Cortical Gray Matter Thickness and Volume Changes and Their Association with Memory Functions in Hyperthyroid Patients.

INTRODUCTION: Hyperthyroidism, characterized by excessive thyroid hormone production, is a common endocrine disorder that affects various physiological processes, including brain function. Recent advancements in neuroimaging techniques have enabled researchers to investigate structural alterations in the brain associated with hyperthyroidism. This study aimed to examine regional cortical thickness and cortical volume differences across the brain between hyperthyroid patients and control subjects. METHODS: We examined localized cortical thicknesses and volumes in 34 hyperthyroid patients and 35 control subjects with high-resolution T1-weighted images using FreeSurfer software and assessed group differences with analysis of covariance (covariates: age, sex, education, and total intracranial volume). Spearman and partial correlations were performed between clinical variables and cortical thicknesses/volumes and between neuropsychological scores and cortical thicknesses/volumes, respectively. RESULTS: Hyperthyroid patients exhibited significantly increased cortical thickness in bilateral superior temporal and superior frontal gyri, along with higher cortical volumes in various regions, including the right superior temporal gyrus, right superior parietal gyrus, right rostral and caudal middle frontal gyrus, and left superior frontal gyrus. Notably, thyroid hormones (fT3, fT4) correlated positively with cortical thicknesses and volumes in the superior temporal gyrus and superior frontal gyrus. Additionally, recognition memory scores negatively correlated with the right superior temporal gyrus and right superior frontal gyrus cortical thickness. CONCLUSION: The observed cortical thickening and increased cortical volume in specific brain areas provide new insights into the pathophysiological mechanism associated with brain impairment in hyperthyroidism.

Motor function deficits in schizophrenia: an fMRI and VBM study.

INTRODUCTION: To investigate whether the motor functional alterations in schizophrenia (SZ) are also associated with structural changes in the related brain areas using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). METHODS: A sample of 14 right-handed SZ patients and 14 right-handed healthy control subjects matched for age, sex, and education were examined with structural high-resolution T1-weighted MRI; fMRI images were obtained during right index finger-tapping task in the same session. RESULTS: fMRI results showed reduced functional activation in the motor areas (contralateral precentral and postcentral gyrus) and ipsilateral cerebellum in SZ subjects as compared to healthy controls (n = 14). VBM analysis also revealed reduced grey matter in motor areas and white matter reduction in cerebellum of SZ subjects as compared to controls. CONCLUSION: The present study provides an evidence for a possible association between structural alterations in the motor cortex and disturbed functional activation in the motor areas in persons affected with SZ during a simple finger-tapping task.

Assessment of abstract reasoning abilities in alcohol-dependent subjects: an fMRI study.

INTRODUCTION: Chronic alcohol abuse has been traditionally associated with impaired cognitive abilities. The deficits are most evident in higher order cognitive functions, such as abstract reasoning, problem solving and visuospatial processing. The present study sought to increase current understanding of the neuropsychological basis of poor abstract reasoning abilities in alcohol-dependent subjects using functional magnetic resonance imaging (fMRI). METHODS: An abstract reasoning task-based fMRI study was carried out on alcohol-dependent subjects (n = 18) and healthy controls (n = 18) to examine neural activation pattern. The study was carried out using a 3-T whole-body magnetic resonance scanner. Preprocessing and post processing was performed using SPM 8 software. RESULTS: Behavioral data indicated that alcohol-dependent subjects took more time than controls for performing the task but there was no significant difference in their response accuracy. Analysis of the fMRI data indicated that for solving abstract reasoning-based problems, alcohol-dependent subjects showed enhanced right frontoparietal neural activation involving inferior frontal gyrus, post central gyrus, superior parietal lobule, and occipito-temporal gyrus. CONCLUSIONS: The extensive activation observed in alcohol dependents as compared to controls suggests that alcohol dependents recruit additional brain areas to meet the behavioral demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting decreased neural efficiency of relevant brain networks or compensatory mechanisms for the execution of task for showing an equivalent performance.

Atrophic kidney-like lesion: A rare benign entity and mimicker of thyroid follicular-like carcinoma of kidney.

