The effects of acute exercise on stress reactivity assessed via a multidimensional approach: a systematic review.

Psychological stress is associated with numerous deleterious health effects. Accumulating evidence suggests acute exercise reduces stress reactivity. As stressors activate a wide array of psychological and physiological systems it is imperative stress responses are examined through a multidimensional lens. Moreover, it seems prudent to consider whether stress responses are influenced by exercise intervention characteristics such as modality, duration, intensity, timing, as well as participant fitness/physical activity levels. The current review therefore examined the role of acute exercise on stress reactivity through a multidimensional approach, as well as whether exercise intervention characteristics and participant fitness/physical activity levels may moderate these effects. Stress reactivity was assessed via heart rate, blood pressure, cortisol, catecholamines, and self-report. A systematic search following PRISMA guidelines of five databases was updated in November 2022. Reviewed studies met the following criteria: English language, participants aged ≥ 18, use of acute exercise, use of a validated stress-inducing task, and assessment(s) of stress reactivity. Thirty-one studies (1386 participants) were included. Acute exercise resulted in reliable reductions to blood pressure and cortisol. Acute exercise yielded mostly negligible effects on heart rate reactivity and negligible effects on self-report measures. As for exercise intervention characteristics, intensity-dependent effects were present, such that higher intensities yielded larger reductions to reactivity measures, while limited evidence was present for duration, modality, and timing-dependent effects. Regarding participant fitness/physical activity levels, the effects on stress reactivity were mixed. Future work should standardize the definitions and assessment time points of stress reactivity, as well as investigate the interaction between physiological and psychological stress responses in real-world contexts.

Increased iron in the substantia nigra pars compacta identifies patients with early Parkinson'sdisease: A 3T and 7T MRI study.

Degeneration in the substantia nigra (SN) pars compacta (SNc) underlies motor symptoms in Parkinson's disease (PD). Currently, there are no neuroimaging biomarkers that are sufficiently sensitive, specific, reproducible, and accessible for routine diagnosis or staging of PD. Although iron is essential for cellular processes, it also mediates neurodegeneration. MRI can localize and quantify brain iron using magnetic susceptibility, which could potentially provide biomarkers of PD. We measured iron in the SNc, SN pars reticulata (SNr), total SN, and ventral tegmental area (VTA), using quantitative susceptibility mapping (QSM) and R2* relaxometry, in PD patients and age-matched healthy controls (HCs). PD patients, diagnosed within five years of participation and HCs were scanned at 3T (22 PD and 23 HCs) and 7T (17 PD and 21 HCs) MRI. Midbrain nuclei were segmented using a probabilistic subcortical atlas. QSM and R2* values were measured in midbrain subregions. For each measure, groups were contrasted, with Age and Sex as covariates, and receiver operating characteristic (ROC) curve analyses were performed with repeated k-fold cross-validation to test the potential of our measures to classify PD patients and HCs. Statistical differences of area under the curves (AUCs) were compared using the Hanley-MacNeil method (QSM versus R2*; 3T versus 7T MRI). PD patients had higher QSM values in the SNc at both 3T (padj = 0.001) and 7T (padj = 0.01), but not in SNr, total SN, or VTA, at either field strength. No significant group differences were revealed using R2* in any midbrain region at 3T, though increased R2* values in SNc at 7T MRI were marginally significant in PDs compared to HCs (padj = 0.052). ROC curve analyses showed that SNc iron measured with QSM, distinguished early PD patients from HCs at the single-subject level with good diagnostic accuracy, using 3T (mean AUC = 0.83, 95 % CI = 0.82-0.84) and 7T (mean AUC = 0.80, 95 % CI = 0.79-0.81) MRI. Mean AUCs reported here are from averages of tests in the hold-out fold of cross-validated samples. The Hanley-MacNeil method demonstrated that QSM outperforms R2* in discriminating PD patients from HCs at 3T, but not 7T. There were no significant differences between 3T and 7T in diagnostic accuracy of QSM values in SNc. This study highlights the importance of segmenting midbrain subregions, performed here using a standardized atlas, and demonstrates high accuracy of SNc iron measured with QSM at 3T MRI in identifying early PD patients. QSM measures of SNc show potential for inclusion in neuroimaging diagnostic biomarkers of early PD. An MRI diagnostic biomarker of PD would represent a significant clinical advance.

