Methodologies for task-fMRI based prognostic biomarkers in response to aphasia treatment.

With the diversity in aphasia coupled with diminished gains at the chronic phase, it is imperative to deliver effective rehabilitation plans. Treatment outcomes have therefore been predicted using lesion-to-symptom mapping, but this method lacks holistic functional information about the language-network. This study, therefore, aims to develop whole-brain task-fMRI multivariate analysis to neurobiologically inspect lesion impacts on the language-network and predict behavioral outcomes in persons with aphasia (PWA) undergoing language therapy. In 14 chronic PWA, semantic fluency task-fMRI and behavioral measures were collected to develop prediction methodologies for post-treatment outcomes. Then, a recently developed imaging-based multivariate method to predict behavior (i.e., LESYMAP) was optimized to intake whole-brain task-fMRI data, and systematically tested for reliability with mass univariate methods. We also accounted for lesion size in both methods. Results showed that both mass univariate and multivariate methods identified unique biomarkers for semantic fluency improvements from baseline to 2-weeks post-treatment. Additionally, both methods demonstrated reliable spatial overlap in task-specific areas including the right middle frontal gyrus when identifying biomarkers of language discourse. Thus whole-brain task-fMRI multivariate analysis has the potential to identify functionally meaningful prognostic biomarkers even for relatively small sample sizes. In sum, our task-fMRI based multivariate approach holistically estimates post-treatment response for both word and sentence production and may serve as a complementary tool to mass univariate analysis in developing brain-behavior relationships for improved personalization of aphasia rehabilitation regimens.

Revealing the Neuroimaging Mechanism of Acupuncture for Poststroke Aphasia: A Systematic Review.

Background: Aphasia is a common symptom in stroke patients, presenting with the impairment of spontaneous speech, repetition, naming, auditory comprehension, reading, and writing function. Multiple rehabilitation methods have been suggested for the recovery of poststroke aphasia, including medication treatment, behavioral therapy, and stimulation approach. Acupuncture has been proven to have a beneficial effect on improving speech functions in repetition, oral speech, reading, comprehension, and writing ability. Neuroimaging technology provides a visualized way to explore cerebral neural activity, which helps reveal the therapeutic effect of acupuncture therapy. In this systematic review, we aim to reveal and summarize the neuroimaging mechanism of acupuncture therapy on poststroke aphasia to provide the foundation for further study. Methods: Seven electronic databases were searched including PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, the Wanfang databases, and the Chinese Scientific Journal Database. After screening the studies according to the inclusion and exclusion criteria, we summarized the neuroimaging mechanism of acupuncture on poststroke aphasia, as well as the utilization of acupuncture therapy and the methodological characteristics. Result: After searching, 885 articles were retrieved. After removing the literature studies, animal studies, and case reports, 16 studies were included in the final analysis. For the acupuncture type, 10 studies used manual acupuncture and 5 studies used electroacupuncture, while body acupuncture (10 studies), scalp acupuncture (7 studies), and tongue acupuncture (8 studies) were applied for poststroke aphasia patients. Based on blood oxygen level-dependent (BOLD) and diffusion tensor imaging (DTI) technologies, 4 neuroimaging analysis methods were used including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), seed-based analysis, and independent component analysis (ICA). Two studies reported the instant acupuncture effect, and 14 studies reported the constant acupuncture's effect on poststroke aphasia patients. 5 studies analyzed the correlation between the neuroimaging outcomes and the clinical language scales. Conclusion: In this systematic review, we found that the mechanism of acupuncture's effect might be associated with the activation and functional connectivity of language-related brain areas, such as brain areas around Broca's area and Wernicke's area in the left inferior temporal gyrus, supramarginal gyrus, middle frontal gyrus, and inferior frontal gyrus. However, these studies were still in the preliminary stage. Multicenter randomized controlled trials (RCT) with large sample sizes were needed to verify current evidence, as well as to explore deeply the neuroimaging mechanisms of acupuncture's effects.

Cerebral perfusion mediated by thalamo-cortical functional connectivity in non-dominant thalamus affects naming ability in aphasia.

