Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

Towards reliable spinal cord fMRI: Assessment of common imaging protocols.

Functional magnetic resonance imaging (fMRI) has revolutionized the investigation of brain function. Similar approaches can be translated to probe spinal mechanisms. However, imaging the spinal cord remains challenging, notably due to its size and location. Technological advances are gradually tackling these issues, though there is yet no consensus on optimal acquisition protocols. In this study, we assessed the performance of three sequences during a simple motor task and at rest, in 15 healthy humans. Building upon recent literature, we selected three imaging protocols: a sequence integrating outer volume suppression (OVS) and two sequences implementing inner field-of-view imaging (ZOOMit) with different spatial and temporal resolutions. Images acquired using the OVS sequence appeared more prone to breathing-induced signal fluctuations, though they exhibited a higher temporal signal-to-noise ratio than ZOOMit sequences. Conversely, the spatial signal-to-noise ratio was higher for the two ZOOMit schemes. In spite of these differences in signal properties, all sequences yielded comparable performance in detecting group-level task-related activity, observed in the expected spinal levels. Nevertheless, our results suggest a superior sensitivity and robustness of patterns imaged using the OVS acquisition scheme. To analyze the data acquired at rest, we deployed a dynamic functional connectivity framework, SpiCiCAP, and we evaluated the ability of the three acquisition schemes to disentangle intrinsic spinal signals. We demonstrated that meaningful subdivisions of the spinal cord's functional architecture could be uncovered for all three sequences, with similar spatio-temporal properties across acquisition parameters. Cleaner and more stable components were, however, obtained using ZOOMit sequences. This study emphasizes the potential of fMRI as a robust tool to image spinal activity in vivo and it highlights specificities and similarities of three acquisition methods. This represents a key step towards the establishment of standardized spinal cord fMRI protocols.

Contribution of interaction force to the sense of hand ownership and the sense of hand agency.

When performing willed actions, we have the unified and coherent experience of owning and controlling our body. Body ownership is believed to emerge from the integration of coherent multisensory signals, while agency is believed to emerge from the coherence between predicted and perceived outcomes of actions. As a consequence, body ownership and agency can both be modulated by multisensory conflicts. The contribution of active movement generation to ownership and agency has not been parametrically explored. Here, we investigated the contribution of interaction force between the agent and the environment to the sense of hand ownership (SO) and the sense of hand agency (SA). By combining robotics and virtual reality, we manipulated the sensorimotor and visual information during immersive scenarios to induce and quantify altered states of SO and SA. First, we demonstrated that SO and SA could be successfully manipulated by our experimental paradigms. Second, we showed that interaction force strongly contributes to SA, but to a lesser extent to SO. Finally, we showed that SO and SA interact beyond their common multisensory basis. Our results, based on two independent studies, provide a direct link between sensorimotor interactions and subjective body experience and demonstrate a new dissociation between SO and SA.

Relation between palm and finger cortical representations in primary somatosensory cortex: A 7T fMRI study.

Many studies focused on the cortical representations of fingers, while the palm is relatively neglected despite its importance for hand function. Here, we investigated palm representation (PR) and its relationship with finger representations (FRs) in primary somatosensory cortex (S1). Few studies in humans suggested that PR is located medially with respect to FRs in S1, yet to date, no study directly quantified the somatotopic organization of PR and the five FRs. Importantly, the link between the somatotopic organization of PR and FRs and their activation properties remains largely unexplored. Using 7T fMRI, we mapped PR and the five FRs at the single subject level. First, we analyzed the cortical distance between PR and FRs to determine their somatotopic organization. Results show that PR was located medially with respect to D5. Second, we tested whether the observed cortical distances would predict the relationship between PR and FRs activations. Using three complementary measures (cross-activations, pattern similarity and resting-state connectivity), we show that the relationship between PR and FRs activations were not determined by their somatotopic organization, that is, there was no gradient moving from D5 to D1, except for resting-state connectivity, which was predicted by the somatotopy. Instead, we show that the representational geometry of PR and FRs activations reflected the physical structure of the hand. Collectively, our findings suggest that the spatial proximity between topographically organized neuronal populations do not necessarily predicts their functional properties, rather the structure of the sensory space (e.g., the hand shape) better describes the observed results.

Get real: Orbitofrontal cortex mediates the ability to sense reality in early adolescents.

