Motor cortical excitability in depressive patients after electroconvulsive therapy and repetitive transcranial magnetic stimulation

Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex are brain stimulation techniques that are used as therapeutic interventions in major depression. However, the exact therapeutic mode of action needs further clarification. In this case report, we describe the impact of these stimulation techniques on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 2 patients who received consecutively both rTMS and ECT. Both patients showed a decrease in motor cortical excitability after response to antidepressant brain stimulation, whereas parameters of motor cortical excitability remained unchanged after the first non-successful intervention. These results suggest that both ECT and rTMS may have an impact on parameters of motor cortical neuronal excitability. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of different antidepressant stimulation techniques.     

The effects of motor cortex rTMS on corticospinal descending activity

Repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex can produce long-lasting changes in the excitability of the motor cortex to single pulse transcranial magnetic stimulation (TMS). rTMS may increase or decrease motor cortical excitability depending critically on the characteristics of the stimulation protocol. However, it is still poorly defined which mechanisms and central motor circuits contribute to these rTMS induced long-lasting excitability changes. We have had the opportunity to perform a series of direct recordings of the corticospinal volley evoked by single pulse TMS from the epidural space of conscious patients with chronically implanted spinal electrodes before and after several protocols of rTMS that increase or decrease brain excitability. These recordings provided insight into the physiological basis of the effects of rTMS and the specific motor cortical circuits involved.     

Modulating cortical excitability in acute stroke: a repetitive TMS study.

OBJECTIVE: Changes in cerebral cortex excitability have been demonstrated after a stroke and are considered relevant for recovery. Repetitive transcranial magnetic stimulation (rTMS) of the brain can modulate cerebral cortex excitability and, when rTMS is given as theta burst stimulation (TBS), LTP- or LTD-like changes can be induced. The aim of present study was to evaluate the effects of TBS on cortical excitability in acute stroke. METHODS: In 12 acute stroke patients, we explored the effects of facilitatory TBS of the affected hemisphere and of inhibitory TBS of the unaffected hemisphere on cortical excitability to single-pulse transcranial magnetic stimulation (TMS) on both sides. The effects produced by TBS in patients were compared with those observed in a control group of age-matched healthy individuals. RESULTS: In patients, both the facilitatory TBS of the affected motor cortex and the inhibitory TBS of the unaffected motor cortex produced a significant increase of the amplitude of MEPs evoked by stimulation of the affected hemisphere. The effects observed in patients were comparable to those observed in controls. CONCLUSIONS: Facilitatory TBS over the stroke hemisphere and inhibitory TBS over the intact hemisphere in acute phase enhance the excitability of the lesioned motor cortex. SIGNIFICANCE: TBS might be useful to promote cortical plasticity in stroke patients.     

Placebo-controlled study of rTMS for the treatment of Parkinson's disease.

The objective of this study is to assess the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for gait and bradykinesia in patients with Parkinson's disease (PD). In a double-blind placebo-controlled study, we evaluated the effects of 25 Hz rTMS in 18 PD patients. Eight rTMS sessions were performed over a 4-week period. Four cortical targets (left and right motor and dorsolateral prefrontal cortex) were stimulated in each session, with 300 pulses each, 100% of motor threshold intensity. Left motor cortex (MC) excitability was assessed using motor evoked potentials (MEPs) from the abductor pollicis brevis. During the 4 weeks, times for executing walking and complex hand movements tests gradually decreased. The therapeutic rTMS effect lasted for at least 1 month after treatment ended. Right-hand bradykinesia improvement correlated with increased MEP amplitude evoked by left MC rTMS after individual sessions, but improvement overall did not correlate with MC excitability. rTMS sessions appear to have a cumulative benefit for improving gait, as well as reducing upper limb bradykinesia in PD patients. Although short-term benefit may be due to MC excitability enhancement, the mechanism of cumulative benefit must have another explanation.     

Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability.

OBJECTIVES: This study explored whether the effects of repetitive transcranial magnetic stimulation (rTMS) on corticospinal excitability are dependent on the stimulation intensity and examined the effect of rTMS on inhibitory function.METHODS: Nine normal volunteers received 15min of 1Hz rTMS at 85 and 115% of the resting motor threshold (RMT). Cortical excitability was measured before and after rTMS.RESULTS: rTMS at both intensities produced an increase in the RMT but only 115% stimulation reduced the size of motor evoked potentials (MEPs). rTMS had no effects on the cortical silent period or cortical inhibition measured with paired pulse TMS.CONCLUSIONS: The effects of 1Hz rTMS on motor cortex excitability are partially dependent on stimulus intensity and the effects of rTMS on motor thresholds and MEP size may differ.     

