Effects of stimulus pulse rate on somatosensory adaptation in the human cortex

BackgroundIntracortical microstimulation (ICMS) of the somatosensory cortex can restore sensation to people with neurological diseases. However, many aspects of ICMS are poorly understood, including the effect of stimulation on percept intensity over time.ObjectiveHere, we evaluate how tactile percepts evoked by ICMS in the somatosensory cortex of a human participant adapt over time.MethodsWe delivered continuous and intermittent ICMS to the somatosensory cortex and assessed the reported intensity of tactile percepts over time in a human participant. Experiments were conducted over approximately one year and linear mixed effects models were used to assess significance.ResultsContinuous stimulation at high frequencies led to rapid decreases in intensity, while low frequency stimulation maintained percept intensity for longer periods. Burst-modulated stimulation extended the time before the intensity began to decrease, but all protocols ultimately resulted in complete sensation loss within 1 min. Intermittent stimulation paradigms with several seconds between stimulus trains evoked intermittent percepts and also led to decreases in intensity on many electrodes, but never resulted in extinction of the sensation after over 3 min of stimulation. Longer breaks between each pulse train resulted in some recovery in the intensity of the stimulus-evoked percepts. For several electrodes, intermittent stimulation had almost no effect on the perceived intensity.ConclusionsIntermittent ICMS paradigms were more effective at maintaining percepts. Given that transient neural activity dominates the response in somatosensory cortex during mechanical contact onsets and offsets, providing brief stimulation trains at these times may more closely represent natural cortical activity and have the additional benefit of prolonging the ability to evoke sensations over longer time periods.     

Sensory percepts induced by microwire array and DBS microstimulation in human sensory thalamus

Background

Microstimulation in human sensory thalamus (ventrocaudal, VC) results in focal sensory percepts in the hand and arm which may provide an alternative target site (to somatosensory cortex) for the input of prosthetic sensory information. Sensory feedback to facilitate motor function may require simultaneous or timed responses across separate digits to recreate perceptions of slip as well as encoding of intensity variations in pressure or touch.

PET-Based Confirmation of Orientation Sensitivity of TMS-Induced Cortical Activation in Humans

BackgroundCurrently, it is difficult to predict precise regions of cortical activation in response to transcranial magnetic stimulation (TMS). Most analytical approaches focus on applied magnetic field strength in the target region as the primary factor, placing activation on the gyral crowns. However, imaging studies support M1 targets being typically located in the sulcal banks.Objective/hypothesisTo more thoroughly investigate this inconsistency, we sought to determine whether neocortical surface orientation was a critical determinant of regional activation.MethodsMR images were used to construct cortical and scalp surfaces for 18 subjects. The angle (θ) between the cortical surface normal and its nearest scalp normal for ～50,000 cortical points per subject was used to quantify cortical location (i.e., gyral vs. sulcal). TMS-induced activations of primary motor cortex (M1) were compared to brain activations recorded during a finger-tapping task using concurrent positron emission tomographic (PET) imaging.ResultsBrain activations were primarily sulcal for both the TMS and task activations (P < 0.001 for both) compared to the overall cortical surface orientation. Also, the location of maximal blood flow in response to either TMS or finger-tapping correlated well using the cortical surface orientation angle or distance to scalp (P < 0.001 for both) as criteria for comparison between different neocortical activation modalities.ConclusionThis study provides further evidence that a major factor in cortical activation using TMS is the orientation of the cortical surface with respect to the induced electric field. The results show that, despite the gyral crown of the cortex being subjected to a larger magnetic field magnitude, the sulcal bank of M1 had larger cerebral blood flow (CBF) responses during TMS.     

