Montreal Neurological Institute Research Articles

Meta-analysis of brain functional images under N-back and DMTS paradigm in human working memory

Objective To study the similarities and differences in brain activation under N-back and DMTS paradigms of working memory. Methods Through searching of BrainMap function database by the combination keywords, a total of 122 articles with 122 experiments (N-back: 67 experiments, 937 subjects, 900 foci; Delayed Matched to Sample: 55 experiments, 806 subjects, 872 foci). Maps were analyzed using the FDR PN (P<0.0001) method based coordinates of the Montreal Neurological Institute (MNI) space. Results In the combine of the N-back and DMTS paradigms, these regions were activated including the bilateral inferior parietal lobe (Left: -36, -52, 44; Right: 38, -52, 48) and insula(Left: -34, 22, 0; Right: 34, 24, 2), the superior frontal gyrus (2, 16, 50) and inferior frontal gyrus (-44, 8, 30)of the left brain, and the middle frontal (46, 36, 24) and sub-gyral (30, 4, 56)of the right brain. The N-back paradigm was similar to the above results, whereas the DMTS paradigm only activated the precentral gyrus (-50, 8, 34) of the left brain and the right insula (34, 24, 4). Conclusion The neural circuit of working memory is the frontal-parietal networks. N-back paradigm with the brain activation consists to the neural circuit of working memory.However, DMTS paradigm activates less brain regions and is inconsistent to the neurons of working memory. Key words: Health controls; Working memory; N-back paradigm; Delayed matched to sample paradigm; Meta-analysis; Brain functional images

Morphological patterns and spatial probability maps of two defining sulci of the posterior ventrolateral frontal cortex of the human brain: the sulcus diagonalis and the anterior ascending ramus of the lateral fissure.

The sulcus diagonalis (ds) and the anterior ascending ramus of the lateral fissure (aalf) are two defining sulci of the posterior ventrolateral frontal cortex, which is also known as the anterior language region in the language dominant hemisphere. The aalf extends dorsally from the lateral fissure, separating the pars opercularis from the pars triangularis of the inferior frontal gyrus. The ds, which is a relatively vertical sulcus, is found within the pars opercularis. Given the proximity and similar orientation of these two sulci, it can be difficult to identify them properly. The present study provides a means of differentiating these two sulci accurately using magnetic resonance imaging (MRI). Voxels within the ds and the aalf were labeled in 40 in vivo MRI volumes (1.5T) that had been linearly registered to the Montreal Neurological Institute stereotaxic space to examine the morphological patterns of these two sulci and classify these patterns based on relations with neighboring sulci. The morphological variability and spatial extent of each sulcus was then quantified in the form of volumetric and surface spatial probability maps. The ds, a rather superficial sulcus, could be identified in 51.25% of hemispheres. The aalf, on the other hand, could be identified in 96.25% of hemispheres and was observed to extend medially, deep below the surface of the hemisphere, to reach the circular sulcus of the insula. Understanding the details of the sulcal morphology of this region, which, in the language dominant left hemisphere, constitutes Broca's area, is crucial to functional and structural neuroimaging studies investigating language.

Voxel-wise radiogenomic mapping of tumor location with key molecular alterations in patients with glioma.

This study aims to evaluate the impact of tumor location on key molecular alterations on a single voxel level in patients with newly diagnosed glioma. A consecutive series of n = 237 patients with newly diagnosed glioblastoma and n = 131 patients with lower-grade glioma was analyzed. Volumetric tumor segmentation was performed on preoperative MRI with a semi-automated approach and images were registered to the standard Montreal Neurological Institute 152 space. Using a voxel-based lesion symptom mapping (VLSM) analysis, we identified specific brain regions that were associated with tumor-specific molecular alterations. We assessed a predefined set of n = 17 molecular characteristics in the glioblastoma cohort and n = 2 molecular characteristics in the lower-grade glioma cohort. Permutation adjustment (n = 1000 iterations) was used to correct for multiple testing, and voxel t-values that were greater than the t-value in >95% of the permutations were retained in the VLSM results (α = 0.05, power > 0.8). Tumor location predilection for isocitrate dehydrogenase (IDH) mutant tumors was found in both glioblastoma and lower-grade glioma cohorts, each showing a concordant predominance in the frontal lobe adjacent to the rostral extension of the lateral ventricles (permutation-adjusted P = 0.021 for the glioblastoma and 0.013 for the lower-grade glioma cohort). Apart from that, the VLSM analysis did not reveal a significant association of the tumor location with any other key molecular alteration in both cohorts (permutation-adjusted P > 0.05 each). Our study highlights the unique properties of IDH mutations and underpins the hypothesis that the rostral extension of the lateral ventricles is a potential location for the cell of origin in IDH-mutant gliomas.

