Triple-pulse Transcranial Magnetic Stimulation Research Articles

Modulating the influence of recent trial history on attentional capture via transcranial magnetic stimulation (TMS) of right TPJ

In visual search, salient yet task-irrelevant distractors in the stimulus array interfere with target selection. This is due to the unwanted shift of attention towards the salient stimulus-the so-called attentional capture effect, which delays deployment of attention onto the target. Although powerful and automatic, attentional capture by a salient distractor is nonetheless antagonized by distractor-filtering mechanisms and is further modulated by cross-trial contingencies: The distractor cost is typically more robust when no distraction has been experienced in the immediate past, compared to when a distractor was present on the immediately preceding trial. Here, we used transcranial magnetic stimulation (TMS) to shed light on the causal role of two crucial nodes of the ventral attention network, namely the Temporo-Parietal Junction (TPJ) and the Middle Frontal Gyrus (MFG), in the exogenous control of attention (i.e., attentional capture) and its history-dependent modulation. Participants were asked to discriminate the direction of a target arrow while ignoring a task-irrelevant salient distractor, when present. Immediately after display onset, 10 Hz triple-pulse TMS was delivered either to TPJ or MFG on the right hemisphere. Results demonstrated that stimulation of right TPJ–but not of right MFG, strongly modulated attentional capture as a function of the type of previous trial, by somewhat enhancing the distractor-related cost when the preceding trial was a distractor-absent trial and significantly decreasing the cost when the preceding trial was a distractor-present trial. These findings indicate that TMS of right TPJ exacerbates the effect of the recent history, likely reflecting enhanced updating of the predictive model that dynamically governs proactive distractor-filtering mechanisms. More generally, the results attest to a role of TPJ in mediating the history-dependent modulation of attentional capture.

No effect of triple-pulse TMS medial to intraparietal sulcus on online correction for target perturbations during goal-directed hand and foot reaches.

Posterior parietal cortex (PPC) is central to sensorimotor processing for goal-directed hand and foot movements. Yet, the specific role of PPC subregions in these functions is not clear. Previous human neuroimaging and transcranial magnetic stimulation (TMS) work has suggested that PPC lateral to the intraparietal sulcus (IPS) is involved in directing the arm, shaping the hand, and correcting both finger-shaping and hand trajectory during movement. The lateral localization of these functions agrees with the comparably lateral position of the hand and fingers within the motor and somatosensory homunculi along the central sulcus; this might suggest that, in analogy, (goal-directed) foot movements would be mediated by medial portions of PPC. However, foot movement planning activates similar regions for both hand and foot movement along the caudal-to-rostral axis of PPC, with some effector-specificity evident only rostrally, near the central regions of sensorimotor cortex. Here, we attempted to test the causal involvement of PPC regions medial to IPS in hand and foot reaching as well as online correction evoked by target displacement. Participants made hand and foot reaches towards identical visual targets. Sometimes, the target changed position 100–117 ms into the movement. We disturbed cortical processing over four positions medial to IPS with three pulses of TMS separated by 40 ms, both during trials with and without target displacement. We timed TMS to disrupt reach execution and online correction. TMS did not affect endpoint error, endpoint variability, or reach trajectories for hand or foot. While these negative results await replication with different TMS timing and parameters, we conclude that regions medial to IPS are involved in planning, rather than execution and online control, of goal-directed limb movements.

Neural mechanisms underlying individual differences in attentional blink

Attentional blink (AB) is a well-known phenomenon that detection of a first target (T1) results in reduced identification of a subsequent target (T2) presented within about 500ms in a rapid serial visual presentation (RSVP) stream. However, the neural bases of AB are still not well established. In the present study, we combined multimodal MRI and transcranial magnetic stimulation(TMS) to examine the brain structure and functional connectivity basis of AB. Based on multimodal MRI data from a large group of subjects, we used individual differences approach to search brain areas whose local gray-matter volume (GMV), and resting-state functional connectivity (RSFC) correlated with individuals’ AB magnitude, which was measured by a classical AB paradigm. Further, triple-pulse TMS was used to verify the causal role of the discovered regions. We finally found that: (i) GMV in right temporo-parietal junction (rTPJ), which is essential for attentional reorienting, was positively correlated with AB magnitude; (ii) RSFC between left inferior frontal junction (lIFJ) and rTPJ was negatively correlated with AB magnitude; (iii) Both the correlation between lIFJ-rTPJ connectivity and AB magnitude, and the correlation between rTPJ GMV and AB magnitude were modulated by T1 performance: both lIFJ-rTPJ connectivity and rTPJ GMV predicted AB magnitude only for individuals with low T1 performance, not for those with high T1 performance; (iv) transient disruption of lIFJ by TMS after T1 onset attenuated theAB magnitude. Taken together, our findings revealed that differences in brain structure of rTPJ and its functional connectivity with lIFJ accounted for individual differences in AB magnitude, and that lIFJ also played a causal role in AB.

