The Effect of Movement Rate and Complexity on Functional Magnetic Resonance Signal Change During Pedaling

We used functional magnetic resonance imaging (fMRI) to record human brain activity during slow (30 RPM), fast (60 RPM), passive (30 RPM), and variable rate pedaling. Ten healthy adults participated. After identifying regions of interest, the intensity and volume of brain activation in each region was calculated and compared across conditions (p \u3c .05). Results showed that the primary sensory and motor cortices (S1, M1), supplementary motor area (SMA), and cerebellum (Cb) were active during pedaling. The intensity of activity in these areas increased with increasing pedaling rate and complexity. The Cb was the only brain region that showed significantly lower activity during passive as compared with active pedaling. We conclude that M1, S1, SMA, and Cb have a role in modifying continuous, bilateral, multijoint lower extremity movements. Much of this brain activity may be driven by sensory signals from the moving limbs

Semantic Memory Functional MRI and Cognitive Function After Exercise Intervention in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer\u27s disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging (fMRI). Seventeen MCI participants and 18 cognitively intact controls, similar in sex, age, education, genetic risk, and medication use, volunteered for a 12-week exercise intervention consisting of supervised treadmill walking at a moderate intensity. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. Before and after the exercise intervention, participants completed an fMRI famous name discrimination task and a neuropsychological battery, Performance on Trial 1 of a list-learning task significantly improved in the MCI participants. Eleven brain regions activated during the semantic memory task showed a significant decrease in activation intensity following the intervention that was similar between groups (p-values ranged 0.048 to 0.0001). These findings suggest exercise may improve neural efficiency during semantic memory retrieval in MCI and cognitively intact older adults, and may lead to improvement in cognitive function. Clinical trials are needed to determine if exercise is effective to delay conversion to AD

Resting Cerebral Blood Flow After Exercise Training in Mild Cognitive Impairment

Background: Exercise training has been associated with greater cerebral blood flow (CBF) in cognitively normal older adults (CN). Alterations in CBF, including compensatory perfusion in the prefrontal cortex, may facilitate changes to the brain’s neural infrastructure. Objective: To examine the effects of a 12-week aerobic exercise intervention on resting CBF and cognition in CN and those with mild cognitive impairment (MCI). We hypothesized individuals with MCI (vs. CN) would exhibit greater whole brain CBF at baseline and that exercise would mitigate these differences. We also expected CBF changes to parallel cognitive improvements. Methods: Before and after a 12-week exercise intervention, 18 CN and 17 MCI participants (aged 61–88) underwent aerobic fitness testing, neuropsychological assessment, and an MRI scan. Perfusion-weighted images were collected using a GE 3T MR system. Repeated measures analyses of covariance were used to test within- and between-group differences over time, followed by post-hoc analyses to examine links between CBF changes and cognitive improvement. Results: At baseline, individuals with MCI (vs. CN) exhibited significantly elevated perfusion in the left insula. Twelve weeks of aerobic exercise reversed this discrepancy. Additionally, exercise improved working memory (measured by the Rey Auditory Verbal Learning Test) and verbal fluency (measured by the Controlled Oral Word Association Test) and differentially altered CBF depending on cognitive status. Among those with MCI, decreased CBF in the left insula and anterior cingulate cortex was associated with improved verbal fluency. Conclusions: Exercise training alters CBF and improves cognitive performance in older adults with and without cognitive impairment. Future studies must evaluate the mediating effects of CBF on the association between exercise training and cognition

Does Physical Activity Influence Semantic Memory Activation in Amnestic Mild Cognitive Impairment?

The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related functional magnetic resonance imaging during fame discrimination. Significantly greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients, (P=0.03), suggesting PA may enhance memory-related caudate activation in aMCI

Flexible Software Platform for Fast-Scan Cyclic Voltammetry Data Acquisition and Analysis

Over the last several decades, fast-scan cyclic voltammetry (FSCV) has proved to be a valuable analytical tool for the real-time measurement of neurotransmitter dynamics in vitro and in vivo. Indeed, FSCV has found application in a wide variety of disciplines including electrochemistry, neurobiology and behavioral psychology. The maturation of FSCV as an in vivo technique led users to pose increasingly complex questions that require a more sophisticated experimental design. To accommodate recent and future advances in FSCV application, our lab has developed High Definition Cyclic Voltammetry (HDCV). HDCV is an electrochemical software suite, and includes data acquisition and analysis programs. The data collection program delivers greater experimental flexibility and better user feedback through live displays. It supports experiments involving multiple electrodes with customized waveforms. It is compatible with TTL-based systems that are used for monitoring animal behavior and it enables simultaneous recording of electrochemical and electrophysiological data. HDCV analysis streamlines data processing with superior filtering options, seamlessly manages behavioral events, and integrates chemometric processing. Furthermore, analysis is capable of handling single files collected over extended periods of time, allowing the user to consider biological events on both sub-second and multi-minute time scales. Here we describe and demonstrate the utility of HDCV for in vivo experiments

