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.

Immediate effect of craniocervical flexion exercise and Mulligan mobilisation in patients with mechanical neck pain - A randomised clinical trial.

Background: Mechanical neck pain (MNP) is one of the most prevalent musculoskeletal pathologies in the present time. Physiotherapy management strategies comprising manual therapy and exercise therapy are routinely administered in patients with MNP. Objective: To compare the immediate effect of craniocervical flexion (CCF) exercise and Mulligan mobilisation on pain, active cervical range of motion (CROM) and CCF test performance in patients with MNP. Methods: This prospective, randomised, single-blinded study involved 26 patients with MNP (16 females; mean age; 31.12±8.40 years) randomised to a single session of active CCF exercise (3 sets of 10 repetitions) or Mulligan mobilisation (3 sets of 6-10 repetitions). Pain intensity was measured on a numerical pain rating scale (NPRS), active CROM was measured using CROM device, and CCF test performance with surface electromyography (EMG) from bilateral sternocleidomastoid (SCM) and anterior scalene (AS) muscles recorded pre- and immediately post-intervention by an assessor blinded to the treatment groups. Mann-Whitney U test was used to analyse between groups and Wilcoxon signed rank test was used to analyse within-group significance for pain and CROM, Cochran-Mantel-Haenszel correlation test was used to analyse the CCF test performance on EMG from the bilateral SCM and AS muscles. Results: Comparison between pre- and post-intervention readings revealed statistically significant within-group (p<0.05) and no between-group significant difference for pain, ROM, and CCF test performance, indicating both interventions were equally effective. Conclusion: Patients with MNP who received active CCF exercise or Mulligan mobilisation exhibited similar reduction in pain intensity and increased CROM and CCF test performance post-intervention. Surprisingly, AS surface EMG amplitudes were increased post-intervention in both groups warranting further exploration of its role in neck pain.

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.

A Multi-Institutional Informed Consent Proposal as a Prevention Tool for Combined Oral Contraceptive Intake and Thrombotic Risk.

Combined oral contraceptives (COC), are among the most widely used contraceptive methods in the world today. Despite the different changes in terms of estrogen/progestogen combinations and dosages, the thromboembolic risk for a woman who takes combined oral contraceptives persists to date. METHODS: The review of relevant literature and international guidelines on prescription of combined oral contraceptives made it possible to create a proposal for informed consent to be used for prescribing. RESULTS: The several sections of our consent proposal were designed according to a rationale in order to cover all the aspects presented by worldwide guidelines: how to take, adverse effects, advertisements, extra-contraceptive benefits and effects, a checklist for condition at risk of thromboembolism, the signature of the woman. CONCLUSIONS: An informed consent to standardize combined oral contraceptives prescription can improve women's eligibility, mitigate thromboembolic risk, and assure legal protection to healthcare providers. In this systematic review in particular, we refer to the Italian medical-legal scenario, to which our group of researchers belongs. However, the model proposed was designed in the respect of main healthcare organization guidelines, and it could be easily used by any center in the world.

Patient and public involvement in research: a review of practical resources for young investigators.

Patient and public involvement (PPI) in every aspect of research will add valuable insights from patients' experiences, help to explore barriers and facilitators to their compliance/adherence to assessment and treatment methods, bring meaningful outcomes that could meet their expectations, needs and preferences, reduce health care costs, and improve dissemination of research findings. It is essential to ensure competence of the research team by capacity building with available resources on PPI. This review summarizes practical resources for PPI in various stages of research projects-conception, co-creation, design (including qualitative or mixed methods), execution, implementation, feedback, authorship, acknowledgement and remuneration of patient research partners, and dissemination and communication of research findings with PPI. We have briefly summarized the recommendations and checklists, amongst others, for PPI in rheumatic and musculoskeletal research (e.g. the European Alliance of Associations for Rheumatology (EULAR) recommendations, the Core Outcome Measures in Effectiveness Trials (COMET) checklist and the Guidance for Reporting Involvement of Patients and the Public (GRIPP) checklist). Various tools that could be used to facilitate participation, communication and co-creation of research projects with PPI are highlighted in the review. We shed light on the opportunities and challenges for young investigators involving PPI in their research projects, and have summarized various resources that could be used to enhance PPI in various phases/aspects of research. A summary of web links to various tools and resources for PPI in various stages of research is provided in Additional file 1.

A Histopathological Study of Endometrial Biopsy Samples in Abnormal Uterine Bleeding.