Atrophic kidney like lesion (AKLL) is a recently described benign entity with only 14 cases reported so far. Genitourinary Pathology Society proposed inclusion of AKLL as a provisional entity in 2021. It mimics thyroid follicular-like carcinoma of kidney as it has a follicular architecture. We report a case of an 18-year-old female with detection of renal mass, while the patient was being investigated for abdominal pain. Mediastinal nodes were also enlarged with detection of necrotizing granulomas on biopsy. Histology revealed a tumor enveloped by a thick capsule with smooth muscle fibers, varying sized follicles, interspersed atrophic tubules, and calcifications. Immunohistochemically, the "cystic follicles" show WT1 +/PAX8 -/CK7-phenotype, while atrophic tubules present between "cystic follicles" harbor WT1 -/PAX8 +/CK7 + phenotype. Morphological diagnosis and differential diagnosis will be discussed.

Primary pleural serous carcinoma of mullerian origin-Report of a rare case.

ABSTRACT: Mullerian tumor arising from pleura is a rare occurrence and under-reported in medical literature. We hereby present such a case in a 47 years old female who presented with pleural effusion. Pleural biopsy revealed a papillary tumor with mild-to-moderate nuclear atypia. Immunohistochemistry profile with positivity for WT1, Pax8, ER, and PR together with negative mesothelial markers and ruling out primary in female genitalia led us to a diagnosis of primary pleural serous carcinoma of mullerian origin. The patient received paclitaxel and carboplatin chemotherapy and is disease-free till now after 2 years of follow-up.

Pre-surgical features of intrinsic brain networks predict single and joint epilepsy surgery outcomes.

Despite the effectiveness of surgical interventions for the treatment of intractable focal temporal lobe epilepsy (TLE), the substrates that support good outcomes are poorly understood. While algorithms have been developed for the prediction of either seizure or cognitive/psychiatric outcomes alone, no study has reported on the functional and structural architecture that supports joint outcomes. We measured key aspects of pre-surgical whole brain functional/structural network architecture and evaluated their ability to predict post-operative seizure control in combination with cognitive/psychiatric outcomes. Pre-surgically, we identified the intrinsic connectivity networks (ICNs) unique to each person through independent component analysis (ICA), and computed: (1) the spatial-temporal match between each person's ICA components and established, canonical ICNs, (2) the connectivity strength within each identified person-specific ICN, (3) the gray matter (GM) volume underlying the person-specific ICNs, and (4) the amount of variance not explained by the canonical ICNs for each person. Post-surgical seizure control and reliable change indices of change (for language [naming, phonemic fluency], verbal episodic memory, and depression) served as binary outcome responses in random forest (RF) models. The above functional and structural measures served as input predictors. Our empirically derived ICN-based measures customized to the individual showed that good joint seizure and cognitive/psychiatric outcomes depended upon higher levels of brain reserve (GM volume) in specific networks. In contrast, singular outcomes relied on systematic, idiosyncratic variance in the case of seizure control, and the weakened pre-surgical presence of functional ICNs that encompassed the ictal temporal lobe in the case of cognitive/psychiatric outcomes. Our data made clear that the ICNs differed in their propensity to provide reserve for adaptive outcomes, with some providing structural (brain), and others functional (cognitive) reserve. Our customized methodology demonstrated that when substantial unique, patient-specific ICNs are present prior to surgery there is a reliable association with poor post-surgical seizure control. These ICNs are idiosyncratic in that they did not match the canonical, normative ICNs and, therefore, could not be defined functionally, with their location likely varying by patient. This important finding suggested the level of highly individualized ICN's in the epileptic brain may signal the emergence of epileptogenic activity after surgery.

Camouflage Detection and Its Association with Cognitive Style: A Functional Connectivity Study.

Background: Individual differences exist in performance in tasks that require visual search, such as camouflage detection (CD). Field dependence/independence (FD/I), as assessed using the Group Embedded Figures Test (GEFT), is an extensively studied dimension of cognitive style that classifies participants based on their visual perceptual styles. Materials and Methods: In the present study, we utilized fMRI on 46 healthy participants to investigate the underlying neural mechanisms specific to the cognitive styles of FD/FI while performing a CD task using both activation magnitude and an exploratory functional connectivity (FC) analysis. Group differences between high and low performers on the two extremes of the accuracy continuum of GEFT were studied. Results: No statistically significant group differences were observed using whole-brain voxel-wise comparison. However, the exploratory FC analysis revealed an enhanced communication between various regions subserving the cognitive traits required for visual search by FI participants over and above their FD counterparts. Conclusion: These enhanced connectivities suggest additional recruitment of cognitive functions to provide computational support that might facilitate superior performance in CD task by the participants who display a field-independent cognitive style.

