Imaging of focal seizures with Electrical Impedance Tomography and depth electrodes in real time.

Intracranial EEG is the current gold standard technique for localizing seizures for surgery, but it can be insensitive to tangential dipole or distant sources. Electrical Impedance Tomography (EIT) offers a novel method to improve coverage and seizure onset localization. The feasibility of EIT has been previously assessed in a computer simulation, which revealed an improved accuracy of seizure detection with EIT compared to intracranial EEG. In this study, slow impedance changes, evoked by cell swelling occurring over seconds, were reconstructed in real time by frequency division multiplexing EIT using depth and subdural electrodes in a swine model of epilepsy. EIT allowed to generate repetitive images of ictal events at similar time course to fMRI but without its significant limitations. EIT was recorded with a system consisting of 32 parallel current sources and 64 voltage recorders. Seizures triggered with intracranial injection of benzylpenicillin (BPN) in five pigs caused a repetitive peak impedance increase of 3.4 ± 1.5 mV and 9.5 ± 3% (N =205 seizures); the impedance signal change was seen already after a single, first seizure. EIT enabled reconstruction of the seizure onset 9 ± 1.5 mm from the BPN cannula and 7.5 ± 1.1 mm from the closest SEEG contact (p<0.05, n =37 focal seizures in three pigs) and it could address problems with sampling error in intracranial EEG. The amplitude of the impedance change correlated with the spread of the seizure on the SEEG (p <<0.001, n =37). The results presented here suggest that combining a parallel EIT system with intracranial EEG monitoring has a potential to improve the diagnostic yield in epileptic patients and become a vital tool in improving our understanding of epilepsy.

Robot-Assisted Stereotactic Biopsies in 377 Consecutive Adult Patients with Supratentorial Diffuse Gliomas: Diagnostic Yield, Safety, and Postoperative Outcomes.

BACKGROUND: Multiple biopsy samples are warranted for the histomolecular diagnosis of diffuse gliomas in the current molecular era, which possibly increases morbidity. OBJECTIVE: We assessed diagnostic yield, safety, and risk factors of postoperative morbidity after robot-assisted serial stereotactic biopsy sampling along 1 biopsy trajectory for diffuse gliomas. METHODS: Observational retrospective analysis of consecutive magnetic resonance imaging-based robot-assisted stereotactic biopsies performed at a single institution to assess the diagnosis of nonresectable newly diagnosed supratentorial diffuse gliomas in adults (2006-2016). RESULTS: In 377 patients, 4.2 ± 1.9 biopsy samples were obtained at 2.6 ± 1.2 biopsy sites. The histopathologic diagnosis was obtained in 98.7% of cases. Preoperative neurologic deficit (P = 0.030), biopsy site hemorrhage ≥20 mm (P = 0.004), and increased mass effect on postoperative imaging (P = 0.014) were predictors of a new postoperative neurologic deficit (7.7%). Postoperative neurologic deficit (P < 0.001) and increased mass effect on postoperative imaging (P = 0.014) were predictors of a Karnofsky Performance Status decrease ≥20 points postoperatively (4.0%). Increased intracranial pressure preoperatively (P = 0.048) and volume of the contrast-enhanced area ≥13 cm3 (P = 0.048) were predictors of an increased mass effect on postoperative imaging (4.4%). Preoperative Karnofsky Performance Status <70 (P = 0.045) and increased mass effect on postoperative imaging (P < 0.001) were predictors of mortality 1 month postoperatively (2.9%). Preoperative neurologic deficit (P = 0.005), preoperative Karnofsky Performance Status <70 (P < 0.001), subventricular zone contact (P = 0.004), contrast enhancement (P = 0.018), and steroid use (P = 0.003), were predictors of the inability to discharge to home postoperatively (37.0%). CONCLUSIONS: Robot-assisted stereotactic biopsy sampling results in high diagnostic accuracy with low complication rates. Multiple biopsy sites and samples do not increase postoperative complications.

Effects of 60-Hertz notch filtering on local abnormal ventricular activities.