INTRODUCTION: Orbitofrontal reality filtering (ORFi) is a memory mechanism that distinguishes whether a thought is relevant to present reality or not. In adults, it is mediated by the orbitofrontal cortex (OFC). This region is still not fully developed in preteenagers, but ORFi is already active from age 7. Here, we probe the neural correlates of ORFi in early adolescents, hypothesizing that OFC mediates the sense of reality in this population. METHODS: Functional magnetic resonance images (fMRI) were acquired in 22 early adolescents during a task composed of two runs: run 1 measuring recognition capacity; run 2 measuring ORFi; each containing two types of images (conditions): distractors (D: images seen for the first time in the current run) and targets (T: images seen for the second time in the current run). Group region of interest (ROI) analysis was performed in a flexible factorial design with two factors (run and condition) using SPM12. RESULTS: We found significant main effects for the experimental run and condition. The bilateral OFC activation was higher during ORFi than during the first run. Additionally, the OFC was more active while processing distractors than targets. CONCLUSION: These results confirm, for the first time, the role of OFC in reality filtering in early adolescents.

Functional imaging of rostrocaudal spinal activity during upper limb motor tasks.

The spinal cord is the main interface between the brain and the periphery. It notably plays a central role in motor control, as spinal motoneurons activate skeletal muscles involved in voluntary movements. Yet, the spinal mechanisms underlying human movement generation have not been completely elucidated. In this regard, functional magnetic resonance imaging (fMRI) represents a potential tool to probe spinal cord function non-invasively and with high spatial resolution. Nonetheless, a thorough characterization of this approach is still lacking, currently limiting its impact. Here, we aimed at systematically quantifying to which extent fMRI can reveal spinal cord activity along the rostrocaudal direction. We investigated changes in the blood oxygenation level dependent signal of the human cervical spinal cord during bimanual upper limb movements (wrist extension, wrist adduction and finger abduction) in nineteen healthy volunteers. Prior to scanning, we recorded the muscle activity associated with these movements in order to reconstruct the theoretical motor-pool output pattern using an anatomy-based mapping of the electromyographic (EMG) waveforms. EMG-derived spinal maps were characterized by distinct rostrocaudal patterns of activation, thus confirming the task-specific features of the different movements. Analogous activation patterns were captured using spinal cord fMRI. Finally, an additional fMRI dataset was acquired from a subset of the participants (n = 6) to deploy a multivoxel pattern analysis, which allowed successful decoding of movements. These combined results suggest that spinal cord fMRI can be used to image rostrocaudal activation patterns reflecting the underlying activity of the motoneuron pools innervating the task-related muscles. Spinal cord fMRI offers the prospect of a novel tool to study motor processes and potentially their modification following neurological motor disorders.

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.

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.

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.

Bilateral Rolandic operculum processing underlying heartbeat awareness reflects changes in bodily self-consciousness.

Exteroceptive bodily signals (including tactile, proprioceptive and visual signals) are important information contributing to self-consciousness. Moreover, prominent theories proposed that visceral signals about internal bodily states are equally or even more important for self-consciousness. Neuroimaging studies have described several brain regions which process signals related to bodily self-consciousness (BSC) based on the integration of exteroceptive signals (e.g. premotor cortex, angular gyrus, supramarginal gyrus and extrastriate body area), and that another brain region, the insula/operculum which is involved in interoception and interoceptive awareness, processes signals critical for self-awareness. Providing evidence for the integration of exteroceptive and interoceptive bodily signals, recent behavioral experiments have demonstrated that the manipulation of interoceptive (e.g. cardiac) signals, coupled with exteroceptive (e.g. visual) signals, also modulates BSC. Does this integration occur within or outside the structures described above? To this end, we adapted a recently designed protocol that uses cardio-visual stimulation to induce altered states of BSC to fMRI. Additionally, we measured neural activity in a classical interoceptive task. We found six brain regions (bilateral Rolandic operculum, bilateral supramarginal gyrus, right frontal inferior operculum and left temporal superior gyrus) that were activated differently during the interoception task as opposed to a control task. The brain regions which showed the highest selectivity for BSC based on our cardio-visual manipulation were found in the bilateral Rolandic operculum. Given our findings, we propose that the Rolandic operculum processes integrated exteroceptive-interoceptive signals that are necessary for interoceptive awareness as well as BSC.

Cortical and subcortical mechanisms of brain-machine interfaces.

Technical advances in the field of Brain-Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole-brain level. Here, we provide a comprehensive and detailed report of the areas active during on-line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG-based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI-actions. Our data revealed an extended cortical-subcortical network involved in operating a motor-imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp 38:2971-2989, 2017. © 2017 Wiley Periodicals, Inc.

