Automated intraoperative central sulcus localization and somatotopic mapping using median nerve stimulation.

Objective. Accurate identification of functional cortical regions is essential in neurological resection. The central sulcus (CS) is an important landmark that delineates functional cortical regions. Median nerve stimulation (MNS) is a standard procedure to identify the position of the CS intraoperatively. In this paper, we introduce an automated procedure that uses MNS to rapidly localize the CS and create functional somatotopic maps.Approach. We recorded electrocorticographic signals from 13 patients who underwent MNS in the course of an awake craniotomy. We analyzed these signals to develop an automated procedure that determines the location of the CS and that also produces functional somatotopic maps.Main results. The comparison between our automated method and visual inspection performed by the neurosurgeon shows that our procedure has a high sensitivity (89%) in identifying the CS. Further, we found substantial concordance between the functional somatotopic maps generated by our method and passive functional mapping (92% sensitivity).Significance. Our automated MNS-based method can rapidly localize the CS and create functional somatotopic maps without imposing additional burden on the clinical procedure. With additional development and validation, our method may lead to a diagnostic tool that guides neurosurgeons and reduces postoperative morbidity in patients undergoing resective brain surgery.

Assessing differential representation of hand movements in multiple domains using stereo-electroencephalographic recordings.

Invasive brain-computer interfaces (BCI) have made great progress in the reconstruction of fine hand movement parameters for paralyzed patients, where superficial measurement modalities including electrocorticography (ECoG) and micro-array recordings are mostly used. However, these recording techniques typically focus on the signals from the sensorimotor cortex, leaving subcortical regions and other cortical regions related to the movements largely unexplored. As an intracranial recording technique for the presurgical assessments of brain surgery, stereo-encephalography (SEEG) inserts depth electrodes containing multiple contacts into the brain and thus provides the unique opportunity for investigating movement-related neural representation throughout the brain. Although SEEG samples neural signals with high spatial-temporal resolutions, its potential of being used to build BCIs has just been realized recently, and the decoding of SEEG activity related to hand movements has not been comprehensively investigated yet. Here, we systematically evaluated the factors influencing the performance of movement decoding using SEEG signals recorded from 32 human subjects performing a visually-cued hand movement task. Our results suggest that multiple regions in both lateral and depth directions present significant neural selectivity to the task, whereas the sensorimotor area, including both precentral and postcentral cortex, carries the richest discriminative neural information for the decoding. The posterior parietal and prefrontal cortex contribute gradually less, but still rich sources for extracting movement parameters. The insula, temporal and occipital cortex also contains useful task-related information for decoding. Under the cortex layer, white matter presents decodable neural patterns but yields a lower accuracy (42.0 ± 0.8%) than the cortex on average (44.2 ± 0.8%, p<0.01). Notably, collectively using neural signals from multiple task-related areas can significantly enhance the movement decoding performance by 6.9% (p<0.01) on average compared to using a single region. Among the different spectral components of SEEG activity, the high gamma and delta bands offer the most informative features for hand movements reconstruction. Additionally, the phase-amplitude coupling strength between these two frequency ranges correlates positively with the performance of movement decoding. In the temporal domain, maximum decoding accuracy is first reached around 2 s after the onset of movement commands. In sum, this study provides valuable insights for the future motor BCIs design employing both SEEG recordings and other recording modalities.

Optimal referencing for stereo-electroencephalographic (SEEG) recordings.

Stereo-electroencephalography (SEEG) is an intracranial recording technique in which depth electrodes are inserted in the brain as part of presurgical assessments for invasive brain surgery. SEEG recordings can tap into neural signals across the entire brain and thereby sample both cortical and subcortical sites. However, even though signal referencing is important for proper assessment of SEEG signals, no previous study has comprehensively evaluated the optimal referencing method for SEEG. In our study, we recorded SEEG data from 15 human subjects during a motor task, referencing them against the average of two white matter contacts (monopolar reference). We then subjected these signals to 5 different re-referencing approaches: common average reference (CAR), gray-white matter reference (GWR), electrode shaft reference (ESR), bipolar reference, and Laplacian reference. The results from three different signal quality metrics suggest the use of the Laplacian re-reference for study of local population-level activity and low-frequency oscillatory activity.

The correlation between accumulation of amyloid beta with enhanced neuroinflammation and cognitive impairment after intraventricular hemorrhage.

