Connected Brain Regions Research Articles

Brain functions and cognition on transient insulin deprivation in type 1 diabetes

BACKGROUNDType 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin-treated individuals with T1D alters brain function.METHODSWe therefore performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ± 0.6 hours of insulin deprivation in 14 individuals with T1D and compared results with those from 14 age-, sex-, and BMI-matched nondiabetic (ND) participants with no interventions.RESULTSInsulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. Participants with T1D showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between participants with T1D and ND participants at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in participants with T1D. Insulin deprivation also reduced brain adenosine triphosphate levels and altered the phosphocreatine/adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between participants with T1D and ND participants were noted, and on insulin deprivation further alterations in functional connectivity between regions, especially cortical and hippocampus-caudate regions, were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition.CONCLUSIONTransient insulin deprivation therefore caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications, as many patients with T1D inadvertently have periods of transient insulin deprivation.TRIAL REGISTRATIONClinicalTrials.gov NCT03392441.FUNDINGClinical and Translational Science Award (UL1 TR002377) from the National Center for Advancing Translational Science; NIH grants (R21 AG60139 and R01 AG62859); the Mayo Foundation.

Altered Functional Connectivity of the Orbital Cortex and Striatum Associated with Catalepsy Induced by Dopamine D1 and D2 Antagonists.

The dopamine system plays an important role in regulating many brain functions, including the motor function. The blockade of dopamine receptors results in a serious motor dysfunction, such as catalepsy and Parkinsonism. However, the neuronal mechanism underlying the drug-induced motor dysfunction is not well understood. Here, we examine brain-wide activation patterns in Fos-enhanced green fluorescent protein reporter mice that exhibit cataleptic behavior induced by SCH39166, a dopamine D1-like receptor antagonist, and raclopride, a dopamine D2-like receptor antagonist. Support vector classifications showed that the orbital cortex (ORB) and striatum including the caudoputamen (CP) and nucleus accumbens (ACB), prominently contribute to the discrimination between brains of the vehicle-treated and both SCH39166- and raclopride-treated mice. Interregional correlations indicated that the increased functional connectivity of functional networks, including the ORB, CP, and ACB, is the common mechanism underlying SCH39166- and raclopride-induced cataleptic behavior. Moreover, the distinct mechanisms in the SCH39166- and raclopride-induced cataleptic behaviors are the decreased functional connectivity between three areas above and the cortical amygdala, and between three areas above and the anterior cingulate cortex, respectively. Thus, the alterations of functional connectivity in diverse brain regions, including the ORB, provide new insights on the mechanism underlying drug-induced movement disorders.

Effect of motor learning with different complexities on EEG spectral distribution and performance improvement

Motor learning can improve movement performance and behavioral measurements, such as reaction time, by inducing brain plasticity. In this study, we investigated the effect of training with different task complexity on Electroencephalographic (EEG) signals. Two types of training (‘simple’ and ‘complex’) were performed by two groups of healthy volunteers. The complex training group (CTG) performed a trace tracking task using their dominant foot and the simple training group (STG) executed repetitive ankle dorsiflexion in the training phase. Frequency analysis was performed to study the effect of training on EEG signals. In addition, the coherence between paired-channels investigated to represent changes in brain region connectivity. Results revealed that the power in the Beta (15−31 Hz) was significantly reduced while gamma band power (32−80 Hz) was significantly enhanced in the CTG compared to the STG mainly in the frontal, central and centro-parietal channels. Theta power was also increased after training in fronto-central channel. Moreover, performance variations were mainly correlated to the beta and gamma power changes. Finally, the connectivity of gamma and beta band increased significantly particularly between frontal and central region in CTG while connectivity score of theta and delta band decreased after training. These findings confirm that training-induced brain plasticity depends on the complexity of the task, more complexity.

