Virtual reality assessment of reaching accuracy in patients with recent cerebellar stroke.

Background: Dysmetria, the inability to accurately estimate distance in motor tasks, is a characteristic clinical feature of cerebellar injury. Even though subjective dysmetria can be quickly detected during the neurological examination with the finger-to-nose test, objective quantification of reaching accuracy for clinical assessment is still lacking. Emerging VR technology allows for the delivery of rich multisensory environmental stimuli with a high degree of control. Furthermore, recent improvements in the hand-tracking feature offer an opportunity to closely examine the speed, accuracy, and consistency of fine hand movements and proprioceptive function. This study aims to investigate the application of virtual reality (VR) with hand tracking in the rapid quantification of reaching accuracy at the bedside for patients with cerebellar stroke (CS). Methods and results: Thirty individuals (10 CS patients and 20 age-matched neurologically healthy controls) performed a simple task that allowed us to measure reaching accuracy using a VR headset (Oculus Quest 2). During this task, the participant was asked to reach for a target placed along a horizontal sixty-degree arc. Once the fingertip passed through the arc, the target immediately extinguished. 50% of the trials displayed a visible, real-time rendering of the hand as the participant reached for the target (visible hand condition), while the remaining 50% only showed the target being extinguished (invisible hand condition). The invisible hand condition isolates proprioception-guided movements by removing the visibility of the participant's hand. Reaching error was calculated as the difference in degrees between the location of the target, and where the fingertip contacted the arc. Both CS patients and age-matched controls displayed higher average reaching error and took longer to perform a reaching motion in the invisible hand condition than in the visible hand condition. Reaching error was higher in CS than in controls in the invisible hand condition but not in the visible hand condition. Average time taken to perform each trial was higher in CS than in controls in the invisible hand conditions but not in the visible hand condition. Conclusions: Reaching accuracy assessed by VR offers a non-invasive and rapid approach to quantifying fine motor functions in clinical settings. Furthermore, this technology enhances our understanding of proprioceptive function in patients with visuomotor disabilities by allowing the isolation of proprioception from vision. Future studies with larger cohorts and longitudinal designs will examine the quantitative changes in reaching accuracy after stroke and explore the long-term benefits of VR in functional recovery.

In Vivo Reflectance Microscopy of Meissner Corpuscles and Bedside Measures of Large Fiber Sensory Function: A Normative Data Cohort.

BACKGROUND AND OBJECTIVES: The goal of this work was to establish age-, sex-, and body dimension-adjusted normal cutoff values for Meissner corpuscle (MC) densities via in vivo reflectance confocal microscopy (RCM), timed vibration sensory thresholds with a 128-Hz tuning fork, and touch-pressure sensory thresholds with standardized monofilaments for clinical and research application. METHODS: Seventy-seven prospectively recruited individuals without signs or symptoms of peripheral neuropathy or a condition or neurotoxin exposure that can alter sensory function underwent cross-sectional evaluation of MC densities via in vivo RCM, monofilament touch-pressure sensory thresholds, and timed vibration sensory thresholds in nondominant upper and lower extremities. Age-, sex-, and body dimension (e.g., height)-adjusted normal values were developed. The fifth percentile for MC densities and timed vibration thresholds and 95th percentile for MF touch-pressure thresholds were selected as normal cutoff points. RESULTS: Participants were 9 to 89 years of age. Age and sex were uniformly distributed. Timed vibration and touch-pressure thresholds were less sensitive with increasing age and were more sensitive in the hand than in the leg or foot within individuals. Timed vibration thresholds did not differ by sex or body dimensions. Touch-pressure thresholds were lower (more sensitive) at the thenar eminence and digit V in the hand in women compared to men but otherwise did not differ by sex at other measurement locations. Body dimensions did not affect touch-pressure thresholds. There were no apparent age-related floor effects for the 5th and 95th percentile normal cutoff values for timed vibration or touch-pressure thresholds, respectively. MC densities also declined with age and were highest at digit V and lowest at the arch within individuals. MC densities were affected by sex or body dimensions at all imaging sites, with lower densities seen in male participants or larger individuals. MC densities were quantifiable in the hand of all participants and were associated with touch-pressure thresholds at all locations. DISCUSSION: This study establishes age-, sex-, and body dimension-adjusted normal cutoff values for 2 easily applied measures of large fiber sensory function and RCM assessment of MC densities for multiple limb locations. These results will aid in the detection and monitoring of peripheral sensory nerve disorders.

Coupled protein synthesis and ribosome-guided piRNA processing on mRNAs.

PIWI-interacting small RNAs (piRNAs) protect the germline genome and are essential for fertility. piRNAs originate from transposable element (TE) RNAs, long non-coding RNAs, or 3´ untranslated regions (3´UTRs) of protein-coding messenger genes, with the last being the least characterized of the three piRNA classes. Here, we demonstrate that the precursors of 3´UTR piRNAs are full-length mRNAs and that post-termination 80S ribosomes guide piRNA production on 3´UTRs in mice and chickens. At the pachytene stage, when other co-translational RNA surveillance pathways are sequestered, piRNA biogenesis degrades mRNAs right after pioneer rounds of translation and fine-tunes protein production from mRNAs. Although 3´UTR piRNA precursor mRNAs code for distinct proteins in mice and chickens, they all harbor embedded TEs and produce piRNAs that cleave TEs. Altogether, we discover a function of the piRNA pathway in fine-tuning protein production and reveal a conserved piRNA biogenesis mechanism that recognizes translating RNAs in amniotes.