Biology subjects

Yeche, M.

Publications and source records attributed to Yeche, M..

3 recordsLinked to original sources

bioRxiv2026

Body-segment coordination as a new predictor of freezing of gait in people with Parkinson disease

Freezing of gait (FOG) in Parkinsons disease (PD) involves impaired integration of posture and locomotion with altered body-segment coordination. We measured coordination using gait kinematics during walking in 16 PD patients with FOG, preoperatively with and without dopaminergic medication (OFF/ON-DOPA), and postoperatively with and without subthalamic deep brain stimulation (OFF/ON-DBS). Body-segment coordination was modeled from acceleration-based intersegmental correlations across trunk, pelvis, and limbs. We tested whether coordination metrics predict individual postoperative FOG severity using LASSO regression with nested cross-validation, including preoperative demographics, clinical scores, gait and coordination metrics. Preoperatively, DOPA decreased trunk-pelvis-upper-limb coordination but increased crossed upper-lower-limbs coupling; while STN-DBS selectively increased inter-upper-limb coordination, with DOPA- and STN-DBS-induced changes being correlated. Whole-body coordination predicted individual postoperative FOG severity, with the most important couplings being the trunk-pelvis and pelvis-lower-limb. Body-segment coordination captures clinically relevant gait metrics in PD, highlighting coordination as a potential biomarker for patient stratification and treatment response.

neuroscience↗

bioRxiv2026

Distinct roles of the human cuneiform and pedunculopontine nuclei in gait initiation and freezing of gait

Freezing of gait in Parkinsons disease (PD) is a major cause of disability, often resistant to dopaminergic therapy and deep brain stimulation (DBS). Its underlying mechanisms remain unclear, mainly because the roles of the human mesencephalic locomotor region (MLR) nuclei are not well understood. Here, we combined rare local field potentials (LFP) recordings from the cuneiform (CuN) and pedunculopontine nuclei (PPN) with biomechanical markers of gait initiation (GI) in four PD patients. We identified functional differences: increases in CuN alpha-band activity precede anticipatory postural adjustments (APA) and correlate with the rhythm of upcoming steps, whereas decreases in PPN beta-band activity occur during APA just before the lead foot lifts off. Imminent freezing is characterized by a breakdown of this organization, marked by mistimed alpha-band surges across the MLR and abnormal PPN beta-band modulation. CuN stimulation selectively improved the stepping rhythm, while PPN stimulation worsened pace or forward vigor. Furthermore, exaggerated mesencephalic alpha-band power was associated with poor clinical responses. These results clarify the individual roles of MLR nuclei in human locomotion and identify pathological alpha dynamics as a biomarker for advancing adaptive neurostimulation.

neuroscience↗

bioRxiv2025

Subthalamic Signature of Freezing of Gait in Parkinson Disease

Freezing of gait (FOG) is a significant disability in Parkinsons disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) only partially alleviates it, with approximately one-third of patients experiencing worsening FOG within a year after surgery. The precise role of STN dysfunction in gait disabilities and FOG remains not fully elucidated. To investigate this, we recorded gait and STN local field potential (LFP) activity in 38 PD patients, both Off and On dopamine medication. Our analysis focused on the relationship between gait performance and STN neuronal activity, particularly examining differences in LFP activity across the posterior-sensorimotor and central-associative regions of the STN. When Off dopamine medication, 12 patients experienced FOG during recordings, with a total of 263 FOG episodes documented. Even in trials without FOG episodes, these patients exhibited altered gait initiation strategies, prioritizing stepping rhythm to manage balance and initiate walking. In contrast, non-FOG patients maintained a higher walking pace. STN activity patterns revealed key differences. In FOG patients, weaker STN alpha/low beta band activity in the STN was associated with walking pace, while stronger decreased low beta band activity correlated with rhythm and balance control. This low beta band association extended from the posterior-sensorimotor to the central-associative STN. In contrast, non-FOG patients showed a more restricted relationship between low beta band activity and gait performance, confined to the posterior STN. As stepping rhythm deteriorated further in FOG patients, FOG episodes occurred. FOG episodes were preceeded by a significant positive relationship between high beta power and rhythm restricted to the posterior STN, with a reverse negative relationship with pace, and a disruption in low beta desynchronization across both posterior and central STN regions. Dopamine medication significantly improved gait patterns, and partially restored STN neuronal activity, reducing differences between FOG and non-FOG patients. These findings differentiate two FOG states, i.e. predisposition and occurrence, each associated with distinct gait initiation strategies and STN activity patterns. They suggest distinct pathophysiological roles of low and high beta band STN activity within specific STN regions in regulating gait and FOG. These findings provide key insights for refining targeted DBS therapies.

neuroscience↗