Quantitative electrophysiological assessments as predictive markers of lower limb motor recovery after spinal cord injury: a pilot study with an adaptive trial design.

STUDY DESIGN: Observational, cohort study. OBJECTIVES: (1) Determine the feasibility and relevance of assessing corticospinal, sensory, and spinal pathways early after traumatic spinal cord injury (SCI) in a rehabilitation setting. (2) Validate whether electrophysiological and magnetic resonance imaging (MRI) measures taken early after SCI could identify preserved neural pathways, which could then guide therapy. SETTING: Intensive functional rehabilitation hospital (IFR). METHODS: Five individuals with traumatic SCI and eight controls were recruited. The lower extremity motor score (LEMS), electrical perceptual threshold (EPT) at the S2 dermatome, soleus (SOL) H-reflex, and motor evoked potentials (MEPs) in the tibialis anterior (TA) muscle were assessed during the stay in IFR and in the chronic stage (>6 months post-SCI). Control participants were only assessed once. Feasibility criteria included the absence of adverse events, adequate experimental session duration, and complete dataset gathering. The relationship between electrophysiological data collected in IFR and LEMS in the chronic phase was studied. The admission MRI was used to calculate the maximal spinal cord compression (MSCC). RESULTS: No adverse events occurred, but a complete dataset could not be collected for all subjects due to set-up configuration limitations and time constraints. EPT measured at IFR correlated with LEMS in the chronic phases (r = -0.67), whereas SOL H/M ratio, H latency, MEPs and MSCC did not. CONCLUSIONS: Adjustments are necessary to implement electrophysiological assessments in an IFR setting. Combining MRI and electrophysiological measures may lead to better assessment of neuronal deficits early after SCI.

Differential effects of the mode of touch, active and passive, on experience-driven plasticity in the S1 cutaneous digit representation of adult macaque monkeys.

This study compared the receptive field (RF) properties and firing rates of neurons in the cutaneous hand representation of primary somatosensory cortex (areas 3b, 1, and 2) of 9 awake, adult macaques that were intensively trained in a texture discrimination task using active touch (fingertips scanned over the surfaces using a single voluntary movement), passive touch (surfaces displaced under the immobile fingertips), or both active and passive touch. Two control monkeys received passive exposure to the same textures in the context of a visual discrimination task. Training and recording extended over 1-2 yr per animal. All neurons had a cutaneous receptive field (RF) that included the tips of the stimulated digits (D3 and/or D4). In area 3b, RFs were largest in monkeys trained with active touch, smallest in those trained with passive touch, and intermediate in those trained with both; i.e., the mode of touch differentially modified the cortical representation of the stimulated fingers. The same trends were seen in areas 1 and 2, but the changes were not significant, possibly because a second experience-driven influence was seen in areas 1 and 2, but not in area 3b: smaller RFs with passive exposure to irrelevant tactile inputs compared with recordings from one naive hemisphere. We suggest that added feedback during active touch and higher cortical firing rates were responsible for the larger RFs with behavioral training; this influence was tempered by periods of more restricted sensory feedback during passive touch training in the active + passive monkeys.NEW & NOTEWORTHY We studied experience-dependent sensory cortical plasticity in relation to tactile discrimination of texture using active and/or passive touch. We showed that neuronal receptive fields in primary somatosensory cortex, especially area 3b, are largest in monkeys trained with active touch, smallest in those trained with passive touch, and intermediate in those trained using both modes of touch. Prolonged, irrelevant tactile input had the opposite influence in areas 1 and 2, favoring smaller receptive fields.

Effects of transcranial direct current stimulation of primary somatosensory cortex on vibrotactile detection and discrimination.

