Adaptive control of movement deceleration during saccades

As you read this text, your eyes make saccades that guide your fovea from one word to the next. Accuracy of these movements require the brain to monitor and learn from visual errors. A current model suggests that learning is supported by two different adaptive processes, one fast (high error sensitivity, low retention), and the other slow (low error sensitivity, high retention). Here, we searched for signatures of these hypothesized processes and found that following experience of a visual error, there was an adaptive change in the motor commands of the subsequent saccade. Surprisingly, this adaptation was not uniformly expressed throughout the movement. Rather, after experience of a single error, the adaptive response in the subsequent trial was limited to the deceleration period. After repeated exposure to the same error, the acceleration period commands also adapted, and exhibited resistance to forgetting during set-breaks. In contrast, the deceleration period commands adapted more rapidly, but suffered from poor retention during these same breaks. State-space models suggested that acceleration and deceleration periods were supported by a shared adaptive state which re-aimed the saccade, as well as two separate processes which resembled a two-state model: one that learned slowly and contributed primarily via acceleration period commands, and another that learned rapidly but contributed primarily via deceleration period commands.     

Learning from sensory and reward prediction errors during motor adaptation

Voluntary motor commands produce two kinds of consequences. Initially, a sensory consequence is observed in terms of activity in our primary sensory organs (e.g., vision, proprioception). Subsequently, the brain evaluates the sensory feedback and produces a subjective measure of utility or usefulness of the motor commands (e.g., reward). As a result, comparisons between predicted and observed consequences of motor commands produce two forms of prediction error. How do these errors contribute to changes in motor commands? Here, we considered a reach adaptation protocol and found that when high quality sensory feedback was available, adaptation of motor commands was driven almost exclusively by sensory prediction errors. This form of learning had a distinct signature: as motor commands adapted, the subjects altered their predictions regarding sensory consequences of motor commands, and generalized this learning broadly to neighboring motor commands. In contrast, as the quality of the sensory feedback degraded, adaptation of motor commands became more dependent on reward prediction errors. Reward prediction errors produced comparable changes in the motor commands, but produced no change in the predicted sensory consequences of motor commands, and generalized only locally. Because we found that there was a within subject correlation between generalization patterns and sensory remapping, it is plausible that during adaptation an individual''s relative reliance on sensory vs. reward prediction errors could be inferred. We suggest that while motor commands change because of sensory and reward prediction errors, only sensory prediction errors produce a change in the neural system that predicts sensory consequences of motor commands.     

Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity

Epidermal keratinocytes form a highly organized stratified epithelium and sustain a competent barrier function together with dermal and hematopoietic cells. The Notch signaling pathway is a critical regulator of epidermal integrity. Here, we show that keratinocyte-specific deletion of total Notch signaling triggered a severe systemic B-lymphoproliferative disorder, causing death. RBP-j is the DNA binding partner of Notch, but both RBP-j–dependent and independent Notch signaling were necessary for proper epidermal differentiation and lipid deposition. Loss of both pathways caused a persistent defect in skin differentiation/barrier formation. In response, high levels of thymic stromal lymphopoietin (TSLP) were released into systemic circulation by Notch-deficient keratinocytes that failed to differentiate, starting in utero. Exposure to high TSLP levels during neonatal hematopoiesis resulted in drastic expansion of peripheral pre- and immature B-lymphocytes, causing B-lymphoproliferative disorder associated with major organ infiltration and subsequent death, a previously unappreciated systemic effect of TSLP. These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations.     

Adipose tissue biomarkers and type 2 diabetes incidence in normoglycemic participants in the MESArthritis Ancillary Study: A cohort study

BackgroundGiven the central role of skeletal muscles in glucose homeostasis, deposition of adipose depots beneath the fascia of muscles (versus subcutaneous adipose tissue [SAT]) may precede insulin resistance and type 2 diabetes (T2D) incidence. This study was aimed to investigate the associations between computed tomography (CT)–derived biomarkers for adipose tissue and T2D incidence in normoglycemic adults.Methods and findingsThis study was a population-based multiethnic retrospective cohort of 1,744 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with normoglycemia (baseline fasting plasma glucose [FPG] less than 100 mg/dL) from 6 United States of America communities. Participants were followed from April 2010 and January 2012 to December 2017, for a median of 7 years. The intermuscular adipose tissue (IMAT) and SAT areas were measured in baseline chest CT exams and were corrected by height squared (SAT and IMAT indices) using a predefined measurement protocol. T2D incidence, as the main outcome, was based on follow-up FPG, review of hospital records, or self-reported physician diagnoses.Participants’ mean age was 69 ± 9 years at baseline, and 977 (56.0%) were women. Over a median of 7 years, 103 (5.9%) participants were diagnosed with T2D, and 147 (8.4%) participants died. The IMAT index (hazard ratio [HR]: 1.27 [95% confidence interval [CI]: 1.15–1.41] per 1-standard deviation [SD] increment) and the SAT index (HR: 1.43 [95% CI: 1.16–1.77] per 1-SD increment) at baseline were associated with T2D incidence over the follow-up. The associations of the IMAT and SAT indices with T2D incidence were attenuated after adjustment for body mass index (BMI) and waist circumference, with HRs of 1.23 (95% CI: 1.09–1.38) and 1.29 (95% CI: 0.96–1.74) per 1-SD increment, respectively. The limitations of this study include unmeasured residual confounders and one-time measurement of adipose tissue biomarkers.ConclusionsIn this study, we observed an association between IMAT at baseline and T2D incidence over the follow-up. This study suggests the potential role of intermuscular adipose depots in the pathophysiology of T2D.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00005487","term_id":"NCT00005487"}}NCT00005487