BACKGROUND: It is known that electrical signals can be affected by notch filtering. OBJECTIVE: We sought to investigate the effect of 60-Hz notch filtering on local abnormal ventricular activities (LAVA) in patients undergoing ventricular tachycardia ablation. METHODS: To ensure catheter stability, only patients undergoing ablation using Stereotaxis mapping catheters were enrolled. Catheter stability was judged by the display on the electroanatomic map and the morphology of the bipolar and unipolar electrograms of the ablation catheter. At sites recording stable LAVA, 60-Hz notch filtering was applied. The duration, amplitude, and morphology of LAVA were compared before and after filtering. The area under LAVA was used to analyze the amplitude of continuous LAVA. RESULTS: A total of 110 LAVA potentials recorded from 13 patients were analyzed. Notch filtering significantly affected the LAVA morphology and reduced their amplitude (the sum of the absolute value of the largest positive and negative voltages before filtering: 0.267 mV [0.191-0.395 mV]; after filtering: 0.172 mV [0.112-0.266 mV]; P < .001). At least 2 high-frequency components were introduced into the LAVA by filtering at 33 sites. The area under continuous LAVA was reduced by 28% from 24.64 cm2 (16.20-33.45 cm2) to 17.53 cm2 (10.52-23.82 cm2) (P < .001). The duration of continuous LAVA was reduced by 12% from 79.2 ms (55.0-93.0 ms) to 69.5 ms (53.0-88.5 ms) (P < .001). CONCLUSION: Notch filtering can distort LAVA by reducing their amplitude, changing their morphology, and shortening their duration, leading to potential false positives and negatives. Mitigating the 60-Hz noise should focus on eliminating the source of noise, not applying notch filtering.

Patient and clinician satisfaction and clinical outcomes of Magseed compared with wire-guided localisation for impalpable breast lesions.

BACKGROUND: Guide-wire localisation remains the most commonly used technique for localisation of impalpable breast lesions in the UK. One alternative is magnetic seed localisation. We aimed to investigate patient and clinician satisfaction in two consecutive cohorts, describe re-excision and positive margin rates, and explore reasons for positive margins and the implications for localisation techniques. METHODS: A single-institution prospective service evaluation of two cohorts of consecutive cases of wire and then Magseed localisation was carried out. Data were collected on patient and clinician satisfaction, clinico-pathological findings, and causes of involved margins. T tests were used to compare continuous variables and Chi-squared test for satisfaction outcomes. RESULTS: 168 consecutive cases used wire-guided localisation (WGL) and 128 subsequent cases used Magseeds. Patients reported less anxiety between localisation and surgery in the Magseed group, and clinicians reported greater ease of use of Magseeds. There were no differences in lesion size, surgical complexity, or re-excision rate between the groups. In a subset of patients receiving standard wide local excision (i.e., excluding mammoplasties), the impact on margin involvement was investigated. There was no significant difference in radiological under-sizing or accuracy of localisation. However, specimen weight and eccentricity of the lesion were statistically significantly lower in the Magseed group. Despite this, re-excision rates were not significantly different (p = 0.4). CONCLUSIONS: This is the first large study of satisfaction with localisation and showed clinician preference for Magseed and a reduction in patient anxiety. It also demonstrated similar positive margin rates despite smaller specimen weights in the Magseed group. Magnetic seed localisation offers an acceptable clinical alternative to guide wire localisation. The impact on local service provision should also be considered.

Computer-Navigated versus Conventional Total Knee Arthroplasty: A Meta-Analysis of Functional Outcomes from Level I and II Randomized Controlled Trials.