BACKGROUND: Abnormal uterine bleeding (AUB) is the most common health issue in women, defined as any bleeding pattern that differs in frequency, duration, and amount. Endometrial sampling and its histopathological examination is the first-line test in patients presenting with AUB. The aim of this study was to analyze the histopathological patterns of endometrium in women with AUB and to find the predominant histopathologic pattern in the different age groups of women with AUB. METHODS: The study was conducted at the Indira Gandhi Medical College and Research Institute, Puducherry, from January 2019 to December 2020. Endometrial biopsies of patients with AUB, in whom gestational causes were ruled out, were included in this study. RESULTS: Out of the 160 cases analyzed, the maximum number of biopsies were from the age group of 41-50 years; the majority of patients presented with complaints of menorrhagia. The bleeding pattern was significantly associated with age groups (p=0.00). Of 160 cases, 104 cases were related to functional causes. The association of functional and organic causes with age group was not significant (p=0.67 and p=0.99, respectively). The most common histological pattern was the normal cyclical pattern showing proliferative (56) and secretory phase (30) in 86 cases. Of 42 cases of endometrial hyperplasia, 9 cases had atypical hyperplasia. The endometrial polyp was the other common organic lesion observed. Only two cases of endometrial carcinoma were reported during the present study period. CONCLUSION: Although a regular cyclical pattern is observed commonly, endometrial sampling should be considered in the peri- and post-menopausal age groups wherein the incidence of endometrial hyperplasia and endometrial carcinoma is more common.

Long-Term Functional Outcome Following Left Hemispherotomy in Adults and Pediatric Participants with Fmri Analysis.

Background and Objective: Hemispherotomy surgery in adults is shrouded in doubts regarding the functional outcome. The age at surgery alone should not be the deciding factor for surgery. Language paradigms were used in functional magnetic resonance imaging (fMRI) to confirm the role played by the age at the onset of seizures to predict the postoperative functional outcome. The objective of the study was to formulate an optimal strategy for patient selection for the left-sided hemispherotomy in adults, based on functional outcome analysis. Materials and Methods: A retrospective analysis of 20 participants (age at surgery 1-26 years) who underwent left hemispherotomy (over a 5-year period) was conducted. The language and motor functional assessments of 18 participants (13 pediatric and five adult participants; attrition of participants- two) were recorded at presentation and during follow-up visits. After approval was obtained from the Institutional Ethics Committee, 13 cooperative participants (eight pediatric and five adult participants) underwent language fMRI. Motor fMRI with both active and passive paradigms was done in 16 participants. Results: All 18 participants with a mean follow-up of 24 months had class I seizure-free outcome. Of these 18, five were adults (mean age = 21 years, range: 18-22 years) and 13 were in the pediatric age group (mean age = 8 years, range: 2-15 years). Postoperatively, four adults retained both verbal fluency and language comprehension at a mean follow-up period of 38 months (range: 24-48 months). Their pre- and post-op language fMRI showed word generation and regional activations for semantic comprehension in the right hemisphere. The motor area activations were seen in the right hemisphere in two and in the left hemisphere in two participants. Among the pediatric participants, four (group I [n = 4/13]) who had good language outcome showed activations in the right hemisphere. In two participants (group II [n = 2/13]) who deteriorated postoperatively, the activations were in the left hemisphere. Five participants (group III [n = 5/13]) who retained the telegraphic language postoperatively had bilateral activations of semantic comprehension areas in fMRI. All 13 pediatric participants had motor area activations seen in the left hemisphere, similar to controls. Conclusion: Left hemispherotomy can be advised to adults with comparably good postoperative language and motor outcome as in the pediatric age group, provided the weakness is acquired perinatally or below the age of 7 years. The fMRI is a valuable tool to aid in patient selection.

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.

Development of strategies to support home-based exercise adherence after stroke: a Delphi consensus.

OBJECTIVE: To develop a set of strategies to enhance adherence to home-based exercises after stroke, and an overarching framework to classify these strategies. METHOD: We conducted a four-round Delphi consensus (two online surveys, followed by a focus group then a consensus round). The Delphi panel consisted of 13 experts from physiotherapy, occupational therapy, clinical psychology, behaviour science and community medicine. The experts were from India, Australia and UK. RESULTS: In round 1, a 10-item survey using open-ended questions was emailed to panel members and 75 strategies were generated. Of these, 25 strategies were included in round 2 for further consideration. A total of 64 strategies were finally included in the subsequent rounds. In round 3, the strategies were categorised into nine domains-(1) patient education on stroke and recovery, (2) method of exercise prescription, (3) feedback and supervision, (4) cognitive remediation, (5) involvement of family members, (6) involvement of society, (7) promoting self-efficacy, (8) motivational strategies and (9) reminder strategies. The consensus from 12 experts (93%) led to the development of the framework in round 4. CONCLUSION: We developed a framework of comprehensive strategies to assist clinicians in supporting exercise adherence among stroke survivors. It provides practical methods that can be deployed in both research and clinical practices. Future studies should explore stakeholders' experiences and the cost-effectiveness of implementing these strategies.

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.

Neonatal PT Improves Neurobehavior and General Movements in Moderate to Late Preterm Infants Born in India: An RCT.

