Subcortical Functional Connectivity Research Articles

Technical principles of direct bipolar electrostimulation for cortical and subcortical mapping in awake craniotomy

IntroductionIntraoperative application of electrical current to the brain is a standard technique during brain surgery for inferring the function of the underlying brain. The purpose of intraoperative functional mapping is to reliably identify cortical areas and subcortical pathways involved in eloquent functions, especially motor, sensory, language and cognitive functions. Material and methodsThe aim of this article is to review the rationale and the electrophysiological principles of the use of direct bipolar electrostimulation for cortical and subcortical mapping under awake conditions. ResultsDirect electrical stimulation is a window into the whole functional network that sustains a particular function. It is an accurate (spatial resolution of about 5mm) and a reproducible technique particularly adapted to clinical practice for brain resection in eloquent areas. If the procedure is rigorously applied, the sensitivity of direct electrical stimulation for the detection of cortical and subcortical eloquent areas is nearly 100%. The main disadvantage of this technique is its suboptimal specificity. Another limitation is the identification of eloquent areas during surgery, which, however, could have been functionally compensated postoperatively if removed surgically. ConclusionDirect electrical stimulation is an easy, accurate, reliable and safe invasive technique for the intraoperative detection of both cortical and subcortical functional brain connectivity for clinical purpose. In our opinion, it is the optimal technique for minimizing the risk of neurological sequelae when resecting in eloquent brain areas.

Resting State fMRI in Mice Reveals Anesthesia Specific Signatures of Brain Functional Networks and Their Interactions.

fMRI studies in mice typically require the use of anesthetics. Yet, it is known that anesthesia alters responses to stimuli or functional networks at rest. In this work, we have used Dual Regression analysis Network Modeling to investigate the effects of two commonly used anesthetics, isoflurane and medetomidine, on rs-fMRI derived functional networks, and in particular to what extent anesthesia affected the interaction within and between these networks. Experimental data have been used from a previous study (Grandjean et al., 2014). We applied multivariate ICA analysis and Dual Regression to infer the differences in functional connectivity between isoflurane- and medetomidine-anesthetized mice. Further network analysis was performed to investigate within- and between-network connectivity differences between these anesthetic regimens. The results revealed five major networks in the mouse brain: lateral cortical, associative cortical, default mode, subcortical, and thalamic network. The anesthesia regime had a profound effect both on within- and between-network interactions. Under isoflurane anesthesia predominantly intra- and inter-cortical interactions have been observed, with only minor interactions involving subcortical structures and in particular attenuated cortico-thalamic connectivity. In contrast, medetomidine-anesthetized mice displayed subcortical functional connectivity including interactions between cortical and thalamic ICA components. Combining the two anesthetics at low dose resulted in network interaction that constituted the superposition of the interaction observed for each anesthetic alone. The study demonstrated that network modeling is a promising tool for analyzing the brain functional architecture in mice and comparing alterations therein caused by different physiological or pathological states. Understanding the differential effects of anesthetics on brain networks and their interaction is essential when interpreting fMRI data recorded under specific physiological and pathological conditions.

Chronic Effects of Blast-Related TBI on Subcortical Functional Connectivity in Veterans - Erratum.

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Chronic Effects of Blast-Related TBI on Subcortical Functional Connectivity in Veterans.

Blast explosions are the most frequent mechanism of traumatic brain injury (TBI) in recent wars, but little is known about their long-term effects. Functional connectivity (FC) was measured in 17 veterans an average of 5.46 years after their most serious blast related TBI, and in 15 demographically similar veterans without TBI or blast exposure. Subcortical FC was measured in bilateral caudate, putamen, and globus pallidus. The default mode and fronto-parietal networks were also investigated. In subcortical regions, between-groups t tests revealed altered FC from the right putamen and right globus pallidus. However, following analysis of covariance (ANCOVA) with age, depression (Center for Epidemiologic Studies Depression Scale), and posttraumatic stress disorder symptom (PTSD Checklist - Civilian version) measures, significant findings remained only for the right globus pallidus with anticorrelation in bilateral temporal occipital fusiform cortex, occipital fusiform gyrus, lingual gyrus, and cerebellum, as well as the right occipital pole. No group differences were found for the default mode network. Although reduced FC was found in the fronto-parietal network in the TBI group, between-group differences were nonsignificant after the ANCOVA. FC of the globus pallidus is altered years after exposure to blast related TBI. Future studies are necessary to explore the trajectory of changes in FC in subcortical regions after blast TBI, the effects of isolated versus repetitive blast-related TBI, and the relation to long-term outcomes in veterans. (JINS, 2016, 22, 631-642).

Altered functional connectivity between medial prefrontal cortex and the inferior brainstem in major depression during appraisal of subjective emotional responses: A preliminary study

ObjectiveWe tested the hypothesis that reduced rostral anterior cingulate cortex (rACC)-subcortical functional connectivity in depressed subjects might account for depression-related autonomic dysregulation. MethodsTen healthy and ten depressed subjects categorized their immediate subjective emotional responses to picture sets while undergoing functional magnetic resonance imaging and electrocardiography. Using an rACC cluster commonly activated in both groups by emotion categorization as a seed region, we then performed voxel-wise functional connectivity analyses to examine rACC connectivity across the brain in depressed and control subjects. ResultsrACC had significantly stronger connectivity with a region of the inferior pons in controls than in depressed subjects. Within-subjects differences in rACC-pons connectivity also significantly correlated with measures of both heart rate variability and depression severity. ConclusionsThese findings support the hypothesis that autonomic dysregulation in depression may be associated with a functional disconnection between rACC and autonomic brainstem nuclei.

