Repetitive Sensory Stimulation Research Articles

Repetitive tactile stimulation changes resting-state functional connectivity-implications for treatment of sensorimotor decline.

Neurological disorders and physiological aging can lead to a decline of perceptual abilities. In contrast to the conventional therapeutic approach that comprises intensive training and practicing, passive repetitive sensory stimulation (RSS) has recently gained increasing attention as an alternative to countervail the sensory decline by improving perceptual abilities without the need of active participation. A particularly effective type of high-frequency RSS, utilizing Hebbian learning principles, improves perceptual acuity as well as sensorimotor functions and has been successfully applied to treat chronic stroke patients and elderly subjects. High-frequency RSS has been shown to induce plastic changes of somatosensory cortex such as representational map reorganization, but its impact on the brain's ongoing network activity and resting-state functional connectivity has not been investigated so far. Here, we applied high-frequency RSS in healthy human subjects and analyzed resting state Electroencephalography (EEG) functional connectivity patterns before and after RSS by means of imaginary coherency (ImCoh), a frequency-specific connectivity measure which is known to reduce over-estimation biases due to volume conduction and common reference. Thirty minutes of passive high-frequency RSS lead to significant ImCoh-changes of the resting state mu-rhythm in the individual upper alpha frequency band within distributed sensory and motor cortical areas. These stimulation induced distributed functional connectivity changes likely underlie the previously observed improvement in sensorimotor integration.

Improved Acuity and Dexterity but Unchanged Touch and Pain Thresholds following Repetitive Sensory Stimulation of the Fingers

Neuroplasticity underlies the brain's ability to alter perception and behavior through training, practice, or simply exposure to sensory stimulation. Improvement of tactile discrimination has been repeatedly demonstrated after repetitive sensory stimulation (rSS) of the fingers; however, it remains unknown if such protocols also affect hand dexterity or pain thresholds. We therefore stimulated the thumb and index finger of young adults to investigate, besides testing tactile discrimination, the impact of rSS on dexterity, pain, and touch thresholds. We observed an improvement in the pegboard task where subjects used the thumb and index finger only. Accordingly, stimulating 2 fingers simultaneously potentiates the efficacy of rSS. In fact, we observed a higher gain of discrimination performance as compared to a single-finger rSS. In contrast, pain and touch thresholds remained unaffected. Our data suggest that selecting particular fingers modulates the efficacy of rSS, thereby affecting processes controlling sensorimotor integration.

Plasticity of Adult Sensorimotor System

Plasticity of Adult Sensorimotor System

Long-term sensory stimulation therapy improves hand function and restores cortical responsiveness in patients with chronic cerebral lesions. Three single case studies

Rehabilitation of sensorimotor impairment resulting from cerebral lesion (CL) utilizes task specific training and massed practice to drive reorganization and sensorimotor improvement due to induction of neuroplasticity mechanisms. Loss of sensory abilities often complicates recovery, and thus the individual's ability to use the affected body part for functional tasks. Therefore, the development of additional and alternative approaches that supplement, enhance, or even replace conventional training procedures would be advantageous. Repetitive sensory stimulation protocols (rSS) have been shown to evoke sensorimotor improvements of the affected limb in patients with chronic stroke. However, the possible impact of long-term rSS on sensorimotor performance of patients with CL, where the incident dated back many years remains unclear. The particular advantage of rSS is its passive nature, which does not require active participation of the subjects. Therefore, rSS can be applied in parallel to other occupations, making the intervention easier to implement and more acceptable to the individual. Here we report the effects of applying rSS for 8, 36, and 76 weeks to the paretic hand of three long-term patients with different types of CL. Different behavioral tests were used to assess sensory and/or sensorimotor performance of the upper extremities prior, after, and during the intervention. In one patient, the impact of long-term rSS on restoration of cortical activation was investigated by recording somatosensory evoked potentials (SEP). After long-term rSS all three patients showed considerable improvements of their sensory and motor abilities. In addition, almost normal evoked potentials could be recorded after rSS in one patient. Our data show that long-term rSS applied to patients with chronic CL can improve tactile and sensorimotor functions, which, however, developed in some cases only after many weeks of stimulation, and continued to further improve on a time scale of months.

