Dual-site Transcranial Magnetic Stimulation Research Articles

Cortico-cortical connectivity is influenced by levodopa in tremor-dominant Parkinson's disease

Resting tremor is the most common presenting motor symptom in Parkinson's disease (PD). The supplementary motor area (SMA) is a main target of the basal-ganglia-thalamo-cortical circuit and has direct, facilitatory connections with the primary motor cortex (M1), which is important for the execution of voluntary movement. Dopamine potentially modulates SMA and M1 activity, and both regions have been implicated in resting tremor. This study investigated SMA-M1 connectivity in individuals with PD ON and OFF dopamine medication, and whether SMA-M1 connectivity is implicated in resting tremor. Dual-site transcranial magnetic stimulation was used to measure SMA-M1 connectivity in PD participants ON and OFF levodopa. Resting tremor was measured using electromyography and accelerometry. Stimulating SMA inhibited M1 excitability OFF levodopa, and facilitated M1 excitability ON levodopa. ON medication, SMA-M1 facilitation was significantly associated with smaller tremor than SMA-M1 inhibition. The current findings contribute to our understanding of the neural networks involved in PD which are altered by levodopa medication and provide a neurophysiological basis for the development of interventions to treat resting tremor.

Probing intrahemispheric interactions with a novel dual-site TMS setup

ObjectiveUsing dual-site transcranial magnetic stimulation (dsTMS), the effective connectivity between the primary motor cortex (M1) and adjacent brain areas such as the dorsal premotor cortex (PMd) can be investigated. However, stimulating two brain regions in close proximity (e.g., ±2.3 cm for intrahemispheric PMd–M1) is subject to considerable spatial restrictions that potentially can be overcome by combining two standard figure-of-eight coils in a novel dsTMS setup. MethodsAfter a technical evaluation of its induced electric fields, the dsTMS setup was tested in vivo (n = 23) by applying a short-interval intracortical inhibition (SICI) protocol. Additionally, the intrahemispheric PMd–M1 interaction was probed. E-field modelling was performed using SimNIBS. ResultsThe technical evaluation yielded no major alterations of the induced electric fields due to coil overlap. In vivo, the setup reliably elicited SICI. Investigating intrahemispheric PMd–M1 interactions was feasible (inter-stimulus interval 6 ms), resulting in modulation of M1 output. ConclusionsThe presented dsTMS setup provides a novel way to stimulate two adjacent brain regions with fewer technical and spatial limitations than previous attempts. SignificanceThis dsTMS setup enables more accurate and repeatable targeting of brain regions in close proximity and can facilitate innovation in the field of effective connectivity.

Connecting the dots: harnessing dual-site transcranial magnetic stimulation to quantify the causal influence of medial frontal areas on the motor cortex.

Dual-site transcranial magnetic stimulation has been widely employed to investigate the influence of cortical structures on the primary motor cortex. Here, we leveraged this technique to probe the causal influence of two key areas of the medial frontal cortex, namely the supplementary motor area and the medial orbitofrontal cortex, on primary motor cortex. We show that supplementary motor area stimulation facilitates primary motor cortex activity across short (6 and 8ms) and long (12ms) inter-stimulation intervals, putatively recruiting cortico-cortical and cortico-subcortico-cortical circuits, respectively. Crucially, magnetic resonance imaging revealed that this facilitatory effect depended on a key morphometric feature of supplementary motor area: individuals with larger supplementary motor area volumes exhibited more facilitation from supplementary motor area to primary motor cortex for both short and long inter-stimulation intervals. Notably, we also provide evidence that the facilitatory effect of supplementary motor area stimulation at short intervals is unlikely to arise from spinal interactions of volleys descending simultaneously from supplementary motor area and primary motor cortex. On the other hand, medial orbitofrontal cortex stimulation moderately suppressed primary motor cortex activity at both short and long intervals, irrespective of medial orbitofrontal cortex volume. These results suggest that dual-site transcranial magnetic stimulation is a fruitful approach to investigate the differential influence of supplementary motor area and medial orbitofrontal cortex on primary motor cortex activity, paving the way for the multimodal assessment of these fronto-motor circuits in health and disease.

