Objective: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent inattention and/or hyperactivity-impulsivity that interferes with functioning or development. Stimulant medication remains its first-line treatment, but perceived ineffectiveness, side effects, and lack of treatment access may pose challenges for adults with ADHD. Physical exercise has received increasing attention in the treatment of children with ADHD, but research in adults is scarce. This paper aims to explore possible mechanisms by which exercise could reduce inattentive, hyperactive, and impulsive symptoms in adults with ADHD. Methods: Respective narrative reviews were conducted on the neurobiology of exercise and of ADHD in adults using relevant search terms in PubMed. Findings were compared to formulate possible mechanisms by which exercise could improve ADHD symptoms in adults. Results: Exercise could reduce ADHD symptoms in adults via enhancement of neuroplasticity and structural integrity in relevant brain regions, improved functional connectivity in cognitive networks, modulation of neurotransmitter release and function, improved hypothalamic-pituitary-adrenal axis function, reduced oxidative stress and neuroinflammation, enhancement of reward and motivation circuitry, and beneficial epigenetic modifications. Limitations: This narrative review relied on a single database and single-author screening with date and language restrictions, and its conclusions are limited by heterogeneous, largely observational evidence, indirect mechanistic data from non-ADHD populations, and few intervention studies in adults with ADHD. Conclusions: Future research should attempt to confirm the efficacy of exercise in reducing ADHD symptoms in adults as well as the proposed mechanisms for such a relationship. Verification of these issues would open the door to an evidence-based, inexpensive, widely available, and broadly beneficial complementary intervention for adults with ADHD.
Background: Gamma-band activity has been linked to cognitive-affective processing in depression. However, its role in deep brain stimulation (DBS) response in treatment-resistant depression (TRD) remains unclear. This exploratory study investigated whether ventral capsule/ventral striatum DBS (VCVS-DBS) modulates gamma activity during cognitive-affective processing and whether DBS-related gamma changes are associated with improvement in depressive symptoms. Methods: Seven participants with TRD completed an affective Multi-Source Interference Task during DBS ON and OFF. Source-localized electroencephalography estimated local gamma power, synchrony, and effective connectivity in fronto-cingulate regions. DBS-and task-related effects were identified with cluster-based permutation testing, and follow-up analyses used Bayesian modeling. Results: During cognitive control under affective context, VCVS-DBS was associated with increased mid-gamma (41-55 Hz) power in left dorsal anterior cingulate cortex (L-dACC) and right ventrolateral prefrontal cortex (R-VLPFC) after affective stimuli. In the time window where power increases overlapped (0.76-0.86 s), DBS was also associated with increased mid-gamma synchrony between these regions. The DBS-related increase in synchrony--not local power--was associated with clinical improvement (Bayesian Spearman rho = 0.52). Granger causality further indicated that effective connectivity shifted toward greater L-dACC influence over R-VLPFC during DBS. Exploratory cross-validation suggested that DBS-related synchrony change and baseline effective connectivity together accounted for individual differences in clinical improvement. Limitations: The primary limitation was the necessarily small sample size, which was partially addressed using Bayesian analyses leveraging extensive within-participant data. Conclusions: These preliminary findings suggest that VCVS-DBS may engage a fronto-cingulate gamma network involved in cognitive-affective control in TRD. They further suggest that clinical response may depend on both baseline dACC-VLPFC network organization and DBS-related modulation of gamma synchrony, highlighting potential relevance to cognitive-affective regulation across psychiatric disorders. Given the small sample size, these findings should be considered hypothesis-generating and require confirmation in larger cohorts.