Distinct perceptive pathways selected with tonic and bursting patterns of thalamic stimulation

BackgroundNovel patterns of electrical stimulation of the brain and spinal cord hold tremendous promise to improve neuromodulation therapies for diverse disorders, including tremor and pain. To date, there are limited numbers of experimental studies in human subjects to help explain how stimulation patterns impact the clinical response, especially with deep brain stimulation.We propose using novel stimulation patterns during electrical stimulation of somatosensory thalamus in awake deep brain stimulation surgeries and hypothesize that stimulation patterns will influence the sensory percept without moving the electrode.MethodsIn this study of 15 fully awake patients, the threshold of perception as well as perceptual characteristics were compared for tonic (trains of regularly-repeated pulses) and bursting stimulation patterns.ResultsIn a majority of subjects, tonic and burst percepts were located in separate, non-overlapping body regions (i.e., face vs. hand) without moving the stimulating electrode (p < 0.001; binomial test). The qualitative features of burst percepts also differed from those of tonic-evoked percepts as burst patterns were less likely to evoke percepts described as tingling (p = 0.013; Fisher’s exact test).ConclusionsBecause somatosensory thalamus is somatotopically organized, percept location can be related to anatomic thalamocortical pathways. Thus, stimulation pattern may provide a mechanism to select for different thalamocortical pathways. This added control could lead to improvements in neuromodulation - such as improved efficacy and side effect attenuation - and may also improve localization for sensory prostheses.     

Percepts evoked by multi-electrode stimulation of human visual cortex

BackgroundDirect electrical stimulation of early visual cortex evokes the perception of small spots of light known as phosphenes. Previous studies have examined the location, size, and brightness of phosphenes evoked by stimulation of single electrodes. While it has been envisioned that concurrent stimulation of many electrodes could be used as the basis for a visual cortical prosthesis, the percepts resulting from multi-electrode stimulation have not been fully characterized.ObjectiveTo understand the rules governing perception of phosphenes evoked by multi-electrode stimulation of visual cortex.MethodsMulti-electrode stimulation was conducted in human epilepsy patients. We examined the number and spatial arrangement of phosphenes evoked by stimulation of individual multi-electrode groups (n = 8), and the ability of subjects to discriminate between the pattern of phosphenes generated by stimulation of different multi-electrode groups (n = 7).ResultsSimultaneous stimulation of pairs of electrodes separated by greater than 4 mm tended to produce perception of two distinct phosphenes. Simultaneous stimulation of three electrodes gave rise to a consistent spatial pattern of phosphenes, but with significant variation in the absolute location, size, and orientation of that pattern perceived on each trial. Although multi-electrode stimulation did not produce perception of recognizable forms, subjects could use the pattern of phosphenes evoked by stimulation to perform simple discriminations.ConclusionsThe number of phosphenes produced by multi-electrode stimulation can be predicted using a model for spread of activity in early visual cortex, but there are additional subtle effects that must be accounted for.     

Pain-related somatosensory evoked magnetic fields induced by controlled ballistic mechanical impacts.

The purpose of this study was to investigate cortical processing of painful compared with tactile mechanical stimulation by means of magnetoencephalography (MEG) using the novel technique of mechanical impact loading. A light, hard projectile is accelerated pneumatically in a guiding barrel and elicits a brief sensation of pain when hitting the skin in free flight. Controllable noxious and innocuous impact velocities facilitate the generation of different, predetermined stimulus intensities. The authors applied painful as well as tactile mechanical impacts to the dorsum of the second, third, and fourth digit of the nondominant hand. Pain-related somatosensory evoked magnetic fields (SSEFs) were compared with those following tactile stimulation in seven healthy volunteers. Contralateral primary sensory cortical area activation was observed within the first 70 msec after tactile as well as painful stimulus intensities. Only painful impacts elicited SSEF responses assigned to the bilateral secondary sensory cortical regions and to the middle part of the contralateral cingulate gyrus, which were active at latency ranges of 55 to 155 msec and 90 to 220 msec respectively. Additional long-latency responses occurred in these cortical areas as long as 280 msec after painful stimulation in three subjects. In contrast to tactile stimulation, painful mechanical impacts elicited SSEF responses in cortical areas demonstrated to be involved in central pain processing by previous MEG and neuroimaging studies. Because of its similarity to natural noxious stimuli and the possibility of adjustable painful and tactile impact velocities, the technique of mechanical impact loading provides a useful method for the neurophysiologic evaluation of cortical pain perception.     

