Effect of neuronavigated repetitive Transcranial Magnetic Stimulation on pain, cognition and cortical excitability in fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep. METHODS: Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy (n = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy. RESULTS: Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity (P < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham. CONCLUSIONS: Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity.

fMRI Analysis of Dissociative Convulsions: A Case-Controlled Study.

Background and Objectives: Dissociative convulsions represent complex biopsychosocial etiopathogenesis and have semiological similarities with epilepsy, which leads to delays in definitive diagnosis as well as treatment. We explored the neurobiological underpinnings of dissociative convulsions using a functional magnetic resonance imaging (fMRI) design targeting cognitive, affective, and resting state characteristics in our subjects. Materials and Methods: Seventeen female patients with dissociative convulsions without any co-morbid psychiatric or neurological illness and 17 matched healthy controls underwent standardized task-based (affective and cognitive) and resting state fMRI. Blood oxygen level-dependent (BOLD) activation results were compared across the groups, and correlation with the severity of dissociation was measured. Results: Patients with dissociative convulsions had lower activation in the left cingulate gyrus, left paracentral lobule, right middle and inferior frontal gyrus, right caudate nucleus, and right thalamus. There was increased resting state functional connectivity (FC) between the left posterior superior temporal gyrus and left superior parietal lobule; left amygdala and Default Mode Network (DMN) of right lateral parietal cortex; right supramarginal gyrus and left cuneus in the patient group. Patients also had decreased FC between the anterior cingulate cortex (ACC) and left thalamus; ACC and right central opercular cortex; DMN of PCC, posterior cingulate gyrus, and right middle temporal lobe. Conclusions: Patients with dissociative convulsions have significant deficits in the areas associated with the processing of emotional, cognitive, memory, and sensory-motor functions. There is a significant correlation between dissociative severity and the functioning of areas involving the processing of emotions, cognition, and memory.

Study of 2D Feature Extraction Techniques for Classification of Spinocerebellar Ataxia Type 12 (SCA12).

Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative genetic disorder triggered by abnormal CAG repeat expansion at locus 5q32. MRI recognises dissimilarities in affected areas of SCA12 patients and healthy subjects. But manual diagnosis is time-consuming and prone to subjective errors. This has motivated us in developing a systematic and authentic decision model for computer-aided diagnosis (CAD) of SCA12. Four different feature extraction techniques are examined in this research work, such as First Order Statistics, GLRLM, GLCM, and GLGCM, to obtain distinguishable characteristics for differentiating SCA12 patients from healthy subjects. The model's performance is measured using sensitivity, specificity, accuracy and F1-score with leave-one-out cross-validation scheme. Our experimental results show that features based on the GLRLM can distinguish SCA12 from healthy subjects with a maximum classification accuracy of 85% among all the different function extraction techniques used.

Correlation of DTI-Derived Measures to Therapy-Mediated Recovery after Stroke: Preliminary Findings.

INTRODUCTION: Corticospinal tracts (CST) forms the basis of motor neurophysiology after stroke. Motor skill recovery has been correlated well to the microstructural properties of CST in both hemispheres. Functional imaging has opened up new possibilities of imaging functionality of cortex and fiber tracts in the brain. We studied therapy-induced changes in blood oxygenation level-dependent (BOLD) and DTI imaging on 20 chronic stroke patients at baseline, 8, and 24 weeks. SETTINGS AND DESIGN: All the patients were subjected to MR imaging on a 1.5 T MR scanner. We used block design for BOLD with alternate baseline and activation cycles (repetition time (TR) =4520 ms, echo time (TE) = 44 ms, slices = 31, slice thickness = 4 mm). DTI parameters were as follows: TE = 76 ms, TR = 10,726 ms, EPI factor = 127, resolution = 128 × 128 matrix, field of view = 230 mm and a slice thickness of 4.0 mm. STATISTICAL ANALYSIS USED: The data was analyzed on SPSS software and tractography/DTI processing software (M/s. Siemens Medical Solutions, Erlangen Germany. RESULTS: The mean axial diffusivity (λ[INSIDE:1]) and radial diffusivity (λ[INSIDE:2]) in the affected hemisphere were 0. 30 and 0.18, respectively. The mean number (FN) ratio (± SD) was 0.27 ± 0.14 at baseline, 0.33 ± 0.19 at 8 weeks, and 0.41 ± 0.23 at 24 weeks. Multivariate regression analysis at baseline showed that rFA was well-correlated to the Fugl-Meyer score (regression coefficient: 0.198, F = 10.382, P = 0.001), MI followed by signal intensity. DISCUSSION: All patients had high % signal intensity after 8 weeks of physiotherapy regime with a greater percentage change in rFA as compared at follow-up suggesting that a focused exercise regime in stroke patients helps in the reconnection of neural and myelin networks. CONCLUSION: Clinical and functional recovery after stroke is well-correlated with the DTI and BOLD parameters i.e., rFA ratios, CST involvement fiber numbers, and % signal intensity of the ipsilesional cortex.

