Language Recovery after Brain Injury: A Structural Network Control Theory Study.

Aphasia recovery after stroke depends on the condition of the remaining, extralesional brain network. Network control theory (NCT) provides a unique, quantitative approach to assess the interaction between brain networks. In this longitudinal, large-scale, whole-brain connectome study, we evaluated whether controllability measures of language-related regions are associated with treated aphasia recovery. Using probabilistic tractography and controlling for the effects of structural lesions, we reconstructed whole-brain diffusion tensor imaging (DTI) connectomes from 68 individuals (20 female, 48 male) with chronic poststroke aphasia who completed a three-week language therapy. Applying principles of NCT, we computed regional (1) average and (2) modal controllability, which decode the ability of a region to (1) spread control input through the brain network and (2) to facilitate brain state transitions. We tested the relationship between pretreatment controllability measures of 20 language-related left hemisphere regions and improvements in naming six months after language therapy using multiple linear regressions and a parsimonious elastic net regression model with cross-validation. Regional controllability of the inferior frontal gyrus (IFG) pars opercularis, pars orbitalis, and the anterior insula were associated with treatment outcomes independently of baseline aphasia severity, lesion volume, age, education, and network size. Modal controllability of the IFG pars opercularis was the strongest predictor of treated aphasia recovery with cross-validation and outperformed traditional graph theory, lesion load, and demographic measures. Regional NCT measures can reflect the status of the residual language network and its interaction with the remaining brain network, being able to predict language recovery after aphasia treatment.SIGNIFICANCE STATEMENT Predicting and understanding language recovery after brain injury remains a challenging, albeit a fundamental aspect of human neurology and neuroscience. In this study, we applied network control theory (NCT) to fully harness the concept of brain networks as dynamic systems and to evaluate their interaction. We studied 68 stroke survivors with aphasia who underwent imaging and longitudinal behavioral assessments coupled with language therapy. We found that the controllability of the inferior frontal regional network significantly predicted recovery in language production six months after treatment. Importantly, controllability outperformed traditional demographic, lesion, and graph-theoretical measures. Our findings shed light on the neurobiological basis of human language and can be translated into personalized rehabilitation approaches.

TheraBracelet Stimulation During Task-Practice Therapy to Improve Upper Extremity Function After Stroke: A Pilot Randomized Controlled Study.

BACKGROUND: Peripheral sensory stimulation has been used in conjunction with upper extremity movement therapy to increase therapy-induced motor gains in patients with stroke. The limitation is that existing sensory stimulation methods typically interfere with natural hand tasks and thus are administered prior to therapy, requiring patients' time commitment. To address this limitation, we developed TheraBracelet. This novel stimulation method provides subthreshold (ie, imperceptible) vibratory stimulation to the wrist and can be used during hand tasks/therapy without interfering with natural hand tasks. OBJECTIVE: The objective was to determine the feasibility of using TheraBracelet during therapy to augment motor recovery after stroke. DESIGN: The design was a triple-blinded pilot randomized controlled trial. METHODS: Twelve chronic stroke survivors were assigned to the treatment or control group. All participants completed 2-hour task practice therapy sessions thrice weekly for 2 weeks. Both groups wore a small vibrator on the paretic wrist, which was turned on to provide TheraBracelet stimulation for the treatment group and turned off for the control group to provide sham stimulation. Outcome measures (Box and Block Test [BBT] and Wolf Motor Function Test [WMFT]) were obtained at baseline, 6 days after therapy, and at follow-up 19 days after therapy. RESULTS: The intervention was feasible with no adverse events. The treatment group significantly improved their BBT scores after therapy and at follow-up compared with baseline, whereas the control group did not. For WMFT, the group × time interaction was short of achieving significance. Large effect sizes were obtained (BBT d = 1.43, WMFT d = 0.87). No indication of desensitization to TheraBracelet stimulation was observed. LIMITATIONS: The limitation was a small sample size. CONCLUSIONS: TheraBracelet could be a promising therapy adjuvant for upper extremity recovery after stroke.

Temporal lobe networks supporting the comprehension of spoken words.

