Repetitive Transcranial Magnetic Stimulation Paradigm Research Articles

Dose and time-dependence of acute intermittent theta-burst stimulation on hippocampus-dependent memory in parkinsonian rats.

The treatment options for cognitive impairments in Parkinson's disease (PD) are limited. Repetitive transcranial magnetic stimulation has been applied in various neurological diseases. However, the effect of intermittent theta-burst stimulation (iTBS) as a more developed repetitive transcranial magnetic stimulation paradigm on cognitive dysfunction in PD remains largely unclear. Our aim was to explore the effect of acute iTBS on hippocampus-dependent memory in PD and the mechanism underlying it. Different blocks of iTBS protocols were applied to unilateral 6-hydroxidopamine-induced parkinsonian rats followed by the behavioral, electrophysiological and immunohistochemical analyses. The object-place recognition and hole-board test were used to assess hippocampus-dependent memory. Sham-iTBS and 1 block-iTBS (300 stimuli) didn't alter hippocampus-dependent memory, hippocampal theta rhythm and the density of c-Fos- and parvalbumin-positive neurons in the hippocampus and medial septum. 3 block-iTBS (900 stimuli) alleviated 6-hydroxidopamine-induced memory impairments, and increased the density of hippocampal c-Fos-positive neurons at 80 min post-stimulation but not 30 min compared to sham-iTBS. Interestingly, 3 block-iTBS first decreased and then increased normalized theta power during a period of 2 h following stimulation. Moreover, 3 block-iTBS decreased the density of parvalbumin-positive neurons in the medial septum at 30 min post-stimulation compared to sham-iTBS. The results indicate that multiple blocks of iTBS elicit dose and time-dependent effects on hippocampus-dependent memory in PD, which may be attributed to changes in c-Fos expression and the power of theta rhythm in the hippocampus.

Accelerated intermittent theta burst stimulation rapidly attenuates suicide ideation in major depression: insights from brain perfusion and functional connectivity

Background: Accelerated repetitive transcranial magnetic stimulation paradigms have been shown to result in fast decreases in depressive symptoms and suicidal ideation. However, the neural working mechanisms behind this prompt reductions on mood and suicidal thoughts, also after having received placebo stimulation, remains to be determined.

Variability and Predictors of Response to Continuous Theta Burst Stimulation: A TMS-EEG Study.

Continuous theta-burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation paradigm reported to decrease the excitability of the stimulated cortical area and which is thought to reflect a form of inhibitory synaptic plasticity. However, since its introduction, the effect of cTBS has shown a remarkable variability in its effects, which are often quantified by measuring the amplitude of motor evoked potentials (MEPs). Part of this inconsistency in experimental results might be due to an intrinsic variability of TMS effects caused by genetic or neurophysiologic factors. However, it is also possible that MEP only reflect the excitability of a sub-population of output neurons; resting EEG power and measures combining TMS and electroencephalography (TMS-EEG) might represent a more thorough reflection of cortical excitability. The aim of the present study was to verify the robustness of several predictors of cTBS response, such as I wave recruitment and baseline MEP amplitude, and to test cTBS after-effects on multiple neurophysiologic measurements such as MEP, resting EEG power, local mean field power (LMFP), TMS-related spectral perturbation (TRSP), and inter-trial phase clustering (ITPC). As a result, we were not able to confirm either the expected decrease of MEP amplitude after cTBS or the ability of I wave recruitment and MEP amplitude to predict the response to cTBS. Resting EEG power, LMFP, TRSP, and ITPC showed a more consistent trend toward a decrease after cTBS. Overall, our data suggest that the effect of cTBS on corticospinal excitability is variable and difficult to predict with common electrophysiologic markers, while its effect might be clearer when probed with combined TMS and EEG.

Subgenual Anterior Cingulate–Medial Orbitofrontal Functional Connectivity in Medication-Resistant Major Depression: A Neurobiological Marker for Accelerated Intermittent Theta Burst Stimulation Treatment?

BackgroundAccelerated repetitive transcranial magnetic stimulation paradigms have been shown to result in fast decreases in depressive symptoms and suicidal ideation. Although the subgenual anterior cingulate cortex (sgACC) region has been put forward as a possible biological marker, so far, no studies evaluated the clinical effects of accelerated intermittent theta burst stimulation (aiTBS) on sgACC functional connectivity (FC). MethodsFifty patients with treatment-resistant depression were enrolled in this registered randomized double-blind sham-controlled crossover aiTBS treatment study. All received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (5 daily sessions spread over 4 days). Forty-four complete resting-state functional magnetic resonance imaging scans were collected. Baseline resting-state functional magnetic resonance imaging scans were compared with a matched healthy control group. Besides depression severity, all patients were also assessed with the Scale for Suicide Ideation and the Beck Hopelessness Scale. ResultsOur main resting-state functional magnetic resonance imaging findings indicate that a positive sgACC FC correlation with the medial orbitofrontal cortex could distinguish aiTBS responders from nonresponders at baseline. Beneficial aiTBS treatment strengthened sgACC–medial orbitofrontal cortex FC patterns. Moreover, this increased FC pattern was associated with a decrease in feelings of hopelessness. ConclusionsClinical response to aiTBS treatment is not only characterized by stronger FC patterns between the sgACC and the medial orbitofrontal cortex, but it is also associated with decreases in hopelessness. Our observations provide a possible neurobiological explanation why accelerated repetitive transcranial magnetic stimulation paradigms may result in prompt attenuation of negative thinking in depressed patients.

