Repetitive transcranial magnetic stimulation (rTMS) is increasingly used to investigate mechanisms of brain functions and plasticity, but also as a promising new therapeutic tool. The effects of rTMS depend on the intensity and frequency of stimulation and consist of changes of cortical excitability, which often persists several minutes after termination of rTMS. While these findings imply that cortical processing can be altered by applying current pulses from outside the brain, little is known about how rTMS persistently affects learning and perception. Here we demonstrate in humans, through a combination of psychophysical assessment of two-point discrimination thresholds and functional magnetic resonance imaging (fMRI), that brief periods of 5 Hz rTMS evoke lasting perceptual and cortical changes. rTMS was applied over the cortical representation of the right index finger of primary somatosensory cortex, resulting in a lowering of discrimination thresholds of the right index finger. fMRI revealed an enlargement of the right index finger representation in primary somatosensory cortex that was linearly correlated with the individual rTMS-induced perceptual improvement indicative of a close link between cortical and perceptual changes. The results demonstrate that repetitive, unattended stimulation from outside the brain, combined with a lack of behavioral information, are effective in driving persistent improvement of the perception of touch. The underlying properties and processes that allow cortical networks, after being modified through TMS pulses, to reach new organized stable states that mediate better performance remain to be clarified.
Functional magnetic resonance imaging and sensory threshold testing demonstrate that brief periods of transcranial magnetic stimulation can induce changes in somatosensory processing.
Dystonia is associated with impaired somatosensory ability. The electrophysiological method of repetitive transcranial magnetic stimulation (rTMS) can be used for non-invasive stimulation of the human cortex and can alter cortical excitability and associated behaviour. Among others, rTMS can alter/improve somatosensory discrimation abilities, as shown in healthy controls.
We applied 5Hz-rTMS over the left primary somatosensory cortex (S1) in 5 patients with right-sided writer's dystonia and 5 controls. We studied rTMS effects on tactile discrimination accuracy and concomitant rTMS-induced changes in hemodynamic activity measured by functional magnetic resonance imaging (fMRI).
Prior to rTMS, patients performed worse on the discrimination task than controls even though fMRI showed greater task-related activation bilaterally in the basal ganglia (BG). In controls, rTMS led to improved discrimination; fMRI revealed this was associated with increased activity of the stimulated S1, bilateral premotor cortex and BG. In dystonia patients, rTMS had no effect on discrimination; fMRI showed similar cortical effects to controls except for no effects in BG.
Improved discrimination after rTMS in controls is linked to enhanced activation of S1 and BG. Failure of rTMS to increase BG activation in dystonia may be associated with the lack of effect on sensory discrimination in this group and may reflect impaired processing in BG-S1 connections. Alternatively, the increased BG activation seen in the baseline state without rTMS may reflect a compensatory strategy that saturates a BG contribution to this task.
writer's cramp; primary dystonia; basal ganglia; sensory discrimination; sensorimotor cortex; premotor cortex; fMRI; TMS; repetitive TMS
1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) is considered to have an inhibitory effect in
healthy people because it suppresses the excitability of the motor or visual cortex that is expressed as an increase in
the motor or the phosphene threshold (PT), respectively. However, the underlying mechanisms and the brain structures
involved in the action of rTMS are still unknown. In this study we used two sessions of simultaneous TMS-functional
magnetic resonance imaging (fMRI), one before and one after, 15 minutes of 1Hz rTMS to map changes in
brain function associated with the reduction in cortical excitability of the primary visual cortex induced by 1 Hz
rTMS, when TMS was applied on the occipital area of healthy volunteers. Two groups were evaluated, one group
composed of people that can see phosphenes, and another of those lacking this perception. The inhibitory effect, induced
by the 1 Hz rTMS, was observed through the increase of the PT, in the first group, but did not lead to a global
reduction in brain activation, instead, showed change in the activation pattern before and after rTMS. Conversely, for
the second group, changes in brain activation were observed just in few brain areas, suggesting that the effect of 1 Hz
rTMS might not be inhibitory for everyone and that the concept of inhibitory/excitatory effect of rTMS may need to be
TMS-functional magnetic resonance imaging; phosphene threshold.
