Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex

The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded – in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands – the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger’s movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation

Psychophysical Investigations into the Role of Low-Threshold C Fibres in Non-Painful Affective Processing and Pain Modulation

We recently showed that C low-threshold mechanoreceptors (CLTMRs) contribute to touch-evoked pain (allodynia) during experimental muscle pain. Conversely, in absence of ongoing pain, the activation of CLTMRs has been shown to correlate with a diffuse sensation of pleasant touch. In this study, we evaluated (1) the primary afferent fibre types contributing to positive (pleasant) and negative (unpleasant) affective touch and (2) the effects of tactile stimuli on tonic muscle pain by varying affective attributes and frequency parameters. Psychophysical observations were made in 10 healthy participants. Two types of test stimuli were applied: stroking stimulus using velvet or sandpaper at speeds of 0.1, 1.0 and 10.0 cm/s; focal vibrotactile stimulus at low (20 Hz) or high (200 Hz) frequency. These stimuli were applied in the normal condition (i.e. no experimental pain) and following the induction of muscle pain by infusing hypertonic saline (5%) into the tibialis anterior muscle. These observations were repeated following the conduction block of myelinated fibres by compression of sciatic nerve. In absence of muscle pain, all participants reliably linked velvet-stroking to pleasantness and sandpaper-stroking to unpleasantness (no pain). Likewise, low-frequency vibration was linked to pleasantness and high-frequency vibration to unpleasantness. During muscle pain, the application of previously pleasant stimuli resulted in overall pain relief, whereas the application of previously unpleasant stimuli resulted in overall pain intensification. These effects were significant, reproducible and persisted following the blockade of myelinated fibres. Taken together, these findings suggest the role of low-threshold C fibres in affective and pain processing. Furthermore, these observations suggest that temporal coding need not be limited to discriminative aspects of tactile processing, but may contribute to affective attributes, which in turn predispose individual responses towards excitatory or inhibitory modulation of pain

Recognition of Depression in Older Medical Inpatients

BACKGROUND: Studies of recognition of depression in older (aged 65 or more) medical inpatients show low rates of recognition of depression by attending physicians. However, few studies have compared different measures of recognition of depression. OBJECTIVES: (1) To compare the validity of four indicators of recognition of depression and a global measure of recognition against a diagnosis of depression and (2) to explore the effect of patient characteristics on recognition of depression. METHODS: In a cohort of 264 medical inpatients 65 years and older (115 with major or minor depression, 78 with no depression), sensitivities, specificities, and diagnostic odds ratios (DOR) of 4 indicators of recognition (symptoms, diagnosis, treatment, and referral) and a global measure of recognition (any of the 4 indicators) were calculated. The associations between patient characteristics (age, sex, history of depression, antidepressant use before admission, severity of depression, comorbidity, duration of hospitalization, disability, and hospital of admission) and recognition were explored using multiple logistic regression. RESULTS: Less than half of the depressed patients were recognized. The indicator with the highest sensitivity was treatment (27.8%, 95% confidence interval [CI] 20.0–37.0), whereas the indicator with the best specificity was diagnosis (96.6%, 95% CI 91.9–98.7). The unadjusted DOR of global recognition was 2.6 (95% CI 1.5, 4.4). Less comorbidity, more severe depression symptoms, a history of depression, longer hospital stay, and antidepressant use before admission were significantly associated with better global recognition. CONCLUSION: Recognition of depression in elderly medical inpatients depends upon the indicator of recognition used

Genetic causes of hypercalciuric nephrolithiasis

Renal stone disease (nephrolithiasis) affects 3–5% of the population and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in over 35% of patients and may occur as a monogenic disorder that is more likely to manifest itself in childhood. Studies of these monogenic forms of hypercalciuric nephrolithiasis in humans, e.g. Bartter syndrome, Dent’s disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal disease, is caused by mutations of the bumetanide-sensitive Na–K–Cl (NKCC2) co-transporter, the renal outer-medullary potassium (ROMK) channel, the voltage-gated chloride channel, CLC-Kb, the CLC-Kb beta subunit, barttin, or the calcium-sensing receptor (CaSR). Dent’s disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is due to mutations of the chloride/proton antiporter 5, CLC-5; ADHH is associated with activating mutations of the CaSR, which is a G-protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium–phosphate co-transporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to hypercalciuria and nephrolithiasis

Feeling fooled: Texture contaminates the neural code for tactile speed.

Motion is an essential component of everyday tactile experience: most manual interactions involve relative movement between the skin and objects. Much of the research on the neural basis of tactile motion perception has focused on how direction is encoded, but less is known about how speed is. Perceived speed has been shown to be dependent on surface texture, but previous studies used only coarse textures, which span a restricted range of tangible spatial scales and provide a limited window into tactile coding. To fill this gap, we measured the ability of human observers to report the speed of natural textures-which span the range of tactile experience and engage all the known mechanisms of texture coding-scanned across the skin. In parallel experiments, we recorded the responses of single units in the nerve and in the somatosensory cortex of primates to the same textures scanned at different speeds. We found that the perception of speed is heavily influenced by texture: some textures are systematically perceived as moving faster than are others, and some textures provide a more informative signal about speed than do others. Similarly, the responses of neurons in the nerve and in cortex are strongly dependent on texture. In the nerve, although all fibers exhibit speed-dependent responses, the responses of Pacinian corpuscle-associated (PC) fibers are most strongly modulated by speed and can best account for human judgments. In cortex, approximately half of the neurons exhibit speed-dependent responses, and this subpopulation receives strong input from PC fibers. However, speed judgments seem to reflect an integration of speed-dependent and speed-independent responses such that the latter help to partially compensate for the strong texture dependence of the former