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.     

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.     

The contribution of the right cerebral hemisphere to the recovery from aphasia: a single longitudinal case study

We examined the role of the right cerebral hemisphere in the recovery from aphasia of HJ, a 50-year-old right-handed and unilingual man who suffered from severe aphasia caused by an extensive left hemisphere (LH) lesion. He was followed-up over 10 months at 4-month intervals, with a lateralized lexical decision task (LDT), an attentional task, and a language battery. Testing started when HJ was 2 months poststroke. In the LDT, words were presented to central vision or lateralized to the left or right visual hemifield. At each test period, we examined the effect of the degree of imageability (high vs. low), and the grammatical class (noun vs. verb) of the targets on HJ's response times and error rates, with left visual field, right visual field, and central vision presentations. The results of the experiment showed that the pattern obtained with the LDT could not be accounted for by fluctuations in attention. There was an interaction of grammatical class with degree of imageability with left visual field displays only. The right hemisphere (RH) was faster with high-imageability words than with low-imageability words, regardless of their grammatical class. There was also an overall RH advantage on response times at 2 and 6 months after onset. This RH predominance coincided with a major recovery of language comprehension and the observation of semantic paralexias, while no major change in language expression was observed at that point. Ten months after onset, the pattern of lateralization changed, and response times for the LDT with either presentation site were equivalent. This LH improvement coincided with some recovery of language expression at the single-word level. The results of this study suggest that, in cases of severe aphasia caused by extensive LH lesions, the RH may play an important role in the recovery process. Furthermore, these results show that the contribution of the two cerebral hemispheres to recovery may vary overtime and affect specific aspects of language.     

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.     

Does long term use of piracetam improve speech disturbances due to ischemic cerebrovascular diseases?

Aphasia causes significant disability and handicap among stroke survivors. Language therapy is recommended for aphasic patients, but not always available. Piracetam, an old drug with novel properties, has been shown to have mild beneficial effects on post-stroke aphasia. In the current study, we investigated the effects of 6 months treatment with piracetam on aphasia following stroke. Thirty patients with first-ever ischemic strokes and related aphasia were enrolled in the study. The scores for the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), and Gülhane Aphasia Test were recorded. The patients were scheduled randomly to receive either 4.8 g piracetam daily or placebo treatment for 6 months. At the end of 24 weeks, clinical assessments and aphasia tests were repeated. The level of improvement in the clinical parameters and aphasia scores was compared between the two groups. All patients had large lesions and severe aphasia. No significant difference was observed between the piracetam and placebo groups regarding the improvements in the NIHSS, BI and mRS scores at the end of the treatment. The improvements observed in spontaneous speech, reading fluency, auditory comprehension, reading comprehension, repetition, and naming were not significantly different in the piracetam and placebo groups, the difference reached significance only for auditory comprehension in favor of piracetam at the end of the treatment. Piracetam is well-tolerated in patients with post-stroke aphasia. Piracetam taken orally in a daily dose of 4.8 g for 6 months has no clear beneficial effect on post-stroke language disorders.     

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.     

Transcortical sensory aphasia in a right-handed patient following watershed infarcts in the right cerebral hemisphere: a 15-month evaluation of another case of crossed aphasia.

Well-documented cases of crossed (transcortical sensory) aphasia, especially those with longitudinal evaluation, are rare. We report a case of crossed transcortical sensory aphasia following watershed infarcts in the right hemisphere, from the moment of the accident until 15 months afterward. The aphasia type, and the course of recovery, is a "mirror" representation of that seen in cases of uncrossed aphasia. Unfortunately, the data do not permit strong conclusions regarding the lateralization of language in association with praxis and visuospatial abilities. This underlines the need for more well-documented (case) studies to come to a better understanding of the mechanisms through which lateralization occurs.     

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.     

Bilateral language: Is the left hemisphere still dominant?

A 13-year-old left-handed boy with a left fronto-parietal vascular malformation evidenced bilateral symmetrical language representation at intracarotid amytal testing. Surgical resection of the parietal motor and frontal premotor area (sparing classical perisylvian language regions) for seizure control resulted in an acute aphasia. Language deficits were still apparent 3 months and to a lesser degree 1 year after surgery. This suggests that when language is bilateral and symmetrical, the left hemisphere may still be dominant or both hemispheres may be necessary to sustain full language competence. Explanations for atypical language localization within the left hemisphere are also discussed.     

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.     

Language and syntactic impairment following stroke in late bilingual aphasics

Purpose

Bilingual aphasia generally affects both languages. However, the age of acquisition of the second language (L2) seems to play a role in the anatomo-functional correlation of the syntactical/grammatical processes, thus potentially influencing the L2 syntactic impairment following a stroke. The present study aims to analyze the influence of late age of acquisition of the L2 on syntactic impairment in bilingual aphasic patients.

