Preserved somatosensory conduction in complete spinal cord injury: Discomplete SCI.

OBJECTIVE: Spinal cord injury (SCI) disrupts the communication between brain and body parts innervated from below-injury spinal segments, but rarely results in complete anatomical transection of the spinal cord. The aim of this study was to investigate residual somatosensory conduction in clinically complete SCI, to corroborate the concept of sensory discomplete SCI. METHODS: We used fMRI with a somatosensory protocol in which blinded and randomized tactile and nociceptive stimulation was applied on both legs (below-injury level) and one arm (above-injury level) in eleven participants with chronic complete SCI. The experimental design accounts for possible confounding mechanical (e.g. vibration) and cortico-cortical top-down mechanisms (e.g. attention/expectation). RESULTS: Somatosensory stimulation on below-level insensate body regions activated the somatotopically corresponding part of the contralateral primary somatosensory cortex in six out of eleven participants. CONCLUSIONS: Our results represent afferent-driven cortical activation through preserved somatosensory connections to the brain in a subgroup of participants with clinically complete SCI, i.e. sensory discomplete SCI. SIGNIFICANCE: Identifying patients with residual somatosensory connections might open the door for new rehabilitative and restorative strategies as well as inform research on SCI-related conditions such as neuropathic pain and spasticity.

Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor.

Essential tremor is effectively treated with deep brain stimulation (DBS), but the neural mechanisms underlying the treatment effect are poorly understood. Essential tremor is driven by a dysfunctional cerebello-thalamo-cerebral circuit resulting in pathological tremor oscillations. DBS is hypothesised to interfere with these oscillations at the stimulated target level, but it is unknown whether the stimulation modulates the activity of the cerebello-thalamo-cerebral circuit during different task states (with and without tremor) in awake essential tremor patients. To address this issue, we used functional MRI in 16 essential tremor patients chronically implanted with DBS in the caudal zona incerta. During scanning, the patients performed unilateral tremor-inducing postural holding and pointing tasks as well as rest, with contralateral stimulation turned On and Off. We show that DBS exerts both task-dependent as well as task-independent modulation of the sensorimotor cerebello-cerebral regions (p â€‹≤ â€‹0.05, FWE cluster-corrected for multiple comparisons). Task-dependent modulation (DBS â€‹× â€‹task interaction) resulted in two patterns of stimulation effects. Firstly, activity decreases (blood oxygen level-dependent signal) during tremor-inducing postural holding in the primary sensorimotor cortex and cerebellar lobule VIII, and activity increases in the supplementary motor area and cerebellar lobule V during rest (p â€‹≤ â€‹0.05, post hoc two-tailed t-test). These effects represent differences at the effector level and may reflect DBS-induced tremor reduction since the primary sensorimotor cortex, cerebellum and supplementary motor area exhibit less motor task-activity as compared to the resting condition during On stimulation. Secondly, task-independent modulation (main effect of DBS) was observed as activity increase in the lateral premotor cortex during all motor tasks, and also during rest (p â€‹≤ â€‹0.05, post hoc two-tailed t-test). This task-independent effect may mediate the therapeutic effects of DBS through the facilitation of the premotor control over the sensorimotor circuit, making it less susceptible to tremor entrainment. Our findings support the notion that DBS in essential tremor is modulating the sensorimotor cerebello-cerebral circuit, distant to the stimulated target, and illustrate the complexity of stimulation mechanisms by demonstrating task-dependent as well as task-independent actions in cerebello-cerebral regions.

Predicting incident falls: Relationship between postural sway and limits of stability in older adults.

