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Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance.

ABSTRACT: Intermittent theta burst stimulation (iTBS) is a noninvasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex. Sixteen healthy participants received iTBS over prefrontal cortex at either 50, 75 or 100% resting motor threshold in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials and oscillations. The n-back task was used to assess changes in working memory performance. The data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS yielded the largest neurophysiological changes. Improvement in reaction time in the 3-back task was supported by the change in alpha power, however, comparison between conditions revealed no significant differences. The assumption that higher intensity results in greater neuromodulatory effects may be false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample.

SUBMITTER: Chung SW

PROVIDER: S-EPMC6866298 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance.

Chung Sung Wook SW Rogasch Nigel C NC Hoy Kate E KE Sullivan Caley M CM Cash Robin F H RFH Fitzgerald Paul B PB

Human brain mapping 20171109 2

Intermittent theta burst stimulation (iTBS) is a noninvasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory may be mecha ...[more]

PMID: 29124791

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Project description:BackgroundWorking memory deficit is one of the most critical complex cognitive impairments in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy, but not still unsatisfactory. Intermittent theta burst stimulation (iTBS), which has recently been used in clinical practice, may have faster and stronger effects comparing the traditional model (10-Hz high-frequency rTMS). A large number of studies have showed that rTMS, especially iTBS, can enhance the neural plasticity of the brain, and cognitive training can improve the cognitive function of schizophrenia. Is there any facilitation effect of iTBS add on cognitive training (such as working memory training, WMT) on cognitive function enhancement in schizophrenia is still unknown.Methods/designThe proposed study is designed of a double-center, double-blinded, randomized controlled trial that will include 200 schizophrenia patients between 18 and 45 years of age. The patients will be randomized to four groups, i.e., the study group (iTBS+WMT), WMS control group (iTBS+ Simple Response Training (SRT)), iTBS control group (sham iTBS+WMT), and placebo control (sham iTBS+SRT). The patients will receive 3 min 20 s of real or sham stimulation, followed by a short 1-2-min rest and 40 min of WMT training or SRT immediately. Neuropsychological and clinical symptom assessments, with functional and structural MRI, will be performed on baseline, post-treatment, and 3- and 6-month follow-up periods. The primary outcome is cognitive function measured by the MATRICS Consensus Cognitive Battery (MCCB). The secondary outcomes are changes in neuroplasticity, as measured by MRI and other behavioral assessments.DiscussionThe aim of our study is to explore the facilitation effects of iTBS added on WMT in improving cognitive function of schizophrenia. That means, patients with schizophrenia will benefit more in cognitive function improvement from the combination training mode of "preheating (iTBS stimulation changes the neural activity of working memory-related brain regions) and ironning (working memory training)." And the long-term effects of this combined training model will be assessed at a 6-month follow-up period. In case of a significant improvement of working memory with a prolonged effect, the iTBS combined with WMT protocol could be considered as a first-line clinical protocol in schizophrenia treatment. More broadly, the potential for increased universality and efficiency of rTMS with the iTBS model to enhance the neural plasticity of the brain should have a more positive effect on cognitive function in schizophrenia.Trial registrationchictr.org.cn ChiCTR1900023405 . Registered on 25 May 2019.

Project description:Introduction:Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. Methods:We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). Results:Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. Conclusion:Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

Project description:BackgroundTheta-band neuronal oscillations in the prefrontal cortex are associated with several cognitive functions. Oscillatory phase is an important correlate of excitability and phase synchrony mediates information transfer between neuronal populations oscillating at that frequency. The ability to extract and exploit the prefrontal theta rhythm in real time in humans would facilitate insight into neurophysiological mechanisms of cognitive processes involving the prefrontal cortex, and development of brain-state-dependent stimulation for therapeutic applications.ObjectivesWe investigate individual source-space beamforming-based estimation of the prefrontal theta oscillation as a method to target specific phases of the ongoing theta oscillations in the human dorsomedial prefrontal cortex (DMPFC) with real-time EEG-triggered transcranial magnetic stimulation (TMS). Different spatial filters for extracting the prefrontal theta oscillation from EEG signals are compared and additional signal quality criteria are assessed to take into account the dynamics of this cortical oscillation.MethodsTwenty two healthy participants were recruited for anatomical MRI scans and EEG recordings with 18 composing the final analysis. We calculated individual spatial filters based on EEG beamforming in source space. The extracted EEG signal was then used to simulate real-time phase-detection and quantify the accuracy as compared to post-hoc phase estimates. Different spatial filters and triggering parameters were compared. Finally, we validated the feasibility of this approach by actual real-time triggering of TMS pulses at different phases of the prefrontal theta oscillation.ResultsHigher phase-detection accuracy was achieved using individualized source-based spatial filters, as compared to an average or standard Laplacian filter, and also by detecting and avoiding periods of low theta amplitude and periods containing a phase reset. Using optimized parameters, prefrontal theta-phase synchronized TMS of DMPFC was achieved with an accuracy of ±55°.ConclusionThis study demonstrates the feasibility of triggering TMS pulses during different phases of the ongoing prefrontal theta oscillation in real time. This method is relevant for brain state-dependent stimulation in human studies of cognition. It will also enable new personalized therapeutic repetitive TMS protocols for more effective treatment of neuropsychiatric disorders.

Project description:BackgroundOver the past decade, the number of experimental and clinical studies using theta-burst-stimulation (TBS) protocols of transcranial magnetic stimulation (TMS) to modulate brain activity has risen substantially. The use of TBS is motivated by the assumption that these protocols can reliably and lastingly modulate cortical excitability despite their short duration and low number of stimuli. However, this assumption, and thus the experimental validity of studies using TBS, is challenged by recent work showing large inter- and intra-subject variability in response to TBS protocols.ObjectivesTo date, the reproducibility of TBS effects in humans has been exclusively assessed with motor evoked potentials (MEPs), which provide an indirect and limited measure of cortical excitability. Here we combined TMS with electroencephalography (TMS-EEG) and report the first comprehensive investigation of (1) direct TMS-evoked cortical responses to intermittent (iTBS) and continuous TBS (cTBS) of the human motor cortex, and (2) reproducibility of both iTBS- and cTBS-induced cortical response modulation against a robust sham control across repeat visits with commonly used cortical responsivity metrics.ResultsWe show that although single pulse TMS generates stable and reproducible cortical responses across visits, the modulatory effects of TBS vary substantially both between and within individuals. Overall, at the group level, most measures of the iTBS and cTBS-induced effects were not significantly different from sham-TBS. Most importantly, none of the significant TBS-induced effects observed in visit-1 were reproduced in visit-2.ConclusionsOur findings suggest that the generally accepted mechanisms of TBS-induced neuromodulation, i.e. through changes in cortical excitability, may not be accurate. Future research is needed to determine the mechanisms underlying the established therapeutic effects of TBS in neuropsychiatry and examine reproducibility of TBS-induced neuromodulation through oscillatory response dynamics.

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Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance.

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Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance.

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