Antidepressant effects of high and low frequency repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex: a double-blind, randomized, placebo-controlled trial

Repetitive transcranial magnetic stimulation (rTMS) has antidepressant effects in patients with major depressive disorder. The mechanisms of action and optimal stimulation parameters remain unclear. To test the hypothesis that rTMS exerts antidepressant effects either by enhancing left dorsolateral prefrontal cortex (DLPFC) excitability or by decreasing right DLPFC excitability, the authors studied 45 patients with unipolar recurrent major depressive disorder in a double-blind, randomized, parallel group, sham-controlled trial. Patients were randomized to receive 1 Hz or 10 Hz rTMS to the left DLPFC, 1 Hz to the right DLPFC or sham TMS. Left 10 Hz and right 1 Hz rTMS showed similar significant antidepressant effects. Other parameters led to no significant antidepressant effects.     

Repetitive transcranial magnetic stimulation to improve mood and motor function in Parkinson's disease

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can produce lasting changes in excitability and activity in cortical regions underneath the stimulation coil (local effect), but also within functionally connected cortical or subcortical regions (remote effects). Since the clinical presentation of Parkinson's disease (PD) is related to abnormal neuronal activity within the basal ganglia and cortical regions, including the primary motor cortex, the premotor cortex and the prefrontal cortex, several studies have used rTMS to improve brain function in PD. Here, we review the studies that have investigated the possible therapeutic effects of rTMS on mood and motor function in PD patients. We highlight some methodological inconsistencies and problems, including the difficulty to define the most effective protocol for rTMS or to establish an appropriate placebo condition. We finally propose future directions of research that may help to improve the therapeutic efficacy of rTMS in PD.     

Muscle vibration and prefrontal repetitive transcranial magnetic stimulation

We previously demonstrated that prefrontal subthreshold repetitive transcranial magnetic stimulation (rTMS) may reduce motor cortex excitability. We have now examined whether muscle vibration (MV) can compensate for this depression. We enrolled 25 healthy volunteers (aged 22 to 37 years) who received 5 HZ, 10% subthreshold prefrontal rTMS for 12 s. The extensor carpi radialis muscle was vibrated with an electromagnetic mechanical stimulator with a stimulation frequency of 120 HZ and 0.5 mm amplitude. Motor evoked potentials (MEPs) from the flexor carpi radialis muscle (FCR) following single-pulse transcranial magnetic stimulation (TMS) were recorded at baseline, and after 4, 8, and 12 s. During prefrontal rTMS, MEPs of the FCR exhibited a serial depression (P = 0.001). This effect did not occur during MV. We conclude that rTMS of the prefrontal cortex may inhibit the corticospinal system. This depression may be compensated by MV, suggesting that vibration changes motor cortex excitability. The underlying mechanism might be an input from Ia sensory afferents to the motor and prefrontal cortex.     

Repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in posttraumatic stress disorder: a double-blind, placebo-controlled study

OBJECTIVE: The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex was studied in patients with posttraumatic stress disorder (PTSD) under double-blind, placebo-controlled conditions. METHOD: Twenty-four patients with PTSD were randomly assigned to receive rTMS at low frequency (1 Hz) or high frequency (10 Hz) or sham rTMS in a double-blind design. Treatment was administered in 10 daily sessions over 2 weeks. Severity of PTSD, depression, and anxiety were blindly assessed before, during, and after completion of the treatment protocol. RESULTS: The 10 daily treatments of 10-Hz rTMS at 80% motor threshold over the right dorsolateral prefrontal cortex had therapeutic effects on PTSD patients. PTSD core symptoms (reexperiencing, avoidance) markedly improved with this treatment. Moreover, high-frequency rTMS over the right dorsolateral prefrontal cortex alleviated anxiety symptoms in PTSD patients. CONCLUSIONS: This double-blind, controlled trial suggests that in PTSD patients, 10 daily sessions of right dorsolateral prefrontal rTMS at a frequency of 10 Hz have greater therapeutic effects than slow-frequency or sham stimulation.     

