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.     

A proposed regional hierarchy in recovery of post-stroke aphasia

Activation studies in patients with aphasia due to stroke or tumours in the dominant hemisphere have revealed effects of disinhibition in ipsilateral perilesional and in contralateral homotopic cortical regions, referred to as collateral and transcallosal disinhibition. These findings were supported by studies with selective disturbance of cortical areas by repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers and in patients with focal brain lesions. Both, collateral as well as transcallosal disinhibition might be relevant for the compensation of lesions within a functional network. From these data a hierarchical organization of recovery of aphasia after stroke and of compensation of language defects due to brain tumours can be deduced, by which the reactivation of undamaged network areas of the ipsilateral hemisphere usually lead to better outcome than the involvement of homotopic contra-lateral regions. rTMS can be used to identify areas relevant for speech production and might play a role in treatment strategies targeted at modulating the activity of contralateral homotopic areas of the functional network which might interfere with language recovery.     

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.     

Can brain stimulation improve semantic joke comprehension?

ABSTRACT

Semantic humour involves a deviation from lexico-semantic rules that introduces ambiguity into interpretation of a situation. The left Inferior Frontal Gyrus (IFG) has been implicated in humour processing (e.g. semantic puns, ambiguity resolution). The present study aimed to examine whether transcranial direct current stimulation (tDCS) over the left IFG would enhance semantic ambiguity resolution. In two sessions, fifteen participants aged 20–35 years received either offline anodal tDCS or sham stimulation for 20?min, after which they read semantically ambiguous humorous sentences, literal (non-ambiguous) sentences, and meaningless sentences, and then performed a semantic judgment task relating to each sentence’s final word. Results showed that ambiguity resolution requires longer processing than literality. However, left IFG stimulation was ineffective in increasing ambiguity resolution. Researchers should target different brain areas in both hemispheres to further explore humour comprehension.     

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.     

经颅直流电刺激对健康人群反应抑制的影响

反应抑制是指抑制不恰当的或不符合当前需要的行为的能力, 研究表明反应抑制主要与额下回、背外侧前额叶和前辅助运动区的功能有关。经颅直流电刺激(tDCS)是一种非侵入式脑刺激技术, 近年来对健康人群使用tDCS刺激相应脑区从而影响反应抑制功能的研究日益增多, 但主要研究结果不一致。阐明tDCS影响反应抑制具体的神经机制、减少tDCS研究的异质性、探索更有效的tDCS刺激方式和确定tDCS效果的年龄依赖性差异已成为目前亟待解决的问题。     

左右侧颞顶联合区对道德意图信息加工能力的共同作用——基于经颅直流电刺激技术

行为人的意图动机是我们对日常行为的对错做出判断的重要依据。以往研究表明,左右侧颞顶联合区(TPJ)都可能与信念意图的整合加工能力相关,尤其是近年来越来越多的神经刺激研究为TPJ区域与心理状态归因能力之间的因果关系提供了证据。然而,这些研究在实验任务的选取,实验设计的优化,实验结论的稳健性上仍然有改进的空间。基于此,本研究开展了两个在设计上互相补充的实验。实验中被试的TPJ区域会接受一段时间的经颅直流电刺激,并完成一系列的道德判断任务,任务是由意图和结果,以及负性和中性2×2双变量构成的4种条件的故事:无伤人、伤人未遂、意外伤人和伤人成功,被试要对故事主角的行为做出谴责程度的道德判断。结合道德判断的谴责程度和决策时间数据发现,当人们在处理信念意图信息时,左右侧TPJ区域可能是协同互动、共同发挥作用的。在激活右侧TPJ并限制左侧TPJ的情况下,人们对负性结果的谴责程度变高,人们变得更加依赖于行为结果做出道德判断;而在限制右侧TPJ并激活左侧TPJ的情况下,人们对负性意图的谴责程度变高,人们变得更加依赖于行为者的动机做出道德判断。     

Enhancing Creativity With Combined Transcranial Direct Current and Random Noise Stimulation of the Left Dorsolateral Prefrontal Cortex and Inferior Frontal Gyrus