The main purpose of this article is to provide an up-to-date systematic review and meta-analysis comparing functional outcomes of total knee arthroplasty using either computer navigation (NAV-TKA) or conventional methods (CON-TKA) from the latest assemblage of evidence. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. All Level I and II randomized controlled trials (RCTs) in PubMed, EMBASE, and Cochrane that compared functional outcomes after NAV- and CON-TKA were included in the review. Selected end points for random effects, pairwise meta-analysis included Knee Society Knee Score (KSKS), KS Function Score (KSFS), KS Total Score (KSTS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and range of motion at three arbitrary follow-up times. A total of 24 prospective RCTs comprising 3,778 knees were included from the initial search. At long-term follow-up (>5 years), NAV-TKA exhibited significantly better raw KSKS (p = 0.001) (low-quality evidence), contrary to CON-TKA, which reflected significantly better raw KSTS (p = 0.004) (high-quality evidence). While change scores (KSKS, WOMAC) from preoperative values favor CON-TKA at short-term (<6 months) and medium-term follow-up (6-60 months), long-term follow-up change scores in KSKS suggest the superiority of NAV-TKA over CON-TKA (p = 0.02) (very low-quality evidence). Overall, sizeable dispersion of nonstatistically significant functional outcomes in the medium term was observed to eventually converge in the long term, with less differences in functional outcome scores between the two treatment methods in short- and long-term follow-up. While raw functional outcome scores reflect no differences between NAV and CON-TKA, long-term follow-up change scores in KSKS suggest superiority of NAV-TKA over its conventional counterpart. Prospective studies with larger power are required to support the pattern of diminishing differences in functional outcome scores from medium- to long-term follow-up between the two modalities.

Subvastus Exposure Compared to Parapatellar Approach in Navigated Sequential Bilateral Total Knee Arthroplasty (SBTKA): A Prospective Randomized Study.

Subvastus approach preserves the quadriceps mechanism and may lead to improved early functional outcomes as compared with a parapatellar approach in primary knee arthroplasty. We performed a prospective randomized study to test the hypothesis if subvastus approach improves patient- and physician-reported outcomes in navigated sequential bilateral knee arthroplasty when compared with the standard parapatellar approach. A total of 93 patients were allotted in each group after power analysis and randomization done by computer-generated sequence: group S by subvastus approach and control group P by parapatellar approach. The patient's ability to walk without an aid, range of motion, blood loss, tourniquet time, complications, Knee Society Score (KSS), Knee Society Functional Score (KSFS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), High Flexion Knee Score (HFKS), and visual analog scale (VAS) for pain were recorded preoperatively and postoperatively at 2 and 6 weeks and 3, 6, and 12 months. Final follow-up was done at 2 years. There was no statistical difference in the patient's ability to achieve a straight leg raise (p = 0.88), walk without an aid (p = 0.25), leaving pain medication (p = 0.48), and mean duration of hospital stay (p = 0.58) between both groups. There was no difference in KSS, FS, KOOS, WOMAC, HFKS, and VAS at 2 weeks and later follow-ups. There was no significant difference in range of motion or lateral retinacular release in both groups. Blood loss was significantly less in group S (p < 0.05), but there was a higher rate of proximal wound dehiscence and delayed healing in subvastus group (p = 0.03). Subvastus approach does not improve patient- and physician-reported outcome measures except blood loss in computer-navigated sequential bilateral knee arthroplasty and has an increased incidence of wound healing problems. The Level of evidence for the study is I.

Automatically detecting bregma and lambda points in rodent skull anatomy images.

Currently, injection sites of probes, cannula, and optic fibers in stereotactic neurosurgery are typically located manually. This step involves location estimations based on human experiences and thus introduces errors. In order to reduce localization error and improve repeatability of experiments and treatments, we investigate an automated method to locate injection sites. This paper proposes a localization framework, which integrates a region-based convolutional network and a fully convolutional network, to locate specific anatomical points on skulls of rodents. Experiment results show that the proposed localization framework is capable of identifying and locatin bregma and lambda in rodent skull anatomy images with mean errors less than 300 µm. This method is robust to different lighting conditions and mouse orientations, and has the potential to simplify the procedure of locating injection sites.

In vivo patch-clamp recordings reveal distinct subthreshold signatures and threshold dynamics of midbrain dopamine neurons.

The in vivo firing patterns of ventral midbrain dopamine neurons are controlled by afferent and intrinsic activity to generate sensory cue and prediction error signals that are essential for reward-based learning. Given the absence of in vivo intracellular recordings during the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. To address this, we established in vivo whole-cell recordings and obtained over 100 spontaneously active, immunocytochemically-defined midbrain dopamine neurons in isoflurane-anaesthetized adult mice. We identified a repertoire of subthreshold membrane potential signatures associated with distinct in vivo firing patterns. Dopamine neuron activity in vivo deviated from single-spike pacemaking by phasic increases in firing rate via two qualitatively distinct biophysical mechanisms: 1) a prolonged hyperpolarization preceding rebound bursts, accompanied by a hyperpolarizing shift in action potential threshold; and 2) a transient depolarization leading to high-frequency plateau bursts, associated with a depolarizing shift in action potential threshold. Our findings define a mechanistic framework for the biophysical implementation of dopamine neuron firing patterns in the intact brain.