Deep Learning‐based Classification of Resting‐state fMRI Independent‐component Analysis

Functional connectivity analyses of fMRI data have shown that the activity of the brain at rest is spatially organized into resting-state networks (RSNs). RSNs appear as groups of anatomically distant but functionally tightly connected brain regions. Inter-RSN intrinsic connectivity analyses may provide an optimal spatial level of integration to analyze the variability of the functional connectome. Here we propose a deep learning approach to enable the automated classification of individual independent-component (IC) decompositions into a set of predefined RSNs. Two databases were used in this work, BIL&GIN and MRi-Share, with 427 and 1811 participants, respectively. We trained a multilayer perceptron (MLP) to classify each IC as one of 45 RSNs, using the IC classification of 282 participants in BIL&GIN for training and a 5-dimensional parameter grid search for hyperparameter optimization. It reached an accuracy of 92 %. Predictions for the remaining individuals in BIL&GIN were tested against the original classification and demonstrated good spatial overlap between the cortical RSNs. As a first application, we created an RSN atlas based on MRi-Share. This atlas defined a brain parcellation in 29 RSNs covering 96 % of the gray matter. Second, we proposed an individual-based analysis of the subdivision of the default-mode network into 4 networks. Minimal overlap between RSNs was found except in the angular gyrus and potentially in the precuneus. We thus provide the community with an individual IC classifier that can be used to analyze one dataset or to statistically compare different datasets for RSN spatial definitions.

Cerebral Metabolite Concentrations Are Associated With Cortical and Subcortical Volumes and Cognition in Older Adults.

BackgroundCerebral metabolites are associated with different physiological processes in brain aging. Cortical and limbic structures play important roles in cognitive aging; however, the relationship between these structures and age remains unclear with respect to physiological underpinnings. Regional differences in metabolite levels may be related to different structural and cognitive changes in aging.MethodsMagnetic resonance imaging and spectroscopy were obtained from 117 cognitively healthy older adults. Limbic and other key structural volumes were measured. Concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) were measured in frontal and parietal regions. Neuropsychological testing was performed including measures of crystallized and fluid intelligence and memory.ResultsNAA in the frontal voxel was associated with limbic and cortical volumes, whereas Cho in parietal cortex was negatively associated with hippocampal and other regional volumes. Hippocampal volume was associated with forgetting, independent of age. Further, parietal Cho and hippocampal volume contributed independent variance to age corrected discrepancy between fluid and crystallized abilities.ConclusionThese findings suggest that physiological changes with age in the frontal and parietal cortices may be linked to structural changes in other connected brain regions. These changes are differentially associated with cognitive performance, suggesting potentially divergent mechanisms.

Opposite effects of one session of 1 Hz rTMS on functional connectivity between pre-supplementary motor area and putamen depending on the dyskinesia state in Parkinson's disease

ObjectiveTo explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF rTMS) on cortico-striatal-cerebellar resting state functional connectivity in Parkinson’s disease (PD), with and without dyskinesias. MethodsBecause there is increasing evidence of an involvement of the pre-supplementary motor area (pre-SMA) in the pathophysiology of levodopa induced dyskinesias, we targeted the right pre-SMA with LF rTMS in 17 PD patients. We explored the effects of one sham-controlled LF rTMS session on resting state functional connectivity of interconnected brain regions by using functional MRI, and how it is modified by levodopa. The clinical effect on motor function and dyskinesias was documented. ResultsAs expected, one LF rTMS session did not alleviate dyskinesias. However, real, and not sham LF rTMS significantly increased the functional connectivity with the right putamen in patients with dyskinesias. In patients without dyskinesias, the real LF rTMS session significantly decreased functional connectivity in the right putamen and the cerebellum. We found no effects on functional connectivity after levodopa ingestion. ConclusionOne session of 1 Hz rTMS has opposing effects on pre-SMA functional connectivity depending on the PD patients' dyskinesia state. SignificancePatients dyskinesias state determines the way LF rTMS affects functional connectivity in late stage PD.

Functional connectivity of the default mode, dorsal attention and fronto-parietal executive control networks in glial tumor patients.

