Common cortical and thalamic mechanisms for language and motor functions.

Purpose: Unicoronal synostosis has been associated with impaired reading, language, and social function. Functional MRI (fMRI) can evaluate brain connectivity in targeted brain regions to compare imaging analysis to previously published clinical performance. fMRI was used in this study to compare brain function connectivity in unicoronal synostosis (UCS) and compare outcomes by cerebral dominance (left versus right-sided UCS). Methods: Twelve adolescents with surgically treated UCS, 7 right-sided and 5 left-sided, were individually matched to age, gender and handedness controls. Resting state fMRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany). Data was collected with intrinsic connectivity distribution and seed-connectivity analysis with BioImage Suite (Yale School of Medicine). Region of interest (ROI) analysis was performed based on Brodmann’s areas (BA) related to emotional, executive, language, motor and visuo-spatial function, left BA5, 6, 7, 18, 19, 37, 39, and 44. BA5, 6, 7 are areas of the frontal and parietal cortex important for visuomotor coordination and complex movement. BA18, 19 are areas of the occipital lobe related to visual information processing. BA 37, 39, and 44 are areas of the fusiform, angular gyri and temporal lobe important for language function. P<0.05 was significant. Results: Compared to controls, all UCS patients demonstrated decreased connectivity in left BA7, bilateral BA39, and right BA41 (p<0.01)), which are areas of the parietal and temporal cortices responsible for vision, language function, and motor coordination. Right UCS patients demonstrated increased connectivity in right BA17, BA18, BA19, BA20, BA36 when compared to controls (p<0.05). In the ROI analysis, right UCS exhibited decreased connectivity between the anterior cingulate cortex and right BA18, 19, and 37 compared to controls (p<0.05). The increased connectivity in BA17-20 (visual processing regions) supports our previous neurocognitive study results of increased visual perception abilities in right UCS patients. The subsequent decreased connectivity between BA18-19 and the anterior cingulate cortex (a section of which is implicated in complex motor coordination) is supported by neurocognitive data that shows decreased visual-motor integration ability in right UCS. This decreased connectivity between the aforementioned areas and the anterior cingulate gyrus despite increased intrinsic connectivity may also imply discordance in connecting emotion and executive function to language and visual information in right UCS patients. Connectivity between the left parahippocampus and right BA36, 37, and 54 was increased (p<0.05). Compared to controls and right UCS, left UCS demonstrated decreased connectivity between left BA6 and left BA17 and 18 (p<0.05). Left UCS patients did not demonstrate significantly different intrinsic or seed-based connectivity to right UCS or controls otherwise. Conclusion: Unilateral coronal synostosis had decreased connectivity and greater potential for neurocognitive dysfunction in regions associated with memory, visual information processing, and motor function. Moreover, left-sided UCS had decreased connectivity in circuits crucial in complex motor movement when compared to right-sided UCS. This study provides data suggestive of long-term sequelae of UCS that varies by sidedness, which may underlie the different phenotypes of neurocognitive impairment found in previous cognitive analyses.

Motor and language deficits before and after surgical resection of mesial frontal tumour

Resection of lesions involving the supplementary motor area (SMA) may result in immediate postoperative motor and speech deficits that are reversible in most cases. In the present study the authors aimed to determine the critical involvement of SMA in the lesioned and healthy hemispheres in this functional recovery. They hypothesized that compensatory mechanisms take place following surgery in the SMA, and that these mechanisms can involve either the lesioned or the non-lesioned hemisphere. In addition, they hypothesized that a correlation will be present between the functional MR imaging (fMR) imaging-related activation in the SMA and the occurrence of a functional deficit during intraoperative cortical stimulation. Twenty-six patients scheduled for resection of space-occupying lesions involving, or in the vicinity of, the SMA were recruited. Patients underwent an fMR imaging examination that included finger-tapping and verb-generation tests to assess for motor and language functions. Intraoperatively direct cortical stimulation (DCS) of the SMA region was performed while patients were monitored for language and motor functions using tests similar to those used for the fMR imaging. Task dysfunction during DCS assessed the critical involvement of the SMA in the tested functions. Neurological evaluations were performed prior to surgery and at 3 time points within a month following surgery. A region of interest-based approach was used to evaluate fMR imaging blood oxygen level-dependent activation level and asymmetry in the SMA. These measurements were later compared with the intraoperative DCS and neurological findings. Functional MR imaging showed greater activation and dominance of the SMA in the lesioned hemisphere in patients who exhibited no motor or language dysfunction during DCS. In addition, patients with the highest activation of the SMA in the lesioned hemisphere for language and motor tests showed stronger coupling of this region with ipsilateral motor and language networks. In contrast, activation in the nonlesioned hemisphere did not correspond with DCS results. The authors' findings demonstrate the necessity of activation in the vicinity of the lesioned SMA for functional compensation in motor and language tasks. It is possible that more effective functional coupling of the SMA with motor and language areas in the same hemisphere prevents dysfunctions following surgical intervention. Importantly, fMR imaging activation in the unaffected SMA was not sufficient for development of functional compensation and, if anything, indicated decompensation.

