Subcortical Functional Connectivity Research Articles

Differences in subcortical functional connectivity in patients with epilepsy.

Epilepsy is a disease characterized by abnormal paroxysmal bioelectrical activity in the brain cortex and subcortical structures. Seizures per se change brain metabolism in epileptic focus and in distal parts of the brain. However, interictal phenomena can also affect functional connectivity (FC) and brain metabolism in other parts of the brain. We hypothesised that epilepsy affects functional connectivity not only among cortical, but also between subcortical, structures of the brain in a resting state condition. Investigating functional connectivity in patients with epilepsy could provide insights into the underlying pathophysiological mechanisms. Better understanding may lead to more effective treatment strategies. Functional connectivity was analysed in 35 patients with epilepsy and in 28 healthy volunteers. The group of patients was divided into generalised and focal epilepsy (temporal and extratemporal subgroups). Each patient and healthy volunteer underwent an fMRI resting-state session. During the study, EEG signals were simultaneously recorded with fMRI to facilitate the subsequent detection of potential interictal epileptiform discharges (IEDs). Their potential impact on BOLD signals was mitigated through linear regression. The data was processed and correlation coefficients (FC values) between the BOLD signal from selected structures of the central nervous system were determined and compared between study groups. The results were presented as significant differences in correlation coefficients between brain/subcortical structures in the epilepsy and control groups. Lower FC values for the epilepsy group compared to the control group were shown for connections related to the MPFC, hippocampus, thalamus, amygdala, and the parahippocampal gyrus. Epilepsy alters the functional connectivity of resting state subcortical networks. Patterns of pathological changes of FC differ between epilepsy subtypes, with predominant lower FC between the hippocampus, parahippocampal gyrus, amygdala and thalamus in patients with epilepsy. This study suggests that epilepsy affects subcortical structures. Identifying distinct patterns of altered FC in epilepsy subtypes may help to tailor treatment strategies. Changes in FC detected by fMRI may precede clinical symptoms, aiding in the early diagnosis of cognitive and emotional disorders in focal epilepsy.

Reconfigurations of cortical manifold structure during reward-based motor learning

Adaptive motor behavior depends on the coordinated activity of multiple neural systems distributed across the brain. While the role of sensorimotor cortex in motor learning has been well established, how higher-order brain systems interact with sensorimotor cortex to guide learning is less well understood. Using functional MRI, we examined human brain activity during a reward-based motor task where subjects learned to shape their hand trajectories through reinforcement feedback. We projected patterns of cortical and striatal functional connectivity onto a low-dimensional manifold space and examined how regions expanded and contracted along the manifold during learning. During early learning, we found that several sensorimotor areas in the dorsal attention network exhibited increased covariance with areas of the salience/ventral attention network and reduced covariance with areas of the default mode network (DMN). During late learning, these effects reversed, with sensorimotor areas now exhibiting increased covariance with DMN areas. However, areas in posteromedial cortex showed the opposite pattern across learning phases, with its connectivity suggesting a role in coordinating activity across different networks over time. Our results establish the neural changes that support reward-based motor learning and identify distinct transitions in the functional coupling of sensorimotor to transmodal cortex when adapting behavior.

A distinctive subcortical functional connectivity pattern linking negative affect and treatment outcome in major depressive disorder

Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. In this naturalistic prospective study (NCT03294525), we aimed to investigate relationships among subcortical functional connectivity (FC), mood symptom profiles and treatment outcome in MDD using multivariate methods. Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) correlation analysis to explore the association between subcortical FC and mood symptom profiles. FC score, reflecting the weighted representation of each individual in this association, was computed. Replication analysis was undertaken in an independent sample (n = 74). We also investigated the relationship between FC score and treatment outcome in the main sample. A distinctive subcortical connectivity pattern was found to be associated with negative affect. In general, higher FC between the caudate, putamen and thalamus was associated with greater negative affect. This association was partly replicated in the independent sample (similarity between the two samples: r = 0.66 for subcortical connectivity, r = 0.75 for mood symptom profile). Lower FC score predicted both remission and response to treatment after 8 weeks of antidepressant monotherapy. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical FC with negative affect. However, while the FC score significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.

