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Gait rehabilitation using auditory cues can help older adults and people with Parkinson’s improve walking performance. While auditory cues are convenient and can reliably modify gait cadence, it is not clear if auditory cues can reliably modify stride length (SL), another key gait performance metric. Existing algorithms also do not address habituation or fluctuation in motor capability, and have not been evaluated with target populations or under dual-task conditions. In this study, we develop an adaptive auditory cueing framework that aims to modulate SL and cadence. The framework monitors the gait parameters and learns a personalized cue-response model to relate the gait parameters to the input cues. The cue-response model is represented using a multi-output Gaussian Process (MOGP) and is used during optimization to select the cue to provide. The adaptive cueing approach is benchmarked against the fixed approach, where cues are provided at a fixed cadence. The two approaches are tested under single and dual-task conditions with 13 older adults (OA) and 8 people with Parkinson’s (PwP). The results show that more than half of the OA and PwP in the study can change both SL and cadence using auditory cues. The fixed approach is best at changing people’s gait without secondary task, however, the addition of the secondary task significantly degrades effectiveness at changing SL. The adaptive approach can maintain the same level of SL change regardless of the presence of the secondary task. A separate analysis is conducted to identify factors that influence the performance of the adaptive framework. Gait information from the previous time step, along with the previous input cue, can improve its prediction accuracy. More diversity in the initialization data can also improve the GP model. Finally, we did not find a strong correlation between stride length and cadence when the parameters are contingent upon input cues.

People with Parkinson's (PwP) experience gait impairments that can be improved through cue training, where visual, auditory, or haptic cues are provided to guide the walker's cadence or step length. There are two types of cueing strategies: open and closed-loop. Closed-loop cueing may be more effective in addressing habituation and cue dependency, but has to date been rarely validated with PwP. In this study, we adapt a human-in-the-loop framework to conduct preliminary analysis with four PwP. The closed-loop framework learns an individualized model of the walker's responsiveness to cues and generates an optimized cue based on the model. In this feasibility study, we determine whether participants in early stages of Parkinson's can respond to the novel cueing framework, and compare the performance of the framework to two alternative cueing strategies (fixed/proportional approaches) in changing the participant's cadence to two target cadences (speed up/slow down). The preliminary results show that the selection of the target cadence has an impact on the participant's gait performance. With the appropriate target, the framework and the fixed approaches perform similarly in slowing the participants' cadence. However, the proposed framework demonstrates better efficiency, explainability, and robustness across participants. Participants also have the highest retention rate in the absence of cues with the proposed framework. Finally, there is no clear benefit of using the proportional approach.

IntroductionNegative affective states contribute to the chronic-relapsing nature of addiction. Mesolimbic dopamine D3 receptors are well placed to modulate emotion and are dysregulated in substance dependence. Selective antagonists might restore dopaminergic hypofunction, thus representing a potential treatment target. We investigated the effects of selective D3 antagonist, GSK598809, on the neural response to negative emotional processing in substance dependent individuals and healthy controls.MethodologyFunctional MRI BOLD response was assessed during an evocative image task, 2 h following acute administration of GSK598809 (60 mg) or placebo in a multi-site, double-blind, pseudo-randomised, cross-over design. Abstinent drug dependent individuals (DD, n = 36) comprising alcohol-only (AO, n = 19) and cocaine-alcohol polydrug (PD, n = 17) groups, and matched controls (n = 32) were presented with aversive and neutral images in a block design (contrast of interest: aversive > neutral). Whole-brain mixed-effects and a priori ROI analyses tested for group and drug effects, with identical models exploring subgroup effects.ResultsNo group differences in task-related BOLD signal were identified between DD and controls. However, subgroup analysis revealed greater amygdala/insular BOLD signal in PD compared with AO groups. Following drug administration, GSK598809 increased BOLD response across HC and DD groups in thalamus, caudate, putamen, and pallidum, and reduced BOLD response in insular and opercular cortices relative to placebo. Multivariate analyses in a priori ROIs revealed differential effects of D3 antagonism according to subgroup in substantia nigra; GSK598809 increased BOLD response in AO and decreased response in PD groups.ConclusionAcute GSK598809 modulates the BOLD response to aversive image processing, providing evidence that D3 antagonism may impact emotional regulation. Enhanced BOLD response within D3-rich mesolimbic regions is consistent with its pharmacology and with attenuation of substance-related hypodopaminergic function. However, the lack of group differences in task-related BOLD response and the non-specific effect of GSK598809 between groups makes it difficult to ascertain whether D3 antagonism is likely to be normalising or restorative in our abstinent populations. The suggestion of differential D3 modulation between AO and PD subgroups is intriguing, raising the possibility of divergent treatment responses. Further study is needed to determine whether D3 antagonism should be recommended as a treatment target in substance dependence.