Cortical oscillatory activity and the induction of plasticity in the human motor cortex

Repetitive transcranial magnetic stimulation paradigms such as continuous theta burst stimulation (cTBS) induce long-term potentiation- and long-term depression-like plasticity in the human motor cortex. However, responses to cTBS are highly variable and may depend on the activity of the cortex at the time of stimulation. We investigated whether power in different electroencephalogram (EEG) frequency bands predicted the response to subsequent cTBS, and conversely whether cTBS had after-effects on the EEG. cTBS may utilize similar mechanisms of plasticity to motor learning; thus, we conducted a parallel set of experiments to test whether ongoing electroencephalography could predict performance of a visuomotor training task, and whether training itself had effects on the EEG. Motor evoked potentials (MEPs) provided an index of cortical excitability pre- and post-intervention. The EEG was recorded over the motor cortex pre- and post-intervention, and power spectra were computed. cTBS reduced MEP amplitudes; however, baseline power in the delta, theta, alpha or beta frequencies did not predict responses to cTBS or learning of the visuomotor training task. cTBS had no effect on delta, theta, alpha or beta power. In contrast, there was an increase in alpha power following visuomotor training that was positively correlated with changes in MEP amplitude post-training. The results suggest that the EEG is not a useful state-marker for predicting responses to plasticity-inducing paradigms. The correlation between alpha power and changes in corticospinal excitability following visuomotor training requires further investigation, but may be related to disengagement of the somatosensory system important for motor memory consolidation.

Electrophysiological correlates of reduced pain perception after theta-burst stimulation

In an earlier study, we reported the antinociceptive effects of a special repetitive transcranial magnetic stimulation paradigm: continuous theta-burst stimulation (cTBS), when applied to human motor cortex. Here, we investigated whether the reduced subjective pain perception of 10 healthy individuals could be measured by changes in laser-evoked potentials, a reflection of pain related activations in the operculoinsular and midcingulate cortex. To minimize the effect of habituation during repeated laser stimulation, a bioadaptive design was used. However, both pain ratings and laser-evoked potential amplitudes were reduced after real and sham cTBS. When compared with sham stimulation, cTBS resulted in a significantly greater diminution of pain ratings and N2-P2 amplitudes on the hand contralateral to the site of motor cortex stimulation.

Selective modulation of intracortical inhibition by low-intensity Theta Burst Stimulation

Theta Burst Stimulation (TBS) is a repetitive transcranial magnetic stimulation paradigm which has effects on both excitatory and inhibitory intracortical pathways when applied at an intensity of 80% of active motor threshold. As intracortical inhibitory pathways have a lower threshold for activation than excitatory pathways, we sought to determine whether it was possible to selectively target cortical inhibitory circuitry by reducing the intensity of TBS to 70% of active motor threshold. Motor evoked potentials (MEPs), short latency intracortical facilitation (SICF), intracortical facilitation (ICF) and short interval intracortical inhibition (SICI) were measured at baseline, 5-20 and 20-35 min following continuous (cTBS) and intermittent (iTBS) low-intensity TBS in nine healthy subjects. Low-intensity cTBS significantly reduced SICI 5-20 min following stimulation, whilst having no effect on MEPs, SICF or ICF. Low-intensity iTBS had no effect on SICI, MEPs, SICF or ICF. It is possible to selectively target intracortical inhibitory networks for modulation by low-intensity TBS, however, responses may critically depend upon the particular paradigm chosen. These findings have important implications for the treatment of neurological disorders where abnormal levels of intracortical inhibition are present, such as Parkinson's disease and focal hand dystonia and requires further investigation.

The role of dorsal premotor area in reaction task: comparing the “virtual lesion” effect of paired pulse or theta burst transcranial magnetic stimulation

We compared the effect on reaction times of transient interference with function of the dorsal premotor cortex (PMd) using a pair (25-ms interval) of transcranial magnetic stimulation (TMS) pulses with long-term interference produced by a new repetitive TMS paradigm known as "theta burst stimulation" (TBS). Pairs of TMS pulses over left PMd increased choice but not simple reaction times of the right hand if given at the onset of the reaction interval. There was no effect of stimulation over right PMd or at a midline parietal control site (Pz). In contrast, TBS over either left or right PMd increased choice RTs of both hands for at least 5-10 min after the end of TBS. Pairs of TMS pulses over left PMd also increased error rates whereas TBS had no effect on error rates despite the effect on RTs. We suggest that TBS leads to widespread changes in activity and more complex effects on behaviour than expected from the paired pulse TMS and conclude that transient and long-term forms of interference with function may influence behavioural tasks in subtly different ways.

P.2.098 A single blind comparison of 3 different repetitive transcranial magnetic stimulation paradigms in the treatment of resistant major depression

P.2.098 A single blind comparison of 3 different repetitive transcranial magnetic stimulation paradigms in the treatment of resistant major depression