Resting-state fMRI Analysis Research Articles

Impact of Low-Level Blast Exposure on Brain Function after a One-Day Tactile Training and the Ameliorating Effect of a Jugular Vein Compression Neck Collar Device.

Special Weapons and Tactics (SWAT) personnel who conduct breacher exercises are at risk for blast-related head trauma. We aimed to investigate the potential impact of low-level blast exposure during breacher training on the neural functioning of working memory and auditory network connectivity. We also aimed to evaluate the effects of a jugular vein compression collar, designed to internally mitigate slosh energy absorption, preserving neural functioning and connectivity, following blast exposure. A total of 23 SWAT personnel were recruited and randomly assigned to a non-collar (n = 11) and collar group (n = 12). All participants completed a 1-day breacher training with multiple blast exposure. Prior to and following training, 18 participants (non-collar, n = 8; collar, n = 10) completed functional magnetic resonance imaging (fMRI) of working memory using N-Back task; 20 participants (non-collar, n = 10; collar, n = 12) completed resting-state fMRI. Key findings from the working memory analysis include significantly increased fMRI brain activation in the right insular, right superior temporal pole, right inferior frontal gyrus, and pars orbitalis post-training for the non-collar group (p < 0.05, threshold-free cluster enhancement corrected), but no changes were noted for the collar group. The elevation in fMRI activation in the non-collar group was found to correlate significantly (n = 7, r = 0.943, p = 0.001) with average peak impulse amplitude experienced during the training. In the resting-state fMRI analysis, significant pre- to post-training increase in connectivity between the auditory network and two discrete regions (left middle frontal gyrus and left superior lateral occipital/angular gyri) was found in the non-collar group, while no change was observed in the collar group. These data provided initial evidence of the impact of low-level blast on working memory and auditory network connectivity as well as the protective effect of collar on brain function following blast exposure, and is congruent with previous collar findings in sport-related traumatic brain injury.

Fronto-Temporal Circuits in Musical Hallucinations: A PET-MR Case Study.

The aim of the study is to investigate morphofunctional circuits underlying musical hallucinations (MH) in a 72-years old female that underwent a simultaneous 18fluoredeoxyglucose positron emission tomography (PET) and advanced magnetic resonance (MR) exam. This represents a particular case of MH occurred in an healthy subject, not displaying neurological or psychopathological disorders, and studied simultaneously with a multimodal approach. For the resting-state fMRI analysis a seed to seed approach was chosen. For the task-based fMRI, 4 different auditory stimuli were presented. Imaging findings were compared with data obtained by ten healthy controls matched for age and sex. Neuropsychological evaluation and questionnaires investigating depression and anxiety were also administered. PET findings showed hypermetabolism of: superior temporal gyri, anterior cingulate, left orbital frontal, and medial temporal cortices. Structural MRI did not show macroscopical lesions except for gliotic spots along the uncinate fascicle pathways with an increased cortical thickness for the right orbitofrontal cortex (p = 0.003). DTI showed increased fractional anisotropy values in the left uncinate fascicle, when compared to controls (p = 0.04). Resting-state fMRI showed increased functional connectivity between the left inferior frontal gyrus and the left temporal fusiform cortex (p = 0.01). Task-based fMRI confirmed PET findings showing an increased activation of the superior temporal gyrus in all the auditory tasks except for the monotone stimulus, with a significant activation of the left orbital frontal cortex only during the song in foreign language, object of MH. Results on cognitive test did not show cognitive impairment, excepting for the performance on Frontal Assessment Battery where the patient fails in the cognitive domains of conceptualization, sensitive to interference, and inhibitory control. The subject did not show depressive or anxiety symptoms. Summarizing, multimodal imaging analyses in the MH case showed a microstructural alteration of the left uncinate fascicle paralleled by an increased metabolism and functional connectivity of cortical regions that receive left uncinate projections (orbital frontal cortex, and medial temporal cortex). This alteration of fronto-hyppocampal circuits could be responsible of retrieval of known songs even in the absence of real stimuli.

