Robot-assisted fMRI assessment of early brain development

Preterm birth can interfere with the intra-uterine mechanisms driving cerebral development during the third trimester of gestation and often results in severe neuro-developmental impairments. Characterizing normal/abnormal patterns of early brain maturation could be fundamental in devising and guiding early therapeutic strategies aimed at improving clinical outcome by exploiting the enhanced early neuroplasticity. Over the last decade the morphology and structure of the developing human brain has been vastly characterized; however the concurrent maturation of brain function is still poorly understood. Task-dependent fMRI studies of the preterm brain can directly probe the emergence of fundamental neuroscientific notions and also provide clinicians with much needed early diagnostic and prognostic information. To date, task-fMRI studies of the preterm population have however been hampered by methodological challenges leading to inconsistent and contradictory results. In this thesis I present a modular and flexible system to provide clinicians and researchers with a simple and reliable solution to deliver computer-controlled stimulation patterns to preterm infants during task-fMRI experiments. The system is primarily aimed at studying the developing sensori-motor system as preterm infants are often affected by neuro-motor dysfunctions such as cerebral palsy. Wrist and ankle robotic stimulators were developed and firstly used to study the emerging somatosensory “homunculus”. The wrist robotic stimulator was then used to characterize the development of the sensori-motor system throughout the mid-to-late preterm period. An instrumented pacifier system was also developed to explore the potential sensorimotor modulation of early sucking activity; however, despite its clear potential to be employed in future fMRI studies, results have not yet been obtained on preterm infants. Functional difficulties associated with prematurity are likely to extend to multi-sensory integration, and the olfactory system currently remains under-investigated despite its clear developmental importance. A custom olfactometer was developed and used to assess its early functionality.Open Acces

Body Topography Parcellates Human Sensory and Motor Cortex

The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand-face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing

Somatotopic mapping of the human somatosensory cortex using functional magnetic resonance imaging (fMRI)

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1996.Includes bibliographical references (leaves 125-129).Anil K. Gehi.M.Eng

Image Quality Analysis of High-Density Diffuse Optical Tomography Incorporating a Subject-Specific Head Model

High-density diffuse optical tomography (HD-DOT) methods have shown significant improvement in localization accuracy and image resolution compared to traditional topographic near infrared spectroscopy of the human brain. In this work we provide a comprehensive evaluation of image quality in visual cortex mapping via a simulation study with the use of an anatomical head model derived from MRI data of a human subject. A model of individual head anatomy provides the surface shape and internal structure that allow for the construction of a more realistic physical model for the forward problem, as well as the use of a structural constraint in the inverse problem. The HD-DOT model utilized here incorporates multiple source-detector separations with continuous-wave data with added noise based on experimental results. To evaluate image quality we quantify the localization error and localized volume at half maximum (LVHM) throughout a region of interest within the visual cortex and systematically analyze the use of whole-brain tissue spatial constraint within image reconstruction. Our results demonstrate that an image quality with less than 10 mm in localization error and 1000 m3 in LVHM can be obtained up to 13 mm below the scalp surface with a typical unconstrained reconstruction and up to 18 mm deep when a whole-brain spatial constraint based on the brain tissue is utilized

Observation of sonified movements engages a basal ganglia frontocortical network

Background: Producing sounds by a musical instrument can lead to audiomotor coupling, i.e. the joint activation of the auditory and motor system, even when only one modality is probed. The sonification of otherwise mute movements by sounds based on kinematic parameters of the movement has been shown to improve motor performance and perception of movements.Results: Here we demonstrate in a group of healthy young non-athletes that congruently (sounds match visual movement kinematics) vs. incongruently (no match) sonified breaststroke movements of a human avatar lead to better perceptual judgement of small differences in movement velocity. Moreover, functional magnetic resonance imaging revealed enhanced activity in superior and medial posterior temporal regions including the superior temporal sulcus, known as an important multisensory integration site, as well as the insula bilaterally and the precentral gyrus on the right side. Functional connectivity analysis revealed pronounced connectivity of the STS with the basal ganglia and thalamus as well as frontal motor regions for the congruent stimuli. This was not seen to the same extent for the incongruent stimuli.Conclusions: We conclude that sonification of movements amplifies the activity of the human action observation system including subcortical structures of the motor loop. Sonification may thus be an important method to enhance training and therapy effects in sports science and neurological rehabilitation.DFG/SFB/TR31/EUDFG/TP/A7/E

