Sensory computations in the cuneate nucleus of macaques.

Tactile nerve fibers fall into a few classes that can be readily distinguished based on their spatiotemporal response properties. Because nerve fibers reflect local skin deformations, they individually carry ambiguous signals about object features. In contrast, cortical neurons exhibit heterogeneous response properties that reflect computations applied to convergent input from multiple classes of afferents, which confer to them a selectivity for behaviorally relevant features of objects. The conventional view is that these complex response properties arise within the cortex itself, implying that sensory signals are not processed to any significant extent in the two intervening structures-the cuneate nucleus (CN) and the thalamus. To test this hypothesis, we recorded the responses evoked in the CN to a battery of stimuli that have been extensively used to characterize tactile coding in both the periphery and cortex, including skin indentations, vibrations, random dot patterns, and scanned edges. We found that CN responses are more similar to their cortical counterparts than they are to their inputs: CN neurons receive input from multiple classes of nerve fibers, they have spatially complex receptive fields, and they exhibit selectivity for object features. Contrary to consensus, then, the CN plays a key role in processing tactile information.

Neural population dynamics in motor cortex are different for reach and grasp.

Low-dimensional linear dynamics are observed in neuronal population activity in primary motor cortex (M1) when monkeys make reaching movements. This population-level behavior is consistent with a role for M1 as an autonomous pattern generator that drives muscles to give rise to movement. In the present study, we examine whether similar dynamics are also observed during grasping movements, which involve fundamentally different patterns of kinematics and muscle activations. Using a variety of analytical approaches, we show that M1 does not exhibit such dynamics during grasping movements. Rather, the grasp-related neuronal dynamics in M1 are similar to their counterparts in somatosensory cortex, whose activity is driven primarily by afferent inputs rather than by intrinsic dynamics. The basic structure of the neuronal activity underlying hand control is thus fundamentally different from that underlying arm control.

Postural Representations of the Hand in the Primate Sensorimotor Cortex.

Manual dexterity requires proprioceptive feedback about the state of the hand. To date, study of the neural basis of proprioception in the cortex has focused primarily on reaching movements to the exclusion of hand-specific behaviors such as grasping. To fill this gap, we record both time-varying hand kinematics and neural activity evoked in somatosensory and motor cortices as monkeys grasp a variety of objects. We find that neurons in the somatosensory cortex, as well as in the motor cortex, preferentially track time-varying postures of multi-joint combinations spanning the entire hand. This contrasts with neural responses during reaching movements, which preferentially track time-varying movement kinematics of the arm, such as velocity and speed of the limb, rather than its time-varying postural configuration. These results suggest different representations of arm and hand movements suited to the different functional roles of these two effectors.

Neural Coding of Contact Events in Somatosensory Cortex.

Manual interactions with objects require precise and rapid feedback about contact events. These tactile signals are integrated with motor plans throughout the neuraxis to achieve dexterous object manipulation. To better understand the role of somatosensory cortex in interactions with objects, we measured, using chronically implanted arrays of electrodes, the responses of populations of somatosensory neurons to skin indentations designed to simulate the initiation, maintenance, and termination of contact with an object. First, we find that the responses of somatosensory neurons to contact onset and offset dwarf their responses to maintenance of contact. Second, we show that these responses rapidly and reliably encode features of the simulated contact events-their timing, location, and strength-and can account for the animals' performance in an amplitude discrimination task. Third, we demonstrate that the spatiotemporal dynamics of the population response in cortex mirror those of the population response in the nerves. We conclude that the responses of populations of somatosensory neurons are well suited to encode contact transients and are consistent with a role of somatosensory cortex in signaling transitions between task subgoals.

Sleep Promotes, and Sleep Loss Inhibits, Selective Changes in Firing Rate, Response Properties and Functional Connectivity of Primary Visual Cortex Neurons.

Recent studies suggest that sleep differentially alters the activity of cortical neurons based on firing rates during preceding wake-increasing the firing rates of sparsely firing neurons and decreasing those of faster firing neurons. Because sparsely firing cortical neurons may play a specialized role in sensory processing, sleep could facilitate sensory function via selective actions on sparsely firing neurons. To test this hypothesis, we analyzed longitudinal electrophysiological recordings of primary visual cortex (V1) neurons across a novel visual experience which induces V1 plasticity (or a control experience which does not), and a period of subsequent ad lib sleep or partial sleep deprivation. We find that across a day of ad lib sleep, spontaneous and visually-evoked firing rates are selectively augmented in sparsely firing V1 neurons. These sparsely firing neurons are more highly visually responsive, and show greater orientation selectivity than their high firing rate neighbors. They also tend to be "soloists" instead of "choristers"-showing relatively weak coupling of firing to V1 population activity. These population-specific changes in firing rate are blocked by sleep disruption either early or late in the day, and appear to be brought about by increases in neuronal firing rates across bouts of rapid eye movement (REM) sleep. Following a patterned visual experience that induces orientation-selective response potentiation (OSRP) in V1, sparsely firing and weakly population-coupled neurons show the highest level of sleep-dependent response plasticity. Across a day of ad lib sleep, population coupling strength increases selectively for sparsely firing neurons-this effect is also disrupted by sleep deprivation. Together, these data suggest that sleep may optimize sensory function by augmenting the functional connectivity and firing rate of highly responsive and stimulus-selective cortical neurons, while simultaneously reducing noise in the network by decreasing the activity of less selective, faster-firing neurons.