Previous research has demonstrated that the cerebellum is involved in emotive and cognitive processes. Furthermore, recent findings suggest high-frequency repetitive transcranial magnetic stimulation (rTMS) to the cerebellum has mood-improving properties. We sought to further explore the effects of cerebellar high-frequency rTMS on implicit processing of emotional stimuli and mood.
In a double-blind, crossover study, 15 healthy volunteers received 15 minutes of 20 Hz (5 s on, 5 s off) rTMS over the medial cerebellum, occipital cortex or sham in a randomized counterbalanced order on 3 consecutive days. A masked emotional faces response task measured implicit emotional processing of happy, fearful and neutral facial expressions. We used positive and negative affect scales to evaluate rTMS-related changes in mood.
High-frequency rTMS over the cerebellum was associated with significant increases in masked emotional responses to happy facial expressions only. We observed no changes in consciously experienced mood.
Although the sham rTMS served as our baseline measurement, additional pre-rTMS data showing that reaction time increases immediately after cerebellar rTMS would have made our results more compelling.
The results replicate and extend previous findings by establishing a direct relation between the cerebellum and emotive information-processing. The parallel between the present effects of high-frequency cerebellar rTMS and short-term antidepressant therapy regarding the change in implicit processing of positive stimuli in the absence of mood changes is notable and warrants further research.
Repetitive transcranial magnetic stimulation (rTMS) was applied to test the role of selected cortical regions in remediating sleep-deprivation–induced deficits in visual working memory (WM) performance. Three rTMS targets were chosen using a functional magnetic resonance imaging (fMRI)–identified network associated with sleep-deprivation–induced WM performance impairment: 2 regions from the network (upper left middle occipital gyrus and midline parietal cortex) and 1 nonnetwork region (lower left middle occipital gyrus). Fifteen participants underwent total sleep deprivation for 48 h. rTMS was applied at 5 Hz during a WM task in a within-subject sham-controlled design. The rTMS to the upper-middle occipital site resulted in a reduction of the sleep-induced reaction time deficit without a corresponding decrease in accuracy, whereas stimulation at the other sites did not. Each subject had undergone fMRI scanning while performing the task both pre- and postsleep deprivation, and the degree to which each individual activated the fMRI network was measured. The degree of performance enhancement with upper-middle occipital rTMS correlated with the degree to which each individual failed to sustain network activation. No effects were found in a subset of participants who performed the same rTMS procedure after recovering from sleep deprivation, suggesting that the performance enhancements seen following sleep deprivation were state dependent.
facilitation; fMRI; sleep deprivation; TMS; working memory
A governing assumption about repetitive transcranial magnetic stimulation (rTMS) has been that it interferes with task-related neuronal activity – in effect, by “injecting noise” into the brain – and thereby disrupts behavior. Recent reports of rTMS-produced behavioral enhancement, however, call this assumption into question. We investigated the neurophysiological effects of rTMS delivered during the delay period of a visual working memory task by simultaneously recording brain activity with electroencephalography (EEG). Subjects performed visual working memory for locations or for shapes, and in half the trials a 10-Hz train of rTMS was delivered to the superior parietal lobule (SPL) or a control brain area. The wide range of individual differences in the effects of rTMS on task accuracy, from improvement to impairment, was predicted by individual differences in the effect of rTMS on power in the alpha-band of the EEG (∼10 Hz): a decrease in alpha-band power corresponded to improved performance, whereas an increase in alpha-band power corresponded to the opposite. The EEG effect was localized to cortical sources encompassing the frontal eye fields and the intraparietal sulcus, and was specific to task (location, but not object memory) and to rTMS target (SPL, not control area). Furthermore, for the same task condition, rTMS-induced changes in cross-frequency phase synchrony between alpha- and gamma-band (>40 Hz) oscillations predicted changes in behavior. These results suggest that alpha-band oscillations play an active role cognitive processes and do not simply reflect absence of processing. Furthermore, this study shows that the complex effects of rTMS on behavior can result from biasing endogenous patterns of network-level oscillations.