Perceptual improvement following repetitive sensory stimulation depends monotonically on stimulation intensity

Electrical repetitive sensory stimulation (rSS) is a direct and effective means of inducing plasticity processes in human beings, and is increasingly being used as a therapeutic intervention. Suprathreshold intensities induce beneficial effects on tactile perception and sensorimotor abilities. However, it is not known whether there is an optimal range of stimulus intensity. We investigated the effect of varied intensities (low, 1.19 ± 0.07 mA; intermediate, 3.33 ± 0.27 mA; and high, 4.42 ± 0.56 mA) on the outcome of a 30-minute electrical rSS applied to the index finger (intermittent high-frequency stimulation, 20 Hz and interburst interval, 5 seconds) in three groups (n = 10 each) of participants. As a marker of perceptual changes, we measured tactile spatial two-point discrimination on the stimulated finger and on the heel of the hand before and after the rSS. rSS improved discrimination performance, with the gain being the highest in the high-intensity group and the lowest in the low-intensity group. Measurements on the heel of the hand revealed small improvements in the high-intensity group, indicative of recruitment processes. rSS of maximal intensity induced the strongest effects, indicative of a monotonic intensity-gain characteristic with no U-shaped dependency.

Three Patterns of Oscillatory Activity Differentially Synchronize Developing Neocortical Networks In Vivo

Coordinated patterns of electrical activity are important for the early development of sensory systems. The spatiotemporal dynamics of these early activity patterns and the role of the peripheral sensory input for their generation are essentially unknown. We performed extracellular multielectrode recordings in the somatosensory cortex of postnatal day 0 to 7 rats in vivo and observed three distinct patterns of synchronized oscillatory activity. (1) Spontaneous and periphery-driven spindle bursts of 1-2 s in duration and approximately 10 Hz in frequency occurred approximately every 10 s. (2) Spontaneous and sensory-driven gamma oscillations of 150-300 ms duration and 30-40 Hz in frequency occurred every 10-30 s. (3) Long oscillations appeared only every approximately 20 min and revealed the largest amplitude (250-750 microV) and longest duration (>40 s). These three distinct patterns of early oscillatory activity differently synchronized the neonatal cortical network. Whereas spindle bursts and gamma oscillations did not propagate and synchronized a local neuronal network of 200-400 microm in diameter, long oscillations propagated with 25-30 microm/s and synchronized 600-800 microm large ensembles. All three activity patterns were triggered by sensory activation. Single electrical stimulation of the whisker pad or tactile whisker activation elicited neocortical spindle bursts and gamma activity. Long oscillations could be only evoked by repetitive sensory stimulation. The neonatal oscillatory patterns in vivo depended on NMDA receptor-mediated synaptic transmission and gap junctional coupling. Whereas spindle bursts and gamma oscillations may represent an early functional columnar-like pattern, long oscillations may serve as a propagating activation signal consolidating these immature neuronal networks.

Corticospinal Facilitation Following Prolonged Proprioceptive Stimulation by Means of Passive Wrist Movement

The purpose of this study was to evaluate the delayed effects of repetitive sensory stimulation with passive wrist movement on corticospinal excitability of the forearm and hand musculature. Motor evoked potential responses to single and double pulse transcranial magnetic stimulation were recorded from the flexor carpi radialis, extensor carpi radialis, and the first dorsal interosseous muscles of the right limb. Data were collected before and after a 1 hour session of passive wrist movement (intervention group, n = 11) or after a same period of rest (control group, n = 9). Motor evoked potential size and area were analyzed to evaluate corticospinal excitability and short interval intracortical inhibition and facilitation. Training with passive movement resulted in a prolonged increase in corticospinal excitability in the flexor carpi radialis and extensor carpi radialis (until at least 1 hour postintervention), but did not evoke significant changes in the levels of short interval intracortical inhibition and facilitation. No such effects were noted in the control group or first dorsal interosseous muscle. Prolonged proprioceptive stimulation with passive wrist movement induces a delayed increase in corticospinal excitability of the forearm muscles. Accordingly, this intervention may promote motor cortical reorganization in the targeted muscles. Results show induced effects from passive movement training that may prove useful for neurorehabilitation therapies.

Cyclic AMP Mediates Serotonin-Induced Synaptic Enhancement of Lateral Giant Interneuron of the Crayfish