OBJECTIVE: Intraventricular hemorrhage (IVH) is found in approximately 40% of intracerebral hemorrhages and is associated with increased mortality and poor functional outcome. Cognitive impairment is one of the complications and occurs due to various pathological changes. Amyloid beta (Aß) accumulation and neuroinflammation, and the Alzheimer disease-like pathology, may contribute to cognitive impairment. Iron, the degradation product of hemoglobin, correlates with Aß. In this study, the authors investigated the correlation between Aß accumulation with enhanced neuroinflammation and cognitive impairment in a rat model of IVH. METHODS: Nine male Sprague-Dawley rats underwent an intraventricular injection of autologous blood. Another 9 rats served as controls. Cognitive function was assessed by the Morris water maze and T-maze rewarded alternation tests. Biomarkers of Aß accumulation, neuroinflammation, and c-Jun N-terminal kinase (JNK) activation were examined. RESULTS: Cognitive function was impaired in the autologous blood injection group compared with the control group. In the blood injection group, Aß accumulation was observed, with a co-located correlation between iron storage protein ferritin and Aß. Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) activity was elevated. Microgliosis and astrogliosis were observed in hippocampal CA1, CA2, CA3, and dentate gyrus areas, with elevated proinflammatory cytokines tumor necrosis factor-α and interleukin-1. Protein levels of phosphorylated JNK were increased after blood injection. CONCLUSIONS: Aß accumulation and enhanced neuroinflammation have a role in cognitive impairment after IVH. A potential therapeutic method requires further investigation.

Endogenous hormone 2-methoxyestradiol suppresses venous hypertension-induced angiogenesis through up- and down-regulating p53 and id-1.

Brain arteriovenous malformations (AVMs) which associate with angiogenesis due to local hypertension, chronic cerebral ischaemia and tissue hypoxia usually lead to haemorrhage, however, the therapeutic medicine for the disease is still lacking. 2-methoxyestradiol (2-ME) has been shown effective in the anti-angiogenic treatment. This study was conducted to examine whether and how 2-ME could improve the vascular malformations. Intracranial venous hypertension (VH) model produced in adult male Sprague-Dawley rats and culture of human umbilical vein endothelial cells (HUVECs) at the anoxia condition were used to induce in vivo and in vitro angiogenesis, respectively. Lentiviral vectors of ID-1 and p53 genes and of their siRNA were intracranially injected into rats and transfected into HUVECs to overexpress and down-regulate these molecules. 2-ME treatment not only reduced the in vivo progression of brain tissue angiogenesis in the intracranial VH rats and the in vitro increases in microvasculature formation, cellular migration and HIF-1α expression induced by anoxia in HUVECs but also reversed the up-regulation of ID-1 and down-regulation of p53 in both the in vivo and in vitro angiogenesis models. All of the anti-angiogenesis effects of 2-ME observed in VH rats and anoxic HUVECs were abrogated by ID-1 overexpression and p53 knockdown. Our data collectively suggest that 2-ME treatment inhibits hypoxia/anoxia-induced angiogenesis dependently on ID-1 down-regulation and p53 up-regulation, providing a potential alternative medical treatment for un-ruptured AVM patients.

Long-Term Outcomes of Surgical Treatment in 181 Patients with Supratentorial Cerebral Cavernous Malformation-Associated Epilepsy.

OBJECTIVE: To evaluate the efficacy of surgery as a treatment for supratentorial cerebral cavernous malformation-associated epilepsy (SCCMAE) and determine the factors that influence outcomes. METHODS: During the 5-year period from 2005 to 2009, this study included 181 consecutive patients who were diagnosed with SCCMAE and surgically treated in a single institution. Each patient was followed up for at least 5 years postoperatively. A time-to-event analysis was performed using Kaplan-Meier curves and Cox regression models to evaluate the associated risk factors. RESULTS: The age at seizure onset was 30.6 ± 14.3 years, and the age at the time of surgery was 33.4 ± 14.6 years. The female/male ratio was 0.81:1. The mean diameter of the cerebral cavernous malformations (CCMs) was 2.0 cm. For CCMs involving eloquent brain areas, the CCM was removed with (in 14 cases) or without (in 28 lesions) the peripheral hemosiderin. None of the patients had long-term neurologic disabilities. An Engel class I outcome was achieved in 89.0%, 83.4%, 81.8%, and 80.1% of the patients after 6 months, 1 year, 2.5 years, and 5-years of follow-up, respectively. In patients who were class I after 1 year, the prevalence of seizure remission 5 years postoperatively was 96.0% (95% confidence interval, 94.4%-97.6%). CONCLUSIONS: This study supports the efficacy of using surgery to treat SCCMAE. A shorter duration of preoperative epilepsy was associated with better seizure control after surgery, and patient status at the 1-year follow-up was a reliable indicator of long-term Engel class I epilepsy control.