A resting state fMRI analysis pipeline for pooling inference across diverse cohorts: an ENIGMA rs-fMRI protocol.

Large-scale consortium efforts such as Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) and other collaborative efforts show that combining statistical data from multiple independent studies can boost statistical power and achieve more accurate estimates of effect sizes, contributing to more reliable and reproducible research. A meta- analysis would pool effects from studies conducted in a similar manner, yet to date, no such harmonized protocol exists for resting state fMRI (rsfMRI) data. Here, we propose an initial pipeline for multi-site rsfMRI analysis to allow research groups around the world to analyze scans in a harmonized way, and to perform coordinated statistical tests. The challenge lies in the fact that resting state fMRI measurements collected by researchers over the last decade vary widely, with variable quality and differing spatial or temporal signal-to-noise ratio (tSNR). An effective harmonization must provide optimal measures for all quality data. Here we used rsfMRI data from twenty-two independent studies with approximately fifty corresponding T1-weighted and rsfMRI datasets each, to (A) review and aggregate the state of existing rsfMRI data, (B) demonstrate utility of principal component analysis (PCA)-based denoising and (C) develop a deformable ENIGMA EPI template based on the representative anatomy that incorporates spatial distortion patterns from various protocols and populations.

Functional Magnetic Resonance Imaging and Oculomotor Dysfunction in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is a significant cause of disability, especially when symptoms become chronic. This chronicity is often linked to oculomotor dysfunction (OMD). To our knowledge, this is the first prospective study to localize aberrations in brain function between mTBI cohorts, by comparing patients with mTBI with OMD with an mTBI control group without OMD, using task and resting-state functional magnetic resonance imaging (fMRI). Ten subjects with mTBI who had OMD (OMD group) were compared with nine subjects with mTBI who had no findings of OMD (control group). These groups were determined by a developmental optometrist using objective testing for OMD. The (convergence) task fMRI data demonstrated significantly decreased brain activity, measured as decreases in the blood oxygen level dependent (BOLD) signal, in the OMD group compared with the control group in three brain regions: the left posterior lingual gyrus, the bilateral anterior lingual gyrus and cuneus, and the parahippocampal gyrus. When doing a seed-based resting state fMRI analysis in the lingual/parahippocampal region, a large cluster covering the left middle frontal gyrus and the dorsolateral pre-frontal cortex (Brodmann areas 9 and 10), with decreased functional correlation in the OMD group, was identified. Together these observations provide evidence for neural networks of interactions involving the control of eye movement for visual processing, reading comprehension, spatial localization and navigation, and spatial working memory that appear to be decreased in mTBI patients with OMD compared with mTBI patients without OMD. The clinical symptomatology associated with post-traumatic OMD correlates well with these MRI findings.

Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [18 F]fallypride PET and functional MRI study.

In addition to probing regional differences in receptor availability, molecular positron emission tomography (PET) is proving useful for investigating perturbations in neurotransmitter networks using interregional correlation analyses. In a multi-modal imaging study, we examined interregional correlationsof dopamine D2/3 receptor availability between striatal and extrastriatal regions using [18 F]fallypride high-resolution PET in 11 patients with schizophrenia receiving low-dose maintenance atypical antipsychotics and 14 healthy control subjects, and investigated resting-state functional connectivity in the same subjects using seed-based functional magnetic resonance imaging (fMRI) analysis. In the healthy control group, there were no significant correlations of [18 F]fallypride binding potential (BPND ) between striatal regions and any cortical areas, whereas the patient group showed significant and widespread inter-correlations. Correlations between BPND in striatum, amygdala and insula with cortex were significantly higher in patients than in controls. In seed-based resting-state fMRI analysis, the healthy controls revealed positive and negative functional connectivity patterns, while patients exhibited a pattern of exclusively positive connectivity. Functional connectivity was significantly higher between striatal regions and extrastriatal areas including cortical regions in patients compared to controls. In this first such report, molecular and functional connectivity between striatal and extrastriatal regions was primarily characterized by increased interregional relationships in treated patients with schizophrenia. The results suggest that the spatial organization of D2/3 receptor availability and related functional connectivity are significantly perturbed in stable outpatients on maintenance antipsychotics. Future studies should include antipsychotic-naïve patients to determine if these relationships are illness-related characteristics, or arising due to chronic antipsychotic treatment.