Cortical and Subcortical Brain Area Atrophy in SCA1 and SCA2 Patients in India: The Structural MRI Underpinnings and Correlative Insight Among the Atrophy and Disease Attributes.

INTRODUCTION: Genetically defined spinocerebellar ataxia (SCA) type 1 and 2 patients have differential clinical profile along with probable distinctive cortical and subcortical neurodegeneration. We compared the degree of brain atrophy in the two subtypes with their phenotypic and genotypic parameters. METHODS: MRI was performed using a 3T scanner (Philips, Achieva) to obtain 3D T1-weighted scans of the whole brain and analyzed by FreeSurfer (version 5.3 and 6 dev.) software. Genetically proven SCA1 (n = 18) and SCA2 (n = 25) patients with age-matched healthy controls (n = 8) were recruited. Clinical severity was assessed by the International Cooperative Ataxia Rating Scale (ICARS). To know the differential pattern of atrophy, the groups were compared using ANOVA/Kruskal-Wallis test and followed by correlation analysis with multiple corrections. Further, machine learning-based classification of SCA subtypes was carried out. RESULT: We found (i) bilateral frontal, parietal, temporal, and occipital atrophy in SCA1 and SCA2 patients; (ii) reduced volume of cerebellum, regions of brain stem, basal ganglia along with the certain subcortical areas such as hippocampus, amygdala, thalamus, diencephalon, and corpus callosum in SCA1 and SCA2 subtypes; (iii) higher subcortical atrophy SCA2 than SCA1 (iv) correlation between brain atrophy and disease attributes; (v) differential predictive pattern of two SCA subtypes using machine learning approach. CONCLUSION: The present study suggests that SCA1 and SCA2 do not differ in cortical thinning while a characteristic pattern of subcortical atrophy SCA2 > SCA1 is observed along with correlation of brain atrophy and disease attributes. This may provide the diagnostic guidance of MRI to SCA subtypes and differential therapies.

Correlating cognition and cortical excitability with pain in fibromyalgia: a case control study.

BACKGROUND: Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal symptoms, primarily attributed to sensitization of somatosensory system carrying pain. Few reports have investigated the impact of fibromyalgia symptoms on cognition, corticomotor excitability, sleepiness, and the sleep quality - all of which can deteriorate the quality of life in fibromyalgia. However, the existing reports are underpowered and have conflicting directions of findings, limiting their generalizability. Therefore, the present study was designed to compare measures of cognition, corticomotor excitability, sleepiness, and sleep quality using standardized instruments in the recruited patients of fibromyalgia with pain-free controls. METHODS: Diagnosed cases of fibromyalgia were recruited from the Rheumatology department for the cross-sectional, case-control study. Cognition (Mini-Mental State Examination, Stroop color-word task), corticomotor excitability (Resting motor threshold, Motor evoked potential amplitude), daytime sleepiness (Epworth sleepiness scale), and sleep quality (Pittsburgh sleep quality index) were studied according to the standard procedure. RESULTS: Thirty-four patients of fibromyalgia and 30 pain-free controls were recruited for the study. Patients of fibromyalgia showed decreased cognitive scores (p = 0.05), lowered accuracy in Stroop color-word task (for color: 0.02, for word: 0.01), and prolonged reaction time (< 0.01, < 0.01). Excessive daytime sleepiness in patients were found (< 0.01) and worsened sleep quality (< 0.01) were found. Parameters of corticomotor excitability were comparable between patients of fibromyalgia and pain-free controls. CONCLUSIONS: Patients of fibromyalgia made more errors, had significantly increased reaction time for cognitive tasks, marked daytime sleepiness, and impaired quality of sleep. Future treatment strategies may include cognitive deficits and sleep disturbances as an integral part of fibromyalgia management.