Reduced Fading of Visual Afterimages after Transcranial Magnetic Stimulation over Early Visual Cortex

In the complete absence of small transients in visual inputs (e.g., by experimentally stabilizing an image on the retina or in everyday life during intent staring), information perceived by the eyes will fade from the perceptual experience. Although the mechanisms of visual fading remain poorly understood, one possibility is that higher level brain regions actively suppress the stable visual signals via targeted feedback onto early visual cortex (EVC). Here, we used positive afterimages and multisensory conflict to induce gestalt-like fading of participants' own hands. In two separate experiments, participants rated the perceived quality of their hands both before and after transcranial magnetic stimulation (TMS) was applied over EVC. In a first experiment, triple-pulse TMS was able to make a faded hand appear less faded after the pulses were applied, compared with placebo pulses. A second experiment demonstrated that this was because triple-pulse TMS slowed down fading of the removed hand that otherwise occurs naturally over time. Interestingly, TMS similarly affected the left and right hands, despite being applied only over the right EVC. Together, our results suggest that TMS over EVC attenuates the effects of visual fading in positive afterimages, and it might do so by crossing transcollosal connections or via multimodal integration sites in which both hands are represented.

The temporal involvement of the left supramarginal gyrus in planning functional grasps: A neuronavigated TMS study

The left supramarginal gyrus (SMG) is a critical structure in tool use actions, including such simple acts as selection of appropriate grasps and, if necessary, their on-line corrections. Yet, its temporal contribution to initial planning of functional grasps of tools is largely unknown. We used MRI-guided, event-related transcranial magnetic stimulation (TMS) to determine the time point when SMG involvement in processing of tools for functional grasp decision was affected most. In Exp. 1, with 15 participants, triple-pulse (10 Hz) TMS was applied to either the left anterior-to-mid SMG (amSMG; subdivisions PFt/PF) or vertex at three different time points: starting from 17 ms (i.e., delivered at 17/117/217 ms), 117 ms (117/217/317 ms) or 217 ms (217/317/417 ms) after stimulus onset. In Exp. 2, with 12 participants, we applied single-pulse TMS to either left amSMG or the left rostral middle frontal gurus (rMFG; area 46) at these same time points relative to stimulus onset. Subject- and item-based analyses of response times (RTs) were performed. Whereas the amSMG and vertex stimulation with triple pulse has revealed differential effects on RTs in general, as well as on tool orientation processing, it gave only vague pointers as to their temporal contributions to the task. Yet, amSMG and rMFG stimulation with single pulse demonstrated that, while the processing in both of these areas can be enhanced at 17 ms and no doubt at 117 ms (as compared to 217 ms), the earliest stimulation facilitated amSMG (vs. rMFG) contribution, and the latest stimulation had the opposite effect, facilitating rMFG (vs. amSMG) contribution to planning functional grasps. These outcomes demonstrate that the critical role of SMG in tool-related actions can be invoked substantially earlier than previously thought.