The Effect of Contact Force on the Responses of Tactile Nerve Fibers to Scanned Textures.

The perception of fine textures relies on highly precise and repeatable spiking patterns evoked in tactile afferents. These patterns have been shown to depend not only on the surface microstructure and material but also on the speed at which it moves across the skin. Interestingly, the perception of texture is independent of scanning speed, implying the existence of downstream neural mechanisms that correct for scanning speed in interpreting texture signals from the periphery. What force is applied during texture exploration also has negligible effects on how the surface is perceived, but the consequences of changes in contact force on the neural responses to texture have not been described. In the present study, we measure the signals evoked in tactile afferents of macaques to a diverse set of textures scanned across the skin at two different contact forces and find that responses are largely independent of contact force over the range tested. We conclude that the force invariance of texture perception reflects the force independence of texture representations in the nerve.

Methodological considerations for a chronic neural interface with the cuneate nucleus of macaques.

While the response properties of neurons in the somatosensory nerves and anterior parietal cortex have been extensively studied, little is known about the encoding of tactile and proprioceptive information in the cuneate nucleus (CN) or external cuneate nucleus (ECN), the first recipients of upper limb somatosensory afferent signals. The major challenge in characterizing neural coding in CN/ECN has been to record from these tiny, difficult-to-access brain stem structures. Most previous investigations of CN response properties have been carried out in decerebrate or anesthetized animals, thereby eliminating the well-documented top-down signals from cortex, which likely exert a strong influence on CN responses. Seeking to fill this gap in our understanding of somatosensory processing, we describe an approach to chronically implanting arrays of electrodes in the upper limb representation in the brain stem in primates. First, we describe the topography of CN/ECN in rhesus macaques, including its somatotopic organization and the layout of its submodalities (touch and proprioception). Second, we describe the design of electrode arrays and the implantation strategy to obtain stable recordings. Third, we show sample responses of CN/ECN neurons in brain stem obtained from awake, behaving monkeys. With this method, we are in a position to characterize, for the first time, somatosensory representations in CN and ECN of primates.NEW & NOTEWORTHY In primates, the neural basis of touch and of our sense of limb posture and movements has been studied in the peripheral nerves and in somatosensory cortex, but coding in the cuneate and external cuneate nuclei, the first processing stage for these signals in the central nervous system, remains an enigma. We have developed a method to record from these nuclei, thereby paving the way to studying how sensory information from the limb is encoded there.

Cortically coordinated NREM thalamocortical oscillations play an essential, instructive role in visual system plasticity.

Two long-standing questions in neuroscience are how sleep promotes brain plasticity and why some forms of plasticity occur preferentially during sleep vs. wake. Establishing causal relationships between specific features of sleep (e.g., network oscillations) and sleep-dependent plasticity has been difficult. Here we demonstrate that presentation of a novel visual stimulus (a single oriented grating) causes immediate, instructive changes in the firing of mouse lateral geniculate nucleus (LGN) neurons, leading to increased firing-rate responses to the presented stimulus orientation (relative to other orientations). However, stimulus presentation alone does not affect primary visual cortex (V1) neurons, which show response changes only after a period of subsequent sleep. During poststimulus nonrapid eye movement (NREM) sleep, LGN neuron overall spike-field coherence (SFC) with V1 delta (0.5-4 Hz) and spindle (7-15 Hz) oscillations increased, with neurons most responsive to the presented stimulus showing greater SFC. To test whether coherent communication between LGN and V1 was essential for cortical plasticity, we first tested the role of layer 6 corticothalamic (CT) V1 neurons in coherent firing within the LGN-V1 network. We found that rhythmic optogenetic activation of CT V1 neurons dramatically induced coherent firing in LGN neurons and, to a lesser extent, in V1 neurons in the other cortical layers. Optogenetic interference with CT feedback to LGN during poststimulus NREM sleep (but not REM or wake) disrupts coherence between LGN and V1 and also blocks sleep-dependent response changes in V1. We conclude that NREM oscillations relay information regarding prior sensory experience between the thalamus and cortex to promote cortical plasticity.

