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Background: Associating temporal variation of biomarkers with the onset of psychotic relapse could help demystify the pathogenesis of psychosis as a pathological brain state, while allowing for timely intervention, thus ameliorating clinical outcome. In this systematic review, we evaluated the predictive accuracy of a broad spectrum of biomarkers for psychotic relapse. We also underline methodological concerns, focusing on the value of prospective studies for relapse onset estimation., Methods: Following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines, a list of search strings related to biomarkers and relapse was assimilated and run against the PubMed and Scopus databases, yielding a total of 808 unique records. After exclusion of studies related to the distinction of patients from controls or treatment effects, the 42 remaining studies were divided into 5 groups, based on the type of biomarker used as a predictor: the genetic biomarker subgroup (n = 4, or 9%), the blood-based biomarker subgroup (n = 15, or 36%), the neuroimaging biomarker subgroup (n = 10, or 24%), the cognitive-behavioral biomarker subgroup (n = 5, or 12%) and the wearables biomarker subgroup (n = 8, or 19%)., Results: In the first 4 groups, several factors were found to correlate with the state of relapse, such as the genetic risk profile, Interleukin-6, Vitamin D or panels consisting of multiple markers (blood-based), ventricular volume, grey matter volume in the right hippocampus, various functional connectivity metrics (neuroimaging), working memory and executive function (cognition). In the wearables group, machine learning models were trained based on features such as heart rate, acceleration, and geolocation, which were measured continuously. While the achieved predictive accuracy differed compared to chance, its power was moderate (max reported AUC = 0.77)., Discussion: The first 4 groups revealed risk factors, but cross-sectional designs or sparse sampling in prospective studies did not allow for relapse onset estimations. Studies involving wearables provide more concrete predictions of relapse but utilized markers such as geolocation do not advance pathophysiological understanding. A combination of the two approaches is warranted to fully understand and predict relapse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Smyrnis, Theleritis, Ferentinos and Smyrnis.)

Background: Deficits in Multisensory Integration (MSI) in ASD have been reported repeatedly and have been suggested to be caused by altered long-range connectivity. Here we investigate behavioral and ERP correlates of MSI in ASD using ecologically valid videos of emotional expressions., Methods: In the present study, we set out to investigate the electrophysiological correlates of audiovisual MSI in young autistic and neurotypical adolescents. We employed dynamic stimuli of high ecological validity (500 ms clips produced by actors) that depicted fear or disgust in unimodal (visual and auditory), and bimodal (audiovisual) conditions., Results: We report robust MSI effects at both the behavioral and electrophysiological levels and pronounced differences between autistic and neurotypical participants. Specifically, neurotypical controls showed robust behavioral MSI for both emotions as seen through a significant speed-up of bimodal response time (RT), confirmed by Miller's Race Model Inequality (RMI), with greater MSI effects for fear than disgust. Adolescents with ASD, by contrast, showed behavioral MSI only for fear. At the electrophysiological level, the bimodal condition as compared to the unimodal conditions reduced the amplitudes of the visual P100 and auditory P200 and increased the amplitude of the visual N170 regardless of group. Furthermore, a cluster-based analysis across all electrodes revealed that adolescents with ASD showed an overall delayed and spatially constrained MSI effect compared to controls., Conclusion: Given that the variables we measured reflect attention, our findings suggest that MSI can be modulated by the differential effects on attention that fear and disgust produce. We also argue that the MSI deficits seen in autistic individuals can be compensated for at later processing stages by (a) the attention-orienting effects of fear, at the behavioral level, and (b) at the electrophysiological level via increased attentional effort ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Stefanou, Dundon, Bestelmeyer, Biscaldi, Smyrnis and Klein.)

Hand gestures are a natural and intuitive form of communication, and integrating this communication method into robotic systems presents significant potential to improve human-robot collaboration. Recent advances in motor neuroscience have focused on replicating human hand movements from synergies also known as movement primitives. Synergies, fundamental building blocks of movement, serve as a potential strategy adapted by the central nervous system to generate and control movements. Identifying how synergies contribute to movement can help in dexterous control of robotics, exoskeletons, prosthetics and extend its applications to rehabilitation. In this paper, 33 static hand gestures were recorded through a single RGB camera and identified in real-time through the MediaPipe framework as participants made various postures with their dominant hand. Assuming an open palm as initial posture, uniform joint angular velocities were obtained from all these gestures. By applying a dimensionality reduction method, kinematic synergies were obtained from these joint angular velocities. Kinematic synergies that explain 98% of variance of movements were utilized to reconstruct new hand gestures using convex optimization. Reconstructed hand gestures and selected kinematic synergies were translated onto a humanoid robot, Mitra, in real-time, as the participants demonstrated various hand gestures. The results showed that by using only few kinematic synergies it is possible to generate various hand gestures, with 95.7% accuracy. Furthermore, utilizing low-dimensional synergies in control of high dimensional end effectors holds promise to enable near-natural human-robot collaboration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Olikkal, Pei, Karri, Satyanarayana, Kakoty and Vinjamuri.)