Naming is a commonly impaired language domain in various types of aphasia. Emerging evidence supports the cortico-subcortical circuitry subserving naming processing, although neurovascular regulation of the non-dominant thalamic and basal ganglia subregions underlying post-stroke naming difficulty remains unclear. Data from 25 subacute stroke patients and 26 age-, sex-, and education-matched healthy volunteers were analyzed. Region-of-interest-wise functional connectivity (FC) was calculated to measure the strength of cortico-subcortical connections. Cerebral blood flow (CBF) was determined to reflect perfusion levels. Correlation and mediation analyses were performed to identify the relationship between cortico-subcortical connectivity, regional cerebral perfusion, and naming performance. We observed increased right-hemispheric subcortical connectivity in patients. FC between the right posterior superior temporal sulcus (pSTS) and lateral/medial prefrontal thalamus (lPFtha/mPFtha) exhibited significantly negative correlations with total naming score. Trend-level increased CBF in subcortical nuclei, including that in the right lPFtha, and significant negative correlations between naming and regional perfusion of the right lPFtha were observed. The relationship between CBF in the right lPFtha and naming was fully mediated by the lPFtha-pSTS connectivity in the non-dominant hemisphere. Our findings suggest that perfusion changes in the right thalamic subregions affect naming performance through thalamo-cortical circuits in post-stroke aphasia. This study highlights the neurovascular pathophysiology of the non-dominant hemisphere and demonstrates thalamic involvement in naming after stroke.

A domain-general perspective on the role of the basal ganglia in language and music: Benefits of music therapy for the treatment of aphasia.

In addition to cortical lesions, mounting evidence on the links between language and the subcortical regions suggests that subcortical lesions may also lead to the emergence of aphasic symptoms. In this paper, by emphasizing the domain-general function of the basal ganglia in both language and music, we highlight that rhythm processing, the function of temporal prediction, motor programming and execution, is an important shared mechanism underlying the treatment of non-fluent aphasia with music therapy. In support of this, we conduct a literature review on the music therapy treating aphasia. The results show that rhythm processing plays a key role in Melodic Intonation Therapy in the rehabilitation of non-fluent aphasia patients with lesions on the basal ganglia. This paper strengthens the correlation between the basal ganglia lesions and language deficits, and provides support to the direction of taking advantage of rhythm as an important point in music therapy in clinical studies.

Increased Functional Connectivity Within Intrinsic Neural Networks in Chronic Stroke Following Treatment with Red/Near-Infrared Transcranial Photobiomodulation: Case Series with Improved Naming in Aphasia.

Objective: To examine effects of four different transcranial, red/near-infrared (NIR), light-emitting diode (tLED) protocols on naming ability in persons with aphasia (PWA) due to left hemisphere (LH) stroke. This is the first study to report beneficial effects from tLED therapy in chronic stroke, and parallel changes on functional magnetic resonance imaging (fMRI). Materials and methods: Six PWA, 2-18 years poststroke, in whom 18 tLED treatments were applied (3 × /week, 6 weeks) using LED cluster heads: 500 mW, red (633 nm) and NIR (870 nm), 22.48 cm2, 22.2 mW/cm2. Results: After Protocol A with bilateral LED placements, including midline, at scalp vertex over left and right supplementary motor areas (L and R SMAs), picture naming was not improved. P1 underwent pre-/postovert, picture-naming task-fMRI scans; P2 could not. After Protocol A, P1 showed increased activation in LH and right hemisphere, including L and R SMAs. After Protocol B with LEDs only on ipsilesional, LH side, naming ability significantly improved for P1 and P2; the fMRI scans for P1 then showed activation only on the ipsilesional LH side. After Protocol C with LED placements on ipsilesional LH side, plus one midline placement over mesial prefrontal cortex (mPFC) at front hairline, a cortical node of the default mode network (DMN), P3 and P4 had only moderate/poor response, and no increase in functional connectivity on resting-state functional-connectivity MRI. After Protocol D, however, with LED placements on ipsilesional LH side, plus over two midline nodes of DMN, mPFC, and precuneus (high parietal) simultaneously, P5 and P6 each had good response with significant increase in functional connectivity within DMN, p < 0.0005; salience network, p < 0.0005; and central executive network, p < 0.05. Conclusions: NIR photons can affect surface brain cortex areas subjacent to where LEDs are applied on the scalp. Improved naming ability was present with optimal Protocol D. Transcranial photobiomodulation may be an additional noninvasive therapy for stroke.

Cognitive and neural mechanisms underlying the mnemonic effect of songs after stroke.