5-HT1A targeting PARCEST agent DO3AM-MPP with potential for receptor imaging: Synthesis, physico-chemical and MR studies.

Contrast enhancement in MRI using magnetization or saturation transfer techniques promises better sensitivity, and faster acquisition compared to T1 or T2 contrast. This work reports the synthesis and evaluation of 5-HT1A targeted PARACEST MRI contrast agent using 1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide (DO3AM) as the bifunctional chelator, and 5-HT1A-antagonist methoxyphenyl piperazine (MPP) as a targeting unit. The multi-step synthesis led to the MPP conjugated DO3AM with 60% yield. CEST-related physicochemical parameters were evaluated after loading DO3AM-MPP with paramagnetic MRI active lanthanides: Gadolinium (Gd-DO3AM-MPP) and Europium (Eu-DO3AM-MPP). Luminescence lifetime measurements with Eu-DO3AM-MPP and computational DFT studies using Gd-DO3AM-MPP revealed the coordination of one water molecule (q = 1.43) with metal-water distance (rM-H2O) of 2.7 Å and water residence time (τm) of 0.23 ms. The dissociation constant of Kd 62 ± 0.02 pM as evaluated from fluorescence quenching of 5-HT1A (protein) and docking score of -4.81 in theoretical evaluation reflect the binding potential of the complex Gd-DO3AM-MPP with the receptor 5-HT1A. Insights of the docked pose reflect the importance of NH2 (amide) and aromatic ring in Gd-DO3AM-MPP while interacting with Ser 374 and Phe 370 in the antagonist binding pocket of 5-HT1A. Gd-DO3AM-MPP shows longitudinal relaxivity 5.85 mM-1s-1 with a water residence lifetime of 0.93 ms in hippocampal homogenate containing 5-HT1A. The potentiometric titration of DO3AM-MPP showed strong selectivity for Gd3+ over physiological metal ions such as Zn2+ and Cu2+. The in vitro and in vivo studies confirmed the minimal cytotoxicity and presential binding of Gd-DO3AM-MPP with 5-HT1A receptor in the hippocampus region of the mice. Summarizing, the complex Gd-DO3AM-MPP can have a potential for CEST imaging of 5-HT1A receptors.

Correlating cognition and cortical excitability with pain in fibromyalgia: a case control study

Abstract Background: Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal symptoms, primarily attributed to sensitization of somatosensory system carrying pain. Few reports have investigated the impact of fibromyalgia symptoms on cognition, corticomotor excitability, sleepiness, and the sleep quality — all of which can deteriorate the quality of life in fibromyalgia. However, the existing reports are underpowered and have conflicting directions of findings, limiting their generalizability. Therefore, the present study was designed to compare measures of cognition, corticomotor excitability, sleepiness, and sleep quality using standardized instruments in the recruited patients of fibromyalgia with pain-free controls. Methods: Diagnosed cases of fibromyalgia were recruited from the Rheumatology department for the cross-sectional, case-control study. Cognition (Mini-Mental State Examination, Stroop color-word task), corticomotor excitability (Resting motor threshold, Motor evoked potential amplitude), daytime sleepiness (Epworth sleepiness scale), and sleep quality (Pittsburgh sleep quality index) were studied according to the standard procedure. Results: Thirty-four patients of fibromyalgia and 30 pain-free controls were recruited for the study. Patients of fibromyalgia showed decreased cognitive scores (p = 0.05), lowered accuracy in Stroop color-word task (for color: 0.02, for word: 0.01), and prolonged reaction time (< 0.01, < 0.01). Excessive daytime sleepiness in patients were found (< 0.01) and worsened sleep quality (< 0.01) were found. Parameters of corticomotor excitability were comparable between patients of fibromyalgia and pain-free controls. Conclusions: Patients of fibromyalgia made more errors, had significantly increased reaction time for cognitive tasks, marked daytime sleepiness, and impaired quality of sleep. Future treatment strategies may include cognitive deficits and sleep disturbances as an integral part of fibromyalgia management.(AU)

