Frequency dependent emotion differentiation and directional coupling in amygdala, orbitofrontal and medial prefrontal cortex network with intracranial recordings.

The amygdala, orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) form a crucial part of the emotion circuit, yet their emotion induced responses and interactions have been poorly investigated with direct intracranial recordings. Such high-fidelity signals can uncover precise spectral dynamics and frequency differences in valence processing allowing novel insights on neuromodulation. Here, leveraging the unique spatio-temporal advantages of intracranial electroencephalography (iEEG) from a cohort of 35 patients with intractable epilepsy (with 71 contacts in amygdala, 31 in OFC and 43 in mPFC), we assessed the spectral dynamics and interactions between the amygdala, OFC and mPFC during an emotional picture viewing task. Task induced activity showed greater broadband gamma activity in the negative condition compared to positive condition in all the three regions. Similarly, beta activity was increased in the negative condition in the amygdala and OFC while decreased in mPFC. Furthermore, beta activity of amygdala showed significant negative association with valence ratings. Critically, model-based computational analyses revealed unidirectional connectivity from mPFC to the amygdala and bidirectional communication between OFC-amygdala and OFC-mPFC. Our findings provide direct neurophysiological evidence for a much-posited model of top-down influence of mPFC over amygdala and a bidirectional influence between OFC and the amygdala. Altogether, in a relatively large sample size with human intracranial neuronal recordings, we highlight valence-dependent spectral dynamics and dyadic coupling within the amygdala-mPFC-OFC network with implications for potential targeted neuromodulation in emotion processing.

Risk and aversion coding in human habenula high gamma activity.

Neurons in the primate lateral habenula fire in response to punishments and are inhibited by rewards. Through its modulation of midbrain monoaminergic activity, the habenula is believed to play an important role in adaptive behavioural responses to punishment and underlie depressive symptoms and their alleviation with ketamine. However, its role in value-based decision-making in humans is poorly understood due to limitations with non-invasive imaging methods which measure metabolic, not neural, activity with poor temporal resolution. Here, we overcome these limitations to more closely bridge the gap between species by recording local field potentials directly from the habenula in 12 human patients receiving deep brain stimulation treatment for bipolar disorder (n = 4), chronic pain (n = 3), depression (n = 3) and schizophrenia (n = 2). This allowed us to record neural activity during value-based decision-making tasks involving monetary rewards and losses. High-frequency gamma (60-240 Hz) activity, a proxy for population-level spiking involved in cognitive computations, increased during the receipt of loss and decreased during receipt of reward. Furthermore, habenula high gamma also encoded risk during decision-making, being larger in amplitude for high compared to low risk. For both risk and aversion, differences between conditions peaked approximately between 400 and 750 ms after stimulus onset. The findings not only demonstrate homologies with the primate habenula but also extend its role to human decision-making, showing its temporal dynamics and suggesting revisions to current models. The findings suggest that habenula high gamma could be used to optimize real-time closed-loop deep brain stimulation treatment for mood disturbances and impulsivity in psychiatric disorders.

Integrated Amygdala, Orbitofrontal and Hippocampal Contributions to Reward and Loss Coding Revealed with Human Intracranial EEG.