Recent Advancement of Technologies and the Transition to New Concepts in Epilepsy Surgery.

Fruitful progress and change have been accomplished in epilepsy surgery as science and technology advance. Stereotactic electroencephalography (SEEG) was originally developed by Talairach and Bancaud at Hôspital Sainte-Anne in the middle of the 20th century. SEEG has survived, and is now being recognized once again, especially with the development of neurosurgical robots. Many epilepsy centers have already replaced invasive monitoring with subdural electrodes (SDEs) by SEEG with depth electrodes worldwide. SEEG has advantages in terms of complication rates as shown in the previous reports. However, it would be more indispensable to demonstrate how much SEEG has contributed to improving seizure outcomes in epilepsy surgery. Vagus nerve stimulation (VNS) has been an only implantable device since 1990s, and has obtained the autostimulation mode which responds to ictal tachycardia. In addition to VNS, responsive neurostimulator (RNS) joined in the options of palliative treatment for medically refractory epilepsy. RNS is winning popularity in the United States because the device has abilities of both neurostimulation and recording of ambulatory electrocorticography (ECoG). Deep brain stimulation (DBS) has also attained approval as an adjunctive therapy in Europe and the United States. Ablative procedures such as SEEG-guided radiofrequency thermocoagulation (RF-TC) and laser interstitial thermal therapy (LITT) have been developed as less invasive options in epilepsy surgery. There will be more alternatives and tools in this field than ever before. Consequently, we will need to define benefits, indications, and limitations of these new technologies and concepts while adjusting ourselves to a period of fundamental transition in our foreseeable future.

Improving maximal safe brain tumor resection with photoacoustic remote sensing microscopy.

Malignant brain tumors are among the deadliest neoplasms with the lowest survival rates of any cancer type. In considering surgical tumor resection, suboptimal extent of resection is linked to poor clinical outcomes and lower overall survival rates. Currently available tools for intraoperative histopathological assessment require an average of 20 min processing and are of limited diagnostic quality for guiding surgeries. Consequently, there is an unaddressed need for a rapid imaging technique to guide maximal resection of brain tumors. Working towards this goal, presented here is an all optical non-contact label-free reflection mode photoacoustic remote sensing (PARS) microscope. By using a tunable excitation laser, PARS takes advantage of the endogenous optical absorption peaks of DNA and cytoplasm to achieve virtual contrast analogous to standard hematoxylin and eosin (H&E) staining. In conjunction, a fast 266 nm excitation is used to generate large grossing scans and rapidly assess small fields in real-time with hematoxylin-like contrast. Images obtained using this technique show comparable quality and contrast to the current standard for histopathological assessment of brain tissues. Using the proposed method, rapid, high-throughput, histological-like imaging was achieved in unstained brain tissues, indicating PARS' utility for intraoperative guidance to improve extent of surgical resection.

Place cell maps slowly develop via competitive learning and conjunctive coding in the dentate gyrus.

Place cells exhibit spatially selective firing fields that collectively map the continuum of positions in environments; how such activity pattern develops with experience is largely unknown. Here, we record putative granule cells (GCs) and mossy cells (MCs) from the dentate gyrus (DG) over 27 days as mice repetitively run through a sequence of objects fixed onto a treadmill belt. We observe a progressive transformation of GC spatial representations, from a sparse encoding of object locations and spatial patterns to increasingly more single, evenly dispersed place fields, while MCs show little transformation and preferentially encode object locations. A competitive learning model of the DG reproduces GC transformations via the progressive integration of landmark-vector cells and spatial inputs and requires MC-mediated feedforward inhibition to evenly distribute GC representations, suggesting that GCs slowly encode conjunctions of objects and spatial information via competitive learning, while MCs help homogenize GC spatial representations.

Comparison between 1.5- and 3-T Magnetic Resonance Acquisitions for Direct Targeting Stereotactic Procedures for Deep Brain Stimulation: A Phantom Study.

