Bayesian Inference for Brain Activity from Functional Magnetic Resonance Imaging Collected at Two Spatial Resolutions.

Neuroradiologists and neurosurgeons increasingly opt to use functional magnetic resonance imaging (fMRI) to map functionally relevant brain regions for noninvasive presurgical planning and intraoperative neuronavigation. This application requires a high degree of spatial accuracy, but the fMRI signal-to-noise ratio (SNR) decreases as spatial resolution increases. In practice, fMRI scans can be collected at multiple spatial resolutions, and it is of interest to make more accurate inference on brain activity by combining data with different resolutions. To this end, we develop a new Bayesian model to leverage both better anatomical precision in high resolution fMRI and higher SNR in standard resolution fMRI. We assign a Gaussian process prior to the mean intensity function and develop an efficient, scalable posterior computation algorithm to integrate both sources of data. We draw posterior samples using an algorithm analogous to Riemann manifold Hamiltonian Monte Carlo in an expanded parameter space. We illustrate our method in analysis of presurgical fMRI data, and show in simulation that it infers the mean intensity more accurately than alternatives that use either the high or standard resolution fMRI data alone.

Exposure-Focused CBT Outperforms Relaxation-Based Control in an RCT of Treatment for Child and Adolescent Anxiety.

OBJECTIVE: The relative contribution of individual cognitive behavioral therapy (CBT) components to treatment outcomes for child anxiety disorders (CADs) is unclear. Recent meta-analyses suggest that exposure may be the primary active ingredient in CBT for CADs, and that relaxation may be relatively less effective. This brief report tests the hypothesis that exposure-focused CBT (EF-CBT) would outperform a relaxation-based active therapy control (Relaxation Mentorship Training; RMT) for the treatment of CADs. METHOD: Participants were 102 youth with CADs (mean age = 11.91, 26 males; 76.4% White, 14.7% Multiracial, 3.9% Black, 3.9% Asian, 0.9% other/do not wish to identify) as part of an ongoing neuroimaging randomized controlled trial. Participants were randomly assigned (ratio 2:1) to receive 12 sessions of EF-CBT (n = 70) or RMT (n = 32). Clinical improvement was measured at Week 12 (Clinical Global Impression - Improvement scale; CGI-I); treatment response was defined as receiving a rating of "very much" or "much improved" on the CGI-I. Anxiety severity was measured at Weeks 1, 6, 9, 12 (Pediatric Anxiety Rating Scale; PARS). Outcome measures were completed by an independent evaluator unaware of condition. RESULTS: EF-CBT exhibited 2.98 times higher odds of treatment completion than RMT; 13 treatment non-completers were included in analyses. Estimated treatment response rates were higher for EF-CBT (57.3%) than for RMT (19.2%). Longitudinal analyses indicated that EF-CBT was associated with faster and more pronounced anxiety reductions than RMT on the PARS (Hedges' g = .77). CONCLUSIONS: Results suggest that EF-CBT without relaxation is effective for CADs, and more effective than a relaxation-based intervention.

Entorhinal volume, aerobic fitness, and recognition memory in healthy young adults: A voxel-based morphometry study.

Converging evidence supports the hypothesis effects of aerobic exercise and environmental enrichment are beneficial for cognition, in particular for hippocampus-supported learning and memory. Recent work in humans suggests that exercise training induces changes in hippocampal volume, but it is not known if aerobic exercise and fitness also impact the entorhinal cortex. In animal models, aerobic exercise increases expression of growth factors, including brain derived neurotrophic factor (BDNF). This exercise-enhanced expression of growth hormones may boost synaptic plasticity, and neuronal survival and differentiation, potentially supporting function and structure in brain areas including but not limited to the hippocampus. Here, using voxel based morphometry and a standard graded treadmill test to determine cardio-respiratory fitness (Bruce protocol; ·VO2 max), we examined if entorhinal and hippocampal volumes were associated with cardio-respiratory fitness in healthy young adults (N=33). In addition, we examined if volumes were modulated by recognition memory performance and by serum BDNF, a putative marker of synaptic plasticity. Our results show a positive association between volume in right entorhinal cortex and cardio-respiratory fitness. In addition, average gray matter volume in the entorhinal cortex, bilaterally, was positively associated with memory performance. These data extend prior work on the cerebral effects of aerobic exercise and fitness to the entorhinal cortex in healthy young adults thus providing compelling evidence for a relationship between aerobic fitness and structure of the medial temporal lobe memory system.