Background: Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common therapeutic option for patients with LD involves Botulinum neurotoxin injections., Objective: Provide empirical evidence that non-invasive vibro-tactile stimulation (VTS) of the skin over the voice box can provide symptom relief to those affected by LD., Methods: Single-group 11-week randomized controlled trial with a crossover between two dosages (20 min of VTS once or 3 times per week) self-administered in-home in two 4-week blocks. Acute effects of VTS on voice and speech were assessed in-lab at weeks 1, 6 and 11. Participants were randomized to receive either 40 Hz or 100 Hz VTS., Main Outcome Measures: Primary: smoothed cepstral peak prominence (CPPS) of the voice signal to quantify voice and speech abnormalities, and perceived speech effort (PSE) ranked by participants as a measure of voice effort (scale 1-10). Secondary: number of voice breaks during continuous speech, the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) inventory as a measure of overall disease severity and the Voice Handicap Index 30-item self report., Results: Thirty-nine people with a confirmed diagnosis of adductor-type LD (mean [SD] age, 60.3 [11.3] years; 18 women and 21 men) completed the study. A single application of VTS improved voice quality (median CPPS increase: 0.41 dB, 95% CI [0.20, 0.61]) and/or reduced voice effort (PSE) by at least 30% in up to 57% of participants across the three study visits. Effects lasted from less than 30 min to several days. There was no effect of dosage and no evidence that the acute therapeutic effects of VTS increased or decreased longitudinally over the 11-week study period. Both 100 and 40 Hz VTS induced measurable improvements in voice quality and speech effort. VTS induced an additional benefit to those receiving Botulinum toxin. Participants, not receiving Botulinum treatment also responded to VTS., Conclusion: This study provides the first systematic empirical evidence that the prolonged use of laryngeal VTS can induce repeatable acute improvements in voice quality and reductions of voice effort in LD., Clinical Trial Registration: ClinicalTrials.gov ID: NCT03746509., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author JK declares that he was an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Konczak, Bhaskaran, Elangovan, Oh, Goding and Watson.)

Whereas studies of the V1 cortex have focused mainly on neural line orientation preference, color inputs are also known to have a strong presence among these neurons. Individual neurons typically respond to multiple colors and nearby neurons have different combinations of preferred color inputs. However, the computations performed by V1 neurons on such color inputs have not been extensively studied. Here we aimed to address this issue by studying how different V1 neurons encode different combinations of inputs composed of four basic colors. We quantified the decoding accuracy of individual neurons from multi-electrode array recordings, comparing multiple individual neurons located within 2 mm along the vertical axis of the V1 cortex of the anesthetized rat. We found essentially all V1 neurons to be good at decoding spatiotemporal patterns of color inputs and they did so by encoding them in different ways. Quantitative analysis showed that even adjacent neurons encoded the specific input patterns differently, suggesting a local cortical circuitry organization which tends to diversify rather than unify the neuronal responses to each given input. Using different pairs of monocolor inputs, we also found that V1 neocortical neurons had a diversified and rich color opponency across the four colors, which was somewhat surprising given the fact that rodent retina express only two different types of opsins. We propose that the processing of color inputs in V1 cortex is extensively composed of multiple independent circuitry components that reflect abstract functionalities resident in the internal cortical processing rather than the raw sensory information per se ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kristensen and Jörntell.)

Introduction: Monitoring biometric data using smartwatches (digital phenotypes) provides a novel approach for quantifying behavior in patients with psychiatric disorders. We tested whether such digital phenotypes predict changes in psychopathology of patients with psychotic disorders., Methods: We continuously monitored digital phenotypes from 35 patients (20 with schizophrenia and 15 with bipolar spectrum disorders) using a commercial smartwatch for a period of up to 14 months. These included 5-min measures of total motor activity from an accelerometer (TMA), average Heart Rate (HRA) and heart rate variability (HRV) from a plethysmography-based sensor, walking activity (WA) measured as number of total steps per day and sleep/wake ratio (SWR). A self-reporting questionnaire (IPAQ) assessed weekly physical activity. After pooling phenotype data, their monthly mean and variance was correlated within each patient with psychopathology scores (PANSS) assessed monthly., Results: Our results indicate that increased HRA during wakefulness and sleep correlated with increases in positive psychopathology. Besides, decreased HRV and increase in its monthly variance correlated with increases in negative psychopathology. Self-reported physical activity did not correlate with changes in psychopathology. These effects were independent from demographic and clinical variables as well as changes in antipsychotic medication dose., Discussion: Our findings suggest that distinct digital phenotypes derived passively from a smartwatch can predict variations in positive and negative dimensions of psychopathology of patients with psychotic disorders, over time, providing ground evidence for their potential clinical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kalisperakis, Karantinos, Lazaridi, Garyfalli, Filntisis, Zlatintsi, Efthymiou, Mantas, Mantonakis, Mougiakos, Maglogiannis, Tsanakas, Maragos and Smyrnis.)