INTRODUCTION: Deep brain stimulation (DBS) is a well-established treatment for movement disorders. High magnetic fields could have an impact on distortion. We evaluated 1.5- and 3-T magnetic resonance imaging (MRI) sequences for accuracy, precision, and trueness of our MRI-guided direct targeting protocol. METHODS: Effects of distortion on MR sequences (T1- and T2-weighted sequences) can be evaluated using a dedicated phantom (Elekta). Field strength capabilities were assessed on Siemens Avanto (1.5 T) and Skyra (3 T) scanners. We assessed the precision of our stereotactic MRI-guided procedure. RESULTS: We focused on the risk of error due to a high field strength. Error values on the localizer box were between 0.4 and 0.7 mm at 1.5 T and between 0.6 and 2 mm at 3 T. The most accurate 1.5-T sequence is the 3D FLASH T1-weighted sequence, which had an accuracy value of 0.6 mm. At 3 T, the accuracy value of the isotropic 3D FLASH T1-weighted sequence was 1.6 mm. CONCLUSION: Given the millimetric size of stereotactic targets and electrodes, lead implantation for neuromodulation therapy needs to be accurate. We demonstrate that 3-T imaging could not be used for stereotaxy in our MRI-guided direct targeting protocol because of a risk of error induced by distortion.

Diagnostic yield of fluorescence-assisted frame-based stereotactic biopsies of intracerebral lesions in comparison with frozen-section analysis.

PURPOSE: Stereotactic biopsies are routinely used to establish a histological diagnosis of unclear cerebral pathologies. Intraoperatively, frozen-section analysis often confirms diagnostic tissue but also exhibits methodological pitfalls. Intraoperative five-aminolevulinic acid (5-ALA)-fluorescence has been described not only in gliomas but also in other cerebral pathologies. In this study, we assessed the 5-ALA contribution to the intraoperative confirmation of diagnostic tissue in frame-based stereotactic biopsies of unclear intracerebral lesions in direct comparison with frozen-section analysis. METHODS: Patients scheduled for stereotactic biopsies of unclear intracerebral pathologies received 5-ALA preoperatively. Obtained samples were intraoperatively analyzed for the presence of 5-ALA-fluorescence. One sample was used for frozen-section and a second one for permanent histopathological analysis. The diagnostic yield of frozen-section and intraoperative 5-ALA-fluorescence was calculated. The inclusion criteria for this retrospective analysis were unclear intracerebral lesions with inconclusive imaging findings and several differential diagnoses. RESULTS: A total of 39 patients with 122 obtained specimens were included. The overall diagnostic yield was 92.3%. 5-ALA-positive samples were obtained in 74.3% (29/39) of patients and all these samples contained diagnostic tissue. 5-ALA-fluorescence confirmed diagnostic tissue with a sensitivity of 100%, a specificity of 27%, a positive predictive value (PPV) of 78%, and a negative predictive value (NPV) of 100%. A clear diagnosis could be predicted by frozen section with a sensitivity of 80%, a specificity of 100%, a PPV of 100%, and NPV of 30%; Fisher's exact test p = 0.01. CONCLUSION: The 5-ALA-fluorescence in stereotactic biopsies of unclear intracerebral pathologies exhibits a high PPV/NPV for intraoperative confirmation of diagnostic tissue and might increase the diagnostic yield of the procedure by overcoming some of the limitations of frozen-section.

CT-Guided Percutaneous Trigeminal Tractotomy-Nucleotomy for Intractable Craniofacial Pain.

