Focal Repetitive Transcranial Magnetic Stimulation Research Articles

Effects of transcranial magnetic stimulation over the left posterior superior temporal gyrus on picture-word interference.

Word-production theories argue that during language production, a concept activates multiple lexical candidates in left temporal cortex, and the intended word is selected from this set. Evidence for theories on spoken-word production comes, for example, from the picture-word interference task, where participants name pictures superimposed by congruent (e.g., picture: rabbit, distractor "rabbit"), categorically related (e.g., distractor "sheep"), or unrelated (e.g., distractor "fork") words. Typically, whereas congruent distractors facilitate naming, related distractors slow down picture naming relative to unrelated distractors, resulting in semantic interference. However, the neural correlates of semantic interference are debated. Previous neuroimaging studies have shown that the left mid-to-posterior STG (pSTG) is involved in the interference associated with semantically related distractors. To probe the functional relevance of this area, we targeted the left pSTG with focal repetitive transcranial magnetic stimulation (rTMS) while subjects performed a picture-word interference task. Unexpectedly, pSTG stimulation did not affect the semantic interference effect but selectively increased the congruency effect (i.e., faster naming with congruent distractors). The facilitatory TMS effect selectively occurred in the more difficult list with an overall lower name agreement. Our study adds new evidence to the causal role of the left pSTG in the interaction between picture and distractor representations or processing streams, only partly supporting previous neuroimaging studies. Moreover, the observed unexpected condition-specific facilitatory rTMS effect argues for an interaction of the task- or stimulus-induced brain state with the modulatory TMS effect. These issues should be systematically addressed in future rTMS studies on language production.

Role of human prefrontal cortex in the modulation of conditioned eyeblink responses

Classical conditioning of the eyeblink reflex (EBC) is a simple form of associative motor learning. EBC is heavily dependent on cerebellar function, but experimental studies also suggest that the prefrontal cortex (PFC) orchestrates a neuronal network which interacts with the cerebellum to mediate the conditioned eyeblink responses (CR).To further investigate the role of PFC for EBC in humans, we aimed in this study at assessing whether acquisition of CR can be modulated by focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the dorsolateral PFC (DLPFC).A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 60 healthy subjects (35 female, 25 male, mean age 28.4 ± 2.4 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. TBS was applied over the DLPFC ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 20) using excitatory intermittent TBS (iTBS), inhibitory continuous TBS (cTBS) or sham stimulation.CR acquisition was significantly enhanced by iTBS (mean total CR incidence 63.1 ± 6.5%) and significantly reduced by cTBS (13 ± 2%) compared to sham stimulation (25.1 ± 6.7%).We provide thus physiological evidence that the acquisition of this type of associative learning is critically modulated by PFC activity in humans.

Perturbation of left posterior prefrontal cortex modulates top-down processing in sentence comprehension

Communication is an inferential process. In particular, language comprehension constantly requires top-down efforts, as often multiple interpretations are compatible with a given sentence. To assess top-down processing in the language domain, our experiment employed ambiguous sentences that allow for multiple interpretations (e.g., The client sued the murderer with the corrupt lawyer., where the corrupt lawyer could either belong to The client or the murderer). Interpretation thus depended on whether participants chunk the words of the sentence into short or long syntactic phrases. In principle, bottom-up acoustic information (i.e., the presence or absence of an intonational phrase boundary at the offset of the murderer) indicates one of the two possible interpretations. Yet, acoustic information often indicates interpretations that require words to be chunked into overly long phrases that would overburden working memory. Processing is biased against these demands, reflected in a top-down preference to chunk words into short rather than long phrases. It is often proposed, but also hotly debated, that the ability to chunk words into short phrases is subserved by the left inferior frontal gyrus (IFG). Here, we employed focal repetitive transcranial magnetic stimulation to perturb the left IFG, which resulted in a further decrease of the aptitude to tolerate long phrases, indicating the inability of the left IFG to assist the chunking of words into phrases. In contrast, the processing of auditory information was not affected. Our findings support a causal top-down role of the left inferior frontal gyrus in the chunking of words into phrases.