Cortical and subcortical functional connectivity and cognitive impairment in Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson’s Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We focus on canonical cortical networks linked to cognition, including the salience network (SAL), frontoparietal network (FPN), and default mode network (DMN), as well as a subcortical basal ganglia network (BGN). We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. In 82 PD patients, we found that lower MoCA scores were linked with lower intra-network connectivity of the FPN. We also found that lower MoCA scores were linked with lower inter-network connectivity between the SAL and the BGN, the SAL and the DMN, as well as the FPN and the DMN. These data elucidate the relationship of cortical and subcortical functional connectivity with cognitive impairments in PD.

Subcortical functional connectivity and its association with walking performance following deployment related mild TBI.

The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred. In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, Service Members and Veterans whose mild TBI occurred outside of deployment, and Service Members and Veterans who had no lifetime history of TBI. FC patterns differed for the two contextual types of mild TBI. Service Members and Veterans with deployment-related mild TBI demonstrated increased FC between the right caudate and lateral occipital regions relative to both the non-deployment mild TBI and TBI-negative groups. When evaluating the association between FC from the caudate and gait, the non-deployment mild TBI group showed a significant positive relationship between walking time and FC with the frontal pole, implicated in navigational planning, whereas the deployment-related mild TBI group trended towards a greater negative association between walking time and FC within the occipital lobes, associated with visuo-spatial processing during navigation. These findings have implications for elucidating subtle motor disruption in Service Members and Veterans with deployment-related mild TBI. Possible implications for future walking performance are discussed.

Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals.

The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.

Whole-brain functional gradients reveal cortical and subcortical alterations in patients with episodic migraine.

Migraine is a type of headache with multiple neurological symptoms. Prior neuroimaging studies in patients with migraine based on functional magnetic resonance imaging have found regional as well as network-level alterations in brain function. Here, we expand on prior studies by establishing whole-brain functional connectivity patterns in patients with migraine using dimensionality reduction techniques. We studied functional brain connectivity in 50 patients with episodic migraine and sex- and age-matched healthy controls. Using dimensionality reduction techniques that project high-dimensional functional connectivity onto low-dimensional representations (i.e., eigenvectors), we found significant between-group differences in the eigenvectors between patients with migraine and healthy controls, particularly in the sensory/motor and limbic cortices. Furthermore, we assessed between-group differences in subcortical connectivity with subcortical weighted manifolds defined by subcortico-cortical connectivity multiplied by cortical eigenvectors and revealed significant alterations in the amygdala. Finally, leveraging supervised machine learning, we moderately predicted headache frequency using cortical and subcortical functional connectivity features, again indicating that sensory and limbic regions play a particularly important role in predicting migraine frequency. Our study confirmed that migraine is a hierarchical disease of the brain that shows alterations along the sensory-limbic axis, and therefore, the functional connectivity in these areas could be a useful marker to investigate migraine symptomatology.

Structural and functional thalamocortical connectivity study in female fibromyalgia

Dysfunctional thalamocortical interactions have been suggested as putative mechanisms of ineffective pain modulation and also suggested as possible pathophysiology of fibromyalgia (FM). However, it remains unclear which specific thalamocortical networks are altered and whether it is related to abnormal pain perception in people with FM. Here, we conducted combined vertex-wise subcortical shape, cortical thickness, structural covariance, and resting-state functional connectivity analyses to address these questions. FM group exhibited a regional shape deflation of the left posterior thalamus encompassing the ventral posterior lateral and pulvinar nuclei. The structural covariance analysis showed that the extent of regional deflation of the left posterior thalamus was negatively covaried with the left inferior parietal cortical thickness in the FM group, whereas those two regions were positively covaried in the healthy controls. In functional connectivity analysis with the left posterior thalamus as a seed, FM group had less connectivity with the periaqueductal gray compared with healthy controls, but enhanced connectivity between the posterior thalamus and bilateral inferior parietal regions, associated with a lower electrical pain threshold at the hand dorsum (pain-free point). Overall, our findings showed the structural thalamic alteration interacts with the cortical regions in a functionally maladaptive direction, leading the FM brain more responsive to external stimuli and potentially contributing to pain amplification.

