Altered cerebellar gray matter and cerebellar-cortex resting-state functional connectivity in patients with bipolar disorder â .

BACKGROUND: Bipolar disorder (BP) is a common psychiatric disorder characterized by extreme fluctuations in mood. Recent studies have indicated the involvement of cerebellum in the pathogenesis of BP. However, no study has focused on the precise role of cerebellum exclusively in patients with bipolar I disorder (BP-I). METHODS: Forty-five patients with BP-I and 40 healthy controls were recruited. All subjects underwent clinical evaluation and Magnetic Resonance diffusion Tension Imaging scans. For structural images, we used a spatially unbiased infratentorial template toolbox to isolate the cerebellum and then preformed voxel-based morphometry (VBM) analyses to assess the difference in cerebellar gray matter volume (GMV) between the two groups. For the functional images, we chose the clusters that survived from VBM analysis as seeds and performed functional connectivity (FC) analysis. Between-group differences were assessed using the independent Students t test or the nonparametric Mann-Whitney U Test. For multiple comparisons, the results were further corrected with Gaussian random field (GRF) approach (voxel-level P < 0.001, cluster-level P < 0.05). RESULTS: Compared with healthy controls, BP-I patients showed significantly decreased GMV in left lobule V and left lobule VI (P < 0.05, GRF corrected). The FC of cerebellum with bilateral superior temporal gyrus, bilateral insula, bilateral rolandic operculum, right putamen, and left precentral gyrus was disrupted in BP-I patients (P < 0.05, GRF corrected). CONCLUSIONS: BP-I patients showed decreased cerebellar GMV and disrupted cerebellar-cortex resting-state FC. This suggests that cerebellar abnormalities may play an important role in the pathogenesis of BP-I.

Cortical correlates in upright dynamic and static balance in the elderly.

Falls are the second most frequent cause of injury in the elderly. Physiological processes associated with aging affect the elderly's ability to respond to unexpected balance perturbations, leading to increased fall risk. Every year, approximately 30% of adults, 65 years and older, experiences at least one fall. Investigating the neurophysiological mechanisms underlying the control of static and dynamic balance in the elderly is an emerging research area. The study aimed to identify cortical and muscular correlates during static and dynamic balance tests in a cohort of young and old healthy adults. We recorded cortical and muscular activity in nine elderly and eight younger healthy participants during an upright stance task in static and dynamic (core board) conditions. To simulate real-life dual-task postural control conditions, the second set of experiments incorporated an oddball visual task. We observed higher electroencephalographic (EEG) delta rhythm over the anterior cortex in the elderly and more diffused fast rhythms (i.e., alpha, beta, gamma) in younger participants during the static balance tests. When adding a visual oddball, the elderly displayed an increase in theta activation over the sensorimotor and occipital cortices. During the dynamic balance tests, the elderly showed the recruitment of sensorimotor areas and increased muscle activity level, suggesting a preferential motor strategy for postural control. This strategy was even more prominent during the oddball task. Younger participants showed reduced cortical and muscular activity compared to the elderly, with the noteworthy difference of a preferential activation of occipital areas that increased during the oddball task. These results support the hypothesis that different strategies are used by the elderly compared to younger adults during postural tasks, particularly when postural and cognitive tasks are combined. The knowledge gained in this study could inform the development of age-specific rehabilitative and assistive interventions.

Neurostructural changes and declining sensorimotor function due to cerebellar cortical degeneration.

