Loss of inhibition in ipsilateral somatosensory areas following altered afferent nerve signaling from the hand.

Cutaneous stimulation of the hand results in increased neural activity in the contralateral primary somatosensory cortex (S1) in humans, whereas an inhibition of neurons is seen in the ipsilateral S1. The aim of this study was to assess changes in neural activity in the S1 bilaterally, with a focus on the ipsilateral hemisphere, following altered afferent nerve signaling from the hand. Three cohorts, all with altered afferent nerve signaling from the hand, participated in the study. There were: 18 patients with traumatic median nerve injury, 10 patients with vibration induced neuropathy and 11 healthy subjects who had their dominant hand and wrist immobilized for 72 h. In addition, 36 healthy subjects were included as controls. Each subject was examined using functional magnetic resonance imaging at 3 T. All three study cohorts showed enlarged activation in the contralateral S1 during tactile stimulation compared to healthy controls. Moreover, inhibition of the ipsilateral S1 was significantly decreased or completely lost. Thus, somatosensory areas of both hemispheres respond to changed afferent nerve signaling from the hand. The loss of inhibition of neurons in the ipsilateral S1 suggests an important role of the ipsilateral hemisphere in the cerebral adaptation following a change in afferent nerve signaling.

Cerebral Reorganization in Patients with Brachial Plexus Birth Injury and Residual Shoulder Problems.

The functional outcome after a brachial plexus birth injury (BPBI) is based on changes in the peripheral nerve and in the central nervous system. Most patients with a BPBI recover, but residual deficits in shoulder function are not uncommon. The aim of this study was to determine cerebral activation patterns in patients with BPBI and also residual symptoms from the shoulder. In seven patients (six females and one male, aged 17-23 years) with a BPBI and residual shoulder problems (Mallet score IV or lower), the cerebral response to active movement of the shoulder and elbow of the injured and healthy arm was monitored using functional magnetic resonance imaging at 3 T. Movements, i.e., shoulder rotation or elbow flexion and extension, of the injured side resulted in a more pronounced and more extended activation of the contralateral primary sensorimotor cortex compared to the activation seen after moving the healthy shoulder and elbow. In addition, moving the shoulder or elbow on the injured side resulted in increased activation in ipsilateral primary sensorimotor areas an also increased activation in associated sensorimotor areas, in both hemispheres, located further posterior in the parietal lobe, which are known to be important for integration of motor tasks and spatial aspects of motor control. Thus, in this preliminary study based on a small cohort, patients with BPBI and residual shoulder problems show reorganization in sensorimotor areas in both hemispheres of the brain. The increased activation in ipsilateral sensorimotor areas and in areas that deal with both integration of motor tasks and spatial aspects of motor control in both hemispheres indicates altered dynamics between the hemispheres, which may be a cerebral compensation for the injury.

Normalized activation in the somatosensory cortex 30 years following nerve repair in children: an fMRI study.

The clinical outcome following a peripheral nerve injury in the upper extremity is generally better in young children than in teenagers and in adults, but the mechanism behind this difference is unknown. In 28 patients with a complete median nerve injury sustained at the ages of 1-13 years (n = 13) and 14-20 years (n = 15), the cortical activation during tactile finger stimulation of the injured and healthy hands was monitored at a median time since injury of 28 years using functional magnetic resonance imaging (fMRI) at 3 Tesla. The results from the fMRI were compared with the clinical outcome and electroneurography. The cortical activation pattern following sensory stimulation of the median nerve-innervated fingers was dependent on the patient's age at injury. Those injured at a young age (1-13 years) had an activation pattern similar to that of healthy controls. Furthermore, they showed a clinical outcome significantly superior (P = 0.001) to the outcome in subjects injured at a later age; however, electroneurographical parameters did not differ between the groups. In subjects injured at age 14-20 years, a more extended activation of the contralateral hemisphere was seen in general. Interestingly, these patients also displayed changes in the ipsilateral hemisphere where a reduced inhibition of somatosensory areas was seen. This loss of ipsilateral inhibition correlated to increasing age at injury as well as to poor recovery of sensory functions in the hand. In conclusion, cerebral changes in both brain hemispheres may explain differences in clinical outcome following a median nerve injury in childhood or adolescence.

Phantom digit somatotopy: a functional magnetic resonance imaging study in forearm amputees.