The dynamics of the human body can be described by the accelerations and masses of the different body parts (e.g., legs, arm, trunk). These body parts can exhibit specific coordination patterns with each other. In human walking, we found that the swing leg cooperates with the upper body and the stance leg in different ways (e.g., in-phase and out-of-phase in vertical and horizontal directions, respectively). Such patterns of self-assistance found in human locomotion could be of advantage in robotics design, in the design of any assistive device for patients with movement impairments. It can also shed light on several unexplained infrastructural features of the CNS motor control. Self-assistance means that distributed parts of the body contribute to an overlay of functions that are required to solve the underlying motor task. To draw advantage of self-assisting effects, precise and balanced spatiotemporal patterns of muscle activation are necessary. We show that the necessary neural connectivity infrastructure to achieve such muscle control exists in abundance in the spinocerebellar circuitry. We discuss how these connectivity patterns of the spinal interneurons appear to be present already perinatally but also likely are learned. We also discuss the importance of these insights into whole body locomotion for the successful design of future assistive devices and the sense of control that they could ideally confer to the user., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seyfarth, Zhao and Jörntell.)

Paradoxes are a special form of reasoning leading to absurd inferences in contrast to logical reasoning that is used to reach valid conclusions. A functional MRI (fMRI) study was conducted to investigate the neural substrates of paradoxical and deductive reasoning. Twenty-four healthy participants were scanned using fMRI, while they engaged in reasoning tasks based on arguments, which were either Zeno's like paradoxes (paradoxical reasoning) or Aristotelian arguments (deductive reasoning). Clusters of significant activation for paradoxical reasoning were located in bilateral inferior frontal and middle temporal gyrus. Clusters of significant activation for deductive reasoning were located in bilateral superior and inferior parietal lobe, precuneus, and inferior frontal gyrus. These results confirmed that different brain activation patterns are engaged for paradoxical vs. deductive reasoning providing a basis for future studies on human physiological as well as pathological reasoning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Belekou, Papageorgiou, Karavasilis, Tsaltas, Kelekis, Klein and Smyrnis.)

Temporal recalibration (TR) may arise to realign asynchronous stimuli after exposure to a short, constant delay between voluntary movement and sensory stimulus. The objective of this study was to determine if awareness of the temporal lag between a motor response (i.e., a keypress) and a sensory event (i.e., a visual flash) is necessary for TR to occur. We further investigated whether manipulating the required motor and perceptual judgment tasks modified the influence of awareness on TR. Participants ( n = 48) were randomly divided between two groups (Group 1: Aware and Group 2: Unaware). The Aware group was told of the temporal lag between their keypress and visual flash at the beginning of the experiment, whereas the Unaware group was not. All participants completed eight blocks of trials, in which the motor task (single or repetitive tap), perceptual judgment task (judging the temporal order of the keypress in relation to the visual flash or judging whether the two stimuli were simultaneous or not), and fixed temporal lag between keypress and visual flash (0 or 100 ms) varied. TR was determined by comparing judgments between corresponding blocks of trials in which the temporal lag was 0 or 100 ms. Results revealed that both the Aware and Unaware groups demonstrated a similar magnitude of TR across all motor and perceptual judgment tasks, such that the magnitude of TR did not vary between Aware and Unaware participants. These results suggest that awareness of a temporal lag does not influence the magnitude of TR achieved and that motor and perceptual judgment task demands do not modulate the influence of awareness on TR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bubna, Lam and Cressman.)

We have previously reported different spike firing correlation patterns among pairs of adjacent pyramidal neurons within the same layer of S1 cortex in vivo , which was argued to suggest that acquired synaptic weight modifications would tend to differentiate adjacent cortical neurons despite them having access to near-identical afferent inputs. Here we made simultaneous single-electrode loose patch-clamp recordings from 14 pairs of adjacent neurons in the lateral thalamus of the ketamine-xylazine anesthetized rat in vivo to study the correlation patterns in their spike firing. As the synapses on thalamic neurons are dominated by a high number of low weight cortical inputs, which would be expected to be shared for two adjacent neurons, and as far as thalamic neurons have homogenous membrane physiology and spike generation, they would be expected to have overall similar spike firing and therefore also correlation patterns. However, we find that across a variety of thalamic nuclei the correlation patterns between pairs of adjacent thalamic neurons vary widely. The findings suggest that the connectivity and cellular physiology of the thalamocortical circuitry, in contrast to what would be expected from a straightforward interpretation of corticothalamic maps and uniform intrinsic cellular neurophysiology, has been shaped by learning to the extent that each pair of thalamic neuron has a unique relationship in their spike firing activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wahlbom, Mogensen and Jörntell.)

