Protein and gene markers of metabolic dysfunction and inflammation together associate with functional connectivity in reward and motor circuits in depression

Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study.Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied.Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmetabolism, lipids imbalance, and blood pressure. Using multiple linear regression models, this study observed that metabolic dysfunction, glucose dysmetabolism, and lipids imbalance were linearly associated with depressive mood, and the association with obesity was U-shaped. The association of metabolic dysfunction, obesity, and glucose dysmetabolism with depressive mood is positive for the younger individuals in our sample and vanishes with aging. The FC of the right superior temporal gyrus with the DMN correlated with both obesity and depressive mood. In participants with higher obesity scores, FC increased with higher GDS scores, while in those with lower GDS scores, FC decreased. Age and blood pressure were associated with a more complex pattern of association between FC of the right supramarginal gyrus and GDS score.Conclusion: The association of metabolic dysfunction with depressive mood is influenced by age and relates with differential patterns of DMN-FC. The combination of the effects of age, mood, and metabolic dysfunction is likely to explain the heterogeneity of DMN-FC, which deserves further investigation with larger and longitudinal studies.

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Differential Changes in Functional Connectivity of Striatum-Prefrontal and Striatum-Motor Circuits in Premanifest Huntington’s Disease

Neurodegenerative Diseases ◽

10.1159/000501616 ◽

2019 ◽

Vol 19 (2) ◽

pp. 78-87 ◽

Cited By ~ 5

Author(s):

Martin Kronenbuerger ◽

Jun Hua ◽

Jee Y.A. Bang ◽

Kia E. Ultz ◽

Xinyuan Miao ◽

...

Keyword(s):

Functional Connectivity ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Cag Repeat ◽

Compensatory Mechanism ◽

Motor Score ◽

Cortical Areas ◽

Motor Circuits ◽

Neurophysiological Studies ◽

Cortical Regions

Background: Huntington’s disease (HD) is a progressive neurodegenerative disorder. The striatum is one of the first brain regions that show detectable atrophy in HD. Previous studies using functional magnetic resonance imaging (fMRI) at 3 tesla (3 T) revealed reduced functional connectivity between striatum and motor cortex in the prodromal period of HD. Neuroanatomical and neurophysiological studies have suggested segregated corticostriatal pathways with distinct loops involving different cortical regions, which may be investigated using fMRI at an ultra-high field (7 T) with enhanced sensitivity compared to lower fields. Objectives: We performed fMRI at 7 T to assess functional connectivity between the striatum and several chosen cortical areas including the motor and prefrontal cortex, in order to better understand brain changes in the striatum-cortical pathways. Method: 13 manifest subjects (age 51 ± 13 years, cytosine-adenine-guanine [CAG] repeat 45 ± 5, Unified Huntington’s Disease Rating Scale [UHDRS] motor score 32 ± 17), 8 subjects in the close-to-onset premanifest period (age 38 ± 10 years, CAG repeat 44 ± 2, UHDRS motor score 8 ± 2), 11 subjects in the far-from-onset premanifest period (age 38 ± 11 years, CAG repeat 42 ± 2, UHDRS motor score 1 ± 2), and 16 healthy controls (age 44 ± 15 years) were studied. The functional connectivity between the striatum and several cortical areas was measured by resting state fMRI at 7 T and analyzed in all participants. Results: Compared to controls, functional connectivity between striatum and premotor area, supplementary motor area, inferior frontal as well as middle frontal regions was altered in HD (all p values <0.001). Specifically, decreased striatum-motor connectivity but increased striatum-prefrontal connectivity were found in premanifest HD subjects. Altered functional connectivity correlated consistently with genetic burden, but not with clinical scores. Conclusions: Differential changes in functional connectivity of striatum-prefrontal and striatum-motor circuits can be found in early and premanifest HD. This may imply a compensatory mechanism, where additional cortical regions are recruited to subserve functions that have been impaired due to HD pathology. Our results suggest the potential value of functional connectivity as a marker for future clinical trials in HD.