T49. Motor cortical circuit interactions in Parkinson’s disease

Introduction Using transcranial magnetic stimulation (TMS), previous work has established that motor cortical inhibitory and facilitatory circuits are aberrant in patients with Parkinson’s disease (PD). Three such circuits are short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF) and short latency afferent inhibition (SAI). They assess GABAAergic, glutamatergic and cholinergic function, respectively. Importantly, these circuits interact with each other and their interactions can be tested using a triple-pulse TMS paradigm, which elicits one circuit in the presence of another. However, these interactions have not been studied in PD. Methods 14 right-handed PD patients (10 males; 65.1 ± 8.0 years) were studied ON and OFF dopaminergic medication. Unified Parkinson’s Disease Rating Scale Part III was used to assess disease severity. 14 right-handed, age-matched healthy participants (8 males; 64.4 ± 7.3 years) served as controls. Surface electromyography measured target muscle (first dorsal interosseous) motor evoked potentials generated by TMS of left M1 in controls and of M1 in the more affected hemisphere in PD patients. SICI was tested at an interstimulus interval (ISI) of 2 ms and SICF at an ISI of 1.5 ms. The interactions between SICI and SICF were evaluated by comparing SICF alone to SICF in the presence of SICI. The latency of the median nerve N20 somatosensory evoked potential plus 2 ms was used as the ISI for SAI. The interactions between SAI and SICI were evaluated by comparing SAI alone to SAI in the presence of SICI and by comparing SICI alone to SICI in the presence of SAI. Repeated measures analyses of variance were applied to test the within-subject effect of condition (circuit A alone; circuit A in the presence of circuit B) and the between-subject factor of group (PD ON; PD OFF; control). Results For the comparison between SAI alone and SAI in the presence of SICI, there was a significant effect of condition, but no effect of group. SAI was disinhibited in the presence of SICI. For the comparison between SICI alone and SICI in the presence of SAI, there was a significant effect of condition, but no effect of group. SICI was disinhibited in the presence of SAI. For the comparison between SICF alone and SICF in the presence of SICI, there was no significant effect of condition or group, or interaction between the two. When groups were tested separately, SICF was facilitated in the presence of SICI in controls, but not in PD ON or OFF. Conclusion While previous studies showed that individual cortical circuits of SICI and SAI are abnormal in PD, our findings suggest the interactions between these circuits are preserved in PD. Thus, abnormal SICI and SAI cannot be attributed to abnormal interaction among these circuits. Our results suggest that the facilitatory effect of SICI on SICF is diminished in PD and is not affected by dopaminergic medications. Altered interaction between cortical circuits may contribute to the pathophysiology of PD.

Differential contributions to the interception of occluded ballistic trajectories by the temporoparietal junction, area hMT/V5+, and the intraparietal cortex

The ability to catch objects when transiently occluded from view suggests their motion can be extrapolated. Intraparietal cortex (IPS) plays a major role in this process along with other brain structures, depending on the task. For example, interception of objects under Earth's gravity effects may depend on time-to-contact predictions derived from integration of visual signals processed by hMT/V5+ with a priori knowledge of gravity residing in the temporoparietal junction (TPJ). To investigate this issue further, we disrupted TPJ, hMT/V5+, and IPS activities with transcranial magnetic stimulation (TMS) while subjects intercepted computer-simulated projectile trajectories perturbed randomly with either hypo- or hypergravity effects. In experiment 1, trajectories were occluded either 750 or 1,250 ms before landing. Three subject groups underwent triple-pulse TMS (tpTMS, 3 pulses at 10 Hz) on one target area (TPJ | hMT/V5+ | IPS) and on the vertex (control site), timed at either trajectory perturbation or occlusion. In experiment 2, trajectories were entirely visible and participants received tpTMS on TPJ and hMT/V5+ with same timing as experiment 1 tpTMS of TPJ, hMT/V5+, and IPS affected differently the interceptive timing. TPJ stimulation affected preferentially responses to 1-g motion, hMT/V5+ all response types, and IPS stimulation induced opposite effects on 0-g and 2-g responses, being ineffective on 1-g responses. Only IPS stimulation was effective when applied after target disappearance, implying this area might elaborate memory representations of occluded target motion. Results are compatible with the idea that IPS, TPJ, and hMT/V5+ contribute to distinct aspects of visual motion extrapolation, perhaps through parallel processing.NEW & NOTEWORTHY Visual extrapolation represents a potential neural solution to afford motor interactions with the environment in the face of missing information. We investigated relative contributions by temporoparietal junction (TPJ), hMT/V5+, and intraparietal cortex (IPS), cortical areas potentially involved in these processes. Parallel organization of visual extrapolation processes emerged with respect to the target's motion causal nature: TPJ was primarily involved for visual motion congruent with gravity effects, IPS for arbitrary visual motion, whereas hMT/V5+ contributed at earlier processing stages.

