Cerebrovascular blood oxygenation level dependent pulsatility at baseline and following acute exercise among healthy adolescents.

Arterial stiffness is linked to cerebral small vessel damage and neurodegeneration, but barriers to accessing deep cerebrovascular anatomy limit our ability to assess the brain. This study describes an adaptation of a cardiac-related scrubbing method as a means of generating blood oxygenation level-dependent pulsatility maps based on the cardiac cycle. We examine BOLD pulsatility at rest, based on the non-parametric deviation from null metric, as well as changes following acute physiological stress from 20 min of moderate-intensity cycling in 45 healthy adolescents. We evaluate the influence of repetition time (TR) and echo time (TE) using simulated and multi-echo empirical data, respectively. There were tissue-specific and voxel-wise BOLD pulsatility decreases 20 min following exercise cessation. BOLD pulsatility detection was comparable over a range of TR and TE values when scan volumes were kept constant; however, short TRs (≤500 ms) and TEs (∼14 ms) acquisitions would yield the most efficient detection. Results suggest cardiac-related BOLD pulsatility may represent a robust and easily adopted method of mapping cerebrovascular pulsatility with voxel-wise resolution.

Reduced cerebrovascular reactivity among adolescents with bipolar disorder.

OBJECTIVES: Cardiovascular disease (CVD) is excessive and premature among individuals with bipolar disorder (BD). Cerebrovascular reactivity (CVR), reflecting vasodilatory capacity of cerebral blood vessels in response to vasoactive substances, is a marker of cerebrovascular health. Despite informative findings in other diseases, CVR has not previously been examined in BD. METHODS: Twenty-five adolescents with BD and 25 age and sex-matched psychiatrically healthy controls (HCs) completed six 15-second breath-holds (BHs) during functional magnetic resonance imaging (fMRI) at 3-Tesla. CVR was determined by comparing blood-oxygenation-level dependent (BOLD) signal changes. Voxel-wise contrasts were analyzed. Body mass index (BMI) was examined as a potential confound. RESULTS: CVR in the posterior cingulate gyrus and periventricular white matter was lower in BD vs HC. After controlling for differences in BMI, additional between-group CVR differences were observed in the temporal poles, supramarginal gyrus, and lingual gyrus. There were no regions in which CVR was significantly greater in BD vs HC. CVR was not associated with mood symptoms. CONCLUSIONS: This preliminary study provides evidence of cerebrovascular dysfunction in BD, including regions known to be susceptible to cerebrovascular dysfunction and/or disease. These findings warrant additional research on the causes and consequences of cerebrovascular dysfunction in early-onset BD.

Sex differences in brain structure among adolescents with bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) is twice as prevalent amongst female as amongst male adolescents. Thus far, little is known regarding the neurostructural substrates underlying this disparity. We therefore examined sex differences in neurostructural magnetic resonane imaging (MRI) phenotypes amongst adolescents with BD. METHODS: T1-weighted structural MRI was acquired from 44 BD (25 female [F] and 19 male [M]) and 58 (28 F and 30 M) healthy control (HC) adolescents (13-21 years old). Whole-brain and region-of-interest (ROI) analyses examined structural volume and cortical thickness using FreeSurfer. ROIs included the ventrolateral prefrontal cortex (vlPFC), anterior cingulate cortex (ACC), amygdala and hippocampus. General linear models evaluated sex-by-diagnosis interactions, controlling for age and intracranial volume. RESULTS: Whole-brain analysis revealed sex-by-diagnosis interactions in the left supramarginal gyrus (SMG) (P = .02, η2  = 0.02) and right inferior parietal lobule (IPL) volumes (P = .04, η2  = 0.01). Sex differences in HCs were found in the SMG (M > F) and IPL (F > M). In BD, sex differences were reversed and of smaller magnitude in the SMG (M < F) and of greater magnitude in the IPL (F > M), driven by trends towards smaller SMG and IPL in BD vs HC male participants (P = .05 and .14). Whole-brain analyses for cortical thickness, and ROI analyses for volume and cortical thickness, were not significant. CONCLUSIONS: Normative sex differences may be disrupted in adolescent BD in the SMG and IPL, heteromodal association network hubs responsible for higher order integration of cognitive and emotional processing. Unexpectedly, these findings may inform our understanding of aberrant brain structure in adolescent BD male patients, rather than female patients. Future work should focus on replication, as well as the impact of puberty status and sex hormones on measures of brain structure and function.

Increased cerebral blood flow among adolescents with bipolar disorder at rest is reduced following acute aerobic exercise.

OBJECTIVE: Cerebral blood flow (CBF) is altered in mood disorders but has not been examined among adolescents with bipolar disorder (BD). Similarly, little is known about the acute neurophysiologic effects of aerobic exercise in BD. We therefore compared CBF between adolescents with and without BD at rest and acutely following a single exercise session. METHODS: Thirty-one adolescents with BD and 20 age and sex-matched controls participated in this study. CBF magnetic resonance images (MRI) were acquired using arterial spin labeling at a baseline as well as 15 and 45min after a single 20-min session of recumbent cycling. Voxel-based CBF analyses compared groups at baseline and after exercise. Clinical, body mass index (BMI) and exercise-induced feelings inventory (EFI) data were examined for their influence on CBF findings. RESULTS: Baseline CBF was increased in medial frontal and middle cingulate regions in BD compared to controls. Analysis of the acute CBF changes revealed pronounced exercise-related decreases in CBF in BD. Exercise-related feelings of exhaustion were associated with CBF changes in frontal but not parietal regions. DISCUSSION: A single bout of moderate-intensity aerobic exercise reduced regional CBF to a greater extent in BD compared to controls; these time dependent CBF responses were associated with exercise-induced feelings of exhaustion.