Large-field repetitive transcranial magnetic stimulation with circular coil in the treatment of functional neurological symptoms

Patients with functional neurological symptoms (FNS) are frequently encountered by neurologists and are difficult to treat. Symptoms are multiple and may appear concurrently or successively in the same patient. To date, few studies have been published on focal repetitive transcranial magnetic stimulation (rTMS) in FNS. This type of stimulation induces a focal current, vertically in the cortex. Results are contradictory, probably because it is difficult to identify a limited cortical area that triggers these symptoms. We assessed the efficacy of another type of rTMS: large-field stimulation by means of a circular coil covering a surface area approximately 20 times greater and inducing a circular current tangentially to the cortex. We analysed two studies on the efficacy of large-field rTMS in functional paralysis and in functional movement disorders. The efficacy of large-field rTMS was very marked in these two studies. We reported several open series, including patients with functional sensory loss, functional visual loss, and non-epileptic seizures. For all patients, one or several sessions of 60 stimuli with circular coil were carried out with a protocol depending on the symptoms. The efficacy of large-field rTMS was dramatic in all patient series. Additionally, we discuss the possible involved mechanism: placebo effect, cognitive behavioural effect or neuromodulatory effect. According to the data from these different studies, large-field rTMS could be a new therapy for patients with FNS. However, controlled studies are mandatory.

Whole-Brain Haemodynamic After-Effects of 1-Hz Magnetic Stimulation of the Posterior Superior Temporal Cortex During Action Observation

The posterior superior temporal sulcus (pSTS) is active when observing biological motion. We investigated the functional connections of the pSTS node within the action observation network by measuring the after-effect of focal repetitive transcranial magnetic stimulation (rTMS) with whole-brain functional magnetic resonance imaging (fMRI). Participants received 1-Hz rTMS over the pSTS region for 10 min and underwent fMRI immediately after. While scanned, they were shown short video clips of a hand grasping an object (grasp clips) or moving next to it (control clips). rTMS-fMRI was repeated for four consecutive blocks. In two blocks we stimulated the left pSTS region and in the other two the right pSTS region. For each side TMS was applied with an effective intensity (95 % of motor threshold) or with ineffective intensity (50 % of motor threshold). Brain regions showing interactive effects of (clip type) × (TMS intensity) were identified in the lateral temporo-occipital cortex, in the anterior intraparietal region and in the ventral premotor cortex. Remote effects of rTMS were mostly limited to the stimulated hemisphere and consisted in an increase of blood oxygen level-dependent responses to grasp clips compared to control clips. We show that the pSTS occupies a pivotal relay position during observation of goal-directed actions.

Transient beneficial effects of excitatory theta burst stimulation in a patient with phonological agraphia after left supramarginal gyrus infarction

We report a patient showing isolated phonological agraphia after an ischemic stroke involving the left supramarginal gyrus (SMG). In this patient, we investigated the effects of focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the left SMG, corresponding to the Brodmann area (BA) 40. The patient and ten control subjects performed a dictational words and nonwords writing task before, and 5 and 30 min after they received excitatory intermittent TBS (iTBS) over the left BA 40, the right hemisphere homologous to BA 40, the Wernicke's area, or the primary visual cortex. ITBS over the left SMG lead to a brief facilitation of phonological non-words writing to dictation. This case study report illustrates that rTMS is able to influence, among other language functions, the phonological loading processes during the written language production in stroke patients.

Spread of electrical activity at cortical level after repetitive magnetic stimulation in normal subjects.

