Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation

Neuroprosthetics research in amputee patients aims at developing new prostheses that move and feel like real limbs. Targeted muscle and sensory reinnervation (TMSR) is such an approach and consists of rerouting motor and sensory nerves from the residual limb towards intact muscles and skin regions. Movement of the myoelectric prosthesis is enabled via decoded electromyography activity from reinnervated muscles and touch sensation on the missing limb is enabled by stimulation of the reinnervated skin areas. Here we ask whether and how motor control and redirected somatosensory stimulation provided via TMSR affected the maps of the upper limb in primary motor (M1) and primary somatosensory (S1) cortex, as well as their functional connections. To this aim, we tested three TMSR patients and investigated the extent, strength, and topographical organization of the missing limb and several control body regions in M1 and S1 at ultra high-field (7 T) functional magnetic resonance imaging. Additionally, we analysed the functional connectivity between M1 and S1 and of both these regions with fronto-parietal regions, known to be important for multisensory upper limb processing. These data were compared with those of control amputee patients (n = 6) and healthy controls (n = 12). We found that M1 maps of the amputated limb in TMSR patients were similar in terms of extent, strength, and topography to healthy controls and different from non-TMSR patients. S1 maps of TMSR patients were also more similar to normal conditions in terms of topographical organization and extent, as compared to non-targeted muscle and sensory reinnervation patients, but weaker in activation strength compared to healthy controls. Functional connectivity in TMSR patients between upper limb maps in M1 and S1 was comparable with healthy controls, while being reduced in non-TMSR patients. However, connectivity was reduced between S1 and fronto-parietal regions, in both the TMSR and non-TMSR patients with respect to healthy controls. This was associated with the absence of a well-established multisensory effect (visual enhancement of touch) in TMSR patients. Collectively, these results show how M1 and S1 process signals related to movement and touch are enabled by targeted muscle and sensory reinnervation. Moreover, they suggest that TMSR may counteract maladaptive cortical plasticity typically found after limb loss, in M1, partially in S1, and in their mutual connectivity. The lack of multisensory interaction in the present data suggests that further engineering advances are necessary (e.g. the integration of somatosensory feedback into current prostheses) to enable prostheses that move and feel as real limbs.

Multiscale body maps in the human brain

Michel Akselrod

A large number of brain regions are dedicated to processing information from the body in order to enable interactions with the environment. During my thesis, I studied the functional organization of brain networks involved in processing bodily information. From the processing of unimodal low-level features to the unique experience of being a unified entity residing in a physical body, the brain processes and integrates bodily information at many different stages. Using ultra high-field functional Magnetic Resonance Imaging (fMRI), I conducted four studies to map and characterize multiscale body representations in the human brain. The goals of my thesis were first to extend the actual knowledge about primary sensorimotor representations, and second to develop novel approaches to investigate more complex and integrated forms of body representations. In studies I and II, I first investigated how natural touch was represented in the three first cortical areas processing tactile information. I applied a mapping procedure to identify in each of these three areas the somatosensory representations of 24 different body parts on hands, feet and legs at the level of single subjects. Using fMRI and resting-state data, I combined classical statistical analyses with modern methods of network analysis to describe the functional properties of the formed network. In study III, I applied these methods to investigate primary somatosensory and motor representations in a rare population of patients. Following limb loss, the targeted muscle and sensory reinnervation (TMSR) procedure enables the intuitive control of a myoelectric prosthesis and creates an artificial map of referred touch on the reinnervated skin. I mapped the primary somatosensory and motor representations of phantom sensations and phantom movements in TMSR patients. I investigated whether sensorimotor training enabled via TMSR was associated with preserved somatosensory and motor representations compared to healthy controls and amputee patients without TMSR. Finally in study IV, I studied brain regions involved in the subjective body experience. Following specific manipulations of sensorimotor information, it is possible to let participants experience a fake or virtual hand as their own and to give them the sensation of being in control of this hand. Using MR-compatible robotics and virtual reality, I investigated the brain regions associated with the alteration of the sense of hand ownership and the sense of hand agency. The present work provides important findings and promising tools regarding the understanding of brain networks processing bodily information. In particular, understanding the functional interactions between primary unimodal cortices and networks contributing to subjective body experience is a necessity to promote modern approaches in the fields of neuroprosthetic and human-machine interactions.