Anodal transcranial direct current stimulation (a-tDCS) of primary somatosensory cortex (S1) has been shown to enhance tactile spatial acuity, but there is little information as to the underlying neuronal mechanisms. We examined vibrotactile perception on the distal phalanx of the middle finger before, during, and after contralateral S1 tDCS [a-, cathodal (c)-, and sham (s)-tDCS]. The experiments tested our shift-gain hypothesis, which predicted that a-tDCS would decrease vibrotactile detection and discrimination thresholds (leftward shift of the stimulus-response function with increased gain/slope) relative to s-tDCS, whereas c-tDCS would have the opposite effects (relative to s-tDCS). The results showed that weak a-tDCS (1 mA, 20 min) led to a reduction in both vibrotactile detection and discrimination thresholds to 73-76% of baseline during the application of the stimulation in subjects categorized as responders. These effects persisted after the end of a-tDCS but were absent 30 min later. Most, but not all, subjects showed a decrease in threshold (8/12 for detection; 9/12 for discrimination). Intersubject variability was explained by a ceiling effect in the discrimination task. c-tDCS had no significant effect on either detection or discrimination threshold. Taken together, our results supported our shift-gain hypothesis for a-tDCS but not c-tDCS.

Tactile texture signals in primate primary somatosensory cortex and their relation to subjective roughness intensity.

This study investigated the hypothesis that a simple intensive code, based on mean firing rate, could explain the cortical representation of subjective roughness intensity and its invariance with scanning speed. We examined the sensitivity of neurons in the cutaneous, finger representation of primary somatosensory cortex (S1) to a wide range of textures [1 mm high, raised-dot surfaces; spatial periods (SPs), 1.5-8.5 mm], scanned under the digit tips at different speeds (40-115 mm/s). Since subjective roughness estimates show a monotonic increase over this range and are independent of speed, we predicted that the mean firing rate of a subgroup of S1 neurons would share these properties. Single-unit recordings were made in four alert macaques (areas 3b, 1 and 2). Cells whose discharge rate showed a monotonic increase with SP, independent of speed, were particularly concentrated in area 3b. Area 2 was characterized by a high proportion of cells sensitive to speed, with or without texture sensitivity. Area 1 had intermediate properties. We suggest that area 3b and most likely area 1 play a key role in signaling roughness intensity, and that a mean rate code, signaled by both slowly and rapidly adapting neurons, is present at the level of area 3b. Finally, the substantial proportion of neurons that showed a monotonic change in discharge limited to a small range of SPs (often independent of response saturation) could play a role in discriminating smaller changes in SP.

Neuronal correlates of tactile speed in primary somatosensory cortex.

Moving stimuli activate all of the mechanoreceptive afferents involved in discriminative touch, but their signals covary with several parameters, including texture. Despite this, the brain extracts precise information about tactile speed, and humans can scale the tangential speed of moving surfaces as long as they have some surface texture. Speed estimates, however, vary with texture: lower estimates for rougher surfaces (increased spatial period, SP). We hypothesized that the discharge of cortical neurons playing a role in scaling tactile speed should covary with speed and SP in the same manner. Single-cell recordings (n = 119) were made in the hand region of primary somatosensory cortex (S1) of awake monkeys while raised-dot surfaces (longitudinal SPs, 2-8 mm; periodic or nonperiodic) were displaced under their fingertips at speeds of 40-105 mm/s. Speed sensitivity was widely distributed (area 3b, 13/25; area 1, 32/51; area 2, 31/43) and almost invariably combined with texture sensitivity (82% of cells). A subset of cells (27/64 fully tested speed-sensitive cells) showed a graded increase in discharge with increasing speed for testing with both sets of surfaces (periodic, nonperiodic), consistent with a role in tactile speed scaling. These cells were almost entirely confined to caudal S1 (areas 1 and 2). None of the speed-sensitive cells, however, showed a pattern of decreased discharge with increased SP, as found for subjective speed estimates in humans. Thus further processing of tactile motion signals, presumably in higher-order areas, is required to explain human tactile speed scaling.

Physical determinants of the shape of the psychophysical curve relating tactile roughness to raised-dot spacing: implications for neuronal coding of roughness.