Methods

Twelve late bilingual participants (speaking French as L2 and either English, German, Italian or Spanish as L1) with stroke-induced aphasia participated in the study. The MAST or BAT aphasia batteries were used to evaluate overall aphasia score. An auditory syntactic judgement task was developed and used to test participants syntactic performance.

Results

The overall aphasia scores did not differ between L1 and L2. In a multiple case analysis, only one patient had lower scores in L2. However, four patients presented significantly lower performances in syntactic processing in the late L2 than in their native language (L1). In these four patients the infarct was localized, either exclusively or at least partially, in the pre-rolandic region.

Conclusion

This pilot study suggests that, in late bilingual aphasics, syntactic judgment abilities may be more severely impaired in L2, and that this syntactic deficit is most likely to occur following anterior lesions.     

Aphasia in left-handers. Comparison of aphasia profiles and language recovery in non-right-handed and matched right-handed patients.

The present retrospective analysis reports two studies. In Study 1, clinical aspects of aphasia are compared in right-handed (RH) and non-right-handed (NRH) patients; in Study 2, recovery from aphasia is compared in RH and NRH aphasic patients with a minimum of 5 months of daily language rehabilitation. From a continuous series of 1200 brain-damaged subjects, 24 NRH patients with a vascular lesion documented by computerized tomography were selected. In 19 cases the lesion was in the left hemisphere and in 5 cases in the right hemisphere. For 14 NRH patients, a RH subject with similar lesion, matched for age, education, length of illness, etiology (ischemic vs. hemorrhagic), and, when possible, sex was found. Presence and type of aphasia were compared in the two patients of the same pair and were found similar except for Pair 14; the RH subject had global aphasia and the NRH had conduction-like aphasia. Fifteen NRH patients were rehabilitated and reexamined at least 5 months after the first examination. Recovery of the 12 patients with a left-hemisphere lesion was compared with recovery of a group of RH subjects and no significant differences were found. Recovery of the three patients with right-hemisphere lesions is described. It is concluded that differences in type of aphasia and recovery between RHs and NRHs have been overemphasized in the past and must be reconsidered.     

Crossed Wernicke's aphasia: a case report

Crossed aphasia is a phenomenon in which an individual sustains a lesion in the right hemisphere (typically non-language dominant), but who exhibits an aphasic syndrome. The authors present a case study of an individual with crossed aphasia (CA) in an attempt to provide anecdotal information for four questions posed by : (a). Is CA a reversal of the normal cerebral hemisphere pattern of language function? (b). Does the presence of aphasia following a right cerebral hemisphere lesion indicate that typical right hemisphere functions (e.g., visual perception) are intact? (c). How may the aphasia's presentation differ from typical left hemisphere aphasias? And (d). is the pattern of improvement following CA similar to that of typical left hemisphere aphasias? We longitudinally examined the communicative-cognitive performance of an adult man with crossed aphasia of the Wernicke's type following a cerebrovascular accident. A 21-week follow-up evaluation indicated improvements in his language functioning from our initial evaluation, but he continued to exhibit a classic, moderately severe Wernicke's aphasia.     

The usefulness of the Western Aphasia Battery for differential diagnosis of Alzheimer dementia and focal stroke syndromes: preliminary evidence.

We assessed the usefulness of the Western Aphasia Battery for distinguishing the language disturbances caused by Alzheimer dementia (AD) from those caused by stroke. Using discriminant function analyses, the multiple variable "aphasia quotient--reading quotient--writing quotient" classified 29 (72.5%) of the 40 patients correctly. These 29 patients included 8 of 10 patients with left hemisphere infarction and fluent aphasia; 6 of 10 with AD; 5 of 10 patients with right hemisphere infarction; and all 10 of the neurologically normal control subjects. The patients with AD and those with right hemisphere stroke were the most difficult to classify using the aphasia battery.     

Anatomical correlates of normal and impaired language in a set of dizygotic twins

This report presents findings for a set of dizygotic twins at age 4 years 9 months. The male was diagnosed as specifically language impaired. For both children, the left-right perisylvian configuration was atypical. Only the male's configuration was symmetrical, a finding in line with autopsy data reported for subjects with "developmental dyslexia" who also may have had a form of language impairment. In addition, the male had an atypical (L greater than R) configuration of the cerebral hemispheres, a finding not seen in his twin, or in a series of volunteers without a history of developmental language impairment. The in utero effects of gonadal hormones that may account for these findings are discussed.     

Hemiplegic writing in severe aphasia

Three patients with severe aphasia and right hemiplegia are described who could write to dictation with the right arm using a limb prosthesis though agraphic with the "intact" left hand. The phenomenon of "hemiplegic writing" is explained as an access to submerged or preprocessing levels in language and action structure, through the use of older proximal motor systems. This interpretation has implications for our understanding of language and brain function, as well as for approaches to the treatment of patients with severe language disorders.     