Neurodegeneration of the cerebellum progresses over years and primarily affects cerebellar cortex. It leads to a progressive loss of control and coordination of gait, posture, speech, fine motor, and oculomotor function. Yet, little is known how the cerebro-cerebellar network compensates for the loss in cerebellar cortical neurons. To address this knowledge gap, we examined 30 people with cerebellar cortical degeneration and a group of 30 healthy controls. We assessed visuomotor performance during a forearm-pointing task to 10°, 25°, and 50° targets. In addition, using MRI imaging, we determined neurodegenerative-induced changes in gray matter volume (GMV) in the cerebro-cerebellar network and correlated them to markers of motor performance. The main results are as follows: first, the relative joint position error (RJPE) during pointing was significantly greater in the ataxia group for all targets confirming the expected motor control deficit. Second, in the ataxia group, GMV was significantly reduced in cerebellar cortex but increased in the deep cerebellar nuclei. Motor error (RJPE) correlated negatively with decreased cerebellar GMV but positively with increased GMV in supplementary motor area (SMA) and premotor cortex. GMV of the deep cerebellar nuclei did not correlate significantly with markers of motor performance. We discuss whether the GMV changes in the cerebellar output nuclei and the extracerebellar efferent targets in secondary motor cortex can be understood as a central compensatory response to the neurodegeneration of the cerebellar cortex.NEW & NOTEWORTHY Neurodegeneration of the cerebellum progresses over years and primarily affects cerebellar cortex. It leads to a progressive loss of control and coordination of movement. We here show that the neurodegenerative process not only leads to cells loss in cerebellar cortex but also induces neurostructural changes in the form of increased gray matter in the efferent targets of the cerebellar cortex, namely, the cerebellar output nuclei, the SMA, and premotor cortex.

The neural correlates of gait improvement by rhythmic sound stimulation in adults with Parkinson's disease - A functional magnetic resonance imaging study.

INTRODUCTION: Adults with Parkinson's disease (PD) experience gait disturbances that can sometimes be improved with rhythmic auditory stimulation (RAS); however, the underlying physiological mechanism for this improvement is not well understood. We investigated brain activation patterns in adults with PD and healthy controls (HC) using functional magnetic resonance imaging (fMRI) while participants imagined gait with or without RAS. METHODS: Twenty-seven adults with PD who could walk independently and walked more smoothly with rhythmic auditory cueing than without it, and 25 age-matched HC participated in this study. Participants imagined gait in the presence of RAS or white noise (WN) during fMRI. RESULTS: In the PD group, gait imagery with RAS activated cortical motor areas, including supplementary motor areas and the cerebellum, while gait imagery with WN additionally recruited the left parietal operculum. In HC, the induced activation was limited to cortical motor areas and the cerebellum for both the RAS and WN conditions. Within- and between-group analyses demonstrated that RAS reduced the activity of the left parietal operculum in the PD group but not in the HC group (condition-by-group interaction by repeated measures analysis of variance, p < 0.05). CONCLUSION: During gait imagery in adults with PD, the left parietal operculum was less activated by RAS than by WN, while no change was observed in HC, suggesting that rhythmic auditory stimulation may support the sensory-motor networks involved in gait, thus alleviating the overload of the parietal operculum and compensating for its dysfunction in these patients.

Time-dependent regulation of perineuronal nets in the cerebellar cortex during abstinence of cocaine-self administration.

RATIONALE: The probability of structural remodeling in brain circuits may be modulated by molecules of perineuronal nets (PNNs) that restrict neuronal plasticity to stabilize circuits. Animal research demonstrates that addictive drugs can remodel PNNs in different brain regions, including the cerebellum. OBJECTIVE: This study aimed to investigate the effects of short versus extended access to cocaine self-administration on PNN expression around Golgi interneurons in the cerebellar cortex after different periods of abstinence. METHODS: After 1 week of training (2 h/day), Sprague-Dawley rats self-administered cocaine daily for 20 days under short (ShA) or extended (LgA) access. PNN expression in the cerebellum was assessed after 1 day, 7 days, and 28 days of forced abstinence. PNNs were immunolabeled using Wisteria floribunda agglutinin (WFA) and captured by confocal microscopy. RESULTS: WFA intensity increased in PNN-bearing Golgi neurons over the abstinence period and a higher proportion of more intense PNNs were formed throughout the first month of abstinence. After the first 24 h of cocaine abstinence, however, we found a reduction in WFA intensity in the cerebellar cortex of rats with ShA to cocaine as compared to naïve animals. When comparing with naïve rats, LgA rats showed consistent PNN upregulation at 28 days of cocaine abstinence. CONCLUSIONS: Our results suggest that cocaine self-administration produces modifications in PNN that enhance conditions for synaptic plasticity in the cerebellar cortex. These modifications are revealed shortly after the cessation of drug intake but PNNs become more intense during protracted abstinence in the LgA group, pointing to the stabilization of drug-induced synaptic changes. These findings indicate that extended access to cocaine self-administration dynamically regulates conditions for plasticity in the cerebellum during abstinence.

