterminate pathophysiology. Several lines of evidence implicate dysfunction in the thalamus, a key node in the distributed neural networks underlying perception, emotion, and cognition. Existing evidence of aberrant thalamic function is based on indirect measures of thalamic activity, but dysfunction has not yet been demonstrated with a causal method.<h4>Objective</h4>To test the hypothesis that direct physiological stimulation of ...[more]

PMID: 22393203

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Project description:ObjectiveA minimally conscious state (MCS) is characterized by discernible behavioral evidence of consciousness that cannot be reproduced consistently. This condition is highly challenging to treat. Recent studies have demonstrated the potential therapeutic effect of non-invasive brain stimulation in patients with MCS. In one patient in an MCS, we delivered simultaneous transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) based on an individual brain network analysis and evaluated the therapeutic effect.MethodsThe directional transfer function (DTF) was calculated based on electroencephalograph (EEG) analysis. Global brain connectivity was calculated based on functional magnetic resonance imaging (fMRI) analysis. By referring to the EEG and fMRI results, we identified inferior parietal lobes (IPLs) as targets. In the 2-week treatment period, 14 sessions were applied to the identified bilateral parietal regions. Simultaneous 1.5-mA anodal tDCS and 5-Hz rTMS were delivered for 20 min per hemisphere in each session. Clinical evaluation scores were recorded weekly throughout the treatment. A second patient given the routine treatment was evaluated as a control.ResultsThe clinical scores of patient 1 with MCS improved after 2 weeks of stimulation treatment, and the effect lasted for up to 1 month. EEG analysis showed a significant increase (p < 0.001) in the DTF value in the gamma band in a bilateral set of posterior regions, and fMRI showed a trend toward normalized activity in the IPLs. The clinical scores of patient 2 with coma did not improve much after 2 weeks of routine treatment. The EEG analysis showed a significant increase (p = 0.021) in the DTF value in the gamma band in a bilateral set of posterior regions.ConclusionThe application of EEG and fMRI to characterize the functional connectivity features of the network in an MCS patient provided a reasonable and accurate stimulation target and verified the changes in functional connectivity resulting from stimulation.

Dataset Information

Probing thalamic integrity in schizophrenia using concurrent transcranial magnetic stimulation and functional magnetic resonance imaging.

Publications

Probing thalamic integrity in schizophrenia using concurrent transcranial magnetic stimulation and functional magnetic resonance imaging.

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