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Structural and functional connectivity of motor circuits after perinatal stroke: A machine learning study

NeuroImage Clinical ◽

10.1016/j.nicl.2020.102508 ◽

2020 ◽

Vol 28 ◽

pp. 102508

Author(s):

Helen L. Carlson ◽

Brandon T. Craig ◽

Alicia J. Hilderley ◽

Jacquie Hodge ◽

Deepthi Rajashekar ◽

...

Keyword(s):

Machine Learning ◽

Functional Connectivity ◽

Learning Study ◽

Perinatal Stroke ◽

Motor Circuits

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Cingulo-Opercular Control Network Supports Disused Motor Circuits in Standby Mode

10.1101/2020.09.03.275479 ◽

2020 ◽

Author(s):

Dillan J. Newbold ◽

Evan M. Gordon ◽

Timothy O. Laumann ◽

Nicole A. Seider ◽

David F. Montez ◽

...

Keyword(s):

Functional Connectivity ◽

Spontaneous Activity ◽

Functional Mri ◽

Executive Control ◽

Resting State ◽

Control Network ◽

Whole Brain ◽

Motor Circuits ◽

Standby Mode ◽

Control Regions

AbstractWhole-brain resting-state functional MRI (rs-fMRI) during two weeks of limb constraint revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula (1). Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions.SignificanceMany studies have examined plasticity in the primary somatosensory and motor cortex during disuse, but little is known about how disuse impacts the brain outside of primary cortical areas. We leveraged the whole-brain coverage of resting-state functional MRI (rs-fMRI) to discover that disuse drives plasticity of distant executive control regions in the cingulo-opercular network (CON). Two complementary analyses, pulse censoring and pulse addition, demonstrated that increased functional connectivity between the CON and disused motor regions was driven by large, spontaneous pulses of activity in the CON and disused motor regions. These results point to a previously unknown role for the CON in supporting motor plasticity and reveal spontaneous activity pulses as a novel mechanism for reorganizing the brain’s functional connections.

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Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2014.08.016 ◽

2015 ◽

Vol 36 (1) ◽

pp. 536-544 ◽

Cited By ~ 19

Author(s):

Zhuo Wang ◽

Yumei Guo ◽

Kalisa G. Myers ◽

Ryan Heintz ◽

Yu-Hao Peng ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Resting State Functional Connectivity ◽

Motor Circuits

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Prior Somatic Stimulation Improves Performance of Acquired Motor Skill by Facilitating Functional Connectivity in Cortico-Subcortical Motor Circuits

Journal of Behavioral and Brain Science ◽

10.4236/jbbs.2012.23039 ◽

2012 ◽

Vol 02 (03) ◽

pp. 343-356 ◽

Cited By ~ 4

Author(s):

Shintaro Uehara ◽

Isao Nambu ◽

Michikazu Matsumura ◽

Shinji Kakei ◽

Eiichi Naito

Keyword(s):

Functional Connectivity ◽

Motor Skill ◽

Motor Circuits

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Serotonergic modulation of walking in Drosophila

10.1101/753624 ◽

2019 ◽

Author(s):

Clare E. Howard ◽

Chin-Lin Chen ◽

Tanya Tabachnik ◽

Rick Hormigo ◽

Pavan Ramdya ◽

...

Keyword(s):

Functional Connectivity ◽

Walking Speed ◽

Expression Patterns ◽

Complex Environments ◽

Serotonergic Receptors ◽

Motor Circuits ◽

Vinegar Fly ◽

Amine Neurotransmitters ◽

Locomotor Behaviors ◽

Serotonergic Modulation

AbstractTo navigate complex environments, animals must generate highly robust, yet flexible, locomotor behaviors. For example, walking speed must be tailored to the needs of a particular environment: Not only must animals choose the correct speed and gait, they must also rapidly adapt to changing conditions, and respond to sudden and surprising new stimuli. Neuromodulators, particularly the small biogenic amine neurotransmitters, allow motor circuits to rapidly alter their output by changing their functional connectivity. Here we show that the serotonergic system in the vinegar fly, Drosophilamelanogaster, can modulate walking speed in a variety of contexts and in response to sudden changes in the environment. These multifaceted roles of serotonin in locomotion are differentially mediated by a family of serotonergic receptors with distinct activities and expression patterns.