The brain has a never-ending internal activity, whose spatiotemporal evolution interacts with external inputs to constrain their impact on brain activity and thereby how we perceive them. We used reproducible touch-related spatiotemporal sensory inputs and recorded intracellularly from rat (Sprague-Dawley, male) neocortical neurons to characterize this interaction. The synaptic responses, or the summed input of the networks connected to the neuron, varied greatly to repeated presentations of the same tactile input pattern delivered to the tip of digit 2. Surprisingly, however, these responses tended to sort into a set of specific time-evolving response types, unique for each neuron. Further, using a set of eight such tactile input patterns, we found each neuron to exhibit a set of specific response types for each input provided. Response types were not determined by the global cortical state, but instead likely depended on the time-varying state of the specific subnetworks connected to each neuron. The fact that some types of responses recurred indicates that the cortical network had a non-continuous landscape of solutions for these tactile inputs. Therefore, our data suggest that sensory inputs combine with the internal dynamics of the brain networks, thereby causing them to fall into one of the multiple possible perceptual attractor states. The neuron-specific instantiations of response types we observed suggest that the subnetworks connected to each neuron represent different components of those attractor states. Our results indicate that the impact of cortical internal states on external inputs is substantially more richly resolvable than previously shown., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Norrlid, Enander, Mogensen and Jörntell.)

In recent years, psychiatric research has focused on the evaluation and implementation of biomarkers in the clinical praxis. Oculomotor function deviances are among the most consistent and replicable cognitive deficits in schizophrenia and have been suggested as viable candidates for biomarkers. In this narrative review, we focus on oculomotor function in first-episode psychosis, recent onset schizophrenia as well as individuals at high risk for developing psychosis. We critically discuss the evidence for the possible utilization of oculomotor function measures as diagnostic, susceptibility, predictive, monitoring, and prognostic biomarkers for these conditions. Based on the current state of research we conclude that there are not sufficient data to unequivocally support the use of oculomotor function measures as biomarkers in schizophrenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Athanasopoulos, Saprikis, Margeli, Klein and Smyrnis.)

Position sense refers to an aspect of proprioception crucial for motor control and learning. The onset of neurological diseases can damage such sensory afference, with consequent motor disorders dramatically reducing the associated recovery process. In regular clinical practice, assessment of proprioceptive deficits is run by means of clinical scales which do not provide quantitative measurements. However, existing robotic solutions usually do not involve multi-joint movements but are mostly applied to a single proximal or distal joint. The present work provides a testing paradigm for assessing proprioception during coordinated multi-joint distal movements and in presence of kinaesthetic perturbations: we evaluated healthy subjects' ability to match proprioceptive targets along two of the three wrist's degrees of freedom, flexion/extension and abduction/adduction. By introducing rotations along the pronation/supination axis not involved in the matching task, we tested two experimental conditions, which differed in terms of the temporal imposition of the external perturbation: in the first one, the disturbance was provided after the presentation of the proprioceptive target, while in the second one, the rotation of the pronation/ supination axis was imposed during the proprioceptive target presentation. We investigated if (i) the amplitude of the perturbation along the pronation/supination would lead to proprioceptive miscalibration; (ii) the encoding of proprioceptive target, would be influenced by the presentation sequence between the target itself and the rotational disturbance. Eighteen participants were tested by means of a haptic neuroergonomic wrist device: our findings provided evidence that the order of disturbance presentation does not alter proprioceptive acuity. Yet, a further effect has been noticed: proprioception is highly anisotropic and dependent on perturbation amplitude. Unexpectedly, the configuration of the forearm highly influences sensory feedbacks, and significantly alters subjects' performance in matching the proprioceptive targets, defining portions of the wrist workspace where kinaesthetic and proprioceptive acuity are more sensitive. This finding may suggest solutions and applications in multiple fields: from general haptics where, knowing how wrist configuration influences proprioception, might suggest new neuroergonomic solutions in device design, to clinical evaluation after neurological damage, where accurately assessing proprioceptive deficits can dramatically complement regular therapy for a better prediction of the recovery path., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 D'Antonio, Galofaro, Zenzeri, Patané, Konczak, Casadio and Masia.)

