SoftHand at the CYBATHLON: a user’s experience

Roughly one-quarter of upper limb prosthesis users reject their prosthesis. Reasons for rejection range from comfort, to cost, aesthetics, function, and more. This paper follows a single user from training wit...

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Using voltage-sensor toxins and their molecular targets to investigate NaV1.8 gating

Abstract

Voltage-gated sodium (Na_V) channel gating is a complex phenomenon which involves a distinct contribution of four integral voltage-sensing domains (VSDI, VSDII, VSDIII, and VSDIV). Utilizing accrued pharmacological and structural insights, we build on an established chimera approach to introduce animal toxin sensitivity in each VSD of an acceptor channel by transferring in portable S3b-S4 motifs from the four VSDs of a toxin-susceptible donor channel (Na_V1.2). By doing so, we observe that in Na_V1.8, a relatively unexplored channel subtype with distinctly slow gating kinetics, VSDI-III participate in channel opening whereas VSDIV can regulate opening as well as fast inactivation. These results illustrate the effectiveness of a pharmacological approach to investigate the mechanism underlying gating of a mammalian Na_V channel complex.

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Model of a bilateral Brown-type central pattern generator for symmetric and asymmetric locomotion

The coordinated activity of muscles is produced in part by spinal rhythmogenic neural circuits, termed central pattern generators (CPGs). A classical CPG model is a system of coupled oscillators that transform locomotor drive into coordinated and gait-specific patterns of muscle recruitment. The network properties of this conceptual model can be simulated by a system of ordinary differential equations with a physiologically-inspired coupling locus of interactions capturing the timing relationship for bilateral coordination of limbs in locomotion. While most similar models are solved numerically, it is intriguing to have a full analytical description of this plausible CPG architecture to illuminate the functionality within this structure and to expand it to include steering control. Here, we provided a closed-form analytical solution contrasted against the previous numerical method. The evaluation time of the analytical solution was decreased by an order of magnitude when compared to the numerical approach (relative errors, <0.01%). The analytical solution tested and supported the previous finding that the input to the model can be expressed in units of the desired limb locomotor speed. Furthermore, we performed parametric sensitivity analysis in the context of controlling steering and documented two possible mechanisms associated with either an external drive or intrinsic CPG parameters. The results identify specific propriospinal pathways that may be associated with adaptations within the CPG structure. The model offered several network configurations that may generate the same behavioral outcomes.

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The assessment of neurovascular coupling with the Addenbrooke's Cognitive Examination: a functional Transcranial Doppler Ultrasonographic Study

Cerebrovascular dysfunction occurs early in dementia and can be identified by Transcranial Doppler ultrasonography (TCD). Few studies have examined cerebral blood flow velocity (CBF_v) responses to a detailed cognitive battery. This study aimed to characterise all CBF_v responses, and the effect of hemispheric dominance, to the Addenbrooke's Cognitive Examination (ACE-III) in healthy volunteers. Forty volunteers underwent continuous bilateral TCD, beat-to-beat blood pressure (MAP) (Finapres), heart rate (HR) (electrocardiogram), and end-tidal CO₂ (ETCO₂) (capnography) monitoring. After 5 minutes baseline, all tasks from the ACE-III were performed in 3 sections (A: attention, fluency, memory, B: language, C: visuospatial, memory). Data are population mean normalised percentage (PM%) change from a twenty second baseline period prior to task initiation. Forty bilateral data sets were obtained (27 female, 37 right-hand dominant). All paradigms produced a sharp increase in CBF_v in both dominant (PM% (range): 3.29 to 9.70%), and non-dominant (PM% (range): 4.34 to 11.63%), hemispheres at task initiation, with associated increases in (MAP) (PM% (range): 3.06 to 16.04%). ETCO₂ did not differ significantly at task initiation (PM% (range): -1.1 to 2.4%, p>0.05). HR differed significantly across the A and C tasks at initiation (PM% (range): -1.1 to 2.4%, p<0.05), but not B tasks. In conclusion, all tasks resulted in increases in CBF_v, differing significantly between paradigms. These results require further investigation in a cognitively impaired population.