Lateralisation of subcortical functional connectivity during and after general anaesthesia

BackgroundArousal and awareness are two important components of consciousness states. Functional neuroimaging has furthered our understanding of cortical and thalamocortical mechanisms of awareness. Investigating the relationship between subcortical functional connectivity and arousal has been challenging owing to the relatively small size of brainstem structures and thalamic nuclei, and their depth in the brain. MethodsResting state functional MRI scans of 72 healthy volunteers were acquired before, during, 1 h after, and 1 day after sevoflurane general anaesthesia. Functional connectivity of subcortical regions of interest vs whole brain and homotopic functional connectivity for assessment of left–right symmetry analyses of both cortical and subcortical regions of interest were performed. Both analyses used high resolution atlases generated from deep brain stimulation applications. ResultsFunctional connectivity in subcortical loci within the thalamus and of the ascending reticular activating system was sharply restricted under anaesthesia, featuring a general lateralisation of connectivity. Similarly, left–right homology was sharply reduced under anaesthesia. Subcortical bilateral functional connectivity was not fully restored after emergence from anaesthesia, although greater restoration was seen between ascending reticular activating system loci and specific thalamic nuclei thought to be involved in promoting and maintaining arousal. Functional connectivity was fully restored to baseline by the following day. ConclusionsFunctional connectivity in the subcortex is sharply restricted and lateralised under general anaesthesia. This restriction may play a part in loss and return of consciousness. Clinical trial registrationNCT02275026.

Reduced Hippocampal-Striatal Interactions during Formation of Durable Episodic Memories in Aging.

Encoding of durable episodic memories requires cross-talk between the hippocampus and multiple brain regions. Changes in these hippocampal interactions could contribute to age-related declines in the ability to form memories that can be retrieved after extended time intervals. Here we tested whether hippocampal–neocortical– and subcortical functional connectivity (FC) observed during encoding of durable episodic memories differed between younger and older adults. About 48 younger (20–38 years; 25 females) and 43 older (60–80 years; 25 females) adults were scanned with fMRI while performing an associative memory encoding task. Source memory was tested ~20 min and ~6 days postencoding. Associations recalled after 20 min but later forgotten were classified as transient, whereas memories retained after long delays were classified as durable. Results demonstrated that older adults showed a reduced ability to form durable memories and reduced hippocampal–caudate FC during encoding of durable memories. There was also a positive relationship between hippocampal–caudate FC and higher memory performance among the older adults. No reliable age group differences in durable memory–encoding activity or hippocampal–neocortical connectivity were observed. These results support the classic theory of striatal alterations as one cause of cognitive decline in aging and highlight that age-related changes in episodic memory extend beyond hippocampal–neocortical connections.

Multimodal brain imaging connectivity analyses of emotional and motivational deficits in depression among women