Comparison of magnetoencephalography,functional MRI,and motor evoked potentials in the localization of the sensory-motor cortex

Abstract

To clarify the topographical relationship between peri-Rolandic lesions and the central sulcus, we carried out presurgical functional mapping by using magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) on 5 patients. The sensory cortex was identified by somatosensory evoked magnetic fields using MEG (magnetic source imaging (MSI)). The motor area of the hand region was identified using f-MRI, during a hand squeezing task. In addition, transcranial magnetic stimulation localized the hand motor area on the scalp, which was mapped onto the MRI. In all cases, the sensory cortical vein or the lack of any functional activation in the area of peri-lesional edema. MEPs were also unable to localize the entire motor strip. Therefore, at present, MSI is considered to be the most reliable method to localize peri-Rolandic lesions. [Neurol Res 1995; 17: 361-367] cortical vein or the lack of any functional activation in the area of peri-lesional edema. MEPs were also unable to localize the entire motor strip. Therefore, at present, MSI is considered to be the most reliable method to localize peri-Rolandic lesions. [Neurol Res 1995; 17: 361-367]     

Direct cortical stimulation with cylindrical depth electrodes in the interhemispheric fissure for leg motor evoked potential monitoring

ObjectiveTo evaluate cylindrical depth electrodes in the interhemispheric fissure as an alternative to subdural strip electrodes for direct cortical stimulation (DCS) leg motor evoked potential (MEP) monitoring.MethodsA cylindrical depth electrode was positioned in the interhemispheric fissure of 37 patients who underwent supratentorial brain surgery. Leg sensory and motor cortices were localized by highest tibial nerve somatosensory evoked potential amplitude and lowest DCS leg MEP threshold; the lowest-threshold electrode was then used for DCS leg MEP monitoring.ResultsIntraoperative leg MEPs were obtained from all the patients in the series. The mean intensity applied for leg MEP monitoring with the cylindrical depth electrode was 15.2 ± 4.0 mA. No complications secondary to neurophysiological monitoring were detected.ConclusionsLower extremity MEPs were consistently recorded using a multi-contact cylindrical depth electrode in the interhemispheric fissure by DCS.SignificanceCylindrical depth electrodes may be a safe and effective alternative for DCS in the interhemispheric fissure, where subdural strips are difficult to place.     

Rapid enhancement of touch from non-informative vision of the hand

Processing in one sensory modality may modulate processing in another. Here we investigate how simply viewing the hand can influence the sense of touch. Previous studies showed that non-informative vision of the hand enhances tactile acuity, relative to viewing an object at the same location. However, it remains unclear whether this Visual Enhancement of Touch (VET) involves a phasic enhancement of tactile processing circuits triggered by the visual event of seeing the hand, or more prolonged, tonic neuroplastic changes, such as recruitment of additional cortical areas for tactile processing. We recorded somatosensory evoked potentials (SEPs) evoked by electrical stimulation of the right middle finger, both before and shortly after viewing either the right hand, or a neutral object presented via a mirror. Crucially, and unlike prior studies, our visual exposures were unpredictable and brief, in addition to being non-informative about touch. Viewing the hand, as opposed to viewing an object, enhanced tactile spatial discrimination measured using grating orientation judgements, and also the P50 SEP component, which has been linked to early somatosensory cortical processing. This was a trial-specific, phasic effect, occurring within a few seconds of each visual onset, rather than an accumulating, tonic effect. Thus, somatosensory cortical modulation can be triggered even by a brief, non-informative glimpse of one's hand. Such rapid multisensory modulation reveals novel aspects of the specialised brain systems for functionally representing the body.     