Altered Motor Unit Discharge Coherence in Paretic Muscles of Stroke Survivors.

After a cerebral stroke, a series of changes at the supraspinal and spinal nervous system can alter the control of muscle activation, leading to persistent motor impairment. However, the relative contribution of these different levels of the nervous system to impaired muscle activation is not well understood. The coherence of motor unit (MU) spike trains is considered to partly reflect activities of higher level control, with different frequency band representing different levels of control. Accordingly, the objective of this study was to quantify the different sources of contribution to altered muscle activation. We examined the coherence of MU spike trains decomposed from surface electromyogram (sEMG) of the first dorsal interosseous muscle on both paretic and contralateral sides of 14 hemispheric stroke survivors. sEMG was obtained over a range of force contraction levels at 40, 50, and 60% of maximum voluntary contraction. Our results showed that MU coherence increased significantly in delta (1-4 Hz), alpha (8-12 Hz), and beta (15-30 Hz) bands on the affected side compared with the contralateral side, but was maintained at the same level in the gamma (30-60 Hz) band. In addition, no significant alteration was observed across medium-high force levels (40-60%). These results indicated that the common synaptic input to motor neurons increased on the paretic side, and the increased common input can originate from changes at multiple levels, including spinal and supraspinal levels following a stroke. All these changes can contribute to impaired activation of affected muscles in stroke survivors. Our findings also provide evidence regarding the different origins of impaired muscle activation poststroke.

Edge orientation signals in tactile afferents of macaques.

The orientation of edges indented into the skin has been shown to be encoded in the responses of neurons in primary somatosensory cortex in a manner that draws remarkable analogies to their counterparts in primary visual cortex. According to the classical view, orientation tuning arises from the integration of untuned input from thalamic neurons with aligned but spatially displaced receptive fields (RFs). In a recent microneurography study with human subjects, the precise temporal structure of the responses of individual mechanoreceptive afferents to scanned edges was found to carry information about their orientation. This putative mechanism could in principle contribute to or complement the classical rate-based code for orientation. In the present study, we further examine orientation information carried by mechanoreceptive afferents of Rhesus monkeys. To this end, we record the activity evoked in cutaneous mechanoreceptive afferents when edges are indented into or scanned across the skin. First, we confirm that information about the edge orientation can be extracted from the temporal patterning in afferent responses of monkeys, as is the case in humans. Second, we find that while the coarse temporal profile of the response can be predicted linearly from the layout of the RF, the fine temporal profile cannot. Finally, we show that orientation signals in tactile afferents are often highly dependent on stimulus features other than orientation, which complicates putative decoding strategies. We discuss the challenges associated with establishing a neural code at the somatosensory periphery, where afferents are exquisitely sensitive and nearly deterministic.

Altered motor unit discharge patterns in paretic muscles of stroke survivors assessed using surface electromyography.

OBJECTIVE: Hemispheric stroke survivors often show impairments in voluntary muscle activation. One potential source of these impairments could come from altered control of muscle, via disrupted motor unit (MU) firing patterns. In this study, we sought to determine whether MU firing patterns are modified on the affected side of stroke survivors, as compared with the analogous contralateral muscle. APPROACH: Using a novel surface electromyogram (EMG) sensor array, coupled with advanced template recognition software (dEMG) we recorded surface EMG signals over the first dorsal interosseous (FDI) muscle on both paretic and contralateral sides. Recordings were made as stroke survivors produced isometric index finger abductions over a large force range (20%-60% of maximum). Utilizing the dEMG algorithm, MU firing rates, recruitment thresholds, and action potential amplitudes were estimated for concurrently active MUs in each trial. MAIN RESULTS: Our results reveal significant changes in the firing rate patterns in paretic FDI muscle, in that the discharge rates, characterized in relation to recruitment force threshold and to MU size, were less clearly correlated with recruitment force than in contralateral FDI muscles. Firing rates in the affected muscle also did not modulate systematically with the level of voluntary muscle contraction, as would be expected in intact muscles. These disturbances in firing properties also correlated closely with the impairment of muscle force generation. SIGNIFICANCE: Our results provide strong evidence of disruptions in MU firing behavior in paretic muscles after a hemispheric stroke, suggesting that modified control of the spinal motoneuron pool could be a contributing factor to muscular weakness in stroke survivors.

Assessing altered motor unit recruitment patterns in paretic muscles of stroke survivors using surface electromyography.