BACKGROUND: We have previously shown that objective measurements of postural sway predicts fall risk, although it is currently unknown how limits of stability (LOS) might influence these results. RESEARCH QUESTION: How integrated postural sway and LOS measurements predict the risk of incident falls in a population-based sample of older adults. METHODS: The sample for this prospective observational study was drawn from the Healthy Ageing Initiative cohort and included data collected between June 2012 and December 2016 for 2396 men and women, all 70 years of age. LOS was compared to postural sway with measurements during eyes-open (EO) and eyes-closed (EC) trials, using the previously validated Wii Force Plate. Fall history was assessed during baseline examination and incident falls were collected during follow-up at 6 and 12 months. Independent predictors of incident falls and additional covariates were investigated using multiple logistic regression models. RESULTS: During follow-up, 337 out of 2396 participants (14%) had experienced a fall. Unadjusted regression models from the EO trial revealed increased fall risk by 6% (OR 1.06, 95% CI 1.02-1.11) per each centimeter squared increase in sway area and by 16% (OR 1.16, 95% CI 1.07-1.25) per 1-unit increase in Sway-Area-to-LOS ratio. Odds ratios were generally lower when analyzing EC trials and only slightly attenuated in fully adjusted models. SIGNIFICANCE: Integrating postural sway and LOS parameters provides valid fall risk prediction and a holistic analysis of postural stability. Future work should establish normative values and evaluate clinical utility of these measures.

Increased postural sway during quiet stance as a risk factor for prospective falls in community-dwelling elderly individuals.

Objective: fall-related injuries constitute major health risks in older individuals, and these risks are projected to increase in parallel with increasing human longevity. Impaired postural stability is a potential risk factor related to falls, although the evidence is inconclusive, partly due to the lack of prospective studies. This study aimed to investigate how objective measures of postural sway predict incident falls. Design, setting and participants: this prospectively observational study included 1,877 community-dwelling individuals aged 70 years who participated in the Healthy Ageing Initiative between June 2012 and December 2015. Measurements: postural sway was measured during eyes-open (EO) and eyes-closed (EC) trials using the Wii Balance Board. Functional mobility, muscle strength, objective physical activity and cognitive performance were also measured. Participants reported incident falls 6 and 12 months after the examination. Results: during follow-up, 255 (14%) prospective fallers were identified. Division of centre of pressure (COP) sway lengths into quintiles revealed a nonlinear distribution of falls for EO trial data, but not EC trial data. After adjustment for multiple confounders, fall risk was increased by 75% for participants with COP sway lengths ≥400 mm during the EO trial (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.09-2.79), and approximately doubled for sway lengths ≥920 mm during the EC trial (OR 1.90, 95% CI 1.12-3.22). Conclusion: objective measures of postural sway independently predict incident falls in older community-dwelling men and women. Further studies are needed to evaluate whether postural sway length is of interest for the prediction of incident falls in clinical settings.

Preserved somatosensory conduction in a patient with complete cervical spinal cord injury.

OBJECTIVE: Neurophysiological investigation has shown that patients with clinically complete spinal cord injury can have residual motor sparing ("motor discomplete"). In the current study somatosensory conduction was assessed in a patient with clinically complete spinal cord injury and a novel methodology for assessing such preservation is described, in this case indicating "sensory discomplete" spinal cord injury. METHODS: Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine the somatosensory system in a healthy subject and in a subject with a clinically complete cervical spinal cord injury, by applying tactile stimulation above and below the level of spinal cord injury, with and without visual feedback. RESULTS: In the participant with spinal cord injury, somatosensory stimulation below the neurological level of the lesion gave rise to BOLD signal changes in the corresponding areas of the somatosensory cortex. Visual feedback of the stimulation strongly modulated the somatosensory BOLD signal, implying that cortico-cortical rather than spino-cortical connections can drive activity in the somatosensory cortex. Critically, BOLD signal change was also evident when the visual feedback of the stimulation was removed, thus demonstrating sensory discomplete spinal cord injury. CONCLUSION: Given the existence of sensory discomplete spinal cord injury, preserved but hitherto undetected somatosensory conduction might contribute to the unexplained variability related to, for example, the propensity to develop decubitus ulcers and neuropathic pain among patients with clinically complete spinal cord injury.

Pleasant human touch is represented in pregenual anterior cingulate cortex.