Thermo-responsive Diblock Copolymer Worm Gels in Non-polar Solvents

Benzyl methacrylate (BzMA) is polymerized using a poly(lauryl methacrylate) macromolecular chain transfer agent (PLMA macro-CTA) using reversible addition–fragmentation chain transfer (RAFT) polymerization at 70 °C in n-dodecane. This choice of solvent leads to an efficient dispersion polymerization, with polymerization-induced self-assembly (PISA) occurring via the growing PBzMA block to produce a range of PLMA–PBzMA diblock copolymer nano-objects, including spheres, worms, and vesicles. In the present study, particular attention is paid to the worm phase, which forms soft free-standing gels at 20 °C due to multiple inter-worm contacts. Such worm gels exhibit thermo-responsive behavior: heating above 50 °C causes degelation due to the onset of a worm-to-sphere transition. Degelation occurs because isotropic spheres interact with each other much less efficiently than the highly anisotropic worms. This worm-to-sphere thermal transition is essentially irreversible on heating a dilute solution (0.10% w/w) but is more or less reversible on heating a more concentrated dispersion (20% w/w). The relatively low volatility of n-dodecane facilitates variable-temperature rheological studies, which are consistent with eventual reconstitution of the worm phase on cooling to 20 °C. Variable-temperature 1H NMR studies conducted in d26-dodecane confirm partial solvation of the PBzMA block at elevated temperature: surface plasticization of the worm cores is invoked to account for the observed change in morphology, because this is sufficient to increase the copolymer curvature and hence induce a worm-to-sphere transition. Small-angle X-ray scattering and TEM are used to investigate the structural changes that occur during the worm-to-sphere-to-worm thermal cycle; experiments conducted at 1.0 and 5.0% w/w demonstrate the concentration-dependent (ir)reversibility of these morphological transitions

DiffN Selection of Tandem Mass Spectrometry Precursors

Current data-dependent acquisition (DDA) approaches select precursor ions for tandem mass spectrometry (MS/MS) characterization based on their absolute intensity, known as a TopN approach. Low-abundance species may not be identified as biomarkers in a TopN approach. Herein, a new DDA approach is proposed, DiffN, which uses the relative differential intensity of ions between two samples to selectively target species undergoing the largest fold changes for MS/MS. Using a dual nano-electrospray (nESI) ionization source which allows samples contained in separate capillaries to be analyzed in parallel, the DiffN approach was developed and validated with well-defined lipid extracts. A dual nESI source and DiffN DDA approach was applied to quantify the differences in lipid abundance between two colorectal cancer cell lines. The SW480 and SW620 lines represent a matched pair from the same patient: the SW480 cells from a primary tumor and the SW620 cells from a metastatic lesion. A comparison of TopN and DiffN DDA approaches on these cancer cell samples highlights the ability of DiffN to increase the likelihood of biomarker discovery and the decreased probability of TopN to efficiently select lipid species that undergo large fold changes. The ability of the DiffN approach to efficiently select precursor ions of interest makes it a strong candidate for lipidomic analyses. This DiffN DDA approach may also apply to other molecule classes (e.g., other metabolites or proteins) that are amenable to shotgun analyses

Flexible Software Platform for Fast-Scan Cyclic Voltammetry Data Acquisition and Analysis

Over the last several decades, fast-scan cyclic voltammetry (FSCV) has proved to be a valuable analytical tool for the real-time measurement of neurotransmitter dynamics in vitro and in vivo. Indeed, FSCV has found application in a wide variety of disciplines including electrochemistry, neurobiology, and behavioral psychology. The maturation of FSCV as an in vivo technique led users to pose increasingly complex questions that require a more sophisticated experimental design. To accommodate recent and future advances in FSCV application, our lab has developed High Definition Cyclic Voltammetry (HDCV). HDCV is an electrochemical software suite that includes data acquisition and analysis programs. The data collection program delivers greater experimental flexibility and better user feedback through live displays. It supports experiments involving multiple electrodes with customized waveforms. It is compatible with transistor–transistor logic-based systems that are used for monitoring animal behavior, and it enables simultaneous recording of electrochemical and electrophysiological data. HDCV analysis streamlines data processing with superior filtering options, seamlessly manages behavioral events, and integrates chemometric processing. Furthermore, analysis is capable of handling single files collected over extended periods of time, allowing the user to consider biological events on both subsecond and multiminute time scales. Here we describe and demonstrate the utility of HDCV for in vivo experiments