Longitudinal Changes of Cerebellar Thickness in Autism Spectrum Disorder.

Many studies have reported abnormal cerebellar volume in patients with autism spectrum disorder (ASD) and that this abnormal volume can change with age. In the present study, we used CERES, an automated and reliable quantitative analysis tool, and adopted a longitudinal design to examine developmental changes in the cerebellar lobular thickness in ASD and quantified the relationship between cerebellar thickness development and clinical symptoms. Nineteen individuals with ASD (16 males; age, 12.53 ±â€¯2.34 years at baseline, interval: 2.33 years) and 14 typically developing controls (TD; 12 males; age, 13.50 ±â€¯1.77 years at baseline, interval: 2.31 years) underwent T1-weighted magnetic resonance imaging at two time points. To explore the relationship between cerebellar lobular thickness and the symptoms of ASD, the correlation of Autism Diagnostic Observation Schedule (ADOS) score with lobular thickness data was calculated. The cerebellar lobule thickness decreased in the right Crus II and the Crus II asymmetry was reduced in individuals with ASD. The reduction in lobular thickness and the asymmetry in Crus II were associated with the severity of stereotyped behavior symptoms. Structural differences and behavioral correlations were concentrated in the right cerebellar Crus II. These results emphasize the importance of the potential functional effect of structural differences in cerebellar subregions on ASD and suggest that the changes of thickness in the right cerebellar Crus II are related to the core profile of ASD.

Neuroprotective Effect of the Inhibitor Salubrinal after Cardiac Arrest in a Rodent Model.

Cardiac arrest (CA) yields poor neurological outcomes. Salubrinal (Sal), an endoplasmic reticulum (ER) stress inhibitor, has been shown to have neuroprotective effects in both in vivo and in vitro brain injury models. This study investigated the neuroprotective mechanisms of Sal in postresuscitation brain damage in a rodent model of CA. In the present study, rats were subjected to 6 min of CA and then successfully resuscitated. Either Sal (1 mg/kg) or vehicle (DMSO) was injected blindly 30 min before the induction of CA. Neurological status was assessed 24 h after CA, and the cortex was collected for analysis. As a result, we observed that, compared with the vehicle-treated animals, the rats pretreated with Sal exhibited markedly improved neurological performance and cortical mitochondrial morphology 24 h after CA. Moreover, Sal pretreatment was associated with the following: (1) upregulation of superoxide dismutase activity and a reduction in maleic dialdehyde content; (2) preserved mitochondrial membrane potential; (3) amelioration of the abnormal distribution of cytochrome C; and (4) an increased Bcl-2/Bax ratio, decreased cleaved caspase 3 upregulation, and enhanced HIF-1α expression. Our findings suggested that Sal treatment improved neurological dysfunction 24 h after CPR (cardiopulmonary resuscitation), possibly through mitochondrial preservation and stabilizing the structure of HIF-1α.

Cerebellar Lobulus Simplex and Crus I Differentially Represent Phase and Phase Difference of Prefrontal Cortical and Hippocampal Oscillations.

The cerebellum has long been implicated in tasks involving precise temporal control, especially in the coordination of movements. Here we asked whether the cerebellum represents temporal aspects of oscillatory neuronal activity, measured as instantaneous phase and difference between instantaneous phases of oscillations in two cerebral cortical areas involved in cognitive function. We simultaneously recorded Purkinje cell (PC) single-unit spike activity in cerebellar lobulus simplex (LS) and Crus I and local field potential (LFP) activity in the medial prefrontal cortex (mPFC) and dorsal hippocampus CA1 region (dCA1). Purkinje cells in cerebellar LS and Crus I differentially represented specific phases and phase differences of mPFC and dCA1 LFP oscillations in a frequency-specific manner, suggesting a site- and frequency-specific cerebellar representation of temporal aspects of neuronal oscillations in non-motor cerebral cortical areas. These findings suggest that cerebellar interactions with cerebral cortical areas involved in cognitive functions might involve temporal coordination of neuronal oscillations.

