Somatotopic Mapping of the Developing Sensorimotor Cortex in the Preterm Human Brain

Dall’Orso S, Steinweg J, Allievi AG, Edwards AD, Burdet E, Arichi T. Somatotopic Mapping of the Developing Sensorimotor Cortex in the Preterm Human Brain. Cerebral Cortex. 2018;28(7):2507-2515

Colocalized Structural and Functional Changes in the Cortex of Patients with Trigeminal Neuropathic Pain

Background: Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level – BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy. Methodology/Principal Findings: Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional (DLPFC, Frontal, Anterior Insula, Cingulate) processing of pain. Both structural and functional (to brush-induced allodynia) scans were obtained and averaged from two different imaging sessions separated by 2–6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions. Conclusions: Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions

Muscles in “Concert”: Study of Primary Motor Cortex Upper Limb Functional Topography

BACKGROUND: Previous studies with Transcranial Magnetic Stimulation (TMS) have focused on the cortical representation of limited group of muscles. No attempts have been carried out so far to get simultaneous recordings from hand, forearm and arm with TMS in order to disentangle a 'functional' map providing information on the rules orchestrating muscle coupling and overlap. The aim of the present study is to disentangle functional associations between 12 upper limb muscles using two measures: cortical overlapping and cortical covariation of each pair of muscles. Interhemispheric differences and the influence of posture were evaluated as well. METHODOLOGY/PRINCIPAL FINDINGS: TMS mapping studies of 12 muscles belonging to hand, forearm and arm were performed. Findings demonstrate significant differences between the 66 pairs of muscles in terms of cortical overlapping: extremely high for hand-forearm muscles and very low for arm vs hand/forearm muscles. When right and left hemispheres were compared, overlapping between all possible pairs of muscles in the left hemisphere (62.5%) was significantly higher than in the right one (53.5% ). The arm/hand posture influenced both measures of cortical association, the effect of Position being significant [p = .021] on overlapping, resulting in 59.5% with prone vs 53.2% with supine hand, but only for pairs of muscles belonging to hand and forearm, while no changes occurred in the overlapping of proximal muscles with those of more distal districts. CONCLUSIONS/SIGNIFICANCE: Larger overlapping in the left hemisphere could be related to its lifetime higher training of all twelve muscles studied with respect to the right hemisphere, resulting in larger intra-cortical connectivity within primary motor cortex. Altogether, findings with prone hand might be ascribed to mechanisms facilitating coupling of muscles for object grasping and lifting -with more proximal involvement for joint stabilization- compared to supine hand facilitating actions like catching. TMS multiple-muscle mapping studies permit a better understanding of motor control and 'plastic' reorganization of motor system

Effects of Hand Transplantation on Cortical Organization

Amputation induces substantial reorganization of the body part somatotopy in primary sensory cortex (S1), and these effects of deafferentation increase with time. Determining whether these changes are reversible is critical for understanding the potential to recover from deafferenting injuries. Here, we report evidence that the representation of a transplanted hand and digits can actually recapture the pre-amputation S1 hand territory in two transplant patients. With limited sensation 4 months post operation, one of the patient's (D.S.) palmar tactile stimulation evoked contralateral S1 responses that were indistinguishable in location and amplitude from those detected in healthy matched controls. The other patient (M.S.) demonstrated not only much improved sensation but also recovered ability to localize tactile stimuli 120+ months after the operation. The results described suggest that even decades after complete deafferentation, restoring afferent input to S1 leads to re-establishment of the gross hand and digits representations within their original territory. Stimulation of the deafferented cortical maps may play an important role in maintaining their viability until the afferent input is restored. Motor imagery and creation of virtual visual feedback of the absent hand with a mirror have been proposed as stimuli. We used fMRI to record neural activity while 11 unilateral hand amputees and matched controls performed aurally-paced thumb-finger sequencing movements with their intact hand (matching hand in case of controls) under visual guidance during four conditions: 1) intact hand (ME), 2) ME with motor imagery of the amputated hand, 3) ME with virtual visual feedback of the amputated hand, and 4) ME with motor imagery and the virtual visual feedback of the amputated hand. In contrast to controls, amputees showed increases in activity during all four conditions within the former functionally-defined sensorimotor hand territory. Movements of the intact hand likely increase activity in the former hand territory as a result of decreased interhemispheric inhibition. This stimulation may maintain deafferented hand representations that can recover soon after the afferent input is restored by hand transplantation

A multimodal approach to investigate brain reorganization after spinal cord injury using functional magnetic resonance imaging and functional near-infrared spectroscopy

