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Publications
A transient neural code for feedback-driven motor corrections during reaching
Nina Kudryashova
Cole Hurwitz
Matthew G. Perich
Matthias H. Hennig
Movement is the result of complex, dynamic interaction between cortical and subcortical circuits. These dynamic interactions implement both … (see more)feedforward motor control, arising from preparatory states, and feedback control, triggered by unexpected sensory events during movement. We show that the neural responses for feedback-driven control can be transient and small in variance, posing difficulties for unsupervised inference methods. We thus propose the Behavior-Aligned Neural Dynamics (BAND) model, which exploits semi-supervised learning to extract latent dynamics that predict both feedforward planned movement and unplanned feedback corrections. Our analysis suggests that motor corrections during movement 1) are encoded on the population level in small neural variability in primary motor (M1), but not dorsal premotor (PMd) cortex; 2) are transient; and 3) are driven by sensory feedback. Our work highlights the importance of targeted closed-loop aware methods to extract and study neural dynamics underlying complex behavioral phenomena.
LRRK2
gene variants are a major genetic risk factor for both familial and sporadic Parkinson’s disease (PD), opening an … (see more)unattended window on the disease’s mechanisms and potential therapies. Investigating the influence of pathogenic variants in
LRRK2
gene on brain structure is a crucial step toward enabling early diagnosis and personalized treatment. Yet, despite its significance, the ways in which
LRRK2
genotype affects brain structure remain largely unexplored. Work in this domain is plagued by small sample sizes and differences in cohort composition, which can obscure genuine distinctions among clinical subgroups. In this study, we overcome such important limitations by combining explicit modeling of population background variation and pattern matching. Specifically, we leveraged a large cohort of 641 participants (including 364 with a PD diagnosis) to examine MRI-detectable cortical atrophy patterns associated with the
LRRK2
pathogenic variants in people with PD and non-manifesting individuals. LRRK2 PD patients exhibited milder cortical thinning compared to sporadic PD, with notable preservation in temporal and occipital regions, suggesting a distinct pattern of neurodegeneration. Non-manifesting LRRK2 carriers showed no significant cortical atrophy, indicating no structural signs of subclinical PD. We further analyzed the relationship between aggregated alpha-synuclein in cerebrospinal fluid and atrophy. We found that those with evidence of aggregated alpha-synuclein experienced pronounced neurodegeneration and increased cortical thinning, possibly defining another aggressive PD subtype. Our findings highlight avenues for distinguishing PD subtypes, which could lead to more targeted treatment approaches and a more complete understanding of Parkinson’s disease progression.