BACKGROUND:While analyzing distance-dependent functional connectivity strength (FCS) yields valuable information about brain activity, whether the FCS alterations found in obsessive-compulsive disorder (OCD) are linked to inter-regional anatomical distance is still unknown. This study investigated distance-associated functional reorganization in OCD and its associations with clinical assessment data and neurotransmitter receptor/transporter densities. METHODS:To quantify FCS across global, long-range, and short-range scales, we analyzed resting-state functional MRI data from 99 OCD patients and 104 matched healthy controls (HCs), followed by a post hoc exploratory seed-based functional connectivity (FC) analysis to further characterize the key brain regions that may contribute to the observed FCS abnormalities. Group differences and correlations with clinical measures (symptom severity, illness duration, and age of onset) and positron emission tomography-derived neurotransmitter receptor/transporter densities were examined. RESULTS:Compared to HCs, OCD patients exhibited reduced long-range FCS in the bilateral fusiform and parahippocampal gyri, primarily driven by weakened connections with frontal, superior/middle temporal, precuneus, and cingulate regions. Short-range FCS was increased in the right dorsolateral prefrontal cortex but decreased in the precentral gyrus and middle cingulate cortex, mainly due to altered local connections involving the middle frontal gyrus, precentral gyrus, precuneus, and cerebellum. These alterations were robust in cross-validation. No significant correlations were found with clinical measures. However, both long- and short-range FCS changes correlated significantly with neurotransmitter receptors/transporter densities, particularly the excitatory-inhibitory ratio profile. LIMITATIONS:Neurotransmitter receptor/transporter maps were derived from publicly available datasets, which may not capture individual variation in receptor density. CONCLUSION:This study highlights distance-dependent functional connectivity reorganization in OCD and its neurochemical underpinnings, providing new insights into the disorder's pathophysiology.
Background: Depression is a common psychological and behavioural symptom experienced by people with migraines. However, the underlying neural mechanisms of depressive symptoms in this population are unclear. Methods: In this study, we investigated the neural mechanisms underlying excitation-inhibition imbalance in patients with migraine accompanied by depressive symptoms (MD) using the Hurst exponent. We used Analysis of covariance to compare differences in the Hurst exponent between patients with MD, patients with migraine accompanied by non-depressive symptoms (MnD), and healthy controls (HC). Spearman's correlation analysis was used to calculate the correlation between the Hurst exponent of different brain regions and clinical variables. Results: Compared with patients with migraine accompanied by MnD, patients with MD showed an increased Hurst exponent in the left lingual gyrus and medial superior frontal cortex. Compared with HC, MD showed an increased Hurst exponent in the right cerebellum crus 1 and right lingual gyrus. Compared with HC, MnD showed an increased Hurst exponent in the left cerebellum crus 2 and medial superior frontal cortex. The Hurst exponent of the medial superior frontal cortex in patients with migraine was significantly positively correlated with depression scores (r = 0.3501, p = 0.0001). Conclusions: Our study has identified imaging features of excitatory-inhibitory imbalance in MD. Imbalances in excitation and inhibition in the medial superior frontal cortex may serve as a promising candidate imaging marker for diagnosing and intervening in depressive symptoms in migraine.
Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by emotional dysregulation, such as emotional instability, and by non-emotional symptoms, including inattention. These symptom domains are dimensionally distributed in the general population and are hypothesized to reflect both overlapping and distinct structural and functional features of cortical and subcortical brain networks. Methods: We applied a dimensional symptom approach in a sample of adults with ADHD (n = 71) and healthy controls (n = 59) to investigate structural brain correlates of inattention and emotional instability, as measured by the Brown Attention-Deficit Disorder Scales. Structural magnetic resonance imaging (MRI) data were analysed to examine cortical and subcortical associations with these symptom dimensions. Performance in an emotional Stroop task was assessed in conjunction with MRI acquisition in a subsample to explore neural correlates of emotion-related cognitive control. Data were collected between 2012 and 2017. Results: Emotional instability was negatively associated with nucleus accumbens volume, independent of inattention symptoms and ADHD diagnosis (β = -0.29, p = 0.016). Additionally, while controlling for inattention symptoms, a negative correlation between emotional instability and cortical surface area was found in a cluster comprising the left dorsolateral prefrontal cortex and right medial/superior frontal cortex. Moreover, cortical thickness in the lateral orbitofrontal cortex was positively associated with performance in the Stroop task in ADHD (r = 0.44, p = 0.027) while being negatively associated in healthy controls (r = -0.40 p = 0.028). Limitations: Medication use within the ADHD group might influence brain-symptom-associations. The cross-sectional design of the study precludes conclusions about causality. Conclusions: These findings suggest that structural alterations in the nucleus accumbens are more strongly related to emotional, rather than attentional symptoms after accounting for their shared variance. Furthermore, altered prefrontal and orbitofrontal morphology may underlie impairments in emotional regulation, supporting the role of frontostriatal circuits in the dimensional expression of emotional instability across clinical and non-clinical populations.