In normal subjects, focal repetitive transcranial magnetic stimulation (rTMS) of the hand motor area evokes muscle potentials (MEPs) from muscles in the hand (target muscles) and the arm (non-target muscles). In this study we investigated the mechanisms underlying the spread of MEPs induced by focal rTMS in non-target muscles. rTMS was delivered with a Magstim stimulator and a figure-of-eight coil placed over the first dorsal interosseus (FDI) motor area of the left hemisphere. Trains of 10 stimuli were given at a suprathreshold intensity (120% of motor threshold) and at frequencies of 5, 10 and 20 Hz at rest. Electromyographic (EMG) activity was recorded simultaneously from the FDI (target muscle) and the contralateral biceps muscle and from the FDI muscle ipsilateral to the side of stimulation (non-target muscle). rTMS delivered in trains to the FDI motor area of the left hemisphere elicited MEPs in the contralateral FDI (target muscle) that gradually increased in amplitude over the course of the train. Focal rTMS trains also induced MEPs in the contralateral biceps (non-target muscle) but did so only after the second or third stimulus; like target-muscle MEPs, in non-target muscle MEPs progressively increased in amplitude during the train. At no frequency did rTMS elicit MEPs in the FDI muscle ipsilateral to the site of stimulation. rTMS left the latency of EMG responses in the FDI and biceps muscles unchanged during the trains of stimuli. The latency of biceps MEPs was longer after rTMS than after a single TMS pulse. In conditioning-test experiments designed to investigate the cortical origin of the spread, a single TMS pulse delivered over the left hemisphere at an interstimulus interval (ISI) of 50, 100 and 150 ms reduced the amplitude of the test MEP evoked by a single TMS pulse delivered over the right hemisphere; and a conditioning rTMS train delivered over the left hemisphere increased the amplitude of the test MEP evoked by a single TMS pulse over the right hemisphere. A conditioning rTMS train delivered over the left hemisphere and paired magnetic shocks (test stimulus) at 3 and 13 ms ISIs over the right hemisphere reduced MEP inhibition at the 3-ms ISI but left the MEP facilitation at 13 ms unchanged. Using a control MEP size matched with that observed after a conditioning contralateral rTMS, we found that paired-pulse inhibition remained unchanged. Yet a single TMS conditioning pulse sufficiently strong to evoke a MEP in the contralateral FDI and biceps muscles simultaneously (as rTMS did) left paired-pulse inhibition unchanged. We conclude that the spread of EMG activity to non-target muscles depends on cortical mechanisms, mainly including changes in the excitability of the interneurones mediating intracortical inhibition.

The Mental Number Line and the Human Angular Gyrus

To investigate the hemispheric organization of a language-independent spatial representation of number magnitude in the human brain we applied focal repetitive transcranial magnetic stimulation (rTMS) to the right or left angular gyrus while subjects performed a number comparison task with numbers between 31 and 99. Repetitive TMS over the angular gyrus disrupted performance of a visuospatial search task, and rTMS at the same site disrupted organization of the putative “number line.” In some cases the pattern of disruption caused by angular gyrus rTMS suggested that this area normally mediates a spatial representation of number. The effect of angular gyrus rTMS on the number line task was specific. rTMS had no disruptive effect when delivered over another parietal region, the supramarginal gyrus, in either the left or the right hemisphere.

Imaging functional activation of the auditory cortex during focal repetitive transcranial magnetic stimulation of the primary motor cortex in normal subjects

Positron emission tomography (PET) during focal repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising approach to study cortical connectivity in awake humans. However, the noise caused by the discharging magnetic coil might have confounding effects on the rTMS-related cortical activation pattern. In twelve healthy volunteers, 18-fluoro-2-deoxy- d-glucose ( 18FDG) PET was employed to visualize the functional activation of the primary auditory cortex (PAC) during 2 Hz rTMS of the left primary sensorimotor hand area. Magnetic stimuli (1800) were applied at an intensity of 140% of motor resting threshold during the uptake period of 18FDG. Though all subjects wore earplugs, rTMS-related noise induced a consistent bilateral increase of regional glucose utilization in the PAC ( P<0.05, corrected). Thus, rTMS-related acoustic input needs to be taken into account in combined rTMS/PET studies.