Ewing sarcoma arising in colon and ovary--Two rare sites of presentation.

Ewing sarcoma is a rare aggressive malignant round cell tumor, primarily presenting in bone and soft tissues. This study presents two cases of this tumor in unusual locations, one in right colon which presented with intussusception and other in ovary which presented clinically as carcinoma ovary. Both the cases showed histomorphology of primitive round cell tumor with characteristic immunohistochemical profile and was confirmed on molecular analysis. We aim to highlight the importance of considering Ewing sarcoma in the differential diagnoses in these locations as they have dismal prognosis with no standard treatment modality.

Brain functional connectivity in patients with hyperthyroidism after anti-thyroid treatment.

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.

Multiple-brain systems dynamically interact during tonic and phasic states to support language integrity in temporal lobe epilepsy.

An epileptogenic focus in the dominant temporal lobe can result in the reorganization of language systems in order to compensate for compromised functions. We studied the compensatory reorganization of language in the setting of left temporal lobe epilepsy (TLE), taking into account the interaction of language (L) with key non-language (NL) networks such as dorsal attention (DAN), fronto-parietal (FPN) and cingulo-opercular (COpN), with these systems providing cognitive resources helpful for successful language performance. We applied tools from dynamic network neuroscience to functional MRI data collected from 23 TLE patients and 23 matched healthy controls during the resting state (RS) and a sentence completion (SC) task to capture how the functional architecture of a language network dynamically changes and interacts with NL systems in these two contexts. We provided evidence that the brain areas in which core language functions reside dynamically interact with non-language functional networks to carry out linguistic functions. We demonstrated that abnormal integrations between the language and DAN existed in TLE, and were present both in tonic as well as phasic states. This integration was considered to reflect the entrainment of visual attention systems to the systems dedicated to lexical semantic processing. Our data made clear that the level of baseline integrations between the language subsystems and certain NL systems (e.g., DAN, FPN) had a crucial influence on the general level of task integrations between L/NL systems, with this a normative finding not unique to epilepsy. We also revealed that a broad set of task L/NL integrations in TLE are predictive of language competency, indicating that these integrations are compensatory for patients with lower overall language skills. We concluded that RS establishes the broad set of L/NL integrations available and primed for use during task, but that the actual use of those interactions in the setting of TLE depended on the level of language skill. We believe our analyses are the first to capture the potential compensatory role played by dynamic network reconfigurations between multiple brain systems during performance of a complex language task, in addition to testing for characteristics in both the phasic/task and tonic/resting state that are necessary to achieve language competency in the setting of temporal lobe pathology. Our analyses highlighted the intra- versus inter-system communications that form the basis of unique language processing in TLE, pointing to the dynamic reconfigurations that provided the broad multi-system support needed to maintain language skill and competency.

Computational support, not primacy, distinguishes compensatory memory reorganization in epilepsy.

Temporal lobe epilepsy is associated with impairment in episodic memory. A substantial subgroup, however, is able to maintain adequate memory despite temporal lobe pathology. Missing from prior work in cognitive reorganization is a direct comparison of temporal lobe epilepsy patients with intact status with those who are memory impaired. Little is known about the regional activations, functional connectivities and/or network reconfigurations that implement changes in primary computations or support functions that drive adaptive plasticity and compensated memory. We utilized task functional MRI on 54 unilateral temporal lobe epilepsy patients and 24 matched healthy controls during the performance of a paired-associate memory task to address three questions: (i) which regions implement paired-associate memory in temporal lobe epilepsy, and do they vary as a function of good versus poor performance, (ii) is there unique functional connectivity present during memory encoding that accounts for intact status by preservation of primary memory computations or the supportive computations that allow for intact memory responses and (iii) what features during memory encoding are most distinctive: is it the magnitude and location of regional activations, or the presence of enhanced functional connections to key structures such as the hippocampus? The study revealed non-dominant hemisphere regions (right posterior temporal regions) involving both increased regional activity and increased modulatory communication with the hippocampi as most important to intact memory in left temporal lobe epilepsy compared to impaired status. The profile involved areas that are neither contralateral homologues to left hemisphere memory areas, nor regions traditionally considered computationally primary for episodic memory. None of these areas of increased activation or functional connectivity were associated with advantaged memory in healthy controls. Our emphasis on different performance levels yielded insight into two forms of cognitive reorganization: computational primacy, where left temporal lobe epilepsy showed little change relative to healthy controls, and computational support where intact left temporal lobe epilepsy patients showed adaptive abnormalities. The analyses isolated the unique regional activations and mediating functional connectivity that implements truly compensatory reorganization in left temporal lobe epilepsy. The results provided a new perspective on memory deficits by making clear that they arise not just from the knockout of a functional hub, but from the failure to instantiate a complex set of reorganization responses. Such responses provided the computational support to ensure successful memory. We demonstrated that by keeping track of performance levels, we can increase understanding of adaptive brain responses and neuroplasticity in epilepsy.