Traumatic Spinal Cord Injury (SCI) results in structural and functional neurological changes at both the brain and the level of the spinal cord. Anatomical studies indicate decreased grey matter volume in sensorimotor and non-sensorimotor regions of the cortex following SCI; whereas, neurophysiological findings mostly report altered functional activity in the sensorimotor nodes of the cortex, subcortex, and cerebellum. Therefore, it is currently unknown whether tissue atrophy observed in non-motor related areas has any concomitant functional consequences. Furthermore, the neural underpinnings of adaptive neuroplasticity after SCI is not well-defined in the current literature. Hence, this dissertation is a pioneer study investigating the structural and functional changes in the whole brain after SCI, with particular focus on subcortical regions, using a multimodal approach employing magnetic resonance imaging (MRI), resting-state functional MRI (fMRI) and functional near-infrared spectroscopy (fNIRS), that may take best advantage of each of these three tools. MRI scans from 23 healthy controls (HC) and 36 individuals with complete SCI within two years of injury were used to demonstrate that both injury level and duration since injury are important factors contributing to recovery. Specifically, cervical level injury when compared to thoracolumbar level injury exhibits a greater loss of cortical grey matter volume in the orbitofrontal cortex, insula, and anterior cingulate cortex. Next, using the fMRI scans of the same participants during a resting-state scan, the intrinsic functional connectivity of the mediodorsal, pulvinar and ventrolateral nuclei of the thalamus to the regions of salient network and the fronto-parietal network is observed to be dynamic and altered in the SCI group. Lastly, a continuous-wave fNIRS is used to reliably measure brain function in individuals with SCI during both dynamic and static tasks while accounting for cerebrovascular reactivity. Five min of resting-state data and 26 min of motor data including finger tapping, finger tapping imagery and ankle tapping were acquired to identify the spatial activation pattern unique to each of the movement type. A breath-hold paradigm is also used to quantify cerebrovascular reactivity as a means to calibrate task activity from neurovascular constraints. Sixteen HC were scanned at two separate visits to determine the sensitivity and test-retest reliability of fNIRS data from the sensorimotor cortex. Following validation, the same procedure was repeated in 13 individuals with paraplegia resulting from SCI and 13 HC to quantify alterations in the cortical activity of the motor cortex and cerebrovascular reactivity between the two groups. Results indicate that SCI group exhibit altered cerebrovascular reactivity with greater delay in response and greater pre-stimulus undershoot. As hypothesized, the hemodynamic response to ankle movement resulted in only a small change in oxyhemoglobin concentration in the sensorimotor cortex of SCI group when compared to HC. The application of fNIRS to assess cortical reorganization following SCI is unique and expands our understanding of the neurophysiology after SCI. It paves the groundwork for extending the implementation of fNIRS to rehabilitation research and other clinical populations with vascular dysfunction. This dissertation is one of the first studies to comprehensively examine both the structural and functional alterations of the brain in humans with complete SCI and opens promising avenues for SCI research using fNIRS modality

Task-based fMRI investigation of the newborn brain: sensorimotor development and learning

Human brain development relies upon the interaction between genetic and environmental factors, and the latter plays a critical role during the perinatal period. In this period, neuronal plasticity through experience-dependent activity is enhanced in the sensory systems, and drive the maturation of the brain. While plasticity is essential for maturation, it is also a source of vulnerability as altered early experiences may interact with the normal course of development. This is particularly evident in infants born preterm, who are prematurely exposed to a sensory-rich environment, and at risk or neurodevelopmental disorders. In keeping with the somatosensory system being at a critical period for development during late gestation, sensorimotor disorders, such as cerebral palsy, are more common in preterm compared with full-term born infants. It is therefore important to understand the normal trajectory of sensorimotor development and how this may be moulded by early sensory experiences. It is well acknowledged that the sensorimotor cortex is topographically organised so that different body parts map to a specific location within the cortex and this map is generally referred to as the ``homunculus". Although the somatotopy has been well characterised in the mature brain, it remains unknown when this organisation emerges during development. Animal studies hints that functional cortical maps might emerge across the equivalent period to the third trimester of human gestation, nevertheless there is currently no evidence. Therefore, I first investigated the topography of the preterm somatosensory cortex in a group of newborn infants. In this purpose I used fMRI and automated robotic tools and measured the functional responses to different sensory simulations (delivered to the mouth, wrists and ankles). The results provide evidence that it is possible to identify distinct areas in the somatosensory cortex devoted to different body parts even in the preterm brain supporting the presence of an immature \textit{homunculus}. Next, I wanted to investigate how activity and development in the sensorimotor system are influenced by experience. Experience-dependent plasticity is the basis of learning (e.g. adaptive behaviour), which is observed in newborn infants. Associative learning in particular has been widely investigated in infants, however, the underlining neuronal processes have previously been poorly understood. To study the neural correlates of associative learning in newborn infants, I developed and used a classical conditioning paradigm in combination with robot-assisted fMRI. The results confirm that associative learning can occur even at this early stage of life and with non-aversive stimuli. More importantly, I could observe learning-induced changes in brain activity within the primary sensory cortices, suggesting that such experience can shape cortical circuitry and is likely to influence early brain development.Open Acces