Unicoronal synostosis (UCS) has been associated with reading, language, and social dysfunction. Limited brain function connectivity studies exist for UCS with none devoted to comparing outcomes by side of synostosis (left versus right-sided UCS). Twelve patients with surgically treated UCS, 7 right-sided and 5 left-sided, were age matched to healthy controls. Resting state functional MRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany). Data was collected with intrinsic connectivity distribution and seed-connectivity analysis using BioImage Suite (Yale School of Medicine). Region of interest analysis was performed based on Brodmann areas related to emotional, executive, language, motor, and visuo-spatial function. Significance was set at P < 0.05. Compared to controls, all UCS patients demonstrated decreased connectivity in areas of the parietal and temporal cortices responsible for visuo-motor coordination and language function. Right UCS patients demonstrated decreased intrinsic connectivity in regions related to complex motor movement and proprioception relative to control subjects. Left UCS patients demonstrated decreased seed connectivity between regions of the parietal lobe and occipital lobe related to motor coordination, visual function, and language compared to right UCS patients. Unicoronal synostosis had decreased functional connectivity in regions associated with memory, visual information processing, and motor function. Moreover, left-sided UCS had decreased connectivity in circuits for motor coordination and language when compared to right-sided UCS. This study provides data suggestive of long-term sequelae of UCS that varies by sidedness, which may be responsible for neurocognitive impairments found in previous cognitive analyses.

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.

An experiment was performed to determine the effect of selective adaptation on the identification of synthetic speech sounds which varied along the phonetic dimension place of articulation. Adaptation with a stimulus of a particular place value led to a reduction in the number of test stimuli identified as having that place value. An identification shift was obtained even when the acoustic information specifying place value for the adapting stimulus (burst-cued) had little in common with the information specifying place value for any of the test stimuli (transition-cued). Removing the vowel portion of an adapting stimulus eliminated identification shift only when the resulting stimulus was no longer perceived as speechlike. The results indicate that at least part of the adaptation effect occurs at a site of phonetic, nor merely acoustic, feature analysis.

Background: Parkinsonism describes Parkinson’s disease and other associated degenerative changes in the brain resulting in movement disorders. The motor cortex, extrapyramidal tracts and nigrostriatal tract are brain regions forming part of the motor neural system and are primary targets for drug or chemotoxins induced Parkinsonism. The cause of Parkinsonism has been described as wide and elusive, however, environmental toxins and drugs accounts for large percentage of spontaneous cases in humans. A common mechanism in the cause and progression of drug/chemotoxin induced Parkinsonism involves calcium signalling in; oxidative stress, autophagy, cytoskeletal instability and excitotoxicity.Aim: This study sets to investigate the effect of targeting calcium controlling receptors, specifically activation of Vitamin D3 receptor (VDR) and inhibition of N-Methyl-D-Aspartate Receptor (NMDAR) in the motor cortex of mice model of drug induced Parkinsonism. Also we demonstrated how these interventions improved neural activity, cytoskeleton, glia/neuron count and motor–cognitive functions in vivo.Methods: Adult mice were separated into six groups of n = 5 animals each. Body weight (5 mg/kg) of haloperidol was administered intraperitoneally for 7 days to block dopaminergic D2 receptors and induce degeneration in the motor cortex following which an intervention of VDR agonist (VDRA), and (or) NMDAR inhibitor was administered for 7 days. A set of control animals received normal saline while a separate group of control animals received the combined intervention of VDRA and NMDAR inhibitor without prior treatment with haloperidol. Behavioral tests for motor and cognitive functions were carried out at the end of the treatment and intervention periods. Subsequently, neural activity in the motor cortex was recorded in vivo using unilateral wire electrodes. We also employed immunohistochemistry to demonstrate neuron, glia, neurofilament and proliferation in the motor cortex after haloperidol treatment and the intervention.Result/Discussion: We observed a decline in motor function and memory index in the haloperidol treatment group when compared with the control. Similarly, there was a decline in neural activity in the motor cortex (a reduced depolarization peak frequency). General cell loss (neuron and glia) and depletion of neurofilament were characteristic anatomical changes seen in the motor cortex of this group. However, Vitamin D3 intervention facilitated an improvement in motor–cognitive function, neural activity, glia/neuron survival and neurofilament expression. NMDAR inhibition and the combined intervention improved motor–cognitive functions but not as significant as values observed in VDRA intervention. Interestingly, animals treated with the combined intervention without prior haloperidol treatment showed a decline in motor function and neural activity.Conclusion: Our findings suggest that calcium mediated toxicity is primary to the cause and progression of Parkinsonism and targeting receptors that primarily modulates calcium reduces the morphological and behavioral deficits in drug induced Parkinsonism. VDR activation was more effective than NMDAR inhibition and a combined intervention. We conclude that targeting VDR is key for controlling calcium toxicity in drug/chemotoxin induced Parkinsonism.

To evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions. Sensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6). For healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke's area, and 93% for the putative Broca's area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke's area, and 77% for the putative Broca's area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results. This integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.

Concomitant with the right hemispheric restitution of language functions after early left hemisphere lesions, suppression effects on originally right hemispheric visuospatial/constructional functions have repeatedly been reported. The present study evaluated this issue in 10 right hemisphere language-dominant patients with temporal lobe epilepsy. Left hemisphere language-dominant patients with left (n = 10) or right (n = 10) temporal lobe epilepsy served as controls. The following results were obtained: in all but one of the right dominant patients, left hemisphere lesions, left hemisphere foci and histories of early left brain damage indicated that secondary language transfer rather than a genetically determination is the more likely cause of the right hemisphere dominance. Despite this transfer, the language functions (comprehension, fluency, reasoning) of the right dominant patients remained significantly impaired. Language generally appeared to be better preserved in patients with an onset of epilepsy before the third year of life or a circumscribed left hemisphere lesion. No suppression effects could be detected on the level of complex cortical language and non-language functions. In contrast, on the level of temporo-limbic memory functions, verbal learning and recognition were left largely intact, albeit mostly at the expense of visuo-spatial learning and memory. The findings of the study thus indicate that the cerebral plasticity of the right hemisphere differs according to the extent of the left-hemisphere lesion, the onset of structural/functional damage and the complexity of the functions requiring restitution. Assuming that language and memory represent neocortical and palaeocortical functions, respectively, the restitution process is seemingly governed by their status in a phylogenetically determined hierarchy of functional importance.

This study represents the first prospective controlled investigation of preoperative versus postoperative (6 months) language function in patients who underwent partial resection of the dominant (n = 15) or nondominant (n = 14) anterior temporal lobe for treatment of medically refractory epilepsy. Language dominance was confirmed by intracarotid sodium amytal test. Thirteen of the 15 patients undergoing anterior temporal lobectomy of the dominant hemisphere were operated on under local anesthesia in order to map language and memory functions intraoperatively. Using a standardized language/aphasia battery, we found a significant trend of worse preoperative language function in patients with dominant hemisphere temporal lobe foci in comparison to patients with nondominant foci. Following anterior temporal lobectomy, neither group showed any significant losses in language function, whereas the dominant hemisphere temporal lobe group showed significant improvement in receptive language comprehension and associative verbal fluency.

We report on 30 cases where we have used cortical stimulation mapping to define the areas representing sensorimotor, language and speech functions under local anesthesia to facilitate resection of space-occupying lesions near these areas. Under the simplistic concept that Broca's area lies in the frontal operculum (inferior frontal gyrus) and that Wernicke's area is located in the posterior perisylvian area (superior temporal, angular and supramarginal gyri), we found language and speech function to be represented outside these areas in up to 4 stimulation sites of 15 patients. The results of cortical stimulation mapping were therefore essential to decide on the optimal access route to the lesions that were located subcortically and on the optimal resection plane in gliomas. After the limits of these areas and of the lesions had been established with stimulation mapping and with intrasurgical microscopic smear preparations, respectively, lesions were safely removed under continuous monitoring of sensorimotor, language and speech function. Immediately after surgery we encountered language and speech deficits in 9 patients (30%), which resolved completely in 5 and incompletely in 4 instances. Thus, language functions were normal in 26 patients (87%) at the end of the follow-up period. It is concluded that use of this technique allows safe and extensive resection of lesions that would otherwise have been considered hazardous to remove or inexcisable.