OBJECT: In this report, we aimed to analyze the outcome results of our patients who underwent percutaneous trigeminal tractotomy (TR) and nucleotomy (NC) procedures, which are defined as destructive procedures targeting the descending trigeminal tractus and nucleus caudalis of the spinal trigeminal nucleus, respectively, for intractable craniofacial pain. METHODS: The medical records of a total of 12 patients who underwent a total of 14 computed tomography (CT)-guided TR-NC procedures at our clinics between 2005 and 2017 were retrospectively reviewed. RESULTS: A significant increase in patients' performance status (p = 0.015) as well as a significant decrease in the VAS score (p < 0.001) were achieved. Grade I pain relief (VAS = 0, no pain) was established in 66.7% of the patients, whereas grade II pain relief was observed in the remaining patients. Two of the patients suffered from recurrent pain after the initial procedure. Both patients underwent a second trigeminal TR-NC procedure, and grade I pain relief was re-established. The mean VAS score at 3-month follow-up was 1.4 ± 1.1, whereas this score at 6-month follow-up was 2 ± 1.3. The trigeminal TR-NC procedure resulted in a significant decrease in patients' VAS scores at 3- and 6-month follow-up visits compared with preoperative VAS scores (p < 0.001). Transient ataxia was noted in only one patient (8.3%) early after the procedure. CONCLUSIONS: The results presented in the current study support the efficacy of the percutaneous CT-guided trigeminal TR-NC procedure in the management of intractable facial pain in selected patients. The use of CT guidance allows direct visualization of the target area, thereby enhancing the safety and success of the procedure.

A device for stereotaxic viral delivery into the brains of neonatal mice.

The increasing interest in manipulating neural circuits in developing brains has created a demand for reliable and accurate methods for delivering viruses to newborn mice. Here we describe a novel 3D-printed mouse neonatal stereotaxic adaptor for intracerebral viral injection that provides enhanced precision and reliability. Using this device, we injected A2a-Cre mice with a Cre-dependent hM4D-mCherry viral construct at postnatal day 1 (P1) and demonstrated selective expression in the striatal indirect pathway neurons on days P7, P11 and P25. Similarly, dopaminergic midbrain neurons were selectively targeted with a Cre-dependent green fluorescent protein virus in Dat-IRES-Cre neonates and expression examined at P25. Our open-source neonatal stereotaxic mouse adaptor facilitates neonatal neuronal targeting, which should improve the ability to label and modify neural circuits in developing mouse brains.

Radioterapia estreotáxica corporal y cirugía mínimamente invasiva en el manejo de las metástasis espinales: un cambio de paradigma / Stereotactic body radiation therapy and minimally invasive surgery in the management of spinal metastases: a change in the paradigm

El objetivo principal del tratamiento en las metástasis espinales es el control local de la enfermedad, el alivio del dolor y el mantenimiento de la deambulación. Clásicamente, se ha recomendado una resección quirúrgica del tumor lo más amplia posible seguida de radioterapia o quimioterapia adyuvante. En la actualidad, la radioterapia estereotáxica corporal (SBRT) en dosis única o hipofraccionada proporciona tasas globales de control local al año superiores al 95% con mínima morbilidad, incluso en histologías que suelen considerarse radiorresistentes. Por otro lado, mediante cirugía de descompresión circunferencial posterolateral y estabilización de la columna es factible crear un espacio de 2-3 mm entre el borde tumoral y la duramadre (separation surgery) suficiente para permitir administrar de forma segura SBRT a dosis ablativas. Dado que con frecuencia se trata de pacientes frágiles, dicha cirugía puede realizarse mediante técnicas mínimamente invasivas, que reducen la agresividad quirúrgica y ayudan a minimizar el retraso de eventuales tratamientos sistémicos

The main goal of treatment in spinal metastatic patients is local control of the disease, pain relief and the maintenance of ambulation. Traditionally, wide surgical resection of the tumour followed by adjuvant radiation and/or chemotherapy has been recommended. Currently, single-fraction or hypofractionated stereotactic body radiation therapy (SBRT) yields a one-year local control rate of over 95% with minimum morbidity, even for tumours previously considered radioresistant. In addition, by posterolateral and circumferential decompression and stabilisation of the spinal cord, it is feasible to create a 2 to 3 mm epidural margin between the dura mater and the tumour (separation surgery), enough to deliver safe and ablative doses of SBRT to the vertebrae. As these patients tend to be frail, such interventions should ideally be minimally invasive, thereby reducing surgical aggressiveness and helping to minimise the delay of any systemic therapies

Subthalamic Nucleus Stimulation Modulates Motor Epileptic Activity in Humans.