Can we manipulate brain connectivity? A systematic review of cortico-cortical paired associative stimulation effects

ObjectiveCortico-cortical paired associative stimulation (ccPAS) is a form of dual-site transcranial magnetic stimulation (TMS) entailing a series of single-TMS pulses paired at specific interstimulus intervals (ISI) delivered to distant cortical areas. The goal of this article is to systematically review its efficacy in inducing plasticity in humans focusing on stimulation parameters and hypotheses of underlying neurophysiology. MethodsA systematic review of the literature from 2009–2023 was undertaken to identify all articles utilizing ccPAS to study brain plasticity and connectivity. Six electronic databases were searched and included. Results32 studies were identified. The studies targeted connections within the same hemisphere or between hemispheres. 28 ccPAS studies were in healthy participants, 1 study in schizophrenia, and 1 in Alzheimer’s disease (AD) patients. 2 additional studies used cortico-cortical repetitive paired associative stimulation (cc-rPAS) in generalized anxiety disorder (GAD) patients. Outcome measures include electromyography (EMG), behavioral measures, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). ccPAS seems to be able to modulate brain connectivity depending on the ISI. ConclusionsccPAS can be used to modulate corticospinal excitability, brain activity, and behavior. Although the stimulation parameters used across studies reviewed in this paper are varied, ccPAS is a promising approach for basic research and potential clinical applications. SignificanceRecent advances in neuroscience have caused a shift of interest from the study of single areas to a more complex approach focusing on networks of areas that orchestrate brain activity. Consequently, the TMS community is also witnessing a change, with a growing interest in targeting multiple brain areas rather than a single locus, as evidenced by an increasing number of papers using ccPAS. In light of this new enthusiasm for brain connectivity, this review summarizes existing literature and stimulation parameters that have proven effective in changing electrophysiological, behavioral, or neuroimaging-derived measures.

Temporal interference for dual site transcranial magnetic stimulation

Dual-site Transcranial Magnetic Stimulation (ds-TMS) is a TMS protocol that involves stimulating two areas of the brain in close succession. This method is useful for studying the connections between two physical parts of the brain. TMS coils are generally designed for use on a single target area in the brain. When ds-TMS targets are in close proximity to one another, using traditional coils in a limited space increases the possibility of errors associated with positioning, resulting in inconsistent pulse strength and trajectory. We developed a single TMS coil that uses temporal interference (TI) to stimulate multiple targets within close proximity without compromising the ideal positioning of either location. TI TMS operates based on the frequency difference of two magnetic fields delivered simultaneously. The frequency difference between the two fields results in an envelope which can be steered to target a different location without moving the coil. We designed a TI-TMS coil and show that the peak induced electric field can be steered 4 cm in either direction (8 cm range) from the center point of the coil while delivering a peak field of 120 V/m, which is above the minimum 100 V/m needed to activate neurons. An experimental model was built using the same dimensions as the simulation model and validated that the physical model is able to steer the magnetic pulse using TI.

No Polarity-specific Modulation of Prefrontal-to-M1 Interhemispheric Inhibition by Transcranial Direct Current Stimulation Over the Lateral Prefrontal Cortex

The lateral prefrontal cortex (PFC) plays a variety of crucial roles in higher-order cognitive functions. Previous works have attempted to modulate lateral PFC function by applying non-invasive transcranial direct current stimulation (tDCS) and demonstrated positive effects on performance of tasks involving cognitive processes. The neurophysiological underpinning of the stimulation effects, however, remain poorly understood. Here, we explored the neurophysiological after-effects of tDCS over the lateral PFC by assessing changes in the magnitude of interhemispheric inhibition from the lateral PFC to the contralateral primary motor cortex (PFC-M1 IHI). Using a dual-site transcranial magnetic stimulation paradigm, we assessed PFC-M1 IHI before and after the application of tDCS over the right lateral PFC. We conducted a double-blinded, crossover, and counterbalanced design where 15 healthy volunteers participated in three sessions during which they received either anodal, cathodal, and sham tDCS. In order to determine whether PFC-M1 IHI could be modulated at all, we completed the same assessment on a separate group of 15 participants as they performed visuo-motor reaction tasks that likely engage the lateral PFC. The results showed that tDCS over the right lateral PFC did not modulate the magnitude of PFC-M1 IHI, whereas connectivity changed when Go/NoGo decisions were implemented in reactions during the motor tasks. Although PFC-M1 IHI is sensitive enough to be modulated by behavioral manipulations, tDCS over the lateral PFC does not have substantial modulatory effects on PFC to M1 functional connectivity, or at least not to the degree that can be detected with this measure.