Hepatocellular carcinoma: Clinicopathologic associations amidst marked phenotypic heterogeneity.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by marked phenotypic and molecular heterogeneity. Clinico-morphologic phenotypes and associations are important surrogate markers of molecular aberrations; therefore have immense relevance for targeted therapy. There is paucity of published literature on critical analysis of HCC heterogeneity and morphological alliance. AIMS: To assess the heterogeneity and dominance of histomorphological features, and to explore clinicopathological associations in HCC. METHODS: Retrospective cross-sectional study of 217 HCC tissue specimens was performed for the assessment of prevalence of major histological patterns, cytological features, and clinicopathological correlation. RESULTS: Homogeneous architecture with a single dominant histological pattern was a rarity. Single pattern constituting ≥50 % of the tumour was found in less than 1/5th of the cases. Macrotrabecular HCC represented 9.2 % of cases. The simultaneous presence of 2-3 patterns or atypical variants and/ or cytological characteristics was recorded in 25 % and 30 % respectively. Significant clinicopathological associations: Pseudoglandular with microtrabecular pattern-cholestasis, showed better differentiation and early-stage; macrotrabecular pattern frequently occurred with pleomorphic giant cells, higher tumour stage, higher AFP levels; solid pattern often showed clear cells. Noticeable mutual exclusions were MD bodies with microtrabecular and pseudoglandular patterns; Compact pattern with neutrophilic clusters and cholestasis. Larger tumours were significantly more heterogeneous; however, heterogeneity did not correlate with outcome CONCLUSIONS: HCC displays immense heterogeneity with an amalgamation of different histomorphological patterns and features; nevertheless, there are certain reproducible associations and omissions. Tumor biopsies agree fairly well with large specimens. Characterization of phenotypic heterogeneity, dominance, associations, and exclusions in individual patients provides vital information.

Avoiding Complications in Endoscopic Trans-Sphenoidal Surgery for Pituitary Adenoma: A Beginner's Perspective.

INTRODUCTION: We aimed to analyze the difficulties and complications experienced while as a beginner in endoscopic transnasal transsphenoidal approach for pituitary adenomas. MATERIALS AND METHODS: We retrospectively analyzed 83 cases done from June 2016 to August 2019. Navigation-guided endoscopic transnasal transsphenoidal approach was used in all the cases. RESULTS: Gross total tumor removal was achieved in 55 (66.26%) patients. We found that gross total resection rate was inversely proportional to Knosp grading, and the extent of resection was found to have a statistically significant correlation with grade of tumor (P < 0.05). Surgery-related complications were present in 33 of our patients. Nasal complications occurred in six patients: three epistaxis (3.6%) and two hyposmia (2.4%) and one case of septal hematoma (1.2%). Postoperative cerebrospinal fluid leak occurred in six (7.2%) cases, two (2.4%) cases had sinusitis, while two (2.4%) cases had meningitis. There was a very rare case of subarachnoid hemorrhage and one case had sellar hematoma. Endocrinologic complications occurred in 15 (18.07%) patients: anterior pituitary deficiency in five (6.02%) patients, transient diabetes insipidus (DI) in nine (10.84%) patients, and permanent DI in one (1.2%) patient. There was no vascular injury or mortality noted in our study. CONCLUSION: Endoscopic approach is an effective modality for pituitary surgery; with patience, learning lessons from your own mistakes and by adopting right technique, learning curve can be flattened significantly.

Primary Myoepithelial Carcinoma of the Clivus: A Rare Presentation.