Transcranial Direct Current Stimulation Ameliorates Tactile Sensory Deficit in Multiple Sclerosis

BackgroundDeficit of tactile sensation in patients with MS is frequent and can be associated with interference with daily life activities. Transcranial direct current stimulation (tDCS) showed to increase tactile discrimination in healthy subjects.ObjectiveIn the present study, we investigated whether tDCS may be effective in ameliorating tactile sensory deficit in MS patients.MethodsPatients received sham or real anodal tDCS of the somatosensory cortex for 5 consecutive days in a randomized, double blind, sham-controlled study. Discrimination thresholds of spatial tactile sensation were measured using the grating orientation task (GOT). As secondary outcomes we also measured subjective perception of tactile sensory deficit through a visual analog scale (VAS), quality of life and overall disability to evaluate the impact of the treatment on patients daily life. Evaluations were performed at baseline and during a 4-week follow-up period.ResultsFollowing anodal but not sham tDCS over the somatosensory cortex, there was a significant improvement of discriminatory thresholds at the GOT and increased VAS for sensation scores. Quality of life, and disability changes were not observed.ConclusionOur results indicate that a five day course of anodal tDCS is able to ameliorate tactile sensory loss with long-lasting beneficial effects and could thus represent a therapeutic tool for the treatment of tactile sensory deficit in MS patients.     

Spatio-temporal prediction modulates the perception of self-produced stimuli.

We investigated why self-produced tactile stimulation is perceived as less intense than the same stimulus produced externally. A tactile stimulus on the palm of the right hand was either externally produced, by a robot or self-produced by the subject. In the conditions in which the tactile stimulus was self-produced, subjects moved the arm of a robot with their left hand to produce the tactile stimulus on their right hand via a second robot. Subjects were asked to rate intensity of the tactile sensation and consistently rated self-produced tactile stimuli as less tickly, intense, and pleasant than externally produced tactile stimuli. Using this robotic setup we were able to manipulate the correspondence between the action of the subjects' left hand and the tactile stimulus on their right hand. First, we parametrically varied the delay between the movement of the left hand and the resultant movement of the tactile stimulus on the right hand. Second, we implemented varying degrees of trajectory perturbation and varied the direction of the tactile stimulus movement as a function of the direction of left-hand movement. The tickliness rating increased significantly with increasing delay and trajectory perturbation. This suggests that self-produced movements attenuate the resultant tactile sensation and that a necessary requirement of this attenuation is that the tactile stimulus and its causal motor command correspond in time and space. We propose that the extent to which self-produced tactile sensation is attenuated (i.e., its tickliness) is proportional to the error between the sensory feedback predicted by an internal forward model of the motor system and the actual sensory feedback produced by the movement.     

Human hand and lip sensorimotor cortex as studied on electrocorticography.

We investigated functional topography of human hand and lip sensorimotor cortex using somatosensory evoked potentials (SEPs) from chronically indwelling subdural grid electrodes (ECoG) in 3 epilepsy patients during stimulation of median nerve, ulnar nerve, and lower lip. We used dipole modeling to determine the cortical location of each peripheral sensory field. The cortical locations were in the postcentral gyrus and showed a clear somatotopic organization from medial superior to lateral inferior in the order: ulnar nerve, median nerve, and lip. The source localizations agreed with the results of cortical stimulations and anatomical features on intraoperative photographs. The cortical regions of median and ulnar nerve each could be modeled by sequential tangential and radial dipoles. The cortical region of lip was different and could be explained mostly by tangential dipoles. These findings suggest a difference in the cortical organization of human lip and hand sensory cortex and are consistent with a larger representation of lip in the posterior bank of central fissure in area 3b than on the gyral surface in area 1, similar to findings in macaque. Further studies in a larger population of patients with ECoG or normal subjects with scalp-EEG and MEG are warranted to test this hypothesis.     