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Alterations of functional connectivity of the motor cortex in Fabry disease

Neurology ◽

10.1212/wnl.0000000000003913 ◽

2017 ◽

Vol 88 (19) ◽

pp. 1822-1829 ◽

Cited By ~ 13

Author(s):

Sirio Cocozza ◽

Antonio Pisani ◽

Gaia Olivo ◽

Francesco Saccà ◽

Lorenzo Ugga ◽

...

Keyword(s):

Functional Connectivity ◽

Motor Cortex ◽

Fabry Disease ◽

Cross Sectional Study ◽

Cerebellar Hemisphere ◽

Cross Sectional ◽

Clinical Variables ◽

Motor Circuits ◽

Fmri Analysis ◽

The Right

Objective:To evaluate the presence of functional connectivity (FC) alterations of the motor circuits in patients with Fabry disease (FD) and their possible correlation with clinical variables with a resting-state (RS) fMRI analysis.Methods:In our cross-sectional study, 32 patients with FD with genetically confirmed classic diagnosis of FD (12 men, mean age 43.3 ± 12.2 years) were enrolled along with 35 healthy controls (HCs) of comparable age and sex (14 men, mean age 42.1 ± 14.5 years). RS-fMRI data were analyzed with a seed-based approach, with 2 different seeds for right and left motor cortex. Patients with FD underwent a clinical examination for the assessment of different motor functions. Correlations with clinical variables were probed with the Spearman correlation coefficient.Results:A reduction of FC was found in patients with FD compared to HCs between both motor cortices and 2 clusters encompassing, for each side, the caudate and lenticular nucleus (p < 5 × 10−4 and p < 10−8 for right and left motor cortex, respectively) and between the left motor cortex and dentate nuclei (p = 0.01) and Crus 1 in the right cerebellar hemisphere (p = 0.001). No significant results emerged in tests for possible correlations of FC with clinical scores.Conclusions:An alteration of the corticostriatal pathway is present in FD, in line with the recently suggested subclinical involvement of motor circuits in this disease. These results shed new light on the pattern of cerebral involvement in FD.

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Amygdala in Action: Functional Connectivity during Approach and Avoidance Behaviors

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01800 ◽

2021 ◽

pp. 1-19

Author(s):

Joana Leitão ◽

Maya Burckhardt ◽

Patrik Vuilleumier

Keyword(s):

Functional Connectivity ◽

Video Game ◽

Goal Pursuit ◽

Partial Least Square ◽

Least Square ◽

Approach And Avoidance ◽

Motor Circuits ◽

Frontoparietal Network ◽

Avoidance Behaviors ◽

Partial Least Square Analysis

Abstract Motivation is an important feature of emotion. By driving approach to positive events and promoting avoidance of negative stimuli, motivation drives adaptive actions and goal pursuit. The amygdala has been associated with a variety of affective processes, particularly the appraisal of stimulus valence that is assumed to play a crucial role in the generation of approach and avoidance behaviors. Here, we measured amygdala functional connectivity patterns while participants played a video game manipulating goal conduciveness through the presence of good, neutral, or bad monsters. As expected, good versus bad monsters elicited opposing motivated behaviors, whereby good monsters induced more approach and bad monsters triggered more avoidance. These opposing directional behaviors were paralleled by increased connectivity between the amygdala and medial brain areas, such as the OFC and posterior cingulate, for good relative to bad, and between amygdala and caudate for bad relative to good monsters. Moreover, in both conditions, individual connectivity strength between the amygdala and medial prefrontal regions was positively correlated with brain scores from a latent component representing efficient goal pursuit, which was identified by a partial least square analysis determining the multivariate association between amygdala connectivity and behavioral motivation indices during gameplay. At the brain level, this latent component highlighted a widespread pattern of amygdala connectivity, including a dorsal frontoparietal network and motor areas. These results suggest that amygdala-medial prefrontal interactions captured the overall subjective relevance of ongoing events, which could consecutively drive the engagement of attentional, executive, and motor circuits necessary for implementing successful goal-pursuit, irrespective of approach or avoidance directions.

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