Resting state functional magnetic resonance imaging (rsfMRI) is an emerging tool to explore the functional connectivity of different brain regions. We aimed to assess the disruption of functional connectivity of the Default Mode Network (DMN), Dorsal Attention Network(DAN) and Fronto-Parietal Network (FPN) in patients with glial tumors. rsfMRI data acquired on 3T-MR of treatment-naive glioma patients prospectively recruited (2015-2019) and matched controls from the 1000 functional-connectomes-project were analyzed using the CONN functional toolbox. Seed-Based Connectivity Analysis (SBCA) and Independent Component Analysis (ICA, with 10 to 100 components) were performed to study reliably the three networks of interest. 35 patients with gliomas (17 WHO grade I-II, 18 grade III-IV) and 70 controls were included. Global increased DMN connectivity was consistently found with SBCA and ICA in patients compared to controls (Cluster1: Precuneus, height: p < 10-6; Cluster2: subcallosum; height: p < 10-5). However, an area of decreased connectivity was found in the posterior corpus callosum, particularly in high-grade gliomas (height: p < 10-5). The DAN demonstrated small areas of increased connectivity in frontal and occipital regions (height: p < 10-6). For the FPN, increased connectivity was noted in the precuneus, posterior cingulate gyrus, and frontal cortex. No difference in the connectivity of the networks of interest was demonstrated between low- and high-grade gliomas, as well as when stratified by their IDH1-R132H (isocitrate dehydrogenase) mutation status. Altered functional connectivity is reliably found with SBCA and ICA in the DMN, DAN, and FPN in glioma patients, possibly explained by decreased connectivity between the cerebral hemispheres across the corpus callosum due to disruption of the connections.

Learning Deficits Accompanied by Microglial Proliferation After the Long-Term Post-Injection of Alzheimer's Disease Brain Extract in Mouse Brains.

Human tauopathy brain injections into the mouse brain induce the development of tau aggregates, which spread to functionally connected brain regions; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostly used mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. To examine whether long-term incubation of Alzheimer's disease (AD) brain in the mouse brain cause functional decline. We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. After a long-term (17-19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test. Aggregated tau pathology in the bilateral hippocampus was more prominent in Tg601 mice than in NTg mice. No significant changes were observed in the number of Neu-N positive cells or astrocytes in the hippocampus, whereas that of Iba-I-positive microglia increased after the AD brain injection. These results potentially implicate tau propagation in functional decline and indicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.

Brain functional networks associated with social bonding in monogamous voles.

Previous studies have related pair-bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially relevant regions have yet to be described. In this study, we used resting-state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair-bonding. Thirty-two male and female prairie voles were scanned at baseline, 24 hr, and 2 weeks after the onset of cohabitation. By using network-based statistics, we identified that the functional connectivity of a corticostriatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.

An Examination of the Association Between Subjective Distress and Functional Connectivity During Discarding Decisions in Hoarding Disorder

BackgroundIndividuals with hoarding disorder (HD) demonstrate exaggerated subjective distress and hyperactivation of cingulate and insular cortex regions when discarding personal possessions. No prior study has sought to determine whether this subjective distress is associated with specific profiles of abnormal brain function in individuals with HD. MethodsWe used multimodal canonical correlation analysis plus joint independent component analysis to test whether five hoarding-relevant domains of subjective distress when deciding to discard possessions (anxiety, sadness, monetary value, importance, and sentimental attachment) are associated with functional magnetic resonance imaging–measured whole-brain functional connectivity in 72 participants with HD and 44 healthy controls. ResultsThree extracted components differed between HD participants and healthy control subjects. Each of these components depicted an abnormal profile of functional connectivity in HD participants relative to control subjects during discarding decisions, and a specific distress response profile. One component pair showed a relationship between anxiety ratings during discarding decisions and connectivity among the pallidum, perirhinal ectorhinal cortex, and dorsolateral prefrontal cortex. Another component comprised sadness ratings during discarding decisions and connectivity in the pallidum, nucleus accumbens, amygdala, and dorsolateral prefrontal cortex. The third component linked HD brain connectivity in several dorsolateral prefrontal cortex regions with perceived importance ratings during discarding decisions. ConclusionsThe findings indicate that in patients with HD, the subjective intensity of anxiety, sadness, and perceived possession importance is related to abnormal functional connectivity in key frontal and emotional processing brain regions. The findings are discussed in terms of emerging neurobiological models of HD.

The interplay of emotional and social conceptual processes during moral reasoning in frontotemporal dementia.