PURPOSE: To examine whether a structured neonatal physical therapy program (SNP) improves neurobehavior and general movements in moderate to late preterm (MLP) infants. METHODS: Sixty MLP infants participated in this clinical trial. After baseline assessment using the Neurobehavioral Assessment of Preterm Infant (NAPI) and Prechtl General Movements (GMs) Assessment, infants were randomly allocated to a usual care (n = 30) or an SNP group (n = 30) and continued receiving usual care. The SNP group received intervention for 90 minutes/day, 6 days/week until discharge. Changes in neurobehavior and GMs were assessed at hospital discharge. RESULTS: Changes in scores on scarf sign and motor development and vigor clusters of NAPI document an improvement in the SNP group. The proportion of infants with poor repertoire GMs also decreased more in the SNP group than in the usual care group. CONCLUSION: The SNP may be effective in improving some aspects of neurobehavior and quality of GMs in MLP infants. WHAT THIS ADDS TO THE EVIDENCE: The addition of a structured neonatal physical therapy program to usual care can promote neurobehavioral organization and improve the quality of general movements in moderate and late preterm infants in India.

Endovascular Management of Iatrogenic Vertebral Artery Transection During Anterior Cervical Spine Surgery: A Case Report.

Anterior surgical approaches to the cervical spinal pathology have become a frequently used technique. Anterior cervical spine surgeries are generally considered to be safe with low incidence of neurological complications. Vertebral artery (VA) injuries are infrequent during an anterior cervical spine approach but can be devastating. A retrospective review of these injuries documents an incidence of 0.3%-0.5%. However, there is no established strategy or guidelines for managing iatrogenic VA injuries. We describe a case of iatrogenic VA injury at C5 vertebral level during an anterior cervical approach for C5 cervical osteoblastoma; successful managed by endovascular coiling using detachable coils achieving complete occlusion. The patient had a good clinical outcome, with no symptoms of vertebrobasilar insufficiency at 2-year follow-up. There is a paradigm shift in the management of the VA injury after introduction of the interventional angiography. Endovascular embolization is a safe and effective treatment option, which offers certain advantages over open surgery such as minimal invasion, lower risk of neurological injury, lower morbidity, and recurrence rates.

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.

Neuronavigation based 10 sessions of repetitive transcranial magnetic stimulation therapy in chronic migraine: an exploratory study.

INTRODUCTION: Chronic migraine is a disease of altered cortical excitability. Repetitive transcranial magnetic stimulation provides a novel non-invasive method to target the nociceptive circuits in the cortex. Motor cortex is one such potential target. In this study, we targeted the left motor cortex using fMRI-guided neuronavigation. MATERIALS AND METHODS: Twenty right-handed patients were randomized into real and sham rTMS group. Baseline subjective pain assessments were done using visual analog scale (VAS) and questionnaires: State-Trait Anxiety Inventory, Becks Depression Inventory, and Migraine Disability Assessment (MIDAS) questionnaire. Objectively, pain was assessed by means of thermal pain thresholds using quantitative sensory testing. For corticomotor excitability parameters, resting motor thresholds and motor-evoked potentials were mapped. For rTMS total, 600 pulses in 10 trains at 10 Hz with an intertrain interval of 60 s were delivered in each session. Ten such sessions were given 5 days per week over 2 consecutive weeks. The duration of each session was 10 min. Real rTMS was administered at 70% of Resting MT. All the tests were repeated post-intervention and after 1 month of follow-up. There are no studies reporting the use of fMRI-based TMS for targeting the motor cortex in CM patients. RESULTS: We observed a significant reduction in the mean VAS rating, headache frequency, and MIDAS questionnaire in real rTMS group which was maintained after 1 month of follow-up. CONCLUSION: Ten sessions of fMRI-based rTMS over the left motor cortex may provide long-term pain relief in CM, but further studies are warranted to confirm our preliminary findings.

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.

Closed-loop digital meditation for neurocognitive and behavioral development in adolescents with childhood neglect.

Adverse childhood experiences are linked to poor attentive behaviors during adolescence, as well as increased risk for mental health disorders in adults. However, no study has yet tested targeted interventions to optimize neurocognitive processes in this population. Here, we investigated closed-loop digital interventions in a double-blind randomized controlled study in adolescents with childhood neglect, and evaluated the outcomes using multimodal assessments of neuroimaging, cognitive, behavioral, and academic evaluations. In the primary neuroimaging results, we demonstrate that a closed-loop digital meditation intervention can strengthen functional connectivity of the dorsal anterior cingulate cortex (dACC) in the cingulo-opercular network, which is critically developing during the adolescent period. Second, this intervention enhanced sustained attention and interference-resolution abilities, and also reduced behavioral hyperactivity at a 1-year follow-up. Superior academic performance was additionally observed in adolescents who underwent the digital meditation intervention. Finally, changes in dACC functional connectivity significantly correlated with improvements in sustained attention, hyperactivity, and academic performance. This first study demonstrates that closed-loop digital meditation practice can facilitate development of important aspects of neurocognition and real-life behaviors in adolescents with early childhood neglect.