Phonological and articulatory impairment in Alzheimer's disease: a case series

We demonstrate that phonological and articulatory impairments may occur at presentation or early in the course of Alzheimer's disease, contrary to claims that these aspects of language production are relatively preserved until the final stages of this disease. Six patients with pathologically confirmed Alzheimer's disease (AD) and four patients with clinically diagnosed dementia of the Alzheimer's type (DAT) presented with one of five different clinical profiles: nonfluent progressive aphasia, mixed progressive aphasia, progressive aphasia diagnosed as DAT from neuropsychological assessment, initial amnestic syndrome with prominent phonological errors, and biparietal syndrome. Analysis of their conversational speech, single-word production, and performance of highly familiar series speech tasks such as counting revealed false start errors, phonological paraphasias, and/or articulatory difficulty. Neuropathological changes were located in left perisylvian regions consistent with speech and language impairment but atypical for Alzheimer's disease.     

Overt naming fMRI pre- and post-TMS: Two nonfluent aphasia patients, with and without improved naming post-TMS

Two chronic, nonfluent aphasia patients participated in overt naming fMRI scans, pre- and post-a series of repetitive transcranial magnetic stimulation (rTMS) treatments as part of a TMS study to improve naming. Each patient received 10, 1-Hz rTMS treatments to suppress a part of R pars triangularis. P1 was a ‘good responder’ with improved naming and phrase length; P2 was a ‘poor responder’ without improved naming.Pre-TMS (10 years poststroke), P1 had significant activation in R and L sensorimotor cortex, R IFG, and in both L and R SMA during overt naming fMRI (28% pictures named). At 3 mo. post-TMS (42% named), P1 showed continued activation in R and L sensorimotor cortex, R IFG, and in R and L SMA. At 16 mo. post-TMS (58% named), he also showed significant activation in R and L sensorimotor cortex mouth and R IFG. He now showed a significant increase in activation in the L SMA compared to pre-TMS and at 3 mo. post-TMS (p < .02; p < .05, respectively). At 16 mo. there was also greater activation in L than R SMA (p < .08). At 46 mo. post-TMS (42% named), this new LH pattern of activation continued. He improved on the Boston Naming Test from 11 pictures named pre-TMS, to scores ranging from 14 to 18 pictures, post-TMS (2–43 mo. post-TMS). His longest phrase length (Cookie Theft picture) improved from three words pre-TMS, to 5–6 words post-TMS.Pre-TMS (1.5 years poststroke), P2 had significant activation in R IFG (3% pictures named). At 3 and 6 mo. post-TMS, there was no longer significant activation in R IFG, but significant activation was present in R sensorimotor cortex. On all three fMRI scans, P2 had significant activation in both the L and R SMA. There was no new, lasting perilesional LH activation across sessions for this patient. Over time, there was little or no change in his activation. His naming remained only at 1–2 pictures during all three fMRI scans. His BNT score and longest phrase length remained at one word, post-TMS.Lesion site may play a role in each patient’s fMRI activation pattern and response to TMS treatment. P2, the poor responder, had an atypical frontal lesion in the L motor and premotor cortex that extended high, near brain vertex, with deep white matter lesion near L SMA. P2 also had frontal lesion in the posterior middle frontal gyrus, an area important for naming (Duffau et al., 2003); P1 did not. Additionally, P2 had lesion inferior and posterior to Wernicke’s area, in parts of BA 21 and 37, whereas P1 did not.The fMRI data of our patient who had good response following TMS support the notion that restoration of the LH language network is linked in part, to better recovery of naming and phrase length in nonfluent aphasia.     

Semantic dementia and persisting Wernicke's aphasia: linguistic and anatomical profiles

Few studies have directly compared the clinical and anatomical characteristics of patients with progressive aphasia to those of patients with aphasia caused by stroke. In the current study we examined fluent forms of aphasia in these two groups, specifically semantic dementia (SD) and persisting Wernicke’s aphasia (WA) due to stroke. We compared 10 patients with SD to 10 age- and education-matched patients with WA in three language domains: language comprehension (single words and sentences), spontaneous speech and visual semantics. Neuroanatomical involvement was analyzed using disease-specific image analysis techniques: voxel-based morphometry (VBM) for patients with SD and overlays of lesion digitized lesion reconstructions in patients with WA. Patients with SD and WA were both impaired on tasks that involved visual semantics, but patients with SD were less impaired in spontaneous speech and sentence comprehension. The anatomical findings showed that different regions were most affected in the two disorders: the left anterior temporal lobe in SD and the left posterior middle temporal gyrus in chronic WA. This study highlights that the two syndromes classically associated with language comprehension deficits in aphasia due to stroke and neurodegenerative disease are clinically distinct, most likely due to distinct distributions of damage in the temporal lobe.