Longitudinal evaluations of somatosensory-motor inhibition in Dopa-responsive dystonia

IntroductionGCH1 mutations have been linked to decreased striatal dopamine and development of dopa-responsive dystonia (DRD) and Parkinsonism. Sensory and sensorimotor integration impairments have been documented in various forms of dystonia.DRD patients with confirmed GCH1 mutations have demonstrated normal short-latency afferent inhibition (SAI), a measure of sensorimotor inhibition, under chronic dopaminergic replacement therapy (DRT), but reduced inhibition after a single l-dopa dose following 24 h withdrawal. Studies have revealed normal SAI in other forms of dystonia but reductions with DRT in Parkinson's disease. Longitudinal changes in sensorimotor inhibition are unknown. MethodsWe analyzed sensorimotor inhibition using two different measures: SAI and somatosensory-motor inhibition using dual-site transcranial magnetic stimulation (ds-TMS). SAI was measured using digit stimulation 25 ms prior to contralateral primary motor cortex (M1) TMS. DS-TMS was measured using TMS over the somatosensory cortex 1 or 2.5 ms prior to ipsilateral M1 stimulation.A total of 20 GCH1 mutation carriers and 20 age-matched controls were included in the study. SAI and ds-TMS were evaluated in GCH1 mutation carriers both OFF and ON DRT compared to controls. Furthermore, longitudinal changes of SAI were examined in a subset of the same individuals that were measured ∼five years earlier. ResultsNeither SAI nor ds-TMS were significantly different in GCH1 mutation carriers relative to controls. No effects of DRT on SAI or ds-TMS were seen but SAI decreased over time in mutation carriers OFF DRT. ConclusionOur longitudinal results suggest changes in SAI that could be associated with plasticity changes in sensorimotor networks.

The Interactions Between Primary Somatosensory and Motor Cortex during Human Grasping Behaviors

Afferent inputs to the primary somatosensory cortex (S1) are differentially processed during precision and power grip in humans. However, it remains unclear how S1 interacts with the primary motor cortex (M1) during these two grasping behaviors. To address this question, we measured short-latency afferent inhibition (SAI), reflecting S1-M1 interactions via thalamo-cortical pathways, using paired-pulse transcranial magnetic stimulation (TMS) during precision and power grip. The TMS coil over the hand representation of M1 was oriented in the posterior-anterior (PA) and anterior-posterior (AP) direction to activate distinct sets of corticospinal neurons. We found that SAI increased during precision compared with power grip when AP, but not PA, currents were applied. Notably, SAI tested in the AP direction were similar during two-digit than five-digit precision grip. The M1 receives movement information from S1 through direct cortico-cortical pathways, so intra-hemispheric S1-M1 interactions using dual-site TMS were also evaluated. Stimulation of S1 attenuated M1 excitability (S1-M1 inhibition) during precision and power grip, while the S1-M1 inhibition ratio remained similar across tasks. Taken together,our findings suggest that distinct neural mechanisms for S1-M1 interactions mediate precision and power grip, presumably by modulating neural activity along thalamo-cortical pathways.

Functional Connectivity at Rest between the Human Medial Posterior Parietal Cortex and the Primary Motor Cortex Detected by Paired-Pulse Transcranial Magnetic Stimulation.