Neurophysiological work in primates and rodents have shown the amygdala plays a central role in reward processing through connectivity with the orbitofrontal cortex (OFC) and hippocampus. However, understanding the role of oscillations in each region and their connectivity in different stages of reward processing in humans has been hampered by limitations with noninvasive methods such as poor spatial and temporal resolution. To overcome these limitations, we recorded local field potentials (LFPs) directly from the amygdala, OFC and hippocampus simultaneously in human male and female epilepsy patients performing a monetary incentive delay (MID) task. This allowed us to dissociate electrophysiological activity and connectivity patterns related to the anticipation and receipt of rewards and losses in real time. Anticipation of reward increased high-frequency gamma (HFG; 60-250 Hz) activity in the hippocampus and theta band (4-8 Hz) synchronization between amygdala and OFC, suggesting roles in memory and motivation. During receipt, HFG in the amygdala was involved in outcome value coding, the OFC cue context-specific outcome value comparison and the hippocampus reward coding. Receipt of loss decreased amygdala-hippocampus theta and increased amygdala-OFC HFG amplitude coupling which coincided with subsequent adjustments in behavior. Increased HFG synchronization between the amygdala and hippocampus during reward receipt suggested encoding of reward information into memory for reinstatement during anticipation. These findings extend what is known about the primate brain to humans, showing key spectrotemporal coding and communication dynamics for reward and punishment related processes which could serve as more precise targets for neuromodulation to establish causality and potential therapeutic applications.SIGNIFICANCE STATEMENT Dysfunctional reward processing contributes to many psychiatric disorders. Neurophysiological work in primates has shown the amygdala, orbitofrontal cortex (OFC), and hippocampus play a synergistic role in reward processing. However, because of limitations with noninvasive imaging, it is unclear whether the same interactions occur in humans and what oscillatory mechanisms underpin them. We addressed this issue by recording local field potentials (LFPs) from all three regions in human epilepsy patients during monetary reward processing. There was increased amygdala-OFC high-frequency coupling when losing money which coincided with subsequent adjustments in behavior. In contrast, increased amygdala-hippocampus high-frequency phase-locking suggested a role in reward memory. The findings highlight amygdala networks for reward and punishment processes that could act as more precise neuromodulation targets to treat psychiatric disorders.

Structural and functional correlates of the response to deep brain stimulation at ventral capsule/ventral striatum region for treatment-resistant depression.

BACKGROUND: Though deep brain stimulation (DBS) shows increasing potential in treatment-resistant depression (TRD), the underlying neural mechanisms remain unclear. Here, we investigated functional and structural connectivities related to and predictive of clinical effectiveness of DBS at ventral capsule/ventral striatum region for TRD. METHODS: Stimulation effects of 71 stimulation settings in 10 TRD patients were assessed. The electric fields were estimated and combined with normative functional and structural connectomes to identify connections as well as fibre tracts beneficial for outcome. We calculated stimulation-dependent optimal connectivity and constructed models to predict outcome. Leave-one-out cross-validation was used to validate the prediction value. RESULTS: Successful prediction of antidepressant effectiveness in out-of-sample patients was achieved by the optimal connectivity profiles constructed with both the functional connectivity (R=0.49 at p<10-4; deviated by 14.4±10.9% from actual, p<0.001) and structural connectivity (R=0.51 at p<10-5; deviated by 15.2±11.5% from actual, p<10-5). Frontothalamic pathways and cortical projections were delineated for optimal clinical outcome. Similarity estimates between optimal connectivity profile from one modality (functional/structural) and individual brain connectivity in the other modality (structural/functional) significantly cross-predicted the outcome of DBS. The optimal structural and functional connectivity mainly converged at the ventral and dorsal lateral prefrontal cortex and orbitofrontal cortex. CONCLUSIONS: Connectivity profiles and fibre tracts following frontothalamic streamlines appear to predict outcome of DBS for TRD. The findings shed light on the neural pathways in depression and may be used to guide both presurgical planning and postsurgical programming after further validation.

Tourette-like syndrome secondary to Kleefstra syndrome 1 with a de novo microdeletion in the EHMT1 gene.

BACKGROUND: Gills de la Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder manifested by motor and vocal tics. Kleefstra syndrome 1 (KS1), a rare genetic disorder, is caused by haploinsufficiency of the EHMT1 gene and is characterized by intellectual disability (ID), childhood hypotonia, and distinctive facial features. Tourette-like syndrome in KS1 has rarely been reported. CASE PRESENTATION: Here we describe a 7-year-old girl presenting involuntary motor and vocal tics, intellectual disability, childhood hypotonia, and dysmorphic craniofacial appearances, as well as comorbidities including attention deficit-hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and self-injurious behavior (SIB). The patient's CNV-seq testing revealed a de novo 320-kb deletion in the 9q34.3 region encompassing the EHMT1 gene. CONCLUSIONS: This is the first case reporting Tourette-like syndrome secondary to KS1 with a de novo microdeletion in the EHMT1 gene. Our case suggests TS with ID and facial anomalies indicate a genetic cause and broadens the phenotypic and genotypic spectrum of both TS and KS1.

Anterior Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Tractography and Lesion Geometry study.