In a cohort study, Shadpour Demehri and colleagues investigate the association between adipose tissue biomarkers and type 2 diabetes incidence in normoglycemic participants in US.     

Interacting adaptive processes with different timescales underlie short-term motor learning

Multiple processes may contribute to motor skill acquisition, but it is thought that many of these processes require sleep or the passage of long periods of time ranging from several hours to many days or weeks. Here we demonstrate that within a timescale of minutes, two distinct fast-acting processes drive motor adaptation. One process responds weakly to error but retains information well, whereas the other responds strongly but has poor retention. This two-state learning system makes the surprising prediction of spontaneous recovery (or adaptation rebound) if error feedback is clamped at zero following an adaptation-extinction training episode. We used a novel paradigm to experimentally confirm this prediction in human motor learning of reaching, and we show that the interaction between the learning processes in this simple two-state system provides a unifying explanation for several different, apparently unrelated, phenomena in motor adaptation including savings, anterograde interference, spontaneous recovery, and rapid unlearning. Our results suggest that motor adaptation depends on at least two distinct neural systems that have different sensitivity to error and retain information at different rates.     

A gain-field encoding of limb position and velocity in the internal model of arm dynamics

Adaptability of reaching movements depends on a computation in the brain that transforms sensory cues, such as those that indicate the position and velocity of the arm, into motor commands. Theoretical consideration shows that the encoding properties of neural elements implementing this transformation dictate how errors should generalize from one limb position and velocity to another. To estimate how sensory cues are encoded by these neural elements, we designed experiments that quantified spatial generalization in environments where forces depended on both position and velocity of the limb. The patterns of error generalization suggest that the neural elements that compute the transformation encode limb position and velocity in intrinsic coordinates via a gain-field; i.e., the elements have directionally dependent tuning that is modulated monotonically with limb position. The gain-field encoding makes the counterintuitive prediction of hypergeneralization: there should be growing extrapolation beyond the trained workspace. Furthermore, nonmonotonic force patterns should be more difficult to learn than monotonic ones. We confirmed these predictions experimentally.     

A mathematical analysis of the force-stiffness characteristics of muscles in control of a single joint system

Feldman (1966) has proposed that a muscle endowed with its spinal reflex system behaves as a non-linear spring with an adjustable resting length. In contrast, because of the length-tension properties of muscles, many researchers have modeled them as non-linear springs with adjustable stiffness. Here we test the merits of each approach: Initially, it is proven that the adjustable stiffness model predicts that isometric muscle force and stiffness are linearly related. We show that this prediction is not supported by data on the static stiffness-force characteristics of reflexive muscles, where stiffness grows non-linearly with force. Therefore, an intact muscle-reflex system does not behave as a non-linear spring with an adjustable stiffness. However, when the same muscle is devoid of its reflexes, the data shows that stiffness grows linearly with force. We aim to understand the functional advantage of the non-linear stiffness-force relationship present in the reflexive muscle. Control of an inverted pendulum with a pair of antagonist muscles is considered. Using an active-state muscle model we describe force development in an areflexive muscle. From the data on the relationship of stiffness and force in the intact muscle we derive the length-tension properties of a reflexive muscle. It is shown that a muscle under the control of its spinal reflexes resembles a non-linear spring with an adjustable resting length. This provides independent evidence in support of the Feldman hypothesis of an adjustable resting length as the control parameter of a reflexive muscle, but it disagrees with his particular formulation. In order to maintain stability of the single joint system, we prove that a necessary condition is that muscle stiffness must grow at least linearly with force at isometric conditions. This shows that co-contraction of antagonist muscles may actually destabilize the limb if the slope of this stiffness-force relationship is less than an amount specified by the change in the moment arm of the muscle as a function of joint configuration. In a reflexive muscle where stiffness grows faster than linearly with force, co-contraction will always lead to an increase in stiffness. Furthermore, with the reflexive muscles, the same level of joint stiffness can be produced by much smaller muscle forces because of the non-linear stiffness-force relationship. This allows the joint to remain stable at a fraction of the metabolic energy cost associated with maintaining stability with areflexive muscles.This work was supported in part by grant no. 1R01 NS 24926 from the NIH (Michael Arbib, PI). R.S. was supported by an IBM Graduate Fellowship in Computer Science