Subregional analysis of striatum iron in Parkinson's disease and rapid eye movement sleep behaviour disorder.

The loss of dopamine in the striatum underlies motor symptoms of Parkinson's disease (PD). Rapid eye movement sleep behaviour disorder (RBD) is considered prodromal PD and has shown similar neural changes in the striatum. Alterations in brain iron suggest neurodegeneration; however, the literature on striatal iron has been inconsistent in PD and scant in RBD. Toward clarifying pathophysiological changes in PD and RBD, and uncovering possible biomarkers, we imaged 26 early-stage PD patients, 16 RBD patients, and 39 age-matched healthy controls with 3 T MRI. We compared mean susceptibility using quantitative susceptibility mapping (QSM) in the standard striatum (caudate, putamen, and nucleus accumbens) and tractography-parcellated striatum. Diffusion MRI permitted parcellation of the striatum into seven subregions based on the cortical areas of maximal connectivity from the Tziortzi atlas. No significant differences in mean susceptibility were found in the standard striatum anatomy. For the parcellated striatum, the caudal motor subregion, the most affected region in PD, showed lower iron levels compared to healthy controls. Receiver operating characteristic curves using mean susceptibility in the caudal motor striatum showed a good diagnostic accuracy of 0.80 when classifying early-stage PD from healthy controls. This study highlights that tractography-based parcellation of the striatum could enhance sensitivity to changes in iron levels, which have not been consistent in the PD literature. The decreased caudal motor striatum iron was sufficiently sensitive to PD, but not RBD. QSM in the striatum could contribute to development of a multivariate or multimodal biomarker of early-stage PD, but further work in larger datasets is needed to confirm its utility in prodromal groups.

Dissociative effects of dorsomedial striatum D1 and D2 receptor antagonism in the regulation of anxiety and learned approach-avoidance conflict decision-making.

The dorsal striatum is traditionally known for its role in sensorimotor integration. However, the dorsomedial striatum (DMS) has also been implicated in cost-benefit conflict processing, a role more readily attributed to the ventral striatum (VS), as a site of limbic-motor integration. We recently showed that dopaminergic D1 (D1R) and D2 receptors (D2R) in the VS exert dissociable control over cue-elicited approach-avoidance decision-making, in the presence of conflicting motivational stimuli. We therefore sought to investigate the contribution of DMS dopaminergic receptors in the regulation of cue-elicited and innate approach-avoidance decision-making. Using a conditioned mixed-valence conflict paradigm, we trained rats in a three-arm radial maze to associate visuotactile cues with appetitive, aversive, and neutral outcomes. Rats then received an intra-DMS or intra-dorsolateral striatum (DLS) microinfusion of D1-like antagonist (SCH23390) or D2-like antagonist (sulpiride), and were then tested for the expression of approach-avoidance behavior in a conflict scenario, wherein the appetitive and aversive cues were superimposed within a single maze arm. The results revealed that DMS (but not DLS) D1R antagonism, suppressed approach towards the conflict arm while DMS (but not DLS) D2R antagonism enhanced approach. All rats were subsequently administered an elevated plus maze test as a measure of innate approach-avoidance conflict (anxiety). DMS D1R antagonism decreased anxiety, while DMS D2R and both DLS D1R and D2R antagonism increased anxiety. Our findings suggest that under motivational conflict, activation of DMS D1-like receptors facilitates approach, while activation of D2-like receptors suppress approach behavior. Furthermore, anxiety is regulated by dorsal striatal-mediated dopaminergic mechanisms.