EPFL2017

Anatomical and functional properties of the foot and leg representation in areas 3b, 1 and 2 of primary somatosensory cortex in humans: A 7T fMRI study

Michel Akselrod, Olaf Blanke, Roger Gassert, Roberto Martuzzi, Andrea Serino, Wietske Van der Zwaag

Primary somatosensory cortex (S1) processes somatosensory information and is composed of multiple subregions. In particular, tactile information from the skin is encoded in three subregions, namely Brodmann areas (BAs) 3b, 1 and 2, with each area representing a complete map of the contralateral body. Although, much is known about the somatotopic organization of the hand in human S1, less research has been carried out regarding the somatotopic maps of the foot and leg in S1. Moreover, a latero-medial S1 organization along the superior part of the postcentral gyrus has been reported when moving from hip to toes, yet to date there is no study investigating leg/foot maps within the different subregions of S1. Using ultra-high field MRI (7T), we mapped six cortical representations of the lower limb (hip to toes) at the single subject level and performed this analysis separately for BAs 3b, 1 and 2. Analyzing the BOLD responses associated with tactile stimulations of the mapped foot and leg regions on each side, we quantified the extent and the strength of activation to determine somatotopic organization. In addition, we investigated whether each mapped representation also responded to the stimulation of other body parts (i.e. response selectivity) and conducted dissimilarity analysis relating these anatomical and functional properties of S1 to the physical structure of the lower limbs. Our data reveal somatotopy for the leg, but not for the foot in all investigated BAs, with large inter-subject variability. We found only minor differences between the properties of the three investigated BAs, suggesting that S1 maps for the lower limbs differ from those described for the hand. We also describe greater extent/strength of S1 activation for the big toe representation (compared to the other mapped representations) within all BAs, suggesting a possible homology between the first digit of upper and lower extremity in humans, and report different patterns of selectivity in the foot representations (i.e. lower selectivity) compared to the other leg representations (i.e. greater selectivity). These data provide a detailed description of human S1 subregions for the foot and leg, highlight the importance of high-resolution mapping studies and of single subject analysis, and indicate potential differences between the lower and the upper limb.

2017

Parallel pathways from motor and somatosensory cortex for controlling whisker movements in mice

Carl Petersen, Varun Sreenivasan

Mice can gather tactile sensory information by actively moving their whiskers to palpate objects in their immediate surroundings. Whisker sensory perception therefore requires integration of sensory and motor information, which occurs prominently in the neocortex. The signalling pathways from the neocortex for controlling whisker movements are currently poorly understood in mice. Here, we delineate two pathways, one originating from primary whisker somatosensory cortex (wS1) and the other from whisker motor cortex (wM1), that control qualitatively distinct movements of contralateral whiskers. Optogenetic stimulation of wS1 drove retraction of contralateral whiskers while stimulation of wM1 drove rhythmic whisker protraction. To map brainstem pathways connecting these cortical areas to whisker motor neurons, we used a combination of anterograde tracing using adenoassociated virus injected into neocortex and retrograde tracing using monosynaptic rabies virus injected into whisker muscles. Our data are consistent with wS1 driving whisker retraction by exciting glutamatergic premotor neurons in the rostral spinal trigeminal interpolaris nucleus, which in turn activate the motor neurons innervating the extrinsic retractor muscle nasolabialis. The rhythmic whisker protraction evoked by wM1 stimulation might be driven by excitation of excitatory and inhibitory premotor neurons in the brainstem reticular formation innervating both intrinsic and extrinsic muscles. Our data therefore begin to unravel the neuronal circuits linking the neocortex to whisker motor neurons.