BackgroundMajor depressive disorder (MDD) is characterized by impaired cortical–subcortical functional connectivity. Apathy adds to functional impairment, but its cerebral basis in MDD remains unknown. Our objective was to describe impairments in functional connectivity during emotional processing in MDD (with varying levels of congruency and attention), and to determine their correlation with apathy.MethodsWe used the Variable Attention Affective Task during functional MRI, followed by diffusion-weighted MRI, to assess 55 right-handed women (30 with MDD and 25 healthy controls) between September 2012 and February 2015. We estimated functional connectivity using generalized psychophysiologic interaction and anatomic connectivity with tract-based spatial statistics. We measured apathy using the Apathy Evaluation Scale.ResultsWe found decreased functional connectivity between the left amygdala and the left anterior cingulate cortex (ACC) during negative stimuli in participants with MDD (t54 = 4.2; p = 0.035, family-wise error [FWE]–corrected). During high-attention stimuli, participants with MDD showed reduced functional connectivity between the right dorsolateral prefrontal cortex (dlPFC) and the right ACC (t54 = 4.06, pFWE = 0.02), but greater functional connectivity between the right dlPFC and the right amygdala (t54 = 3.35, p = 0.048). Apathy was associated with increased functional connectivity between the right dlPFC and the right ACC during high-attention stimuli (t28 = 5.2, p = 0.01) and increased fractional anisotropy in the right posterior cerebellum, the anterior and posterior cingulum and the bilateral internal capsule (all pFWE < 0.05).LimitationsLimitations included a moderate sample size, concomitant antidepressant therapy and no directed connectivity.ConclusionWe found that MDD was associated with impairments in cortical–subcortical functional connectivity during negative stimuli that might alter the recruitment of networks engaged in attention. Apathy-related features suggested networks similar to those observed in degenerative disorders, but possible different mechanisms.

Parcellation of the human amygdala using recurrence quantification analysis

Several previous attempts have been made to divide the human amygdala into smaller subregions based on the unique functional properties of the subregions. Although these attempts have provided valuable insight into the functional heterogeneity in this structure, the possibility that spatial patterns of functional characteristics can quickly change over time has rarely been considered in previous studies. In the present study, we explicitly account for the dynamic nature of amygdala activity. Our goal was not only to develop another parcellation method but also to augment existing methods with novel information about amygdala subdivisions. We performed state-specific amygdala parcellation using resting-state fMRI (rsfMRI) data and recurrence quantification analysis (RQA). RsfMRI data from 102 subjects were acquired with a 3T Trio Siemens scanner. We analyzed values of several RQA measures across all voxels in the amygdala and found two amygdala subdivisions, the ventrolateral (VL) and dorsomedial (DM) subdivisions, that differ with respect to one of the RQA measures, Shannon's entropy of diagonal lines. Compared to the DM subdivision, the VL subdivision can be characterized by a higher value of entropy. The results suggest that VL activity is determined and influenced by more brain structures than is DM activity. To assess the biological validity of the obtained subdivisions, we compared them with histological atlases and currently available parcellations based on structural connectivity patterns (Anatomy Probability Maps) and cytoarchitectonic features (SPM Anatomy toolbox). Moreover, we examined their cortical and subcortical functional connectivity. The obtained results are similar to those previously reported on parcellation performed on the basis of structural connectivity patterns. Functional connectivity analysis revealed that the VL subdivision has strong connections to several cortical areas, whereas the DM subdivision is mainly connected to subcortical regions. This finding suggests that the VL subdivision corresponds to the basolateral subdivision of the amygdala (BLA), while the DM subdivision has some characteristics typical of the centromedial amygdala (CMA). The similarity in functional connectivity patterns between the VL subdivision and BLA, as well as between the DM subdivision and CMA, confirm the utility of our parcellation method. Overall, the study shows that parcellation based on BOLD signal dynamics is a powerful tool for identifying distinct functional systems within the amygdala. This tool might be useful for future research on functional brain organization.

