Andreas Weibull

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.

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.

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.

Investigation of spatial resolution, partial volume effects and smoothing in functional MRI using artificial 3D time series

This work addresses the balance between temporal signal-to-noise ratio (tSNR) and partial volume effects (PVE) in functional magnetic resonance imaging (fMRI) and investigates the impact of the choice of spatial resolution and smoothing. In fMRI, since physiological time courses are monitored, tSNR is of greater importance than image SNR. Improving SNR by an increase in voxel volume may be of negligible benefit when physiological fluctuations dominate the noise. Furthermore, at large voxel volumes, PVE are more pronounced, leading to an overall loss in performance. Artificial fMRI time series, based on high-resolution anatomical data, were used to simulate BOLD activation in a controlled manner. The performance was subsequently quantified as a measure of how well the resulted activation matched the simulated activation. The performance was highly dependent on the spatial resolution. At high contrast-to-noise ratio (CNR), the optimal voxel volume was small, i.e. in the region of 2(3) mm(3). It was also shown that using a substantially larger voxel volume in this case could potentially negate the CNR benefits. The optimal smoothing kernel width was dependent on the CNR, being larger at poor CNR. At CNR >1, little or no smoothing proved advantageous. The use of artificial time series gave an opportunity to quantitatively investigate the effects of partial volume and smoothing in single subject fMRI. It was shown that a proper choice of spatial resolution and smoothing kernel width is important for fMRI performance.

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

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.

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.

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 patients 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.

Analysis of brain and muscle activity during low-level tooth clenching – a feasibility study with a novel biting device

In electromyographic (EMG) and functional magnetic resonance imaging (fMRI) studies, muscle and brain activity was compared during low levels of tooth clenching using a novel biting device to control bite force. A total of 21 healthy subjects performed motor tasks, comprising tooth clenching at 5, 10 and 20 N. During all measurements, subjects kept the novel bite device between the anterior teeth during tooth clenching. The EMG study (n = 15) characterised jaw muscle activity for the three motor tasks and demonstrated significant differences in root mean square (RMS) EMG amplitude between 5-, 10- and 20-N tooth clenching (F = 46.21, P < 0.001). There were no differences in variability of muscle activity between the three tooth-clenching levels. In an fMRI pilot study (n = 6), statistical comparisons were used to identify brain regions with significant activation in the subtraction of baseline from 5- or 20-N tooth-clenching activity. 5- and 20-N tooth clenching significantly and bilaterally activated the sensorimotor cortex, supplementary motor area, cerebellum and basal ganglia (P < 0.05, corrected for multiple comparisons). However, activation of each brain region did not differ significantly between two tooth-clenching tasks. Based on these preliminary findings, we propose that the novel biting device may be useful in further fMRI studies on controlled jaw muscle activation patterns in different craniofacial pain conditions. In addition, our fMRI result suggests that there are no significant differences in brain activity within low levels of tooth clenching with controlled force.

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.

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

Abstract 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.