The lateral giant (LG)-mediated escape behavior of the crayfish habituates readily on repetitive sensory stimulation. Recent studies suggested that the biogenic amines serotonin and octopamine modulate the time course of recovery and/or re-depression of the LG response after habituation. However, little is known of how serotonin and octopamine effect LG habituation and what second-messenger cascades they may activate. To investigate the effect of biogenic amines on LG habituation, serotonin and octopamine were superfused before presenting repetitive sensory stimulation. Serotonin and octopamine increased the number of stimuli needed to habituate the LG response. Their effects were mimicked by mixed application of a cAMP analogue [8-(4-chlorophenylthio)-cAMP (CPT-cAMP)] and a phosphodiesterase inhibitor [3-isobutyl-1-methylxanthine (IBMX)] but not by a cGMP analogue (8-bromoguanosine 3',5'-cyclic monophosphate). Perfusion of the adenylate cyclase inhibitor (SQ22536) abolished the effect of serotonin but not that of octopamine. To investigate the site of action of each biogenic amines in the neural circuit meditating LG escape, the effect of drugs on directly and indirectly elicited postsynaptic potentials in LG was investigated. Serotonin, octopamine, and a mixture of CPT-cAMP and IBMX increased both the direct and indirect synaptic inputs. Simultaneous application of SQ22536 abolished the effect of serotonin on both inputs but did not block the effect of octopamine. Direct injection of the cAMP analogue (Sp-isomer of adenosine-3',5'-cyclic monophosphorothioate) into LG increased both the direct and indirect inputs to LG. These results indicate that serotonin mediates an increase in cAMP levels in LG, but octopamine acts independently of cAMP and cGMP.

Decrease in excitability of LG following habituation of the crayfish escape reaction

Crayfish escapes from threatening stimuli to the abdomen by tailflipping upwards and forwards. This lateral giant (LG)-mediated escape reaction habituates readily upon repetitive sensory stimulation. Using an isolated abdominal nerve cord preparation, we have analyzed the change in LG activity by applying additional sensory stimulation after different periods following habituation to characterize the retention of LG habituation. Results show that the LG mediated response habituates more quickly, but the retention time is shorter, as repetitive sensory stimulation is applied at progressively shorter inter-stimulus time intervals. The spike response of LG recovers quickly, within several minutes after habituation, but they fail to spike when an additional stimulus is applied after specific long periods following habituation. The critical period of the delay for this decrease in excitability of LG is dependent on the inter-stimulus time interval of the initial repetitive stimulus. As the inter-stimulus interval became longer, the delay needed for decrease in excitability became shorter. Furthermore, the local injection of 10(-6) mol l-1 octopamine into the neuropil just following habituation promotes the achievement of decrease in excitability. No effects were observed when 10(-6) mol l-1 serotonin and tyramine were injected. These results suggested octopamine promotes decrease in excitability of LG following habituation.

Tactile stimulation of the hand causes bilateral cortical activation: a functional magnetic resonance study in humans

The purpose of the present study was to assess the somatotopy of the cortical sensory representation of the fingers using a natural tactile stimulation of the glabrous skin. Multislice echoplanar imaging techniques were utilized to investigate blood oxygen level dependent (BOLD) signal changes as a measure of cortical activation. Repetitive sensory stimulation of the glabrous skin of digit II–III and digit IV–V resulted in a multifocal signal increase in a restricted area near the central sulcus in the contralateral hemisphere with a considerable overlap between the activated areas of digit II–III and digit IV–V. In addition, in all subjects tactile stimulation resulted in ipsilateral signal increase near the central sulcus, which was 15–22% of the contralateral effect. Stimulation of digit II–III caused significantly ( P<0.05) more activated voxels than digit IV–V in the contralateral hemisphere for both hands and for the left hand in the ipsilateral hemisphere. These findings suggest an ipsilateral activation of the primary somatosensory cortex during a natural tactile stimulation of the digits in humans.

Sensorimotor pathways involved in interjoint reflex action of an insect leg

Coordination of motor output between leg joints is crucial for the generation of posture and active movements in multijointed appendages of legged organisms. We investigated in the stick insect the information flow between the middle leg femoral chordotonal organ (fCO), which measures position and movement in the femur-tibia (FT) joint and the motoneuron pools supplying the next proximal leg joint, the coxa-trochanteral (CT) joint. In the inactive animal, elongation of the fCO (by flexing the FT joint) induced a depolarization in eight of nine levator trochanteris motoneurons, with a suprathreshold activation of one to three motoneurons. Motoneurons of the depressor trochanteris muscle were inhibited by fCO elongation. Relaxation signals, i.e., extension of the FT joint, activated both levator and depressor motoneurons; i.e., both antagonistic muscles were coactivated. Monosynaptic as well as polysynaptic pathways contribute to interjoint reflex actions in the stick insect leg. fCO afferents were found to induce short latency EPSPs in levator motoneurons, providing evidence for direct connections between fCO afferents and levator motoneurons. In addition, neuronal pathways via intercalated interneurons were identified that transmit sensory information from the fCO onto levator and/or depressor motoneurons. Finally, we describe two kinds of alterations in interjoint reflex action: (a) With repetitive sensory stimulation, this interjoint reflex action shows a habituation-like decrease in strength. (b) In the actively moving animal, interjoint reflex action in response to fCO elongation, mimicking joint flexion, qualitatively remained the same sign, but with a marked increase in strength, indicating an increased influence of sensory signals from the FT joint onto the adjacent CT joint in the active animal.

