Optical Imaging-Based Guidance of Viral Microinjections and Insertion of a Laminar Electrophysiology Probe Into a Predetermined Barrel in Mouse Area S1BF.

Wide-field Optical Imaging of Intrinsic Signals (OI-IS; Grinvald et al., 1986) is a method for imaging functional brain hemodynamic responses, mainly used to image activity from the surface of the cerebral cortex. It localizes small functional modules - such as cortical columns - with great spatial resolution and spatial specificity relative to the site of increases in neuronal activity. OI-IS is capable of imaging responses either through an intact or thinned skull or following a craniotomy. Therefore, it is minimally invasive, which makes it ideal for survival experiments. Here we describe OI-IS-based methods for guiding microinjections of optogenetics viral vectors in proximity to small functional modules (S1 barrels) of the cerebral cortex and for guiding the insertion of electrodes for electrophysiological recording into such modules. We validate our proposed methods by tissue processing of the cerebral barrel field area, revealing the track of the electrode in a predetermined barrel. In addition, we demonstrate the use of optical imaging to visualize the spatial extent of the optogenetics photostimulation, making it possible to estimate one of the two variables that conjointly determine which region of the brain is stimulated. Lastly, we demonstrate the use of OI-IS at high-magnification for imaging the upper recording contacts of a laminar probe, making it possible to estimate the insertion depth of all contacts relative to the surface of the cortex. These methods support the precise positioning of microinjections and recording electrodes, thus overcoming the variability in the spatial position of fine-scale functional modules.

Postcentral gyrus resection of opercular gliomas is a risk factor for motor deficits caused by damaging the radiologically invisible arteries supplying the descending motor pathway.

BACKGROUND: Postoperative motor deficits are among the worst morbidities of glioma surgery. We aim to investigate factors associated with postoperative motor deficits in patients with frontoparietal opercular gliomas. METHODS: Thirty-four patients with frontoparietal opercular gliomas were retrospectively investigated. We examined the postoperative ischemic changes and locations obtained from MRI. RESULTS: Twenty-one patients (62%) presented postoperative ischemic changes. Postoperative MRI was featured with ischemic changes, all located at the subcortical area of the resection cavity. Six patients had postoperative motor deficits, whereas 28 patients did not. Compared to those without motor deficits, those with motor deficits were associated with old age, pre- and postcentral gyri resection, and postcentral gyrus resection (P = 0.023, 0,024, and 0.0060, respectively). A merged image of the resected cavity and T1-weighted brain atlas of the Montreal Neurological Institute showed that a critical area for postoperative motor deficits is the origin of the long insular arteries (LIAs) and the postcentral gyrus. Detail anatomical architecture created by the Human Connectome Project database and T2-weighted images showed that the subcortical area of the operculum of the postcentral gyrus is where the medullary arteries supply, and the motor pathways originated from the precentral gyrus run. CONCLUSIONS: We verified that the origin of the LIAs could damage the descending motor pathways during the resection of frontoparietal opercular gliomas. Also, we identified that motor pathways run the subcortical area of the operculum of the postcentral gyrus, indicating that the postcentral gyrus is an unrecognized area of damaging the descending motor pathways.

Tooth-brushing epilepsy: an SEEG study and surgical treatment.

We report a patient with reflex tooth-brushing-triggered epilepsy, associated with a post-central lesion within the right somatosensory face area. Contralateral facial sensory and motor phenomena, associated with contralateral upper limb extension, were present at seizure onset after gingival stimulation, but seizures could also be induced by contact with solid food or liquids. Spontaneous seizures also were recorded. Secondary generalization was infrequent. Stereoelectroencephalography implantation was performed, with seizure recording and cortical/subcortical stimulation for mapping, to identify the precise extent of surgical resection. Complete postoperative control of epilepsy was achieved, accompanied by a mild and transient neurological deficit. [Published with video sequence].

Spatial reorganisation of the somatosensory cortex in a patient with a low-grade glioma.

Multiple authors have speculated that functional plasticity of the neural networks required for speech and motor function may occur in the setting of low-grade brain tumours. Here, we present the case of a 39-year-old right-handed woman found on presentation for intermittent right-hand tingling and twitching to have a low-grade glioma involving the somatosensory cortex on both structural and functional MRI. Intraoperative awake mapping identified gyral dissociation of the somateosensory areas for right arm and leg sensation. These findings demonstrate that brain plasticity may be dramatic in the setting of a low-grade glioma, and emphasise the critical need for careful brain mapping when considering tumour resection in these patients.