Cooperative social behaviour in humans hinges upon our unique ability to make appropriate moral decisions in accordance with our ethical values. The complexity of the neurocognitive mechanisms underlying moral reasoning is revealed when this capacity breaks down. Patients with the behavioural variant of frontotemporal dementia (bvFTD) display striking moral transgressions in the context of atrophy to frontotemporal regions supporting affective and social conceptual processing. Developmental studies have highlighted the importance of social knowledge to moral decision making in children, yet the role of social knowledge in relation to moral reasoning impairments in neurodegeneration has largely been overlooked. Here, we sought to examine the role of affective and social conceptual processes in personal moral reasoning in bvFTD, and their relationship to the integrity and structural connectivity of frontotemporal brain regions. Personal moral reasoning across varying degrees of conflict was assessed in 26 bvFTD patients and compared with demographically matched Alzheimer's disease patients (n = 14), and healthy older adults (n = 22). Following each moral decision, we directly probed participants' subjective emotional experience as an index of their affective response, while social norm knowledge was assessed via an independent task. While groups did not differ significantly in terms of their moral decisions, bvFTD patients reported feeling 'better' about their decisions than healthy control subjects. In other words, although bvFTD patients could adjudicate between different courses of action in the moral scenarios, their affective responses to these decisions were highly irregular. This blunted emotional reaction was exclusive to the personal high-conflict condition, with 61.5% of bvFTD patients reporting feeling 'extremely good' about their decisions, and was correlated with reduced knowledge of socially acceptable behaviour. Voxel-based morphometry analyses revealed a distributed network of frontal, subcortical, and lateral temporal grey matter regions involved in the attenuated affective response to moral conflict in bvFTD. Crucially, diffusion-tensor imaging implicated the uncinate fasciculus as the pathway by which social conceptual knowledge may influence emotional reactions to personal high-conflict moral dilemmas in bvFTD. Our findings suggest that altered moral behaviour in bvFTD reflects the dynamic interplay between degraded social conceptual knowledge and blunted affective responsiveness, attributable to atrophy of, and impaired information transfer between, frontal and temporal cortices. Delineating the mechanisms of impaired morality in bvFTD provides crucial clinical information for understanding and treating this challenging symptom, which may help pave the way for targeted behavioural interventions.

Effects of an Allostatic Closed-Loop Neurotechnology (HIRREM) on Brain Functional Connectivity Laterality in Military-Related Traumatic Stress.

ABSTRACTBACKGROUND AND PURPOSEBrain asymmetries are reported in posttraumatic stress disorder, but many aspects of laterality and traumatic stress remain underexplored. This study explores lateralization changes in resting state brain network functional connectivity in a cohort with symptoms of military‐related traumatic stress, associated with use of a closed‐loop neurotechnology, HIRREM.METHODSEighteen participants (17 males, mean age 41 years [SD = 7]) received 19.5 (1.1) HIRREM sessions over 12 days. Whole brain resting magnetic resonance imaging was done pre‐ and post‐HIRREM. Laterality of functional connectivity was assessed on a whole brain basis, and in six predefined networks or regions. Laterality of connectivity within networks or regions was assessed separately from laterality of connections between networks or regions.RESULTSBefore HIRREM, significant laterality effects of connection type (ipsilateral for either side, or contralateral in either direction) were observed for the whole brain, within networks or regions, and between networks or regions. Post‐HIRREM, there were significant changes for within‐network or within‐region analysis in the motor network, and changes for between‐network or between‐region analyses for the salience network and the motor cortex.CONCLUSIONSAmong military service members and Veterans with symptoms of traumatic stress, asymmetries of network and brain region connectivity patterns were identified prior to usage of HIRREM. A variety of changes in lateralized patterns of brain connectivity were identified postintervention. These laterality findings may inform future studies of brain connectivity in traumatic stress disorders, with potential to point to mechanisms of action for successful intervention.