Creativity is a fundamental human accomplishment from scientific advances to composing music. The left dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) are important metacontrol hubs in flexibility and persistence brain states, respectively. Those hubs are related to divergent thinking, insight problem-solving, and convergent thinking. In this double-blind, between-subjects study, 81 healthy participants were randomly assigned to one of three groups (n = 27) that received a combined transcranial direct current stimulation–transcranial random noise stimulation (tDCS-tRNS) protocol with the anode over the left DLPFC and cathode over the left IFG (+DLPFC−IFG), the opposite montage (−DLPFC+IFG), and a sham group (+DLPFC−IFG). Both active tDCS-tRNS groups received 20 min of 1 mA tDCS with 1 mA (100–500 Hz) tRNS. Creativity was assessed before (baseline) and during stimulation with the Unusual Uses, Picture Completion (PC), Remote Association test (RAT), Matchstick Arithmetic (MA), and Nine-dot (ND) problems. Only the +DLPFC−IFG group had significantly higher scores compared with sham in the RAT (p = .009), PC fluency (p = .018), PC originality (p = .007), ND (p = .007), and MA (p = .032). Overall, −DLPFC+IFG had greater scores in all creativity tests compared with sham. Implications from the metacontrol theory are discussed.     

Transcranial alternating brain stimulation at alpha frequency reduces hemispatial neglect symptoms in stroke patients

Background/ObjectiveNon-invasive brain stimulation techniques such as transcranial alternating current stimulation (tACS) may help alleviate attention deficits in stroke patients with hemispatial neglect by modulating oscillatory brain activity. We applied high-definition (HD)-tACS at alpha frequency over the contralesional hemisphere to support unilateral oscillatory alpha activity and correct for the pathologically altered attention bias in neglect patients.MethodsWe performed a within-subject, placebo-controlled study in which sixteen stroke patients with hemispatial neglect underwent 10 Hz (alpha) as well as sham (placebo) stimulation targeting the contralesional posterior parietal cortex. Attentional bias was measured with a computerized visual detection paradigm and two standard paper-and-pencil neglect tests.ResultsWe revealed a significant shift of attentional resources after alpha-HD-tACS, but not sham tACS, toward the ipsilateral and thus contralesional hemifield leading to a reduction in neglect symptoms, measured with a computerized visual detection paradigm and a widely used standard paper and pencil neglect tests.ConclusionsWe showed a significant alpha-HD-tACS-induced shift of attentional resources toward the contralesional hemifield, thus leading to a reduction in neglect symptoms. Importantly, HD-tACS effects persisted after the stimulation itself had ended. This tACS protocol, based on intrinsic oscillatory processes, may be an effective and well-tolerated treatment option for neglect.     

From the left to the right: How the brain compensates progressive loss of language function

In normal right-handed subjects language production usually is a function oft the left brain hemisphere. Patients with aphasia following brain damage to the left hemisphere have a considerable potential to compensate for the loss of this function. Sometimes, but not always, areas of the right hemisphere which are homologous to language areas of the left hemisphere in normal subjects are successfully employed for compensation but this integration process may need time to develop. We investigated right-handed patients with left hemisphere brain tumors as a model of continuously progressive brain damage to left hemisphere language areas using functional neuroimaging and transcranial magnetic stimulation (TMS) to identify factors which determine successful compensation of lost language function. Only patients with slowly progressing brain lesions recovered right-sided language function as detected by TMS. In patients with rapidly progressive lesions no right-sided language function was found and language performance was linearly correlated with the lateralization of language related brain activation to the left hemisphere. It can thus be concluded that time is the factor which determines successful integration of the right hemisphere into the language network for compensation of lost left hemisphere language function.     

