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Rice, D.

Publications and source records attributed to Rice, D..

3 recordsLinked to original sources

When Noise Isnt Simply Noise: Deterministic Postural Drive During Noisy Galvanic Vestibular Stimulation (nGVS)

Age- and disease-related vestibular decline can cause dizziness and postural instability, motivating interventions such as noisy galvanic vestibular stimulation (nGVS). nGVS is commonly delivered at "subsensory" amplitudes and explained by stochastic resonance, yet because galvanic stimulation directly modulates vestibular afferents, even imperceptible currents may also exert deterministic effects on balance. This study examined whether low-amplitude nGVS (<1 mA), as typically used in stochastic resonance paradigms, directly influences postural behavior through stimulus-response coupling. Twenty healthy young adults stood on a force plate with feet together and eyes closed on either a rigid surface or 10-cm foam. In randomized order, they completed 300-second trials with band-limited (0-30 Hz), zero-mean nGVS at {+/-}0, 0.1, 0.2, 0.3, 0.5, and 0.7 mA. Coupling between the stimulation waveform and mediolateral ground-reaction force was assessed using coherence and time-cumulant density. Mean coherence was significant mainly at higher amplitudes (0.5-0.7 mA) on both surfaces, whereas time-cumulant density identified significant time-locked vestibular-evoked response components at much lower amplitudes, down to 0.1 mA. These included an early response around 135-155 ms and a later, prominent response around 360-410 ms. Individually, significant coherence was common at 0.5-0.7 mA (15-19 of 20 participants), while cumulant-based responses appeared in some participants even at 0.1 mA. Responses were clearer on foam, consistent with greater vestibular reliance when somatosensory input is less reliable. Overall, low-amplitude nGVS can entrain postural output, suggesting that balance changes during "subsensory" stimulation may reflect both stochastic-resonance-like effects and deterministic vestibular drive, underscoring the need to quantify coupling alongside performance outcomes.

neuroscience↗

Dev-Atlas: A reference atlas of functional brain networks for typically developing adolescents

Adolescence is a critical period for neural changes, including maturation of the brains cognitive networks, but also a period of increased vulnerability to psychopathology. It is well accepted that the brain is functionally organized into multiple interacting networks and extensive literature has demonstrated that the spatial and functional organization of these networks shows major age-related changes across the lifespan, but particularly during adolescence. Yet, there is limited option for a reference functional brain atlas derived from typically developing adolescents, which is especially problematic as the reliable and reproducible identification of functional brain networks crucially depends on the use of such reference functional atlases. In this context, we utilized resting-state functional MRI data from a total of 1,391 typically developing youth between the ages of 8 and 17 years to create a new adolescent-specific reference atlas of functional brain networks. We further investigated the impact of age and sex on these networks. Using a multiscale individual component clustering algorithm (MICCA), we identified 24 reliable functional brain networks, classified within six domains: Default-Mode (5 networks), Control (4 networks), Salience (3 networks), Attention (4 networks), Somatomotor (5 networks), and Visual (3 networks). We identified reliable and large effects of age on the spatial topography of these majority of networks, as well as on the functional network connectivity (FNC) between networks. The DMN showed reduced FNC with the other networks with older age. Sex effects were not as widespread. No significant sex-by-age interactions were detected. Overall, we created a novel brain atlas, named Dev-Atlas, focused on a typically developing sample, with the hope that this atlas can be used in future independent developmental network neuroscience studies. Dev-Atlas is freely available to the research community.

neuroscience↗

Molecular basis of human asparagine synthetase inhibitor specificity

Expression of the enzyme human asparagine synthetase (ASNS) promotes metastatic progression in breast cancer, which affects L-asparagine levels and tumor cell invasiveness. Human ASNS has therefore emerged as a bona fide drug target for cancer therapy. We have reported a slow-onset, tight binding ASNS inhibitor with nanomolar affinity, but our compound exhibits poor cell permeability. On the other hand, we show here that this inhibitor exhibits remarkable selectivity for the human ASNS in HCT-116 cell lysates. By determining the first high-resolution (1.85 [A]) X-ray crystal structure for human ASNS, we have built a computational model of the enzyme complexed to our inhibitor, which provides the first insights into the intermolecular interactions mediating specificity. These findings should facilitate the development of a second generation of ASNS inhibitors, leading to the discovery of drugs to prevent metastasis.

biochemistry↗