Changes in motor responses induced by cerebellar stimulation during classical forelimb flexion conditioning in cat.

1. The ability of somaesthetic sensory inputs to produce structural changes in the connectivities of the central nervous structures involved in motor activity was tested with an alpha type of classical conditioning in chronically prepared adult cats. Repetitive sensory stimulation was applied at constant intervals after the activation of the motor circuits originating in the neurons or efferent axons of the cerebellar nuclei. A conditional stimulation (CS) applied to interpositus neurons was consistently paired with an unconditional stimulation (UCS) applied to the dorsal skin of the forelimb extremity to induce associative sensorimotor conditioning. The sites at which the conditional and unconditional stimuli were applied set up a simplified sensorimotor circuit including pathways transmitting both these stimuli and others mediating the expression of the conditioned responses. 2. To test the changes resulting from the conditioning, electrodes were implanted into the various relay structures on the cerebellar efferent pathways (ventrolateral nucleus motor cortex). The forelimb motor responses elicited by stimulating these relay structures were recorded with a potentiometer placed at the elbow joint. The angular displacement (amplitude) and latency of the responses and the percentage response rates were systematically quantified throughout the conditioning procedure and at test sessions carried out after the daily conditioning routines. 3. It was observed that daily repetition of paired CS-UCS led to an increase in the response rates and amplitudes of the forelimb flexions, which already began to occur very slightly on the first 4 or 5 days in response to the alpha conditioning, whereas the CS when applied alone failed to produce any changes in this initial response. Likewise, after the acquisition phase, repeated presentation of either the CS alone or the CS preceded by the UCS led to the extinction of the conditioned response, thus indicating that the observed changes were of an associative nature and that they depended on interactions between the motor and sensory inputs occurring somewhere in the CNS. In fact, the effects of conditioning were not generalized, but involved only a circumscribed circuit originating in the cerebellar neurons stimulated by the CS, which were activated concomitantly with the sensory pathways. 4. The conditioned response amplitudes were enhanced by 2.5-3 times their initial value. This enhancement persisted at the end of acquisition or after several days of consolidation, even when the paired CS-UCS sessions were interrupted for a period of 15 days to 2 mo.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional imaging of brain responses to repetitive sensory stimulation: sources estimated from EEG and SPECT.

This study examined the effect of modality of stimulation on two measures of cerebral function: (a) the scalp distribution of sensory evoked potentials and (b) the cerebral distribution of radiolabelled HMPAO. Steady-state stimulation in the auditory, somatosensory or visual modality was presented to six subjects. Scalp potentials were measured from a distribution of electrodes, and the radiopharmaceutical was injected through an indwelling intravenous catheter midway through the stimulation/recording session. Equivalent dipole sources estimated from the spatial distribution of the scalp potentials were found to be consistent with regions of high HMPAO uptake as imaged by Single Photon Emission Computed Tomography (SPECT).

Neuromagnetic evidence of synchronized spontaneous activity in the brain following repetitive sensory stimulation.

Neuromagnetic measurements in the visual and somatosensory modalities reveal that, following repetitive stimulation, the brain persists in emitting synchronized after-discharges in the form of oscillations with highly specific spectral composition. In the visual modality, this rhythmic activity is centered at the frequency of the resting alpha rhythm and it is most readily induced by stimulation of the same frequency. This suggests that the phenomenon is due to synchronization of the generators responsible for the natural rhythms by the steady-state stimulation and that these generators behave as resonant oscillators. The phenomenon could then be referred to as Synchronized Spontaneous Activity (SSA). The discovery of this phenomenon has important implications for modelling the dynamics of normal evoked and spontaneous cerebral activity as well as for the understanding of pathological conditions such as photically induced epilepsies.