Myoepithelial tumor (MET) of bone is an unusual tumor of uncertain differentiation and histogenesis. Although its presence in various bones has been reported sparsely, the presentation in clivus as primary myoepithelial carcinoma (MEC) has never been reported. They resemble their salivary gland counterparts morphologically and immunohistochemically, but harbor distinct molecular phenotype. At present, moderate nuclear atypia is the acceptable criteria to differentiate MEC from myoepithelioma. Because of their rarity, wide histopathological spectrum, and intraosseous location, MET of bone is easily confused with a variety of primary bone and cartilaginous tumors. Application of immunohistochemistry and, if required, molecular testing are required for making a correct diagnosis. In this article, we describe an extremely rare case of a primary MEC arising from the clivus, which owing to unusual location and immunohistochemical profile was diagnostically challenging.

Individual differences in trait anxiety are associated with gray matter alterations in hypothalamus: Preliminary neuroanatomical evidence.

Trait anxiety is particularly a prone phenotype for the development of anxiety disorders and depression. Studying the neural underpinnings of trait anxiety can further inform our understanding of the etiology of these disorders. To investigate the structural correlates of trait anxiety, high resolution structural images were acquired from 76 right-handed healthy participants and gray matter volumes were extracted from a priori regions of interest (ROIs) that were earlier implicated in anxiety like behaviour (i.e., hippocampus, amygdala, anterior cingulate cortex, thalamus, hypothalamus and prefrontal (dorsolateral, rostrolateral, ventrolateral) cortex. In a partial correlation analysis (with age, gender, and Beck Depression Inventory (BDI) scores as covariates of no interest), trait anxiety was found to be negatively correlated with the gray matter volume of hypothalamus bilaterally and positively correlated with the gray matter volume of left thalamus. In a hierarchical multiple regression analysis, grey matter volume of hypothalamus and left thalamus were found to be the significant predictors of trait anxiety. Our findings thus suggest that a smaller gray matter volume in the hypothalamus and an increase in the gray matter volume of left thalamus is related to a disposition to high anxiety personality trait.

Aberrant intra and inter network resting state functional connectivity in thyrotoxicosis.

Thyroid hormones epigenetically play an important role in the regularisation of neural networks and in neural differentiation during brain development. The present study aimed to explore the intra and inter network resting state functional connectivity changes underlying the neurobehavioural symptoms in thyrotoxicosis. To understand the pathophysiological changes, we investigated the correlation between functional connectivity and clinical and behavioural measures. Twenty-eight freshly diagnosed thyrotoxicosis patients suffering with symptoms such as palpitation, loss of weight, trembling and heat intolerance from days to weeks and 28 healthy controls were recruited for the study. Thyrotoxicosis patients showed significantly decreased functional connectivity in sensorimotor network, fronto-temporal network, default mode network, right fronto-parietal network, left fronto-parietal network and salience network. Inter network functional connectivity was significantly reduced between the basal ganglia network and sensorimotor network and increased between the salience network and fronto-temporal network in thyrotoxicosis. Cognitive functions such as visual retention, recognition of objects, mental balance and performance on neuropsychological tests (ie, the Bender Gestalt test, Nahar-Benson test and Mini Mental State Examination) also showed significant decline in thyrotoxicosis patients. The altered intrinsic resting state functional connectivity might underlie these cognitive deficits. The increased functional connectivity between the salience network and fronto-temporal network suggests the recruitment of additional neuronal circuitry needed to compensate for the neuropathology in the primary neural network in thyrotoxicosis.

Assessment of the metabolic profile in Type 2 diabetes mellitus and hypothyroidism through proton MR spectroscopy.

The metabolic changes in the brain of patients affected with Type 2 diabetes mellitus (DM) alone, both Type 2 DM and hypothyroidism and hypothyroidism only were investigated using proton magnetic resonance spectroscopy ((1)H MRS). Single-voxel spectroscopy was carried out in right and left frontal lobe white matter, left parietal white matter and left occipital gray matter. Choline (Cho)/creatine (Cr) value was found to be increased in the left occipital gray matter of the subjects affected with Type 2 DM and both Type 2 DM and hypothyroidism as compared to controls. No significant change in the Cho/Cr value in the occipital gray matter was observed in hypothyroid subjects as compared to controls. However, they showed an increased level of Cho/Cr in the frontal white matter. High Cho is associated with altered membrane phospholipid metabolism. The high Cho in frontal white matter in hypothyroids and occipital gray matter in diabetic patients suggests that, though both the diseases are endocrine disorders, they differ from each other in terms of regional brain metabolite changes.