Recurrent Papillary Glioneuronal Tumor.

BACKGROUND: Papillary glioneuronal tumors (PGNTs) are rare World Health Organization grade I neoplasms that are characterized by a benign course and excellent response to surgical resection. A few reports exist of tumors with more aggressive clinical and histologic features. In this report we detail the case of an unusually aggressive PGNT in a 67-year-old woman. CASE DESCRIPTION: The patient had a 3-year history of seizures and was diagnosed with a frontoparietal mass on imaging. She underwent subtotal resection with a histologic diagnosis of PGNT. Less than a year after surgery, the patient experienced recurrence of disease and underwent reresection and adjuvant radiation treatment. The patient's disease continued to progress despite radiation treatment, so adjuvant temozolomide was initiated. Molecular testing was performed and revealed a TERT promotor mutation, an FGFR3-TACC3 oncogenic fusion, and a copy number loss in CDKN2A/CDKN2B. CONCLUSIONS: PGNTs, while typically benign, can rarely recur after surgery. Molecular testing should be performed on all PGNTs to help possibly identify more aggressive tumors and potentially reveal novel treatment options.

In Vivo Femtosecond Laser Subsurface Cortical Microtransections Attenuate Acute Rat Focal Seizures.

Recent evidence shows that seizures propagate primarily through supragranular cortical layers. To selectively modify these circuits, we developed a new technique using tightly focused, femtosecond infrared laser pulses to make as small as ~100 µm-wide subsurface cortical incisions surrounding an epileptic focus. We use this "laser scalpel" to produce subsurface cortical incisions selectively to supragranular layers surrounding an epileptic focus in an acute rodent seizure model. Compared with sham animals, these microtransections completely blocked seizure initiation and propagation in 1/3 of all animals. In the remaining animals, seizure frequency was reduced by 2/3 and seizure propagation reduced by 1/3. In those seizures that still propagated, it was delayed and reduced in amplitude. When the recording electrode was inside the partially isolated cube and the seizure focus was on the outside, the results were even more striking. In spite of these microtransections, somatosensory responses to tail stimulation were maintained but with reduced amplitude. Our data show that just a single enclosing wall of laser cuts limited to supragranular layers led to a significant reduction in seizure initiation and propagation with preserved cortical function. Modification of this concept may be a useful treatment for human epilepsy.

Sensation, movement and learning in the absence of barrel cortex.

For many of our senses, the role of the cerebral cortex in detecting stimuli is controversial1-17. Here we examine the effects of both acute and chronic inactivation of the primary somatosensory cortex in mice trained to move their large facial whiskers to detect an object by touch and respond with a lever to obtain a water reward. Using transgenic mice, we expressed inhibitory opsins in excitatory cortical neurons. Transient optogenetic inactivation of the primary somatosensory cortex, as well as permanent lesions, initially produced both movement and sensory deficits that impaired detection behaviour, demonstrating the link between sensory and motor systems during active sensing. Unexpectedly, lesioned mice had recovered full behavioural capabilities by the subsequent session. This rapid recovery was experience-dependent, and early re-exposure to the task after lesioning facilitated recovery. Furthermore, ablation of the primary somatosensory cortex before learning did not affect task acquisition. This combined optogenetic and lesion approach suggests that manipulations of the sensory cortex may be only temporarily disruptive to other brain structures that are themselves capable of coordinating multiple, arbitrary movements with sensation. Thus, the somatosensory cortex may be dispensable for active detection of objects in the environment.

Variability and bias between magnetoencephalography systems in non-invasive localization of the primary somatosensory cortex.