Multiple vibrissae sensory regions in rat cerebellum: A (14C) 2‐deoxyglucose study

Repetitive tactile sensory stimulation of the right mystacial vibrissae (whiskers) was performed in awake, adult rats. Regions of increased (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically in cerebellum. Predominantly ipsilateral activation of multiple discrete granule cell regions occurred in paramedian lobule, crus 2, crus 1, lobulus simplex, and anterior lobe hemisphere. Bilateral and contralateral activation of cerebellum did occur. Multiple small patches, as well as large granule cell regions, were activated. Mossy fiber afferents from the spinal trigeminal nuclei (particularly interpolaris), principal trigeminal sensory nucleus, and superior colliculus could account for metabolic activation of the granular layer. The slight metabolic activation of the molecular layer could have occurred from climbing or parallel fibers. Comparisons of the paramedian lobule granule cell regions activated during repetitive sensory stimulation of the vibrissae (RSSV) to those activated during vibrissae motor cortex stimulation (VMIS) showed regions only activated by RSSV, regions only activated by VMIS, and regions activated by both RSSV and VMIS. The granule cell regions activated during RSSV and VMIS were usually adjacent to or overlapping each other. Regions only activated during RSSV or only during VMIS could represent technical problems in trying to compare vibrissae motor and sensory pathways in two different groups of animals. Alternatively, cerebellar regions activated only during RSSV could process vibrissae tactile inputs. Regions activated only during VMIS could process vibrissae motor and perhaps proprioceptive sensory input. Regions activated during both RSSV and VMIS might process vibrissae proprioceptive sensory input and/or might represent loci where vibrissae motor, proprioceptive sensory, and tactile sensory convergence occur. The results raise the possibility that vibrissae motor, proprioceptive sensory, and tactile sensory pathways could be processed in separate granule cell patches in parts of cerebellum and in the same granule cell patches in other parts of cerebellum.

Vibrissae tactile stimulation: (14C) 2-deoxyglucose uptake in rat brainstem, thalamus, and cortex.

The right mystacial vibrissae of awake, adult rats were stroked at 4-6 times/second and brain regions which increased (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically. The ventral parts of the ipsilateral spinal trigeminal nuclei pars caudalis (Sp5c), pars interpolaris (Sp5i), pars oralis (Sp5o), and the principal trigeminal sensory (Pr5) nuclei were activated. The lateral part of the ipsilateral facial (VII) nucleus (the region which innervates the vibrissae muscles) was also activated possibly via excitatory, trigeminal (Sp5c, Sp5i, Sp5o, Pr5) sensory afferents. A number of regions were activated contralateral to the sensory stimulus. Discrete patches of (14C) 2DG uptake occurred in deep layers of the superior colliculus (SCsgp). Dorsolateral and dorsomedial parts of the ventrobasal nucleus (VB), and posterior, dorsolateral parts of the reticular nucleus (R) of thalamus were activated, along with broad portions of the primary somatosensory cortex (SI) and second somatosensory cortex (SII). Though all layers of SI and SII cortex increased 2DG uptake, VB thalamic afferents to layers IV and Vc-Vla presumably accounted for the greater activation of these cortical layers during repetitive sensory stimulation of the vibrissae (RSSV). Activation of the above structures fits well with known anatomical data. However, the pattern of activation during RSSV was very different from that previously described during vibrissae motor cortex stimulation (VMIS). RSSV and VMIS both produced similar repetitive movements of all the mystacial vibrissae. However, only a few overlapping brain regions were activated during both RSSV and VMIS. These RSSV-VMIS overlap zones included Sp5o; rostral Sp5i; lateral VII; SCsgp; ventrobasal-posteromedial and ventrobasal-ventrolateral zones in thalamus; and a rostral region of SI probably anterior to the Woolsey vibrissae barrelfield in the dysgranular somatosensory (SI) cortex. Since RSSV and VMIS would both be expected to activate vibrissae proprioceptors, we have hypothesized that vibrissae proprioceptive input was processed in part in the RSSV-VMIS overlap zones. Convergence of motor-sensory inputs and other types of processing could have also occurred in these overlap zones.

Neuronal habituation and sensitization in the reticular formation of the rat

Plasticity of reticular formation neuronal responses to repetitive sensory stimulation was studied in locally anesthetized paralyzed rats. Eighty-four percent of neuronal responses studied (n = 80) showed either decrement, increment, or increment followed by decrement in responses to repetitive sensory stimulation. Effects of stimulus parameters on neuronal plasticity were similar to effects reported for plasticity of behavioral and neuronal responses in other organisms. Spontaneous activity usually decreased as a result of stimulus repetition, although exceptions were noted. Latency from stimulus onset to first spike discharge increased during the course of stimulus repetition. Dishabituation was evident for many of the units tested, particularly for strong extra stimuli such as tail pinches. No differential location of neurons within the reticular core with respect to characteristics of plasticity was observed.