Diffusion Tensor Imaging in Patients with Glioblastoma Multiforme Using the Supertoroidal Model.

PURPOSE: Diffusion Tensor Imaging (DTI) is a powerful imaging technique that has led to improvements in the diagnosis and prognosis of cerebral lesions and neurosurgical guidance for tumor resection. Traditional tensor modeling, however, has difficulties in differentiating tumor-infiltrated regions and peritumoral edema. Here, we describe the supertoroidal model, which incorporates an increase in surface genus and a continuum of toroidal shapes to improve upon the characterization of Glioblastoma multiforme (GBM). MATERIALS AND METHODS: DTI brain datasets of 18 individuals with GBM and 18 normal subjects were acquired using a 3T scanner. A supertoroidal model of the diffusion tensor and two new diffusion tensor invariants, one to evaluate diffusivity, the toroidal volume (TV), and one to evaluate anisotropy, the toroidal curvature (TC), were applied and evaluated in the characterization of GBM brain tumors. TV and TC were compared with the mean diffusivity (MD) and fractional anisotropy (FA) indices inside the tumor, surrounding edema, as well as contralateral to the lesions, in the white matter (WM) and gray matter (GM). RESULTS: The supertoroidal model enhanced the borders between tumors and surrounding structures, refined the boundaries between WM and GM, and revealed the heterogeneity inherent to tumor-infiltrated tissue. Both MD and TV demonstrated high intensities in the tumor, with lower values in the surrounding edema, which in turn were higher than those of unaffected brain parenchyma. Both TC and FA were effective in revealing the structural degradation of WM tracts. CONCLUSIONS: Our findings indicate that the supertoroidal model enables effective tensor visualization as well as quantitative scalar maps that improve the understanding of the underlying tissue structure properties. Hence, this approach has the potential to enhance diagnosis, preoperative planning, and intraoperative image guidance during surgical management of brain lesions.

The multisensory function of the human primary visual cortex.

It has been nearly 10 years since Ghazanfar and Schroeder (2006) proposed that the neocortex is essentially multisensory in nature. However, it is only recently that sufficient and hard evidence that supports this proposal has accrued. We review evidence that activity within the human primary visual cortex plays an active role in multisensory processes and directly impacts behavioural outcome. This evidence emerges from a full pallet of human brain imaging and brain mapping methods with which multisensory processes are quantitatively assessed by taking advantage of particular strengths of each technique as well as advances in signal analyses. Several general conclusions about multisensory processes in primary visual cortex of humans are supported relatively solidly. First, haemodynamic methods (fMRI/PET) show that there is both convergence and integration occurring within primary visual cortex. Second, primary visual cortex is involved in multisensory processes during early post-stimulus stages (as revealed by EEG/ERP/ERFs as well as TMS). Third, multisensory effects in primary visual cortex directly impact behaviour and perception, as revealed by correlational (EEG/ERPs/ERFs) as well as more causal measures (TMS/tACS). While the provocative claim of Ghazanfar and Schroeder (2006) that the whole of neocortex is multisensory in function has yet to be demonstrated, this can now be considered established in the case of the human primary visual cortex.

Stroking or Buzzing? A Comparison of Somatosensory Touch Stimuli Using 7 Tesla fMRI.

Studying body representations in the brain helps us to understand how we humans relate to our own bodies. The in vivo mapping of the somatosensory cortex, where these representations are found, is greatly facilitated by the high spatial resolution and high sensitivity to brain activation available at ultra-high field. In this study, the use of different stimulus types for somatotopic mapping of the digits at ultra-high field, specifically manual stroking and mechanical stimulation, was compared in terms of sensitivity and specificity of the brain responses. Larger positive responses in digit regions of interest were found for manual stroking than for mechanical stimulation, both in terms of average and maximum t-value and in terms of number of voxels with significant responses to the tactile stimulation. Responses to manual stroking were higher throughout the entire post-central sulcus, but the difference was especially large on its posterior wall, i.e. in Brodmann area 2. During mechanical stimulation, cross-digit responses were more negative than during manual stroking, possibly caused by a faster habituation to the stimulus. These differences indicate that manual stroking is a highly suitable stimulus for fast somatotopic mapping procedures, especially if Brodmann area 2 is of interest.

Distinct contributions of Brodmann areas 1 and 2 to body ownership.

