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

Background and Objectives:To establish age-, gender- and body dimension-adjusted normal cut-off values for Meissner’s corpuscle (MC) densities via in-vivo reflectance confocal microscopy (RCM), timed vibration sensory thresholds using a 128Hz tuning fork, and touch-pressure sensory thresholds using standardized monofilaments, for clinical and research application.Methods:77 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 non-dominant upper and lower extremities. Age-, gender-, and body dimension- (e.g., height) adjusted normal values were developed. The 5th percentile for MC densities and timed vibration thresholds and 95th percentile for MF touch-pressure thresholds were selected as normal cut-off points.Results:Subjects were aged 9 to 89 years old. Age and gender 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 gender 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 gender 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 gender or body dimensions at all imaging sites, with lower densities seen in males 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-, gender- and body dimension-adjusted normal cut-off values for two 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.

The Making of the Experimental Subject: Apparatus, Automatism, and the Anxiety of the Early Avant-Garde

This essay presents the experimental subject as a figure of modernity. It addresses notions of control, sensory thresholds, automatism, and human agency through a study of experimental psychology and psychological apparatus from the late 19th century to the First World War, juxtaposing this with notions of experimentation in early 20th-century avant-garde movements. The human subject of experimental psychology, defined by its inexpression as it awaits the stimuli of testing and measurement, is treated as a prototype for the present-day user of technological interfaces.

Critical information thresholds underlying concurrent face recognition functions

Humans rapidly and automatically recognise faces on multiple different levels, yet little is known about how the brain achieves these manifold categorisations concurrently. We bring a new perspective to this emerging issue by probing the relative informational dependencies of two of the most important aspects of human face processing: categorisation of the stimulus as a face (generic face recognition) and categorisation of its familiarity (familiar face recognition). Recording electrophysiological responses to a large set of natural images progressively increasing in image duration (Expt. 1) or spatial frequency content (Expt. 2), we contrasted critical sensory thresholds for these recognition functions as driven by the same face encounters. Across both manipulations, individual observer thresholds were consistently lower for distinguishing faces from other objects than for distinguishing familiar from unfamiliar faces. Moreover, familiar face recognition displayed marked inter-individual variability compared to generic face recognition, with no systematic relationship evident between the two thresholds. Scalp activation was also more strongly right-lateralised at the generic face recognition threshold than at the familiar face recognition threshold. These results suggest that high-level recognition of a face as a face arises based on minimal sensory input (i.e., very brief exposures/coarse resolutions), predominantly in right hemisphere regions. In contrast, the amount of additional sensory evidence required to access face familiarity is highly idiosyncratic and recruits wider neural networks. These findings underscore the neurofunctional distinctions between these two recognition functions, and constitute an important step forward in understanding how the human brain recognises various dimensions of a face in parallel.Significance StatementThe relational dynamics between different aspects of face recognition are not yet well understood. We report relative informational dependencies for two concurrent, ecologically relevant face recognition functions: distinguishing faces from objects, and recognising people we know. Our electrophysiological data show that for a given face encounter, the human brain requires less sensory input to categorise that stimulus as a face than to recognise whether the face is familiar. Moreover, where sensory thresholds for distinguishing faces from objects are remarkably consistent across observers, they vary widely for familiar face recognition. These findings shed new light on the multifaceted nature of human face recognition by painting a more comprehensive picture of the concurrent evidence accumulation processes initiated by seeing a face.

