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.     

Repetitive transcranial magnetic stimulation may induce language switching in bilingual patients

The dorsolateral prefrontal cortex (DLPFC) may participate in the process of language switching in multilingual individuals. We present two cases of bilingual patients who experienced unexpected language switching after receiving high-frequency, repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC as a treatment for major depression. These preliminary findings support the role of the DLPFC in language switching in polyglots and highlight the potential value of rTMS for non-invasively investigating language function in humans. Further investigation is warranted.     

Modulation of N400 in chronic non-fluent aphasia using low frequency Repetitive Transcranial Magnetic Stimulation (rTMS)

Low frequency Repetitive Transcranial Magnetic Stimulation (rTMS) has previously been applied to language homologues in non-fluent populations of persons with aphasia yielding significant improvements in behavioral language function up to 43 months post stimulation. The present study aimed to investigate the electrophysiological correlates associated with the application of rTMS through measurement of the semantic based N400 Event-related brain potentials (ERP) component. Low frequency (1 Hz) rTMS was applied to the anterior portion of the homologue to Broca’s area (pars triangularis), for 20 min per day for 10 days, using a stereotactic neuronavigational system. Twelve non-fluent persons with aphasia, 2-6 years post stroke were stimulated. Six participants were randomly assigned to receive real stimulation and six participants were randomly assigned to receive a blind sham control condition. ERP measures were recorded at baseline, 1 week and 2 months subsequent to stimulation. The findings demonstrate treatment related changes observed in the stimulation group when compared to the placebo control group at 2 months post stimulation indicating neuromodulation of N400 as a result of rTMS. No treatment related changes were identified in the stimulation group, when compared to the sham group from baseline to 1 week post stimulation. The electrophysiological results represent the capacity of rTMS to modulate neural language networks and measures of lexical-semantic function in participants with non-fluent aphasia and suggest that time may be an important factor in brain reorganization subsequent to rTMS.     

Reperfusion of Specific Brain Regions by Raising Blood Pressure Restores Selective Language Functions in Subacute Stroke

We report a series of six single subject studies examining the effects of pharmacological blood pressure elevation on regional brain perfusion and language function. Previous reports indicate that hypoperfusion of specific brain regions, as delineated by magnetic resonance perfusion weighted imaging (PWI), is associated with disruption of selective lexical functions. On this basis, we hypothesized that reperfusion of the same regions, in the absence of infarct in that region, would restore the associated lexical function. We present five patients with impaired lexical-semantics associated with poor perfusion, but not infarction, of Brodmann's area 22 (BA 22), and one patient with impaired lexical-semantics and a superimposed deficit in retrieving the phonological representations of words, associated with poor perfusion Brodmann's area 37 (BA 37) as well as BA 22. Each patient was treated with induced blood pressure elevation to increase perfusion of the ischemic and dysfunctional tissue. Daily testing of naming and comprehension, with stimulus sets matched for frequency, familiarity, and length, showed improved lexical-semantics in the patients who showed reperfusion of BA 22 and improved oral naming (but not lexical-semantics) in the patient who showed reperfusion of BA 37. These cases illustrate that loss of function with hypoperfusion of a circumscribed area of the brain, and recovery of the same function with improved perfusion of that brain region, can reveal brain/language relationships prior to reorganization after brain injury.     

Disruption of semantic influence on writing following a left prefrontal lesion

We report a patient with impaired spontaneous writing, written naming, and homophone spelling, consistent with a disruption of semantic influence on writing. However, writing to dictation by both the phonological and lexical spelling systems was intact. In addition, general semantic abilities were spared, as indicated by preserved auditory and reading comprehension. We propose that our patient could not incorporate meaning into writing because of a disruption of both direct and indirect connections between semantics and the orthographic output lexicon. The writing dysfunction was accompanied by a similar impairment of speech output, suggesting that it was part of a more general disturbance of semantic influence on language production following left prefrontal damage.     

Neuro-cognitive aspects of “OM” sound/syllable perception: A functional neuroimaging study

The sound “OM” is believed to bring mental peace and calm. The cortical activation associated with listening to sound “OM” in contrast to similar non-meaningful sound (TOM) and listening to a meaningful Hindi word (AAM) has been investigated using functional magnetic resonance imaging (MRI). The behaviour interleaved gradient technique was employed in order to avoid interference of scanner noise. The results reveal that listening to “OM” sound in contrast to the meaningful Hindi word condition activates areas of bilateral cerebellum, left middle frontal gyrus (dorsolateral middle frontal/BA 9), right precuneus (BA 5) and right supramarginal gyrus (SMG). Listening to “OM” sound in contrast to “non-meaningful” sound condition leads to cortical activation in bilateral middle frontal (BA9), right middle temporal (BA37), right angular gyrus (BA 40), right SMG and right superior middle frontal gyrus (BA 8). The conjunction analysis reveals that the common neural regions activated in listening to “OM” sound during both conditions are middle frontal (left dorsolateral middle frontal cortex) and right SMG. The results correspond to the fact that listening to “OM” sound recruits neural systems implicated in emotional empathy.     

