Low frequency rTMS effects on sensorimotor synchronization

Previous studies using low frequency (1 Hz) rTMS over the motor and premotor cortex have examined repetitive movements, but focused either on motor aspects of performance such as movement speed, or on variability of the produced intervals. A novel question is whether TMS affects the synchronization of repetitive movements with an external cue (sensorimotor synchronization). In the present study participants synchronized finger taps with the tones of an auditory metronome. The aim of the study was to examine whether motor and premotor cortical inhibition induced by rTMS affects timing aspects of synchronization performance such as the coupling between the tap and the tone and error correction after a metronome perturbation. Metronome sequences included perturbations corresponding to a change in the duration of a single interval (phase shifts) that were either small and below the threshold for conscious perception (10 ms) or large and perceivable (50 ms). Both premotor and motor cortex stimulation induced inhibition, as reflected in a lengthening of the silent period. Neither motor nor premotor cortex rTMS altered error correction after a phase shift. However, motor cortex stimulation made participants tap closer to the tone, yielding a decrease in tap-tone asynchrony. This provides the first neurophysiological demonstration of a dissociation between error correction and tap-tone asynchrony in sensorimotor synchronization. We discuss the results in terms of current theories of timing and error correction.

The role of areas MT+/V5 and SPOC in spatial and temporal control of manual interception: an rTMS study

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.

Resting state cortico-thalamic-striatal connectivity predicts pesponse to dorsomedial prefrontal rTMS in major depressive disorder

Despite its high toll on society, there has been little recent improvement in treatment efficacy for Major Depressive Disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting state functional connectivity predicted response to treatment with rapid transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased sgACC-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work.

Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal rTMS in major depression

Background Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain’s emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. Methods Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode. Results Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region. Conclusions The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection.

Poor tolerance of motor cortex rTMS in chronic migraine

Background:
Two small studies had evaluated the efficacy of rTMS in migraine. One tested high frequency rTMS over the dorsolateral prefrontal cortex while the other evaluated 1 Hz rTMS over the vertex.
Aim:
To test the feasibility of 10 Hz rTMS of motor cortex as an adjunctive therapy in patients with chronic migraine.
Materials and Methods:
We randomized (2:1 ratio) chronic migraine patients on medical preventive treatment to receive either rTMS or sham therapy for 10 sessions. rTMS (80% resting motor threshold, 10Hz, 20 trains, 5 secs/train, inter-train interval 1 min, total 1000 stimuli/session) was applied over the right motor cortex.
Result:
Nine patients were randomized. Six received rTMS
and three had sham therapy. Three patients in the rTMS arm withdrew from the study due to increased headache frequency and discomfort from the treatment. The remaining six cases (3 rTMS, 3 sham) completed the study. The study was prematurely stopped due to the significant worsening of headache from rTMS. No significant differences in outcome measures were found between real and sham rTMS.
Conclusion:
Although the study was terminated prematurely, the high dropout rate (50%) due to worsening headaches suggested that rTMS over the motor cortex is poorly tolerated in chronic migraine.

Can the `yin and yang` BDNF hypothesis be used to predict the effects of rTMS treatment in neuropsychiatry?

Repetitive transcranial magnetic stimulation (rTMS) is a novel technique of non-invasive brain stimulation which has been used to treat several neuropsychiatric disorders such as major depressive disorder, chronic pain and epilepsy. Recent studies have shown that the therapeutic effects of rTMS are associated with plastic changes in local and distant neural networks. In fact, it has been suggested that rTMS induces long-term potentiation (LTP) and long-term depression (LTD) - like effects. Besides the initial positive clinical results; the effects of rTMS are stilt mixed. Therefore new toots to assess the effects of plasticity non-invasively might be useful to predict its therapeutic effects and design novel therapeutic approaches using rTMS. In this paper we propose that brain-derived neurotrophic factor (BDNF) might be such a tool. Brain-derived neurotrophic factor is a neurotrophin that plays a key role in neuronal survival and synaptic strength, which has also been studied in several neuropsychiatric disorders. There is robust evidence associating BDNF with the LTP/LTD processes, and indeed it has been proposed that BNDF might index an increase or decrease of brain activity - the `yin and yang` BDNF hypothesis. In this article, we review the initial studies combining measurements of BDNF in rTMS clinical trials and discuss the results and potential usefulness of this instrument in the field of rTMS. (C) 2008 Elsevier Ltd. All rights reserved.