Faculty Bibliography

This article is part of the Physical Review Research collection titled Physics of Neuroscience. To generate actions in the face of physiological delays, the brain must predict the future. Here we explore how prediction may lie at the core of brain function by considering a neuron predicting the future of a scalar time series input. Assuming that the dynamics of the lag vector (a vector composed of several consecutive elements of the time series) are locally linear, normal mode decomposition decomposes the dynamics into independently evolving (eigen)modes allowing for straightforward prediction. We propose that a neuron learns the top mode and projects its input onto the associated subspace. Under this interpretation, the temporal filter of a neuron corresponds to the left eigenvector of a generalized eigenvalue problem. We mathematically analyze the operation of such an algorithm on noisy observations of synthetic data generated by a linear system. Interestingly, the shape of the temporal filter varies with the signal-to-noise ratio (SNR): a noisy input yields a monophasic filter and a growing SNR leads to multiphasic filters with progressively greater number of phases. Such variation in the temporal filter with input SNR resembles that observed experimentally in biological neurons.

PURPOSE OF REVIEW/OBJECTIVE:Kidney stones affect an increasing proportion of the population. We suggest that these trends are in part influenced by exposure to higher temperatures as a result of climate change and urbanization. The changing epidemiology of kidney stones is a topic worthy of discussion due to the economic and healthcare burden the condition poses as well as the quality-of-life disruption faced by individuals with kidney stones. RECENT FINDINGS/RESULTS:The relationship between heat and kidney stones is well supported. Exposure to high temperatures has been shown to increase risk for stone development within a short time frame. Effects are modified by factors such as sex, comorbid conditions, and population vulnerability and adaptability. Urban heat islands (UHIs) likely exaggerate the effect of increasing global surface temperature. The concentration of UHIs often coincides with historic redlining practices in the United States, potentially contributing to observed disparities in kidney health among minoritized populations. As global surface temperature increases and urbanization trends continue, a greater proportion of the world's population is exposed to significant temperature extremes each year, leading to the expectation that kidney stone prevalence will continue to increase. SUMMARY/CONCLUSIONS:This work describes the effect of increasing global surface temperature as a result of climate change on kidney stone disease and kidney health. These effects may result in further perpetuation of significant kidney stone related social disparities. We suggest strategies to mitigate the effects of heat exposure on stone formation.

NEW FINDINGS/RESULTS:What is the topic of this review? Hereditary sensory and autonomic neuropathy type III (HSAN III). What advances does it highlight? In individuals with (HSAN III) functional muscle spindles appear to be absent throughout the body, though myelinated cutaneous afferents are present. The former may explain the poor proprioception at the knee joint, while the latter may explain why increasing cutaneous feedback improves proprioception at the knee. Reaching and lifting small objects was greatly compromised, arguing for an important role of muscles spindles in sensorimotor control. ABSTRACT/UNASSIGNED:Hereditary sensory and autonomic neuropathy type III (HSAN III), also known as familial dysautonomia or Riley-Day syndrome, results from an autosomal recessive genetic mutation that causes a selective loss of specific sensory neurones, leading to greatly elevated pain and temperature thresholds, poor proprioception, marked ataxia and disturbances in blood pressure control. Stretch reflexes are absent throughout the body, which can be explained by the absence of functional muscle spindle afferents - assessed by intraneural microelectrodes inserted into peripheral nerves in the upper and lower limbs. This also explains the greatly compromised proprioception at the knee joint, as assessed by passive joint-angle matching. Moreover, there is a tight correlation between loss of proprioceptive acuity at the knee and the severity of gait impairment. Surprisingly, proprioception is normal at the elbow, suggesting that participants are relying more on sensory cues from the overlying skin; microelectrode recordings have shown that myelinated tactile afferents in the upper and lower limbs appear to be normal. Nevertheless, the lack of muscle spindles does affect sensorimotor control in the upper limb: in addition to poor performance in the finger-to-nose test, manual performance in the Purdue pegboard task is much worse than in age-matched healthy controls. Unlike those rare individuals with large-fibre sensory neuropathy, in which both muscle spindle and cutaneous afferents are absent, those with HSAN III present as a means of assessing sensorimotor control following the selective loss of muscle spindle afferents.

SIGNIFICANCE/UNASSIGNED:An array of techniques for targeted neuromodulation is emerging, with high potential in brain research and therapy. Calcium imaging or other forms of functional fluorescence imaging are central solutions for monitoring cortical neural responses to targeted neuromodulation, but often are confounded by thermal effects that are inter-mixed with neural responses. AIM/UNASSIGNED:Here, we develop and demonstrate a method for effectively suppressing fluorescent thermal transients from calcium responses. APPROACH/UNASSIGNED: RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:The developed method for canceling transient thermal fluorescence quenching could also find applications with optical stimulation techniques to monitor thermal effects and disentangle them from neural responses. This approach may help deepen our understanding of the mechanisms and macroscopic effects of ultrasound neuromodulation, further paving the way for tailoring the stimulation regimes toward specific applications.