文盲与非文盲汉字字形和语音加工的脑机制

利用功能性磁共振成像(fMRI)技术探讨文盲和非文盲汉字字形和语音加工脑机制的差异。实验1使用汉字字形和图形比较了中国人文盲和非文盲字形加工过程脑机制的左侧差异。实验2使用汉字语音和纯音比较了文盲和非文盲语音加工过程脑机制的双侧差异。结果表明文盲与非文盲汉字字形和语音加工脑机制不同,且非文盲的脑活动强。     

Near space functioning of the human angular and supramarginal gyri

The posterior parietal cortex (PPC) has been associated with the encoding of events in peripersonal space, but little is known about the precise segregation of parietal areas involved specifically in ‘near‐space’ visuospatial processing. This study applied transcranial magnetic stimulation (TMS) to two parietal areas: the right angular gyrus (ANG) and the right supramarginal gyrus (SMG) in addition to a control site, cortical visual area V5, while subjects performed symmetry judgements on lines presented simultaneously in the left and right visual fields. Eight subjects performed the task with the stimuli presented either in peripersonal or extra personal space. As expected, TMS over the right ANG caused subjects to report lines as being longer ipsilateral to the stimulation site, but only in near space. TMS of the right SMG, however, induced a bias shift in both near and far space, but the change only reached significance in near space. Our findings suggest that, consistent with its role in somatosensory functions, the SMG, like the ANG, is specialised for near space.     

Pure agraphia in Romaji after left inferior frontal gyrus infarction: A case of selective deficit in syllable-to-grapheme conversion in Japanese

The Japanese writing system employs two distinct categories of characters: Kana and Kanji. The difference between Kana and Kanji writing corresponds roughly to that between phonological and lexical systems in Western languages. When typing, most Japanese use alphabetical characters based purely on phonological rules. In particular, the Romaji system is used, in which a syllable consists of a single vowel, a consonant–vowel compound (e.g., ka, ki), or a sequence of consonant–y(semivowel)–vowel (e.g., kya, kyu). We describe a right-handed Japanese patient who developed pure agraphia that affected Romaji writing but preserved Kana and Kanji writing and who had a lesion in the left pars opercularis of the inferior frontal gyrus that extended to the anterior precentral gyrus. The patient demonstrated literal paragraphia in spelling Romaji across modalities. Our findings suggested that the patient’s agraphia in Romaji after a confined left frontal infarction was manifested by a selective impairment in syllable-to-grapheme conversion.     

The role of motion direction selective extrastriate regions in reading: a transcranial magnetic stimulation study

Why reading ability is correlated with motion processing ability is perplexing. Activity in motion direction processing regions (Area V5/MT+) was perturbed by means of repetitive transcranial magnetic stimulation (rTMS) to examine its effect on reading. A functional probe (significant shortening of the motion aftereffect) was used to identify Area V5/MT+. Right-handed participants (8 m, 8 f) received three 7.5 min blocks of rTMS, after which two phonological and one orthographic reading tasks were administered. Application of rTMS to Area V5/MT+ (as compared to a non-rTMS baseline) significantly decreased performance only during non-word naming. The pattern of naming errors and the absence of deficits on the second phonological task were not consistent with a role for Area V5/MT+ in phonological decoding. Instead, its role in reading may be limited to image stabilization and/or letter localization.     

TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia

This study sought to discover if an optimum 1 cm² area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions.     

Writing with the right hemisphere

We studied writing abilities in a strongly right-handed man following a massive stroke that resulted in virtually complete destruction of the language-dominant left hemisphere. Writing was characterized by sensitivity to lexical-semantic variables (i.e., word frequency, imageability, and part of speech), semantic errors in writing to dictation and written naming, total inability to use the nonlexical phonological spelling route, and agrammatism in spontaneous writing. The reliance on a lexical-semantic strategy in spelling, semantic errors, and impaired phonology and syntax were all highly consistent with the general characteristics of right hemisphere language, as revealed by studies of split-brain patients and adults with dominant hemispherectomy. In addition, this pattern of writing closely resembled the syndrome of deep agraphia. These observations provide strong support for the hypothesis that deep agraphia reflects right hemisphere writing.     

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.     