Transcranial magnetic stimulation in depression

Among the new therapeutic techniques in psychiatry, transcranial magnetic stimulation (TMS) seems to bring a profit in the treatment of depressions. It uses the principle of inductance to generate a magnetic current, which in turn activates cortical neurons. Stimulation is highly focused and interests specific regions of the cerebral cortex. This therapeutic technique is generally well tolerated. Side effects are rare, the most hampering one is epileptic seizures. It is favored by high frequencies (above 5 Hz) and arises mainly with patients having a history of personal or family epileptic seizures. The first open trials, quickly confirmed by controlled studies showed the efficiency of TMS in depression. With depression, double blind randomized trials, using high frequencies, stimulation of the left dorsolateral prefrontal cortex give positive results with significant decrease of scores on depressive scales applied to resistant and non resistant depressions. Some studies have stimulated the right dorsolateral prefrontal cortex using low frequencies. The decrease of scores is also significant on depressive scales. The modulating effect of rTMS on cortical excitability of the brain justifies this distinction between high and low frequencies, high frequencies having a facilitating effect whereas low frequencies have an inhibitory effect.     

Subthreshold prefrontal repetitive transcranial magnetic stimulation reduces motor cortex excitability

The prefrontal cortex plays an important role in central motor control. We have examined whether prefrontal repetitive transcranial magnetic stimulation (rTMS) induces changes of motor cortex excitability determined by motor evoked potentials (MEPs) following single-pulse TMS. We studied 18 healthy volunteers stimulated at 5 Hz with 10% subthreshold prefrontal vs. occipital rTMS for 12 s. MEPs from the flexor carpi radialis muscle after single-pulse vertex stimulation were recorded during rTMS at 0, 4, 8, and 12 s. MEP areas decreased significantly after 8 s of prefrontal rTMS (P < 0. 05) but not after occipital rTMS. We conclude that rTMS of the prefrontal cortex may inhibit the primary motor areas.     

Premotor transcranial direct current stimulation (tDCS) affects primary motor excitability in humans

Recent studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex (PM) modifies the excitability of the ipsilateral primary motor cortex (M1). Transcranial direct current stimulation (tDCS) is a new method to induce neuroplasticity in humans non-invasively. tDCS generates neuroplasticity directly in the cortical area under the electrode, but might also induce effects in distant brain areas, caused by activity modulation of interconnected areas. However, this has not yet been tested electrophysiologically. We aimed to study whether premotor tDCS can modify the excitability of the ipsilateral M1 via cortico-cortical connectivity. Sixteen subjects received cathodal and anodal tDCS of the PM and eight subjects of the dorsolateral prefrontal cortex. Premotor anodal, but not premotor cathodal or prefrontal tDCS, modified selectively short intracortical inhibition/intracortical facilitation (SICI/ICF), while motor thresholds, single test-pulse motor-evoked potential and input–output curves were stable throughout the experiments. Specifically, anodal tDCS decreased intracortical inhibition and increased paired-pulse excitability. The selective influence of premotor tDCS on intracortical excitability of the ipsilateral M1 suggests a connectivity-driven effect of tDCS on remote cortical areas. Moreover, this finding indirectly substantiates the efficacy of tDCS to modulate premotor excitability, which might be of interest for applications in diseases accompanied by pathological premotor activity.     

Use of repetitive transcranial magnetic stimulation in pain relief

Repetitive transcranial magnetic stimulation (rTMS) of the cerebral cortex is a noninvasive strategy that could have the potential to relieve severe chronic pain, at least partially and transiently. The most studied target of stimulation is the precentral (motor) cortex, but other targets, such as the dorsolateral prefrontal cortex or the parietal cortex, could be of interest. Analgesic effects have been produced by rTMS in patients with neuropathic pain, fibromyalgia or visceral pain. Therapeutic applications of rTMS in pain syndromes are limited by the short duration of the induced effects, but prolonged pain relief can be obtained by performing rTMS sessions every day for several weeks. In patients who respond to rTMS but relapse, surgical implantation of epidural cortical electrodes and a pulse generator can be proposed to make clinical effects more permanent. The rate of improvement produced by rTMS may be predictive for the outcome of the implanted procedure. The place of rTMS as a therapeutic tool in the management of chronic pain remains to be determined.     