Improved neurocognitive performance in FIV infected cats following treatment with the p75 neurotrophin receptor ligand LM11A-31

HIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective treatment options. Neurotrophin based therapies have excellent potential to stabilize and repair the nervous system. A novel non-peptide ligand, LM11A-31, that targets the p75 neurotrophin receptor (p75NTR) has been identified as a small bioavailable molecule capable of strong neuroprotection with minimal side effects. To evaluate the neuroprotective effects of LM11A-31 in a natural infection model, we treated cats chronically infected with feline immunodeficiency virus (FIV) with 13 mg/kg LM11A-31 twice daily over a period of 10 weeks and assessed effects on cognitive functions, open field behaviors, activity, sensory thresholds, plasma FIV, cerebrospinal fluid (CSF) FIV, peripheral blood mononuclear cell provirus, CD4 and CD8 cell counts and general physiology. Between 12 and 18 months post-inoculation, cats began to show signs of neural dysfunction in T maze testing and novel object recognition, which were prevented by LM11A-31 treatment. Anxiety-like behavior was reduced in the open field and no changes were seen in sensory thresholds. Systemic FIV titers were unaffected but treated cats exhibited a log drop in CSF FIV titers. No significant adverse effects were observed under all conditions. The data indicate that LM11A-31 is likely to be a potent adjunctive treatment for the control of neurodegeneration in HIV infected individuals.Author SummaryThere are no effective treatments to halt the progression of most neurodegenerative diseases including HIV-associated neurodegeneration. Neurotrophins have the potential to provide strong neuroprotection but it has been difficult to develop usable interventions. A new drug, LM11A-31, that targets the p75 neurotrophin receptor has been developed that provides potent neuroprotection, is orally bioavailable and has the potential to prevent disease progression. The current studies were designed to evaluate the effects of the compound in an animal model of active HIV infection in preparation for a human clinical trial. Treatment of chronically infected animals with LM11A-31 normalized deficits in T maze performance, novel object recognition and open field behavior with no measurable adverse effects. Potential adverse effects associated with natural neurotrophins such as changes in sensory perception and increased systemic viral burden were not observed. A decrease in CSF FIV titers and a slight improvement in the CD4:CD8 ratio suggested that LM11A-31 may have beneficial effects beyond the anticipated neuroprotective effects. These findings are similar to beneficial effects seen in other animal models of neurodegeneration and CNS injury and support the use of LM11A-31 as an adjunctive neuroprotective agent for the treatment of HIV infected individuals.

1,1,6-Trimethyl-1,2-dihydronaphthalene (TDN) Sensory Thresholds in Riesling Wine

1,1,6-Trimethyl-1,2-dihydronaphthalene (TDN) is an aroma compound responsible for the kerosene/petrol notes in Riesling wines. In the current article, three sensory thresholds for TDN were determined in young Riesling wine: detection threshold (about 4 µg/L), recognition threshold (10–12 µg/L), and rejection threshold (71–82 µg/L). It was demonstrated that an elevated content of free SO2 in wine may have a certain masking effect on the TDN aroma perception. In addition, the influence of wine serving temperature on the recognition of kerosene/petrol notes was studied. It was found, that a lower wine serving temperature (about 11 °C) facilitated identification of the TDN aroma compared to the same wine samples at room temperature.

Unique Relationships Between Autistic Traits and Visual, Auditory, and Tactile Sensory Thresholds in Typically Developing Adults

Autism spectrum disorder (ASD) refers to neurodevelopmental disorders characterized by symptoms such as social deficits and restricted interests and behavior. Several studies have investigated specific sensory processing in relation to ASD traits. However, findings appear to be inconsistent and inconclusive because of variation in ASD traits among participants and differences in the tasks adopted. In this study, we investigated relationships between sensory thresholds in visual, auditory, and tactile modalities and various ASD traits to account for individual variability of traits in typically developing adults using the same experimental tasks. We estimated detection and discrimination thresholds for brightness, sound pressure, and vibrotactile stimulus strength. We also estimated the degree of ASD traits in each participant with a questionnaire. We found that higher tactile detection and visual discrimination thresholds were related to ASD traits in difficulty of communication. A lower tactile discrimination threshold and higher visual detection threshold was also related to the ASD trait of strong focus of attention. These findings suggest the existence of unique relationships between particular low-level sensory processing and specific ASD traits, indicating that irregularities in sensory processing may underlie variation in ASD traits.