Effect of tDCS on Fine Motor Control of Patients in Subacute and Chronic Post-Stroke Stages

Abstract

In this study we compared the effects of transcranial direct current stimulation (tDCS) in the subacute and chronic stages of post-stroke recovery. Anodal/sham tDCS was applied to the primary motor cortex of stroke patients in these stages of recovery in a cross-over design. The Jebsen–Taylor hand function test was employed. The repeated-measure ANOVA showed significant influence of the stimulation type and test performance time (during/after tDCS) with no overall influence of recovery stage. The interaction TYPE*TIME*STAGE was significant. The effect after anodal tDCS in the subacute stage was significantly higher compared to the effects in all relevant conditions including the chronic stage. Therefore, tDCS treatment in the subacute stage of recovery can be superior, at least for some patients, to treatment in the chronic stage.     

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。     

Parietal versus temporal lobe components in spatial cognition: Setting the mid‐point of a horizontal line

Recent anatomo‐clinical correlation studies have extended to the superior temporal gyrus, the right hemisphere lesion sites associated with the left unilateral spatial neglect, in addition to the traditional posterior‐inferior‐parietal localization of the responsible lesion (supramarginal gyrus, at the temporo‐parietal junction). The study aimed at teasing apart, by means of repetitive transcranial magnetic stimulation (rTMS), the contribution of the inferior parietal lobule (angular gyrus versus supramarginal gyrus) and of the superior temporal gyrus of the right hemisphere, in making judgments about the mid‐point of a horizontal line, a widely used task for detecting and investigating spatial neglect. rTMS trains at 25 Hz frequency were delivered over the inferior parietal lobule (angular gyrus and supramarginal gyrus), the superior temporal gyrus and the anterior parietal lobe of the right hemisphere, in 10 neurologically unimpaired participants, performing a line bisection judgment task. rTMS of the inferior parietal lobule at the level of the supramarginal gyrus brought about a rightward error in the bisection judgment, ipsilateral to the side of the rTMS, with stimulation over the other sites being ineffective. The neural correlates of computing the mid‐point of a horizontal segment include the right supramarginal gyrus in the inferior parietal lobule and do not extend to the angular gyrus and the superior temporal gyrus. These rTMS data in unimpaired subjects constrain the evidence from lesion studies in brain‐damaged patients, emphasizing the major role of a subset of relevant regions.     

Transcranial direct current stimulation versus intermittent theta-burst stimulation for the improvement of working memory performance

Non-invasive brain stimulation (NIBS) techniques have been increasingly used over the dorsolateral prefrontal cortex (DLPFC) to enhance working memory (WM) performance. Notwithstanding, NIBS protocols have shown either small or inconclusive cognitive effects on healthy and neuropsychiatric samples. Therefore, we assessed working memory performance and safety of transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and both therapies combined vs placebo over the neuronavigated left DLPFC of healthy participants. Twenty-four subjects were included to randomly undergo four sessions of NIBS, once a week: tDCS alone, iTBS alone, combined interventions and placebo. The 2-back task and an adverse effect scale were applied after each NIBS session. Results revealed a significantly faster response for iTBS (b= -21.49, p= 0.04), but not for tDCS and for the interaction tDCS vs. iTBS (b= 13.67, p= 0.26 and b= 40.5, p= 0.20, respectively). No changes were observed for accuracy and no serious adverse effects were found among protocols. Although tolerable, an absence of synergistic effects for the combined protocol was seen. Nonetheless, future trials accessing different outcomes for the combined protocols, as well as studies investigating iTBS over the left DLPFC for cognition and exploring sources of variability for tDCS are encouraged.     

Neural substrates of word generation during stroke recovery: the influence of cortical hypoperfusion

Several studies have demonstrated reorganization of cognitive and motor function caused by stroke. This study examined the influence of hypoperfused brain regions, in addition to the area of the infarct itself, on reorganization of the cognitive processes underlying word generation in stroke patients. In addition, we also sought to determine the influence of hypoperfusion on the blood oxygen level dependent/(BOLD) effect. Subjects with left and right subacute or chronic subcortical strokes, along with normal controls, were imaged while performing a verbal fluency task (word generation). The study population included six normal subject and six stroke patients with subcortical infarcts and cortical hypoperfusion in the middle cerebral artery territory who had recovered or improved markedly in word fluency. While normal subjects displayed a left-lateralized fronto-temporo-parietal and bilateral cingulo-striatal-thalamic-cerebellar network, the activation pattern of stroke patients was determined both by the hypoperfused regions and infarcted areas of the brain. Specifically, patients showed diminished BOLD effect in the cortical regions that were hypoperfused, even though their infarcts were subcortical, and showed increased BOLD effect in the homologous regions of the normal hemisphere. This finding raises the possibility that cortical hypoperfusion in the absence of infarct can cause shift of language functions to the opposite, intact hemisphere. However, reduced BOLD effect in the task relative to rest was found in hypoperfused regions in two patients, raising the possibility that regional function persisted, even though vascular reactivity was impaired. Results illustrate the complexities of functional imaging studies of recovery in patients with vascular lesions.     