OBJECTIVES: Magnetoencephalography (MEG) provides functional neuroimaging data for pre-surgical planning in patients with epilepsy or brain tumour. For mapping the primary somatosensory cortex (S1), MEG data are acquired while a patient undergoes median nerve stimulation (MNS) to localize components of the somatosensory evoked field (SEF). In clinical settings, only one MEG imaging session is usually possible due to limited resources. As such, it is important to have an a priori estimate of the expected variability in localization. Variability in S1 localization between mapping sessions using the same MEG system has been previously measured as 8 mm. There are different types of MEG systems available with varied hardware and software, and it is not known how using a different MEG system will impact on S1 localization. PATIENTS AND METHODS: In our study, healthy participants underwent the MNS procedure with two different MEG systems (Vector View and CTF). We compared the location, amplitude and latency of SEF components between data from each system to quantify variability and bias between MEG systems. RESULTS: We found 8-11 mm variability in S1 localization between the two MEG systems, and no evidence for a systematic bias in location, amplitude or latency between the two systems. CONCLUSION: These findings suggest that S1 localization is not biased by the type of MEG system used, and that differences between the two systems are not a major contributor to variability in localization.

Neurologic Outcome After Resection of Parietal Lobe Including Primary Somatosensory Cortex: Implications of Additional Resection of Posterior Parietal Cortex.

OBJECTIVE: Postoperative neurologic outcomes after primary somatosensory cortex (S1) resection have not been well documented. This study was designed to evaluate the neurologic deterioration that follows resection of the S1 areas and to assess the risk factors associated with these morbidities. METHODS: We reviewed 48 consecutive patients with medically intractable epilepsy who underwent resection of the S1 and/or the adjacent cortex. The 48 patients were categorized into 4 groups according to the resected area as seen on postoperative magnetic resonance images: group 1 (resection of S1 only; n = 4), 2 (the posterior parietal cortex [PPC] only; n = 24), 3 (S1 and PPC; n = 10), and 4 (S1 and precentral gyrus; n = 10). RESULTS: After the resection of S1 areas, 19 patients (40%) experienced neurologic worsening, including 6 (13%) with permanent and 13 (27%) with transient deficits. Patients with permanent deficits included 2 with motor dysphasia, 1 with dysesthesia, 2 with equilibrium impairments, and 1 with fine movement disturbance of the hand. The overall and permanent neurologic risks were 25% and 0% in group 1, 17% and 4% in group 2, 80% and 20% in group 3, and 60% and 30% in group 4, respectively. Multivariate analysis determined that the resection of both S1 and PPC was the only significant risk factor for neurologic deficits (P = 0.002). CONCLUSIONS: The neurologic risk of the resection of S1 and/or its adjacent cortical areas was 40%. The additional resection of the PPC was significantly associated with the development of postoperative neurologic impairments.

Central lobe epilepsy surgery - (functional) results and how to evaluate them.

OBJECT: To evaluate whether central lobe epilepsy (CLE) surgery in the pericentral area implies inevitable function loss and to determine how postsurgical functional outcomes are perceived by the patient. METHODS: We included all 22 people with epilepsy (PWE) who received central lobe epilepsy (CLE) surgery in the pre- and postcentral gyri between 1995 and 2015 in the University Medical Center Utrecht. We determined function loss and followed-up on quality of life (AQoL-8D), mobility (Rivermead Mobility Index RMI) and self-evaluation of the surgery. To compare this with the literature, a systematic review was conducted, with specific regard for studies that included functional outcome. RESULTS: Our own cohort showed newly developed functional loss in 54.4% postoperatively. Follow-up questionnaires were returned by 11/19 PWE (the other 3 could not be contacted). The mean AQoL-8d score was 0.74 (SD 0.16) and the mean RMI score was 13.7 (SD 3.0). This mean AQoL-8d was slightly lower than the Western mean population scores (0.86 and 0.87 respectively). RMI scores and postoperative functional deficits were both significantly related to how well PWE scored on the AQoL-8d. 72.7% of the PWE became seizure free after surgery (Engel class 1A). All PWE were happy with the CLE surgery and would recommend this type of surgery to other PWE. Becoming seizure-free, gaining better functioning and having more energy were reported as the most important reasons. The literature provided 475 unique papers, of which 25 were selected for critical appraisal. Six studies were of adequate quality and provided sufficient information to extract results. Prevalence of postoperative neurological deficit varied between 0 and 50%. No information is given on patient's perceptions. CONCLUSIONS: About half of central lobe resections do not result in new neurological deficits. The patient's perspective is important in CLE surgery, but neglected in the literature. PWE may report being satisfied with the results of surgery despite new deficits and impact on quality of life. Counseling in CLE surgery should take these findings into account. Neurologists and neurosurgeons should not by default refrain from CLE surgery and think a PWE will not accept a deficit.

