Gait and Balance Changes with Investigational Peripheral Nerve Cell Therapy during Deep Brain Stimulation in People with Parkinson’s Disease

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the role of APNG implantation alone. We hypothesized that APNG might improve gait and balance deficits associated with PD. Results: While people with a degenerative movement disorder typically worsen with time, none of the gait parameters significantly changed across visits in this 24 month study. The postural stability item in the UPDRS did not worsen from baseline to the 24-month follow-up. However, we measured gait and balance improvements in the two most affected individuals, who had moderate PD. In these two individuals, we observed an increase in gait velocity and step length that persisted over 6 and 24 months. Conclusions: Participants did not show worsening of gait and balance performance in the off therapy state two years after surgery, while the two most severely affected participants showed improved performance. Further studies may better address the long-term maintanenace of these results

Rhythm and groove as cognitive mechanisms of dance intervention in Parkinson's disease.

Parkinson's disease (PD) is associated with a loss of internal cueing systems, affecting rhythmic motor tasks such as walking and speech production. Music and dance encourage spontaneous rhythmic coupling between sensory and motor systems; this has inspired the development of dance programs for PD. Here we assessed the therapeutic outcome and some underlying cognitive mechanisms of dance classes for PD, as measured by neuropsychological assessments of disease severity as well as quantitative assessments of rhythmic ability and sensorimotor experience. We assessed prior music and dance experience, beat perception (Beat Alignment Test), sensorimotor coupling (tapping to high- and low-groove songs), and disease severity (Unified Parkinson's Disease Rating Scale in PD individuals) before and after four months of weekly dance classes. PD individuals performed better on UPDRS after four months of weekly dance classes, suggesting efficacy of dance intervention. Greater post-intervention improvements in UPDRS were associated with the presence of prior dance experience and with more accurate sensorimotor coupling. Prior dance experience was additionally associated with enhanced sensorimotor coupling during tapping to both high-groove and low-groove songs. These results show that dance classes for PD improve both qualitative and quantitative assessments of disease symptoms. The association between these improvements and dance experience suggests that rhythmic motor training, a mechanism underlying dance training, impacts improvements in parkinsonian symptoms following a dance intervention

A cerebellum-like circuit in the lateral line system of fish cancels mechanosensory input associated with its own movements

Author Posting. © Company of Biologists, 2020. This article is posted here by permission of Company of Biologists for personal use, not for redistribution. The definitive version was published in Journal of Experimental Biology 223 (2020): jeb.204438, doi:10.1242/jeb.204438.An animal's own movement exerts a profound impact on sensory input to its nervous system. Peripheral sensory receptors do not distinguish externally generated stimuli from stimuli generated by an animal's own behavior (reafference) – although the animal often must. One way that nervous systems can solve this problem is to provide movement-related signals (copies of motor commands and sensory feedback) to sensory systems, which can then be used to generate predictions that oppose or cancel out sensory responses to reafference. Here, we studied the use of movement-related signals to generate sensory predictions in the lateral line medial octavolateralis nucleus (MON) of the little skate. In the MON, mechanoreceptive afferents synapse on output neurons that also receive movement-related signals from central sources, via a granule cell parallel fiber system. This parallel fiber system organization is characteristic of a set of so-called cerebellum-like structures. Cerebellum-like structures have been shown to support predictive cancellation of reafference in the electrosensory systems of fish and the auditory system of mice. Here, we provide evidence that the parallel fiber system in the MON can generate predictions that are negative images of (and therefore cancel) sensory input associated with respiratory and fin movements. The MON, found in most aquatic vertebrates, is probably one of the most primitive cerebellum-like structures and a starting point for cerebellar evolution. The results of this study contribute to a growing body of work that uses an evolutionary perspective on the vertebrate cerebellum to understand its functional diversity in animal behavior.This work was supported by National Science Foundation (NSF) and Wesleyan University grants to D.B. Funding for K.E.P. while performing these experiments came in part from a grant from the HHMI Hughes V award for undergraduate education to Wesleyan University (52005211) in the form of a summer research fellowship. A.K. was supported in part by an NSF-REU Award (1659604) and a Wesleyan University Summer Research Fellowship. K.E.P. is currently supported through funding from the Simons Society of Fellows as a Junior Fellow.2021-01-1

Reproductive Rights and Medico-Legal Education Post-Dobbs: A Fireside Chat

The Supreme Court’s 2022 decision in Dobbs v. Jackson Women’s Health Organization was a pivotal moment that reshaped the landscape of abortion policy and delivery of abortion care in the United States. To create a space for critical reflection on the implications of Dobbs for the teaching and learning of abortion care in both medical and legal education, the authors engage in a dialogue highlighting the varied perspectives of professionals and professionals-in-training in both the medical and legal professions. As new attacks on reproductive autonomy continue at both state and federal levels, we foreshadow a tumultuous landscape for abortion policy in the next several decades and describe the impact and ramifications of widespread restrictions on abortion care at all levels of medical training and practice; collaboration between physicians and attorneys will be essential to forge a path ahead

Reproductive Rights and Medico-Legal Education Post-Dobbs: A Fireside Chat

The Supreme Court’s 2022 decision in Dobbs v. Jackson Women’s Health Organization was a pivotal moment that reshaped the landscape of abortion policy and delivery of abortion care in the United States. To create a space for critical reflection on the implications of Dobbs for the teaching and learning of abortion care in both medical and legal education, the authors engage in a dialogue highlighting the varied perspectives of professionals and professionals-in-training in both the medical and legal professions. As new attacks on reproductive autonomy continue at both state and federal levels, we foreshadow a tumultuous landscape for abortion policy in the next several decades and describe the impact and ramifications of widespread restrictions on abortion care at all levels of medical training and practice; collaboration between physicians and attorneys will be essential to forge a path ahead

Gait and Balance Changes with Investigational Peripheral Nerve Cell Therapy during Deep Brain Stimulation in People with Parkinson’s Disease

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the role of APNG implantation alone. We hypothesized that APNG might improve gait and balance deficits associated with PD. Results: While people with a degenerative movement disorder typically worsen with time, none of the gait parameters significantly changed across visits in this 24 month study. The postural stability item in the UPDRS did not worsen from baseline to the 24-month follow-up. However, we measured gait and balance improvements in the two most affected individuals, who had moderate PD. In these two individuals, we observed an increase in gait velocity and step length that persisted over 6 and 24 months. Conclusions: Participants did not show worsening of gait and balance performance in the off therapy state two years after surgery, while the two most severely affected participants showed improved performance. Further studies may better address the long-term maintanenace of these results