Auditory word comprehension is a cognitive process that involves the transformation of auditory signals into abstract concepts. Traditional lesion-based studies of stroke survivors with aphasia have suggested that neocortical regions adjacent to auditory cortex are primarily responsible for word comprehension. However, recent primary progressive aphasia and normal neurophysiological studies have challenged this concept, suggesting that the left temporal pole is crucial for word comprehension. Due to its vasculature, the temporal pole is not commonly completely lesioned in stroke survivors and this heterogeneity may have prevented its identification in lesion-based studies of auditory comprehension. We aimed to resolve this controversy using a combined voxel-based-and structural connectome-lesion symptom mapping approach, since cortical dysfunction after stroke can arise from cortical damage or from white matter disconnection. Magnetic resonance imaging (T1-weighted and diffusion tensor imaging-based structural connectome), auditory word comprehension and object recognition tests were obtained from 67 chronic left hemisphere stroke survivors. We observed that damage to the inferior temporal gyrus, to the fusiform gyrus and to a white matter network including the left posterior temporal region and its connections to the middle temporal gyrus, inferior temporal gyrus, and cingulate cortex, was associated with word comprehension difficulties after factoring out object recognition. These results suggest that the posterior lateral and inferior temporal regions are crucial for word comprehension, serving as a hub to integrate auditory and conceptual processing. Early processing linking auditory words to concepts is situated in posterior lateral temporal regions, whereas additional and deeper levels of semantic processing likely require more anterior temporal regions.10.1093/brain/awx169_video1awx169media15555638084001.

Speech entrainment enables patients with Broca's aphasia to produce fluent speech.

A distinguishing feature of Broca's aphasia is non-fluent halting speech typically involving one to three words per utterance. Yet, despite such profound impairments, some patients can mimic audio-visual speech stimuli enabling them to produce fluent speech in real time. We call this effect 'speech entrainment' and reveal its neural mechanism as well as explore its usefulness as a treatment for speech production in Broca's aphasia. In Experiment 1, 13 patients with Broca's aphasia were tested in three conditions: (i) speech entrainment with audio-visual feedback where they attempted to mimic a speaker whose mouth was seen on an iPod screen; (ii) speech entrainment with audio-only feedback where patients mimicked heard speech; and (iii) spontaneous speech where patients spoke freely about assigned topics. The patients produced a greater variety of words using audio-visual feedback compared with audio-only feedback and spontaneous speech. No difference was found between audio-only feedback and spontaneous speech. In Experiment 2, 10 of the 13 patients included in Experiment 1 and 20 control subjects underwent functional magnetic resonance imaging to determine the neural mechanism that supports speech entrainment. Group results with patients and controls revealed greater bilateral cortical activation for speech produced during speech entrainment compared with spontaneous speech at the junction of the anterior insula and Brodmann area 47, in Brodmann area 37, and unilaterally in the left middle temporal gyrus and the dorsal portion of Broca's area. Probabilistic white matter tracts constructed for these regions in the normal subjects revealed a structural network connected via the corpus callosum and ventral fibres through the extreme capsule. Unilateral areas were connected via the arcuate fasciculus. In Experiment 3, all patients included in Experiment 1 participated in a 6-week treatment phase using speech entrainment to improve speech production. Behavioural and functional magnetic resonance imaging data were collected before and after the treatment phase. Patients were able to produce a greater variety of words with and without speech entrainment at 1 and 6 weeks after training. Treatment-related decrease in cortical activation associated with speech entrainment was found in areas of the left posterior-inferior parietal lobe. We conclude that speech entrainment allows patients with Broca's aphasia to double their speech output compared with spontaneous speech. Neuroimaging results suggest that speech entrainment allows patients to produce fluent speech by providing an external gating mechanism that yokes a ventral language network that encodes conceptual aspects of speech. Preliminary results suggest that training with speech entrainment improves speech production in Broca's aphasia providing a potential therapeutic method for a disorder that has been shown to be particularly resistant to treatment.

How common is brain atrophy in patients with medial temporal lobe epilepsy?