Whereas, there is data to support that cuneothalamic projections predominantly reach a topographically confined volume of the rat thalamus, the ventroposterior lateral (VPL) nucleus, recent findings show that cortical neurons that process tactile inputs are widely distributed across the neocortex. Since cortical neurons project back to the thalamus, the latter observation would suggest that thalamic neurons could contain information about tactile inputs, in principle regardless of where in the thalamus they are located. Here we use a previously introduced electrotactile interface for producing sets of highly reproducible tactile afferent spatiotemporal activation patterns from the tip of digit 2 and record neurons throughout widespread parts of the thalamus of the anesthetized rat. We find that a majority of thalamic neurons, regardless of location, respond to single pulse tactile inputs and generate spike responses to such tactile stimulation patterns that can be used to identify which of the inputs that was provided, at above-chance decoding performance levels. Thalamic neurons with short response latency times, compatible with a direct tactile afferent input via the cuneate nucleus, were typically among the best decoders. Thalamic neurons with longer response latency times as a rule were also found to be able to decode the digit 2 inputs, though typically at a lower decoding performance than the thalamic neurons with presumed direct cuneate inputs. These findings provide support for that tactile information arising from any specific skin area is widely available in the thalamocortical circuitry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wahlbom, Enander and Jörntell.)

Neuroanatomy suggests that adjacent neocortical neurons share a similar set of afferent synaptic inputs, as opposed to neurons localized to different areas of the neocortex. In the present study, we made simultaneous single-electrode patch clamp recordings from two or three adjacent neurons in the primary somatosensory cortex (S1) of the ketamine-xylazine anesthetized rat in vivo to study the correlation patterns in their spike firing during both spontaneous and sensory-evoked activity. One difference with previous studies of pairwise neuronal spike firing correlations was that here we identified several different quantifiable parameters in the correlation patterns by which different pairs could be compared. The questions asked were if the correlation patterns between adjacent pairs were similar and if there was a relationship between the degree of similarity and the layer location of the pairs. In contrast, our results show that for putative pyramidal neurons within layer III and within layer V, each pair of neurons is to some extent unique in terms of their spiking correlation patterns. Interestingly, our results also indicated that these correlation patterns did not substantially alter between spontaneous and evoked activity. Our findings are compatible with the view that the synaptic input connectivity to each neocortical neuron is at least in some aspects unique. A possible interpretation is that plasticity mechanisms, which could either be initiating or be supported by transcriptomic differences, tend to differentiate rather than harmonize the synaptic weight distributions between adjacent neurons of the same type.

Haptic loss severely compromises the fine motor control of many daily manual tasks. Today, no widely accepted assessment protocols of haptic function are in clinical use. This is primarily due to the scarcity of fast, objective measures capable of characterizing mild to severe forms of haptic dysfunction with appropriate resolution. This study introduces a novel curvature-perception assessment system called the Minnesota Haptic Function Test™ that seeks to overcome the shortcomings of current clinical assessments. Aims: The purpose of this study was threefold: (1) apply the test to a sample of young healthy adults to establish test-specific adult norms for haptic sensitivity and acuity; (2) establish the reliability of this instrument; (3) demonstrate clinical efficacy in a limited sample of cancer survivors who may exhibit haptic dysfunction due to chemotherapy-induced peripheral neuropathy. Method: Participants manually explored two curved surfaces successively and made verbal judgments about their curvature. A Bayesian-based adaptive algorithm selected presented stimulus pairs based on a subject's previous responses, which ensured fast convergence toward a threshold. Haptic sensitivity was assessed by obtaining detection thresholds in 26 adults (19-34 years). Haptic acuity was assessed by obtaining just-noticeable-difference thresholds in a second sample of 28 adults (19-25 years). Nine cancer survivors (18-25 years) with suspected peripheral neuropathy completed the acuity assessment. Test-retest reliability of the algorithm was calculated. Results: First, the test yielded values that are consistent with those reported in the literature. Mean detection threshold for curvature of the healthy adults was 0.782 (SD ± 0.320 m -1 ). The corresponding mean discrimination threshold was 1.030 (SD ± 0.462 m -1 ). Second, test-retest reliability of the algorithm was assessed in a simulation, yielding an average correlation between repeated simulated thresholds of r  = 0.93. Third, the test documented that 86% of the cancer survivors had acuity thresholds above the 75th percentile of the normative cohort, and 29% had thresholds above the normal range, indicating that the instrument can detect and differentiate between unaffected perception, and mild or more severe forms of haptic loss. Conclusion: We here provide evidence that this new method to assess haptic perception of curvature is valid, reliable, and clinically practicable.

