Rapid modulation of distributed brain activity by Transcranial Magnetic Stimulation of human motor cortex

This paper reviews the effects of single and repetitive transcranial magnetic stimuli (rTMS) delivered to one cortical area and measured across distributed brain regions using electrophysiological measures (e.g. motor thresholds, motor evoked potentials, paired-pulse stimulation), functional neuroimaging (including EEG, PET and fMRI) and behavioural measures. Discussion is restricted to changes in excitability in the primary motor cortex and behaviour during motor tasks following transcranial magnetic stimulation delivered to primary motor and premotor areas. Trains of rTMS have lasting effects on the excitability of intrinsic and corticofugal neurones, altering the responsiveness of local and remote sites. These effects lead to distributed changes in synaptic activity at rest, and during a range of motor tasks. It is possible to impair or improve performance following rTMS, but for most simple motor tasks performance is unaltered. Changes in distributed activity observed with functional imaging during motor behaviour may represent compensatory activity, enabling maintenance of performance; stimulation of additional cortical areas appears to impair performance. A detailed understanding of the distributed changes in excitability following rTMS may facilitate future attempts to modulate motor behaviour in the healthy brain and for therapeutic purposes.     

经颅直流电刺激技术在增强健康个体认知功能中的应用及其影响因素

经颅直流电刺激作为一种无创脑刺激技术,已在临床治疗及康复领域有广泛应用。随着研究的深入和人类对于自身认知需求的提高,近年来也有研究者开始尝试使用该技术增强健康个体的认知功能。本文从感知觉、注意、记忆、学习和复杂任务五个方面对目前经颅直流电刺激技术在健康个体认知增强领域的研究现状进行梳理和总结,讨论了机制和影响因素,以及未来面临的问题和挑战。     

Poststimulation time interval-dependent effects of motor cortex anodal tDCS on reaction-time task performance

Anodal transcranial direct current stimulation (tDCS) induces long-term potentiation-like plasticity, which is associated with long-lasting effects on different cognitive, emotional, and motor performances. Specifically, tDCS applied over the motor cortex is considered to improve reaction time in simple and complex tasks. The timing of tDCS relative to task performance could determine the efficacy of tDCS to modulate performance. The aim of this study was to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min) applied over the left primary motor cortex (M1) versus sham stimulation on performance of a go/no-go simple reaction-time task carried out at three different time points after tDCS—namely, 0, 30, or 60 min after stimulation. Performance zero min after anodal tDCS was improved during the whole course of the task. Performance 30 min after anodal tDCS was improved only in the last block of the reaction-time task. Performance 60 min after anodal tDCS was not significantly different throughout the entire task. These findings suggest that the motor cortex excitability changes induced by tDCS can improve motor responses, and these effects critically depend on the time interval between stimulation and task performance.     

The role of the primary motor cortex during skill acquisition on a two-degrees-of-freedom movement task

One can partially eliminate motor skills acquired through practice in the hours immediately following practice by applying repetitive transcranial stimulation (rTMS) over the primary motor cortex. The disruption of acquired levels of performance has been demonstrated on tasks that are ballistic in nature. The authors investigated whether motor recall on a discrete aiming task is degraded following a disruption of the primary motor cortex induced via rTMS. Participants (N = 16) maintained acquired performance levels and patterns of muscle activity following the application of rTMS, despite a reduction in corticospinal excitability. Disruption of the primary motor cortex during a consolidation period did not influence the retention of acquired skill in this type of discrete visuomotor task.     

基于非侵入性脑刺激的认知增强：方法、伦理和应用

作为人类追求卓越的方式之一,基于非侵入性脑刺激的认知增强成为众多学科和公众关注的问题。首先阐述了非侵入性脑刺激的两种主要技术手段(经颅磁刺激和经颅直流刺激)的技术原理及其在提升健康个体认知功能上的应用,并分析了这两种技术可能带来的安全、自主选择、公平等伦理问题,最后总结了该认知增强技术在体育和军事等两个具体领域的应用。未来可进一步提高技术手段的深部脑区刺激能力及该增强技术的持续和真实效果。     

经颅电刺激与视功能调控

经颅电刺激(Transcranial Electrical Stimulation, TES)通过电极将特定模式的低强度电流作用于大脑头皮以调控皮层活动, 是一种非侵入、无创的神经刺激方法。根据刺激电流的模式的不同, TES分为经颅直流电刺激(tDCS), 经颅交流电刺激(tACS)和经颅随机电刺激(tRNS)。TES能对视功能诸如光幻视阈值、视野、对比敏感度、视知觉运动等进行一定程度上的调控, 并且能够与传统的视觉知觉学习训练相结合以调控视觉功能。对于不同的视觉功能, 不同的TES参数和模式的调控效果有所不同。     