Development and Validation of a Comprehensive Neuropsychological and Language Rehabilitation for Stroke Survivors: A Home-Based Caregiver-Delivered Intervention Program.

CONTEXT: Aphasia is a major disabling condition after a stroke that profoundly affects the quality of life of stroke survivors (SS) and their caregivers. Comprehensive neuropsychological rehabilitation has emerged as a complementary intervention that helps in improving the associated cognitive and psychological deficits and quality of life following a brain injury. A standardized, simple, and easy to administer intervention that can be delivered as a home-based intervention can assist in faster recovery. AIMS: To describe the development, validation, and feasibility of a home-based, caregiver-delivered comprehensive neuropsychological and language rehabilitation for SS. METHODS AND MATERIAL: A culture-specific picture and task-based 8-week training workbook and manual were developed based on extensive review and focused group discussions. This intervention targeted areas of language (comprehension, fluency, and naming) and cognition (working memory, attention and concentration, executive functioning, and response inhibition). It was standardized on 40 healthy controls (HC) and 15 SS. Before recruitment, written informed consent was obtained from each patient, their primary caregiver, and the HCs. RESULTS: All tasks were found to be effective in discriminating the performance of SS from the HC. The performance of the HC with respect to the errors and the time taken for each task was used for the hierarchical arrangement of the tasks. The developed intervention was later validated on 15 SS where they significantly improved in the pre-post assessment of language functioning (P < 0.001), quality of life (P < 0.001), and depression (P < 0.001). CONCLUSIONS: This intervention can be feasible to administer as a home-based intervention and may help to alleviate language and neuropsychological complaints after stroke in low-literate or mixed-cultural populations. Further, large sample size studies are recommended.

Evaluation of memory in persons with mesial temporal lobe sclerosis: A combined fMRI and VBM study.

Persons with drug refractory TLE have the option of being managed by surgery. They may develop memory impairment with specific etiology of mesial temporal sclerosis and anterior temporal lobe resection (ATLR). The study evaluated the semantic verbal memory outcomes in pre- and post-surgery temporal lobe epilepsy (TLE) patients using functional MRI and voxel morphometric methods. Twenty consecutive persons with drug-resistant epilepsy (DRE) and 20 healthy controls were recruited after obtaining the institute ethics approval. The fMRI scans were performed on a 1.5 T MR Scanner using standardized semantic verbal memory tasks using a native Hindi paradigm, before and after an anterior temporal lobectomy (in cases). A task-based functional connectivity (FC) was estimated using a conn toolbox. Data analysis was carried out using the statistical parametric imaging (SPM12) and CAT12 toolbox. Post-surgery TLE group showed increased robust FC in the right middle and posterior temporal regions as compared to pre-surgery session. A significant reduction in grey matter volume was observed in the left temporal lobe post-operatively as compared to presurgery and healthy control groups. In the post-surgery TLE group, neuropsychological scores were reduced in specific PGI domains such as visuospatial, working memory, and executive functioning. Our results may help in understanding of memory reorganization in TLE post-operatively.

Safety and Feasibility of Autologous Mesenchymal Stem Cell Transplantation in Chronic Stroke in Indian patients. A four-year follow up.