Forearm amputees often experience non-painful sensations in their phantom when the amputation stump is touched. Cutaneous stimulation of specific stump areas may be perceived as stimulation of specific phantom fingers (stump hand map). The neuronal basis of referred phantom limb sensations is unknown. We used functional magnetic resonance imaging to demonstrate a somatotopic map of the phantom fingers in the hand region of the primary somatosensory cortex after tactile stump stimulation. The location and extent of phantom finger activation in the primary somatosensory cortex corresponded well to the location of normal fingers in a reference population. Stimulation of the stump hand map resulted in an increased bilateral activation of the primary somatosensory cortex compared with stimulation of forearm regions outside the stump hand map. Increased activation was also seen in contralateral posterior parietal cortex and premotor cortex. Ipsilateral primary somatosensory cortex activation might represent a compensatory mechanism and activation of the non-primary fronto-parietal areas might correspond to awareness of the phantom limb, which is enhanced when experiencing the referred sensations. It is concluded that phantom sensation elicited by stimulation of stump hand map areas is associated with activation of finger-specific somatotopical representations in the primary somatosensory cortex. This suggests that the primary somatosensory cortex could be a neural substrate of non-painful phantom sensations. The stump hand map phenomenon might be useful in the development of prosthetic hand devices.

Cerebral changes after injury to the median nerve: a long-term follow up.

Injury to the peripheral nerves in the upper extremity results in changes in the nerve, and at multiple sites throughout the central nervous system (CNS). We studied the long-term effects of an injury to the median nerve in the forearm with a focus on changes in the CNS. Four patients with isolated injuries of the median nerve in their 20s were examined a mean of 14 years after the injury. Cortical activation was monitored during tactile stimulation of the fingers of the injured and healthy hand using functional magnetic resonance imaging at 3 Tesla. The neurophysiological state and clinical outcome were also examined. Activation in the primary somatosensory cortex was substantially larger during tactile stimulation of the injured hand than with stimulation of the uninjured hand. We also saw a redistribution of hemispheric dominance. Stimulation of the injured median nerve resulted in a substantially increased dominance of the contralateral hemisphere. However, stimulation of the healthy ulnar nerve resulted in a decreased dominance of the contralateral hemisphere. Neurophysiology showed low sensory amplitudes, velocity, and increased motor latency in the injured nerve. Clinically there were abnormalities predominately in the sensory domain. However, there was an overall improved mean result compared with a five year follow-up in the same subjects. The cortical changes could be the result of cortical reorganisation after a changed afferent signal pattern from the injured nerve. Even though the clinical function improved over time it did not return to normal, and neither did the cortical response.

Can resting-state functional MRI serve as a complement to task-based mapping of sensorimotor function? A test-retest reliability study in healthy volunteers.

PURPOSE: To investigate if resting-state functional MRI (fMRI) reliably can serve as a complement to task-based fMRI for presurgical mapping of the sensorimotor cortex. MATERIALS AND METHODS: Functional data were obtained in 10 healthy volunteers using a 3 Tesla MRI system. Each subject performed five bilateral finger tapping experiments interleaved with five resting-state experiments. Following preprocessing, data from eight volunteers were further analyzed with the general linear model (finger tapping data) and independent component analysis (rest data). Test-retest reliability estimates (hit rate and false alarm rate) for resting-state fMRI activation of the sensorimotor network were compared with the reliability estimates for task-evoked activation of the sensorimotor cortex. The reliability estimates constituted a receiver operating characteristics curve from which the area under the curve (AUC) was calculated. Statistical testing was performed to compare the two groups with respect to reliability. RESULTS: The AUC was generally higher for the task experiments, although median AUC was not significantly different on a group level. Also, the two groups showed comparable levels of within-group variance. CONCLUSION: Test-retest reliability was comparable between resting-state measurements and task-based fMRI, suggesting that presurgical mapping of functional networks can be a supplement to task-based fMRI in cases where patient status excludes task-based fMRI.

Cerebral and clinical effects of short-term hand immobilisation.

In this work, functional changes in the sensorimotor cortex following unilateral hand immobilisation were investigated in 11 healthy volunteers. Sensory and motor function of both hands was also assessed. Cortical activation was monitored with functional magnetic resonance imaging at 3 T. All examinations were performed prior to and directly after 72 h of immobilisation of the dominant hand and wrist. Following unilateral immobilisation, cortical activation increased substantially during tactile stimulation of the non-immobilised hand. This was particularly evident in the ipsilateral somatosensory cortex. Additionally, a redistribution of hemispheric dominance towards zero lateralisation was seen. A bilateral cortical activation increase was also seen during performance of a finger-tapping task by the non-immobilised hand, although this increase was less prominent than during tactile stimulation. In contrast, performance of the finger-tapping task with the immobilised hand resulted in an activation decrease, predominantly in the ipsilateral sensorimotor cortex. This site was anatomically close to the regional activation increase of the non-immobilised hand. These functional changes were associated with reduced grip strength, dexterity and tactile discrimination of the immobilised hand, and simultaneously improved tactile discrimination of the non-immobilised hand. This suggests that brain adaptation following hand immobilisation includes inter-hemispheric dynamics. In summary, the improved sensory function of the non-immobilised hand following unilateral immobilisation is associated with cortical expansion, predominantly contralateral to the immobilised hand, and a redistribution of hemispheric dominance. Both cortical and clinical effects of immobilisation were identified after 72 h, suggesting rapid inter-hemispheric plasticity using existing neural substrates.

