Lizbeth Cárdenas-Morales

Mechanisms and Applications of Theta-burst rTMS on the Human Motor Cortex

Theta-burst Stimulation (TBS) is a novel form of repetitive transcranial magnetic stimulation (rTMS). Applied over the primary motor cortex it has been successfully used to induce changes in cortical excitability. The advantage of this stimulation paradigm is that it is able to induce strong and long lasting effects using a lower stimulation intensity and a shorter time of stimulation compared to conventional rTMS protocols. Since its first description, TBS has been used in both basic and clinical research in the last years and more recently it has been expanded to other domains than the motor system. Its capacity to induce synaptic plasticity could lead to therapeutic implications for neuropsychiatric disorders. The neurobiological mechanisms of TBS are not fully understood at present; they may involve long-term potentiation (LTP)- and depression (LTD)-like processes, as well as inhibitory mechanisms modulated by GABAergic activity. This article highlights current hypotheses regarding the mechanisms of action of TBS and some central factors which may influence cortical responses to TBS. Furthermore, previous and ongoing research performed in the field of TBS on the motor cortex is summarized.

The value of neuronavigated rTMS for the treatment of depression

Repetitive transcranial magnetic stimulation (rTMS) has been increasingly evaluated as a therapeutic tool for the treatment of depression, using various stimulation parameters and protocols. Heterogeneous results have been reported with regard to clinical outcome, at least partly due to the variety of procedures for coil placement above the desired site of stimulation. This article reviews the strategies for coil positioning in the treatment of depression. Considering preliminary clinical evidence, neuronavigated rTMS appears desirable to treat depression, compared to the standard targeting procedure (5cm anterior to the motor cortex). Coil positioning strategy might improve in the future by taking into consideration the individual abnormalities revealed by functional neuroimaging data.

Network Connectivity and Individual Responses to Brain Stimulation in the Human Motor System

The mechanisms driving cortical plasticity in response to brain stimulation are still incompletely understood. We here explored whether neural activity and connectivity in the motor system relate to the magnitude of cortical plasticity induced by repetitive transcranial magnetic stimulation (rTMS). Twelve right-handed volunteers underwent functional magnetic resonance imaging during rest and while performing a simple hand motor task. Resting-state functional connectivity, task-induced activation, and task-related effective connectivity were assessed for a network of key motor areas. We then investigated the effects of intermittent theta-burst stimulation (iTBS) on motor-evoked potentials (MEP) for up to 25 min after stimulation over left primary motor cortex (M1) or parieto-occipital vertex (for control). ITBS-induced increases in MEP amplitudes correlated negatively with movement-related fMRI activity in left M1. Control iTBS had no effect on M1 excitability. Subjects with better response to M1-iTBS featured stronger preinterventional effective connectivity between left premotor areas and left M1. In contrast, resting-state connectivity did not predict iTBS aftereffects. Plasticity-related changes in M1 following brain stimulation seem to depend not only on local factors but also on interconnected brain regions. Predominantly activity-dependent properties of the cortical motor system are indicative of excitability changes following induction of cortical plasticity with rTMS.

Exploring the after-effects of theta burst magnetic stimulation on the human motor cortex: A functional imaging study

Theta burst stimulation (TBS) is a protocol of subthreshold repetitive transcranial magnetic stimulation (rTMS) inducing changes in cortical excitability. From functional imaging studies with conventional subthreshold rTMS protocols, it remains unclear what type of modulation occurs (direction and dependency to neural activity) and whether putative effects are bound to unspecific changes in cerebral perfusion or require a functional challenge. In a within‐subjects (n = 17) repeated measurement design including real TBS and a control session without stimulation, we examined neural activation in a choice‐reaction task after application of intermittent TBS, a protocol, which enhances cortical excitability over the left motor cortex (M1). Brain activity was monitored by blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging interleaved with measuring regional cerebral blood flow (rCBF) at rest using MR‐based perfusion imaging. On a separate day, TMS‐induced compound muscle action potentials (cMAPs) amplitude of the right hand was measured after excitatory TBS. Compared to control, a significant decrease in BOLD signal due to right hand motor activity during the choice‐reaction task was observed mainly in the stimulated M1 and motor‐related remote areas after stimulation. This decrease might represent a facilitating effect, because cMAPs amplitude increased upon TBS compared to control. No changes in rCBF at rest were observed. The data demonstrate that subthreshold intermittent TBS targets both the stimulated cortical area as well as remote areas. The facilitation changing the efficacy of neural signal transmission seems to be reflected by a BOLD signal decrease, whereas the network at rest does not appear to be affected. Hum Brain Mapp, 2011.

Transcranial magnetic stimulation in depression--lessons from the multicentre trials.

Looking at novelties and advances in medicine in particular in the treatment of major depressive disorder no principally new antidepressant treatment strategy has been established in clinical routine in the last fifty years. However, regarding the considerable issue of treatment resistance in depression, new therapeutic strategies are urgently required. In this context, repetitive transcranial magnetic stimulation above the dorsolateral prefrontal cortex has been proposed as a potential new treatment option for depression; furthermore, in October 2008 a first rTMS-device (NeuroStar TMS Therapy System) was approved by the FDA for the treatment of treatment resistant major refractory depression in adults. Yet, despite now nearly two decades of research in this field, no final answer concerning its validity for antidepressant treatment in the clinical practice is given. Numerous studies with small sample sizes and heterogeneous designs have been performed in this field yielding to different results. These were subjected to meta-analyses, assessing the antidepressant effect of rTMS, which are briefly summarized in this article. Further, multicentre-trials with larger numbers of patients were performed, which are presented and critically discussed here in more detail. This short review shall thus provide an overview of the current status of knowledge concerning rTMS in depression and it also provides some recommendations for future research in this field.

Exploring the affective component of pain perception during aversive stimulation in borderline personality disorder.

In a pilot study, affective components of pain were assessed using repetitive peripheral magnetic stimulation (rPMS) in patients with borderline personality disorder and healthy controls. Significant differences in pain thresholds and in affective components of pain between both groups were found. rPMS was well tolerated and suitable for assessing pain.

Neural activation in humans during a simple motor task differs between BDNF polymorphisms

The BDNF Val66Met polymorphism has been linked to decreased synaptic plasticity involved in motor learning tasks. We investigated whether individual differences in this polymorphism may promote differences in neural activity during a two-alternative forced-choice motor performance. In two separate sessions, the BOLD signal from 22 right-handed healthy men was measured during button presses with the left and right index finger upon visual presentation of an arrow. 11 men were Val66Val carriers (ValVal group), the other 11 men carried either the Val66Met or the Met66Met polymorphism (Non-ValVal group). Reaction times, resting and active motor thresholds did not differ between ValVal and Non-ValVal groups. Compared to the ValVal group the Non-ValVal group showed significantly higher BOLD signals in the right SMA and motor cingulate cortex during motor performance. This difference was highly consistent for both hands and across all four sessions. Our finding suggests that this BDNF polymorphism may not only influence complex performance during motor learning but is already associated with activation differences during rather simple motor tasks. The higher BOLD signal observed in Non-ValVal subjects suggests the presence of cumulative effects of the polymorphism on the motor system, and may reflect compensatory functional activation mediating equal behavioral performance between groups.