Aneesha K. Suresh

Sleep promotes cortical response potentiation following visual experience.

STUDY OBJECTIVES Sleep has been hypothesized to globally reduce synaptic strength. However, recent findings suggest that in the context of learning and memory consolidation, sleep may promote synaptic potentiation. We tested the requirement for sleep in a naturally occurring form of experience-dependent synaptic potentiation in the adult mouse visual cortex (V1), which is initiated by patterned visual experience. DESIGN Visual responses were recorded in individual V1 neurons before and after presentation of an oriented grating stimulus, and after subsequent sleep or sleep deprivation. MEASUREMENTS AND RESULTS We find that V1 response potentiation-associated with a shift in orientation preference in favor of the presented stimulus-occurs only after sleep and only during the entrained circadian sleep phase, and is blocked by sleep deprivation. Induction of plasticity following stimulus presentation is associated with an increase in principal neuron firing in V1, which is present in all behavioral states and occurs regardless of time of day. Sleep dependent potentiation is proportional to phase-locking of neuronal activity with thalamocortical spindle oscillations. CONCLUSIONS Our results suggest that sleep can promote cortical synaptic potentiation in vivo, and that this potentiation may be mediated by slow wave sleep spindles. CITATION Aton SJ, Suresh A, Broussard C, Frank MG. Sleep promotes cortical response potentiation following visual experience.

Alterations in the Peak Amplitude Distribution of the Surface Electromyogram Poststroke

We introduce a new method to examine the spinal motoneuron involvement after stroke using a surface electromyography (EMG) recording system. Fourteen chronic stroke survivors with mild to severe muscle weakness participated in the study. Surface EMG signals were collected from the first dorsal interosseous muscle while subjects performed isometric index finger abduction with paretic or contralateral hand at different matched force levels. Compared with the contralateral muscles, different patterns of peak amplitude distribution were observed at the paretic muscles, which could be induced by motor unit pathological alterations following a stroke. Compared with the conventional electrophysiological methods, the peak amplitude distribution analysis proposed in this study provides a convenient approach to help identify specific mechanisms of muscle weakness and other symptoms after stroke.

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.

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.

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

Significance Previous studies have demonstrated a role of state-specific neural activity in plasticity; however, a mechanism for these changes has yet to be elucidated. Here, we demonstrate that sensory response changes occur in thalamic neurons immediately following novel visual experience, but that subsequent nonrapid eye movement (NREM) oscillations are required for subsequent response changes in the primary visual cortex (V1). Consequently, we show that disruption of NREM oscillations specifically blocks sleep-dependent plasticity in V1. We conclude that following a novel sensory experience, neural activity patterns unique to NREM facilitate transfer of information from the visual thalamus to the V1, leading to adaptive response changes in V1 neurons. 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.

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.

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.

Power spectral analysis of surface EMG in stroke: A preliminary study

The objective of this preliminary study was to examine the utility of power spectral analysis of recorded surface EMG signals in identifying altered MUAP characteristics in hand muscles of stroke survivors. We derived parameters from EMG power spectral analysis, such as frequency range and median frequency and made comparisons between data obtained from the affected and contralateral sides of stroke subjects. The goal was to identify whether power spectral analysis of the surface EMG could be used to infer changes in action potential characteristics that can occur in post-stroke muscle. We utilized both a standard single differential electrode (Delsys, Inc.) and in a separate set of experiments, a sensor array electrode (Delsys, Inc.) that consists of 5 slender cylindrical probes. Recordings were made during isometric force contractions at varying levels. Utilizing a novel decomposition system (Delsys, Inc.) and the sensor array electrode, we were able to derive MUAP parameters, such as p-p amplitude and p-p duration. Preliminary results suggest that there were significant differences in the median frequency values between the stroke and contralateral side of three tested stroke subjects; however, this did not follow the differences in MUAP p-p duration values. There were also significant differences in the median frequency recorded from the sensor array electrode as compared to the single differential electrode on both the stroke and contralateral sides of our tested stroke subjects, as expected. We discuss the possible explanations for our results, specifically pertaining to the clinical scores for each subject.

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.