经颅直流电刺激技术在物质依赖治疗中的应用

物质依赖是一种慢性、复发性脑部疾病, 给个体及社会带来极大损害。研究发现, 经颅直流电刺激(transcranial direct current stimulation, tDCS)可以通过调节背外侧前额叶(dorsolateral prefrontal cortex, DLPFC)脑区的兴奋性降低物质依赖者的渴求, 并改善受损的认知功能。tDCS具有副作用小、操作简便、费用低廉等优点, 因此在物质依赖治疗领域应用前景广泛。未来应考虑确定最佳的刺激参数及刺激位置, 同时考虑物质依赖者的种类及个体差异, 与其他疗法结合使用, 并进一步深入探索tDCS治疗物质依赖的神经机制。     

Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in subacute stroke patients

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus (Wernicke’s area) or the right Wernicke’s area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients who received sham tDCS. All patients received conventional speech and language therapy during each period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients before and after tDCS sessions. After intervention, all patients had significant improvements in aphasia quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved significantly more in patients treated with a cathode, as compared to patients in the other groups. These results are consistent with the role of Wernicke’s area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke.     

Enhancing picture naming with transcranial magnetic stimulation

The enhancement of cognitive function in healthy subjects by medication, training or intervention yields increasing political, social and ethical attention. In this paper facilitatory effects of single-pulse TMS and repetitive TMS on a simple picture naming task are presented. A significant shortening of picture naming latencies was observed after single-pulse TMS over Wernicke's area. The accuracy of the response was not affected by this speed effect. After TMS over the dominant motor cortex or over the non-dominant temporal lobe, however, no facilitation of picture naming was observed. In the rTMS experiments only rTMS of Wernicke's area had an impact on picture naming latencies resulting in a shortening of naming latencies without affecting the accuracy of the response. rTMS over the visual cortex, Broca's area or over the corresponding sites in the non-dominant hemisphere had no effect. Single-pulse TMS is able to facilitate lexical processes due to a general preactivation of language-related neuronal networks when delivered over Wernicke's area. Repetitive transcranial magnetic stimulation over Wernicke's area also leads to a brief facilitation of picture naming possibly by shortening linguistic processing time. Whether TMS or rTMS can be used to aid linguistic therapy in the rehabilitation phase of aphasic patients should be subject of further investigations.     

Influence of Motor Cortex Stimulation During Motor Training on Neuroplasticity as a Potential Therapeutic Intervention

Rehabilitation options to promote neuroplasticity may be enhanced when patients are engaged in motor practice during repetitive transcranial magnetic stimulation (rTMS). Twelve participants completed 3 separate sessions: motor practice, motor practice with rTMS, and rTMS only: motor practice consisted of 30 isometric contractions and subthreshold rTMS was 30, 3-s trains at 10 Hz. Assessments included the Box and Block Test (BBT), force steadiness (10% of the maximum voluntary contraction), and TMS (cortical excitability, intracortical inhibition, and intracortical facilitation). Participants significantly increased BBT scores following the combined condition. Force steadiness improved after all 3 conditions (p < .05). TMS outcomes depended on intervention condition with significant increases in facilitation following the motor practice plus rTMS condition. All interventions influenced motor control, yet are likely modulated differently when combining motor practice plus rTMS. These results help guide the clinical utility of rTMS as an intervention to influence motor control.     

Transcranial Direct Current Stimulation of the Left Temporal Lobe Modulates Insight

Creativity is the ability to come up with new and original solutions to problems. It is characterized along a dipole spectrum, with the opposing ends defined as convergent and divergent thinking. Previous studies have provided evidence that various cognitive functions and insight into non-verbal problems can be enhanced using non-invasive brain stimulation. The aim of this pilot study was to investigate whether convergent and divergent thinking, as well as insight, can be modulated by transcranial direct current stimulation (tDCS) over the anterior temporal lobe (ATL). Bilateral tDCS (1.5 mA, 20 minutes) was used to modulate activity of the right (AR tDCS) and the left (AL tDCS) ATL. Twenty-one participants performed a divergent thinking test (DTT) during tDCS, while a Remote Associates Task (RAT) was administered before and after tDCS to assess convergent thinking. A control experiment, using a Simple Reaction Time (SRT) Task, was conducted in 10 subjects before and after ATL tDCS in order to investigate whether its effects reflect attention or motor effects on the dominant hand. Results from this preliminary study showed that AL tDCS reduced RAT reaction times (RTs) by 20%. Both AL and AR tDCS did not change RAT accuracy, or the DTT total or sub-item scores. No differences were found in the SRT task after either AL or AR tDCS. These findings suggest that left but not right ATL is involved in convergent thinking. Conversely, both left and right temporal cortex tDCS-induced excitability changes failed to modulate divergent thinking. Limitations are discussed.     

Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis

Recent studies have used non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), to increase dorsolateral prefrontal cortex (DLPFC) activity and, consequently, working memory (WM) performance. However, such experiments have yielded mixed results, possibly due to small sample sizes and heterogeneity of outcomes. Therefore, our aim was to perform a systematic review and meta-analyses on NIBS studies assessing the n-back task, which is a reliable index for WM. From the first data available to February 2013, we looked for sham-controlled, randomized studies that used NIBS over the DLPFC using the n-back task in PubMed/MEDLINE and other databases. Twelve studies (describing 33 experiments) matched our eligibility criteria. Active vs. sham NIBS was significantly associated with faster response times (RTs), higher percentage of correct responses and lower percentage of error responses. However, meta-regressions showed that tDCS (vs. rTMS) presented only an improvement in RT, and not in accuracy. This could have occurred in part because almost all tDCS studies employed a crossover design, possibly due to the reliable tDCS blinding. Study design was also associated with no improvement in correct responses in the active vs. sham groups. To conclude, rTMS of the DLPFC significantly improved all measures of WM performance whereas tDCS significantly improved RT, but not the percentage of correct and error responses. Mechanistic insights on the role of DLPFC in WM are further discussed, as well as how NIBS techniques could be used in neuropsychiatric samples presenting WM deficits, such as major depression, dementia and schizophrenia.     

Motor Cortex Plasticity in Children With Spastic Cerebral Palsy: A Systematic Review

A review of the literature was performed to answer the following questions: Does motor cortex excitability correlate with motor function? Do motor cortex excitability and cortex activation change after a rehabilitation program that results in improvements in motor outcomes? Can the 10–20 electroencephalography (EEG) system be used to locate the primary motor cortex when employing transcranial direct current stimulation? Is there a bihemispheric imbalance in individuals with cerebral palsy similar to what is observed in stroke survivors? the authors found there is an adaptation in the geometry of motor areas and the cortical representation of movement is variable following a brain lesion. The 10–20 EEG system may not be the best option for locating the primary motor cortex and positioning electrodes for noninvasive brain stimulation in children with cerebral palsy.     

Brain stimulation and conscious experience

Libet discovered that a substantial duration (> 0.5-1.0 s) of direct electrical stimulation of the surface of the somatosensory cortex at threshold currents is required before human subjects can report that a conscious somatosensory experience had occurred. Using a reaction time method we confirm that a similarly long stimulation duration at threshold currents is required for activation of elementary visual experiences (phosphenes) in human subjects following stimulation of the surface of the striate cortex. However, the reaction times for the subject to respond to the cessation of the visual experience after the end of electrical stimulation could be as brief as 225-242 ms. We also carried out extensive studies in cats under a variety of anesthetic conditions using the same electrodes and parameters of stimulation employed in the human studies to study the patterns of neuronal activity beneath the stimulating surface electrode. Whereas sufficiently strong currents can activate neurons within milliseconds, stimulating currents close to threshold activate sustained neural activity only after at least 350-500 ms. When currents are close to threshold, some neurons are inhibited for several hundreds of millisecond before the balance between inhibition and excitation shifts towards excitation. These results suggest that the prolonged latencies, i.e., latencies beyond 200-250 ms, for the emergence of conscious experience following direct cortical stimulation result from a delay in the sustained activation of underlying cortical neurons at threshold currents rather than being due to any unusually long duration in central processing time. Intracellular records from cortical neurological cells during repetitive electrical stimulation of the surface of the feline striate cortex demonstrate that such stimulation induces a profound depolarizing shift in membrane potential that may persist after each stimulus train. Such a depolarization is evidence that extracellular K+ concentrations have increased during electrical stimulation. Such an increase in extracellular K+ progressively increases cortical excitability until the threshold for sustained activation of cortical neurons is reached and then exceeded. Consequently, the long latency for threshold activation of cortical neurons depends upon a dynamically increasing cortical facilatory process that begins hundreds of milliseconds before there is sustained activation of such neurons. In some cases, this facilatory process must overcome an initial stimulus-induced inhibition before neuronal firing commences.     