Although body ownership--i.e. the feeling that our bodies belong to us--modulates activity within the primary somatosensory cortex (S1), it is still unknown whether this modulation occurs within a somatotopically defined portion of S1. We induced an illusory feeling of ownership for another person's finger by asking participants to hold their palm against another person's palm and to stroke the two joined index fingers with the index and thumb of their other hand. This illusion (numbness illusion) does not occur if the stroking is performed asynchronously or by the other person. We combined this somatosensory paradigm with ultra-high field functional magnetic resonance imaging finger mapping to study whether illusory body ownership modulates activity within different finger-specific areas of S1. The results revealed that the numbness illusion is associated with activity in Brodmann area (BA) 1 within the representation of the finger stroking the other person's finger and in BA 2 contralateral to the stroked finger. These results show that changes in bodily experience modulate the activity within certain subregions of S1, with a different finger-topographical selectivity between the representations of the stroking and of the stroked hand, and reveal that the high degree of somatosensory specialization in S1 extends to bodily self-consciousness.

The brain network reflecting bodily self-consciousness: a functional connectivity study.

Several brain regions are important for processing self-location and first-person perspective, two important aspects of bodily self-consciousness. However, the interplay between these regions has not been clarified. In addition, while self-location and first-person perspective in healthy subjects are associated with bilateral activity in temporoparietal junction (TPJ), disturbed self-location and first-person perspective result from damage of only the right TPJ. Identifying the involved brain network and understanding the role of hemispheric specializations in encoding self-location and first-person perspective, will provide important information on system-level interactions neurally mediating bodily self-consciousness. Here, we used functional connectivity and showed that right and left TPJ are bilaterally connected to supplementary motor area, ventral premotor cortex, insula, intraparietal sulcus and occipitotemporal cortex. Furthermore, the functional connectivity between right TPJ and right insula had the highest selectivity for changes in self-location and first-person perspective. Finally, functional connectivity revealed hemispheric differences showing that self-location and first-person perspective modulated the connectivity between right TPJ, right posterior insula, and right supplementary motor area, and between left TPJ and right anterior insula. The present data extend previous evidence on healthy populations and clinical observations in neurological deficits, supporting a bilateral, but right-hemispheric dominant, network for bodily self-consciousness.

Human finger somatotopy in areas 3b, 1, and 2: a 7T fMRI study using a natural stimulus.

To study the properties of human primary somatosensory (S1) cortex as well as its role in cognitive and social processes, it is necessary to noninvasively localize the cortical representations of the body. Being arguably the most relevant body parts for tactile exploration, cortical representations of fingers are of particular interest. The aim of the present study was to investigate the cortical representation of individual fingers (D1-D5), using human touch as a stimulus. Utilizing the high BOLD sensitivity and spatial resolution at 7T, we found that each finger is represented within three subregions of S1 in the postcentral gyrus. Within each of these three areas, the fingers are sequentially organized (from D1 to D5) in a somatotopic manner. Therefore, these finger representations likely reflect distinct activations of BAs 3b, 1, and 2, similar to those described in electrophysiological work in non-human primates. Quantitative analysis of the local BOLD responses revealed that within BA3b, each finger representation is specific to its own stimulation without any cross-finger responsiveness. This finger response selectivity was less prominent in BA 1 and in BA 2. A test-retest procedure highlighted the reproducibility of the results and the robustness of the method for BA 3b. Finally, the representation of the thumb was enlarged compared to the other fingers within BAs 1 and 2. These findings extend previous human electrophysiological and neuroimaging data but also reveal differences in the functional organization of S1 in human and nonhuman primates.

Multisensory origin of the subjective first-person perspective: visual, tactile, and vestibular mechanisms.

In three experiments we investigated the effects of visuo-tactile and visuo-vestibular conflict about the direction of gravity on three aspects of bodily self-consciousness: self-identification, self-location, and the experienced direction of the first-person perspective. Robotic visuo-tactile stimulation was administered to 78 participants in three experiments. Additionally, we presented participants with a virtual body as seen from an elevated and downward-directed perspective while they were lying supine and were therefore receiving vestibular and postural cues about an upward-directed perspective. Under these conditions, we studied the effects of different degrees of visuo-vestibular conflict, repeated measurements during illusion induction, and the relationship to a classical measure of visuo-vestibular integration. Extending earlier findings on experimentally induced changes in bodily self-consciousness, we show that self-identification does not depend on the experienced direction of the first-person perspective, whereas self-location does. Changes in bodily self-consciousness depend on visual gravitational signals. Individual differences in the experienced direction of first-person perspective correlated with individual differences in visuo-vestibular integration. Our data reveal important contributions of visuo-vestibular gravitational cues to bodily self-consciousness. In particular we show that the experienced direction of the first-person perspective depends on the integration of visual, vestibular, and tactile signals, as well as on individual differences in idiosyncratic visuo-vestibular strategies.