INTRODUCTION: A bilateral anterior capsulotomy effectively treats refractory obsessive-compulsive disorder (OCD). We investigated the geometry of lesions and disruption of white matter pathways within the anterior limb of the internal capsule (ALIC) in patients with different outcomes. METHODS: In this retrospective study, we analyzed data from 18 patients with refractory OCD who underwent capsulotomies. Patients were grouped into "responders" and "nonresponders" based on the percentage of decrease in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) after surgery. We investigated neurobehavioral adverse effects and analyzed the overlap between lesions and the ventromedial prefrontal (vmPFC) and dorsolateral prefrontal (dlPFC) pathways. Probabilistic maps were constructed to investigate the relationship between lesion location and clinical outcomes. RESULTS: Of the 18 patients who underwent capsulotomies, 12 were responders (>35% improvement in YBOCS), and six were nonresponders. The vmPFC pathway was more involved than the dlPFC pathway in responders (p = 0.01), but no significant difference was observed in nonresponders (p = 0.10). The probabilistic voxel-wise efficacy map showed a relationship between ventral voxels within the ALIC with symptom improvement. Weight gains occurred in 11/18 (61%) patients and could be associated with medial voxels within the ALIC. CONCLUSION: The optimal outcome after capsulotomy in refractory OCD is linked to vmPFC disruption in the ALIC. Medial voxels within the ALIC could be associated with weight gains following capsulotomy.

Combined quantitative T2 mapping and [18F]FDG PET could improve lateralization of mesial temporal lobe epilepsy.

OBJECTIVES: To investigate whether quantitative T2 mapping is complementary to [18F]FDG PET in epileptogenic zone detection, thus improving the lateralization accuracy for drug-resistant mesial temporal lobe epilepsy (MTLE) using hybrid PET/MR. METHODS: We acquired routine structural MRI, T2-weighted FLAIR, whole brain T2 mapping, and [18F]FDG PET in 46 MTLE patients and healthy controls on a hybrid PET/MR scanner, followed with computing voxel-based z-score maps of patients in reference to healthy controls. Asymmetry indexes of the hippocampus were calculated for each imaging modality, which then enter logistic regression models as univariate or multivariate for lateralization. Stereoelectroencephalography (SEEG) recordings and clinical decisions were collected as gold standard. RESULTS: Routine structural MRI and T2w-FLAIR lateralized 47.8% (22/46) of MTLE patients, and FDG PET lateralized 84.8% (39/46). T2 mapping combined with [18F]FDG PET improved the lateralization accuracy by correctly lateralizing 95.6% (44/46) of MTLE patients. The asymmetry indexes of hippocampal T2 relaxometry and PET exhibit complementary tendency in detecting individual laterality, especially for MR-negative patients. In the quantitative analysis of z-score maps, the ipsilateral hippocampus had significantly lower SUVR (LTLE, p < 0.001; RTLE, p < 0.001) and higher T2 value (LTLE, p < 0.001; RTLE, p = 0.001) compared to the contralateral hippocampus. In logistic regression models, PET/T2 combination resulted in the highest AUC of 0.943 in predicting lateralization for MR-negative patients, followed by PET (AUC = 0.857) and T2 (AUC = 0.843). CONCLUSIONS: The combination of quantitative T2 mapping and [18F]FDG PET could improve lateralization for temporal lobe epilepsy. KEY POINTS: • Quantitative T2 mapping and18F-FDG PET are complementary in the characterization of hippocampal alterations of MR-negative temporal lobe epilepsy patients. • The combination of quantitative T2 and18F-FDG PET obtained from hybrid PET/MR could improve lateralization for temporal lobe epilepsy.

Dynamic analysis on simultaneous iEEG-MEG data via hidden Markov model.