Dynamic protein changes in the perihaemorrhagic zone of Surgically Treated Intracerebral Haemorrhage Patients.

The secondary injury cascades exacerbating the initial brain injury following intracerebral haemorrhage (ICH) are incompletely understood. We used dual microdialysis (MD) catheters placed in the perihaemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) at time of surgical ICH evacuation in ten patients (range 26-70 years). Routine interstitial MD markers (including glucose and the lactate/pyruvate ratio) were analysed and remaining microdialysate was analysed by two-dimensional gel electrophoresis (2-DE) and nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS). Two time intervals were analysed; median 2-10 hours post-surgery (time A) and median 68-76 hours post-ICH onset (time B). Using 2-DE, we quantified 232 ± 31 different protein spots. Two proteins differed between the MD catheters at time A, and 12 proteins at time B (p < 0.05). Thirteen proteins were significantly altered between time A and time B in the SNX and seven proteins in the PHZ, respectively. Using nLC-MS/MS ca 800 proteins were identified out of which 76 were present in all samples. At time A one protein was upregulated and two downregulated, and at time B, seven proteins were upregulated, and four downregulated in the PHZ compared to the SNX. Microdialysis-based proteomics is feasible for study of secondary injury mechanisms and discovery of biomarkers after ICH.

The presence of cerebral white matter lesions and lower skin microvascular perfusion predicts lower cognitive performance in type 1 diabetes patients with retinopathy but not in healthy controls-A longitudinal study.

OBJECTIVE: Cognitive impairments in type 1 diabetes may result from hyperglycemia-associated cerebral microangiopathy. We aimed to identify cerebral microangiopathy and skin microvascular dysfunction-as a surrogate marker for generalized microvascular function-as predictors of cognitive performance over time. METHODS: In this prospective cohort study, 25 type 1 diabetes patients with proliferative retinopathy and 25 matched healthy controls underwent neurocognitive testing at baseline and after follow-up (3.8 ± 0.8 years). At baseline, 1.5-T cerebral magnetic resonance imaging was used to detect WML and cerebral microbleeds. Skin capillary perfusion was assessed by means of capillary microscopy. RESULTS: In type 1 diabetes patients, but not in healthy controls, the presence of WML (ß = -0.419; P = 0.037) as well as lower skin capillary perfusion (baseline: ß = 0.753; P < 0.001; peak hyperemia: ß = 0.743; P = 0.001; venous occlusion: ß = 0.675; P = 0.003; capillary recruitment: ß = 0.549; P = 0.022) at baseline was associated with lower cognitive performance over time, independent of age, sex, HbA1c, and severe hypoglycemia. The relationship between WML and lower cognitive performance was significantly reduced after adjusting for capillary perfusion. CONCLUSIONS: These data fit the hypothesis that cerebral microangiopathy is a manifestation of generalized microvascular dysfunction, leading to lower cognitive performance.

Cerebral perfusion abnormalities in patients with persistent postural-perceptual dizziness (PPPD): a SPECT study.

Persistent postural-perceptual dizziness (PPPD) is a recently defined syndrome with chronic dizziness interrupting daily life. Although the high levels of anxiety and functional changes in postural control strategy and multi-sensory information processing and integration may be underlying the pathophysiology, its neural mechanisms are poorly understood. The aim of this study was to examine the regional cerebral blood flow (rCBF) in patients with PPPD using single photon emission computed tomography (SPECT). A total of 25 patients with PPPD and 25 healthy controls participated in the study. All participants underwent brain SPECT and the patients completed the Dizziness Handicap Inventory. SPECT images were compared between the groups, and the correlation of rCBF and disease severity/duration was assessed in patients. Compared with controls, PPPD patients showed a significantly decreased rCBF in the insula and frontal lobe, mainly in the left posterior insula, bilateral superior frontal gyrus, right inferior frontal gyrus, right precentral gyrus, and left medial orbital gyrus. Additionally, PPPD patients showed a significant rCBF increase in the bilateral cerebellum compared with controls. The results of our study suggest that the altered rCBF in the insular, frontal, and cerebellar cortices might be reflecting the process of maladaptation and the compensatory responses for the changes in PPPD.