Lateralized Connectivity between Globus Pallidus and Motor Cortex is Associated with Freezing of Gait in Parkinson’s Disease

Freezing of gait (FoG) is a brief, episodic absence or marked reduction of forward progression of the feet, despite the intention to walk, that is common in people with Parkinson’s disease (PD). We hypothesized that not only motor, but higher level cognitive and attention areas may be impaired in freezers. In this study, we aimed to characterize differences in cortical and subcortical functional connectivity specific to FoG. We examined resting state neuroimaging and objective measures of FoG severity and gait from 103 individuals (28 PD + FoG, 36 PD − FoG and 39 healthy controls). Inertial sensors were used to quantify freezing severity and gait. Groups with and without FoG were matched on age, disease severity, cognitive status, and levodopa medication. MRI data was processed using surface-based registration. High-quality imaging data were used to characterize differences in connectivity specific to FoG using a pre-defined set of Regions of Interest (ROIs) and validated using whole-brain connectivity analysis. Associations between functional connectivity and objective measures of FoG were determined via predictive modeling using hold-out cross validation. We found that connectivity between the left globus pallidus (GP) and left somatosensory cortex and between two brain areas in the default and insular/vestibular networks exhibited significant differences specific to FoG and were also strong and significant predictors of FoG severity. Our findings suggest that the interplay among motor, default and vestibular areas of the left cortex are critical in the pathology of FoG.

Beyond diagnosis: Cross-diagnostic features in canonical resting-state networks in children with neurodevelopmental disorders

Children with neurodevelopmental disorders (NDDs) share common behavioural manifestations despite distinct categorical diagnostic criteria. Here, we examined canonical resting-state network connectivity in three diagnostic groups (autism spectrum disorder, attention-deficit/hyperactivity disorder and paediatric obsessive–compulsive disorder) and typically developing controls (TD) in a large single-site sample (N = 407), applying diagnosis-based and dimensional approaches to understand underlying neurobiology across NDDs. Each participant’s functional network graphs were computed using five graph metrics. In diagnosis-based comparisons, an analysis of covariance was performed to compare all NDDs to TD, followed by pairwise comparisons between NDDs. In the dimensional approach, participants’ functional network graphs were correlated with continuous behavioural measures, and a data-driven k-means clustering analysis was applied to determine if subgroups of participants were seen, without diagnostic information having been included. In the diagnosis-based comparisons, children with NDDs did not differ significantly from the TD group and the NDD categorical groups also did not differ significantly from each other, across all graph metrics. In the dimensional, diagnostic-independent approach, however, subcortical functional connectivity was significantly correlated with participants’ general adaptive functioning across all participants. The clustering analysis identified an optimal solution of two clusters, and participants assigned in the same data-driven cluster were highly heterogeneous in diagnosis. Neither cluster exclusively contained a specific diagnostic group, nor did NDDs separate cleanly from TDs. Each participant’s distance ratio between the two clusters was significantly correlated with general adaptive functioning, social deficits and attentional problems. Our results suggest the neurobiological similarity and dissimilarity between NDDs need to be investigated beyond DSM/ICD-based, behaviourally-defined diagnostic categories.

Human menstrual cycle variation in subcortical functional brain connectivity: a multimodal analysis approach

Increasing evidence suggests that endogenous sex steroid changes affect human brain functional connectivity, which could be obtained by resting-state fMRI (RS-fMRI). Nevertheless, RS studies on the menstrual cycle (MC) are underrepresented and yield inconsistent results. We attribute these inconsistencies to the use of various methods in exploratory approaches and small sample sizes. Hormonal fluctuations along the MC likely elicit subtle changes that, however, may still have profound impact on network dynamics when affecting key brain nodes. To address these issues, we propose a ROI-based multimodal analysis approach focusing on areas of high functional relevance to adequately capture these changes. To that end, sixty naturally cycling women underwent RS-fMRI in three different cycle phases and we performed the following analyses: (1) group-independent component analyses to identify intrinsic connectivity networks, (2) eigenvector centrality (EC) as a measure of centrality in the global connectivity hierarchy, (3) amplitude of low-frequency fluctuations (ALFF) as a measure of oscillatory activity and (4) seed-based analyses to investigate functional connectivity from the ROIs. For (2)–(4), we applied a hypothesis-driven ROI approach in the hippocampus, caudate and putamen. In the luteal phase, we found (1) decreased intrinsic connectivity of the right angular gyrus with the default mode network, (2) heightened EC for the hippocampus, and (3) increased ALFF for the caudate. Furthermore, we observed (4) stronger putamen–thalamic connectivity during the luteal phase and stronger fronto-striatal connectivity during the pre-ovulatory phase. This hormonal modulation of connectivity dynamics may underlie behavioural, emotional and sensorimotor changes along the MC.