Gray matter reorganization underpinnings of antidepressant treatment of persistent depressive disorder

Brain gray matter is organized in a manner with interconnected brain regions, resulting in a notable covariance pattern that recapitulates either the functional coactivation or structural connectivity of brain regions, which is believed to underpin psychiatric disorders such as depression. This study aimed to investigate whether and how antidepressants took effect in treating depression and reducing symptoms by altering the gray matter covariance pattern. We combined structural magnetic resonance imaging (MRI) scans acquired in two randomized, double-blind, placebo-controlled trial (RCT) studies of the treatment using serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant medications in patients with persistent depressive disorder (PDD). One was an RCT of 10-week duloxetine medication that consisted of patients who received duloxetine (N = 21) or placebo (N = 21), and the other was an RCT of 12-week desvenlafaxine medication that consisted of 19 and 17 patients respectively who received desvenlafaxine or placebo. We examined treatment effect on gray matter volume (GMV) and topological organization of GMV covariance pattern (i.e., GMV-based network). We found a treatment-by-time effect on GMV in the angular gyrus and cuneus areas, whereas the GMV change rate of the cuneus was inversely correlated with the response rate. We observed a significant increase in the local efficiency of the GMV-based network following medication treatment compared with placebo. Our findings provide preliminary evidence for a GMV-based network-specific reconfiguration caused by antidepressants compared to placebo and the cuneus may be a possible candidate region to predict antidepressant response.

Dynamic Causal Modeling on the Identification of Interacting Networks in the Brain: A Systematic Review.

Dynamic causal modeling (DCM) has long been used to characterize effective connectivity within networks of distributed neuronal responses. Previous reviews have highlighted the understanding of the conceptual basis behind DCM and its variants from different aspects. However, no detailed summary or classification research on the task-related effective connectivity of various brain regions has been made formally available so far, and there is also a lack of application analysis of DCM for hemodynamic and electrophysiological measurements. This review aims to analyze the effective connectivity of different brain regions using DCM for different measurement data. We found that, in general, most studies focused on the networks between different cortical regions, and the research on the networks between other deep subcortical nuclei or between them and the cerebral cortex are receiving increasing attention, but far from the same scale. Our analysis also reveals a clear bias towards some task types. Based on these results, we identify and discuss several promising research directions that may help the community to attain a clear understanding of the brain network interactions under different tasks.

Reduced concentrations of vaginal metabolites involved in steroid hormone biosynthesis are associated with increased vulvar vestibular pain and vaginal muscle tenderness in provoked vestibulodynia: An exploratory metabolomics study.

Provoked vestibulodynia (PVD) is a chronic vulvar pain disorder characterized by hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Knowledge regarding pathophysiological mechanisms contributing to the etiology and production of symptoms in PVD remains incomplete but is considered multifactorial. Using a cross-sectional observational study design, data from untargeted metabolomic profiling of vaginal fluid and plasma in women with PVD and healthy women was combined with pain testing and brain imaging in women with PVD to test the hypotheses that women with PVD compared to healthy women show differences in vaginal and plasma metabolites involved in steroid hormone biosynthesis. Steroid hormone metabolites showing group differences were correlated with vulvar vestibular pain and vaginal muscle tenderness and functional connectivity of brain regions involved in pain processing in women with PVD to provide insight into the functional mechanisms linked to the identified alterations. Sensitivity analyses were also performed to determine the impact of hormonal contraceptive use on the study findings. Women with PVD compared to healthy controls had significant reductions primarily in vaginal fluid concentrations of androgenic, pregnenolone and progestin metabolites involved in steroidogenesis, suggesting localized rather than systemic effects in vagina and vulvar vestibule. The observed reductions in androgenic metabolite levels showed large effect size associations with increased vulvar vestibular pain and vulvar muscle tenderness and decreases in androgenic and progestin metabolites were associated with decreased connectivity strength in primary sensorimotor cortices. Women with PVD showed symptom-associated reductions in vaginal fluid concentrations of metabolites involved in the biosynthesis of steroid hormones previously shown to affect the integrity of vulvar and vaginal tissue and nociceptive processing. Deficiency of certain steroids may be an important mechanism contributing to the pathophysiology of symptoms in PVD may provide potential diagnostic markers that could lead to new targets for therapeutic intervention.

Seeding-Competent Tau in Gray Matter Versus White Matter of Alzheimer's Disease Brain.