Whereas functional localization historically has been a key concept in neuroscience, direct neuronal recordings show that input of a particular modality can be recorded well outside its primary receiving areas in the neocortex. Here, we wanted to explore if such spatially unbounded inputs potentially contain any information about the quality of the input received. We utilized a recently introduced approach to study the neuronal decoding capacity at a high resolution by delivering a set of electrical, highly reproducible spatiotemporal tactile afferent activation patterns to the skin of the contralateral second digit of the forepaw of the anesthetized rat. Surprisingly, we found that neurons in all areas recorded from, across all cortical depths tested, could decode the tactile input patterns, including neurons of the primary visual cortex. Within both somatosensory and visual cortical areas, the combined decoding accuracy of a population of neurons was higher than for the best performing single neuron within the respective area. Such cooperative decoding indicates that not only did individual neurons decode the input, they also did so by generating responses with different temporal profiles compared to other neurons, which suggests that each neuron could have unique contributions to the tactile information processing. These findings suggest that tactile processing in principle could be globally distributed in the neocortex, possibly for comparison with internal expectations and disambiguation processes relying on other modalities.

Monoamines are presumed to be diffuse metabotropic neuromodulators of the topographically and temporally precise ionotropic circuitry which dominates CNS functions. Their malfunction is strongly implicated in motor and cognitive disorders, but their function in behavioral and cognitive processing is scarcely understood. In this paper, the principles of such a monoaminergic function are conceptualized for locomotor control. We find that the serotonergic system in the ventral spinal cord scales ionotropic signals and shows topographic order that agrees with differential gain modulation of ionotropic subcircuits. Whereas the subcircuits can collectively signal predictive models of the world based on life-long learning, their differential scaling continuously adjusts these models to changing mechanical contexts based on sensory input on a fast time scale of a few 100 ms. The control theory of biomimetic robots demonstrates that this precision scaling is an effective and resource-efficient solution to adapt the activation of individual muscle groups during locomotion to changing conditions such as ground compliance and carried load. Although it is not unconceivable that spinal ionotropic circuitry could achieve scaling by itself, neurophysiological findings emphasize that this is a unique functionality of metabotropic effects since recent recordings in sensorimotor circuitry conflict with mechanisms proposed for ionotropic scaling in other CNS areas. We substantiate that precision scaling of ionotropic subcircuits is a main functional principle for many monoaminergic projections throughout the CNS, implying that the monoaminergic circuitry forms a network within the network composed of the ionotropic circuitry. Thereby, we provide an early-level interpretation of the mechanisms of psychopharmacological drugs that interfere with the monoaminergic systems.

Perception of limb and body positions is known as proprioception. Sensory feedback, especially from proprioceptive receptors, is essential for motor control. Aging is associated with a decline in position sense at proximal joints, but there is inconclusive evidence of distal joints being equally affected by aging. In addition, there is initial evidence that physical activity attenuates age-related decline in proprioception. Our objectives were, first, to establish wrist proprioceptive acuity in a large group of seniors and compare their perception to young adults, and second, to determine if specific types of training or regular physical activity are associated with preserved wrist proprioception. We recruited community-dwelling seniors ( n = 107, mean age, 70 ± 5 years, range, 65-84 years) without cognitive decline (Mini Mental State Examination-brief version ≥13/16) and young adult students ( n = 51, mean age, 20 ± 1 years, range, 19-26 years). Participants performed contralateral and ipsilateral wrist position sense matching tasks with a bimanual wrist manipulandum to a 15° flexion reference position. Systematic error or proprioceptive bias was computed as the mean difference between matched and reference position. The respective standard deviation over five trials constituted a measure of random error or proprioceptive precision . Current levels of physical activity and previous sport, musical, or dance training were obtained through a questionnaire. We employed longitudinal mixed effects linear models to calculate the effects of trial number, sex, type of matching task and age on wrist proprioceptive bias and precision. The main results were that relative proprioceptive bias was greater in older when compared to young adults (mean difference: 36% ipsilateral, 88% contralateral, p < 0.01). Proprioceptive precision for contralateral but not for ipsilateral matching was smaller in older than in young adults (mean difference: 38% contralateral, p < 0.01). Longer years of dance training were associated with smaller bias during ipsilateral matching ( p < 0.01). Other types of training or physical activity levels did not affect bias or precision. Our findings demonstrate that aging is associated with a decline in proprioceptive bias in distal arm joints, but age does not negatively affect proprioceptive precision. Further, specific types of long-term dance related training may attenuate age-related decline in proprioceptive bias.