Input-specific long-term potentiation in the rat lateral amygdala of horizontal slices

Long-term potentiation (LTP) at input synapses to the lateral nucleus of the amygdala (LA) is a candidate mechanism for memory storage during fear learning. Cellular mechanisms of LTP have been nearly exclusively investigated in coronal brain slices. In our experiments, we used a horizontal brain slice preparation of rats that preserved most of the connections to cortical areas and the hippocampus. The stimulation electrodes were located either within the external capsule (EC) or the LA. The aim of the present study was to investigate the mechanisms of LTP induced either by weak theta burst stimulation (TBS) or strong high frequency stimulation (HFS) using the two different stimulation sites. Whereas both TBS and HFS of afferences running through the LA induced stable LTP, TBS failed to induce LTP of EC-inputs to the LA. The present findings also show that LTP in the LA exhibits vulnerability at different time windows after induction. The time window was dependent on the kind of stimulated afferences. Later LTP becomes resistant to disruption by low frequency stimulation. We could show that both used inputs depended on NMDA receptors for LTP-induction. LTP induced by stimulation of fibers within the LA was not altered by nifedipine (10 microM). In contrast, EC-induced LTP was dependent on L-type voltage-gated calcium channels (VGCC). Finally, we found a higher magnitude of LTP in females using TBS, whereas HFS did not cause gender-specific differences. Our study supports the conclusion that the form of LA-LTP depend on which afferences are activated and what pattern of stimulation is used to induce LTP.     

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.     

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.     

The behavioral complications of pallidal stimulation: a case report

We report a case of recurrent manic episodes associated with chronic deep brain stimulation (DBS) targeting globus pallidus (GP) in the treatment of Parkinson's disease (PD). Cardinal PD symptoms and dyskinesia improved with DBS, and neuropsychological testing found improvements in visuospatial measures associated with left DBS and in verbal memory with right DBS when compared to the patient's preoperative baseline. Under conditions of right, left, and bilateral DBS, the patient experienced bouts of mania and hypomania lasting several days at a time. Positron emission tomography (PET) with (15)O-labeled water was performed after his first manic episode under four conditions: no stimulation, right DBS, left DBS, and bilateral DBS. Although no manic switch occurred during the course of the PET study, all three DBS conditions were associated with decreases in regional flow in the left parahippocampus and hippocampus and right mid-cingulate gyrus. Increases in flow in left inferior frontal area, bilateral insula, dorsolateral prefrontal cortex, and cuneus were common to all DBS conditions. GP stimulation in PD may be associated with behavioral and cognitive effects. Distributed blood flow changes observed with pallidal DBS support a role for the pallidum in cognition and affective regulation.     

Repetitive transcranial magnetic stimulation induced slow wave activity modification: A possible role in disorder of consciousness differential diagnosis?

Slow wave activity (SWA) generation depends on cortico–thalamo-cortical loops that are disrupted in patients with chronic Disorders of Consciousness (DOC), including the Unresponsive Wakefulness Syndrome (UWS) and the Minimally Conscious State (MCS). We hypothesized that the modulation of SWA by means of a repetitive transcranial magnetic stimulation (rTMS) could reveal residual patterns of connectivity, thus supporting the DOC clinical differential diagnosis. We enrolled 10 DOC individuals who underwent a 24 hh polysomnography followed by a real or sham 5 Hz-rTMS over left primary motor area, and a second polysomnographic recording. A preserved sleep-wake cycle, a standard temporal progression of sleep stages, and a SWA perturbation were found in all of the MCS patients and in none of the UWS individuals, only following the real-rTMS. In conclusion, our combined approach may improve the differential diagnosis between MCS patients, who show a partial preservation of cortical plasticity, and UWS individuals, who lack such properties.     

Singaporean kindergartners' phonological awareness and English writing skills

This article describes the phonological awareness and English writing skills among a sample of 297 Singaporean kindergarten children, stratified by ethnicity (Chinese, Malay, and Indian), and examines the relationship between oral language and writing skills in this multilingual population. Overall, Singaporean kindergartners, nearly all of whom were bilingual, scored higher on English writing but lower on English oral language skills than U.S. norms. Despite literacy instruction that emphasized whole-word memorization, phonological awareness statistically significantly predicted English writing scores, controlling for English vocabulary, ethnicity, sex, and an interaction between English vocabulary and sex. The current study's findings highlight the possibility of developing high literacy skills among bilingual learners with low oral language skills. In addition, the study demonstrates children's development of phonological awareness in the absence of phonological awareness or phonics instruction and supports the theory that both alphabetic (phonological) processes and logographic (whole-word) processes contribute to successful English literacy achievement.     

Efficacy of neurostimulation to treat symptoms of Mal de Debarquement Syndrome. A preliminary study using repetitive transcranial magnetic stimulation

Mal de debarquement syndrome (MdDS) is a rare and poorly understood condition of perceived continual motion. Using a multiple‐case design (n = 13; 8 f; 63.5 ± 12.6 years), this study investigated the efficacy of eight 20‐min sessions, over 4 weeks, of repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral pre‐frontal cortex. Compared to sham, rTMS demonstrated improvement in balance and confidence in daily living activities. rTMS shows promise for the treatment of MdDS. However, larger trials with longer intervention periods are required.