DYNAMICS OF FUNCTIONAL CONNECTIVITY WITHIN CORTICAL MOTOR NETWORK DURING MOTOR LEARNING IN STROKE - CORRELATIONS WITH "TRUE" MOTOR RECOVERY

Arm motor recovery after stroke is usually incomplete; six months after onset about two-thirds of patients suffer from arm motor impairment that significantly impacts the individual's activities of daily living. Thus, novel concepts beyond current strategies for arm motor rehabilitation after stroke are needed. An essential approach for this is to better understand whether motor learning-related neural changes in stroke are similar with those in healthy controls and how these neural changes relate to recovery of the pre-morbid movement pattern or "true" recovery. Abnormal task-related activation in primary and non-primary motor cortices has been a consistent finding in functional MRI studies of stroke. Disturbed functional network architecture, e.g., the influence that one motor area exerts over another, also impacts stroke recovery. The outcome measures chosen to evaluate recovery are also important for the interpretation of these brain changes. Thus, the long-range goal of this work was to longitudinally investigate the changes in cortical motor function at two levels, regional (micro-circuitry, regional activation) and network (macro-circuitry, functional connectivity), following an arm-focused motor training in chronic stroke survivors and how these brain changes relate to recovery of the pre-morbid movement pattern or "true" recovery. In the Chapter I, we reviewed the literature concerning the pathophysiology of stroke, neural substrates of motor control, and motor learning principles and neural substrates in healthy and pathological (stroke) brain. In the Chapter II, we examined the relationships between task-related motor activation and clinical and kinematic metrics of arm motor impairment in survivors of subcortical stroke. We found evidence that primary motor activation was significantly correlated to kinematic metrics of arm motor impairment, but not with clinical metrics. In the Chapter III, we longitudinally investigated the regional changes in motor-related activation (functional MRI) in primary and non-primary motor areas following an arm-focused motor training in stroke survivors and age-sex matched healthy controls. We demonstrated that similar changes in the motor areas contralateral to the trained arm were found with training in both stroke and healthy participants. We also demonstrated a significant increase in motor performance in both groups as well as a normalization of the correlations between bilateral motor activation and movement kinematics in participants with stroke. In the Chapter IV, we also investigated the changes in functional connectivity between primary and non-primary motor areas following an arm-focused motor training and how these changes correlate with "true" motor recovery. We demonstrated significant enhanced functional connectivity in motor areas contralateral to the trained hand (or ipsilesional), although no "normalization" of the inter-hemispheric inhibition following training in our survivors. We also showed a "normalization" of the relationships between cortical motor functional connectivity and movement kinematics. In the Chapter V, we concluded that the present dissertation work support the hypotheses that motor system is plastic at different levels, regional and network, even in the chronic stage of stroke and some of these changes are similar with those reported in healthy controls. Further, these changes provide a substrate for "true" recovery. These findings promote the use of neuroimaging and kinematic metrics to improve our understanding of the neural substrates underlying reorganization in remaining intact brain structures after stroke. Such an approach may further enable monitoring recovery or compensation based on this reorganization and evaluating new treatment regimes that assist motor recovery

Evolution of the speech‐ready brain: The voice/jaw connection in the human motor cortex

A prominent model of the origins of speech, known as the “frame/content” theory, posits that oscillatory lowering and raising of the jaw provided an evolutionary scaffold for the development of syllable structure in speech. Because such oscillations are nonvocal in most nonhuman primates, the evolution of speech required the addition of vocalization onto this scaffold in order to turn such jaw oscillations into vocalized syllables. In the present functional MRI study, we demonstrate overlapping somatotopic representations between the larynx and the jaw muscles in the human primary motor cortex. This proximity between the larynx and jaw in the brain might support the coupling between vocalization and jaw oscillations to generate syllable structure. This model suggests that humans inherited voluntary control of jaw oscillations from ancestral species, but added voluntary control of vocalization onto this via the evolution of a new brain area that came to be situated near the jaw region in the human motor cortex