OBJECTIVE: Pharmaco-refractory focal motor epileptic seizures pose a significant challenge. Deep brain stimulation (DBS) is a recently recognized therapeutic option for the treatment of refractory epilepsy. To identify the specific target for focal motor seizures, we evaluate the modulatory effects of the subthalamic nucleus (STN) stimulation because of the critical role of STN in cortico-subcortical motor processing. METHODS: Seven patients with epilepsy with refractory seizures who underwent chronic stereoelectroencephalography (SEEG) monitoring were studied in presurgical evaluation. Seizure onset zone was hypothesized to be partially involved in the motor areas in 6 patients. For each patient, one electrode was temporally implanted into the STN that was ipsilateral to the seizure onset zone. The cortical-subcortical seizure propagation was systemically evaluated. The simultaneously electrophysiological responses over distributed cortical areas to STN stimulation at varied frequencies were quantitatively assessed. RESULTS: We observed the consistent downstream propagation of seizures from the motor cortex toward the ipsilateral STN and remarkable cortical responses on motor cortex to single-pulse STN stimulation. Furthermore, we showed frequency-dependent upstream modulatory effect of STN stimulation on motor cortex specifically. In contrast to the enhanced effects of low frequency stimulation, high-frequency stimulation of the STN can significantly reduce interictal spikes, high-frequency oscillations over motor cortex disclosing effective connections to the STN. INTERPRETATION: This result showed that the STN is not only engaged in as a propagation network of focal motor seizures but STN stimulation can profoundly modulate the epileptic activity of motor cortex in humans, suggesting a mechanism-based alternative for patients suffering from refractory focal motor seizures. ANN NEUROL 2020;88:283-296.

Tactics: an open-source platform for planning, simulating and validating stereotactic surgery.

Frame-based stereotaxy is widely used for planning and implanting deep-brain electrodes. In 2013, as part of a clinical study on deep-brain stimulation for treatment-resistant depression, our group identified a need for software to simulate and plan stereotactic procedures. Shortcomings in extant commercial systems encouraged us to develop Tactics. Tactics is purpose-designed for frame-based stereotactic placement of electrodes. The workflow is far simpler than commercial systems. By simulating specific electrode placement, immediate in-context view of each electrode contact, and the cortical entry site are available within seconds. Post implantation, electrode placement is verified by linearly registering post-operative images. Tactics has been particularly helpful for invasive electroencephalography electrodes where as many as 20 electrodes are planned and placed within minutes. Currently, no commercial system has a workflow supporting the efficient placement of this many electrodes. Tactics includes a novel implementation of automated frame localization and a user-extensible mechanism for importing electrode specifications for visualization of individual electrode contacts. The system was systematically validated, through comparison against gold-standard techniques and quantitative analysis of targeting accuracy using a purpose-built imaging phantom mountable by a stereotactic frame. Internal to our research group, Tactics has been used to plan over 300 depth-electrode targets and trajectories in over 50 surgical cases, and to plan dozens of stereotactic biopsies. Source code and pre-built binaries for Tactics are public and open-source, enabling use and contribution by the extended community.

Adaptable Angled Stereotactic Approach for Versatile Neuroscience Techniques.

Stereotactic surgery is an essential tool in the modern neuroscience lab. However, the ability to precisely and accurately target difficult-to-reach brain regions still presents a challenge, particularly when targeting brain structures along the midline. These challenges include avoiding of the superior sagittal sinus and third ventricle and the ability to consistently target selective and discrete brain nuclei. In addition, more advanced neuroscience techniques (e.g., optogenetics, fiber photometry, and two-photon imaging) rely on targeted implantation of significant hardware to the brain, and spatial limitations are a common hindrance. Presented here is a modifiable protocol for stereotactic targeting of rodent brain structures using an angled coronal approach. It can be adapted to 1) mouse or rat models, 2) various neuroscience techniques, and 3) multiple brain regions. As a representative example, it includes the calculation of stereotactic coordinates for targeting of the mouse hypothalamic ventromedial nucleus (VMN) for an optogenetic inhibition experiment. This procedure begins with the bilateral microinjection of an adeno-associated virus (AAV) encoding a light-sensitive chloride channel (SwiChR++) to a Cre-dependent mouse model, followed by the angled bilateral implantation of fiberoptic cannulae. Using this approach, findings show that activation of a subset of VMN neurons is required for intact glucose counterregulatory responses to insulin-induced hypoglycemia.