Task-related fronto-striatal functional connectivity during working memory performance in schizophrenia

Working memory (WM) deficits and associated brain dysfunction are among the most well replicated candidate endophenotypic processes in schizophrenia. However, previous studies demonstrate inconsistent over- and under-activation of dorsolateral and ventrolateral prefrontal cortices (DLPFC; VLPFC), inferior parietal lobule (IPL) during WM performance, as well as subcortical structures including the striatum, and dysfunctional connectivity among fronto-striatal regions in schizophrenia. However, no previous study has investigated task-related functional connectivity (FC) of DLPFC and striatal regions using a seed-based method; here we employed this method to assess patterns of cortical and subcortical functional connectivity among WM structures during a standard 2-back WM task performed by 28 schizophrenia (SZ) and 28 healthy controls (HC). Initial group comparisons of blood oxygenation level dependent (BOLD) responses during the WM task revealed significantly greater bilateral activity in the striatum in SZ relative to HC, but there was no significant group difference in WM cortical activity (right DLPFC, VLPFC or IPL). Analyses of FC within the cortico-subcortical WM network in the HC group revealed positive performance-related FC between the right DLPFC and the right caudate, and between the right VLPFC and the right IPL; this pattern was absent in SZ. In contrast, SZ patients showed negative performance-related functional connectivity between the left putamen and the right VLPFC. Direct group comparisons in functional connectivity showed significantly greater performance-related FC between the VLPFC and bilateral putamen, as well as unilaterally between the VLPFC and the right IPL, in HC. Results suggest a critical dysfunction of cortico-striatal connectivity underpinning information retrieval for SZ patients during WM performance.

Aberrant cortico–subcortical functional connectivity among women with poor motor control: Toward uncovering the substrate of hyperkinetic perseveration

ObjectiveHyperkinetic perseveration (HKP) refers to perseverative repetition of rudimentary motor output. Although HKP is known to be associated with brain injuries and certain neurodegenerative disorders (primarily those involving the frontal lobes and the basal ganglia), an increased tendency to exhibit HKP is also commonly associated with apparently normal aging (i.e., in the absence of known neuropathology). The purpose of the present study was to examine anomalies in brain functioning associated with HKP tendencies in a non-injured brain. MethodThe present study examined functional MRI connectivity patterns associated with HKP in a sample of 24 “young” (ages 25–35 years) and 20 “old” (ages 65–75 years) healthy community dwelling women. Participants performed a motor learning task (the Push-Turn-Taptap task: PTT) known to elicit HKP. On a separate day, participants were scanned on a Siemens 3T Trio MR scanner with a 12-channel head coil, while performing a block-design motor sequence learning task that was designed to be a scanner analog for the PTT task. Cortico–subcortical connectivity patterns involving two subcortical regions of interest (putamen and thalamus) and three cortical regions (sensory-motor cortex, Brodmann Area 6, inferior frontal gyrus) were examined. ResultsOlder participants exhibited a higher rate of HKP compared to younger participants. Age-related HKP was associated with hemispheric asymmetry marked by a relatively stronger right-hemisphere cortico–subcortical connectivity involving the sensory-motor cortex and, to a lesser extent, Brodmann Area 6. These patterns were distinct from connectivity patterns associated with aging alone. ConclusionsHKP is related to anomalies involving frontal–subcortical circuits. Future research should examine specific components of the basal-ganglia circuitry.

Auditory Resting-State Network Connectivity in Tinnitus: A Functional MRI Study

The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI “resting-state” connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress leading to disabling chronic tinnitus.

Cortical functional connectivity decodes subconscious, task-irrelevant threat-related emotion processing

It is currently unclear to what extent cortical structures are required for and engaged during subconscious processing of biologically salient affective stimuli (i.e. the 'low-road' vs. 'many-roads' hypotheses). Here we show that cortical-cortical and cortical-subcortical functional connectivity (FC) contain substantially more information, relative to subcortical-subcortical FC (i.e. 'subcortical alarm' and other limbic regions), that predicts subliminal fearful face processing within individuals using training data from separate subjects. A plot of classification accuracy vs. number of selected whole-brain FC features revealed 92% accuracy when learning was based on the top 8 features from each training set. The most informative FC was between right amygdala and precuneus, which increased during subliminal fear conditions, while left and right amygdala FC decreased, suggesting a bilateral decoupling of this key limbic region during processing of subliminal fear-related stimuli. Other informative FC included angular gyrus, middle temporal gyrus and cerebellum. These findings identify FC that decodes subliminally perceived, task-irrelevant affective stimuli, and suggest that cortical structures are actively engaged by and appear to be essential for subliminal fear processing.

Subcortical functional connectivity and verbal episodic memory in healthy elderly—A resting state fMRI study

Imaging research into age-related changes in episodic memory has mainly focused on changes in cortical areas in the medial temporal lobe and the hippocampus. However, several lines of evidence indicate that subcortical structures such as the basal ganglia and the thalamus are also involved in episodic memory function. Recent studies have revealed age-related changes in functional connectivity between different brain areas, as measured by resting state fMRI. It remains to be shown whether functional connectivity measures in the basal ganglia and the thalamus can be associated with age-related changes in memory function. Here, we investigate this question by applying high model order spatial independent component analysis to resting state fMRI data in a cohort of 100 healthy elderly and relate connectivity features to verbal episodic memory function as assessed by the California Verbal Learning Test (CVLT). We identified five components that were located within different parts of the thalamus and the basal ganglia. Two of these components demonstrated negative correlations between their functional connectivity level and CVLT performance. We also found negative correlations between connectional strength within subcortical structures and CVLT performance. These results indicate a previously undocumented role for the putamen and the thalamus in verbal episodic memory function in aging.