Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Future water resources for food production in five South Asian river basins and potential for adaptation--a modeling study.

The Indian subcontinent faces a population increase from 1.6 billion in 2000 towards 2 billion around 2050. Therefore, expansion of agricultural area combined with increases in productivity will be necessary to produce the food needed in the future. However, with pressure on water resources already being high, and potential effects of climate change still uncertain, the question rises whether there will be enough water resources available to sustain this production. The objective of this study is to make a spatially explicit quantitative analysis of water requirements and availability for current and future food production in five South Asian basins (Indus, Ganges, Brahmaputra, Godavari and Krishna), in the absence or presence of two different adaptation strategies: an overall improvement in irrigation efficiency, and an increase of reservoir storage capacity. The analysis is performed by using the coupled hydrology and crop production model LPJmL. It is found that the Godavari and Krishna basins will benefit most from an increased storage capacity, whereas in the Ganges and the Indus water scarcity mainly takes place in areas where this additional storage would not provide additional utility. Increasing the irrigation efficiency will be beneficial in all basins, but most in the Indus and Ganges, as it decreases the pressure on groundwater resources and decreases the fraction of food production that would become at risk because of water shortage. A combination of both options seems to be the best strategy in all basins. The large-scale model used in this study is suitable to identify hotspot areas and support the first step in the policy process, but the final design and implementation of adaptation options requires supporting studies at finer scales.

Snowmelt contributions to discharge of the Ganges.

Himalayan headwaters supply large quantities of runoff derived from snowmelt and monsoon rainfall to the Ganges River. Actual snowmelt contribution to discharge in the Ganges remains conjectural under both present and future climatic conditions. As snowmelt is likely to be perturbed through climatic warming, four hydrological models, VIC, JULES, LPJmL and SWAT, appropriate for coupling with regional climate models, were used to provide a baseline estimate of snowmelt contribution to flow at seasonal and annual timescales. The models constrain estimates of snowmelt contributions to between 1% and 5% of overall basin runoff. Snowmelt is, however, significant in spring months, a period in which other sources of runoff are scarce.

Land atmosphere feedbacks and their role in the water resources of the Ganges basin.

The northern Indian subcontinent has frequently been identified as a hotspot for land atmosphere interactions. It is also a region with the highest concentration of irrigated land and highest (and increasing) population density in the world. The available water in the region with which to grow food depends on the Asian monsoon, groundwater and melt from Himalayan snows. Any changes or disruptions to these sources of water could threaten the food supply. It is therefore essential to understand how the land surface, and in particular irrigated land, interacts with the atmosphere. It is anticipated that the interactions will occur on many scales. To an extent the magnitude and form of these will depend on the depth of the atmosphere which is affected. Thus at the local, or micro, scale it is the surface layer (some 10 s m deep) which is cooled and moistened by the evaporation of irrigated water, at the meso-scale the Planetary boundary layer (up to 1 or 2 km) will be modified - with possible atmospheric moistening, increased cloud and rain formation and at very large scales the whole dynamics of the south Asian Monsoon will be affected. This illustrates a strong interaction between the Asian monsoon and the regional topography. Of considerable significance is the finding in this paper that up to 60% of the evaporation from irrigated areas in the summer months is ultimately recycled to Himalayan rainfall and so feedbacks to river flows in the Ganges.

Application of regional climate models to the Indian winter monsoon over the western Himalayas.

The Himalayan region is characterized by pronounced topographic heterogeneity and land use variability from west to east, with a large variation in regional climate patterns. Over the western part of the region, almost one-third of the annual precipitation is received in winter during cyclonic storms embedded in westerlies, known locally as the western disturbance. In the present paper, the regional winter climate over the western Himalayas is analyzed from simulations produced by two regional climate models (RCMs) forced with large-scale fields from ERA-Interim. The analysis was conducted by the composition of contrasting (wet and dry) winter precipitation years. The findings showed that RCMs could simulate the regional climate of the western Himalayas and represent the atmospheric circulation during extreme precipitation years in accordance with observations. The results suggest the important role of topography in moisture fluxes, transport and vertical flows. Dynamical downscaling with RCMs represented regional climates at the mountain or even event scale. However, uncertainties of precipitation scale and liquid-solid precipitation ratios within RCMs are still large for the purposes of hydrological and glaciological studies.