Neurofibrillary pathology of abnormally hyperphosphorylated tau spreads along neuroanatomical connections, underlying the progression of Alzheimer's disease (AD). The propagation of tau pathology to axonally connected brain regions inevitably involves trafficking of seeding-competent tau within the axonal compartment of the neuron. To determine the seeding activity of tau in cerebral gray and white matters of AD. Levels of total tau, hyperphosphorylation of tau, and SDS- and β-mercaptoethanol-resistant high molecular weight tau (HMW-tau) in crude extracts from gray and white matters of AD frontal lobes were analyzed by immuno-blots. Tau seeding activity was quantitatively assessed by measuring RIPA buffer-insoluble tau in HEK-293FT/tau151-391 cells treated with brain extracts. We found a comparable level of soluble tau in gray matter versus white matter of control brains, but a higher level of soluble tau in gray matter than white matter of AD brains. In AD brains, tau is hyperphosphorylated in both gray and white matters, with a higher level in the former. The extracts of both gray and white matters of AD brains seeded tau aggregation in HEK-293FT/tau151-391 cells but the white matter showed less potency. Seeding activity of tau in brain extracts was positively correlated with the levels of tau hyperphosphorylation and HMW-tau. RIPA-insoluble tau, but not RIPA-soluble tau, was hyperphosphorylated tau at multiple sites. Both gray and white matters of AD brain contain seeding-competent tau that can template aggregation of hyperphosphorylated tau, but the seeding potency is markedly higher in gray matter than in white matter.

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Structural and functional correlates of subthalamic deep brain stimulation-induced apathy in Parkinson’s disease

BackgroundNotwithstanding the large improvement in motor function in Parkinson’s disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role. ObjectiveWe studied whether apathy in DBS-treated PD patients could be a stimulation effect. MethodsIn 26 PD patients we acquired apathy scores before and >6 months after DBS of the subthalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed ≥6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy. ResultsAverage apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex. ConclusionsThe present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms.

OptoNet II: An Advanced MATLAB-Based Toolbox for Functional Cortical Connectivity Analysis With Surrogate Tests Using fNIRS

Cortical connectivity analysis is a widely used method for understanding the causes of neurological disorders and related brain mechanisms. Although there exist numerous activity analysis toolboxes for functional near-infrared spectroscopy (fNIRS), there are only a few cortical connectivity analysis toolboxes. In 2019, we released a MATALB toolbox named OptoNet, which has helped researchers to analyze brain networks using fNIRS. In this study, we developed an advanced MATLAB toolbox, named OptoNet II, to add new features that overcome the shortcomings of OptoNet. With these new features, OptoNet II can efficiently analyze cortical connectivity according to brain region using any fNIRS channel sets and can present the results of two connectivity analyses with auto-thresholding based on surrogate tests. To evaluate the efficacy of the new functions, the finger-tapping task experiment was carried out before and after transcranial direct current stimulation (tDCS) in the primary motor area. OptoNet II can efficiently show the effects of tDCS on functional brain region connectivity, which has been difficult to confirm by conventional methods. In this article, we propose the OptoNet II as a useful and efficient toolbox for researchers who want to perform cortical connectivity analysis using fNIRS.

Study of functional connectivity of central motor system in Parkinson’s disease using copula theory

BackgroundParkinson’s disease (PD) is a neurodegenerative disease characterized by tremor, stiffness, and slowness of movement. Many studies showed an abnormality of functional connectivity in different brain regions at rest. In this study, we aimed to investigate the linear and non-linear connectivity of individual regions to differentiate PD from healthy control. Materials and methodsResting-state fMRI data from 25 Parkinson's individuals and 18 healthy individuals were randomly obtained from the PPMI database. Brain regions involved in the movement and basal ganglia were defined as regions of interest. Functional connectivity between these regions was assessed using correlation, and five types of copula family test (linear and non-linear). Discriminative features were selected from different copula parameters and correlation coefficients statistically and used in the discriminant analysis by clustering and classification methods. ResultsWe find non-linear connections, which may be used as the distinguishing characteristics of PD from controls. The strongest of these were related to the non-linear relationship between the left motor cortex and the right prefrontal cortex, which resulted from three non-linear families of the copula (Gumbel, Frank, Clayton). The best result of k-fold classification belonged to Frank copula with 97.67% accuracy in differentiating PD from healthy controls. ConclusionWe found that non-linear copula tests are superior to simple linear correlation calculation in identifying changes of functional connectivity in PD.