Transient subcortical functional connectivity upon emergence from propofol sedation in human male volunteers: evidence for active emergence

BackgroundEmergence from sedation entails rapid increase in the levels of both awareness and wakefulness, the two axes of consciousness. Functional MRI (fMRI) studies of emergence from sedation often focus on the recovery period, with no description of the moment of emergence. We hypothesised that by focusing on the moment of emergence, novel insights, primarily about subcortical activity and increased wakefulness, will be gained. MethodsWe conducted a resting state fMRI analysis of 17 male subjects (20–40 yr old) gradually entering into and emerging from deep sedation (average computed propofol concentrations of 2.41 and 1.11 μg ml−1, respectively), using target-controlled infusion of propofol. ResultsFunctional connectivity analysis revealed a robust spatiotemporal signature of return of consciousness, in which subcortical seeds showed transient positive correlations that rapidly turned negative shortly after emergence. Elements of this signature included four components of the ascending reticular activating system: the ventral tegmentum area, the locus coeruleus, median raphe, and the mammillary body. The involvement of the rostral dorsolateral pontine tegmentum, which is specifically impaired in comatose patients with pontine lesions, in emergence was previously unknown. ConclusionsEmergence from propofol sedation is characterised, and possibly driven, by a transient activation of brainstem loci. Some of these loci are known components of the ascending reticular activating system, whereas an additional locus was found that is also impaired in comatose patients.

Segmented Echo Planar Imaging Improves Detection of Subcortical Functional Connectivity Networks in the Rat Brain

Susceptibility artifacts in the vicinity of aural and nasal cavities result in significant signal drop-out and image distortion in echo planar imaging of the rat brain. These effects may limit the study of resting state functional connectivity in deep brain regions. Here, we explore the use of segmented EPI for resting state fMRI studies in the rat, and assess the relative merits of this method compared to single shot EPI. Sequences were evaluated in terms of signal-to-noise ratio, geometric distortions, data driven detection of resting state networks and group level correlations of time series. Multishot imaging provided improved SNR, temporal SNR and reduced geometric distortion in deep areas, while maintaining acceptable overall image quality in cortical regions. Resting state networks identified by independent component analysis were consistent across methods, but multishot EPI provided a more robust and accurate delineation of connectivity patterns involving deep regions typically affected by susceptibility artifacts. Importantly, segmented EPI showed reduced between-subject variability and stronger statistical significance of pairwise correlations at group level over the whole brain and in particular in subcortical regions. Multishot EPI may represent a valid alternative to snapshot methods in functional connectivity studies, particularly for the investigation of subcortical regions and deep gray matter nuclei.

Aberrant "deep connectivity" in autism: A cortico-subcortical functional connectivity magnetic resonance imaging study.