P218 Cerebellar involvement in facial emotion discrimination: A TMS study

The contribution of cerebellum to affective processing has been neglected for a long time. Recently, an increasing number of studies on both healthy participants and patients with cerebellar abnormalities pointed to a possible role of the cerebellum in the emotions regulation and perception. In this study, we aimed to investigate the involvement of the cerebellum in emotion discrimination by means of transcranial magnetic stimulation (TMS). We presented participants with pairs of faces with different emotional expressions (happy or angry) and we asked them to indicate whether the two faces showed the same or a different emotion. Triple-pulse TMS (20 Hz) was delivered between the first and the second face presentation over the left cerebellum, the primary visual cortex and the vertex (control site). Analyses suggest that cerebellar TMS impaired participants’ performance in emotion discrimination, in line with previous evidence on the link between cerebellum and emotional processing.

Task-related changes in intracortical inhibition assessed with paired- and triple-pulse transcranial magnetic stimulation.

Recent research has demonstrated a task-related modulation of postsynaptic intracortical inhibition within primary motor cortex for tasks requiring isolated (abduction) or synergistic (precision grip) muscle activation. The current study sought to investigate task-related changes in pre- and postsynaptic intracortical inhibition in motor cortex. In 13 young adults (22.5 ± 3.5 yr), paired-pulse transcranial magnetic stimulation (TMS) was used to measure short (SICI)- and long-interval intracortical inhibition (LICI) (i.e., postsynaptic motor cortex inhibition) in first dorsal interosseous muscle, and triple-pulse TMS was used to investigate changes in SICI-LICI interactions (i.e., presynaptic motor cortex inhibition). These measurements were obtained at rest and during muscle activation involving isolated abduction of the index finger and during a precision grip using the index finger and thumb. SICI was reduced during abduction and precision grip compared with rest, with greater reductions during precision grip. The modulation of LICI during muscle activation depended on the interstimulus interval (ISI; 100 and 150 ms) but was not different between abduction and precision grip. For triple-pulse TMS, SICI was reduced in the presence of LICI at both ISIs in resting muscle (reflecting presynaptic motor cortex inhibition) but was only modulated at the 150-ms ISI during index finger abduction. Results suggest that synergistic contractions are accompanied by greater reductions in postsynaptic motor cortex inhibition than isolated contractions, but the contribution of presynaptic mechanisms to this disinhibition is limited. Furthermore, timing-dependent variations in LICI provide additional evidence that measurements using different ISIs may not represent activation of the same cortical process.

Programs for action in superior parietal cortex: A triple-pulse TMS investigation

Converging evidence from neurological patients and functional brain imaging studies strongly supports the notion that the posterior parietal cortex (PPC), especially in the left hemisphere, plays a critical role in both the programming (i.e., setting the initial movement parameters of the reach) and the online control of goal-directed reaching movements. Importantly, however, there is no clear consensus on how different subregions within the PPC contribute to the programming and online control of reaching. In the current study, we investigated the role of the inferior (IPL) and superior (SPL) parietal lobules in reach programming using MRI-guided event-related transcranial magnetic stimulation (TMS). Specifically, we applied triple-pulse (tp) TMS to either the left IPL or the left SPL at different time points during reaching movements either at target onset (programming) or at movement onset (online control) while participants (n=16) made pointing movements to targets in the periphery without visual feedback of the moving hand. Stimulating the SPL but not the IPL resulted in a significant increase in endpoint errors when tp-TMS was applied during the programming phase compared to the online control phase. In short, these data demonstrate that the SPL plays a critical role in real-time movement programming.

