Ipsilesional and contralesional regions participate in the improvement of poststroke aphasia: a transcranial direct current stimulation study

In the past few years, noninvasive cerebral stimulations have been used to modulate language task performance in healthy and aphasic patients. In this study, a dual transcranial direct current stimulation (tDCS) on anterior and posterior language areas was applied for 2 weeks to a patient with a possible crossed aphasia following a right hemisphere stroke. Inhibitory cathodal stimulation of the right Brodmann areas (BA) 44/45 and simultaneous anodal stimulation of the left BA 44/45 improved the patient’s performance in picture naming. Conversely, the same bilateral montage on BA 39/40 did not produce any significant improvement; finally, electrode polarity inversion over BA 39/40 yielded a further improvement compared with the first anterior stimulation. Our findings suggest that ipsilesional and contralesional areas could be useful in poststroke functional reorganization and provide new evidences for the therapeutic value of tDCS in aphasia.     

Effects of anodal transcranial direct current stimulation over lower limb primary motor cortex on motor learning in healthy individuals

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which alters motor functions in healthy humans and in neurological patients. Most studies so far investigated the effects of tDCS on mechanisms underlying improvements in upper limb performance. To investigate the effect of anodal tDCS over the lower limb motor cortex (M1) on lower limb motor learning in healthy volunteers, we conducted a randomized, single‐blind and sham‐controlled study. Thirty‐three (25.81 ± 3.85, 14 female) volunteers were included, and received anodal or sham tDCS over the left M1 (M1‐tDCS); 0.0625 mA/cm² anodal tDCS was applied for 15 min during performance of a visuo‐motor task (VMT) with the right leg. Motor learning was monitored for performance speed and accuracy based on electromyographic recordings. We also investigated the influence of electrode size and baseline responsivity to transcranial magnetic stimulation (TMS) on the stimulation effects. Relative to baseline measures, only M1‐tDCS applied with small electrodes and in volunteers with high baseline sensitivity to TMS significantly improved VMT performance. The computational analysis showed that the small anode was more specific to the targeted leg motor cortex volume when compared to the large anode. We conclude that anodal M1‐tDCS modulates VMT performance in healthy subjects. As these effects critically depend on sensitivity to TMS and electrode size, future studies should investigate the effects of intensified tDCS and/or model‐based different electrode positions in low‐sensitivity TMS individuals.     

Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.

BACKGROUND: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). METHODS: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. RESULTS: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. CONCLUSIONS: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.     

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation ( P  = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.     

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease

OBJECTIVES: Cognitive impairment is a common feature in Parkinson's disease (PD) and is an important predictor of quality of life. Past studies showed that some aspects of cognition, such as working memory, can be enhanced following dopaminergic therapy and transcranial magnetic stimulation. The aim of our study was to investigate whether another form of noninvasive brain stimulation, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability, is associated with a change in a working memory task performance in PD patients. METHODS: We studied 18 patients (12 men and 6 women) with idiopathic PD. The patients performed a three-back working memory task during active anodal tDCS of the left dorsolateral prefrontal cortex (LDLPFC), anodal tDCS of the primary motor cortex (M1) or sham tDCS. In addition, patients underwent two different types of stimulation with different intensities: 1 and 2 mA. RESULTS: The results of this study show a significant improvement in working memory as indexed by task accuracy, after active anodal tDCS of the LDLPFC with 2 mA. The other conditions of stimulation: sham tDCS, anodal tDCS of LDLPFC with 1 mA or anodal tDCS of M1 did not result in a significant task performance change. CONCLUSION: tDCS may exert a beneficial effect on working memory in PD patients that depends on the intensity and site of stimulation. This effect might be explained by the local increase in the excitability of the dorsolateral prefrontal cortex.     