Pragmatic abilities in multiple sclerosis: The contribution of the temporo-parietal junction

Recent studies showed that multiple sclerosis (MS) patients might experience communicative deficits, specifically in pragmatics (i.e., the ability to integrate the context-dependent aspects of language). A crucial region for pragmatics is the temporo-parietal junction, in particular the so-called Geschwind’s area (GA), which is involved in high-level language processes, including the comprehension of narratives, metaphor, and irony. We evaluated the relationship between pragmatic abilities, measured through the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) test, and the functional connectivity (FC) of the bilateral GAs, assessed through a seed-based analysis of Resting-State fMRI in patients with MS. A positive correlation was observed between APACS scores and the FC for both the right and the left GA and the paracingulate cortex. Our findings suggest that the brain FC for social communication involves connections extending over both hemispheres, including right and left GAs and right and left paracingulate cortex, possibly impaired in patients with MS. This study offers preliminary evidence for future researches enrolling also a control sample to explore the involvement of GA in pragmatics in neurological disorders as well as in healthy conditions.

Cerebellum and cognition in progressive MS patients: functional changes beyond atrophy?

The cerebellum is a predilection site of pathology in progressive multiple sclerosis (PMS) patients, contributing to cognitive deficits. Aim of this study was to investigate lobular cerebellar functional connectivity (FC) in PMS patients in relation to cognition. In this cross-sectional study, resting state fMRI analysis was carried out on 29 PMS patients (11 males, mean age 51.2 ± 11.9years) and 22 age- and sex-matched healthy controls (HC) (11 males, mean age 49.6 ± 8.8years). Data were analyzed with a seed-based approach, with four different seeds placed at the level of cerebellar Lobule VI, Crus I, Crus II and Lobule VIIb, accounting for cerebellar structural damage. Cognitive status was assessed with the BICAMS battery. Correlations between fMRI data and clinical variables were probed with the Spearman correlation coefficient. When testing FC differences between PMS and HC without taking into account cerebellar structural damage, PMS patients showed a reduction of FC between Crus II/Lobule VIIb and the right frontal pole (p = 0.001 and p = 0.002, respectively), with an increased FC between Lobule VIIb and the right precentral gyrus (p < 0.001). After controlling for structural damage, PMS patients still showed a reduced FC between Crus II and right frontal pole (p = 0.005), as well as an increased FC between Lobule VIIb and right precentral gyrus (p = 0.003), with the latter showing an inverse correlation with BVMT scores (r = - 0.393; p = 0.03). PMS patients show cerebellar FC rearrangements that are partially independent from cerebellar structural damage, and are likely expression of a maladaptive functional rewiring.

Weighted Random Support Vector Machine Clusters Analysis of Resting-State fMRI in Mild Cognitive Impairment.

The identification of abnormal cognitive decline at an early stage becomes an increasingly significant conundrum to physicians and is of major interest in the studies of mild cognitive impairment (MCI). Support vector machine (SVM) as a high-dimensional pattern classification technique is widely employed in neuroimaging research. However, the application of a single SVM classifier may be difficult to achieve the excellent classification performance because of the small-sample size and noise of imaging data. To address this issue, we propose a novel method of the weighted random support vector machine cluster (WRSVMC) in which multiple SVMs were built and different weights were given to corresponding SVMs with different classification performances. We evaluated our algorithm on resting state functional magnetic resonance imaging (RS-fMRI) data of 93 MCI patients and 105 healthy controls (HC) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The maximum accuracy given by the WRSVMC is 87.67%, demonstrating excellent diagnostic power. Furthermore, the most discriminative brain areas have been found out as follows: gyrus rectus (REC.L), precentral gyrus (PreCG.R), olfactory cortex (OLF.L), and middle occipital gyrus (MOG.R). These findings of the paper provide a new perspective for the clinical diagnosis of MCI.