Effects of repetitive transcranial magnetic stimulation in subjects with sleep disorders

In this review, we aimed at identifying the studies that have employed repetitive transcranial magnetic stimulation (rTMS) in patients with sleep disorders. Low-frequency (LF) rTMS stimulating the right dorsolateral prefrontal cortex (DLPFC) or the posterior parietal cortex (PPC) was found to be effective to reduce cortical hyperexcitability and improve the sleep quality in subjects with chronic primary insomnia (PI). Both high-frequency (HF) and LF rTMS applied over the primary motor cortex or the supplementary motor cortex seem to have transient beneficial effects in patients with restless legs syndrome (RLS). Stimulation of upper airway muscles during sleep by isolated TMS and by rTMS twitch can improve airflow dynamics in obstructive sleep apnea syndrome (OSAS) patients without arousal. A single case report study indicates that HF rTMS over the left DLPFC might represent an alternative choice for symptom control in narcoleptic patients with cataplexy, and a pilot study also raises the possibility of therapeutic benefits from rTMS in patients with sleep bruxism. rTMS may also exert intrinsic effects on hypersomnia in depressed adolescents.In conclusion, rTMS may contribute to the development of new non-pharmacological therapeutic options for several sleep disorders. rTMS might be useful as therapeutical tool in particular in patients with PI, RLS, OSAS and narcolepsy, while its effect in other sleep disorders (ie, parasomnias) has not yet been explored. rTMS integrated with clinical, sleep-related, and neuroimaging data may represent an effective tool in modulating cortical excitability and inducing short-term synaptic plasticity. Further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up warranted to verify the initial findings, and to expand clinical and research interest towards neuromodulation in the different sleep disorders.     

Repetitive transcranial magnetic stimulation (rTMS): insights into the treatment of Parkinson's disease by cortical stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is a potent tool that can be used to modify activity of targeted cortical areas. Significant clinical effects have been obtained in patients with Parkinson's disease (PD) by stimulating different cortical regions with rTMS at inhibitory (low) or excitatory (high) frequency. These effects were thought to result from plastic changes in motor cortical networks. Actually cortical dysfunction has been documented in PD by neuroimaging and neurophysiologic studies showing either hypo- or hyper-activation of various brain areas. In addition, cortical excitability studies using transcranial magnetic stimulation disclosed significant alterations in intracortical facilitatory or inhibitory processes according to the resting state or to phases of movement preparation or execution. These observations clearly support the therapeutic potential of cortical neuromodulation in PD. Motor cortex stimulation could impact on any station within the cortico-basal ganglia-thalamo-cortical loops that are involved in motor control, providing alleviation of parkinsonian symptoms. Depending on the target, cortical stimulation might improve motor performance or other symptoms associated with PD, like depression. Clinical application of rTMS to treat PD patients is limited by the short duration of the effects beyond the time of stimulation, even if long-lasting improvements have been observed after repeated rTMS sessions. In any case, the place of cortical stimulation in the therapeutic management of PD patients remains to be determined, as an alternative or a complementary technique to deep brain stimulation. The rTMS technique could be used to better define the targets and the parameters of stimulation subsequently applied in chronic epidural stimulation.     

Therapeutic and neurophysiologic aspects of transcranial magnetic stimulation in schizophrenia.

The use of repetitive transcranial magnetic stimulation (rTMS) in psychiatry provides the therapeutic field with a new tool. Since its introduction in the mid 1980s, the vast majority of studies have focussed on depression. A growing body of evidence suggests that rTMS is effective in the treatment of depression if dorsolateral prefrontal cortex is stimulated. Less is known about its efficacy in schizophrenia. Neuroimaging investigations in schizophrenia suggest abnormalities in the prefrontal and temporoparietal cortex (TPC), which are correlated with psychopathological dimensions. Based on its modulatory effect, rTMS seems to be a promising tool in exploring cortical excitability and reducing auditory hallucinations (AH) and negative symptoms. Neurophysiologic studies of patients suffering from schizophrenia using rTMS indicate high cortical excitability and a lack of transcallosal inhibition. In the therapeutic field, researches provide encouraging results, even though some studies indicate limited benefits. The most promising therapeutic effect seems to be the capability of rTMS to reduce AH if TPC is targeted using slow-frequency. The current paper aims to provide a review of the literature of the use of rTMS in schizophrenia.     

Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's disease.