Infants' sex affects neural responses to affective touch in early infancy

Social touch is closely related to the establishment and maintenance of social bonds in humans, and the sensory brain circuit for gentle brushing is already active soon after birth. Brain development is known to be sexually dimorphic, but the potential effect of sex on brain activation to gentle touch remains unknown. Here, we examined brain activation to gentle skin stroking, a tactile stimulation that resembles affective or social touch, in term-born neonates. Eighteen infants aged 11–36 days, recruited from the FinnBrain Birth Cohort Study, were included in the study. During natural sleep, soft brush strokes were applied to the skin of the right leg during functional magnetic resonance imaging (fMRI) at 3 cm/s velocity. We examined potential differ- ences in brain activation between males (n = 10) and females (n = 8) and found that females had larger blood oxygenation level dependent (BOLD) responses (brushing vs. rest) in bilateral orbitofrontal cortex (OFC), right ventral striatum and bilateral inferior striatum, pons, and cerebellum compared to males. Moreover, the psychophysiologi- cal interactions (PPI) analysis, setting the left and right OFC as seed regions, revealed significant differences between males and females. Females exhibited stronger PPI connectivity between the left OFC and posterior cingulate or cuneus. Our work sug- gests that social touch neural responses are different in male and female neonates, which may have major ramifications for later brain, cognitive, and social development. Finally, many of the sexually dimorphic brain responses were subcortical, not captured by surface-based neuroimaging, indicating that fMRI will be a relevant technique for future studies

Rubber hand illusion induced by touching the face ipsilaterally to a deprived hand: evidence for plastic "somatotopic" remapping in tetraplegics

Background: Studies in animals and humans indicate that the interruption of body-brain connections following spinal cord injury (SCI) leads to plastic cerebral reorganization.Objective: To explore whether inducing the Rubber Hand Illusion (RHI) via synchronous multisensory visuo-tactile bodily stimulation may reveal any perceptual correlates of plastic remapping in SCI.Methods: In 16 paraplegic, 16 tetraplegic and 16 healthy participants we explored whether RHI may be induced by tactile stimuli involving not only the left hand but also the left hemi-face. Touching the participants actual hand or face was either synchronous or asynchronous with tactile stimuli seen on a rubber hand. We assessed two components of the illusion, namely perceived changes in the real hand in space (indexed by proprioceptive drift) and ownership of the rubber hand (indexed by subjective responses to an ad-hoc questionnaire).Results: Proprioceptive drift and ownership were found in the healthy group only in the condition where the left real and fake hand were touched simultaneously. In contrast, no drift was found in the SCI patients who, however, showed ownership after both synchronous and asynchronous hand stroking. Importantly, only tetraplegics showed the effect also after synchronous face stroking.Conclusions: RHI may reveal plastic phenomena in SCI. In hand representation-deprived tetraplegics, stimuli on the face (represented contiguously in the somatic and motor systems), drive the sense of hand ownership. This hand-face remapping phenomenon may be useful for restoring a sense of self in massively deprived individuals

Mécanismes cérébraux de la régulation de la douleur : perception de la douleur et hypoalgésie induite psychologiquement

Objectif : Cette thèse a pour but de préciser les mécanismes neuropsychologiques de la douleur, de la régulation endogène de la douleur et de l'hypoalgésie induite psychologiquement (HIP) par la synthèse de près de trente ans de recherche imagerie cérébrale fonctionnelle. Méthodologie : Étant donné l'abondance des études sur le sujet et le manque d'intégration de leurs résultats, la technique de métaanalyse quantitative basée sur les coordonnées d'activation cérébrale fut privilégiée dans cette thèse, telle qu’implémentée dans l'algorithme ALE (Activation Likelyhood Estimate). Une force supplémentaire de cette thèse repose sur la rigueur du processus de sélection des articles. En effet, les études incluses dans les métaanalyses devaient satisfaire des critères stricts d'inclusion, ceci dans le but de favoriser la précision et la validité des conclusions subséquentes. Étude 1 : Le premier article visait à identifier les aires cérébrales impliquées dans la réduction de la douleur par des méthodes psychologiques d'interventions. Les articles retenus portent sur une variété de méthodes d'intervention, telles que le placebo, l'hypnose, la méditation, la perception de contrôle sur la stimulation douloureuse et l'induction d'émotions. Les résultats indiquent que l'HIP implique un vaste réseau d'activation qui comprend le cortex cingulaire antérieur, l'insula antérieure, les zones orbitofrontale et préfrontale latérale, ainsi que les régions pariétale, temporale et souscorticales. Ces activations reflèteraient l'implication des mécanismes neuropsychologiques cognitifs et émotionnels sous-tendent les interventions psychologiques ciblées par ces études, incluant la conscience de soi et la motivation. De plus, les divergences de patron d'activation entre les approches ont été explorées, notamment pour le placebo et la distraction. Étude 2 : Le deuxième article a identifié des patrons d'activations préférentiellement associés à la perception de la douleur, à l'HIP, ainsi que des activations communément associées à la douleur et l'HIP. Les résultats indiquent que 1) la perception de la douleur est associée à l'activation d'aires somatosensorielles et motrices, ce qui pourrait être le reflet de la préparation d'une action adaptative, 2) l'HIP est liée à l'engagement de régions préfrontales antéromédianes et orbitales, possiblement en lien avec des processus motivationnels et émotionnels, et 3) la douleur et l'HIP sont associés à l'activation d'aires préfrontales dorsolatérales, de l'insula antérieure et du cortex cingulaire moyen, ce qui pourrait refléter l'engagement spontané pendant la douleur de mécanismes endogènes de régulation descendante. Conclusion : Par ces études, cette thèse fait le point sur les mécanismes cérébraux impliqués différentiellement dans la perception de la douleur, dans sa régulation endogène et dans l'hypoalgésie induite psychologiquement.Objective: This thesis aims to clarify the neuropsychological mechanisms of pain, of the endogenous regulation of pain and of psychologically induced hypoalgesia (PIH), through the synthesis of almost thirty years of functional brain imaging research. Methodology: Given the abundance of studies in this domain and the lack of integration of their results, we used the quantitative meta-analysis technique based on brain activation using the ALE (Activation likelihood Estimate) statistic. The strength of this thesis lies in the globalized perspective of the litterature, and in the rigor of the article selection process from which results were extracted. Indeed, the studies included in the meta-analyses needed to meet strict inclusion criteria in order to strengthen the accuracy and the validity of subsequent conclusions. Study 1: The first article is aimed at identifying brain areas involved in pain reduction through psychological methods of intervention. Chosen articles that covered a variety of approaches, such as placebo, hypnosis, meditation, perception of control over the stimulation, and induction of emotions. Analysis across these various studies indicated that PIH involves a broad network of activation that includes the anterior cingulate cortex, anterior insulae, orbital and lateral prefrontal and frontal areas, as well as parietal, temporal and subcortical regions. This activation network may reflect the involvement of diverse neuropsychological mechanisms in the various affective, self-awareness, cognitive and motivational processes underlying the psychological interventions targeted by these studies. In addition, we explored some specific patterns of brain activity related to placebo and distraction, in comparison to other approaches. We propose several hypotheses regarding the distinctive neuropsychological processes underlying these approaches. Study 2: The second article aimed at investigating patterns of brain activity preferentially associated with pain perception or with PIH. First we assessed patterns of increased and decreased activity during experimental pain in healthy volunteers. Second we determined the brain regions preferentially activated during pain perception or during PIH with subtraction analyses. Using a conjunction analysis, we also determined a set of brain regions possibly involved in regulatory processes activated spontaneously during acute of pain. Our results indicate that 1) somatosensory and motor areas are preferentially related to pain perception, which may reflect the preparation of a motor response, 2) dorsolateral prefrontal areas, anterior insula and the anterior midcingulate cortex were associated with both pain and PIH and may reflect the spontaneous activation of top-down regulation mechanisms during pain, and 3) antero-medial and orbital prefrontal regions were preferentially associated with PIH, which may indicate motivational and emotional processes associated with the engagement of an externally driven hypoalgesic procedure