While there have been many descriptions of characteristic motion findings in left bundle branch block (LBBB), there are few published descriptions of such findings in right bundle branch block (RBBB). The purpose of this study was to assess the frequency of particular regional motion findings in cardiac magnetic resonance imaging (CMR) studies of patients with RBBB, compared with normal subjects. We focused on three distinctive motion patterns that can be seen in RBBB during early systole: delayed apex-ward motion of the RV base, "reverse septal flash", and "basal bulge". The presence and relative magnitude of these findings were independently scored by four experienced observers, in 3-chamber and 4-chamber CMR cines, for both normal subjects and patients with RBBB. These motion patterns were found to be strongly associated with the presence of RBBB. While only moderately sensitive, they were quite specific for RBBB, when present. In particular, with ROC analysis, a combined feature set of the findings in the 4-chamber view had an area under the curve of 0.81.This previously undescribed set of RBBB-associated early-systolic regional motion features (delayed apex-ward motion of the RV base, "reverse septal flash", and "basal bulge") is strongly suggestive of RBBB when present, particularly in the 4-chamber view. Although here evaluated with CMR, it is also likely to be associated with RBBB when seen with other cardiac imaging modalities.

In the COMET trial of patients with late-onset Pompe disease, greater improvement in upright forced vital capacity (FVC) % predicted was observed with avalglucosidase alfa (AVA) vs alglucosidase alfa (ALGLU) (estimated treatment difference: 2.43%). The pre-specified mixed model repeated measures (MMRM) analysis demonstrated non-inferiority of AVA (P = 0.0074) and narrowly missed superiority (P = 0.063; 95% CI: -0.13-4.99). We report superiority of AVA in two post-hoc analyses that account for an extreme outlier participant with low FVC and severe chronic obstructive pulmonary disease at baseline: MMRM excluding the outlier (P = 0.013) and non-parametric analysis of all data with repeated measures analysis of covariance (P = 0.019).

AIM/UNASSIGNED:Oral cancer patients suffer pain at the site of the cancer, which degrades quality of life (QoL). The University of California San Francisco Oral Cancer Pain Questionnaire (UCSFOCPQ), the only validated instrument specifically designed for measuring oral cancer pain, measures the intensity and nature of pain and the level of functional restriction due to pain. PURPOSE/UNASSIGNED:The aim of this study was to compare pain reported by untreated oral cancer patients on the UCSFOCPQ with pain they reported on the Brief Pain Inventory (BPI), an instrument widely used to evaluate cancer and non-cancer pain. PATIENTS AND METHODS/UNASSIGNED:The correlation between pain measured by the two instruments and clinical characteristics were analyzed. Thirty newly diagnosed oral cancer patients completed the UCSFOCPQ and the BPI. RESULTS/UNASSIGNED:Pain severity measurements made by the UCSFOCPQ and BPI were concordant; however, the widely used BPI average pain over 24 hours score appeared less sensitive to detect association of oral cancer pain with clinical characteristics of patients prior to treatment (nodal status, depth of invasion, DOI). A BPI average score that includes responses to questions that measure both pain severity and interference with function performs similarly to the UCSFOCPQ in detection of associations with nodal status, pathologic T stage (pT stage), stage and depth of invasion (DOI). CONCLUSION/UNASSIGNED:Pain assessment instruments that measure sensory and interference dimensions of oral cancer pain correlate with biologic features and clinical behavior.

BACKGROUND/UNASSIGNED:Young-onset dementia (YOD) refers to dementia occurring before the age of 65, with Alzheimer's disease being the most common form, posing distinct challenges for spousal caregivers. OBJECTIVE/UNASSIGNED:This study aims to investigate the unique experiences of spousal caregivers of persons with YOD in China, where dementia-specific community care services and primary healthcare professionals are relatively lacking, in order to inform the tailored support services development. METHODS/UNASSIGNED:This qualitative-design study utilized semi-structured interviews with 11 spousal caregivers of persons with YOD dwelling in the community. Traditional content analysis was employed to analyze the interview data. RESULTS/UNASSIGNED:Limited dementia-specific healthcare professionals and low public awareness made diagnosing and accepting YOD a prolonged and challenging journey. Spousal caregivers faced skepticism when seeking diagnosis, exacerbating their burden and emotional stress. Disparities in healthcare professionals and insufficient collaboration between institutions worsened the situation. YOD significantly impacted family dynamics and led to changes in emotional communication within the family. The stigma surrounding YOD raised concerns among spousal caregivers about their children's future in marriage and career, emphasizing genetic risks. CONCLUSIONS/UNASSIGNED:In settings where dementia-specific community care services and primary healthcare professionals are limited and unevenly distributed, integrating support services at both the primary and community levels is crucial for families dealing with YOD in the community. Additionally, raising public awareness about YOD can foster a more understanding and supportive environment, addressing challenges related to stigma faced by affected families, contributing to increased investment in supporting resources, and encouraging individuals to seek help early on.