工作记忆刷新及其训练效应——经颅直流电刺激的作用

工作记忆刷新是执行功能的重要成分之一。以往研究结合n-back任务和经颅直流电刺激（transcranial direct current stimulation ,tDCS）技术探究刷新能力,发现tDCS技术能够一定程度上增强刷新训练效果并引起大脑神经元相关活动的变化,其增强效果能够维持一定的时间,且能够迁移到其他认知任务之中。但tDCS的干预效果在各项研究中存在一定的差异性。其作用效果会受到训练任务与训练方式、电流强度、电极布局和训练时间间隔等因素的影响。未来研究可以探索tDCS结合刷新训练的最佳刺激参数,以获得最优化的干预效果。     

Transcranial magnetic stimulation in child psychiatry: disturbed motor system excitability in hypermotoric syndromes

Normal development and dysfunctions of motor system excitability can be investigated in vivo by means of single‐ and paired‐pulse transcranial magnetic stimulation (TMS). While different TMS‐parameters show different developmental time courses between 8 and 16 years of age, distinct dysfunctional patterns of motor system excitability can be demonstrated in child psychiatric disorders with hypermotoric behavior: in tic disorder, a shortened cortical silent period can be stated providing evidence for deficient inhibitory mechanisms within the sensorimotor loop, probably primarily at the level of the basal ganglia. In attention deficit hyperactivity disorder (ADHD), a decreased intracortical inhibition indicates deficient inhibitory mechanisms within the motor cortex (but enhancement of intracortical inhibition after oral intake of 10 mg methylphenidate). In children with comorbid ADHD and tic disorder, the findings of a reduced intracortical inhibition as well as a shortened cortical silent period provide evidence for additive effects at the level of motor system excitability. Thus, TMS allows us to obtain substantial insight into both the normal development and the neurobiological basis of hypermotoric syndromes in child psychiatry.     

经颅直流电刺激在注意缺陷多动障碍治疗中的应用

经颅直流电刺激(tDCS)治疗注意缺陷多动障碍(ADHD)主要是选取患者的背外侧前额叶(DLPFC)作为刺激区域, 通过调节其皮层兴奋性, 从而缓解其ADHD的症状和改善其受损的认知功能。针对tDCS在ADHD治疗研究中的问题, 未来可从有效性、确定最佳刺激参数、个体差异、不同亚型及与其他疗法联合使用等五个方面来进一步研究。     

Changes in excitability in motor cortex (representation of foreleg) of the dog depending on signal signification of flexor reaction during elaboration of trans switching

Excitability in a cortical representation of a foreleg was determined during elaboration of transswitching in dogs in three variations depending upon the stimulus used as a Conditioned stimulus (CS). If the flexor reaction to direct stimulation of the motor cortex was used as a CS, excitability changes of opposite signs appeared in the cortical representation of the foreleg, the threshold of flexion decreased in the alimentary situation and increased in the defense situation. Such changes in excitability were observed during instrumental conditioned transswitching. If subthreshold stimulation of the motor cortex was used as the CS, the threshold of flexion increased in both situations in approximately equal degree.     

Mechanisms of aphasia recovery after stroke and the role of noninvasive brain stimulation

One of the most frequent symptoms of unilateral stroke is aphasia, the impairment or loss of language functions. Over the past few years, behavioral and neuroimaging studies have shown that rehabilitation interventions can promote neuroplastic changes in aphasic patients that may be associated with the improvement of language functions. Following left hemisphere strokes, the functional reorganization of language in aphasic patients has been proposed to involve both intrahemispheric interactions between damaged left hemisphere and perilesional sites and transcallosal interhemispheric interactions between the lesioned left hemisphere language areas and homotopic regions in the right hemisphere. A growing body of evidence for such reorganization comes from studies using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), two safe and noninvasive procedures that can be applied clinically to modulate cortical excitability during post-stroke language recovery. We discuss a hierarchical model for the plastic changes in language representation that occur in the setting of dominant hemisphere stroke and aphasia. We further argue that TMS and tDCS are potentially promising tools for enhancing functional recovery of language and for further elucidating mechanisms of plasticity in patients with aphasia.     

The cortical representation of centrally presented words: A magnetic stimulation study

The right and left visual fields each project to the contralateral cerebral hemispheres. The current study aimed to investigate the extent of the functional overlap of the two hemifields along the vertical meridian. We applied repetitive transcranial magnetic stimulation (rTMS) over the left and right occipital cortex to investigate whether the foveal representation of words is bilaterally represented or is split between the two hemispheres. Employing a lateralized lexical decision task, we first showed a double dissociation between the stimulated cortical site and performance; right visual field (RVF) but not left visual field (LVF) performance was impaired when the left visual cortex was stimulated, and LVF but not RVF performance was impairred when the right visual cortex was stimulated. Unilateral stimulation also significantly impaired lexical decision latencies to centrally presented words. These findings support the suggestion that foveal representation of words is split. We discuss future strategies for the use of TMS in further tests of the split representation account.