Preoperative Mapping of the Supplementary Motor Area in Patients with Brain Tumor Using Resting-State fMRI with Seed-Based Analysis.

The supplementary motor area can be a critical region in the preoperative planning of patients undergoing brain tumor resection because it plays a role in both language and motor function. While primary motor regions have been successfully identified using resting-state fMRI, there is variability in the literature regarding the identification of the supplementary motor area for preoperative planning. The purpose of our study was to compare resting-state fMRI to task-based fMRI for localization of the supplementary motor area in a large cohort of patients with brain tumors presenting for preoperative brain mapping. Sixty-six patients with brain tumors were evaluated with resting-state fMRI using seed-based analysis of hand and orofacial motor regions. Rates of supplementary motor area localization were compared with those in healthy controls and with localization results by task-based fMRI. Localization of the supplementary motor area using hand motor seed regions was more effective than seeding using orofacial motor regions for both patients with brain tumor (95.5% versus 34.8%, P < .001) and controls (95.2% versus 45.2%, P < .001). Bilateral hand motor seeding was superior to unilateral hand motor seeding in patients with brain tumor for either side (95.5% versus 75.8%/75.8% for right/left, P < .001). No difference was found in the ability to identify the supplementary motor area between patients with brain tumors and controls. In addition to task-based fMRI, seed-based analysis of resting-state fMRI represents an equally effective method for supplementary motor area localization in patients with brain tumors, with the best results obtained with bilateral hand motor region seeding.

Non-linear ICA Analysis of Resting-State fMRI in Mild Cognitive Impairment

Compared to linear independent component analysis (ICA), non-linear ICA is more suitable for the decomposition of mixed components. Existing studies of functional magnetic resonance imaging (fMRI) data by using linear ICA assume that the brain's mixed signals, which are caused by the activity of brain, are formed through the linear combination of source signals. But the application of the non-linear combination of source signals is more suitable for the mixed signals of brain. For this reason, we investigated statistical differences in resting state networks (RSNs) on 32 healthy controls (HC) and 38 mild cognitive impairment (MCI) patients using post-nonlinear ICA. Post-nonlinear ICA is one of the non-linear ICA methods. Firstly, the fMRI data of all subjects was preprocessed. The second step was to extract independent components (ICs) of fMRI data of all subjects. In the third step, we calculated the correlation coefficient between ICs and RSN templates, and selected ICs of the largest spatial correlation coefficient. The ICs represent the corresponding RSNs. After finding out the eight RSNs of MCI group and HC group, one sample t-tests were performed. Finally, in order to compare the differences of RSNs between MCI and HC groups, the two-sample t-tests were carried out. We found that the functional connectivity (FC) of RSNs in MCI patients was abnormal. Compared with HC, MCI patients showed the increased and decreased FC in default mode network (DMN), central executive network (CEN), dorsal attention network (DAN), somato-motor network (SMN), visual network(VN), MCI patients displayed the specifically decreased FC in auditory network (AN), self-referential network (SRN). The FC of core network (CN) did not reveal significant group difference. The results indicate that the abnormal FC in RSNs is selective in MCI patients.