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Ih Interacts with Somato-Dendritic Structure to Determine Frequency Response to Weak Alternating Electric Field Stimulation

Transcranial current stimulation (tCS) modulates brain dynamics using weak electric fields. Given the pathological changes in brain network oscillations in neurological and psychiatric illnesses, using alternating electric field waveforms that engage rhythmic activity has been proposed as a targeted, network-level treatment approach. Previous studies have investigated the effects of electric fields at the neuronal level. However, the biophysical basis of the cellular response to electric fields has remained limited. Here, we characterized the frequency-dependent response of different compartments in a layer V pyramidal neuron to exogenous electric fields to dissect the relative contributions of voltage-gated ion channels and neuronal morphology. Hyperpolarization-activated cation current (I_h) in the distal dendrites was the primary ionic mechanism shaping the model response to electric field stimulation and caused subthreshold resonance in the tuft at 20 ± 4 Hz. In contrast, subthreshold I_h-mediated resonance in response to local sinusoidal current injection was present in all model compartments at 11 ± 2 Hz. The frequencies of both resonance responses were modulated by I_h conductance density. We found that the difference in resonance frequency between the two stimulation types can be explained by the fact that exogenous electric fields simultaneously polarize the membrane potentials at the distal ends of the neuron (relative to field direction) in opposite directions. Our results highlight the role of I_h in shaping the cellular response to electric field stimulation and suggest that the common model of tCS as a weak somatic current injection fails to capture the cellular effects of electric field stimulation.

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Time course of functional recovery during first three months after surgical transection and repair of nerves to feline soleus and lateral gastrocnemius muscles

Locomotion outcomes after peripheral nerve injury and repair in cats have been described in the literature for the period immediately following the injury (muscle denervation period) and then again for an ensuing period of long-term recovery (at three months and longer) resulting in muscle self-reinnervation. Little is known about the changes in muscle activity and walking mechanics during mid-recovery, i.e. the early reinnervation period that takes place between 5 and 10 weeks of recovery. Here, we investigated hindlimb mechanics and EMG activity of ankle extensors in six cats during level and slope walking before and every two weeks thereafter in a 14-week period of recovery after the soleus (SO) and lateral gastrocnemius (LG) muscle nerves in one hindlimb were surgically transected and repaired. We found that the continued increase in SO and LG EMG magnitudes and corresponding changes in hindlimb mechanics coincided with the formation of neuromuscular synapses revealed in muscle biopsies. Throughout the recovery period, EMG magnitude of SO and LG during the stance phase and the duration of the stance-related activity were load-dependent, similar to those in the intact synergistic medial gastrocnemius and plantaris. These results and the fact that EMG activity of ankle extensors and locomotor mechanics during level and upslope walking recovered 14 weeks after nerve transection and repair suggest that loss of the stretch reflex in self-reinnervated muscles may be compensated by the recovered force-dependent feedback in self-reinnervated muscles, by increased central drive and increased gain in intermuscular motion-dependent pathways from intact ankle extensors.

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Clustering of Heading Selectivity and Perception-Related Activity in the Ventral Intraparietal Area

The ventral intraparietal area (VIP) of the macaque brain is a multimodal cortical region, with many cells tuned to both optic flow and vestibular stimuli. Responses of many VIP neurons also show robust correlations with perceptual judgments during a fine heading discrimination task. Previous studies have shown that heading tuning based on optic flow is represented in a clustered fashion in VIP. However, it is unknown whether vestibular self-motion selectivity is clustered in VIP. Moreover, it is not known whether stimulus- and choice-related signals in VIP show clustering in the context of a heading discrimination task. To address these issues, we compared the response characteristics of isolated single units (SUs) with those of the undifferentiated multiunit (MU) activity corresponding to several neighboring neurons recorded from the same microelectrode. We find that MU activity typically shows selectivity similar to that of simultaneously recorded SUs, for both the vestibular and visual stimulus conditions. In addition, the choice-related activity of MU signals, as quantified using choice-probabilities (CPs), is correlated with the choice-related activity of SUs. Overall, these findings suggest that both sensory and choice-related signals regarding self-motion are clustered in VIP.

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