Sung melody provides a mnemonic cue that can enhance the acquisition of novel verbal material in healthy subjects. Recent evidence suggests that also stroke patients, especially those with mild aphasia, can learn and recall novel narrative stories better when they are presented in sung than spoken format. Extending this finding, the present study explored the cognitive mechanisms underlying this effect by determining whether learning and recall of novel sung vs. spoken stories show a differential pattern of serial position effects (SPEs) and chunking effects in non-aphasic and aphasic stroke patients (N = 31) studied 6 months post-stroke. The structural neural correlates of these effects were also explored using voxel-based morphometry (VBM) and deterministic tractography (DT) analyses of structural MRI data. Non-aphasic patients showed more stable recall with reduced SPEs in the sung than spoken task, which was coupled with greater volume and integrity (indicated by fractional anisotropy, FA) of the left arcuate fasciculus. In contrast, compared to non-aphasic patients, the aphasic patients showed a larger recency effect (better recall of the last vs. middle part of the story) and enhanced chunking (larger units of correctly recalled consecutive items) in the sung than spoken task. In aphasics, the enhanced chunking and better recall on the middle verse in the sung vs. spoken task correlated also with better ability to perceive emotional prosody in speech. Neurally, the sung > spoken recency effect in aphasic patients was coupled with greater grey matter volume in a bilateral network of temporal, frontal, and parietal regions and also greater volume of the right inferior fronto-occipital fasciculus (IFOF). These results provide novel cognitive and neurobiological insight on how a repetitive sung melody can function as a verbal mnemonic aid after stroke.

Recurring Thalamic Symptoms Due to Intracranial Dural Arteriovenous Fistula: Report of Unusual Case and Treatment Outcome.

BACKGROUND: Initial clinical presentation of dural arteriovenous fistula (DAVF) with predominantly thalamic symptoms is rare and has not been reported until now. CASE DESCRIPTION: A young child presenting with complaints of tinnitus and mild right hemiparesis was evaluated with an initial magnetic resonance imaging, which revealed a Borden type 2 DAVF in the right transverse sinus with retrograde venous drainage and cortical venous reflux. Flow-related small aneurysms were also noted in the left basal vein of Rosenthal (BVR). Two days later, his motor power deteriorated and he developed right hemisensory loss and severe thalamic pain. Aphasia was atypical and mimicked the transcortical type. Repeat imaging revealed expanding thrombosed aneurysm of BVR with mass effect and edema on thalamocapsular region. Initial antiedema measures reversed the neurologic deficits; however, they recurred, necessitating an urgent endovascular intervention. Angiogram revealed an extensive high-flow DAVF in the right transverse-sigmoid sinus and torcula with preferential retrograde venous drainage into deep veins and left BVR. He underwent staged embolization of DAVF, resulting in significant obliteration of shunt. Neurologic deficits improved in the postoperative period, and the patient remained clinically asymptomatic at 6 months of follow-up. CONCLUSIONS: DAVF presenting with recurrent predominantly thalamic symptoms is rare. Atypical transcortical aphasia rather than fluent aphasia is an unusual clinical manifestation of thalamic pathology and could result from the involvement of specific thalamic nuclei. Preferential high flow into BVR in the presence of venous anomalies could potentially induce architectural weakness of the venous wall and precipitate aneurysm formation. Embolization of the DAVF can potentially reverse this unusual neurologic condition.

Pure word deafness following left temporal damage: Behavioral and neuroanatomical evidence from a new case.

Pure Word Deafness (PWD) is a rare disorder, characterized by selective loss of speech input processing. Its most common cause is temporal damage to the primary auditory cortex of both hemispheres, but it has been reported also following unilateral lesions. In unilateral cases, PWD has been attributed to the disconnection of Wernicke's area from both right and left primary auditory cortex. Here we report behavioral and neuroimaging evidence from a new case of left unilateral PWD with both cortical and white matter damage due to a relatively small stroke lesion in the left temporal gyrus. Selective impairment in auditory language processing was accompanied by intact processing of nonspeech sounds and normal speech, reading and writing. Performance on dichotic listening was characterized by a reversal of the right-ear advantage typically observed in healthy subjects. Cortical thickness and gyral volume were severely reduced in the left superior temporal gyrus (STG), although abnormalities were not uniformly distributed and residual intact cortical areas were detected, for example in the medial portion of the Heschl's gyrus. Diffusion tractography documented partial damage to the acoustic radiations (AR), callosal temporal connections and intralobar tracts dedicated to single words comprehension. Behavioral and neuroimaging results in this case are difficult to integrate in a pure cortical or disconnection framework, as damage to primary auditory cortex in the left STG was only partial and Wernicke's area was not completely isolated from left or right-hemisphere input. On the basis of our findings we suggest that in this case of PWD, concurrent partial topological (cortical) and disconnection mechanisms have contributed to a selective impairment of speech sounds. The discrepancy between speech and non-speech sounds suggests selective damage to a language-specific left lateralized network involved in phoneme processing.