Introduction: Stem cell (SC) therapy has been envisioned as a therapeutic vehicle to promote recovery in resistant neurological diseases. Knowing the logistics and paradigms in recovery processes after Stroke, clinicians have pioneered the transplantation therapy. This study presents four-year follow up of our previous trial transplanting bone-marrow-derived animal-free culture expanded intravenous mesenchymal stem cells (MSCs) in chronic stroke which was published in 2010. Methods: We performed an open-label, pilot trial on 12 patients with chronic stroke. Patients were allocated to two groups, those who received intravenous autologous ex vivo cultured mesenchymal stem cells (MSC group) or those who did not (control group), all followed for four years from the day of cell transplantation. Results: The reports have been optimistic regarding safety as we did not find any cell related side effects / mortality till 208th week. We observed that modified Barthel Index showed statistical significant improvement at 156 and 208 weeks of transplantation (95 % CI : -10.27 to 0.07; p =0.041) follow up in the MSC group as compared to controls. The 2nd and 3rd quartile for mBI in MSC group was 89 & 90 respectively suggesting good performance of patients in the stem cell group. The impairment scales i.e., Fugl Meyer, Ashworth tone scale, strength of hand muscles (MRC) did not show any significant improvement at 208th week which is similar to our previous published report. Conclusion: This follow up study primarily indicates safety, tolerance and applicability of autologous mesenchymal stem cells in Stroke. MSCs may act as "chaperones" or work through paracrine mechanisms leading to functional recovery post stroke.

BOLD fMRI and DTI in strabismic amblyopes following occlusion therapy.

Evaluation of brain cluster activation using the functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) was sought in strabismic amblyopes. In this hospital-based case-control cross-sectional study, fMRI and DTI were conducted in strabismic amblyopes before initiation of any therapy and after visual recovery following the administration of occlusion therapy. FMRI was performed in 10 strabismic amblyopic subjects (baseline group) and in 5 left strabismic amblyopic children post-occlusion therapy after two-line visual improvement. Ten age-matched healthy children with right ocular dominance formed control group. Structural and functional MRI was carried out on 1.5T MR scanner. The visual task consisted of 8 Hz flickering checkerboard with red dot and occasional green dot. Blood-oxygen-level-dependent (BOLD) fMRI was analyzed using statistical parametric mapping and DTI on NordicIce (NordicNeuroLab) softwares. Reduced occipital activation was elicited when viewing with the amblyopic eye in amblyopes. An 'ipsilateral to viewing eye' pattern of calcarine BOLD activation was observed in controls and left amblyopes. Activation of cortical areas associated with visual processing differed in relation to the viewing eye. Following visual recovery on occlusion therapy, enhanced activity in bilateral hemispheres in striate as well as extrastriate regions when viewing with either eye was seen. Improvement in visual acuity following occlusion therapy correlates with hemodynamic activity in amblyopes.

Stem cell therapy: a clinical trial of stroke.

BACKGROUND: The alarming disability burden and a high prevalence rate of stroke in India has encouraged the researchers to develop regenerative therapies to reduce clinical deficits. This study evaluates safety, feasibility and efficacy of autologous mononuclear and mesenchymal cell transplantation in stroke patients evaluated on clinical scores and functional imaging (fMRI and DTI). METHODS: Forty (n=40) stroke patients were recruited with the inclusion criteria as: 3 months to 2 years of index event, power of hand muscles of at least 2; Brunnstrom stage: 2-5; conscious and comprehendible. Fugl Meyer (FM), modified Barthel Index (mBI), Medical Research Council (MRC) grade for strength, Ashworth tone scale and functional imaging was used for assessments at baseline, 8 weeks and 24 weeks. 50-60 million cells in 250 ml saline were infused intravenously over 2-3 h. RESULTS: The safety test profile was normal with no mortality or cell related adverse reactions in stem cell patients. Among outcome parameters, only modified Barthel Index (mBI) showed statistical significant improvement (p<0.05) in the stem cell group. An increased number of cluster activation in Brodmann areas BA 4, BA 6 was observed post stem cell infusion indicating neural plasticity. CONCLUSION: Autologous intravenous stem cell therapy is safe and feasible. Stem cells act as "scaffolds" for neural transplantation and may aid in repair mechanisms in stroke.