Is Virtual Reality Surgical Performance Influenced by Force Feedback Device Utilized?

The study objectives were to assess if surgical performance and subjective assessment of a virtual reality simulator platform was influenced by changing force feedback devices. Participants used the NeuroVR (formerly NeuroTouch) simulator to perform 5 practice scenarios and a realistic scenario involving subpial resection of a virtual reality brain tumor with simulated bleeding. The influence of force feedback was assessed by utilizing the Omni and Entact haptic systems. Tier 1, tier 2, and tier 2 advanced metrics were used to compare results. Operator subjective assessment of the haptic systems tested utilized seven Likert criteria (score 1 to 5). The study is carried out at the McGill Neurosurgical Simulation Research and Training Centre, Montreal Neurological Institute and Hospital, Montreal, Canada. Six expert operators in the utilization of the NeuroVR simulator platform. No significant differences in surgical performance were found between the two haptic devices. Participants significantly preferred the Entact system on all 7 Likert criteria of subjective assessment. Our results show no statistical differences in virtual reality surgical performance utilizing the two bimanual haptic devices tested. Subjective assessments demonstrated that participants preferred the Entact system. Our results suggest that to maximize realism of the training experience educators employing virtual reality simulators may find it useful to assess expert opinion before choosing a force feedback device.

Post-operative electrode location and clinical efficacy of subthalamic nucleus deep brain stimulation in Meige syndrome

BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) has recently been shown to be an effective treatment for Meige syndrome but efficacy of symptomatic improvement and its relationship to factors in DBS remains to be explored. ObjectivesThis study explored the relationship of electrode contact location in bilateral STN-DBS with clinical efficacy in Meige syndrome patients through retrospective analysis. MethodsPre- and post-operative magnetic resonance (MR) images of Meige syndrome patients (n = 15) were analysed. Clinical outcomes were evaluated with the Burke–Fahn–Marsden Dystonia Scale (BFMDRS). The location of active contacts in Montreal Neurological Institute (MNI) standard space and volume of activated STN tissue were determined and related to clinical outcomes. ResultsAt the last follow up (mean = 14.8 ± 4.0 months; range = 11–24 months), Meige syndrome patients (n = 14) showed improved BFMDRS scores (mean improvement = 70.9%, p = 0.001) compared to pre-operative assessment. Active contacts of stimulation given from coordinates in the MNI space (mean left side: x = −12.5 ± 1.2 mm, y = −13.3 ± 1.7 mm, z = −5.5 ± 2.5 mm; mean right side: x = 12.7 ± 1.4 mm, y = −12.7 ± 1.7 mm, z = −6.4 ± 2.4 mm) were found mainly clustered in the dorsolateral STN. While there were no significant differences in patients grouped by their degree of symptomatic improvement (<30%, 30–70% and >70%) with their respective coordinates, the volume of activated tissue within the STN of patients was significantly correlated to the BFMDRS improvement (R = 0.6, p = 0.02). ConclusionsThese findings further support the stimulation of the dorsolateral STN for effective alleviation of symptoms in Meige syndrome patients and indicate that specific factors of DBS can be considered to predict clinical efficacy.

Neuronal Mechanisms Recording the Stream of Consciousness-A Reappraisal of Wilder Penfield's (1891-1976) Concept of Experiential Phenomena Elicited by Electrical Stimulation of the Human Cortex.

Research on memory has been a major focus in the neurosciences over the past decades. An important advance was achieved by Wilder Penfield at the Montreal Neurological Institute, who reported from the 1930s to the 1950s about experiential phenomena induced by electrical brain stimulation in humans, implying neuronal causation of memory. Since then, neuroscientists have addressed the topic of memory from a range of subdisciplines; however, these reports by Penfield and his group as well as those on patient H. M. by Brenda Milner at the same institution continue to be referenced as groundbreaking. Further experimental work by Nobel laureates Eric Kandel and John O'Keefe, as well as by Edvard and May-Britt Moser related Penfield's patient documentation to experiential phenomena. However, our reassessment of Penfield's original patient documentation questions the stance that he had uncovered the "storehouse of memories." Human memory must be regarded more as context sensitive and as representative of an active reconstructive process, than as a simple recording of events. Hence, strategies aiming at naturalizing all phenomena of mind (including memory) to cellular and molecular mechanisms cannot convincingly refer to Penfield's electrophysiological studies alone as evidence that memories are solely caused by neuronal firing patterns.