OBJECTIVE: The advancement of surface electromyogram (sEMG) recording and signal processing techniques has allowed us to characterize the recruitment properties of a substantial population of motor units (MUs) non-invasively. Here we seek to determine whether MU recruitment properties are modified in paretic muscles of hemispheric stroke survivors. APPROACH: Using an advanced EMG sensor array, we recorded sEMG during isometric contractions of the first dorsal interosseous muscle over a range of contraction levels, from 20% to 60% of maximum, in both paretic and contralateral muscles of stroke survivors. Using MU decomposition techniques, MU action potential amplitudes and recruitment thresholds were derived for simultaneously activated MUs in each isometric contraction. MAIN RESULTS: Our results show a significant disruption of recruitment organization in paretic muscles, in that the size principle describing recruitment rank order was materially distorted. MUs were recruited over a very narrow force range with increasing force output, generating a strong clustering effect, when referenced to recruitment force magnitude. Such disturbances in MU properties also correlated well with the impairment of voluntary force generation. SIGNIFICANCE: Our findings provide direct evidence regarding MU recruitment modifications in paretic muscles of stroke survivors, and suggest that these modifications may contribute to weakness for voluntary contractions.

Changes in motoneuron afterhyperpolarization duration in stroke survivors.

Hemispheric brain injury resulting from a stroke is often accompanied by muscle weakness in limbs contralateral to the lesion. In the present study, we investigated whether weakness in contralesional hand muscle in stroke survivors is partially attributable to alterations in motor unit activation, including alterations in firing rate modulation range. The afterhyperpolarization (AHP) potential of a motoneuron is a primary determinant of motoneuron firing rate. We examined differences in AHP duration in motoneurons innervating paretic and less impaired (contralateral) limb muscles of hemiparetic stroke survivors as well as in control subjects. A novel surface EMG (sEMG) electrode was used to record motor units from the first dorsal interosseous muscle. The sEMG data were subsequently decomposed to derive single-motor unit events, which were then utilized to produce interval (ISI) histograms of the motoneuron discharges. A modified version of interval death rate (IDR) analysis was used to estimate AHP duration. Results from data analyses performed on both arms of 11 stroke subjects and in 7 age-matched control subjects suggest that AHP duration is significantly longer for motor units innervating paretic muscle compared with units in contralateral muscles and in units of intact subjects. These results were supported by a coefficient of variation (CV) analysis showing that paretic motor unit discharges have a lower CV than either contralateral or control units. This study suggests that after stroke biophysical changes occur at the motoneuron level, potentially contributing to lower firing rates and potentially leading to less efficient force production in paretic muscles.

Examination of afterhyperpolarization duration changes in motoneurons innervating paretic muscles in stroke survivors.

The after hyperpolarization (AHP) of a motoneuron is a primary determinant of motoneuron firing rate. Any increase in its duration or amplitude could alter normal motor unit (MU) firing rate properties in stroke, and potentially impact muscle force generation. The objective of this preliminary study was to examine potential differences in afterhyperpolarization (AHP) duration of motoneurons innervating paretic and contralateral limb muscles of hemiparetic stroke survivors. A novel surface EMG (sEMG) electrode was used to record from the first dorsal interosseous muscle (FDI) of three hemiparetic stroke survivors. sEMG data was decomposed to derive single motor unit (SMU) events, which were subsequently utilized to produce interval (ISI) histograms of the motor unit discharge. Interval Death Rate (IDR) analysis was then used to transform ISI histograms into death rate plots. [1] The prescribed IDR analysis method [1] involves a final transformation of death rate plots into an estimated AHP time course. The present study uses a modified method of interpreting death rate plots in order to determine AHP duration. AHP durations from this analysis are similar to durations obtained from ISI variability analysis. [2] Results from three subjects indicate that on average, motor units on the paretic side have a longer AHP duration than the contralateral side, potentially contributing to lower firing rates, and to less efficient force production in paretic muscles.

Impaired motor unit control in paretic muscle post stroke assessed using surface electromyography: a preliminary report.

The objective of this preliminary study was to examine the possible contribution of disordered control of motor unit (MU) recruitment and firing patterns in muscle weakness post-stroke. A novel surface EMG (sEMG) recording and decomposition system was used to record sEMG signals and extract single MU activities from the first dorsal interosseous muscle (FDI) of two hemiparetic stroke survivors. To characterize MU reorganization, an estimate of the motor unit action potential (MUAP) amplitude was derived using spike triggered averaging of the sEMG signal. The MUs suitable for further analysis were selected using a set of statistical tests that assessed the variability of the morphological characteristics of the MUAPs. Our preliminary results suggest a disrupted orderly recruitment based on MUAP size, a compressed recruitment range, and reduced firing rates evident in the paretic muscle compared with the contralateral muscle of one subject with moderate impairment. In contrast, the MU organization was largely similar bilaterally for the subject with minor impairment. The preliminary results suggest that MU organizational changes with respect to recruitment and rate modulation can contribute to muscle weakness post-stroke. The contrasting results of the two subjects indicate that the degree of MU reorganization may be associated with the degree of the functional impairment, which reveals the differential diagnostic capability of the sEMG decomposition system.