PURPOSE: It is unclear whether extrahippocampal brain damage in patients with medial temporal lobe epilepsy (MTLE) is a homogeneous phenomenon, as most data relates to the average volume reduction in groups of patients. This study aimed to evaluate where and how much atrophy is to be expected in an individual patient with MTLE. METHODS: High-resolution T(1) magnetic resonance imaging (MRI) was obtained from 23 consecutive patients with unilateral MTLE and from a matched control group. Parametric tests of voxel-based gray matter volume evaluated mean regional atrophy in MTLE compared with controls. Gray matter images were then submitted to a voxel by voxel calculation of the fitted receiver operating characteristic (ROC) curve area, plotting the sensitivity versus 1-specificity for a binary classifier (MTLE vs. controls). The area under the curve (AUC) was calculated for each voxel and a resulting three-dimensional map of gray matter voxel-wise AUCs was obtained. RESULTS: On average, patients with MTLE showed atrophy in the ipsilateral hippocampus and on a limbic network. Elevated AUC was demonstrated in the ipsilateral hippocampus and medial temporal lobe, the ipsilateral thalamus and occipitotemporal cortex, the ipsilateral cerebellum, the cingulate, the contralateral insula, and the occipitoparietal and dorsolateral prefrontal cortex. CONCLUSION: This study suggests that the medial temporal lobe, occipitotemporal areas, the cerebellum, the cingulate cortex, the ipsilateral insula, and thalamus are more likely to be atrophied in randomly selected patients with MTLE. Structures such as the orbitofrontal cortex, the contralateral medial temporal areas and insula, the putamen, and the caudate may be atrophied, but not as consistently.

Extrahippocampal gray matter loss and hippocampal deafferentation in patients with temporal lobe epilepsy.

PURPOSE: Medial temporal epilepsy (MTLE) is associated with extrahippocampal brain atrophy. The mechanisms underlying brain damage in MTLE are unknown. Seizures may lead to neuronal damage, but another possible explanation is deafferentation from loss of hippocampal connections. This study aimed to investigate the relationship between hippocampal deafferentation and brain atrophy in MTLE. METHODS: Three different MRI studies were performed involving 23 patients with unilateral MTLE (8 left and 15 right) and 34 healthy controls: (1) voxel-based morphometry (VBM), (2) diffusion tensor imaging (DTI) and (3) probabilistic tractography (PT). VBM was employed to define differences in regional gray matter volume (GMV) between controls and patients. Voxel-wise analyses of DTI evaluated differences in fractional anisotropy (FA), mean diffusivity (MD) and hippocampal PT. Z-scores were computed for regions-of-interest (ROI) GMV and peri-hippocampal FA and MD (to quantify hippocampal fiber integrity). The relationship between hippocampal deafferentation and regional GMV was investigated through the association between ROI Z scores and hippocampal fiber integrity. RESULTS: Patients with MTLE exhibited a significant reduction in GMV and FA in perihippocampal and limbic areas. There was a decrease in hippocampal PT in patients with MTLE in limbic areas. A significant relationship between loss of hippocampal connections and regional GMV atrophy was found involving the putamen, pallidum, middle and inferior temporal areas, amygdala and ceberellar hemisphere. DISCUSSION: There is a relationship between hippocampal disconnection and regional brain atrophy in MTLE. These results indicate that hippocampal deafferentation plays a contributory role in extrahippocampal brain damage in MTLE.

Spatial attention evokes similar activation patterns for visual and auditory stimuli.

Neuroimaging studies suggest that a fronto-parietal network is activated when we expect visual information to appear at a specific spatial location. Here we examined whether a similar network is involved for auditory stimuli. We used sparse fMRI to infer brain activation while participants performed analogous visual and auditory tasks. On some trials, participants were asked to discriminate the elevation of a peripheral target. On other trials, participants made a nonspatial judgment. We contrasted trials where the participants expected a peripheral spatial target to those where they were cued to expect a central target. Crucially, our statistical analyses were based on trials where stimuli were anticipated but not presented, allowing us to directly infer perceptual orienting independent of perceptual processing. This is the first neuroimaging study to use an orthogonal-cuing paradigm (with cues predicting azimuth and responses involving elevation discrimination). This aspect of our paradigm is important, as behavioral cueing effects in audition are classically only observed when participants are asked to make spatial judgments. We observed similar fronto-parietal activation for both vision and audition. In a second experiment that controlled for stimulus properties and task difficulty, participants made spatial and temporal discriminations about musical instruments. We found that the pattern of brain activation for spatial selection of auditory stimuli was remarkably similar to what we found in our first experiment. Collectively, these results suggest that the neural mechanisms supporting spatial attention are largely similar across both visual and auditory modalities.