Dynamic functional connectivity markers of objective trait mindfulness

While mindfulness is commonly viewed as a skill to be cultivated through practice, untrained individuals can also vary widely in dispositional mindfulness. Prior research has identified static neural connectivity correlates of this trait. Here, we use dynamic functional connectivity (DFC) analysis of resting-state fMRI to study time-varying connectivity patterns associated with naturally varying and objectively measured trait mindfulness. Participants were selected from the top and bottom tertiles of performers on a breath-counting task to form high trait mindfulness (HTM; N = 21) and low trait mindfulness (LTM; N = 18) groups. DFC analysis of resting state fMRI data revealed that the HTM group spent significantly more time in a brain state associated with task-readiness – a state characterized by high within-network connectivity and greater anti-correlations between task-positive networks and the default-mode network (DMN). The HTM group transitioned between brain states more frequently, but the dwell time in each episode of the task-ready state was equivalent between groups. These results persisted even after controlling for vigilance. Across individuals, certain connectivity metrics were weakly correlated with self-reported mindfulness as measured by the Five Facet Mindfulness Questionnaire, though these did not survive multiple comparisons correction. In the static connectivity maps, HTM individuals had greater within-network connectivity in the DMN and the salience network, and greater anti-correlations between the DMN and task-positive networks. In sum, DFC features robustly distinguish HTM and LTM individuals, and may be useful biological markers for the measurement of dispositional mindfulness.

T131. KNCQ Channel Opener Ezogabine_x000B_as a Treatment for Depression: A Preliminary Resting State fMRI Analysis

Preclinical studies utilizing a rodent social defeat stress model of depression have established that hyperactivity of the ventral tegmental area may be involved in the pathophysiology of major depressive disorder. Friedman et al. demonstrated that systemic administration of ezogabine, an FDA-approved KCNQ-type potassium channel opener, normalized VTA hyperactivity as well as depressive behaviors.

Task-positive and task-negative networks in major depressive disorder: A combined fMRI and EEG study

BackgroundThe study of intrinsic connectivity networks, i.e., sets of brain regions that show a high degree of interconnectedness even in the absence of a task, showed that major depressive disorder (MDD) patients demonstrate an increased connectivity within the default mode network (DMN), which is active in a resting state and is implicated in self-referential processing, and a decreased connectivity in task-positive networks (TPNs), which increase their activity in attention tasks. Cortical localization of this ‘dominance’ of the DMN over the TPN in MDD patients is not fully understood. Besides, this effect has been investigated using fMRI and its electrophysiological underpinning is not known. MethodIn this study, we tested the dominance hypothesis using seed-based connectivity analysis of resting-state fMRI and EEG data obtained in 41 MDD patients and 23 controls. ResultsIn MDD patients, as compared to controls, insula, pallidum/putamen, amygdala, and left dorso- and ventrolateral prefrontal cortex are more strongly connected with DMN than with TPN seeds. In EEG, all significant effects were obtained in the delta frequency band. LimitationsfMRI and EEG data were not obtained simultaneously during the same session. ConclusionsIn MDD patients, major emotion and attention regulation circuits are more strongly connected with DMN than with TPN implying they are more prepared to respond to internally generated self-related thoughts than to environmental challenges.

Neuroimaging in neurodevelopmental disorders: focus on resting-state fMRI analysis of intrinsic functional brain connectivity.

Resting-state fMRI assessment of instrinsic functional brain connectivity (rs-fcMRI) in autism spectrum disorders (ASD) allows assessment of participants with a wide range of functioning levels, and collection of multisite databases that facilitate large-scale analysis. These heterogeneous multisite data present both promise and methodological challenge. Herein, we provide an overview of recent (1 October 2016-1 November 2017) empirical research on ASD rs-fcMRI, focusing on work that helps clarify how best to leverage the power of these data. Recent research indicates that larger samples, careful atlas selection, and attention to eye status of participants will improve the sensitivity and power of resting-state fMRI analyses conducted using multisite data. Use of bandpass filters that extend into a slightly higher frequency range than typical defaults may prevent loss of disease-relevant information. Connectivity-based parcellation as an approach to region of interest analyses may allow for improved understanding of functional connectivity disruptions in ASD. Treatment approaches using rs-fcMRI to determine target engagement, predict treatment, or facilitate neurofeedback demonstrate promise. Rs-fcMRI data have great promise for biomarker identification and treatment development in ASD; however, ongoing methodological development and evaluation is crucial for progress.

