The Effects of Age, from Young to Middle Adulthood, and Gender on Resting State Functional Connectivity of the Dopaminergic Midbrain

Abstract

Dysfunction of the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is implicated in psychiatric disorders including attention-deficit/ hyperactivity disorder (ADHD), addiction, schizophrenia and movement disorders such as Parkinson’s disease (PD). Although the prevalence of these disorders varies by age and sex, the underlying neural mechanism is not well understood. The objective of this study was to delineate the distinct resting state functional connectivity (rsFC) of the VTA and SNc and examine the effects of age, from young to middle-adulthood, and sex on the rsFC of these two dopaminergic structures in a data set of 250 healthy adults (18–49 years of age, 104 men). Using blood oxygenation level dependent (BOLD) signals, we correlated the time course of the VTA and SNc to the time courses of all other brain voxels. At a corrected threshold, paired t-test showed stronger VTA connectivity to bilateral angular gyrus and superior/middle and orbital frontal regions and stronger SNc connectivity to the insula, thalamus, parahippocampal gyrus (PHG) and amygdala. Compared to women, men showed a stronger VTA/SNc connectivity to the left posterior orbital gyrus. In linear regressions, men but not women showed age-related changes in VTA/SNc connectivity to a number of cortical and cerebellar regions. Supporting shared but also distinct cerebral rsFC of the VTA and SNc and gender differences in age-related changes from young and middle adulthood in VTA/SNc connectivity, these new findings help advance our understanding of the neural bases of many neuropsychiatric illnesses that implicate the dopaminergic systems.

Acupuncture Treatment Modulates the Connectivity of Key Regions of the Descending Pain Modulation and Reward Systems in Patients with Chronic Low Back Pain

“…Dennis and Melzack demonstrated that dopaminergic agents improve symptoms of pain and promote analgesia [98]. Studies have also shown that the VTA sends projections to the nucleus accumbens (NCs), limbic system (e.g., hippocampus and amygdala), and prefrontal cortex (e.g., mPFC, ACC, and OFC), forming the mesocorticolimbic system [27][28][29][30][31].…”

“…Studies have found that chronic pain is a hypodopaminergic state [24][25][26]. The ventral tegmental area (VTA), a key structure in the midbrain, sends dopaminergic neural projections to the ventral striatum (i.e., nucleus accumbens), limbic system (e.g., hippocampus and amygdala), and prefrontal cortex (e.g., mPFC, ACC, and OFC), forming the mesocorticolimbic system [27][28][29][30][31]. In a recent study, we found that chronic low back pain was associated with VTA functional connectivity alterations [32], and preclinical studies have suggested that targeting reward/motivation circuits may promote recovery from chronic pain [23].…”

Exploring Age-Related Changes in Resting State Functional Connectivity of the Amygdala: From Young to Middle Adulthood

“…Brain imaging data were preprocessed using Statistical Parametric Mapping (SPM 8, Wellcome Department of Imaging Neuroscience, University College London, United Kingdom) following previous work ( Kann et al, 2016 ; Li et al, 2017 ; Peterson et al, 2017 ; Zhang S. et al, 2017 ; Hu et al, 2018 ). Images from the first five TRs at the beginning of each trial were discarded to enable the signal to achieve steady-state equilibrium between RF pulsing and relaxation.…”

Sex‐related pattern of intrinsic brain connectivity in drug‐naïve Parkinson's disease patients

“…Genetic, biological, and chemical sex‐related differences are known to influence specific physiological variables, which can, in turn, affect fMRI signal . Indeed, previous RS and task‐related fMRI studies have shown both topological and regional sex‐related differences in healthy subjects, some specific for dopamine‐related functions . Nevertheless, to date there is no fMRI study investigating the neural correlates of sex difference in PD patients.…”