Cerebellar Cortex as a Therapeutic Target for Neurostimulation.

Non-invasive stimulation of the cerebellum is growingly applied both in the clinic and in research settings to modulate the activities of cerebello-cerebral loops. The anatomical location of the cerebellum, the high responsiveness of the cerebellar cortex to magnetic/electrical stimuli, and the implication of the cerebellum in numerous cerebello-cerebral networks make the cerebellum an ideal target for investigations and therapeutic purposes. In this mini-review, we discuss the potentials of cerebellar neuromodulation in major brain disorders in order to encourage large-scale sham-controlled research and explore this therapeutic aid further.

Electrophysiological Correlates of Blast-Wave Induced Cerebellar Injury.

Understanding the mechanisms underlying traumatic neural injury and the sequelae of events in the acute phase is important for deciding on the best window of therapeutic intervention. We hypothesized that evoked potentials (EP) recorded from the cerebellar cortex can detect mild levels of neural trauma and provide a qualitative assessment tool for progression of cerebellar injury in time. The cerebellar local field potentials evoked by a mechanical tap on the hand and collected with chronically implanted micro-ECoG arrays on the rat cerebellar cortex demonstrated substantial changes both in amplitude and timing as a result of blast-wave induced injury. The results revealed that the largest EP changes occurred within the first day of injury, and partial recoveries were observed from day-1 to day-3, followed by a period of gradual improvements (day-7 to day-14). The mossy fiber (MF) and climbing fiber (CF) mediated components of the EPs were affected differentially. The behavioral tests (ladder rung walking) and immunohistological analysis (calbindin and caspase-3) did not reveal any detectable changes at these blast pressures that are typically considered as mild (100-130 kPa). The results demonstrate the sensitivity of the electrophysiological method and its use as a tool to monitor the progression of cerebellar injuries in longitudinal animal studies.

Modulation of Cerebellar Cortical Plasticity Using Low-Intensity Focused Ultrasound for Poststroke Sensorimotor Function Recovery.

BACKGROUND: Stroke affects widespread brain regions through interhemispheric connections by influencing bilateral motor activity. Several noninvasive brain stimulation techniques have proved their capacity to compensate the functional loss by manipulating the neural activity of alternative pathways. Over the past few decades, brain stimulation therapies have been tailored within the theoretical framework of modulation of cortical excitability to enhance adaptive plasticity after stroke. OBJECTIVE: However, considering the vast difference between animal and human cerebral cortical structures, it is important to approach specific neuronal target starting from the higher order brain structure for human translation. The present study focuses on stimulating the lateral cerebellar nucleus (LCN), which sends major cerebellar output to extensive cortical regions. METHODS: In this study, in vivo stroke mouse LCN was exposed to low-intensity focused ultrasound (LIFU). After the LIFU exposure, animals underwent 4 weeks of rehabilitative training. RESULTS: During the cerebellar LIFU session, motor-evoked potentials (MEPs) were generated in both forelimbs accompanying excitatory sonication parameter. LCN stimulation group on day 1 after stroke significantly enhanced sensorimotor recovery compared with the group without stimulation. The recovery has maintained for a 4-week period in 2 behavior tests. Furthermore, we observed a significantly decreased level of brain edema and tissue swelling in the affected hemisphere 3 days after the stroke. CONCLUSIONS: This study provides the first evidence showing that LIFU-induced cerebellar modulation could be an important strategy for poststroke recovery. A longer follow-up study is, however, necessary in order to fully confirm the effects of LIFU on poststroke recovery.

Reduced structural complexity of the right cerebellar cortex in male children with autism spectrum disorder.