The medial posterior parietal cortex (PPC) is involved in the complex processes of visuomotor integration. Its connections to the dorsal premotor cortex, which in turn is connected to the primary motor cortex (M1), complete the fronto-parietal network that supports important cognitive functions in the planning and execution of goal-oriented movements. In this study, we wanted to investigate the time-course of the functional connectivity at rest between the medial PPC and the M1 using dual-site transcranial magnetic stimulation in healthy humans. We stimulated the left M1 using a suprathreshold test stimulus to elicit motor-evoked potentials in the hand, and a subthreshold conditioning stimulus was applied over the left medial PPC at different inter-stimulus intervals (ISIs). The conditioning stimulus affected the M1 excitability depending on the ISI, with inhibition at longer ISIs (12 and 15 ms). We suggest that these modulations may reflect the activation of different parieto-frontal pathways, with long latency inhibitions likely recruiting polisynaptic pathways, presumably through anterolateral PPC.

Reduced SMA-M1 connectivity in older than younger adults measured using dual-site TMS.

With advancing age comes a decline in voluntary movement control. Growing evidence suggests that an age-related decline in effective connectivity between the supplementary motor area and primary motor cortex (SMA-M1) might play a role in an age-related decline of bilateral motor control. Dual-site transcranial magnetic stimulation (TMS) can be used to measure SMA-M1 effective connectivity. In the current study, we aimed to (1) replicate previous dual-site TMS research showing reduced SMA-M1 connectivity in older than younger adults and (2) examine whether SMA-M1 connectivity is associated with bilateral motor control in independent samples of younger (n = 30) and older adults (n = 30). SMA-M1 connectivity was measured using dual-site TMS with interstimulus intervals of 6, 7 and 8 ms, and bilateral motor control was measured using the Purdue Pegboard, Four Square Step Test and the Timed Up and Go task. Findings from this study showed that SMA-M1 connectivity was reduced in older than in younger adults, suggesting that the direct excitatory connections between SMA and M1 had reduced efficacy in older than younger adults. Furthermore, greater SMA-M1 connectivity was associated with better bimanual motor control in older adults. Thus, SMA-M1 connectivity in older adults might underpin, in part, the age-related decline in bilateral motor control. These findings contribute to our understanding of age-related declines in motor control and provide a physiological basis for the development of interventions to improve bimanual and bilateral motor control.

Neurophysiological modulations in the (pre)motor-motor network underlying age-related increases in reaction time and the role of GABA levels – a bimodal TMS-MRS study

It has been argued that age-related changes in the neurochemical and neurophysiological properties of the GABAergic system may underlie increases in reaction time (RT) in older adults. However, the role of GABA levels within the sensorimotor cortices (SMC) in mediating interhemispheric interactions (IHi) during the processing stage of a fast motor response, as well as how both properties explain interindividual differences in RT, are not yet fully understood.In this study, edited magnetic resonance spectroscopy (MRS) was combined with dual-site transcranial magnetic stimulation (dsTMS) for probing GABA+ levels in bilateral SMC and task-related neurophysiological modulations in corticospinal excitability (CSE), and primary motor cortex (M1)-M1 and dorsal premotor cortex (PMd)-M1 IHi, respectively. Both CSE and IHi were assessed during the preparatory and premotor period of a delayed choice RT task. Data were collected from 25 young (aged 18–33 years) and 28 older (aged 60–74 years) healthy adults.Our results demonstrated that older as compared to younger adults exhibited a reduced bilateral CSE suppression, as well as a reduced magnitude of long latency M1-M1 and PMd-M1 disinhibition during the preparatory period, irrespective of the direction of the IHi. Importantly, in older adults, the GABA+ levels in bilateral SMC partially accounted for task-related neurophysiological modulations as well as individual differences in RT. In contrast, in young adults, neither task-related neurophysiological modulations, nor individual differences in RT were associated with SMC GABA+ levels.In conclusion, this study contributes to a comprehensive initial understanding of how age-related differences in neurochemical properties and neurophysiological processes are related to increases in RT.