BACKGROUND: Intracranial electroencephalography (iEEG) recordings are used for clinical evaluation prior to surgical resection of the focus of epileptic seizures and also provide a window into normal brain function. A major difficulty with interpreting iEEG results at the group level is inconsistent placement of electrodes between subjects making it difficult to select contacts that correspond to the same functional areas. Recent work using time delay embedded hidden Markov model (HMM) applied to magnetoencephalography (MEG) resting data revealed a distinct set of brain states with each state engaging a specific set of cortical regions. Here we use a rare group dataset with simultaneously acquired resting iEEG and MEG to test whether there is correspondence between HMM states and iEEG power changes that would allow classifying iEEG contacts into functional clusters. METHODS: Simultaneous MEG-iEEG recordings were performed at rest on 11 patients with epilepsy whose intracranial electrodes were implanted for pre-surgical evaluation. Pre-processed MEG sensor data was projected to source space. Time delay embedded HMM was then applied to MEG time series. At the same time, iEEG time series were analyzed with time-frequency decomposition to obtain spectral power changes with time. To relate MEG and iEEG results, correlations were computed between HMM probability time courses of state activation and iEEG power time course from the mid contact pair for each electrode in equally spaced frequency bins and presented as correlation spectra for the respective states and iEEG channels. Association of iEEG electrodes with HMM states based on significant correlations was compared to that based on the distance to peaks in subject-specific state topographies. RESULTS: Five HMM states were inferred from MEG. Two of them corresponded to the left and the right temporal activations and had a spectral signature primarily in the theta/alpha frequency band. All the electrodes had significant correlations with at least one of the states (p < 0.05 uncorrected) and for 27/50 electrodes these survived within-subject FDR correction (q < 0.05). These correlations peaked in the theta/alpha band. There was a highly significant dependence between the association of states and electrodes based on functional correlations and that based on spatial proximity (p = 5.6e-6,χ2 test for independence). Despite the potentially atypical functional anatomy and physiological abnormalities related to epilepsy, HMM model estimated from the patient group was very similar to that estimated from healthy subjects. CONCLUSION: Epilepsy does not preclude HMM analysis of interictal data. The resulting group functional states are highly similar to those reported for healthy controls. Power changes recorded with iEEG correlate with HMM state time courses in the alpha-theta band and the presence of this correlation can be related to the spatial location of electrode contacts close to the individual peaks of the corresponding state topographies. Thus, the hypothesized relation between iEEG contacts and HMM states exists and HMM could be further explored as a method for identifying comparable iEEG channels across subjects for the purposes of group analysis.

Dynamic changes in rhythmic and arrhythmic neural signatures in the subthalamic nucleus induced by anaesthesia and tracheal intubation.

BACKGROUND: Subcortical structures, including the basal ganglia, have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. How the basal ganglia contribute to the loss and recovery of consciousness during anaesthesia has, however, not yet been well characterised. METHODS: Twelve patients with advanced Parkinson's disease, who were undergoing deep brain stimulation (DBS) electrode implantation in the subthalamic nucleus (STN), were included in this study. Local field potentials (LFPs) were recorded from the DBS electrodes and EEG was recorded from the scalp during induction of general anaesthesia (with propofol and sufentanil) and during tracheal intubation. Neural signatures of loss of consciousness and of the expected arousal during intubation were sought in the STN and EEG recordings. RESULTS: Propofol-sufentanil anaesthesia resulted in power increases in delta, theta, and alpha frequencies, and broadband power decreases in higher frequencies in both STN and frontal cortical areas. This was accompanied by increased STN-frontal cortical coherence only in the alpha frequency band (119 [68]%; P=0.0049). We observed temporal activity changes in STN after tracheal intubation, including power increases in high-beta (22-40 Hz) frequency (98 [123]%; P=0.0064) and changes in the power-law exponent in the power spectra at lower frequencies (2-80 Hz), which were not observed in the frontal cortex. During anaesthesia, the dynamic changes in the high-gamma power in STN LFPs correlated with the power-law exponent in the power spectra at lower frequencies (2-80 Hz). CONCLUSIONS: Apart from similar activity changes in both STN and cortex associated with anaesthesia-induced unresponsiveness, we observed specific neuronal activity changes in the STN in response to the anaesthesia and tracheal intubation. We also show that the power-law exponent in the power spectra in the STN was modulated by tracheal intubation in anaesthesia. Our results support the hypothesis that subcortical nuclei may play an important role in the loss and return of responsiveness.

Deep Brain Stimulation of Nucleus Accumbens with Anterior Capsulotomy for Drug Addiction: A Case Report.