This study mapped the development of proprioception in healthy, typically developing children by objectively measuring forearm position sense acuity. We assessed position sense acuity in a cross-sectional sample of 308 children (5-17 years old; M/F = 127/181) and a reference group of 26 healthy adults (18-25 years old; M/F = 12/14) using a body-scalable bimanual manipulandum that allowed forearm flexion/extension in the horizontal plane. The non-dominant forearm was passively displaced to one of three target positions. Then participants actively matched the target limb position with their dominant forearm. Each of three positions was matched five times. Position error (PE), calculated as the mean difference between the angular positions of the matching and reference arms, measured position sense bias or systematic error. The respective standard deviation of the differences between the match and reference arm angular positions (SDPdiff) indicated position sense precision or random error. The main results are as follows: First, systematic error, measured by PE, did not change significantly from early childhood to late adolescence (Median PE at 90° target: -2.85° in early childhood; -2.28° in adolescence; and 1.30° in adults). Second, response variability as measured by SDPdiff significantly decreased with age (Median SDPdiff at 90° target: 9.66° in early childhood; 5.30° in late adolescence; and 3.97° in adults). The data of this large cross-sectional sample of children document that proprioceptive development in typically developing children is characterized as an age-related improvement in precision, not as a development or change in bias. In other words, it is the reliability of the perceptual response that improves between early childhood and adulthood. This study provides normative data against which position sense acuity in pediatric patient populations can be compared. The underlying neurophysiological processes that could explain the observed proprioceptive development include changes in the tuning of muscle spindles at the spinal level, the maturation of supraspinal somatosensory pathways and the development of interhemispheric callosal connections responsible for the transfer of somatosensory information.

Objective: Numerous reports advocate that training of the proprioceptive sense is a viable behavioral therapy for improving impaired motor function. However, there is little agreement of what constitutes proprioceptive training and how effective it is. We therefore conducted a comprehensive, systematic review of the available literature in order to provide clarity to the notion of training the proprioceptive system., Methods: Four major scientific databases were searched. The following criteria were subsequently applied: (1) A quantified pre- and post-treatment measure of proprioceptive function. (2) An intervention or training program believed to influence or enhance proprioceptive function. (3) Contained at least one form of treatment or outcome measure that is indicative of somatosensory function. From a total of 1284 articles, 51 studies fulfilled all criteria and were selected for further review., Results: Overall, proprioceptive training resulted in an average improvement of 52% across all outcome measures. Applying muscle vibration above 30 Hz for longer durations (i.e., min vs. s) induced outcome improvements of up to 60%. Joint position and target reaching training consistently enhanced joint position sense (up to 109%) showing an average improvement of 48%. Cortical stroke was the most studied disease entity but no clear evidence indicated that proprioceptive training is differentially beneficial across the reported diseases., Conclusions: There is converging evidence that proprioceptive training can yield meaningful improvements in somatosensory and sensorimotor function. However, there is a clear need for further work. Those forms of training utilizing both passive and active movements with and without visual feedback tended to be most beneficial. There is also initial evidence suggesting that proprioceptive training induces cortical reorganization, reinforcing the notion that proprioceptive training is a viable method for improving sensorimotor function.

We employed spectral Granger causality analysis on a full set of 56 electroencephalographic recordings acquired during the execution of either a 2D movement pointing or a perceptual (yes/no) change detection task with memory and non-memory conditions. On the basis of network characteristics across frequency bands, we provide evidence for the full dissociation of the corresponding cognitive processes. Movement-memory trial types exhibited higher degree nodes during the first 2 s of the delay period, mainly at central, left frontal and right-parietal areas. Change detection-memory trial types resulted in a three-peak temporal pattern of the total degree with higher degree nodes emerging mainly at central, right frontal, and occipital areas. Functional connectivity networks resulting from non-memory trial types were characterized by more sparse structures for both tasks. The movement-memory trial types encompassed an apparent coarse flow from frontal to parietal areas while the opposite flow from occipital, parietal to central and frontal areas was evident for the change detection-memory trial types. The differences among tasks and conditions were more profound in α (8-12 Hz) and β (12-30 Hz) and less in γ (30-45 Hz) band. Our results favor the hypothesis which considers spatial working memory as a by-product of specific mental processes that engages common brain areas under different network organizations.

We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT) and the dorsal spinocerebellar tract (DSCT), respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF) and the ipsilateral LF (iLF) at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e., that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn (dh) DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.