OBJECTIVE: To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson's disease (PD). METHODS: Repetitive transcranial magnetic stimulation (rTMS) was performed on the left motor cortical area corresponding to the right hand in 12 'off-drug' patients with PD. The effects of subthreshold rTMS applied at 0.5 Hz (600 pulses) or at 10 Hz (2000 pulses) using a 'real' or a 'sham' coil were compared to those obtained by a single dose of l-dopa. The assessment included a clinical evaluation by the Unified Parkinson's Disease Rating Scale and timed motor tasks, and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques. RESULTS: 'Real' rTMS at 10 or 0.5 Hz, but not 'sham' stimulation, improved motor performance. High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation, while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking. Concomitantly, 10 Hz rTMS increased intracortical facilitation, while 0.5 Hz rTMS restored intracortical inhibition. CONCLUSIONS: Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds. The effects on cortical excitability were opposite to previous observations made in healthy subjects, suggesting a reversed balance of cortical excitability in patients with PD compared to normals. However, the underlying mechanisms of these changes remain to determine, as well as the relationship with clinical presentation and response to l-dopa therapy. SIGNIFICANCE: The present study gives some clues to appraise the role of the primary motor cortex in PD. Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application, but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD.     

Visual and motor cortex excitability: a transcranial magnetic stimulation study.

OBJECTIVES: Phosphene thresholds (PTs) to transcranial magnetic stimulation over the occipital cortex and motor thresholds (MTs) have been used increasingly as measures of the excitability of the visual and motor cortex. MT has been utilized as a guide to the excitability of other, non-motor cortical areas such as dorsolateral prefrontal cortex. The aims of this study were to compare the PTs to MTs; to assess their stability across sessions; and to investigate their relation to MTs. METHODS: PTs and MTs were determined using focal transcranial magnetic stimulation over the visual and motor cortex. RESULTS: PTs were shown to be significantly higher than MTs. Both PTs and MTs were stable across sessions. No correlation between PTs and MTs could be established. CONCLUSIONS: Phosphene threshold is a stable parameter of the visual cortex excitability. MTs were not related to the excitability of non-motor cortical areas.     

The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain.

Chronic motor cortex stimulation using implanted epidural stimulation was proposed to treat chronic, drug-resistant neuropathic pain. Various studies showed that repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex could also relieve neuropathic pain, at least partially and transiently. Controlled rTMS studies with other cortical targets, such as the dorsolateral prefrontal cortex, are in waiting. The mechanisms of action of rTMS on chronic pain are mostly unknown. The changes induced by rTMS in neural activities may occur at the stimulated cortical site as well as in remote structures along functional anatomical connections. Compared to chronic implanted procedure, the main limitation of rTMS application is the short duration of clinical effects. Repeated daily rTMS sessions have proved some efficacy to induce long-lasting pain relief that could have therapeutic potential. However, rTMS-induced analgesia varies with the site and parameters of stimulation, in particular the stimulus rate. The efficacious rTMS parameters could differ from those used in chronic epidural stimulation. Differences in the pattern of the current fields respectively induced in the brain by these two techniques might explain this finding. Actually, stimulation parameters remain to be optimised and clinical efficacy to be confirmed by multicentre randomised trials, before considering rTMS as therapeutic tool for patients with chronic pain in neurological practice.     

Transcranial magnetic stimulation in migraine: a review of facts and controversies

There is compelling evidence that cortical excitability is modified in migraine patients between attacks. Transcranial magnetic stimulation (TMS) is a non-invasive tool to investigate this abnormality. Repetitive transcranial magnetic stimulation (rTMS) activates the underlying cortex at high, but inhibits it at low stimulation frequencies. This is a review of published results obtained in migraineurs with TMS and rTMS over motor or visual cortices. Prevalence and/or threshold data of phosphenes induced by single pulse TMS of the visual cortex are contradictory, some favouring increased, others decreased interictal excitability. The discrepancies may be due to differences in methodology and poor reliability of phosphene reporting. In a recent rTMS study of the occipital cortex we have found evidence in favour of an interictal decrease of the preactivation excitability level by using amplitude of visual evoked potentials and its habituation during sustained stimulation as indices of cortical excitability. The hypothesis of increased cortical excitability, taken in its strict physiological sense of a decreased response threshold and/or an increased response to a single suprathreshold stimulus, may thus not be any longer tenable. The long lasting effects of rTMS allow in future studies to assess metabolic changes of the cortex and subcortical structures with functional imaging methods and to explore novel therapeutic strategies for migraine.