Transcranial direct current stimulation (tDCS) of the human sensorimotor cortex during physical rehabilitation induces plasticity in the injured brain that improves motor performance. Bi-hemispheric tDCS is a noninvasive technique that modulates cortical activation by delivering weak current through a pair of anodal–cathodal (excitation–suppression) electrodes, placed on the scalp and centered over the primary motor cortex of each hemisphere. To quantify tDCS-induced plasticity during motor performance, sensorimotor cortical activity was mapped during an event-related, wrist flexion task by functional near-infrared spectroscopy (fNIRS) before, during, and after applying both possible bi-hemispheric tDCS montages in eight healthy adults. Additionally, torque applied to a lever device during isometric wrist flexion and surface electromyography measurements of major muscle group activity in both arms were acquired concurrently with fNIRS. This multiparameter approach found that hemispheric suppression contralateral to wrist flexion changed resting-state connectivity from intra-hemispheric to inter-hemispheric and increased flexion speed ($p<0.05$). Conversely, exciting this hemisphere increased opposing muscle output resulting in a decrease in speed but an increase in accuracy ($p<0.05$ for both). The findings of this work suggest that tDCS with fNIRS and concurrent multimotor measurements can provide insights into how neuroplasticity changes muscle output, which could find future use in guiding motor rehabilitation.

Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children ($10.2±2.1$ years old) with hemiplegic cerebral palsy was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger-tapping task and the resting-state functional connectivity were quantified before, immediately after, and 6 months after CIMT. These fNIRS-based metrics were used to help explain changes in clinical scores of manual performance obtained concurrently with imaging time points. Five age-matched healthy children ($9.8±1.3$ years old) were also imaged to provide comparative activation metrics for normal controls. Interestingly, the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted 6 months later. In contrast to this improved localized activation response, the laterality index and resting-state connectivity metrics that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed 6 months later. In addition, for the subjects measured in this work, there was either a trade-off between improving unimanual versus bimanual performance when sensorimotor activation patterns normalized after CIMT, or an improvement occurred in both unimanual and bimanual performance but at the cost of very abnormal plastic changes in sensorimotor activity.

Recent advances in plasmonic nanopore technologies have enabled the use of concurrently acquired bimodal optical-electrical data for improved quantification of molecular interactions. This work presents the use of a new plasmonic nanosensor employing self-induced back-action (SIBA) for optical trapping to enable SIBA-actuated nanopore electrophoresis (SANE) for quantifying antibody-ligand interactions. T-cell receptor-like antibodies (TCRmAbs) engineered to target peptide-presenting major histocompatibility complex (pMHC) ligands, representing a model of target ligands presented on the surface of cancer cells, were used to test the SANE sensor’s ability to identify specific antibody-ligand binding. Cancer-irrelevant TCRmAbs targeting the same pMHCs were also tested as a control. It was found that the sensor could provide bimodal molecular signatures that could differentiate between antibody, ligand and the complexes that they formed, as well as distinguish between specific and non-specific interactions. Furthermore, the results suggested an interesting phenomenon of increased antibody-ligand complex bound fraction detected by the SANE sensor compared to that expected for corresponding bulk solution concentrations. A possible physical mechanism and potential advantages for the sensor’s ability to augment complex formation near its active sensing volume at concentrations lower than the free solution equilibrium binding constant ( K _D ) are discussed.

A plasmonic nanopore sensor enabling detection of bimodal optical and electrical molecular signatures was fabricated and tested for its ability to characterize low affinity ligand-receptor interactions. This plasmonic nanosensor uses self-induced back-action (SIBA) for optical trapping to enable SIBA-actuated nanopore electrophoresis (SANE) through a nanopore located immediately below the optical trap volume. A natural killer (NK) cell inhibitory receptor heterodimer molecule CD94/NKG2A was synthesized to target a specific peptide-presenting Qa-1 ^b Qdm ligand as a simplified model of low-affinity interactions between immune cells and peptide-presenting cancer cells that occurs during cancer immunotherapy. A cancer-irrelevant Qa-1 ^b GroEL ligand was also targeted by the same receptor as a control experiment to test for non-specific binding. The analysis of different pairs of bimodal SANE sensor signatures enabled discrimination of ligand, receptor and their complexes and enabled differentiating between specific and non-specific ligand interactions. We were able to detect ligand-receptor complex binding at concentrations over 500 times lower than the free solution equilibrium binding constant ( K _D ). Additionally, SANE sensor measurements enabled estimation of the fast dissociation rate ( k _off ) for this low-affinity specific ligand-receptor system, previously shown to be challenging to quantify with commercial technologies. The k _off value of targeted peptide-presenting ligands is known to correlate with the subsequent activation of immune cells in vivo , suggesting the potential utility of the SANE senor as a screening tool in cancer immunotherapy.

When performing physical exercise, the contracting muscles elicit demand for oxygen, which is supplied by increased blood flow. The brain must register and simultaneously integrate input from feedforward (i.e., central command) and feedback (e.g., exercise pressor reflex) neural mechanisms to make necessary cardiovascular adjustments to meet the metabolic demand of the exercise.^1,2 During exercise involving the arms, peripheral fatigue sets in, as characterized by reduced force-generating capability of the muscles that subsequently evolves into central fatigue, resulting in decreased neural drive to the muscles, after prolonged physical activity.^{1 – 6} Central fatigue’s contribution to peripheral fatigue is less understood and functional brain imaging during fatiguing exercises is being investigated as a tool to help elucidate the underlying mechanisms.^{3 – 11} Neural pathways gradually alter their connectivity (neuroplasticity), which affects regulation of the cardiovascular system both at rest and during exercise. Physically active individuals exhibit exercise-related neuroplasticity and have improved cardiovascular health, whereas inactive individuals may be predisposed to higher incidences of cardiovascular disease.^1,5,12