Brain plasticity after implanted peroneal nerve electrical stimulation to improve gait in chronic stroke patients: Two case reports.

BACKGROUND: Recent studies have shown that stimulation of the peroneal nerve using an implantable 4-channel peroneal nerve stimulator could improve gait in stroke patients. OBJECTIVES: To assess structural cortical and regional cerebral metabolism changes associated with an implanted peroneal nerve electrical stimulator to correct foot drop related to a central nervous system lesion. METHODS: Two stroke patients presenting a foot drop related to a central nervous system lesion were implanted with an implanted peroneal nerve electrical stimulator. Both patients underwent clinical evaluations before implantation and one year after the activation of the stimulator. Structural magnetic resonance imaging (MRI) and [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) were acquired before and one year after the activation of the stimulator. RESULTS: Foot drop was corrected for both patients after the implantation of the stimulator. After one year of treatment, patient 1 improved in three major clinical tests, while patient 2 only improved in one test. Prior to treatment, FDG-PET showed a significant hypometabolism in premotor, primary and supplementary motor areas in both patients as compared to controls, with patient 2 presenting more widespread hypometabolism. One year after the activation of the stimulator, both patients showed significantly less hypometabolism in the damaged motor cortex. No difference was observed on the structural MRI. CONCLUSION: Clinical improvement of gait under peroneal nerve electrical stimulation in chronic stroke patients presenting foot drop was paralleled to metabolic changes in the damaged motor cortex.

Sedation of Patients With Disorders of Consciousness During Neuroimaging: Effects on Resting State Functional Brain Connectivity.

BACKGROUND: To reduce head movement during resting state functional magnetic resonance imaging, post-coma patients with disorders of consciousness (DOC) are frequently sedated with propofol. However, little is known about the effects of this sedation on the brain connectivity patterns in the damaged brain essential for differential diagnosis. In this study, we aimed to assess these effects. METHODS: Using resting state functional magnetic resonance imaging 3T data obtained over several years of scanning patients for diagnostic and research purposes, we employed a seed-based approach to examine resting state connectivity in higher-order (default mode, bilateral external control, and salience) and lower-order (auditory, sensorimotor, and visual) resting state networks and connectivity with the thalamus, in 20 healthy unsedated controls, 8 unsedated patients with DOC, and 8 patients with DOC sedated with propofol. The DOC groups were matched for age at onset, etiology, time spent in DOC, diagnosis, standardized behavioral assessment scores, movement intensities, and pattern of structural brain injury (as assessed with T1-based voxel-based morphometry). RESULTS: DOC were associated with severely impaired resting state network connectivity in all but the visual network. Thalamic connectivity to higher-order network regions was also reduced. Propofol administration to patients was associated with minor further decreases in thalamic and insular connectivity. CONCLUSIONS: Our findings indicate that connectivity decreases associated with propofol sedation, involving the thalamus and insula, are relatively small compared with those already caused by DOC-associated structural brain injury. Nonetheless, given the known importance of the thalamus in brain arousal, its disruption could well reflect the diminished movement obtained in these patients. However, more research is needed on this topic to fully address the research question.

Results of a prospective study (CATS) on the effects of thalamic stimulation in minimally conscious and vegetative state patients.

OBJECTIVE Deep brain stimulation of the thalamus was introduced more than 40 years ago with the objective of improving the performance and attention of patients in a vegetative or minimally conscious state. Here, the authors report the results of the Cortical Activation by Thalamic Stimulation (CATS) study, a prospective multiinstitutional study on the effects of bilateral chronic stimulation of the anterior intralaminar thalamic nuclei and adjacent paralaminar regions in patients affected by a disorder of consciousness. METHODS The authors evaluated the clinical and radiological data of 29 patients in a vegetative state (unresponsive wakefulness syndrome) and 11 in a minimally conscious state that lasted for more than 6 months. Of these patients, 5 were selected for bilateral stereotactic implantation of deep brain stimulating electrodes into their thalamus. A definitive consensus for surgery was obtained for 3 of the selected patients. All 3 patients (2 in a vegetative state and 1 in a minimally conscious state) underwent implantation of bilateral thalamic electrodes and submitted to chronic stimulation for a minimum of 18 months and a maximum of 48 months. RESULTS In each case, there was an increase in desynchronization and the power spectrum of electroencephalograms, and improvement in the Coma Recovery Scale-Revised scores was found. Furthermore, the severity of limb spasticity and the number and severity of pathological movements were reduced. However, none of these patients returned to a fully conscious state. CONCLUSIONS Despite the limited number of patients studied, the authors confirmed that bilateral thalamic stimulation can improve the clinical status of patients affected by a disorder of consciousness, even though this stimulation did not induce persistent, clinically evident conscious behavior in the patients. Clinical trial registration no.: NCT01027572 ( ClinicalTrials.gov ).