Touch massage (TM) is a form of pleasant touch stimulation used as treatment in clinical settings and found to improve well-being and decrease anxiety, stress, and pain. Emotional responses reported during and after TM have been studied, but the underlying mechanisms are still largely unexplored. In this study, we used functional magnetic resonance (fMRI) to test the hypothesis that the combination of human touch (i.e. skin-to-skin contact) with movement is eliciting a specific response in brain areas coding for pleasant sensations. The design included four different touch conditions; human touch with or without movement and rubber glove with or without movement. Force (2.5 N) and velocity (1.5 cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale) and human touch was rated as most pleasant, particularly in combination with movement. The fMRI results revealed that TM stimulation most strongly activated the pregenual anterior cingulate cortex (pgACC). These results are consistent with findings showing pgACC activation during various rewarding pleasant stimulations. This area is also known to be activated by both opioid analgesia and placebo. Together with these prior results, our finding furthers the understanding of the basis for positive TM treatment effects.

Slowly adapting mechanoreceptors in the borders of the human fingernail encode fingertip forces.

There are clusters of slowly adapting (SA) mechanoreceptors in the skin folds bordering the nail. These "SA-IInail" afferents, which constitute nearly one fifth of the tactile afferents innervating the fingertip, possess the general discharge characteristics of slowly adapting type II (SA-II) tactile afferents located elsewhere in the glabrous skin of the human hand. Little is known about the signals in the SA-IInail afferents when the fingertips interact with objects. Here we show that SA-IInail afferents reliably respond to fingertip forces comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to the finger pad while recording impulse activity in 17 SA-IInail afferents. Ramp-and-hold forces (amplitude 4 N, rate 10 N/s) were applied normal to the skin, and at 10, 20, or 30 degrees from the normal in eight radial directions with reference to the primary site of contact (25 force directions in total). All afferents responded to the force stimuli, and the responsiveness of all but one afferents was broadly tuned to a preferred direction of force. The preferred directions among afferents were distributed all around the angular space, suggesting that the population of SA-IInail afferents could encode force direction. We conclude that signals in the population of SA-IInail afferents terminating in the nail walls contain vectorial information about fingertip forces. The particular tactile features of contacted surfaces would less influence force-related signals in SA-IInail afferents than force-related signals present in afferents terminating in the volar skin areas that directly contact objects.

How a lateralized brain supports symmetrical bimanual tasks.

A large repertoire of natural object manipulation tasks require precisely coupled symmetrical opposing forces by both hands on a single object. We asked how the lateralized brain handles this basic problem of spatial and temporal coordination. We show that the brain consistently appoints one of the hands as prime actor while the other assists, but the choice of acting hand is flexible. When study participants control a cursor by manipulating a tool held freely between the hands, the left hand becomes prime actor if the cursor moves directionally with the left-hand forces, whereas the right hand primarily acts if it moves with the opposing right-hand forces. In neurophysiological (electromyography, transcranial magnetic brain stimulation) and functional magnetic resonance brain imaging experiments we demonstrate that changes in hand assignment parallels a midline shift of lateralized activity in distal hand muscles, corticospinal pathways, and primary sensorimotor and cerebellar cortical areas. We conclude that the two hands can readily exchange roles as dominant actor in bimanual tasks. Spatial relationships between hand forces and goal motions determine hand assignments rather than habitual handedness. Finally, flexible role assignment of the hands is manifest at multiple levels of the motor system, from cortical regions all the way down to particular muscles.

Functional neuroimaging studies of human somatosensory cortex.

Two studies were carried out to assess the applicability of echoplanar fMRI at 3.0 T to the analysis of somatosensory mechanisms in humans. Vibrotactile stimulation of the tips of digits two and five reliably generated significant clusters of activation in primary (SI) and secondary (SII) somatosensory cortex, area 43, the pre-central gyrus, posterior insula, posterior parietal cortex and posterior cingulate. Separation of these responses by digit in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study employed microneurographic techniques in which individual median-nerve mechanoreceptive afferents were isolated, physiologically characterized, and microstimulated in conjunction with fMRI. Hemodynamic responses, observed in every case, were robust, focal, and physiologically orderly. These techniques will enable more detailed studies of the representation of the body surface in human somatosensory cortex, the relationship of that organization to short-term plasticity in responses to natural tactile stimuli, and effects of stimulus patterning and unimodal/cross-modal attentional manipulations. They also present unique opportunities to investigate the basic physiology of the BOLD effect, and to optimize the operating characteristics of two important human functional neuroimaging modalities-high-field fMRI and high-resolution EEG-in an unusually specific and well-characterized neurophysiological setting.