† These authors have contributed equally to this work.Physical exercise, particularly aerobic exercise, is documented as providing a low cost regimen to counter well-documented cognitive declines including memory, executive function, visuospatial skills, and processing speed in normally aging adults. Prior aging studies focused largely on the effects of medium to long term (>6 months) exercise training; however, the shorter term effects have not been studied. In the present study, we examined changes in brain blood flow, cognition, and fitness in 37 cognitively healthy sedentary adults (57-75 years of age) who were randomized into physical training or a wait-list control group. The physical training group received supervised aerobic exercise for 3 sessions per week 1 h each for 12 weeks. Participants' cognitive, cardiovascular fitness and resting cerebral blood flow (CBF) were assessed at baseline (T1), mid (T2), and post-training (T3). We found higher resting CBF in the anterior cingulate region in the physical training group as compared to the control group from T1 to T3. Cognitive gains were manifested in the exercise group's improved immediate and delayed memory performance from T1 to T3 which also showed a significant positive association with increases in both left and right hippocampal CBF identified earlier in the time course at T2. Additionally, the two cardiovascular parameters, VO 2 max and rating of perceived exertion (RPE) showed gains, compared to the control group. These data suggest that even shorter term aerobic exercise can facilitate neuroplasticity to reduce both the biological and cognitive consequences of aging to benefit brain health in sedentary adults.

Complex mental activity induces improvements in cognition, brain function, and structure in animals and young adults. It is not clear to what extent the aging brain is capable of such plasticity. This study expands previous evidence of generalized cognitive gains after mental training in healthy seniors. Using 3 MRI-based measurements, that is, arterial spin labeling MRI, functional connectivity, and diffusion tensor imaging, we examined brain changes across 3 time points pre, mid, and post training (12 weeks) in a randomized sample (n = 37) who received cognitive training versus a control group. We found significant training-related brain state changes at rest; specifically, 1) increases in global and regional cerebral blood flow (CBF), particularly in the default mode network and the central executive network, 2) greater connectivity in these same networks, and 3) increased white matter integrity in the left uncinate demonstrated by an increase in fractional anisotropy. Improvements in cognition were identified along with significant CBF correlates of the cognitive gains. We propose that cognitive training enhances resting-state neural activity and connectivity, increasing the blood supply to these regions via neurovascular coupling. These convergent results provide preliminary evidence that neural plasticity can be harnessed to mitigate brain losses with cognitive training in seniors.

Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age-and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects.MRI | orbitofrontal cortex | functional connectivity | resting state fMRI | diffusion tensor imaging

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Functional magnetic resonance imaging (fMRI) has been used to infer age-differences in neural activity from the hemodynamic response function (HRF) that characterizes the blood-oxygen-level-dependent (BOLD) signal over time. BOLD literature in healthy aging lacks consensus in age-related HRF changes, the nature of those changes, and their implications for measurement of age differences in brain function. Between-study discrepancies could be due to small sample sizes, analysis techniques, and/or physiologic mechanisms. We hypothesize that, with large sample sizes and minimal analysis assumptions, age-related changes in HRF parameters could reflect alterations in one or more components of the neural-vascular coupling system. To assess HRF changes in healthy aging, we analyzed the large population-derived dataset from the Cambridge Center for Aging and Neuroscience (CamCAN) study (Shafto et al., 2014). During scanning, 74 younger (18–30 years of age) and 173 older participants (54–74 years of age) viewed two checkerboards to the left and right of a central fixation point, simultaneously heard a binaural tone, and responded via right index finger button-press. To assess differences in the shape of the HRF between younger and older groups, HRFs were estimated using FMRIB’s Linear Optimal Basis Sets (FLOBS) to minimize a priori shape assumptions. Group mean HRFs were different between younger and older groups in auditory, visual, and motor cortices. Specifically, we observed increased time-to-peak and decreased peak amplitude in older compared to younger adults in auditory, visual, and motor cortices. Changes in the shape and timing of the HRF in healthy aging, in the absence of performance differences, support our hypothesis of age-related changes in the neural-vascular coupling system beyond neural activity alone. More precise interpretations of HRF age-differences can be formulated once these physiologic factors are disentangled and measured separately.