oscillations; alpha band; transcranial magnetic stimulation; rTMS; electroencephalography; working memory; spatial
Repetitive transcranial magnetic stimulation (rTMS) is an established technique for non-invasive stimulation of human cortex. Although studies have shown an influence of rTMS on single cortical regions and on simple behavioral response patterns, its influences on the dynamics of task-related activity in cortical networks have not been characterized. We provide such a characterization by showing that 5 Hz rTMS over primary somatosensory cortex (SI) induces a reconfiguration of activity patterns in a sensorimotor network, comprising the stimulated region and ipsilateral primary motor cortex (MI). These plastic changes endure for up to 120 min and are correlated with behavioral improvement in discrimination. Dynamic causal modeling showed that this reconfiguration could be explained by an rTMS-induced increase in SI excitability (self-connection) and an increase in the effective connectivity from SI to MI. Thus, our data demonstrate that rTMS can temporarily induce behaviorally relevant reorganization within a complex cortical network underlying human somatosensory experience.
functional magnetic resonance imaging; repetitive transcranial stimulation; sensorimotor coupling; effective connectivity; plasticity; perception
During the last decade, repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has become established as a treatment for various mental diseases. The rational of prefrontal stimulation has been adapted from the mode of action known from rTMS using motor-evoked potentials though little is known about the precise effect of rTMS at prefrontal sites. The objective of the current study is to investigate the inhibitory effect of prefrontal 1 Hz rTMS by stimulating the generators of event-related potentials (ERP) which are located in the prefrontal cortex. Thus, 1 Hz rTMS was applied offline over the left dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal cortex (MPFC) in 18 healthy subjects who subsequently underwent a GoNogo task. Both active conditions were compared to sham rTMS within a randomized and counterbalanced cross-over design in one day. ERPs were recorded during task performance and the N2 and the P3 were analysed. After 1 Hz rTMS of the left DLPFC (but not of the MPFC), an inhibitory effect on the N2 amplitude was observed, which was related to inhibitory control. In contrast, after 1 Hz rTMS of the MPFC (but not at the left DLPFC) a trend towards an increased P3 amplitude was found. There was no significant modulation of latencies and behavioural data. The results argue in favour of an inhibitory effect of 1 Hz rTMS on N2 amplitudes in a GoNogo task. Our findings suggest that rTMS may mildly modulate prefrontally generated ERP immediately after stimulation, even where behavioural effects are not measurable. Thus, combined rTMS-ERP approaches need to be further established in order to serve as paradigms in experimental neuroscience and clinical research.
Chronic high-frequency repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has recently received increasing interests as a therapeutic procedure for neurodegenerative diseases. To identify the metabolism mechanism underlying the improving effects of rTMS, we observed that high frequency (25Hz) rTMS for 14 days could reverse the decline of the performance of the passive avoidance task in aged mice. We further investigated the metabolite profiles in the prefrontal cortex (PFC) in those mice and found that rTMS could also reverse the metabolic abnormalities of gamma-aminobutyric acid, N-acetyl aspartic, and cholesterol levels to the degree similar to the young mice. These data suggested that the rTMS could ameliorate the age-related cognitive impairment and improving the metabolic profiles in PFC, and potentially can be used to improve cognitive decline in the elderly.