The number of studies examining functional brain networks in Autism Spectrum Disorder (ASD) has risen over the last decade and has characterized ASD as a disorder of altered brain connectivity. However, these studies have focused largely on cortical structures, and only a few studies have examined cortico-subcortical connectivity in regions like thalamus and basal ganglia in ASD. The goal of this study was to characterize the functional connectivity between cortex and subcortical regions in ASD using the Autism Brain Imaging Data Exchange (ABIDE-II). Resting-state functional magnetic resonance imaging data were used from 168 typically developing (TD) and 138 ASD participants across different sites from the ABIDE II dataset. Functional connectivity of basal ganglia and thalamus to unimodal and supramodal networks was examined in this study. Overconnectivity (ASD > TD) was found between unimodal (except for medial visual network) and subcortical regions, and underconnectivity (TD > ASD) was found between supramodal (except for default mode and dorsal attention networks) and subcortical regions; positive correlations between ASD phenotype and unimodal-subcortical connectivity were found and negative ones with supramodal-subcortical connectivity. These findings suggest that brain networks heavily involved in sensory processing had higher connectivity with subcortical regions, whereas those involved in higher-order thinking showed decreased connectivity in ASD. In addition, brain-behavior correlations indicated a relationship between ASD phenotype and connectivity. Thus, differences in cortico-subcortical connectivity may have a significant impact on basic and higher-order cognitive processes in ASD. Autism Res 2019, 12: 384-400 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study focused on examining the functional connectivity (synchronization of brain activity across regions) of two types of brain networks (unimodal and supramodal) with subcortical areas (thalamus and basal ganglia) in children, adolescents, and adults with autism spectrum disorder (ASD) and how this relates to ASD phenotype. ASD participants showed overconnectivity in unimodal networks and underconnectivity in supramodal networks. These findings provide new insights into cortico-subcortical connections between basic sensory and high-order cognitive processes.

Differential patterns of age-related cortical and subcortical functional connectivity in 6-to-10 year old children: A connectome-wide association study.

IntroductionTypical brain development is characterized by specific patterns of maturation of functional networks. Cortico‐cortical connectivity generally increases, whereas subcortico‐cortical connections often decrease. Little is known about connectivity changes amongst different subcortical regions in typical development.MethodsThis study examined age‐ and gender‐related differences in functional connectivity between and within cortical and subcortical regions using two different approaches. The participants included 411 six‐ to ten‐year‐old typically developing children sampled from the population‐based Generation R study. Functional connectomes were defined in native space using regions of interest from subject‐specific FreeSurfer segmentations. Connections were defined as: (a) the correlation between regional mean time‐series; and (b) the focal maximum of voxel‐wise correlations within FreeSurfer regions. The association of age and gender with each functional connection was determined using linear regression. The preprocessing included the exclusion of children with excessive head motion and scrubbing to reduce the influence of minor head motion during scanning.ResultsCortico‐cortical associations echoed previous findings that connectivity shifts from short to long‐range with age. Subcortico‐cortical associations with age were primarily negative in the focal network approach but were both positive and negative in the mean time‐series network approach. Between subcortical regions, age‐related associations were negative in both network approaches. Few connections had significant associations with gender.ConclusionsThe present study replicates previously reported age‐related patterns of connectivity in a relatively narrow age‐range of children. In addition, we extended these findings by demonstrating decreased connectivity within the subcortex with increasing age. Lastly, we show the utility of a more focal approach that challenges the spatial assumptions made by the traditional mean time series approach.

Toward precision medicine: tailoring interventional strategies based on noninvasive brain stimulation for motor recovery after stroke.

To support the recovery of disability and the reduced functional capacity influencing the independence of daily life after focal brain lesions like stroke, the application of noninvasive brain stimulation (NIBS) by repetitive transcranial magnetic stimulation or transcranial electric stimulation has been found useful in the last decades. Still, a positive influence on the recovery seems to be restricted to specific subgroups of patients. Therefore, a closer look on individual parameters influencing the recovery course and the effect of NIBS is needed. Neuroimaging studies investigated alterations in neuronal network settings during the recovery process from stroke and can explain a relevant amount of variance in residual motor function. In this regard for instance, the microstructural integrity of the corticospinal tract and its influence on cortical and subcortical functional and structural connectivity alterations shows a relevant impact on individual recovery from the acute to the chronic state. Based on this understanding, a 'one-suits-all' NIBS strategy for clinical application appears insufficient and understanding of therapeutic susceptibility to NIBS gained from structural and functional imaging studies will help to develop patient-tailored NIBS-based interventional strategies towards precision medicine, as a promising future prospective within this field.