There are conflicting reports as to whether the shape of the psychometric relation between perceived roughness and tactile element spacing [spatial period (SP)] follows an inverted U-shape or a monotonic linear increase. This is a critical issue because the former result has been used to assess neuronal codes for roughness. We tested the hypothesis that the relation's shape is critically dependent on tactile element height (raised dots). Subjects rated the roughness of low (0.36 mm)- and high (1.8 mm)-raised-dot surfaces displaced under their fingertip. Inverted U-shaped curves were obtained as the SP of low-dot surfaces was increased (1.3-6.2 mm, tetragonal arrays); a monotonic increase was observed for high-dot surfaces. We hypothesized that roughness is not a single sensory continuum across the tested SPs of low-dot surfaces, predicting that roughness discrimination would show deviations from the invariant relation between threshold (ΔS) and the value of the standard (S) surface (Weber fraction, ΔS/S) expected for a single continuum. The results showed that Weber fractions were increased for SPs on the descending limb of the inverted U-shaped curve. There was also an increase in the Weber fraction for high-dot surfaces but only at the peak (3 mm), corresponding to the SP at which the slope of the psychometric function showed a modest decline. Together the results indicate that tactile roughness is not a continuum across low-dot SPs of 1.3-6.2 mm. These findings suggest that correlating the inverted U-shaped function with neuronal codes is of questionable validity. A simple intensive code may well contribute to tactile roughness.

A critical speed for gating of tactile detection during voluntary movement.

This study addressed the paradoxical observation that movement is essential for tactile exploration, and yet is accompanied by movement-related gating or suppression of tactile detection. Knowing that tactile gating covaries with the speed of movement (faster movements, more gating), we hypothesized that there would be no tactile gating at slower speeds of movement, corresponding to speeds commonly used during tactile exploration (<200 mm/s). Subjects (n = 21) detected the presence or absence of a weak electrical stimulus applied to the skin of the right middle finger during two conditions: rest and active elbow extension. Movement speed was systematically varied from 50 to ~1,000 mm/s. No subject showed evidence of tactile gating at the slowest speed tested, 50 mm/s (rest versus movement), but all subjects showed decreased detection at one or more higher speeds. For each subject, we calculated the critical speed, corresponding to the speed at which detection fell to 0.5 (chance). The mean critical speed was 472 mm/s and >200 mm/s in almost all subjects (19/21). This result is consistent with our hypothesis that subjects optimize the speed of movement during tactile exploration to avoid speeds associated with tactile gating. This strategy thus maximizes the quality of the tactile feedback generated during tactile search and improves perception.

Tactile perception of roughness: raised-dot spacing, density and disposition.

Recently, we showed that tactile speed estimates are modified by the spatial parameters of moving raised-dot surfaces, specifically dot spacing but not dot disposition (regular, irregular) or density. The purpose of this study was to determine the extent to which tactile roughness perception resembles tactile speed with respect to its dependence and/or independence of the spatial properties of raised-dot surfaces. Subjects scaled the roughness of surfaces displaced under the finger. Dot spacing (centre-to-centre) ranged from 1.5 to 8.5 mm in the direction of the scan (longitudinal). Mean dot density varied from 2.2 to 46.2 dots/cm2. Dot disposition was varied: repeating rows (periodic) or quasi-random (non-periodic). In the first experiment (n = 8), the periodic and non-periodic surfaces were matched for mean dot density. Roughness showed a monotonic increase with 1/dot density, but non-periodic surfaces were judged to be smoother than the periodic surfaces. Subjective equality was obtained when the data were re-expressed relative to longitudinal SP. In the second experiment (n = 7), the periodic and non-periodic surfaces were matched for longitudinal dot spacing. Perceptual equivalence was observed when the results were plotted relative to dot spacing, but not 1/dot density. Dot spacing in the orthogonal direction (transverse) was excluded as a contributing factor. Thus, as found for tactile speed scaling, roughness is critically dependent on longitudinal dot spacing, but independent of dot disposition and dot density (over much of the tested range). These results provide a set of predictions to identify cortical neurones that play critical roles in roughness appreciation.