Can exercise shape your brain? Cortical differences associated with judo practice.

Experimental animal studies have shown that physical exercise, associated with planning and execution of complex movements, are related to changes in brain structure. In humans, changes in cortical tissue density in relation to physical activity are yet to be fully determined and quantified. We investigated differences on gray matter volume in judo players by using voxel-based morphometry. Comparison between a group of eight internationally competitive judo players and a group of 18 healthy controls showed a significantly higher gray matter tissue density in brain areas of judo players.

Disrupted thalamic prefrontal pathways in patients with idiopathic dystonia.

There are quantifiable abnormalities in water diffusion properties of the white matter in thalamic and prefrontal areas in patients with idiopathic dystonia (ID). However, it is unclear which pathways are disrupted in these patients. Using probabilistic tractography of high resolution DTI, we reconstructed thalamic prefrontal pathways in seven patients with ID and seven matched controls. Resulting fibers were registered onto the stereotaxic space and submitted to a voxel-wise statistical analysis comparing patients and controls. Patients with ID exhibited less thalamic prefrontal connections, particularly involving fibers traveling from the thalamus to the middle frontal gyrus. These results corroborate neurophysiologic findings of reduced and asynchronous thalamic prefrontal input, and emphasize the structural correlates of the pathophysiology of ID.

What is in a name? Spatial brain circuits are used to track discourse references.

Pronouns are commonly used instead of explicitly repeating a name, and, in many cases, we comprehend language faster when pronouns are used instead of repetitive references. This is surprising because pronouns are often ambiguous, whereas repeated names provide precise reference. We used functional MRI to investigate the neural correlates of this paradoxical preference. Reading repeated names elicited more activation than pronouns in the middle and inferior temporal gyri and intraparietal sulcus. The temporal lobe activation suggests that repeated names but not pronouns evoke multiple representations that have to be integrated. The intraparietal sulcus activation suggests that this integration relies on brain regions used for spatial attention and perceptual integration.

Voxel-based morphometry of the thalamus in patients with refractory medial temporal lobe epilepsy.

Previous research has suggested that patients with refractory medial temporal lobe epilepsy (MTLE) show gray matter atrophy both within the temporal lobes as well as in the thalamus. However, these studies have not distinguished between different nuclei within the thalamus. We examined whether thalamic atrophy correlates with the nuclei's connections to other regions in the limbic system. T1-weighted MRI scans were obtained from 49 neurologically healthy control subjects and 43 patients diagnosed with chronic refractory MTLE that was unilateral in origin (as measured by ictal EEG and hippocampal atrophy observed on MRI). Measurements of gray matter concentration (GMC) were made using automated segmentation algorithms. GMC was analyzed both voxel-by-voxel (preserving spatial precision) as well as using predefined regions of interest. Voxel-based morphometry revealed intense GMC reduction in the anterior portion relative to posterior thalami. Furthermore, thalamic atrophy was greater ipsilateral to the MTLE origin than on the contralateral side. Here we demonstrate that the thalamic atrophy is most intense in the thalamic nuclei that have strong connections with the limbic hippocampus. This finding suggests that thalamic atrophy reflects this region's anatomical and functional association with the limbic system rather than a general vulnerability to damage.

Heavy coffee drinking and epilepsy.

Dietary habits have been rarely associated with seizure frequency in patients with epilepsy. We report a case of a man with a partial symptomatic epilepsy whose daily habit of heavy coffee drinking was associated with an increased seizure frequency. This patient witnessed a dramatic decrease in the frequency of his seizures after stopping coffee ingestion. Caffeine is a global stimulant and the reduction of its intake may help in the treatment of epilepsy.