Enriched environment and Mash1 transfection affect neural stem cell differentiation after transplantation into the adult somatosensory cortex.

Neural stem cell (NSC) transplantation is a promising therapeutic modality for various nervous-system disorders; however, poor survival and differentiation of the transplanted NSCs limit their therapeutic efficacy. This study elucidated the effect of additive rehabilitative therapy with enriched environment (EE) and of achaete-scute homolog 1 (Mash1) and neurogenin2 (Ngn2) transduction on the fate of NSCs (P28-P35) transplanted into the primary somatosensory cortex (PSC) of mice. NSCs transplanted into the PSC differentiated into neurons and astrocytes and exhibited typical excitatory and synaptic response in mice housed in standard cages or in the EE. After EE exposure, significantly enhanced differentiation of transplanted NSCs into neuronal nuclear antigen-positive neurons was observed, whereas marked inhibition of the differentiation of transplanted NSCs into astrocytes was noted. Additionally, the proportion of GAD+ cells among GFP+/NeuN+ cells decreased following EE exposure. Furthermore, Mash1-transduced NSCs exhibited significantly enhanced populations of glutamic acid decarboxylase-negative neurons, whereas Ngn2-transduced NPCs did not.

El test cuantitativo sensorial y su importancia en la valoración de la radiculopatía lumbosacra / Quantitative sensory testing and its importance in the assessment of lumbosacral radiculopathy

La lumbalgia crónica constituye hasta dos tercios de los motivos de consulta en las Unidades de Dolor. La radiculopatía secundaria a hernia discal lumbar constituye una de las causas más importantes de lumbalgia crónica. Conocer los mecanismos nociceptivos y valorar de forma objetiva el dolor neuropático secundario a esta entidad, es de gran importancia para el enfoque terapéutico óptimo de estos pacientes. En este contexto, el Test Cuantitativo Sensorial (QST) se establece como una prueba psicofísica no invasiva que permite determinar la alteración de las fibras del Sistema Somatoensorial, o detectar precozmente neuropatí- as periféricas cuyo resultado es normal con otros exámenes de rutina, entre otras muchas utilidades prácticas. Ello hace que esta técnica sea de especial interés en el estudio de la génesis del dolor

Low back chronic pain extends up to two-thirds of the consultations in Pain Units. Radiculopathy secondary to lumbar disc herniation is one of the most important causes of low back pain. Knowing the nociceptive mechanisms and objectively assessing secondary neuropathic pain implies a great importance for the optimal therapeutic approach of these patients. In this context, the Quantitative Sensory Testing (QST) is an non invassive examination that allows to determine the alteration of the fibers of the Somato-Sensory System, or to detect early peripheral neuropathies whose result is normal with other routine exams, among many other practical uses. This technique brings a special interest in the study of pain genesis

Transsynaptic Coordination of the Formation of Morphofunctional Contacts between the Brain and the Neurotransplant: an Ulrastructural Study.

We studied the role of neurotransmitter signaling mediated by synaptic vesicles in the formation of aberrant functional connections between fascia dentata grafts and the somatosensory neocortex in adult rats. Quantitative analysis of the different populations of synaptic vesicles in the ectopic giant axonal endings of granular neurons was performed and the results were compared with the normal. Two pools of small clear vesicles (rapidly releasable pool and pool of reserve vesicles circulating in the active zone) and one pool of large dense-core vesicles were analyzed. Significant differences from the control suggest that synaptic integration of the transplants into the recipient brain is coordinated by transsynaptic signaling and mediated by different populations of synaptic vesicles.

Unilateral and Bilateral Cortical Resection: Effects on Spike-Wave Discharges in a Genetic Absence Epilepsy Model.