The cerebellum contains 80% of all neurons in the human brain and contributes prominently to implicit learning and predictive processing across motor, sensory, and cognitive domains. As morphological features of the cerebellum in atypically developing individuals remain unexplored in-vivo, this is the first study to use high-resolution 3D fractal analysis to estimate fractal dimension (FD), a measure of structural complexity of an object, of the left and right cerebellar cortex (automatically segmented from Magnetic Resonance Images using FreeSurfer), in male children with Autism Spectrum Disorders (ASD) (N = 20; mean age: 8.8 years old, range: 7.13-10.27) and sex, age, verbal-IQ, and cerebellar volume-matched typically developing (TD) boys (N = 18; mean age: 8.9 years old, range: 6.47-10.52). We focus on an age range within the 'middle and late childhood' period of brain development, between 6 and 12 years. A Mann-Whitney U test revealed a significant reduction in the FD of the right cerebellar cortex in ASD relative to TD boys (P = 0.0063, Bonferroni-corrected), indicating flatter and less regular surface protrusions in ASD relative to TD males. Consistent with the prediction that the cerebellum participates in implicit learning, those ASD boys with a higher (vs. lower) PIQ>VIQ difference showed higher, more normative complexity values, closer to TD children, providing new insight on our understanding of the neurological basis of differences in verbal and performance cognitive abilities that often characterize individuals with ASD.

Possible ameliorative effect of Vitamin C on cerebellar toxicity induced by gibberellic acid during late pregnancy and early postnatal periods in albino rats

Gibberellic acid (GA3) is a plant growth regulator, widely used in agriculture in Egypt. The goal of this study was to illustrate the histopathological effects of (GA3) on the growing cerebellar cortex and the possible ameliorative effect of vitamin C. Fifty female Sprague-Dawly rats were classified into the following groups: Group I (control group); Group II (GA3-treated group), which received intra-gastric daily dose of GA3 55 mg/kg from the 14th day of pregnancy until the day 14 after delivery; Group III (GA3 & Vitamin C treated group), which received intra-gastric daily dose GA3, 55 mg/kg simultaneously with 100 mg of Vitamin C /kg from the 14th day of pregnancy till day 14 after delivery; and Group IV (Vitamin C-treated group), which received intra-gastric daily dose 100 mg of Vitamin C / kg from the 14th day of pregnancy till day 14 after delivery. One month after delivery, cerebella of pups from all groups were extracted and examined. The cerebellar cortex of GA3-treated group revealed degenerated and displaced Purkinje and granular nerve cells with prominent spongiosis in the molecular layer. Vitamin C administration resulted in marked regression of the previously mentioned neurotoxic effects. In conclusion: results of the current study revealed that maternal exposure to GA3 during pregnancy and lactation caused delayed development of the offsprings' cerebellar cortex. The co-administration of Vitamin C greatly reduced these neuro-toxic effects of GA3 exposure

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Lobular patterns of cerebellar resting-state connectivity in adults with Autism Spectrum Disorder.

Autism spectrum disorder is a neurodevelopmental disorder characterized by core deficits in social functioning. Core autistics traits refer to poor social and imagination skills, poor attention-switching/strong focus of attention, exceptional attention to detail, as expressed by the autism-spectrum quotient. Over the years, the importance of the cerebellum in the aetiology of autism spectrum disorder has been acknowledged. Neuroimaging studies have provided a strong support to this view, showing both structural and functional connectivity alterations to affect the cerebellum in autism spectrum disorder. According to the underconnectivity theory, disrupted connectivity within cerebello-cerebral networks has been specifically implicated in the aetiology of autism spectrum disorder. However, inconsistent results have been generated across studies. In this study, an integrated approach has been used in a selected population of adults with autism spectrum disorder to analyse both cerebellar morphometry and functional connectivity. In individuals with autism spectrum disorder, a decreased cerebellar grey matter volume affected the right Crus II, a region showing extensive connections with cerebral areas related to social functions. This grey matter reduction correlates with the degree of autistic traits as measured by autism-spectrum quotient. Interestingly, altered functional connectivity was found between the reduced cerebellar Crus II and contralateral cerebral regions, such as frontal and temporal areas. Overall, the present data suggest that adults with autism spectrum disorder present with specific cerebellar structural alterations that may affect functional connectivity within cerebello-cerebral modules relevant to social processing and account for core autistics traits.

Relationship altered between functional T1ρ and BOLD signals in bipolar disorder.