Lesion localization of speech comprehension deficits in chronic aphasia.

OBJECTIVE: Voxel-based lesion-symptom mapping (VLSM) was used to localize impairments specific to multiword (phrase and sentence) spoken language comprehension. METHODS: Participants were 51 right-handed patients with chronic left hemisphere stroke. They performed an auditory description naming (ADN) task requiring comprehension of a verbal description, an auditory sentence comprehension (ASC) task, and a picture naming (PN) task. Lesions were mapped using high-resolution MRI. VLSM analyses identified the lesion correlates of ADN and ASC impairment, first with no control measures, then adding PN impairment as a covariate to control for cognitive and language processes not specific to spoken language. RESULTS: ADN and ASC deficits were associated with lesions in a distributed frontal-temporal parietal language network. When PN impairment was included as a covariate, both ADN and ASC deficits were specifically correlated with damage localized to the mid-to-posterior portion of the middle temporal gyrus (MTG). CONCLUSIONS: Damage to the mid-to-posterior MTG is associated with an inability to integrate multiword utterances during comprehension of spoken language. Impairment of this integration process likely underlies the speech comprehension deficits characteristic of Wernicke aphasia.

Aphasia and unilateral spatial neglect due to acute thalamic hemorrhage: clinical correlations and outcomes.

Thalamic hemorrhages are associated with a variety of cognitive dysfunctions, and it is well known that such cognitive changes constitute a limiting factor of recovery of the activities of daily living (ADL). The relationship between cognitive dysfunction and hematomas is unclear. In this study, we investigated the relationship between aphasia/neglect and hematoma volume, hematoma type, and the ADL. One hundred fifteen patients with thalamic hemorrhage (70 men and 45 women) were studied. Their mean age was 68.9 ± 10.3 years, and patients with both left and right lesions were included. We calculated hematoma volume and examined the presence or absence of aphasia/neglect and the relationships between these dysfunctions and hematoma volume, hematoma type, and the ADL. Fifty-nine patients were found to have aphasia and 35 were found to have neglect. Although there was no relationship between hematoma type and cognitive dysfunction, hematoma volume showed a correlation with the severity of cognitive dysfunction. The ADL score and ratio of patient discharge for patients with aphasia/neglect were lower than those for patients without aphasia/neglect. We observed a correlation between the hematoma volume in thalamic hemorrhage and cognitive dysfunction. Aphasia/neglect is found frequently in patients with acute thalamic hemorrhage and may influence the ADL.

An fMRI study showing the effect of acupuncture in chronic stage stroke patients with aphasia.

Acupuncture is used as a treatment in stroke patients with aphasia, yet the underlying neural mechanisms are unknown. This study aims to examine the relationship between changes in language function and brain activation using functional magnetic resonance imaging in chronic stroke patients with aphasia who underwent an 8-week acupuncture protocol. Seven chronic stroke patients were identified from a stroke database of a regional acute hospital in Hong Kong between January and July 2007. Patients were treated three times a week over a period of 8 weeks. Four acupoints were stimulated on the weak side of the patient's body. No other rehabilitation was given during the study period. Changes in language function were measured by aphasia quotient (AQ) of Cantonese Aphasia Battery (CAB). Functional magnetic resonance imaging blood oxygen level dependent signals were used to demonstrate the correlation between changes in AQ and brain activation after treatment. The patients were divided into well-recovered and poorly- recovered groups based on their CAB scores at entry. The well-recovered group showed significant improvement in CAB scores after receiving acupuncture treatment. A significant correlation between changes in AQ and blood oxygen level dependent activation in the lesioned Wernicke's speech area was found. These preliminary results suggest that acupuncture may be beneficial to language recovery in chronic stroke patients.

Dural arteriovenous fistulas with aggressive course: clinical and angiographic correlations in two patients.

Cranial dural arteriovenous fistulas (DAVFs) usually present with non-aggressive symptoms. We here report two patients who presented a peculiar clinical picture related to DAVFs, with focal neurological signs and haemorrhagic (case 1) or ischaemic lesions (case 2) respectively. The clinical and angiographic findings and putative pathophysiological mechanisms are discussed.

Akinetic mutism and mixed transcortical aphasia following left thalamo-mesencephalic infarction.

A 54-year-old man developed somnolent akinetic mutism and acute mixed transcortical aphasia following a left thalamo-mesencephalic infarction. He also exhibited behavioural changes, namely apathy, slowness, lack of spontaneity, disinhibition, perseveration, gait apraxia and incontinence consistent with frontal lobe dysfunction. Presumably the akinetic mutism and language dysfunction were due to the thalamic stroke. All the manifestations could be related to interruption of the frontal-subcortical circuitry.