Voxel-based 18F-FET PET segmentation and automatic clustering of tumor voxels: A significant association with IDH1 mutation status and survival in patients with gliomas.

IntroductionAim was to develop a full automatic clustering approach of the time-activity curves (TAC) from dynamic 18F-FET PET and evaluate its association with IDH1 mutation status and survival in patients with gliomas.MethodsThirty-seven patients (mean age: 45±13 y) with newly diagnosed gliomas and dynamic 18F-FET PET before any histopathologic investigation or treatment were retrospectively included. Each dynamic 18F-FET PET was realigned to the first image and spatially normalized in the Montreal Neurological Institute template. A tumor mask was semi-automatically generated from Z-score maps. Each brain tumor voxel was clustered in one of the 3 following centroids using dynamic time warping and k-means clustering (centroid #1: slowly increasing slope; centroid #2: rapidly increasing followed by slowly decreasing slope; and centroid #3: rapidly increasing followed by rapidly decreasing slope). The percentage of each dynamic 18F-FET TAC within tumors and other conventional 18F-FET PET parameters (maximum and mean tumor-to-brain ratios [TBRmax and TBRmean], time-to-peak [TTP] and slope) was compared between wild-type and IDH1 mutant tumors. Their prognostic value was assessed in terms of progression free-survival (PFS) and overall survival (OS) by Kaplan-Meier estimates.ResultsTwenty patients were IDH1 wild-type and 17 IDH1 mutant. Higher percentage of centroid #1 and centroid #3 within tumors were positively (P = 0.016) and negatively (P = 0.01) correlated with IDH1 mutated status. Also, TBRmax, TBRmean, TTP, and slope discriminated significantly between tumors with and without IDH1 mutation (P range 0.01 to 0.04). Progression occurred in 22 patients (59%) at a median of 13.1 months (7.6–37.6 months) and 13 patients (35%) died from tumor progression. Patients with a percentage of centroid #1 > 90% had a longer survival compared with those with a percentage of centroid #1 < 90% (P = 0.003 for PFS and P = 0.028 for OS). This remained significant after stratification on IDH1 mutation status (P = 0.029 for PFS and P = 0.034 for OS). Compared to other conventional 18F-FET PET parameters, TTP and slope were associated with PFS and OS (P range 0.009 to 0.04).ConclusionsBased on dynamic 18F-FET PET acquisition, we developed a full automatic clustering approach of TAC which appears to be a valuable noninvasive diagnostic and prognostic marker in patients with gliomas.

Wilder Graves Penfield

Neurosurgeon whose scientific contributions span epilepsy to cortical representation. A great sportsman and a pioneer of functional neurosurgery, he was born in Spokane, WA, USA, on Jan 26, 1891, and died in Montreal, Canada, on April 5, 1976, aged 85 years. When Wilder Graves Penfield was eight years old, his father, Charles Samuel Penfield, abandoned the family. His mother, Jean Jefferson, then moved with her children to Hudson, in Wisconsin, where she founded the Galahad School for Boys. Penfield received his secondary education in this school, and eventually attended Princeton University (NJ, USA). Although he first studied philosophy, Penfield ultimately decided to pursue medicine, the profession of both his grandfather and father, because that seemed to him the most direct way to “make the world a better place in which to live”. To pay for his medical education, he coached the Princeton freshman football team. At that time, he was awarded a Rhodes Scholarship and was accepted to Merton College (University of Oxford, Oxford, UK) to study medicine. The College granted him special permission to defer his entrance until the end of the autumn of 1914, so that he could fulfill his agreement to coach the Princeton Varsity football team. Before moving to Oxford, he also managed the baseball team, excelled at wrestling, and worked his way up to first string tackle in the football team, all while maintaining outstanding academic qualifications. At the University of Oxford, Penfield met the two great physicians who most influenced his career path: Charles Scott Sherrington, a neurophysiologist who won the Nobel Prize in Physiology or Medicine in 1932 for the study of reflexes and muscle innervation, and William Osler, a pathologist who is now considered one of the fathers of modern medicine. Subsequently, Penfield entered the Johns Hopkins University School of Medicine (Baltimore, MD, USA), where he finished his degree in 1918. He then completed an internship in Boston (MA, USA) under the guidance of neurosurgeon Harvey Cushing. After returning to the UK to complete a research fellowship at the National Hospital for Neurology and Neurosurgery in London, in 1921 he accepted a post as Associate Professor in Surgery at Columbia University (New York City, NY, USA). However, after a few years in New York City, he felt that the best place to carry out his research ambitions was Canada, specifically at McGill University (Montreal, Quebec, Canada), where he moved in 1928, and where the Montreal Neurological Institute (MNI) would open in 1934. At McGill and the MNI, Penfield mapped brain responses to electrical stimulation in the course of bringing therapeutic relief to conscious patients under local anesthesia, and catalogued a great quantity of information about brain physiology. He also recorded important observations on basic functions, such as language, sensitivity, and motility, and on their preservation. In collaboration with his colleague Herbert Jasper, Penfield also created what is now known as “the Montreal procedure”, by which patients with drug-resistant epilepsy were treated while conscious, so that the relevant brain areas could be targeted accurately during surgery, thus reducing side effects and complications. Through his work in mapping the cerebral cortex via stimulation, Penfield created the so-called homunculus. Even today, the homunculus is used in neurophysiology as a cortical representation of various parts of the human body. Penfield retired from the McGill medical faculty in 1954, and gave up his directorship of MNI six years later.