A Randomized, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain : A Pilot Trial

Objectives Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment. Materials and Methods This prospective, randomized, double-blind, Sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations, and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control. Results We prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of >= 30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17-20% pain relief), with no difference between M1, S2, or Sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response. Conclusions S2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.Peer reviewe

Simultaneous measurements of kinematics and fMRI: compatibility assessment and case report on recovery evaluation of one stroke patient

<p>Abstract</p> <p>Background</p> <p>Correlating the features of the actual executed movement with the associated cortical activations can enhance the reliability of the functional Magnetic Resonance Imaging (fMRI) data interpretation. This is crucial for longitudinal evaluation of motor recovery in neurological patients and for investigating detailed mutual interactions between activation maps and movement parameters.</p> <p>Therefore, we have explored a new set-up combining fMRI with an optoelectronic motion capture system, which provides a multi-parameter quantification of the performed motor task.</p> <p>Methods</p> <p>The cameras of the motion system were mounted inside the MR room and passive markers were placed on the subject skin, without any risk or encumbrance. The versatile set-up allows 3-dimensional multi-segment acquisitions including recording of possible mirror movements, and it guarantees a high inter-sessions repeatability.</p> <p>We demonstrated the integrated set-up reliability through compatibility tests. Then, an fMRI block-design protocol combined with kinematic recordings was tested on a healthy volunteer performing finger tapping and ankle dorsal- plantar-flexion. A preliminary assessment of clinical applicability and perspectives was carried out by pre- and post rehabilitation acquisitions on a hemiparetic patient performing ankle dorsal- plantar-flexion. For all sessions, the proposed method integrating kinematic data into the model design was compared with the standard analysis.</p> <p>Results</p> <p>Phantom acquisitions demonstrated the not-compromised image quality. Healthy subject sessions showed the protocols feasibility and the model reliability with the kinematic regressor. The patient results showed that brain activation maps were more consistent when the images analysis included in the regression model, besides the stimuli, the kinematic regressor quantifying the actual executed movement (movement timing and amplitude), proving a significant model improvement. Moreover, concerning motor recovery evaluation, after one rehabilitation month, a greater cortical area was activated during exercise, in contrast to the usual focalization associated with functional recovery. Indeed, the availability of kinematics data allows to correlate this wider area with a higher frequency and a larger amplitude of movement.</p> <p>Conclusions</p> <p>The kinematic acquisitions resulted to be reliable and versatile to enrich the fMRI images information and therefore the evaluation of motor recovery in neurological patients where large differences between required and performed motion can be expected.</p