BACKGROUND: Drug addiction is one of the most prevalent and costly health problems worldwide. Over the past decade, deep brain stimulation (DBS) has increasingly been used for the treatment of drug addiction. Simultaneous DBS of nucleus accumbens (NAc) and the anterior limb of the internal capsule (ALIC) has successfully been used for preventing heroin relapse. However, the excessive energy consumption speeds up battery depletion, which puts a burden on patients. By comparison, anterior capsulotomy is usually more convenient for patients and its clinical efficacy is similar to that of ALIC DBS. Accordingly, NAc DBS combined with anterior capsulotomy may also be an effective, yet more convenient, intervention for drug addiction and relapse prevention. CASE DESCRIPTION: The patient was a 28-year-old man with a polysubstance use disorder (bucinnazine, morphine, and hypnotics) for 13 years. After bilateral NAc DBS combined with bilateral anterior capsulotomy, his craving for the three drugs decreased markedly, and he remained abstinent throughout the follow-up period of approximately 1-year. Moreover, psychiatric and neuropsychological assessments showed significant improvements in depression, anxiety, sleep, quality of life, and most aspects of cognitive functioning. His overall health status was also improved. CONCLUSIONS: NAc DBS combined with anterior capsulotomy is a promising surgical treatment for drug addiction.

Long non-coding RNA Linc00320 inhibits glioma cell proliferation through restraining Wnt/ß-catenin signaling.

Recent efforts have revealed that numerous oncogenic lncRNAs have been found play pivotal role in Glioma progression while there is little know about anti-oncogenic lncRNAs in Glioma. In current study, we found a HMGB1 regulated lncRNA, Linc00320, is significantly decreased in Glioma malignant tissues and its low expression predicts poor prognosis. Moreover, we found that the nucleus localized Linc00320 inhibits Glioma cell proliferation both in vitro and in vivo. In addition, we found that Linc00320 binds to ß-catenin and inhibits the activity of Wnt/ß-catenin signaling by disrupting ß-catenin binds to TCF4 in Glioma cells. Taken together, we firstly demonstrated the tumor suppressive lncRNA, Linc00320, is down-regulated in Glioma tissues and inhibits Glioma cell proliferation by restraining Wnt/ß-catenin signaling through segregating ß-catenin and TCF4 and revealed the novel HMGB1/Linc00320/ß-catenin axis in Glioma progression.

Predictors of meaningful improvement in quality of life after selective amygdalohippocampectomy in Chinese patients with refractory temporal lobe epilepsy: A prospective study.

PURPOSE: Our aim was to determine the independent predictors of minimum clinically important difference (MCID) in quality of life (QOL) after selective amygdalohippocampectomy (SAH) among Chinese patients with refractory mesial temporal lobe epilepsy (MTLE). METHODS: We conducted a prospective study and enrolled 50 consecutive patients with refractory MTLE who underwent SAH after their presurgical evaluations. The variables independently associated with MCID in the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) overall score 1 year after SAH were analyzed by multiple binary logistic regression analysis. RESULTS: Significant improvements in the QOLIE-31 overall score and all subscale scores were observed after SAH (p < 0.001). Among 50 patients with refractory MTLE, 78% reached the criteria for MCID of QOL overall score after SAH. In the multiple binary logistic regression model, the presurgical independent predictors of significant improvement by MCID in QOL were absence of depression diagnosis (adjusted odds ratio [OR] = 8.391, 95% confidence interval [CI] = 1.240-56.776, p = 0.029) and good cognitive function (adjusted OR = 8.427, 95% CI = 1.115-63.670, p = 0.039); the postoperative independent predictor was seizure freedom (adjusted OR = 8.477, 95% CI = 1.195-60.122, p = 0.032). The sensitivity and specificity for significant improvement in the QOL were 97.4% and 45.5% respectively, with an overall model accuracy of 86.0%. CONCLUSIONS: Presurgical depression, cognitive function, and postsurgical seizure freedom are independent predictors for meaningful improvement in QOL after SAH among the Chinese patients with refractory MTLE. Preoperative evaluation of patients with refractory MTLE should consider the cognitive dysfunction and psychological disorders.

Utility of stereo-electroencephalography recording guided by magnetoencephalography in the surgical treatment of epilepsy patients with negative magnetic resonance imaging results.