Modulation of moving phosphene thresholds by transcranial direct current stimulation of V1 in human

Small moving sensations, so-called moving phosphenes are perceived, when V5, a visual area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if only V5 takes part in movement perception or other visual areas are also involved in this process. In this study we tested the involvement of V1 in the perception of moving phosphenes by applying transcranial direct current stimulation (tDCS) to this area. tDCS is a non-invasive stimulation technique known to modulate cortical excitability in a polarity-specific manner. Moving and stationary phosphene thresholds (PT) were measured by TMS before, immediately after and 10, 20 and 30 min after the end of 10 min cathodal and anodal tDCS in nine healthy subjects. Reduced PTs were detected immediately and 10 min after the end of anodal tDCS while cathodal stimulation resulted in an opposite effect. Our results show that the excitability shifts induced by V1 stimulation can modulate moving phosphene perception. tDCS elicits transient, but yet reversible effects, thus presenting a promising tool for neuroplasticity research.     

Modulation of decision‐making in a gambling task in older adults with transcranial direct current stimulation

Cognitive performance usually declines in older adults as a result of neurodegenerative processes. One of the cognitive domains usually affected is decision‐making. Based on our recent findings suggesting that non‐invasive brain stimulation can improve decision‐making in young participants, we studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex of older adult subjects can change balance of risky and safe responses as it can in younger individuals. Twenty‐eight subjects (age range from 50 to 85 years) performed a gambling risk task while receiving either anodal tDCS over the right and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS over the left with cathodal tDCS over the right DLPFC, or sham stimulation. Our main finding was a significant group effect showing that participants receiving left anodal/right cathodal stimulation chose more often high‐risk prospects as compared with participants receiving sham or those receiving right anodal/left cathodal stimulation. This result is contrary to previous findings in young subjects, suggesting that modulation of cortical activity in young and elderly results in opposite behavioral effects; thus supporting fundamental changes in cognitive processing in the elderly.     

Transcranial direct current stimulation improves word retrieval in healthy and nonfluent aphasic subjects

A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernicke's area (position CP5 of the International 10-20 EEG System) while they learned 20 new "words" (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernicke's area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernicke's area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.     

Improved naming after transcranial direct current stimulation in aphasia

Transcranial direct current stimulation (tDCS) has been proposed as an adjuvant technique to improve functional recovery after ischaemic stroke. This study evaluated the effect of tDCS over the left frontotemporal areas in eight chronic non-fluent post-stroke aphasic patients. The protocol consisted of the assessment of picture naming (accuracy and response time) before and immediately after anodal or cathodal tDCS (2 mA, 10 minutes) and sham stimulation. Whereas anodal tDCS and sham tDCS failed to induce any changes, cathodal tDCS significantly improved the accuracy of the picture naming task by a mean of 33.6% (SEM 13.8%).     

Repetitive transcranial magnetic stimulation effects on language function depend on the stimulation parameters.

In previous studies it has been shown that picture-naming latencies can be facilitated with both suprathreshold single and repetitive transcranial magnetic stimulation (TMS/rTMS) over Wernicke's area. The aim of this study was to investigate whether low-frequency rTMS (1 Hz) or high-frequency rTMS (20 Hz) at subthreshold intensities is also capable of influencing picture naming. In 16 healthy right-hand male subjects, trains of 1 Hz or 20 Hz were applied over either Wernicke's area, Broca's area, or the primary visual cortex. The subjects had to name 20 black-and-white line drawings, which were shown immediately after rTMS and again 2 minutes later. Naming latency could be facilitated only immediately after Wernicke's area stimulation at a frequency of 20 Hz and at an intensity of 55% of the maximal stimulator output, which was more than the motor threshold. All other stimulation procedures failed to influence naming latencies. These results indicate that language functions can be facilitated in healthy subjects only by high-frequency rTMS with intensities at or above the motor threshold.     

