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Functional neuroimaging of the baboon during concurrent image-guided transcranial magnetic stimulation.

ABSTRACT: Transcranial magnetic stimulation (TMS) has well-established applications in basic neuroscience and promising applications in neurological and psychiatric disorders. However the underlying mechanisms of TMS-induced alterations in brain function are not well understood. As a result, treatment design parameters are determined ad hoc and not informed by any coherent theory or model. Once the mechanisms underlying TMS's modulatory effects on brain systems are better understood and modeled, TMS's potential as a therapeutic and/or investigative tool will be more readily explored and exploited. An animal model is better suited to study different TMS variables, therefore we developed a baboon model to facilitate testing of some of the current theoretical models of TMS interactions with brain regions. We have demonstrated the feasibility of this approach by successfully imaging cerebral blood flow (CBF) changes with H(2)(15)O positron emission tomography imaging during high-frequency, suprathreshold repetitive TMS in the primary motor cortex of five healthy, adult baboons.

SUBMITTER: Salinas FS

PROVIDER: S-EPMC3139451 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Functional neuroimaging of the baboon during concurrent image-guided transcranial magnetic stimulation.

Salinas Felipe S FS Szabó C Ákos CÁ Zhang Wei W Jones Lisa L Leland M Michelle MM Wey Hsiao-Ying HY Duong Timothy Q TQ Fox Peter T PT Narayana Shalini S

NeuroImage 20110530 4

Transcranial magnetic stimulation (TMS) has well-established applications in basic neuroscience and promising applications in neurological and psychiatric disorders. However the underlying mechanisms of TMS-induced alterations in brain function are not well understood. As a result, treatment design parameters are determined ad hoc and not informed by any coherent theory or model. Once the mechanisms underlying TMS's modulatory effects on brain systems are better understood and modeled, TMS's pot ...[more]

PMID: 21664276

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Project description: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.

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.

Project description:Recent studies have synchronized transcranial magnetic stimulation (TMS) application with pre-defined brain oscillatory phases showing how brain response to perturbation depends on the brain state. However, none have investigated whether phase-dependent TMS can possibly modulate connectivity with homologous distant brain regions belonging to the same network. In the framework of network-targeted TMS, we investigated whether stimulation delivered at a specific phase of ongoing brain oscillations might favour stronger cortico-cortical (c-c) synchronization of distant network nodes connected to the stimulation target. Neuronavigated TMS pulses were delivered over the primary motor cortex (M1) during ongoing electroencephalography recording in 24 healthy individuals over two repeated sessions 1 month apart. Stimulation effects were analysed considering whether the TMS pulse was delivered at the time of a positive (peak) or negative (trough) phase of μ-frequency oscillation, which determines c-c synchrony within homologous areas of the sensorimotor network. Diffusion weighted imaging was used to study c-c connectivity within the sensorimotor network and identify contralateral regions connected with the stimulation spot. Depending on when during the μ-activity the TMS-pulse was applied (peak or trough), its impact on inter-hemispheric network synchrony varied significantly. Higher M1-M1 phase-lock synchronization after the TMS-pulse (0-200 ms) in the μ-frequency band was found for trough compared to peak stimulation trials in both study visits. Phase-dependent TMS delivery might be crucial not only to amplify local effects but also to increase the magnitude and reliability of the response to the external perturbation, with implications for interventions aimed at engaging more distributed functional brain networks. KEY POINTS: Synchronized transcranial magnetic stimulation (TMS) pulses with pre-defined brain oscillatory phases allow evaluation of the impact of brain states on TMS effects. TMS pulses over M1 at the negative peak of the μ-frequency band induce higher phase-lock synchronization with interconnected contralateral homologous regions. Cortico-cortical synchronization changes are linearly predicted by the fibre density and cross-section of the white matter tract that connects the two brain regions. Phase-dependent TMS delivery might be crucial not only to amplify local effects but also to increase the magnitude and reliability of within-network synchronization.

Project description:The neurobiology of major depressive disorder (MDD) remains incompletely understood, and many individuals fail to respond to standard treatments. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has emerged as a promising antidepressant therapy. However, the heterogeneity of response underscores a pressing need for biomarkers of treatment outcome. We acquired resting state functional magnetic resonance imaging (rsfMRI) data in 47 MDD individuals prior to 5-8 weeks of rTMS treatment targeted using the F3 beam approach and in 29 healthy comparison subjects. The caudate, prefrontal cortex, and thalamus showed significantly lower blood oxygenation level-dependent (BOLD) signal power in MDD individuals at baseline. Critically, individuals who responded best to treatment were associated with lower pre-treatment BOLD power in these regions. Additionally, functional connectivity (FC) in the default mode and affective networks was associated with treatment response. We leveraged these findings to train support vector machines (SVMs) to predict individual treatment responses, based on learned patterns of baseline FC, BOLD signal power and clinical features. Treatment response (responder vs. nonresponder) was predicted with 85-95% accuracy. Reduction in symptoms was predicted to within a mean error of ±16% (r = .68, p < .001). These preliminary findings suggest that therapeutic outcome to DLPFC-rTMS could be predicted at a clinically meaningful level using only a small number of core neurobiological features of MDD, warranting prospective testing to ascertain generalizability. This provides a novel, transparent and physiologically plausible multivariate approach for classification of individual response to what has become the most commonly employed rTMS treatment worldwide. This study utilizes data from a larger clinical study (Australian New Zealand Clinical Trials Registry: Investigating Predictors of Response to Transcranial Magnetic Stimulation for the Treatment of Depression; ACTRN12610001071011; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336262).

Dataset Information

Functional neuroimaging of the baboon during concurrent image-guided transcranial magnetic stimulation.

Publications

Functional neuroimaging of the baboon during concurrent image-guided transcranial magnetic stimulation.

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