Triple-pulse TMS to study interactions between neural circuits in human cortex

Transcranial magnetic stimulation (TMS) is a widely used brain stimulation technique that allows noninvasive examination of different excitatory and inhibitory circuits at the systems level in the intact human brain. In recent years, considerable knowledge has been accumulated about the physiology ofseveral of these facilitatory and inhibitory processes individually. However, activity in the corresponding neural circuits is not independent of each other. This paper reviews the experiments using triple-pulse TMS that are specifically designed to study interactions between intracortical circuits. These studies have provided evidence for a complex network of interconnected neural circuits within and across cerebral hemispheres. The current knowledge about the functional organization of this network, its pharmacology and functional implications for human motor control are discussed in detail. These findings have clinical relevance because specific interactions between neural circuits may be impaired in neurologic and psychiatric disorders. We conclude that triple-pulse TMS studies will help to integrate and better understand the physiologic processes involved in human motor behavior.

Effects of short interval intracortical inhibition and intracortical facilitation on short interval intracortical facilitation in human primary motor cortex

Short interval intracortical facilitation (SICF) can be elicited by transcranial magnetic stimulation (TMS) of the motor cortex (M1) with a suprathreshold first stimulus (S1) followed by a subthreshold second stimulus (S2). SICF occurs at three distinct phases and is likely to be related to the generation of indirect (I) waves. Short interval intracortical inhibition (SICI) is an inhibitory phenomenon and intracortical facilitation (ICF) is an excitatory phenomenon occurring in the M1 that can be studied with TMS. We studied the interactions between SICI/ICF and SICF in 17 healthy subjects. Six experiments were conducted. The first experiment examined the effects of different S1 intensities on SICI, ICF and SICF at three peaks. The effects of SICI on SICF were tested by a triple-pulse TMS protocol in the second experiment. We performed Experiments 3-5 to further test the interactions between SICI and SICF with various strengths of SICI, at SICF peaks and troughs, and with SICF generated by different current direction which preferentially generates late I waves. The effects of ICF on SICF were examined in Experiment 6. The results showed that ICF and SICF decreased whereas SICI increased with higher S1 intensities. SICI facilitated SICF mediated by late I waves both at the peaks and the troughs of SICF. The increase of SICF in the presence of SICI correlated to the strength of SICI. ICF decreased the third peak of SICF. We conclude that SICI facilitates SICF at neuronal circuits responsible for generating late I waves through disinhibition, while ICF may have the opposite effects.

The timing and intensity of transcranial magnetic stimulation, and the scalp site stimulated, as variables influencing motor sequence performance in healthy subjects

The increasing therapeutic use of transcranial magnetic stimulation (TMS) in disorders of cortical excitability raises the need for reliable stimulus variables. Stimulation of cortical motor areas influences motor programming and execution. We investigated the effects of TMS delivered over various cortical motor areas during the reaction time (RT) on the execution of sequential rapid arm movements in healthy subjects. Subjects performed a five-submovement (S1-S5) motor sequence mainly involving upper limb proximal muscles. RT and movement time (MT) were measured. We delivered late (close to movement onset) and early (close to the go signal) TMS over the primary motor area (M1-FDI hot-spot for the first dorsal interosseus, M1-D hot-spot for the deltoid muscle), the premotor (PM) area, and the supplementary motor area (SMA), using subthreshold and suprathreshold intensity, single and triple pulses. The motor sequence showed a characteristic pattern of submovement duration, S2-S3-S4 being faster than S1 and S5. Late TMS prolonged RT only when high-intensity pulses were delivered over M1-FDI. Single- and triple-pulse TMS over M1-D or M1-FDI significantly prolonged MT with a dose-related effect. Suprathreshold triple-pulse TMS over the PM-but not over the SMA-also lengthened the MT but did not change RT. Early triple-pulse TMS reduced the RT independently from the stimulus intensity and scalp site. SMA and PM-but not M1-D-stimulation also reduced the MT. Single-pulse TMS over the SMA, despite being delivered through a double-cone coil, did not change RT or MT. TMS-induced changes in the kinematics of a sequential arm movement depend closely on the timing of TMS interference, the scalp site stimulated, and the intensity (and number) of stimuli delivered. Late TMS interference inhibits, whereas early interference facilitates, motor performance. The cortical motor region most sensitive to TMS-induced inhibition is that below the scalp site for M1-FDI. In contrast, TMS-induced facilitation has no strict topographic organization. Particularly for MT (although inhibitory and facilitatory effects both depend on stimulation at high intensities) intensity is less crucial than timing of interference and scalp site.