Objective: It is challenging for neurosurgeons to perform surgeries on patients without detectable structural lesions. Therefore, this retrospective study aimed to explore the outcome of stereo-electroencephalography (SEEG) in suspicious areas guided by magnetoencephalography (MEG)-magnetic resonance imaging (MRI) reconstruction in MRI-negative epilepsy patients. Methods: This study included 47 patients with negative-MRI epilepsy. Seizure outcome at 24 months was assessed using a modified Engel's classification. Accordingly, class I and II were considered favorable outcomes, whereas classes III and IV were unfavorable. Furthermore, patients were classified into a consistent group if the results of MEG and SEEG indicated the same area of the brain. The relationship between surgical outcome and the concordance of MEG and SEEG was analyzed. Results: A complete seizure-free condition was achieved in 22 (47%) patients. Sex, handedness, age and duration of illness were not significantly associated with seizure-free outcome (p = .187 [Pearson chi-squared test]). The number of patients with favorable outcome (Engle I and II) was as high as 68% at the time of follow-up. Furthermore, more seizure-free patients were found in the SEEG and MEG consistent group. Conclusions: SEEG is a valuable tool in the pre-evaluation for resective epilepsy surgery, particularly in negative-MRI epilepsy patients; MEG greatly facilitates localization for SEEG electrode implantation. However, none of these tools are absolutely sensitive and reliable; therefore, collecting as much information as possible is necessary to achieve satisfactory results in epilepsy surgery.

Lead fixation in deep brain stimulation: comparison of three lead anchoring devices in China.

BACKGROUND: The accuracy of deep brain stimulation (DBS) depends on precise electrode positioning, which has been pursued for ideal treatment outcomes. As a critical component of DBS, the fixation performance of lead anchoring devices has been widely studied. Possible reasons for lead shift were analyzed in the current study and we further provided effective solutions to reduce potential manual errors. METHODS: Seventy-nine patients who received DBS implantations at the Ruijin Hospital from April to November 2017 were retrospectively reviewed. Intraoperative lead shifts were measured by C-arm fluoroscopy. Lead adjustment counts were recorded and compared among three lead fixation devices: Stimloc™ (Medtronic, Minneapolis, MN, USA), TouchLoc (SceneRay, Suzhou, China), and the traditional lead anchoring device. RESULTS: Mean (± SD) distances of lead shifts were 0.29 ± 2.42 mm in Stimloc devices, 0.43 ± 0.55 mm in TouchLoc devices, and 1.52 ± 1.05 mm in traditional devices (p < 0.0001). Average numbers of adjustments in this series were 0.3 ± 0.5 in Stimloc devices, 0.3 ± 1.3 in TouchLoc devices, and 1.1 ± 1.0 in traditional devices (p = 0.0001). Pairwise comparisons among the three devices (TouchLoc vs. Stimloc: p = 0.273; TouchLoc vs. Traditional: p = 0.0001; Stimloc vs. traditional: p < 0.0001) suggested significant differences, which were mainly attributed to the traditional devices. CONCLUSIONS: Three lead anchoring devices have been compared for their performance in the accuracy of lead fixation, in which the newly designed lead fixation devices have presented its advantages to the traditional one. In addition to the application of the Stimloc and TouchLoc devices, verification by C-arm fluoroscopy should be performed to provide an intuitive view of the depth deviation of electrode position during DBS electrode implantation.

Spinal Cord Stimulation Combined with Anterior Cingulotomy to Manage Refractory Phantom Limb Pain.

BACKGROUND: Phantom limb pain (PLP) is an intractable and debilitating disease without satisfactory treatment options presently available. Central reorganization, peripheral changes, and psychiatric factors contribute to its development; thus, a neuropsychiatry-orientated combined therapy could be promising. OBJECTIVES: We used a combined strategy with the aims of demonstrating its therapeutic outcomes on PLP. METHODS: The patient initially received spinal cord stimulation (SCS) implantation and then anterior cingulotomy (ACING) 2 years later. We administered the Hamilton Depression Scale-24, Hamilton Anxiety Scale, Pain Rating Index, Numerical Pain Rating Scale, and the Short Form (36) Health Survey to assess its outcomes at 5 time points, namely the time before performing SCS implantation, 1 year and 2 years after SCS implantation, and 1 year and 2 years after SCS combined with ACING. RESULTS: Excellent pain relief and significant improvement in depression symptoms were observed in this patient with PLP who underwent SCS combined with ACING. CONCLUSIONS: This report suggests that SCS combined with ACING is efficacious for PLP. However, further studies are warranted.

