Neurochemical Effects of Theta Burst Stimulation as Assessed by Magnetic Resonance Spectroscopy

Centre for Functional Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom.
Journal of Neurophysiology (Impact Factor: 2.89). 05/2009; 101(6):2872-7. DOI: 10.1152/jn.91060.2008
Source: PubMed


Continuous theta burst stimulation (cTBS) is a novel transcranial stimulation technique that causes significant inhibition of synaptic transmission for <or=1 h when applied over the primary motor cortex (M1) in humans. Here we use magnetic resonance spectroscopy to define mechanisms mediating this inhibition by noninvasively measuring local changes in the cortical concentrations of gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx). cTBS to the left M1 led to an increase in GABA compared with stimulation at a control site without significant change in Glx. This direct evidence for increased GABAergic interneuronal activity is framed in terms of a new hypothesis regarding mechanisms underlying cTBS.

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Available from: Charlotte J Stagg, Nov 17, 2014
    • "In addition, we applied continuous theta burst (cTBS) transcranial magnetic stimulation (TMS) to the PFC to assess the effect on local synaptic physiology in both the young and aged cohorts. cTBS is a TMS protocol (Huang et al. 2005) that affects GABAergic interneuronal circuits in motor cortex (Stagg et al. 2009; Di Lazzaro et al. 2012), and thus, it is hypothesized that this intervention will preferentially affect the inhibitory connections within the prefrontal cortex and further that this will have a behavioral effect on memory performance by disrupting these GABAergic circuits. Our overall goal was to elucidate the cellular and synaptic source of age-related intrinsic connectivity deficits identified in the PFC that may contribute to whole-brain functional connectivity and behavioral impairments. "
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    ABSTRACT: Memory impairments and heightened prefrontal cortical (PFC) activity are hallmarks of cognitive and neurobiological human aging. While structural integrity of PFC gray matter and interregional white matter tracts are thought to impact memory processing, the balance of neurotransmitters within the PFC itself is less well understood. We used fMRI to establish whole-brain networks involved in a memory encoding task and dynamic causal models (DCMs) for fMRI to determine the causal relationships between these areas. These data revealed enhanced connectivity from PFC to medial temporal cortex that negatively correlated with recall ability. To better understand the intrinsic activity within the PFC, DCM for EEG was employed after continuous theta burst transcranial magnetic stimulation (TMS) to the PFC to assess the effect on excitatory/inhibitory (E/I) synaptic ratios and behavior. These data revealed that the young cohort had a stable E/I ratio that was unaffected by the TMS intervention, while the aged cohort exhibited lower E/I ratios driven by a greater intrinsic inhibitory tone. TMS to the aged cohort resulted in decreased intrinsic inhibition and a decrement in memory performance. These results demonstrate increased top-down influence of PFC upon medial temporal lobe in healthy aging that is associated with decreased memory and may be due to unstable local inhibitory tone within the PFC.
    No preview · Article · Sep 2015 · Cerebral Cortex
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    • "Theta-burst TMS decreases the magnitude of evoked potentials in motor [50] and somatosensory [67] regions, decreases motor excitability [68], increases saccade latencies [69], and increases phosphene thresholds [70]. Furthermore, studies of theta-burst TMS have suggested that it alters inhibitory systems, as assessed with electrophysiological recordings from the spinal cord [68] and MR spectroscopy measurements [71] in humans, and with electrophysiological recordings and measurement of protein expression in rats [72]. "
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    ABSTRACT: Transcranial Magnetic Stimulation (TMS) is an important tool for testing causal relationships in cognitive neuroscience research. However, the efficacy of TMS can be variable across individuals and difficult to measure. This variability is especially a challenge when TMS is applied to regions without well-characterized behavioral effects, such as in studies using TMS on multi-modal areas in intrinsic networks. Here, we examined whether perfusion fMRI recordings of Cerebral Blood Flow (CBF), a quantitative measure sensitive to slow functional changes, reliably index variability in the effects of stimulation. Twenty-seven participants each completed four combined TMS-fMRI sessions during which both resting state Blood Oxygen Level Dependent (BOLD) and perfusion Arterial Spin Labeling (ASL) scans were recorded. In each session after the first baseline day, continuous theta-burst TMS (TBS) was applied to one of three locations: left dorsolateral prefrontal cortex (L dlPFC), left anterior insula/frontal operculum (L aI/fO), or left primary somatosensory cortex (L S1). The two frontal targets are components of intrinsic networks and L S1 was used as an experimental control. CBF changes were measured both before and after TMS on each day from a series of interleaved resting state and perfusion scans. Although TBS led to weak selective increases under the coil in CBF measurements across the group, individual subjects showed wide variability in their responses. TBS-induced changes in rCBF were related to TBS-induced changes in functional connectivity of the relevant intrinsic networks measured during separate resting-state BOLD scans. This relationship was selective: CBF and functional connectivity of these networks were not related before TBS or after TBS to the experimental control region (S1). Furthermore, subject groups with different directions of CBF change after TBS showed distinct modulations in the functional interactions of targeted networks. These results suggest that CBF is a marker of individual differences in the effects of TBS.
    Full-text · Article · Jul 2014 · PLoS ONE
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    • "Previously, MRS has been used to demonstrate an increase in GABA concentration following the application of cTBS to the motor cortex [11], raising the question of whether such effects are reproducible in non-motor cortical areas. Furthermore, the application of MRS to study functional changes in GABA is a relatively new and unconfirmed approach, the implementation of which can differ widely between laboratories. "
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    ABSTRACT: This series of experiments investigated the neural basis of conscious vision in humans using a form of transcranial magnetic stimulation (TMS) known as continuous theta burst stimulation (cTBS). Previous studies have shown that occipital TMS, when time-locked to the onset of visual stimuli, can induce a phenomenon analogous to blindsight in which conscious detection is impaired while the ability to discriminate 'unseen' stimuli is preserved above chance. Here we sought to reproduce this phenomenon using offline occipital cTBS, which has been shown to induce an inhibitory cortical aftereffect lasting 45-60 minutes. Contrary to expectations, our first experiment revealed the opposite effect: cTBS enhanced conscious vision relative to a sham control. We then sought to replicate this cTBS-induced potentiation of consciousness in conjunction with magnetoencephalography (MEG) and undertook additional experiments to assess its relationship to visual cortical excitability and levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA; via magnetic resonance spectroscopy, MRS). Occipital cTBS decreased cortical excitability and increased regional GABA concentration. No significant effects of cTBS on MEG measures were observed, although the results provided weak evidence for potentiation of event related desynchronisation in the β band. Collectively these experiments suggest that, through the suppression of noise, cTBS can increase the signal-to-noise ratio of neural activity underlying conscious vision. We speculate that gating-by-inhibition in the visual cortex may provide a key foundation of consciousness.
    Full-text · Article · Jun 2014 · PLoS ONE
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