Test Re-test Reliability of Dual-site TMS Measures of SMA-M1 Connectivity Differs Across Inter-stimulus Intervals in Younger and Older Adults

Dual-site transcranial magnetic stimulation (TMS) is a promising tool to measure supplementary motor area and primary motor cortex (SMA-M1) connectivity in younger and older adults, and could be used to understand the pathophysiology of movement disorders. However, test re-test reliability of dual-site TMS measures of SMA-M1 connectivity has not been established. We examined the reliability of SMA-M1 connectivity using dual-site TMS in two sessions in 30 younger and 30 older adults. For dual-site TMS, a conditioning pulse delivered to SMA (140% of active motor threshold) preceded a test pulse delivered to M1 (intensity that elicited MEPs of ~1 mV) by inter-stimulus intervals (ISI) of 6 ms, 7 ms, and 8 ms. Moderate intraclass correlation coefficients (ICC) were found for SMA-M1 connectivity at an ISI of 7 ms in younger (ICC: 0.69) and older adults (ICC: 0.68). Poor ICCs were found for SMA-M1 connectivity at ISIs of 6 ms and 8 ms in both age groups (ICC range: 0.01–0.40). We report evidence for stable measures of SMA-M1 connectivity at an ISI of 7 ms in both age groups. These findings are foundational for future research developing evidence-based interventions to strengthen SMA-M1 connectivity to improve bilateral motor control in older adults and populations with movement disorders.

Unravelling Ipsilateral Interactions Between Left Dorsal Premotor and Primary Motor Cortex: A Proof of Concept Study

Few studies have identified the intrahemispheric functional connectivity between the ipsilateral dorsal premotor cortex (PMd) and the primary motor hand area (M1hand) due to technical limitations. In this proof-of-concept study, a novel neuronavigated dsTMS set-up was employed, combining stimulation over left PMd and left M1hand using the edge of a butterfly coil and a small cooled-coil. This arrangement was warranted because coil (over)heating and inter coil distance are limiting factors when investigating connectivity between stimulation targets in close proximity and over a longer duration. The proposed set-up was designed to deal with these limitations. Specifically, the effect of four dual-site transcranial magnetic stimulation (dsTMS) protocols on twenty-eight right-handed participants (12 males) was evaluated. These protocols differed in stimulus order, interstimulus interval and current direction induced in PMd. A structural scan with electric (E-)field modeling was obtained from seven participants prior to dsTMS, demonstrating that PMd and M1hand were effectively stimulated. Results indicate that one protocol, in which a latero-medial current was induced in PMd 2.8 ms prior to stimulation over M1hand, induced a sex-mediated effect. In males, significant inhibition of motor-evoked potentials was identified, whereas females demonstrated a facilitatory effect that did not survive correction for multiple comparisons. E-field simulations revealed that the E-field induced by the coil targeting PMd was maximal in PMd, with weaker E-field strengths extending to regions beyond PMd. Summarizing, the current dsTMS set-up enabled stimulating at an inter-target distance of 35 mm without any indications of coil-overheating.

Reduced Cerebellar Brain Inhibition Measured Using Dual-Site TMS in Older Than in Younger Adults.

Dual-site transcranial magnetic stimulation (TMS) can be used to measure the cerebellar inhibitory influence on the primary motor cortex, known as cerebellar brain inhibition (CBI), which is thought to be important for motor control. The aim of this study was to determine whether age-related differences in CBI (measured at rest) were associated with an age-related decline in bilateral motor control measured using the Purdue Pegboard task, the Four Square Step Test, and a 10-m walk. In addition, we examined test re-test reliability of CBI measured using dual-site TMS with a figure-of-eight coil in two sessions. There were three novel findings. First, CBI was less in older than in younger adults, which is likely underpinned by an age-related loss of Purkinje cells. Second, greater CBI was associated with faster 10-m walking performance in older adults, but slower 10-m walking performance in younger adults. Third, moderate intraclass correlation coefficients (ICCs: 0.53) were found for CBI in younger adults; poor ICCs were found for CBI (ICC: 0.40) in older adults. Together, these results have important implications for the use of dual-site TMS to increase our understanding of age- and disease-related changes in cortical motor networks, and the role of functional connectivity in motor control.