Hippocampal subfield and medial temporal cortical persistent activity during working memory reflects ongoing encoding.

Previous neuroimaging studies support a role for the medial temporal lobes in maintaining novel stimuli over brief working memory (WM) delays, and suggest delay period activity predicts subsequent memory. Additionally, slice recording studies have demonstrated neuronal persistent spiking in entorhinal cortex, perirhinal cortex (PrC), and hippocampus (CA1, CA3, subiculum). These data have led to computational models that suggest persistent spiking in parahippocampal regions could sustain neuronal representations of sensory information over many seconds. This mechanism may support both WM maintenance and encoding of information into long term episodic memory. The goal of the current study was to use high-resolution fMRI to elucidate the contributions of the MTL cortices and hippocampal subfields to WM maintenance as it relates to later episodic recognition memory. We scanned participants while they performed a delayed match to sample task with novel scene stimuli, and assessed their memory for these scenes post-scan. We hypothesized stimulus-driven activation that persists into the delay period-a putative correlate of persistent spiking-would predict later recognition memory. Our results suggest sample and delay period activation in the parahippocampal cortex (PHC), PrC, and subiculum (extending into DG/CA3 and CA1) was linearly related to increases in subsequent memory strength. These data extend previous neuroimaging studies that have constrained their analysis to either the sample or delay period by modeling these together as one continuous ongoing encoding process, and support computational frameworks that predict persistent activity underlies both WM and episodic encoding.

Structural differences in hippocampal and prefrontal gray matter volume support flexible context-dependent navigation ability.

Spatial navigation is a fundamental part of daily life. Humans differ in their individual abilities to flexibly navigate their world, and a critical question is how this variability relates to differences in underlying brain structure. Our experiment examined individual differences in the ability to flexibly navigate routes that overlap with, and must be distinguished from, previously learned trajectories. We related differences in flexible navigation performance to differences in brain morphology in healthy young adults using voxel-based morphometry. Our findings provide novel evidence that individual differences in gray matter volume in the hippocampus and dorsolateral prefrontal cortex correlate with our ability rapidly to learn and flexibly navigate routes through our world.

Interaction between serum BDNF and aerobic fitness predicts recognition memory in healthy young adults.

Convergent evidence from human and non-human animal studies suggests aerobic exercise and increased aerobic capacity may be beneficial for brain health and cognition. It is thought growth factors may mediate this putative relationship, particularly by augmenting plasticity mechanisms in the hippocampus, a brain region critical for learning and memory. Among these factors, glucocorticoids, brain derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF), hormones that have considerable and diverse physiological importance, are thought to effect normal and exercise-induced hippocampal plasticity. Despite these predictions, relatively few published human studies have tested hypotheses that relate exercise and fitness to the hippocampus, and none have considered the potential links to all of these hormonal components. Here we present cross-sectional data from a study of recognition memory; serum BDNF, cortisol, IGF-1, and VEGF levels; and aerobic capacity in healthy young adults. We measured circulating levels of these hormones together with performance on a recognition memory task, and a standard graded treadmill test of aerobic fitness. Regression analyses demonstrated BDNF and aerobic fitness predict recognition memory in an interactive manner. In addition, IGF-1 was positively associated with aerobic fitness, but not with recognition memory. Our results may suggest an exercise adaptation-related change in the BDNF dose-response curve that relates to hippocampal memory.