Resting State BOLD Variability in Alzheimer's Disease: A Marker of Cognitive Decline or Cerebrovascular Status?

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that may benefit from early diagnosis and intervention. Therefore, there is a need to identify early biomarkers of AD using non-invasive techniques such as functional magnetic resonance imaging (fMRI). Recently, novel approaches to the analysis of resting-state fMRI data have been developed that focus on the moment-to-moment variability in the blood oxygen level dependent (BOLD) signal. The objective of the current study was to investigate BOLD variability as a novel early biomarker of AD and its associated psychophysiological correlates.Method: Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2 database from 19 participants with AD and 19 similarly aged controls. For each participant, a map of BOLD signal variability (SDBOLD) was computed as the standard deviation of the BOLD timeseries at each voxel. Group comparisons were performed to examine global differences in resting state SDBOLD in AD versus healthy controls. Correlations were then examined between participant SDBOLD maps and (1) ADNI-derived composite scores of memory and executive function and (2) neuroimaging markers of cerebrovascular status.Results: Between-group comparisons revealed significant (p < 0.05) increases in SDBOLD in patients with AD relative to healthy controls in right-lateralized frontal regions. Lower memory scores and higher WMH burden were associated with greater SDBOLD in the healthy control group (p < 0.1), but not individuals with AD.Conclusion: The current study provides proof of concept of a novel resting state fMRI analysis technique that is non-invasive, easily accessible, and clinically compatible. To further explore the potential of SDBOLD as a biomarker of AD, additional studies in larger, longitudinal samples are needed to better understand the changes in SDBOLD that characterize earlier stages of disease progression and their underlying psychophysiological correlates.

Mapping brain functional alterations in betel-quid chewers using resting-state fMRI and network analysis.

The World Health Organization regards betel quid (BQ) as a human carcinogen, and DSM-IV and ICD-10 dependence symptoms may develop with its heavy use. BQ's possible effects of an enhanced reward system and disrupted inhibitory control may increase the likelihood of habitual substance use. The current study aimed to employ resting-state fMRI to examine the hypothesized enhanced reward system (e.g., the basal forebrain system) and disrupted inhibitory control (e.g., the prefrontal system) in BQ chewers. The current study recruited three groups of 48 male participants: 16 BQ chewers, 15 tobacco- and alcohol-user controls, and 17 healthy controls. We used functional connectivity (FC), mean fractional amplitude of low-frequency fluctuations (mfALFF), and mean regional homogeneity (mReHo) to evaluate functional alternations in BQ chewers. Graph theoretical analysis (GTA) and network-based statistical (NBS) analysis were also performed to identify the functional network differences among the three groups. Our hypothesis was partially supported: the enhanced reward system for the BQ chewers (e.g., habitual drug-seeking behavior) was supported; however, their inhibitory control was relatively preserved. In addition, we reported that the BQ chewers may have enhanced visuospatial processing and decreased local segregation. The current results (showing an enhanced reward system in the chewers) provided the clinicians with important insight for the future development of an effective abstinence treatment.

The reorganization of functional architecture in the early-stages of Parkinson's disease