Cortical reorganization in an astronaut's brain after long-duration spaceflight.

To date, hampered physiological function after exposure to microgravity has been primarily attributed to deprived peripheral neuro-sensory systems. For the first time, this study elucidates alterations in human brain function after long-duration spaceflight. More specifically, we found significant differences in resting-state functional connectivity between motor cortex and cerebellum, as well as changes within the default mode network. In addition, the cosmonaut showed changes in the supplementary motor areas during a motor imagery task. These results highlight the underlying neural basis for the observed physiological deconditioning due to spaceflight and are relevant for future interplanetary missions and vestibular patients.

Cerebral response to subject's own name showed high prognostic value in traumatic vegetative state.

BACKGROUND: Previous studies have shown the prognostic value of stimulation elicited blood-oxygen-level-dependent (BOLD) signal in traumatic patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS). However, to the best of our knowledge, no studies have focused on the relevance of etiology and level of consciousness in patients with disorders of consciousness (DOC) when explaining the relationship between BOLD signal and both outcome and signal variability. We herein propose a study in a large sample of traumatic and non-traumatic DOC patients in order to ascertain the relevance of etiology and level of consciousness in the variability and prognostic value of a stimulation-elicited BOLD signal. METHODS: 66 patients were included, and the response of each subject to his/her own name said by a familiar voice (SON-FV) was recorded using fMRI; 13 patients were scanned twice in the same day, respecting the exact same conditions in both cases. A behavioral follow-up program was carried out at 3, 6, and 12 months after scanning. RESULTS: Of the 39 VS/UWS patients, 12 (75%) out of 16 patients with higher level activation patterns recovered to minimally conscious state (MCS) or emergence from MCS (EMCS) and 17 (74%) out of 23 patients with lower level activation patterns or no activation had a negative outcome. Taking etiology into account for VS/UWS patients, a higher positive predictive value was assigned to traumatic patients, i.e., up to 92% (12/13) patients with higher level activation pattern achieved good recovery whereas 11 out of 13 (85%) non-traumatic patients with lower level activation or without activation had a negative clinical outcome. The reported data from visual analysis of fMRI activation patterns were corroborated using ROC curve analysis, which supported the correlation between auditory cortex activation volume and VS/UWS patients' recovery. The average brain activity overlap in primary and secondary auditory cortices in patients scanned twice was 52%. CONCLUSIONS: The activation type and volume in auditory cortex elicited by SON-FV significantly correlated with VS/UWS patients' prognosis, particularly in patients with traumatic etiology, however, this could not be established in MCS patients. Repeated use of this simple fMRI task might help obtain more reliable prognostic information.

Posterior cingulate cortex-related co-activation patterns: a resting state FMRI study in propofol-induced loss of consciousness.

BACKGROUND: Recent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating connectivity is an intrinsic phenomenon of brain dynamics that persists during anesthesia. Lately, point process analysis applied on functional data has revealed that much of the information regarding brain connectivity is contained in a fraction of critical time points of a resting state dataset. In the present study we want to extend this methodology for the investigation of resting state fMRI spatial pattern changes during propofol-induced modulation of consciousness, with the aim of extracting new insights on brain networks consciousness-dependent fluctuations. METHODS: Resting-state fMRI volumes on 18 healthy subjects were acquired in four clinical states during propofol injection: wakefulness, sedation, unconsciousness, and recovery. The dataset was reduced to a spatio-temporal point process by selecting time points in the Posterior Cingulate Cortex (PCC) at which the signal is higher than a given threshold (i.e., BOLD intensity above 1 standard deviation). Spatial clustering on the PCC time frames extracted was then performed (number of clusters = 8), to obtain 8 different PCC co-activation patterns (CAPs) for each level of consciousness. RESULTS: The current analysis shows that the core of the PCC-CAPs throughout consciousness modulation seems to be preserved. Nonetheless, this methodology enables to differentiate region-specific propofol-induced reductions in PCC-CAPs, some of them already present in the functional connectivity literature (e.g., disconnections of the prefrontal cortex, thalamus, auditory cortex), some others new (e.g., reduced co-activation in motor cortex and visual area). CONCLUSION: In conclusion, our results indicate that the employed methodology can help in improving and refining the characterization of local functional changes in the brain associated to propofol-induced modulation of consciousness.