Structural equation modeling approach between salience network dysfunction, depressed mood, and subjective quality of life in schizophrenia: an ICA resting-state fMRI study.

PurposeQuality of life (QOL) is an important clinical outcome for patients with schizophrenia, and recent studies have focused on subjective QOL. We evaluated the causal relationship between psychosocial aspect of subjective QOL, symptoms, cognitive functions, and salience network (SN) dysfunction in schizophrenia using structural equation modeling (SEM).Patients and methodsWe performed a cross-sectional study of 21 patients with symptomatically stabilized schizophrenia and 21 age-, sex-, and education level-matched healthy controls who underwent resting-state functional magnetic resonance imaging. We evaluated SN dysfunction in schizophrenia using independent component analysis (ICA). We rated participant psychopathology using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Calgary Depression Scale for Schizophrenia (CDSS). We rated psychosocial aspect of subjective QOL using the Schizophrenia Quality of Life Scale (SQLS) psychosocial subscale. We applied SEM to examine the relationships between SN dysfunction, PANSS positive and negative scores, CDSS total scores, BACS composite scores, and SQLS psychosocial subscale scores.ResultsIn second-level analysis after group ICA, patient group had significant lower right pallidum functional connectivity (FC) within the SN than the controls did (Montreal Neurological Institute [MNI] [x y z] = [22 −2 −6]) (p = 0.027, family-wise error [FWE] corrected). In SEM, we obtained a good fit for an SEM model in which SN dysfunction causes depressed mood, which in turn determines psychosocial aspect of subjective QOL (chi-squared p = 0.9, root mean square error of approximation (RMSEA) < 0.001, comparative fit index [CFI] = 1.00, and standardized root mean square residual [SRMR]= 0.020).ConclusionWe found a continuous process by which SN dysfunction causes depressed moods that determine psychosocial aspect of subjective QOL in schizophrenia. This is the first report that offers a unified explanation of functional neuroimaging, symptoms, and outcomes. Future studies combining neuroimaging techniques and clinical assessments would elucidate schizophrenia’s pathogenesis.

F88. Standardized naming convention for high density EEG

High density EEG (hdEEG) systems and Electrical Source Imaging (ESI) techniques have revolutionized our ability to assess the potential sources of epileptiform activity and other EEG features. HdEEG interpretation is limited by lack of standardized electrode position nomenclature and montages. Inefficient visual review of hdEEG remains a major barrier to incorporating these techniques into clinical care. The aim of this project is to propose an electrode map and nomenclature with digitized electrode locations for easy integration with neuroimaging studies and ESI. The 256 channel EEG net (Geodesic Sensor Net, Electrical Geodesics, Inc.) includes electrode locations approximating the International 10–20 and 10–10 systems, but intervening electrodes do not have a standardized location, and many electrodes over the cheeks and face do not have positions defined by the 10–10 or 10–5 systems. We co-registered average 256 channel EEG net electrode positions to the 10–10 positions based on the Montreal Neurologic Institute using Curry 7.0 software. then clustered the 256 electrode locations to their closest 10–10 electrodes tested several channel layouts (montages) allowing rapid transition from global views (all head regions) to focal views (subregions corresponding to 10–10 electrode coordinates). 256 electrode locations were successfully clustered around their closest 10–10 electrode, deemed its cardinal point. All 256 electrodes within a cluster received the same initial letters according to the 10–10 electrode at its center. Within a cluster, the first subscript identified its position either anterior (a) or posterior (p) to the cardinal 10–10 electrode. The second subscript identified its position either superior (s) or inferior (i) to the cardinal 10–10 electrode. The last subscript, numerical, identified the proximity of the nonstandard electrode relative to the cardinal 10–10 electrode, compared to the other nonstandard electrodes in that cluster. Therefore, the closest nonstandard electrode would have the subscript as 1, and each subscript would increase in numeric value as distance from the cardinal 10–10 electrode increases. Electrode position nomenclature which builds upon the international standard 10–10 system allows electroencephalographers to identify spatial areas of interest in hdEEG relative to positions in routine use. A standard viewing montage for hdEEG and its application with ESI both boosts efficiency when reviewing data, and also improves accuracy in recognizing epileptiform discharges. Furthermore, combining the montage with electrode geopositions will provide greater continuity and ease of use across analysis techniques that would potentially increase adoption of source analysis in clinical care. Our proposed system could also be expanded to higher numbers of electrodes or additional positions on the face or head and is not limited to a specific hdEEG system or electrode count.