Cortical changes in dental technicians exposed to vibrating tools.

To study the cortical reorganization after long time exposure to hand-held vibrating tools, we investigated 10 dental technicians with sensory neuropathy after long time exposure to vibrating tools and 10 controls for cortical changes using functional magnetic resonance imaging at 3 T. The activated volumes corresponding to individual fingers in the hand area of S1 were significantly larger in the neuropathy group than in controls. Activation in the primary motor cortex did not differ significantly from controls. These changes are likely the result of cortical reorganization following long-term non-physiological sensory input and they can partly explain the symptoms seen in vibration-induced neuropathy.

Rapid cortical reorganisation and improved sensitivity of the hand following cutaneous anaesthesia of the forearm.

The cortical representation of various body parts constantly changes based on the pattern of afferent nerve impulses. As peripheral nerve injury results in a cortical and subcortical reorganisation this has been suggested as one explanation for the poor clinical outcome seen after peripheral nerve repair in humans. Cutaneous anaesthesia of the forearm in healthy subjects and in patients with nerve injuries results in rapid improvement of hand sensitivity. The mechanism behind the improvement is probably based on a rapid cortical and subcortical reorganisation. The aim of this work was to study cortical changes following temporary cutaneous forearm anaesthesia. Ten healthy volunteers participated in the study. Twenty grams of a local anaesthetic cream (EMLA) was applied to the volar aspect of the right forearm. Functional magnetic resonance imaging was performed during sensory stimulation of all fingers of the right hand before and during cutaneous forearm anaesthesia. Sensitivity was also clinically assessed before and during forearm anaesthesia. A group analysis of functional magnetic resonance image data showed that, during anaesthesia, the hand area in the contralateral primary somatosensory cortex expanded cranially over the anaesthetised forearm area. Clinically right hand sensitivity in the volunteers improved during forearm anaesthesia. No significant changes were seen in the left hand. The clinically improved hand sensitivity following forearm anaesthesia is probably based on a rapid expansion of the hand area in the primary somatosensory cortex which presumably results in more nerve cells being made available for the hand in the primary somatosensory cortex.

Improved sensibility of the foot after temporary cutaneous anesthesia of the lower leg.

Cutaneous anesthesia (EMLA_cream) of the forearm results in rapid improvement of hand sensibility, and here we applied this concept in the lower extremity. This double-blind study with 40 volunteers randomized to cutaneous application of anesthetic cream to the lower leg showed a significant improvement 2 h after treatment in touch thresholds in the EMLA group as compared with the placebo group. In 12 volunteers, fMRI examination was performed before and after treatment. Improvement was not associated with a visible cortical expansion of the cortical foot area. This novel finding may have considerable therapeutic potential in the treatment of foot sensibility disturbances in various neuropathies, such as diabetic neuropathy.

Optimizing the mapping of finger areas in primary somatosensory cortex using functional MRI.

Functional magnetic resonance imaging mapping of the finger somatotopy in the primary somatosensory cortex requires a reproducible and precise stimulation. The highly detailed functional architecture in this region of the brain also requires careful consideration in choice of spatial resolution and postprocessing parameters. The purpose of this study is therefore to investigate the impact of spatial resolution and level of smoothing during tactile stimulation using a precise stimuli system. Twenty-one volunteers were scanned using 2(3) mm(3) and 3(3) mm(3) voxel volume and subsequently evaluated using three different smoothing kernel widths. The overall activation reproducibility was also evaluated. Using a high spatial resolution proved advantageous for all fingers. At 2(3) mm(3) voxel volume, activation of the thumb, middle finger and little finger areas was seen in 89%, 67% and 50% of the volunteers, compared to 78%, 61% and 33% at 3(3) mm(3), respectively. The sensitivity was comparable for nonsmoothed and slightly smoothed (4 mm kernel width) data; however, increasing the smoothing kernel width from 4 to 8 mm resulted in a critical decrease ( approximately 50%) in sensitivity. In repeated measurements of the same subject at six different days, the localization reproducibility of all fingers was within 4 mm (1 S.D. of the mean). The precise computer-controlled stimulus, together with data acquisition at high spatial resolution and with only minor smoothing during evaluation, could be a very useful strategy in studies of brain plasticity and rehabilitation strategies in hand and finger disorders and injuries.