Electrocorticographic Temporal Alteration Mapping: A Clinical Technique for Mapping the Motor Cortex with Movement-Related Cortical Potentials.

We propose electrocorticographic temporal alteration mapping (ETAM) for motor cortex mapping by utilizing movement-related cortical potentials (MRCPs) within the low-frequency band [0.05-3] Hz. This MRCP waveform-based temporal domain approach was compared with the state-of-the-art electrocorticographic frequency alteration mapping (EFAM), which is based on frequency spectrum dynamics. Five patients (two epilepsy cases and three tumor cases) were enrolled in the study. Each patient underwent intraoperative direct electrocortical stimulation (DECS) procedure for motor cortex localization. Moreover, the patients were required to perform simple brisk wrist extension task during awake craniotomy surgery. Cross-validation results showed that the proposed ETAM method had high sensitivity (81.8%) and specificity (94.3%) in identifying sites which exhibited positive DECS motor responses. Moreover, although the sensitivity of the ETAM and EFAM approaches was not significantly different, ETAM had greater specificity compared with EFAM (94.3 vs. 86.1%). These results indicate that for the intraoperative functional brain mapping, ETAM is a promising novel approach for motor cortex localization with the potential to reduce the need for cortical electrical stimulation.

Minocycline is effective in intracerebral hemorrhage by inhibition of apoptosis and autophagy.

BACKGROUND: Intracerebral hemorrhage is the least treatable type of stroke and affects millions of people worldwide. Treatment for ICH varies from medicine to surgery, but the rate of mortality and mobility still remains high. Minocycline is a tetracycline antibiotic increasingly recognized for its neuroprotective potential. In earlier studies, we demonstrated that many secondary injuries caused by ICH could be significantly reduced by injection of minocycline in rat models. The following research investigates the role of minocycline in reducing brain injury. METHODS: Twenty-four rats were administered 100µl autologous arterial blood injections into the right basal ganglia, treated with minocycline or vehicle and euthanized on the 1st, 3rd, and 7th day. Immunohistochemistry, TUNEL, and western blot analysis were performed to analyze the effects of minocycline on apoptosis and autophagy. RESULTS: After the injection of minocycline, TUNEL-positive cells were remarkably reduced on days 1, 3 and 7; Beclin-1, LC3BII/I, caspase-3/8 were all suppressed after treatment. The relationship between Cathepsin D and minocycline remained unknown. CONCLUSIONS: Our studies suggest the potential medicinal value of minocycline, through both anti-autophagy and anti-apoptosis pathways.

Classifying multiple types of hand motions using electrocorticography during intraoperative awake craniotomy and seizure monitoring processes-case studies.

In this work, some case studies were conducted to classify several kinds of hand motions from electrocorticography (ECoG) signals during intraoperative awake craniotomy & extraoperative seizure monitoring processes. Four subjects (P1, P2 with intractable epilepsy during seizure monitoring and P3, P4 with brain tumor during awake craniotomy) participated in the experiments. Subjects performed three types of hand motions (Grasp, Thumb-finger motion and Index-finger motion) contralateral to the motor cortex covered with ECoG electrodes. Two methods were used for signal processing. Method I: autoregressive (AR) model with burg method was applied to extract features, and additional waveform length (WL) feature has been considered, finally the linear discriminative analysis (LDA) was used as the classifier. Method II: stationary subspace analysis (SSA) was applied for data preprocessing, and the common spatial pattern (CSP) was used for feature extraction before LDA decoding process. Applying method I, the three-class accuracy of P1~P4 were 90.17, 96.00, 91.77, and 92.95% respectively. For method II, the three-class accuracy of P1~P4 were 72.00, 93.17, 95.22, and 90.36% respectively. This study verified the possibility of decoding multiple hand motion types during an awake craniotomy, which is the first step toward dexterous neuroprosthetic control during surgical implantation, in order to verify the optimal placement of electrodes. The accuracy during awake craniotomy was comparable to results during seizure monitoring. This study also indicated that ECoG was a promising approach for precise identification of eloquent cortex during awake craniotomy, and might form a promising BCI system that could benefit both patients and neurosurgeons.