Normal brain aging is accompanied by patterns of functional and structural change.Alzheimer's disease (AD), a representative neurodegenerative disease, has been linked to accelerated brain aging at respective age ranges. Here, we developed a deep learning-based brain age prediction model using fluorodeoxyglucose (FDG) PET and structural MRI and tested how the brain age gap relates to degenerative cognitive syndromes including mild cognitive impairment, AD, frontotemporal dementia, and Lewy body dementia. Occlusion analysis, performed to facilitate interpretation of the model, revealed that the model learns an age-and modality-specific pattern of brain aging. The elevated brain age gap in dementia cohorts was highly correlated with the cognitive impairment and AD biomarker. However, regions generating brain age gaps were different for each diagnosis group of which the AD continuum showed similar patterns to normal aging in the CU.

Dopamine (DA) modulates central neuronal activity through both phasic (second to second) and tonic (minutes to hours) terminal release. Conventional fast-scan cyclic voltammetry (FSCV), in combination with carbon fiber microelectrodes, has been used to measure phasic DA release in vivo by adopting a background subtraction procedure to remove background capacitive currents. However, measuring tonic changes in DA concentrations using conventional FSCV has been difficult because background capacitive currents are inherently unstable over long recording periods. To measure tonic changes in DA concentrations over several hours, we applied a novel charge-balancing multiple waveform FSCV (CBM-FSCV), combined with a dual background subtraction technique, to minimize temporal variations in background capacitive currents. Using this method, in vitro, charge variations from a reference time point were nearly zero for 48 h, whereas with conventional background subtraction, charge variations progressively increased. CBM-FSCV also demonstrated a high selectivity against 3,4-dihydroxyphenylacetic acid and ascorbic acid, two major chemical interferents in the brain, yielding a sensitivity of 85.40 ± 14.30 nA/μM and limit of detection of 5.8 ± 0.9 nM for DA while maintaining selectivity. Recorded in vivo by CBM-FSCV, pharmacological inhibition of DA reuptake (nomifensine) resulted in a 235 ± 60 nM increase in tonic extracellular DA concentrations, while inhibition of DA synthesis (α-methyl-dl-tyrosine) resulted in a 72.5 ± 4.8 nM decrease in DA concentrations over a 2 h period. This study showed that CBM-FSCV may serve as a unique voltammetric technique to monitor relatively slow changes in tonic extracellular DA concentrations in vivo over a prolonged time period.

No abstract

These results provide evidence that brain signals are different depending on the movement conditions or effectors. Thus, the two-staged method could be useful if BCIs are used to generalize for both unimanual and bimanual operations in human applications and in various neuro-prosthetics fields.

Background: In the field of translational neuroscience research, it is critical to utilize a large animal model to test the feasibility, safety, and functionality of novel therapies. Here, we describe a protocol for the development of a large animal model of tremor. Methods: In a pig model, tremor was induced with harmaline and measured with wireless accelerometers attached to the limbs. Three different doses of harmaline were tested and three repetitive injections were made at 72-hour intervals. To fully characterize the drug-induced tremor, onset time, tremor amplitude, maintained duration, and peak tremor frequency were analyzed. Results: Harmaline-induced tremor appeared immediately following intravenous injection of harmaline. Tremor was maintained over 2 hours. Its frequency was 10-16 Hz, which was independent of doses. Dose-dependent responses were observed in tremor amplitude, triggering time, and tremor-maintained duration. Repetitive injection of harmaline desensitized the harmaline effect. Discussion: We provide a detailed protocol for training, drug injection, device selection, and tremor recording optimized to create a swine model of tremor with harmaline. Our protocol provides reliable tremor in pigs and suggests pig as a valid translational large animal model of tremor.