INTRODUCTION: Functional neuroimaging typically relies on the blood-oxygen-level-dependent (BOLD) contrast, which is sensitive to the influx of oxygenated blood following neuronal activity. A new method, functional T1 relaxation in the rotating frame (fT1ρ) is thought to reflect changes in local brain metabolism, likely pH, and may more directly measure neuronal activity. These two methods were applied to study activation of the visual cortex in participants with bipolar disorder as compared to controls. METHODS: Thirty-nine participants with bipolar disorder and 32 healthy controls underwent functional neuroimaging during a flashing checkerboard paradigm. Functional images were acquired in alternating blocks of BOLD and fT1ρ. Linear mixed-effect models were used to examine the relationship between these two functional imaging modalities and to test whether that relationship was altered in bipolar disorder. RESULTS: BOLD and fT1ρ signal were strongly related in visual and cerebellar areas during the task in controls. The relationship between these two measures was reduced in bipolar disorder within the visual areas, cerebellum, striatum, and thalamus. CONCLUSIONS: These results support a distinct mechanisms underlying BOLD and fT1ρ signals. The weakened relationship between these imaging modalities may provide a novel tool for measuring pathology in bipolar disorder and other psychiatric illnesses.

Localizing value of electrical source imaging: Frontal lobe, malformations of cortical development and negative MRI related epilepsies are the best candidates.

OBJECTIVE: We aimed to prospectively assess the anatomical concordance of electric source localizations of interictal discharges with the epileptogenic zone (EZ) estimated by stereo-electroencephalography (SEEG) according to different subgroups: the type of epilepsy, the presence of a structural MRI lesion, the aetiology and the depth of the EZ. METHODS: In a prospective multicentric observational study, we enrolled 85 consecutive patients undergoing pre-surgical SEEG investigation for focal drug-resistant epilepsy. Electric source imaging (ESI) was performed before SEEG. Source localizations were obtained from dipolar and distributed source methods. Anatomical concordance between ESI and EZ was defined according to 36 predefined sublobar regions. ESI was interpreted blinded to- and subsequently compared with SEEG estimated EZ. RESULTS: 74 patients were finally analyzed. 38 patients had temporal and 36 extra-temporal lobe epilepsy. MRI was positive in 52. 41 patients had malformation of cortical development (MCD), 33 had another or an unknown aetiology. EZ was medial in 27, lateral in 13, and medio-lateral in 34. In the overall cohort, ESI completely or partly localized the EZ in 85%: full concordance in 13 cases and partial concordance in 50 cases. The rate of ESI full concordance with EZ was significantly higher in (i) frontal lobe epilepsy (46%; p = 0.05), (ii) cases of negative MRI (36%; p = 0.01) and (iii) MCD (27%; p = 0.03). The rate of ESI full concordance with EZ was not statistically different according to the depth of the EZ. SIGNIFICANCE: We prospectively demonstrated that ESI more accurately estimated the EZ in subgroups of patients who are often the most difficult cases in epilepsy surgery: frontal lobe epilepsy, negative MRI and the presence of MCD.

Optogenetic neuronal stimulation of the lateral cerebellar nucleus promotes persistent functional recovery after stroke.

Stroke induces network-wide changes in the brain, affecting the excitability in both nearby and remotely connected regions. Brain stimulation is a promising neurorestorative technique that has been shown to improve stroke recovery by altering neuronal activity of the target area. However, it is unclear whether the beneficial effect of stimulation is a result of neuronal or non-neuronal activation, as existing stimulation techniques nonspecifically activate/inhibit all cell types (neurons, glia, endothelial cells, oligodendrocytes) in the stimulated area. Furthermore, which brain circuit is efficacious for brain stimulation is unknown. Here we use the optogenetics approach to selectively stimulate neurons in the lateral cerebellar nucleus (LCN), a deep cerebellar nucleus that sends major excitatory output to multiple motor and sensory areas in the forebrain. Repeated LCN stimulations resulted in a robust and persistent recovery on the rotating beam test, even after cessation of stimulations for 2 weeks. Furthermore, western blot analysis demonstrated that LCN stimulations significantly increased the axonal growth protein GAP43 in the ipsilesional somatosensory cortex. Our results demonstrate that pan-neuronal stimulations of the LCN is sufficient to promote robust and persistent recovery after stroke, and thus is a promising target for brain stimulation.