IntroductionThe study aim was to identify longitudinal abnormalities of functional connectivity and its relation with motor disability in early to moderately advanced stages of Parkinson's disease patients. Methods3.0T structural and resting-state functional MRI was performed in healthy subjects (n = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2 ± 1.2 years at baseline with a clinical follow-up of 1.5 ± 0.3 years. Resting-state fMRI analysis included region-to-region connectivity in correlation with UPDRS-III scores and computation of Global Efficiency and Degree Centrality. ResultsAt baseline, patients' connectivity increased between the cerebellum and somatomotor network, and decreased between motor regions (Rolandic operculum, precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate connectivity. At 1.5 years follow-up, connectivity remained altered in the same regions identified at baseline. The cerebellum showed additional hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala compared to controls. These differences correlated with UPDRS-III scores. Seed-based connectivity revealed increased involvement of the default mode network with precentral gyrus in patients at follow-up investigation. ConclusionResting-state fMRI identified marked disturbances of the overall architecture of connectivity in Parkinson's disease. The noted alterations in cortical motor areas were associated with cerebellar hyperconnectivity in early to moderately advanced stages of Parkinson's disease suggesting ongoing attempts of recovery and compensatory mechanism for affected functions. The potential to identify connectivity alterations in regions related to both motor and attentional functions requires further evaluation as an objective marker to monitor disease progression, and medical, as well as surgical interventions.

Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort

Delineation of functional topography is critical to the evolving understanding of the cerebellum's role in a wide range of nervous system functions. We used data from the Human Connectome Project (n = 787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting-state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohen's d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non-motor tasks in the same participants, and convergent resting-state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?).

Tumor Tissue Detection using Blood-Oxygen-Level-Dependent Functional MRI based on Independent Component Analysis

Accurate delineation of gliomas from the surrounding normal brain areas helps maximize tumor resection and improves outcome. Blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) has been routinely adopted for presurgical mapping of the surrounding functional areas. For completely utilizing such imaging data, here we show the feasibility of using presurgical fMRI for tumor delineation. In particular, we introduce a novel method dedicated to tumor detection based on independent component analysis (ICA) of resting-state fMRI (rs-fMRI) with automatic tumor component identification. Multi-center rs-fMRI data of 32 glioma patients from three centers, plus the additional proof-of-concept data of 28 patients from the fourth center with non-brain musculoskeletal tumors, are fed into individual ICA with different total number of components (TNCs). The best-fitted tumor-related components derived from the optimized TNCs setting are automatically determined based on a new template-matching algorithm. The success rates are 100%, 100% and 93.75% for glioma tissue detection for the three centers, respectively, and 85.19% for musculoskeletal tumor detection. We propose that the high success rate could come from the previously overlooked ability of BOLD rs-fMRI in characterizing the abnormal vascularization, vasomotion and perfusion caused by tumors. Our findings suggest an additional usage of the rs-fMRI for comprehensive presurgical assessment.

Discrete Modules and Mesoscale Functional Circuits for Thermal Nociception within Primate S1 Cortex.

This study addresses one long-standing question of whether functional separations are preserved for somatosensory modalities of touch, heat, and cold nociception within primate primary somatosensory (S1) cortex. This information is critical for understanding how the nature of pain is represented in the primate brain. Using a combination of submillimeter-resolution fMRI and microelectrode local field potential (LFP) and spike recordings, we identified spatially segregated cortical zones for processing touch and nociceptive heat and cold stimuli in somatotopically appropriate areas 3a, 3b, 1, and 2 of S1 in male monkeys. The distances between zones were comparable (∼3.4 mm) across stimulus modalities (heat, cold, and tactile), indicating the existence of uniform, modality-specific modules. Stimulus-evoked LFP maps validated the fMRI maps in areas 3b and 1. Isolation of heat and cold nociceptive neurons from the fMRI zones confirmed the validity of using fMRI to probe nociceptive regions and circuits. Resting-state fMRI analysis revealed distinct intrinsic functional circuits among functionally related zones. We discovered distinct modular structures and networks for thermal nociception within S1 cortex, a finding that has significant implications for studying chronic pain syndromes and guiding the selection of neuromodulation targets for chronic pain management.SIGNIFICANCE STATEMENT Primate S1 subregions contain discrete heat and cold nociceptive modules. Modules with the same properties exhibit strong functional connection. Nociceptive fMRI response coincides with LFP and spike activities of nociceptive neurons. Functional separation of heat and cold pain is retained within primate S1 cortex.