Testing the involvement of the prefrontal cortex in lucid dreaming: A tDCS study

Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to increase dream lucidity. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants’ self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed.     

Initial right hemisphere activation of subordinate word meanings is not due to homotopic callosal inhibition

Previous results (Burgess & Simpson, 1988a) have suggested that subordinate meanings are activated in the right hemisphere only when they have been inhibited in the left hemisphere. Such findings are consistent with a homotopic callosal inhibition view of hemispheric interaction (Cook, 1986). The current study employed prime-target stimulus onset asynchronies intermediate to those used by Burgess and Simpson and obtained equivalent priming of subordinate meanings over visual fields. These data rule out homotopic callosal inhibition as the mechanism responsible for initial activation of subordinate meanings in the right hemisphere and challenge homotopic inhibition as a general mechanism of interhemispheric interaction.     

Alteration of hypnotic experience following transcranial electrical stimulation of the left prefrontal cortex

BackgroundRecent studies of neurostimulation reported alteration of hypnotizability and hypnotic phenomena after inhibition of the dorsolateral prefrontal cortex (DLPFC), but the different assessments of hypnosis and the stimulation parameters still left open many questions about the role of this brain region in hypnotizability. We aimed to administer inhibitory transcranial direct current stimulation (tDCS) over the left DLPFC to observe effects of stimulation on the hypnotic experience and the feeling of agency.Methodsa procedure of hypnotic induction with suggestions was repeated twice: before and after the unilateral cathodal tDCS over the left DLPFC. The experience was assessed through a phenomenological assessment of hypnosis and sense of agency in thirty-three participants randomly assigned to the sham or the active group.Resultsactive (inhibitory) tDCS enhanced the hypnotizability by 15.4% and altered a few dimensions of consciousness such as self-awareness and absorption. No changes emerged on the feeling of agency and pass rates for suggestions.ConclusionstDCS reflects a promising tool to alter the hypnotic phenomena and the responsiveness to hypnotic procedures. Neurocognitive implications are discussed for the construct of hypnotizability as well as for the role of the left DLPFC in the dimensions of consciousness such as self-awareness.     

Does transcranial direct current stimulation during writing alleviate upper limb freezing in people with Parkinson’s disease? A pilot study

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can boost motor performance in Parkinson’s disease (PD) when it is applied at rest. However, the potential supplementary therapeutic effect of the concurrent application of tDCS during the training of motor tasks is largely unknown. The present study examined the effects of tDCS on upper limb motor blocks during a freezing-provoking writing task (the funnel task) requiring up- and down-stroke movements at alternating amplitudes. Ten PD patients and 10 age-matched controls underwent two sessions of writing combined with 20 min of anodal or sham tDCS on the left M1 in a randomized cross-over design. The primary outcome was the number of upper limb freezing episodes during five trials of the funnel task on a touch-sensitive tablet. PD patients showed a significant reduction in freezing episodes during tDCS compared to sham. No effects of tDCS were found for the amplitude, variability and speed of the strokes outside the freezing episodes. However, patients who reported freezing episodes in daily life (N = 6) showed a beneficial effect of tDCS on stroke characteristics. These results indicate a subgroup-dependent variability in response to non-invasive brain stimulation applied during the performance of motor tasks in PD. This warrants future studies to examine tDCS as an adjuvant tool for training programs aimed to reduce motor deficits related to freezing.     

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.