Instructed delay discharge in primary and secondary somatosensory cortex within the context of a selective attention task.

The neuronal mechanisms that contribute to tactile perception were studied using single-unit recordings from the cutaneous hand representation of primate primary (S1) and secondary (S2) somatosensory cortex. This study followed up on our recent observation that S1 and S2 neurons developed a sustained change in discharge during the instruction period of a directed-attention task. We determined the extent to which the symbolic light cues, which signaled the modality (tactile, visual) to attend and discriminate, elicited changes in discharge rate during the instructed delay (ID) period of the attention task and the functional importance of this discharge. ID responses, consisting of a sustained increase or decrease in discharge during the 2-s instruction period, were present in about 40% of the neurons in S1 and S2. ID responses in both cortical regions were very similar in most respects (frequency, sign, latency, amplitude), suggesting a common source. A major difference, however, was related to attentional modulation during the ID period: attentional influences were almost entirely restricted to S2 and these effects were always superimposed on the ID response (additive effect). These findings suggest that the underlying mechanisms for ID discharge and attention are independent. ID discharge significantly modified the initial response to the standard stimuli (competing texture and visual stimuli), usually enhancing responsiveness. We also showed that tactile detection in humans is enhanced during the ID period. Together, the results suggest that ID discharge represents a priming mechanism that prepares cortical areas to receive and process sensory inputs.

Tactile speed scaling: contributions of time and space.

A major challenge for the brain is to extract precise information about the attributes of tactile stimuli from signals that co-vary with multiple parameters, e.g., speed and texture in the case of scanning movements. We determined the ability of humans to estimate the tangential speed of surfaces moved under the stationary fingertip and the extent to which the physical characteristics of the surfaces modify speed perception. Scanning speed ranged from 33 to 110 mm/s (duration of motion constant). Subjects could scale tactile scanning speed, but surface structure was essential because the subjects were poor at scaling the speed of a moving smooth surface. For textured surfaces, subjective magnitude estimates increased linearly across the range of speeds tested. The spatial characteristics of the surfaces influenced speed perception, with the roughest surface (8 mm spatial period, SP) being perceived as moving 15% slower than the smoother, textured surfaces (2-3 mm SP). Neither dot disposition (periodic, non periodic) nor dot density contributed to the results, suggesting that the critical factor was dot spacing in the direction of the scan. A single monotonic relation between subjective speed and temporal frequency (speed/SP) was obtained when the ratings were normalized for SP. This provides clear predictions for identifying those cortical neurons that play a critical role in tactile motion perception and the underlying neuronal code. Finally, the results were consistent with observations in the visual system (decreased subjective speed with a decrease in spatial frequency, 1/SP), suggesting that stimulus motion is processed similarly in both sensory systems.

Independent controls of attentional influences in primary and secondary somatosensory cortex.

The neuronal mechanisms underlying enhanced perception of tactile stimuli with directed attention were investigated using single-unit recordings from primary (S1, n = 53) and secondary (S2, n = 50) somatosensory cortex in macaque monkeys. Neuronal responses to textures scanned under the digit tips (spatial periods, SP, of 2, 3.7 or 4.7 mm) were recorded while attention was directed either to discriminating a change in texture or to the reward and also in a neutral no-task condition. Cell discharge was quantified in three periods of the trials: salient Delta texture (directed attention), postreward, and static (both cases, attention directed to the reward). S1 texture- and non-texture-sensitive cells, as well as S2 non-texture-sensitive cells, showed a modest enhancement of discharge during the salient Delta texture period (approximately 25%) but no change in response gain, consistent with an additive increase in neuronal responsiveness with directed attention. In contrast, S2 texture-related cells showed a larger enhancement with directed attention to salient inputs (82%) and increased response gain, suggesting that directed attention produces a multiplicative increase in S2 responsiveness. During the postreward period, and also in no-task testing, S1 texture-sensitive cells preserved their sensitivity to SP. In contrast, S2 texture-, but not non-texture-, sensitive cells showed a marked suppression of discharge and decreased gain after the discrimination response. Together, the results support the notion that S2 discharge reflects stimulus parameters in relation to ongoing behavioral demands. The results also support the existence of two independent attentional mechanisms in somatosensory cortex, one generalized (S1 and S2), and the other focused on S2 texture-related cells.