Rare Coexistence of Acute Monoblastic Leukemia with Chronic Lymphocytic Leukemia.

Acute monoblastic leukemia (AMoL) is a rare hematopoietic neoplasm, and simultaneous occurrence of acute monoblastic leukemia with chronic lymphocytic leukemia is very rare and only a few cases have been reported in the literature. We here report a rare case of dual hematological malignancy in an 85-year-old male. The peripheral blood and bone marrow examination revealed dual population of atypical cells, comprising large cells with opened-up chromatin having monocytic appearance and small mature-appearing lymphocytes. Flowcytometric immunophenotyping confirmed the monocytic lineage of cells, whereas small lymphocytes showed the immunophenotype consistent with chronic lymphocytic leukemia (CLL). The final diagnosis was made as acute monoblastic leukemia with associated CLL. This is a rare case scenario, and this highlights the importance of careful morphological examination and flowcytometric immunophenotyping in the exact characterization of hematopoietic malignancies.

Trait anxiety and neural efficiency of abstract reasoning: An fMRI investigation.

Worries preoccupy the working memory capacity in anxious individuals, thereby affecting their performance during tasks that require efficient attention regulation. According to the attentional control theory (ACT), trait anxiety affects the processing efficiency, i.e. the effort required for task performance, more than the accuracy of task performance. We investigated the relation between trait anxiety and neural response for a reasoning task in healthy subjects. Functional magnetic resonance imaging (fMRI) was carried out on 22 healthy participants and blood oxygenation level dependent (BOLD) contrast estimates were extracted from a priori regions of interest (ROIs) that were earlier implicated in reasoning (i.e., bilaterally caudate head, globus pallidus, thalamus, prefrontal cortex [[ostral, dorsal and ventral regions]] inferior parietal lobule and middle occipital gyrus). Controlling for the effects of age, gender, state anxiety and depressive symptoms, for equivalent levels of task performance, trait anxiety of the participants was found to be associated with an increase in task related BOLD activation in right globus pallidus, left thalamus and left middle occipital gyrus. Our results suggest a reduced processing efficiency for reasoning in high trait anxiety subjects and provides important brain-behaviour relationships with respect to sub-clinical anxiety.

Alteration in intrinsic and extrinsic functional connectivity of resting state networks associated with subclinical hypothyroid.

Subclinical hypothyroidism (SCH) is characterized by mild elevation of thyroid stimulating hormone (TSH) (range 5-10 µIU/ml) and normal free triiodothyronine (FT3) and free thyroxine (FT4). The cognitive function impairment is well known in thyroid disorders such as hypothyroidism and hyperthyroidism, but little is known about deficits in brain functions in SCH subjects. Also, whether hormone-replacement treatment is necessary or not in SCH subjects is still debatable. In order to have an insight into the cognition of SCH subjects, intrinsic and extrinsic functional connectivity (FC) of the resting state networks (RSNs) was studied. For resting state data analysis we used an unbiased, data-driven approach based on Independent Component Analysis (ICA) and dual-regression that can emphasize widespread changes in FC without restricting to a set of predefined seeds. 28 SCH subjects and 28 matched healthy controls (HC) participated in the study. RSN analysis showed significantly decreased intrinsic FC in somato-motor network (SMN) and right fronto-parietal attention network (RAN) and increased intrinsic FC in default mode network (DMN) in SCH subjects as compared to control subjects. The reduced intrinsic FC in the SMN and RAN suggests neuro-cognitive alterations in SCH subjects in the corresponding functions which were also evident from the deficit in the neuropsychological performance of the SCH subjects on behavioural tests such as digit span, delayed recall, visual retention, recognition, Bender Gestalt and Mini-Mental State Examination (MMSE). We also found a significant reduction in extrinsic network FC between DMN and RAN; SMN and posterior default mode network (PDMN); and increased extrinsic FC between SMN and anterior default mode network (ADMN) in SCH subjects as compared to controls. An altered extrinsic FC in SCH suggests functional reorganization in response to neurological disruption. The partial correlation analysis between intrinsic and extrinsic RSNs FC and neuropsychological performances as well as clinical indices give interesting insights into brain-behavior relationship in SCH subjects. This article is protected by copyright. All rights reserved.