Manual interception, such as catching or hitting an approaching ball, requires the hand to contact a moving object at the right location and at the right time. Many studies have examined the neural mechanisms underlying the spatial aspects of goal-directed reaching, but the neural basis of the spatial and temporal aspects of manual interception are largely unknown. Here, we used repetitive transcranial magnetic stimulation (rTMS) to investigate the role of the human middle temporal visual motion area (MT+/V5) and superior parieto-occipital cortex (SPOC) in the spatial and temporal control of manual interception. Participants were required to reach-to-intercept a downward moving visual target that followed an unpredictably curved trajectory, presented on a screen in the vertical plane. We found that rTMS to MT+/V5 influenced interceptive timing and positioning, whereas rTMS to SPOC only tended to increase the spatial variance in reach end points for selected target trajectories. These findings are consistent with theories arguing that distinct neural mechanisms contribute to spatial, temporal, and spatiotemporal control of manual interception.
interception; rTMS; SPOC; MT+; spatial behavior; timing of action
The neural basis of temporal processing is unclear. We addressed this important issue by performing two experiments in which repetitive transcranial magnetic stimulation (rTMS) was administered in different sessions to the left or right supramarginal gyrus (SMG) or vertex; in both tasks, two visual stimuli were presented serially and subjects were asked to judge if the second stimulus was longer than the first (standard) stimulus. rTMS was presented on 50% of trials. Consistent with a previous literature demonstrating the effect of auditory clicks on temporal judgment, rTMS was associated with a tendency to perceive the paired visual stimulus as longer in all conditions. Crucially, rTMS to the right SMG was associated with a significantly greater subjective prolongation of the associated visual stimulus in both experiments. These findings demonstrate that the right SMG is an important element of the neural system underlying temporal processing and, as discussed, have implications for neural and cognitive models of temporal perception and attention.
This randomized, placebo-controlled, double-blind pilot study evaluated the impact of repetitive transcranial magnetic stimulation (rTMS) on clinical, cognitive, and social performance in women suffering with postpartum depression.
Fourteen patients were randomized to receive 20 sessions of sham rTMS or active 5 Hz rTMS over the left dorsolateral prefrontal cortex. Psychiatric clinical scales and a neuropsychological battery were applied at baseline (pretreatment), week 4 (end of treatment), and week 6 (follow-up, posttreatment week 2).
The active rTMS group showed significant improvement 2 weeks after the end of rTMS treatment (week 6) in Hamilton Depression Rating Scale (P = 0.020), Global Assessment Scale (P = 0.037), Clinical Global Impression (P = 0.047), and Social Adjustment Scale-Self Report-Work at Home (P = 0.020).
This study suggests that rTMS has the potential to improve the clinical condition in postpartum depression, while producing marginal gains in social and cognitive function.
transcranial magnetic stimulation; postpartum depression; clinical performance; cognitive performance; social performance
Cortical excitability changes as well as imbalances in excitatory and inhibitory circuits play a distinct pathophysiological role in chronic tinnitus. Repetitive transcranial magnetic stimulation (rTMS) over the temporoparietal cortex was recently introduced to modulate tinnitus perception. In the current study, the effect of theta-burst stimulation (TBS), a novel rTMS paradigm was investigated in chronic tinnitus. Twenty patients with chronic tinnitus completed the study. Tinnitus severity and loudness were monitored using a tinnitus questionnaire (TQ) and a visual analogue scale (VAS) before each session. Patients received 600 pulses of continuous TBS (cTBS), intermittent TBS (iTBS) and intermediate TBS (imTBS) over left inferior temporal cortex with an intensity of 80% of the individual active or resting motor threshold. Changes in subjective tinnitus perception were measured with a numerical rating scale (NRS).
TBS applied to inferior temporal cortex appeared to be safe. Although half of the patients reported a slight attenuation of tinnitus perception, group analysis resulted in no significant difference when comparing the three specific types of TBS. Converting the NRS into the VAS allowed us to compare the time-course of aftereffects. Only cTBS resulted in a significant short-lasting improvement of the symptoms. In addition there was no significant difference when comparing the responder and non-responder groups regarding their anamnestic and audiological data. The TQ score correlated significantly with the VAS, lower loudness indicating less tinnitus distress.
TBS does not offer a promising outcome for patients with tinnitus in the presented study.