Effects of a cross-modal manipulation of attention on somatosensory cortical neuronal responses to tactile stimuli in the monkey.

The role of attention in modulating tactile sensitivity in primary (SI) and secondary somatosensory cortex (SII) was addressed using a cross-modal manipulation of attention, somatosensory versus visual. Two adult monkeys (Macaca mulatta) were trained to perform two tasks: tactile discrimination of a change in the texture of a surface presented to digits 3 and 4 and visual discrimination of a change in the intensity of a light. In each trial, standard texture (2 mm spatial period, SP) and visual stimuli were presented. These were followed by an increase in SP and/or luminance. Each trial was preceded by an instruction cue (colored light) that directed the animal to attend and respond to the change in one modality while ignoring any change in the other modality. The two tasks were interleaved during the recording, on a trial-by-trial basis. Extracellular recordings were made from 178 neurons (SI, 102; SII, 76), all with a cutaneous receptive field on the stimulated digit tips. Discharge was quantified in both tasks during the instruction, the standard-stimuli, and the texture-change periods. The results showed that selective attention to tactile stimuli had qualitatively and quantitatively greater and earlier effects in SII than SI. Twenty-four of 102 SI cells showed a significant change in discharge with the direction of attention. For almost all cells (20/24), discharge was enhanced when attention was directed toward the tactile stimuli; the effects were most frequent in the analysis interval that encompassed the change in SP (16/24). A significantly higher proportion of SII cells were attention-sensitive (47/76). The effects were concentrated in the texture-change period (39/47) but also included earlier periods in the trial (instruction period, n = 15; standard-stimuli period, n = 32). Attention-related modulation that spanned all three intervals (n = 11) likely reflected baseline changes in discharge. For the texture-sensitive cells (43 in SI, 37 in SII), the mean change in discharge frequency (post texture change - pre-texture change) in each task was significantly increased in SII but not SI with selective attention. The results are consistent with a two-stage modulation of parietal cortical discharge, an initial stage (SI) in which there is some enhancement of sensory responses to the salient feature, the texture change, and a second stage (SII) in which baseline changes occur, along with further feature selection. These controls may be independently exerted on SI and SII, or they may reflect top-down controls from SII to SI.

Central neural mechanisms contributing to the perception of tactile roughness.

This paper summarizes recent work showing that tactile roughness appreciation increases in a nearly linear fashion as tactile element spacing or spatial period (SP, distance centre-to-centre between raised dots in these experiments) is increased from 1.5 to 8.5 mm. Although a previous study had reported a U-shaped psychophysical function peaking at a nominal SP of 3.2 mm, differences in the surfaces (including changing SP in only one dimension as compared with two and higher dot heights that minimized contact with the smooth floor) likely contributed to the difference in the results. Roughness estimates were also unaffected by a 2-fold change in scanning speed (50 vs. 95 mm/s). Parallel recordings from neurones in primary somatosensory cortex (SI) during a texture discrimination task indicate that the discharge frequency of many SI cells shows a monotonic relation with SP (up to 5 mm tested). For some cells, the texture signals were ambiguous because discharge frequency co-varied with both texture and the scanning speed, as has also been reported for the peripheral mechanoreceptors that are activated by textured surfaces. Yet other SI cells showed a speed-invariant response to surface texture, consistent with perceptual constancy for roughness over a range of scanning speeds. We suggest that such a discharge pattern could be based on a simple intensive, or mean rate, code: an invariant central representation of surface texture could be obtained by subtracting a speed-varying signal from the ambiguous signals that co-vary with roughness and speed.