Digit somatotopy in the human cerebellum: a 7T fMRI study.

The representation of the human body in the human cerebellum is still relatively unknown, compared to the well-studied homunculus in the primary somatosensory cortex. The investigation of the body representation in the cerebellum and its somatotopic organisation is complicated because of the relatively small dimensions of the cerebellum, compared to the cerebrum. Somatotopically organised whole-body homunculi have previously been reported in both humans and rats. However, whether individual digits are represented in the cerebellum in a somatotopically organised way is much less clear. In this study, the high spatial resolution and high sensitivity to the blood oxygenation level dependent (BOLD) signal of 7T fMRI were employed to study the BOLD responses in the human cerebellum to the stroking of the skin of individual digits, the hand and forearm. For the first time, a coarse somatotopic organisation of the digits, ordered from D1-D5, could be visualised in individual human subjects in both the anterior (lobule V) and the posterior (lobule VIII) lobes of the cerebellum using a somatosensory stimulus. The somatotopic gradient in lobule V was found consistently in the posterior to anterior direction, with the thumb most posterior, while the direction of the somatotopic gradient in lobule VIII differed between subjects. No somatotopic organisation was found in Crus I. A comparison of the digit patches with the hand patch revealed that the digit regions are completely covered by the hand region in both the anterior and posterior lobes of the cerebellum, in a non-somatotopic manner. These results demonstrate the promise of ultra-high field, high-resolution fMRI for studies of the cerebellum.

Functional MRI connectivity as a predictor of the surgical outcome of epilepsy.

PURPOSE: In planning epilepsy surgery, it is important to be able to assess the likelihood of success of surgery for each patient so that the possible risk and benefit can be properly considered. In this study, functional connectivity was investigated as a means for predicting surgical outcome from the preoperative functional magnetic resonance imaging (fMRI) of epilepsy patients. METHODS: Resting-state simultaneous electroencephalography (EEG)-fMRI data were collected from 18 patients with intractable epilepsy before surgery and from 14 healthy subjects. For each patient, EEG-spike correlated fMRI analysis was performed and an activation cluster that overlapped the most with the planned resection area for each patient was chosen as the seed for the functional connectivity analysis. After the functional connectivity maps were computed, laterality indices of functional connectivity were contrasted between patients who had seizures after surgeries (seizure-recurrence group) and those who did not have them for at least a year (seizure-free group). KEY FINDINGS: Patients in the seizure-recurrence group had less-lateralized functional connectivity than patients in the seizure-free group (t(16) = 2.3, after control subtracted and Fisher transformed, p < 0.05, two-tailed). SIGNIFICANCE: This study suggests the potential for using preoperative fMRI connectivity analysis as a predictive outcome measure. If confirmed by further research, a high laterality will be an important addition to the other predictors of better surgical outcome such as febrile seizures, mesial temporal sclerosis, tumors, abnormal MRI, and EEG/MRI concordance.

A whole-brain voxel based measure of intrinsic connectivity contrast reveals local changes in tissue connectivity with anesthetic without a priori assumptions on thresholds or regions of interest.

The analysis of spontaneous fluctuations of functional magnetic resonance imaging (fMRI) signals has recently gained attention as a powerful tool for investigating brain circuits in a non-invasive manner. Correlation-based connectivity analysis investigates the correlations of spontaneous fluctuations of the fMRI signal either between a single seed region of interest (ROI) and the rest of the brain or between multiple ROIs. To do this, a priori knowledge is required for defining the ROI(s) and without such knowledge functional connectivity fMRI cannot be used as an exploratory tool for investigating the functional organization of the brain and its modulation under different conditions. In this work we examine two indices that provide voxel based maps reflecting the intrinsic connectivity contrast (ICC) of individual tissue elements without the need for defining ROIs and hence require no a priori information or assumptions. These voxel based ICC measures can also be used to delineate regions of interest for further functional or network analyses. The indices were applied to the study of sevoflurane anesthesia-induced alterations in intrinsic connectivity. In concordance with previous studies, the results show that sevoflurane affects different brain circuits in a heterogeneous manner. In addition ICC analyses revealed changes in regions not previously identified using conventional ROI connectivity analyses, probably because of an inappropriate choice of the ROI in the earlier studies. This work highlights the importance of such voxel based connectivity methodology.