Background and Purpose
Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke.
Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed.
Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p<0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group.
According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits.
Stroke; Repetitive transcranial magnetic stimulation; Functional MRI; Motor function; Cortico-basal ganglia-thalamocortical circuits
Neuroimaging studies have shown both dorsolateral prefrontal (DLPFC) and inferior parietal cortex (iPARC) activation during probabilistic association learning. Whether these cortical brain regions are necessary for probabilistic association learning is presently unknown. Participants' ability to acquire probabilistic associations was assessed during disruptive 1 Hz repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC, left iPARC, and sham using a crossover single-blind design. On subsequent sessions, performance improved relative to baseline except during DLPFC rTMS that disrupted the early acquisition beneficial effect of prior exposure. A second experiment examining rTMS effects on task-naive participants showed that neither DLPFC rTMS nor sham influenced naive acquisition of probabilistic associations. A third experiment examining consecutive administration of the probabilistic association learning test revealed early trial interference from previous exposure to different probability schedules. These experiments, showing disrupted acquisition of probabilistic associations by rTMS only during subsequent sessions with an intervening night's sleep, suggest that the DLPFC may facilitate early access to learned strategies or prior task-related memories via consolidation. Although neuroimaging studies implicate DLPFC and iPARC in probabilistic association learning, the present findings suggest that early acquisition of the probabilistic cue-outcome associations in task-naive participants is not dependent on either region.
consolidation; dorsolateral prefrontal cortex; inferior parietal cortex; probabilistic association learning; repetitive transcranial magnetic stimulation
The ability to discard a prepared action plan in favor of an alternative action is critical when facing sudden environmental changes. We tested whether the functional contribution of left supramarginal gyrus (SMG) during action reprogramming depends on the functional integrity of left dorsal premotor cortex (PMd). Adopting a dual-site repetitive transcranial magnetic stimulation (rTMS) strategy, we first transiently disrupted PMd with “offline” 1Hz rTMS and then applied focal “online” rTMS to SMG whilst human subjects performed a spatially-precued reaction time task. Effective online rTMS of SMG but not sham rTMS of SMG increased errors when subjects had to reprogram their action in response to an invalid precue regardless of the type of preceding offline rTMS. This suggests that left SMG primarily contributes to the online updating of actions by suppressing invalidly prepared responses. Online rTMS of SMG additionally increased reaction times for correct responses in invalidly-precued trials, but only after offline rTMS of PMd. We infer that offline rTMS caused an additional dysfunction of PMd which increased the functional relevance of SMG for rapid activation of the correct response, and sensitized SMG to the disruptive effects of online rTMS. These results not only provide causal evidence that left PMd and SMG jointly contribute to action reprogramming, but also that the respective functional weight of these areas can be rapidly redistributed. This mechanism might constitute a generic feature of functional networks that allows for rapid functional compensation in response to focal dysfunctions.
action reprogramming; transcranial magnetic stimulation; parietal cortex; premotor cortex; virtual lesion
The transient visual response of feline dorsal lateral geniculate nucleus (dLGN) cells was studied under control conditions and during the application of repetitive transcranial magnetic stimulation at 1 Hz (rTMS@1Hz) on the primary visual cortex (V1). The results show that rTMS@1Hz modulates the firing mode of Y cells, inducing an increase in burst spikes and a decrease in tonic firing. On the other hand, rTMS@1Hz modifies the spatiotemporal characteristics of receptive fields of X cells, inducing a delay and a decrease of the peak response, and a change of the surround/center amplitude ratio of RF profiles. These results indicate that V1 controls the activity of the visual thalamus in a different way in the X and Y pathways, and that this feedback control is consistent with functional roles associated with each cell type.