Modified Fluorodeoxyglucose Metabolism in Motor Circuitry by Subthalamic Deep Brain Stimulation.

BACKGROUND: Adjustment of the motor circuitry has been described in the treatment of Parkinson disease (PD). OBJECTIVES: To evaluate the modulation of the motor circuitry of PD patients by subthalamic deep brain stimulation (STN DBS) using 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). METHODS: Resting-state brain 18F-FDG PET imaging was performed for 8 PD patients before surgery and also 1 year after STN DBS treatment; changes in regional glucose metabolism were identified. The PD-related pattern (PDRP) of metabolic covariation was also evaluated. In addition, the correlations between glucose metabolism and clinical alleviation were determined. RESULTS: Pronounced elevations in parietal and occipital glucose metabolism due to STN DBS modification were found; an obvious reduction in caudate, putamen, cerebellum, and frontal cortex glucose metabolism was detected after STN DBS interventions. The alleviation of rigidity correlated with an increment in glucose metabolism in the parietal lobe. STN DBS inhibited the PDRP; the decrease in the PDRP correlated with the inhibition of the glucose metabolism of the caudate and the augmented glucose metabolism of the occipital lobe. CONCLUSION: STN DBS modulates cortical function through the cortical-striatothalamocortial motor circuitry and cerebellothalamocortical motor circuitry.

Tetraspanin 8-rictor-integrin α3 complex is required for glioma cell migration.

The malignant glioma remains one of the most aggressive human malignancies with extremely poor prognosis. Glioma cell invasion and migration are the main causes of death. In the current study, we studied the expression and the potential functions of tetraspanin 8 (Tspan8) in malignant gliomas. We found that Tspan8 expression level is high in both malignant glioma tissues and in several human glioma cell lines, where it formed a complex integrin α3 and rictor, the latter is a key component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2). Disruption of this complex, through siRNA-mediated knockdown of anyone of these three proteins, inhibited U251MG glioma cell migration in vitro. We further showed that Tspan8-rictor association appeared required for mTORC2 activation. Knockdown of Tspan8 by the targeted siRNAs prevented mTOR-rictor (mTORC2) assembly as well as phosphorylation of AKT (Ser-473) and protein kinase C α (PKCα) in U251MG cells. Together, these results demonstrate that over-expressed Tspan8 in malignant glioma forms a complex with rictor and integrin α3 to mediate mTORC2 activation and glioma cell migration. Therefore, targeting Tspan8-rictor-integrin α3 complex may provide a potential therapeutic intervention for malignant glioma.

Long-term follow-up of mri-guided bilateral anterior capsulotomy in patients with refractory schizophrenia.

AIM: To determine whether there is a long-term benefit of MRI-guided bilateral anterior capsulotomy in the treatment of refractory schizophrenia. METHODS: 116 patients (16 patients did not complete the follow-up evaluation) with refractory schizophrenia who underwent capsulotomy were included. The treatment effect was evaluated using a series of international rating scales. Evaluations were performed at baseline, 3 weeks and 24 months after surgery. RESULTS: The rate of effectiveness was 74% according to the Clinical Global Impression evaluation, and there was an obvious improvement based on the statistical analysis for Positive and Negative Symptom Scale (baseline vs. 24 months after surgery, 6.86 ± 8.12, 10.70 ± 8.70 vs. 26.65 ± 4.85, 21.66 ± 7.19), Brief Psychiatric Rating Scale (14.75 ± 13.21 vs. 44.97 ± 9.36), Activities of Daily Living Scale (18.06 ± 6.58 vs. 24.61 ± 8.95), Social Disability Screening Schedule (6.69 ± 6.12 vs. 15.06 ± 3.18) and Global Assessment Scale (74.35 ± 12.75 vs. 48.74 ± 9.18). Among all the symptoms of schizophrenia, aggressive behavior (82% response rate), hallucination, (71% response rate) and delusion (70% response rate) showed the best response. CONCLUSION: Our research indicates that capsulotomy is a relatively safe and effective intervention for patients with refractory schizophrenia. It could be an alternative therapy for those patients with chronic and severe schizophrenia. But there must be strict inclusion criteria considering the complications and irreversibility of this procedure.

Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory.

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.