RESEARCH QUESTION: Recent discoveries have challenged the traditional view that the thalamus is the primary source driving spike-and-wave discharges (SWDs). At odds, SWDs in genetic absence models have a cortical focal origin in the deep layers of the perioral region of the somatosensory cortex. The present study examines the effect of unilateral and bilateral surgical resection of the assumed focal cortical region on the occurrence of SWDs in anesthetized WAG/Rij rats, a well described and validated genetic absence model. METHODS: Male WAG/Rij rats were used: 9 in the resected and 6 in the control group. EEG recordings were made before and after craniectomy, after unilateral and after bilateral removal of the focal region. RESULTS: SWDs decreased after unilateral cortical resection, while SWDs were no longer noticed after bilateral resection. This was also the case when the resected areas were restricted to layers I-IV with layers V and VI intact. CONCLUSIONS: These results suggest that SWDs are completely abolished after bilateral removal of the focal region, most likely by interference with an intracortical columnar circuit. The evidence suggests that absence epilepsy is a network type of epilepsy since interference with only the local cortical network abolishes all seizures.

A programmable high-voltage compliance neural stimulator for deep brain stimulation in vivo.

Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design.

On the origin of painful somatosensory seizures.

OBJECTIVE: To explore whether painful somatosensory seizures (PSS) are generated in the primary somatosensory cortex (SI area) or in the operculo-insular cortex. METHODS: We analyzed ictal recordings and data from stimulation using intracerebral electrodes exploring the operculo-insular cortex (including secondary somatosensory [SII] region), SI area,and other areas of the pain matrix (cingulate gyrus and supplementary motor area) in a case series study of 5 patients with PSS. RESULTS: Clinical features of PSS were different from those of seizures arising from the SI area: (1)pain intensity was higher; (2) pain spreading was not from one somatotopic territory to adjacentones; and (3) the spatial extent of pain was large, fitting better with the size of somatosensory receptive fields of the insula and SII region than of the SI area. The insula and SII region were systematically involved at the onset of seizures, rapidly followed by the opercular portion of SI area.The upper part of SI cortex was involved at a lesser degree, with some delay, and pain duration did not correlate in time with that of the discharge in SI. Ictal pain was consistently reproduced by stimulation of the insula or SII region but never by stimulating the SI area. CONCLUSIONS: These data strongly suggest that PSS originate in the operculo-insular cortex and not in the SI area and corroborate the concept that this region is involved in the sensory discriminative processing of pain inputs. Pain at the onset of PSS has a high value for localizing the epileptogenic area.

Outcome of bipolar electrocoagulation with lesionectomy in the treatment of epilepsy involving eloquent areas.

BACKGROUND/AIMS: We have demonstrated previously that bipolar electrocoagulation on functional cortex (BCFC) is a safe and effective approach for epilepsy involving eloquent areas. Here, we report the results of BCFC with lesionectomy for patients with epileptogenic foci partially overlapping eloquent areas. METHODS: Forty patients who had been treated with lesionectomy with BCFC were retrospectively reviewed with regard to seizure outcome and neurological deficits. Ten similar patients who had received lesionectomy with multiple subpial transections (MST) were examined as a control group. RESULTS: In the lesionectomy group with BCFC, Engel class I was achieved in 18 (45%) patients, class II in 8 (20%) patients, class III in 8 (20%) patients and class IV in 6 (15%) patients. Five (12.5%) patients developed mild hemiparesis and 1 (2.5%) patient mild sensory dysphasia. In the lesionectomy group with MST, Engel class I was achieved in 3 (30%) patients, class II in 2 (20%) patients, class III in 3 (30%) patients and class IV in 2 (20%) patients. Two (20%) patients developed mild hemiparesis and 1 (10%) patient moderate hemiparesis. All these complications recovered within 1-12 months. CONCLUSIONS: Compared with MST, the outcome of BCFC with lesionectomy is similar. But since MST leads to mechanical injury, while BCFC causes thermal injury, the complications of BCFC seem less severe.

A programmable closed-loop recording and stimulating wireless system for behaving small laboratory animals.

A portable 16-channels microcontroller-based wireless system for a bi-directional interaction with the central nervous system is presented in this work. The device is designed to be used with freely behaving small laboratory animals and allows recording of spontaneous and evoked neural activity wirelessly transmitted and stored on a personal computer. Biphasic current stimuli with programmable duration, frequency and amplitude may be triggered in real-time on the basis of the recorded neural activity as well as by the animal behavior within a specifically designed experimental setup. An intuitive graphical user interface was developed to configure and to monitor the whole system. The system was successfully tested through bench tests and in vivo measurements on behaving rats chronically implanted with multi-channels microwire arrays.