Orientation selectivity is a fundamental, emergent property of neurons in early visual cortex, and discovery of that property [1, 2] dramatically shaped how we conceptualize visual processing [3–6]. However, much remains unknown about the neural substrates of these basic building blocks of perception, and what is known primarily stems from animal physiology studies. To probe the neural concomitants of orientation processing in humans, we employed repetitive transcranial magnetic stimulation (rTMS) to attenuate neural responses evoked by stimuli presented within a local region of the visual field. Previous physiological studies have shown that rTMS can significantly suppress the neuronal spiking activity, hemodynamic responses, and local field potentials within a focused cortical region [7, 8]. By suppressing neural activity with rTMS, we were able to dissociate components of the neural circuitry underlying two distinct aspects of orientation processing: selectivity and contextual effects. Orientation selectivity gauged by masking was unchanged by rTMS, whereas an otherwise robust orientation repulsion illusion was weakened following rTMS. This dissociation implies that orientation processing relies on distinct mechanisms, only one of which was impacted by rTMS. These results are consistent with models positing that orientation selectivity is largely governed by the patterns of convergence of thalamic afferents onto cortical neurons, with intracortical activity then shaping population responses contained within those orientation-selective cortical neurons.
Auditory verbal hallucinations (AVH) in patients with schizophrenia can respond to repetitive transcranial magnetic stimulation (TMS). We report the therapeutic utility of rTMS in a 48 year-old patient with a 20-year history of severe depression (five suicidal gestures and previous failure of ECT) and internal AVH. First, 20Hz rTMS to left prefrontal cortex for three weeks significantly improved depression (BDI-II: 89% change, lasting 14 months along with weekly/biweekly maintenance treatments), but AVH remained unchanged. The patient also underwent a further course of left temporo-parietal 1Hz rTMS and amelioration of AVH severity was achieved (PSYRATS-AH: 53% change) and maintained at 1-year follow-up. AVH respond to rTMS in disorders other than schizophrenia. Furthermore, targeted rTMS to different brain regions can address diverse symptoms in neuropsychiatric conditions.
Transcranial magnetic stimulation; auditory verbal hallucinations; psychotic depressive disorder; treatment; 1-year follow-up
Repetitive transcranial magnetic stimulation (rTMS) has been used to improve language behavior, including naming, in stroke patients with chronic, nonfluent aphasia. Part 1 of this paper reviews functional imaging studies related to language recovery in aphasia. Part 2 reviews the rationale for using rTMS to treat nonfluent aphasia (based on functional imaging); and presents our current rTMS protocol. We present language results from our rTMS studies, and imaging results from overt naming fMRI scans obtained pre- and post- a series of rTMS treatments. Part 3 presents results from a pilot study where rTMS treatments were followed immediately by constraint-induced language therapy. Part 4 reviews our diffusion tensor imaging study that examined possible connectivity of arcuate fasciculus to different parts of Broca’s area (pars triangularis, PTr; pars opercularis, POp); and to ventral premotor cortex (vPMC). The potential role of mirror neurons in R POp and vPMC in aphasia recovery is discussed.
Theta burst stimulation (TBS) is a special repetitive transcranial magnetic stimulation (rTMS) paradigm, where bursts of low-intensity stimuli are applied in the theta frequency. The aim of this study was to investigate the effect of neuronavigated TBS over primary somatosensory cortex (SI) on laser-evoked potentials (LEPs) and acute pain perception induced with Tm : YAG laser stimulation. The amplitude changes of the N1, N2, and P2 components of LEPs and related subjective pain rating scores of 12 healthy subjects were analyzed prior to and following continuous TBS (cTBS), intermittent TBS (iTBS), intermediate TBS (imTBS), and sham stimulation. Our results demonstrate that all active TBS paradigms significantly diminished the amplitude of the N2 component, when the hand contralateral to the site of TBS was laser-stimulated. Sham stimulation condition had no significant effect. The subjective pain perception also decreased during the experimental sessions, but did not differ significantly from the sham stimulation condition. The main finding of our study is that TBS over SI diminished the amplitude of the N2 component evoked from the contralateral side without any significant analgesic effects. Furthermore, imTBS produced responses similar to those observed by other forms of TBS induced excitability changes in the SI.