Reduced Facilitation of Parietal-Motor Functional Connections in Older Adults.

Age-related changes in cortico-cortical connectivity in the human motor network in older adults are associated with declines in hand dexterity. Posterior parietal cortex (PPC) is strongly interconnected with motor areas and plays a critical role in many aspects of motor planning. Functional connectivity measures derived from dual-site transcranial magnetic stimulation (dsTMS) studies have found facilitatory inputs from PPC to ipsilateral primary motor cortex (M1) in younger adults. In this study, we investigated whether facilitatory inputs from PPC to M1 are altered by age. We used dsTMS in a conditioning-test paradigm to characterize patterns of functional connectivity between the left PPC and ipsilateral M1 and a standard pegboard test to assess skilled hand motor function in 13 young and 13 older adults. We found a PPC-M1 facilitation in young adults but not older adults. Older adults also showed a decline in motor performance compared to young adults. We conclude that the reduced PPC-M1 facilitation in older adults may be an early marker of age-related decline in the neural control of movement.

Altered frontal-mediated inhibition and white matter connectivity in pediatric chronic tic disorders.

Tics are unique from most movement disorders, in that they are partially suppressible. As part of the inhibitory motor network, the pre-supplementary motor area is engaged in motor control and may be involved in tic physiology. We used dual-site transcranial magnetic stimulation to assess inhibitory connectivity between right pre-supplementary motor area and left primary motor cortex, which has previously been demonstrated in healthy adults. We also used diffusion tensor imaging to investigate white matter connectivity in children with chronic tics. Twelve children with chronic tic disorder and fourteen typically developing controls underwent MRI with diffusion tensor imaging indices analysis followed by single and paired-pulse transcranial magnetic stimulation with conditioning pulse over the right pre-supplementary motor area followed by left motor cortex test pulse. Neurophysiologic and imaging data relationships to measures of tic severity and suppressibility were also evaluated in tic patients. Pre-supplementary motor area-mediated inhibition of left motor cortex was present in healthy control children but not in chronic tic disorder participants. Less inhibition correlated with worse tic suppressibility (ρ = -0.73, p = 0.047). Imaging analysis showed increased fractional anisotropy in the right superior longitudinal fasciculus, corpus callosum, corona radiata and posterior limb of the internal capsule (p < 0.05) in tic participants, which correlated with lower self-reported tic suppressibility (ρ = -0.70, p = 0.05). Physiologic data revealed impaired frontal-mediated motor cortex inhibition in chronic tic participants, and imaging analysis showed abnormalities in motor pathways. Collectively, the neurophysiologic and neuroanatomic data correlate with tic suppressibility, supporting the relevancy to tic pathophysiology.

Cortico-cortical connectivity: the road from basic neurophysiological interactions to therapeutic applications.

Transcranial magnetic stimulation (TMS) based methods are emerging as a unique approach to evaluate in real-time brain electrical activity in healthy and pathological conditions. By applying TMS pulses in two different bran areas within a short temporal frame of few milliseconds, it is possible to investigate their physiological interactions. These paradigms, collectively termed dual-site TMS, have been inspired by Professor John Rothwell's work, based on the idea that applying a conditioning stimulus over a cortical area may activate putative pathways projecting onto a second target area, thus providing a unique opportunity to test the causal effects between interconnected brain areas. This review highlights the most important features of dual-coil TMS protocols, mainly pioneered in Professor John Rothwell's lab. In the first part, I reviewed development of dual-site TMS protocols leading to the discovery of a distributed system of short-latency interactions within the human parieto-frontal network, likely mediated by direct anatomical pathways. In the second part, the physiological role of these dual-site TMS evoked pathways is considered, describing how these functional interactions are not fixed but vary depending on the brain activation, the condition and on the precise time window in which they are explored. Then, I reviewed recent advances showing that the repeated coupling of interconnected neuronal populations, by means of dual-coil TMS, is able to induce spike-time-dependent plasticity and to determine selective potentiation of physiological connectivity between two human brain regions. Finally, the therapeutic implications of these novel discoveries are discussed, pointing to multi-site TMS as a novel tool to identify early features of synaptic dysfunctions, to monitor disease progression and potentially to provide novel therapeutic approaches by reshaping plasticity in different neurological and psychiatric conditions.

Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation.

Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has provided important insights into fundamental processes of the brain like cognition, learning, and motor control. However, this approach cannot provide causal evidence for the involvement of brain areas of interest. Transcranial magnetic stimulation (TMS) is a powerful, noninvasive tool for studying the human brain that can overcome this limitation by transiently modifying brain activity. Here, we highlight recent advances using a paired-pulse, dual-site TMS method with two coils that causally probes cortico-cortical interactions in the human motor system during different task contexts. Additionally, we describe a dual-site TMS protocol based on cortical paired associative stimulation (cPAS) that transiently enhances synaptic efficiency in two interconnected brain areas by applying repeated pairs of cortical stimuli with two coils. These methods can provide a better understanding of the mechanisms underlying cognitive-motor function as well as a new perspective on manipulating specific neural pathways in a targeted fashion to modulate brain circuits and improve behavior. This approach may prove to be an effective tool to develop more sophisticated models of brain-behavior relations and improve diagnosis and treatment of many neurological and psychiatric disorders.

Using Dual-Site Transcranial Magnetic Stimulation to Probe Connectivity between the Dorsolateral Prefrontal Cortex and Ipsilateral Primary Motor Cortex in Humans.

Dual-site transcranial magnetic stimulation to the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) can be used to probe functional connectivity between these regions. The purpose of this study was to characterize the effect of DLPFC stimulation on ipsilateral M1 excitability while participants were at rest and contracting the left- and right-hand first dorsal interosseous muscle. Twelve participants were tested in two separate sessions at varying inter-stimulus intervals (ISI: 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, and 20 ms) at two different conditioning stimulus intensities (80% and 120% of resting motor threshold). No significant effect on ipsilateral M1 excitability was found when applying a conditioning stimulus over DLPFC at any specific inter-stimulus interval or intensity in either the left or right hemisphere. Our findings suggest neither causal inhibitory nor faciliatory influences of DLPFC on ipsilateral M1 activity while participants were at rest or when performing an isometric contraction in the target hand muscle.

Somatosensory-motor cortex interactions measured using dual-site transcranial magnetic stimulation

BackgroundDual-site transcranial magnetic stimulation (ds-TMS) is a neurophysiological technique to measure functional connectivity between cortical areas. Objective/HypothesisTo date, no study has used ds-TMS to investigate short intra-hemispheric interactions between the somatosensory areas and primary motor cortex (M1). MethodsWe examined somatosensory-M1 interactions in the left hemisphere in six experiments using ds-TMS. In Experiment 1 (n = 16), the effects of different conditioning stimulus (CS) intensities on somatosensory-M1 interactions were measured with 1 and 2.5 ms inter-stimulus intervals (ISIs). In Experiment 2 (n = 16), the time-course of somatosensoy-M1 interactions was studied using supra-threshold CS intensity at 6 different ISIs. In Experiment 3 (n = 16), the time-course of short-interval cortical inhibition (SICI) and effects of different CS intensities on SICI were measured similar to Experiments 1 and 2. Experiment 4 (n = 13) examined the effects of active contraction on SICI and somatosensory-M1 inhibition. Experiments 5 and 6 (n = 10) examined the interactions between SAI with either 1 ms SICI or somatosensory-M1 inhibition. ResultsExperiments 1 and 2 revealed reduced MEP amplitudes when applying somatosensory CS 1 ms prior to M1 TS with 140 and 160% CS intensities. Experiment 3 demonstrated that SICI at 1 and 2.5 ms did not correlate with somatosensory-M1 inhibition. Experiment 4 found that SICI but not somatosensory-M1 inhibition was abolished with active contraction. The results of Experiments 5–6 showed SAI was disinhibited in presence of somatosensory-M1 while SAI was increased in presence of SICI. ConclusionCollectively, the results support the notion that the somatosensory areas inhibit the ipsilateral M1 at very short latencies.