Cortical stimulation improves skilled forelimb use following a focal ischemic infarct in the rat

Abstract

Improving functional recovery following cerebral strokes in humans will likely involve augmenting brain plasticity. This study examined skilled forelimb behavior, neocortical evoked potentials, and movement thresholds to assess cortical electrical stimulation concurrent with rehabilitative forelimb usage following a focal ischemic insult. Adult rats were trained on a task that required skilled usage of both forelimbs. They then underwent an acute focal ischemic insult to the caudal forelimb area of sensorimotor cortex contralateral to their preferred forelimb. During the same procedure, they also received a stimulation electrode over the infarct area and two depth electrodes anterior to the lesion to record evoked potentials. One week following the surgery, rats received cortical stimulation during performance of the skilled task. Evoked potentials and movement thresholds were also determined. Functional assessment revealed that cortical stimulation resulted in superior performance compared to the no stimulation group, and this was initially due to a shift in forelimb preference. Cortical stimulation also resulted in enhanced evoked potentials and a reduction in the amount of current required to elicit a movement, in a stimulation frequency dependent manner. This study suggests that cortical stimulation, concurrent with rehabilitative training, results in better forelimb usage that may be due to augmented synaptic plasticity.     

Evaluation of lip sensory disturbance using somatosensory evoked magnetic fields

ObjectiveTo evaluate lip sensory dysfunction in patients with inferior alveolar nerve injury by lip-stimulated somatosensory evoked fields (SEFs).MethodsSEFs were recorded following electrical lip stimulation in 6 patients with unilateral lip sensory disturbance and 10 healthy volunteers. Lip stimulation was applied non-invasively to each side of the lip with the same intensity using pin electrodes.ResultsAll healthy volunteers showed the earliest response clearly and consistently at around 25 ms (P25m) and at least one of the following components, P45m, P60m, or P80m, over the contralateral hemisphere. The ranges of the peak latencies were 23–33, 42–50, 56–67, and 72–98 ms for right-side stimulation and 23–34, 46–49, 52–68, and 71–90 ms for left-side stimulation. Affected-side stimulation did not evoke P25m component in any patients, but invoked traceable responses in 5 patients whose latencies were 57, 89, 65, 53, and 54 ms. Unaffected-side stimulation induced P25m in 2 patients at 27 and 25 ms, but not in the other 4 patients.ConclusionThe P25m component of lip SEFs can be an effective parameter to indicate lip sensory abnormality.SignificanceLip sensory dysfunction can be objectively evaluated using magnetoencephalography.     

A case of combined sensation disturbance and clumsiness of the left hand caused by an infarction localized to brodmann areas 1 and 2]

A 70-year-old woman was admitted to our hospital with a complaint of numbness and clumsiness of the left hand. On physical examination 23 days after the onset of cerebral infarction, she showed no apparent muscle weakness. Although her elementary somatosensory function was mostly intact with a minimal joint position sensation disturbance, she showed disturbances in tactile recognition, two-point discrimination, and weight perception. She also had difficulty in discrete finger movement of her left hand, especially when her eyes were closed. Brain MRI disclosed a small infarction localized to Brodmann areas 1 and 2 in the right postcentral gyrus. In the left median nerve short-latency somatosensory evoked potentials (s-SEPs), the N20 potential was normally evoked. This finding also indicated that the area 3b was preserved. The sensory symptoms observed in this patient were compatible with the hierarchical somatosensory processing model in the postcentral gyrus proposed by Iwamura et al, in which the elementary sensation recognized in area 3 is transferred to areas 1 and 2, and then processed to discriminative sensation. The disturbed discrete finger movement in this patient probably resulted from impaired tactile recognition which could be compensated for by visual information.     

Sensory deficits of a nerve root lesion can be objectively documented by somatosensory evoked potentials elicited by painful infrared laser stimulations: a case study.

Somatosensory evoked potentials (SEPs) in response to painful laser stimuli were measured in a patient with a unilateral sensory deficit due to radiculopathy at cervical levels C7 and C8. Laser evoked potentials (LEPs) were compared with SEPs using standard electrical stimulation of median and ulnar nerves at the wrist and mechanical stimulation of the fingertips by means of a mechanical stimulator. Early and late ulnar and median nerve SEPs were normal. Mechanical stimulation resulted in w shaped early SEPs from all five fingertips with some degree of abnormality at the fourth and fifth digits of the affected hand. Late LEPs were completely absent for stimulations at affected dermatomes and normal in the unaffected control dermatomes. The border between skin areas with normal or absent LEPs was very sharp and fitted the dermatomes of intact C6 and damaged C7 and C8 nerve roots. It is suggested that pain dermatomes are narrower than tactile dermatomes because thin fibres of the nociceptive system, activated by laser stimuli, probably do not overlap between adjacent spinal segments to the same extent as thick fibres of the mechanoreceptive system, activated by standard electrical or mechanical stimulation.     