Theta burst transcranial magnetic stimulation; Primary somatosensory cortex; Laser-evoked potentials; Pain; Neuronavigation
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. Increased metabolism in the anterior cingulate cortex (ACC) is a known predictor for antidepressant response. The authors assessed whether increased theta power within the ACC predicts rTMS response in participants with vascular depression. Sixty-five participants were randomized to active or sham rTMS. Outcome was assessed using the Hamilton Depression Rating Scale. Electroencephalography was obtained, and comparisons were made among each group with a normative database using low-resolution electromagnetic tomography. Results suggest that vascular depression participants respond well to rTMS and that increased low-theta power in the subgenual ACC predicts response to rTMS.
Tinnitus, the perception of sound and noise in absence of an auditory stimulus, has been shown to be associated with maladaptive neuronal reorganization and increased activity of the temporoparietal cortex. Transient modulation of tinnitus by repetitive transcranial magnetic stimulation (rTMS) indicated that these areas are critically involved in the pathophysiology of tinnitus and suggested new treatment strategies. However, the therapeutic efficacy of rTMS in tinnitus is still unclear, individual response is variable, and the optimal stimulation area disputable. Recently, continuous theta burst stimulation (cTBS) has been put forward as an effective rTMS protocol for the reduction of pathologically enhanced cortical excitability.
48 patients with chronic subjective tinnitus will be included in this randomized, placebo controlled, three-arm trial. The treatment consists of two trains of cTBS applied bilaterally to the secondary auditory cortex, the temporoparietal associaction cortex, or to the lower occiput (sham condition) every working day for four weeks. Primary outcome measure is the change of tinnitus distress as quantified by the Tinnitus Questionnaire (TQ). Secondary outcome measures are tinnitus loudness and annoyance as well as tinnitus change during and after treatment. Audiologic and speech audiometric measurements will be performed to assess potential side effects. The aim of the present trail is to investigate effectiveness and safety of a four weeks cTBS treatment on chronic tinnitus and to compare two areas of stimulation. The results will contribute to clarify the therapeutic capacity of rTMS in tinnitus.
The trial was registered with the clinical trials register of (NCT00518024).
Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children.
TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available.
In a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition.
TMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation.
The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition.
Aphasia affects 1/3 of stroke patients with improvements noted only in some of them. The goal of this exploratory study was to provide preliminary evidence regarding safety and efficacy of fMRI-guided excitatory repetitive transcranial magnetic stimulation (rTMS) applied to the residual left-hemispheric Broca’s area for chronic aphasia treatment.
We enrolled 8 patients with moderate or severe aphasia >1 year after LMCA stroke. Linguistic battery was administered pre-/post-rTMS; a semantic decision/tone decision (SDTD) fMRI task was used to localize left-hemispheric Broca’s area. RTMS protocol consisted of 10 daily treatments of 200 seconds each using an excitatory stimulation protocol called intermittent theta burst stimulation (iTBS). Coil placement was targeted individually to the left Broca’s.
6/8 patients showed significant pre-/post-rTMS improvements in semantic fluency (p=0.028); they were able to generate more appropriate words when prompted with a semantic category. Pre-/post-rTMS fMRI maps showed increases in left fronto-temporo-parietal language networks with a significant left-hemispheric shift in the left frontal (p=0.025), left temporo-parietal (p=0.038) regions and global language LI (p=0.018). Patients tended to report subjective improvement on Communicative Activities Log (mini-CAL; p=0.075). None of the subjects reported ill effects of rTMS.
FMRI-guided, excitatory rTMS applied to the affected Broca’s area improved language skills in patients with chronic post-stroke aphasia; these improvements correlated with increased language lateralization to the left hemisphere. This rTMS protocol appears to be safe and should be further tested in blinded studies assessing its short- and long-term safety/efficacy for post-stroke aphasia rehabilitation.
aphasia; language; fMRI; rTMS; rehabilitation; stroke