Recovery from nonfluent aphasia after melodic intonation therapy: a PET study.

We examined mechanisms of recovery from aphasia in seven nonfluent aphasic patients, who were successfully treated with melodic intonation therapy (MIT) after a lengthy absence of spontaneous recovery. We measured changes in relative cerebral blood flow (CBF) with positron emission tomography (PET) during hearing and repetition of simple words, and during repetition of MIT-loaded words. Without MIT, language tasks abnormally activated right hemisphere regions, homotopic to those activated in the normal subject, and deactivated left hemisphere language zones. In contrast, repeating words with MIT reactivated Broca's area and the left prefrontal cortex, while deactivating the counterpart of Wernicke's area in the right hemisphere. The recovery process induced by MIT in these patients probably coincides with this reactivation of left prefrontal structures. In contrast, the right hemisphere regions abnormally activated during simple language tasks seem to be associated with the initial persistence of the aphasia. This study supports the idea that abnormal activation patterns in the lesioned brain are not necessarily related to the recovery process.

Language disturbances from paramedian thalamic infarcts: a CT method for lesion location.

The authors describe the case of three patients suffering from language disorder secondary to mesencephalo-thalamic infarcts. One of them showed the clinical features of transcortical motor aphasia, while the other two presented the typical pattern of the so-called "thalamic aphasia". The CT-stereotaxic method for lesion localization disclosed that the dorso-medial was the mostly involved thalamic nucleus in each case. Since this nucleus is connected both with Broca's and Wernike's areas, the authors suggest that the more or less extensive involvement of the fibres connecting these structures may be responsible for the different aphasic features presented in these cases.

Subcortical structures in aphasia. An analysis based on (F-18)-fluorodeoxyglucose, positron emission tomography, and computed tomography.

Subcortical structural damage that includes the anterior and posterior internal capsule, caudate, thalamus, lenticular nuclei, and insula has been shown to cause aphasias. A critical question that has not been resolved is whether the role of these structures on behavior is a direct one or whether it is indirect through the cortex. We have used pathway analysis to evaluate computed tomography, glucose metabolic, and language data from 47 aphasic patients to answer this question. For fluency (from the Western Aphasia Battery), subcortical structural damage had direct and indirect (through frontal lobe) effects on the behavior. For a comprehension task (sequential commands), subcortical damage had no direct effect and only a slight indirect effect through the temporal lobe. Thus, both direct and indirect effects of subcortical damage can be demonstrated for specific behavioral measures.

Aphasia with predominantly subcortical lesion sites: description of three capsular/putaminal aphasia syndromes.

Nine cases of subcortical aphasia with capsular/putaminal (C/P) lesion sites demonstrated on computed tomographic (CT) scans were studied. Eight cases were occlusive-vascular in etiology and one was hemorrhagic. Three subcortical aphasia syndromes and three C/P lesion site patterns were observed. Patients with C/P lesion sites with anterior-superior white-matter lesion extension had good comprehension, grammatical, but slow, dysarthric speech, and lasting right hemiplegia. Patients with C/P lesion sites with posterior white-matter lesion extension across the auditory radiations in the temporal isthmus had poor comprehension, fluent Wernicke-type speech, and lasting right hemiplegia. Patients with C/P lesion sites with both anterior-superior and posterior extension were globally aphasic and had lasting right hemiplegia. Although these cases of C/P subcortical aphasia shared certain well-known features of Broca's and Wernicke's cortical aphasia syndromes, they did not completely resemble cases of either Broca's, Wernicke's, global, or thalamic aphasia in neurologic findings, CT scan lesion sites, or language behavior. Further study of the subcortical aphasias associated with these C/P lesion sites seems to be warranted.

Aphasia with nonhemorrhagic lesions in the basal ganglia and internal capsule.

Atypical aphasia syndromes were associated with circumscribed nonhemorrhagic infarctions of the anterior limb of the internal capsule and of the striatum, in the dominant hemisphere. None of the several cases could be classified in terms of the classic cortical aphasia syndromes, nor did they correspond to the description of aphasia produced by hemorrhage in the thalamus or putamen. Control subjects without aphasia had lesions in the same structures of the nondominant hemisphere, or they had comparably circumscribed damage, which was located lateral or caudal to the previously indicated locus. The findings raise the question of participation of the dominant striatum, and of the connectional systems that course in the anterior limb of the internal capsule, in language processing.