The enhancement of cortical excitability over the DLPFC before and during training impairs categorization in the prototype distortion task

The present study investigated the effects of transcranial weak electrical stimulation techniques applied to the right and left dorsolateral prefrontal cortex (DLPFC) on categorization learning measured using a variant of the prototype distortion task.During the training phase of this task subjects saw low- and high distortions of a prototype dot-pattern. 60 participants received 10 min of either anodal or cathodal transcranial direct current (tDCS), transcranial random noise (tRNS) or sham stimulation before and during the training. We have assessed the effects of the intervention during a test phase, where the subjects had to decide whether the consecutive high- and low-distortion versions of the prototype or random patterns that were presented belonged to the category established in the training phase.Our results show that the categorization of prototypes is significantly impaired by the application of anodal tDCS and tRNS to the DLPFC. The prototype-effect, observable in the case of the sham stimulation group, was severed in all active stimulation conditions.     

Transcranial direct current stimulation disrupts tactile perception

The excitability of the cerebral cortex can be modulated by various transcranial stimulation techniques. Transcranial direct current stimulation (tDCS) offers the advantage of portable equipment and could, therefore, be used for ambulatory modulation of brain excitability. However, modulation of cortical excitability by tDCS has so far mostly been shown by indirect measures. Therefore, we examined whether tDCS has a direct behavioral/perceptional effect. We compared tactile discrimination of vibratory stimuli to the left ring finger prior to, during and after tDCS applied for 7 min at 1-mA current intensity in 13 subjects. Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a within-subject design. The active electrode was placed over the corresponding somatosensory cortex at C4 according to the 10-20 EEG system and the reference electrode at the forehead above the contralateral orbita. Cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while anodal and sham stimulation did not. Thus, cortical processing can be modulated in a behaviorally/perceptually meaningful way by weak transcranial current stimulation applied through portable technology. This finding offers a new perspective for the treatment of conditions characterized by alterations of cortical excitability.     

Efficacy of semantic–phonological treatment combined with tDCS for verb retrieval in a patient with aphasia

Recent studies reported enhanced performance on language tasks induced by transcranial direct current stimulation (tDCS) in patients with aphasia. One chronic patient with non-fluent aphasia received 20 sessions of a verb anomia training combined with off-line bihemispheric tDCS applied to the dorsolateral prefrontal cortex (DLPFC) – anodal tDCS over left DLPFC plus cathodal tDCS over right DLPFC. A significant improvement in verb naming was observed at all testing times (4, 12, 24, and 48 weeks from post-entry/baseline testing) for treated and untreated verbs. Our findings show beneficial effects of verb anomia training in combination with tDCS in chronic aphasic patient, suggesting a long-lasting effect of this treatment.     

Right parietal cortex mediates recognition memory for melodies

Functional brain imaging studies have highlighted the significance of right‐lateralized temporal, frontal and parietal brain areas for memory for melodies. The present study investigated the involvement of bilateral posterior parietal cortices (PPCs) for the recognition memory of melodies using transcranial direct current stimulation (tDCS). Participants performed a recognition task before and after tDCS. The task included an encoding phase (12 melodies), a retention period, as well as a recognition phase (24 melodies). Experiment 1 revealed that anodal tDCS over the right PPC led to a deterioration of overall memory performance compared with sham. Experiment 2 confirmed the results of Experiment 1 and further showed that anodal tDCS over the left PPC did not show a modulatory effect on memory task performance, indicating a right lateralization for musical memory. Furthermore, both experiments revealed that the decline in memory for melodies can be traced back to an interference of anodal stimulation on the recollection process (remember judgements) rather than to familiarity judgements. Taken together, this study revealed a causal involvement of the right PPC for memory for melodies and demonstrated a key role for this brain region in the recollection process of the memory task.     