We have shown that when subjects reach with continuous, misaligned visual feedback of their hand, their reaches are adapted and proprioceptive sense of hand position is recalibrated to partially match the visual feedback (Salomonczyk et al., 2011). It is unclear if similar changes arise after reaching with visual feedback that is provided only at the end of the reach (i.e., terminal feedback), when there are shorter temporal intervals for subjects to experience concurrent visual and proprioceptive feedback. Subjects reached to targets with an aligned hand-cursor that provided visual feedback at the end of each reach movement across a 99-trial training block, and with a rotated cursor over three successive blocks of 99 trials each. After each block, no cursor reaches, to measure aftereffects, and felt hand positions were measured. Felt hand position was determined by having subjects indicate the position of their unseen hand relative to a reference marker. We found that subjects adapted their reaches following training with rotated terminal visual feedback, yet slightly less (i.e., reach aftereffects were smaller), than subjects from a previous study who experienced continuous visual feedback. Nonetheless, current subjects recalibrated their sense of felt hand position in the direction of the altered visual feedback, but this proprioceptive change increased incrementally over the three rotated training blocks. Final proprioceptive recalibration levels were comparable to our previous studies in which subjects performed the same task with continuous visual feedback. Thus, compared to reach training with continuous, but altered visual feedback, subjects who received terminal altered visual feedback of the hand produced significant but smaller reach aftereffects and similar changes in hand proprioception when given extra training. Taken together, results suggest that terminal feedback of the hand is sufficient to drive motor adaptation, and also proprioceptive recalibration.

To any model of brain function, the variability of neuronal spike firing is a problem that needs to be taken into account. Whereas the synaptic integration can be described in terms of the original Hodgkin-Huxley (H-H) formulations of conductance-based electrical signaling, the transformation of the resulting membrane potential into patterns of spike output is subjected to stochasticity that may not be captured with standard single neuron H-H models. The dynamics of the spike output is dependent on the normal background synaptic noise present in vivo, but the neuronal spike firing variability in vivo is not well studied. In the present study, we made long-term whole cell patch clamp recordings of stationary spike firing states across a range of membrane potentials from a variety of subcortical neurons in the non-anesthetized, decerebrated state in vivo. Based on the data, we formulated a simple, phenomenological model of the properties of the spike generation in each neuron that accurately captured the stationary spike firing statistics across all membrane potentials. The model consists of a parametric relationship between the mean and standard deviation of the inter-spike intervals, where the parameter is linearly related to the injected current over the membrane. This enabled it to generate accurate approximations of spike firing also under inhomogeneous conditions with input that varies over time. The parameters describing the spike firing statistics for different neuron types overlapped extensively, suggesting that the spike generation had similar properties across neurons.

Spinocerebellar systems are likely to be crucial for cerebellar hallmark functions such as coordination. However, in terms of cerebellar functional analyses, these are perhaps among the least explored systems. The aim of the present study is to achieve activation of a single component of the spinocerebellar systems and to explore to what extent it can influence the spike output of granule cells, Golgi cells, molecular layer (ML) interneurons (stellate and basket cells) and Purkinje cells (PCs). For this purpose, we took advantage of a unique arrangement discovered in neuroanatomical studies, in which the spinal border cell (SBC) component of the ventral spinocerebellar system was found to be the only spinocerebellar tract which ascends in the contralateral lateral funiculus (coLF) and have terminations in sublobulus C1 of the paramedian lobule in the posterior cerebellum. Using electrical stimulation of this tract, we find a subset of the cerebellar cortical neurons in this region to be moderately or powerfully activated. For example, some of our granule cells displayed high intensity responses whereas the majority of the granule cells displayed no response at all. The finding that more than half of the PCs were activated by stimulation of the SBC tract indicated that this system is capable of directly influencing cerebellar cortical output. The implications of these findings for the view of the integrative functions of the cerebellar cortex are discussed.

Musician's dystonia (MD) is a neurological motor disorder characterized by involuntary contractions of those muscles involved in the play of a musical instrument. It is task-specific and initially only impairs the voluntary control of highly practiced musical motor skills. MD can lead to a severe decrement in a musician's ability to perform. While the etiology and the neurological pathomechanism of the disease remain unknown, it is known that MD like others forms of focal dystonia is associated with somatosensory deficits, specifically a decreased precision of tactile and proprioceptive perception. The sensory component of the disease becomes also evident by the patients' use of "sensory tricks" such as touching dystonic muscles to alleviate motor symptoms. The central premise of this paper is that the motor symptoms of MD have a somatosensory origin and are not fully explained as a problem of motor execution. We outline how altered proprioceptive feedback ultimately leads to a loss of voluntary motor control and propose two scenarios that explain why sensory tricks are effective. They are effective, because the sensorimotor system either recruits neural resources normally involved in tactile-proprioceptive (sensory) integration, or utilizes a fully functioning motor efference copy mechanism to align experienced with expected sensory feedback. We argue that an enhanced understanding of how a primary sensory deficit interacts with mechanisms of sensorimotor integration in MD provides helpful insights for the design of more effective behavioral therapies.