Neural interface of mirror therapy in chronic stroke patients: a functional magnetic resonance imaging study.

BACKGROUND: Recovery in stroke is mediated by neural plasticity. Neuro-restorative therapies improve recovery after stroke by promoting repair and function. Mirror neuron system (MNS) has been studied widely in humans in stroke and phantom sensations. MATERIALS AND METHODS: Study subjects included 20 patients with chronic stroke and 10 healthy controls. Patients had clinical disease-severity scores, functional magnetic resonance imaging (fMRI) and diffuse tensor imaging (DTI) at baseline, 8 and at 24 weeks. Block design with alternate baseline and activation cycles was used with a total of 90 whole brain echo planar imaging (EPI) measurements (timed repetition (TR) = 4520 ms, timed echo (TE) = 44 ms, slices = 31, slice thickness = 4 mm, EPI factor 127, matrix = 128 × 128, FOV = 230 mm). Whole brain T1-weighted images were acquired using 3D sequence (MPRage) with 120 contiguous slices of 1.0 mm thickness. The mirror therapy was aimed via laptop system integrated with web camera, mirroring the movement of the unaffected hand. This therapy was administered for 5 days in a week for 60-90 min for 8 weeks. RESULTS: All the patients showed statistical significant improvement in Fugl Meyer and modified Barthel Index (P < 0.05) whereas the change in Medical Research Council (MRC) power grade was not significant post-therapy (8 weeks). There was an increase in the laterality index (LI) of ipsilesional BA 4 and BA 6 at 8 weeks exhibiting recruitment and focusing principles of neural plasticity. CONCLUSIONS: Mirror therapy simulated the "action-observation" hypothesis exhibiting recovery in patients with chronic stroke. Therapy induced cortical reorganization was also observed from our study.

Functional mapping of language networks in the normal brain using a word-association task.

BACKGROUND: Language functions are known to be affected in diverse neurological conditions, including ischemic stroke, traumatic brain injury, and brain tumors. Because language networks are extensive, interpretation of functional data depends on the task completed during evaluation. AIM: The aim was to map the hemodynamic consequences of word association using functional magnetic resonance imaging (fMRI) in normal human subjects. MATERIALS AND METHODS: Ten healthy subjects underwent fMRI scanning with a postlexical access semantic association task vs lexical processing task. The fMRI protocol involved a T2*-weighted gradient-echo echo-planar imaging (GE-EPI) sequence (TR 4523 ms, TE 64 ms, flip angle 90°) with alternate baseline and activation blocks. A total of 78 scans were taken (interscan interval = 3 s) with a total imaging time of 587 s. Functional data were processed in Statistical Parametric Mapping software (SPM2) with 8-mm Gaussian kernel by convolving the blood oxygenation level-dependent (BOLD) signal with an hemodynamic response function estimated by general linear method to generate SPM{t} and SPM{F} maps. RESULTS: Single subject analysis of the functional data (FWE-corrected, P≤0.001) revealed extensive activation in the frontal lobes, with overlaps among middle frontal gyrus (MFG), superior, and inferior frontal gyri. BOLD activity was also found in the medial frontal gyrus, middle occipital gyrus (MOG), anterior fusiform gyrus, superior and inferior parietal lobules, and to a smaller extent, the thalamus and right anterior cerebellum. Group analysis (FWE-corrected, P≤0.001) revealed neural recruitment of bilateral lingual gyri, left MFG, bilateral MOG, left superior occipital gyrus, left fusiform gyrus, bilateral thalami, and right cerebellar areas. CONCLUSIONS: Group data analysis revealed a cerebellar-occipital-fusiform-thalamic network centered around bilateral lingual gyri for word association, thereby indicating how these areas facilitate language comprehension by activating a semantic association network of words processed postlexical access. This finding is important when assessing the extent of cognitive damage and/or recovery and can be used for presurgical planning after optimization.