Current intensity‐ and polarity‐specific online and aftereffects of transcranial direct current stimulation: An fMRI study

Transcranial direct current stimulation (tDCS) induces polarity‐ and dose‐dependent neuroplastic aftereffects on cortical excitability and cortical activity, as demonstrated by transcranial magnetic stimulation (TMS) and functional imaging (fMRI) studies. However, lacking systematic comparative studies between stimulation‐induced changes in cortical excitability obtained from TMS, and cortical neurovascular activity obtained from fMRI, prevent the extrapolation of respective physiological and mechanistic bases. We investigated polarity‐ and intensity‐dependent effects of tDCS on cerebral blood flow (CBF) using resting‐state arterial spin labeling (ASL‐MRI), and compared the respective changes to TMS‐induced cortical excitability (amplitudes of motor evoked potentials, MEP) in separate sessions within the same subjects (n = 29). Fifteen minutes of sham, 0.5, 1.0, 1.5, and 2.0‐mA anodal or cathodal tDCS was applied over the left primary motor cortex (M1) in a randomized repeated‐measure design. Time‐course changes were measured before, during and intermittently up to 120‐min after stimulation. ROI analyses indicated linear intensity‐ and polarity‐dependent tDCS after‐effects: all anodal‐M1 intensities increased CBF under the M1 electrode, with 2.0‐mA increasing CBF the greatest (15.3%) compared to sham, while all cathodal‐M1 intensities decreased left M1 CBF from baseline, with 2.0‐mA decreasing the greatest (?9.3%) from sham after 120‐min. The spatial distribution of perfusion changes correlated with the predicted electric field, as simulated with finite element modeling. Moreover, tDCS‐induced excitability changes correlated more strongly with perfusion changes in the left sensorimotor region compared to the targeted hand‐knob region. Our findings reveal lasting tDCS‐induced alterations in cerebral perfusion, which are dose‐dependent with tDCS parameters, but only partially account for excitability changes.     

Specific and nonspecific effects of transcranial magnetic stimulation on picture-word verification

Repetitive transcranial magnetic stimulation (rTMS) can temporarily impair or improve performance, including language processing. It remains unclear, however, (i) which scalp sites are most appropriate to achieve the desired effects and (ii) which experimental setups produce facilitation or inhibition of language functions. We assessed the effects of TMS at different stimulation sites on picture-word verification in healthy volunteers. Twenty healthy volunteers with left language lateralization, as determined by functional transcranial Dopplersonography, performed picture-word verification prior to and after rTMS (1 Hz for 600 s at 110% of subjects' resting motor thresholds). Stimulation sites were the classical language areas (Broca's and Wernicke's), their homolog brain regions of the right hemisphere, and the occipital cortex. Additionally, sham stimulation over Broca's area was applied in a subsample of 11 subjects. As a control task, 10 volunteers performed a colour-tone matching task under the same experimental conditions. There was a general nonspecific arousal effect for both verum and sham TMS for both the picture-word verification and for the control task. However, superimposed there were opposite effects on picture-word verification for stimulation of Wernicke's area and Broca's area, namely a relative inhibition in the case of Wernicke's area and a relative facilitation in the case of Broca's area. These results demonstrate that low frequency rTMS has both general arousing effects and domain-specific effects.     

Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex

Stimulation with weak electrical direct currents has been shown to be capable of inducing stimulation-polarity-dependent prolonged diminutions or elevations of cortical excitability, most probably elicited by a hyper- or depolarization of resting membrane potentials. The aim of the present study was to test if cognitive task and motor exercise practiced during the stimulation are able to modify transcranial direct current stimulation-induced plasticity in the left primary motor cortex in 12 healthy subjects. Motor evoked potentials were recorded before and after 10 min of anodal and cathodal transcranial direct current stimulation. In Experiment 1, subjects were required to sit passively during the stimulation, in Experiment 2 the subject's attention was directed towards a cognitive test and in Experiment 3 subjects were instructed to push a ball in their right hand. Both the cognitive task and motor exercise modified transcranial direct current stimulation-induced plasticity; when performing the cognitive task during stimulation the motor cortex excitability was lower after anodal stimulation and higher after cathodal stimulation, compared with the passive condition. When performing the motor exercise, the motor cortex excitability was lower after both anodal and cathodal stimulation, compared with the passive condition. Our results show that transcranial direct current stimulation-induced plasticity is highly dependent on the state of the subject during stimulation.     

How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.     

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.