BackgroundPost-stroke aphasia concurrent with upper limb (UL) motor dysfunction is very common and difficult to rehabilitate. Although mirror therapy (MT) has demonstrated efficacy in treating aphasia and UL motor dysfunction separately, it has not been utilized to address both conditions simultaneously. Our study introduces a novel Synchronous Mirror Therapy (SMT) system that integrates speech-language therapy with UL motor training to evaluate its clinical feasibility, preliminary efficacy, and potential cortical mechanisms.MethodFifteen patients and five therapists participated in this study. The patients had aphasia and UL motor dysfunction and underwent the SMT intervention ten times. They were evaluated through functional assessment scales (Aphasia Quotient of Western Aphasia Battery (WAB-AQ); Assessment of Fugl-Meyer Upper Limb scale (FMA-UL); Action Research Arm Test (ARAT)) and three questionnaires, and functional near-infrared (fNIRS) test. We analyzed the questionnaire results, functional changes before and after SMT, and differences between the SMT intervention and rest periods.ResultsNine patients underwent all SMT treatment sessions. Patients and therapists gave high ratings for SMT. Compared with before SMT interventions, significant improvements were observed in language function (WAB-AQ: p = 0.008) and UL motor function (FMA-UL: p = 0.007; ARAT: p = 0.016) after all SMT interventions, along with significant changes in three fNIRS channels (channel 9, p < 0.001; channel 20, p = 0.005; channel 30, p = 0.046) during the SMT intervention.ConclusionThe SMT intervention demonstrated feasibility and received positive feedback from both patients and therapists. The results indicate potential benefits of SMT in improving language and UL motor function for post-stroke patients. fNIRS findings suggest possible enhanced cortical activation during SMT, which may be associated with neural recovery processes. While encouraging, this still necessitates validation through larger sample sizes and rigorous randomized controlled designs.

A prospective study of patients undergoing computerized tomography (CT)-guided stereotactic biopsy of nonpolar tumors in the dominant hemisphere was undertaken to determine if stereotactic biopsy caused a deterioration of language functions. Language was assessed using the Western Aphasia Battery (WAB) and the Boston Naming Test (BNT) before and after a biopsy sample was obtained. Of 16 patients studied, five (31%) were dysphasic preoperatively. After the biopsy the Aphasia Quotient (AQ), derived from the WAB, had significantly deteriorated in four (80%) of these patients, whereas in the fifth it remained relatively unchanged. One of these patients with an extensive infiltrating hemispheric oligoastrocytoma subsequently recovered normal language function after radiotherapy. In 10 of the 11 patients who had normal language function preoperatively there were no deleterious changes after biopsy in either the WAB subtest or BNT scores. In the other patient whose WAB score was normal preoperatively, there was a significant deterioration in postoperative AQ. This patient, who declined steroid therapy before and after biopsy, had a glioblastoma multiforme in Wernicke's area. A postoperative CT scan revealed no changes from what was shown on preoperative scan. This clinical study shows that CT-guided stereotactic biopsy of nonpolar tumors in the dominant hemisphere using the Brown-Roberts-Wells system and the Sedan-Nashold biopsy cannula carries a 9% risk (95% confidence intervals 0-26%) of impairing language functions if the patient is not dysphasic preoperatively. If the patient is dysphasic preoperatively, there is a very high risk of aggravating the dysphasia with stereotactic biopsy.

Wada test is well-known to assess lateralization of memory and language functions; however, super-selective Wada (ss-Wada) to evaluate motor leg function is rare. We present a ss-Wada test within the anterior cerebral artery (ACA) to assess the motor function of the leg. Retrospective chart review. Comprehensive phase-I/II surgical evaluation revealed an ictal focus around the left post-central gyrus with immediate involvement around the left para-central regions. To avoid potential right leg motor dysfunction with the surgery, the patient underwent a ss-Wada procedure. Angiography revealed bilateral ACAs were supplied by the left A1 segment. Super-selective microcatheter injection of amobarbital into the left ACA was performed to avoid cross-filling the contralateral ACA. The ss-Wada test confirmed no right leg motor impairment. Afterward, a craniotomy with direct cortical stimulation confirmed that the left-sided ictal/peri-ictal zone had no clear leg motor function. The patient underwent disconnection of that region and remained seizure-free at 10-month post-op follow-up without any motor or sensory deficits in the right limbs. This case demonstrates the proof of concept for ss-Wada in assessing lower extremity motor function. The ss-Wada procedure accurately predicted no motor deficits in the right leg, consistent with preserved motor function post-surgery.

In this paper the authors demonstrate the concordance between magnetic source (MS) imaging and direct cortical stimulation for mapping receptive language cortex. In 13 consecutive surgical patients, cortex specialized for receptive language functions was identified noninvasively by obtaining activation maps aided by MS imaging in the context of visual and auditory word-recognition tasks. Surgery was then performed for treatment of medically intractable seizure disorder (eight patients), and for resection of tumor (four), or angioma (one). Mapping of language areas with cortical stimulation was performed intraoperatively in 10 patients and extraoperatively in three. Cortical stimulation mapping verified the accuracy of the MS imaging-based localization in all cases. Information provided by MS imaging can be especially helpful in cases of atypical language representation, including bihemispheric representation, and location of language in areas other than those expected within the dominant hemisphere, such as the anterior portion of the superior temporal gyrus, the posteroinferior portion of the middle temporal gyrus, the basal temporal cortex, and the lateral temporooccipital cortex.