Eye movements and the perceived location of phosphenes generated by intracranial primary visual cortex stimulation in the blind

BackgroundRestoring sight for the blind using electrical stimulation of the visual pathways is feasible but demands an understanding of the spatial mapping of the visual world at the site of targeted stimulation, whether in the retina, thalamus, or cortex. While a visual cortex stimulator can bypass the eye and create visual percepts, there is an inherent dissociation between this stimulation and eye movements. It is unknown whether and how robustly the brain maintains the oculomotor circuitry in patients with bare- or no-light perception.ObjectiveTo critically and quantitatively evaluate the effect of eye movements have on phosphene locations elicited by cortical stimulation that bypasses the eyes in order to restore sight in blind subjects.MethodsThe NeuroPace Responsive Neurostimulator (RNS) and the Orion visual cortical prosthesis devices were used to electrically stimulate the visual cortex of blind subjects with bare or no light perception. Eye positions were recorded synchronized with stimulation and the location of the percepts were measured using a handheld marker.ResultsThe locations of cortical stimulation-evoked percepts are shifted based on the eye position at the time of stimulation. Measured responses can be remapped based on measured eye positions to determine the retinotopic locations associated with the implanted electrodes, with remapped responses having variance limited by pointing error.ConclusionsEye movements dominate the perceived location of cortical stimulation-evoked phosphenes, even after years of blindness. By accounting for eye positions, we can mimic retinal mapping as in natural sight.     

Lumbosacral evoked potentials (LSEPs) and cortical somatosensory evoked potentials (SEPs) in patients with lesions of the conus medullaris and cauda equina

Evoked potentials from unilateral stimulation of the posterior tibial nerve at the knee were recorded over the spinous processes S1, L4, L2, T12 and from the 'lower extremity' portion of the sensory cortex (Cz) in 29 patients who exhibited clinical and electromyographic signs of conus medullaris or cauda equina lesions. Simultaneous recording of the lumbosacral evoked potentials (LSEPs) and cortical somatosensory evoked potentials (SEPs) permitted evaluation of the relative effectiveness of the peripheral stimulus in eliciting responses in the lumbosacral segments of the spinal cord and in the cortex of the brain. In patients with cauda equina lesion, each major component of LSEP can be absent or the peak can have a reduced amplitude and a prolonged latency. The degree of impairment of the LSEP runs in parallel to the degree of severeness of the cauda equina lesion. The recording of LSEP responses with surface electrodes represents a reliable test for the detection of mild cauda equina abnormalities, but the surface recording technique is not sensitive enough to differentiate between severe incomplete and severe complete cauda equina lesions. On the other hand, concurrent recording of responses evoked at lumbosacral and cortical levels by the same stimuli did detect instances in which the first-order afferents were capable of delivering an adequate volley of impulses to evoke a sizeable cortical response without evidence of an associated postsynaptic response in the spinal cord. Such findings are good evidence of a problem localized in the gray matter of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic Validity of Sensory Over-Responsivity: A Review of the Literature and Case Reports

Atypical responses to sensory stimulation are frequently reported to co-occur with diagnoses such as autism, ADHD, and Fragile-X syndrome. It has also been suggested that children and adults may present with atypical sensory responses while failing to meet the criteria for other medical or psychological diagnoses. This may be particularly true for individuals with over-responsivity to sensation. This article reviews the literature related to sensory over-responsivity and presents three pediatric cases that present a profile of having sensory over-responsivity without a co-occurring diagnosis. Findings from these cases provide very preliminary evidence to support the suggestion that sensory over-responsivity can occur as a sole diagnosis. Within this small group, tactile over-responsivity was the most common and pervasive form of this condition.