Human Motor Thalamus Reconstructed in 3D from Continuous Sagittal Sections with Identified Subcortical Afferent Territories.

Classification and delineation of the motor-related nuclei in the human thalamus have been the focus of numerous discussions for a long time. Difficulties in finding consensus have for the most part been caused by paucity of direct experimental data on connections of individual nuclear entities. Kultas-Ilinsky et al. (2011) showed that distribution of glutamic acid decarboxylase isoform 65 (GAD65), the enzyme that synthesizes inhibitory neurotransmitter γ-aminobutyric acid, is a reliable marker that allows to delineate connectionally distinct nuclei in the human motor thalamus, namely the territories innervated by nigral, pallidal, and cerebellar afferents. We compared those immunocytochemical staining patterns with underlying cytoarchitecture and used the latter to outline the three afferent territories in a continuous series of sagittal Nissl-stained sections of the human thalamus. The 3D volume reconstructed from the outlines was placed in the Talairach stereotactic coordinate system relative to the intercommissural line and sectioned in three stereotactic planes to produce color-coded nuclear maps. This 3D coordinate-based atlas was coregistered to the Montreal Neurological Institute (MNI-152) space. The current report proposes a simplified nomenclature of the motor-related thalamic nuclei, presents images of selected histological sections and stereotactic maps illustrating topographic relationships of these nuclei as well as their relationship with adjacent somatosensory afferent region. The data are useful in different applications such as functional MRI and diffusion tractography. The 3D dataset is publicly available under an open license and can also be applicable in clinical interventions in the thalamus.

Automatic lesion detection and segmentation of 18F-FET PET in gliomas: A full 3D U-Net convolutional neural network study.

IntroductionAmino-acids positron emission tomography (PET) is increasingly used in the diagnostic workup of patients with gliomas, including differential diagnosis, evaluation of tumor extension, treatment planning and follow-up. Recently, progresses of computer vision and machine learning have been translated for medical imaging. Aim was to demonstrate the feasibility of an automated 18F-fluoro-ethyl-tyrosine (18F-FET) PET lesion detection and segmentation relying on a full 3D U-Net Convolutional Neural Network (CNN).MethodsAll dynamic 18F-FET PET brain image volumes were temporally realigned to the first dynamic acquisition, coregistered and spatially normalized onto the Montreal Neurological Institute template. Ground truth segmentations were obtained using manual delineation and thresholding (1.3 x background). The volumetric CNN was implemented based on a modified Keras implementation of a U-Net library with 3 layers for the encoding and decoding paths. Dice similarity coefficient (DSC) was used as an accuracy measure of segmentation.ResultsThirty-seven patients were included (26 [70%] in the training set and 11 [30%] in the validation set). All 11 lesions were accurately detected with no false positive, resulting in a sensitivity and a specificity for the detection at the tumor level of 100%. After 150 epochs, DSC reached 0.7924 in the training set and 0.7911 in the validation set. After morphological dilatation and fixed thresholding of the predicted U-Net mask a substantial improvement of the DSC to 0.8231 (+ 4.1%) was noted. At the voxel level, this segmentation led to a 0.88 sensitivity [95% CI, 87.1 to, 88.2%] a 0.99 specificity [99.9 to 99.9%], a 0.78 positive predictive value: [76.9 to 78.3%], and a 0.99 negative predictive value [99.9 to 99.9%].ConclusionsWith relatively high performance, it was proposed the first full 3D automated procedure for segmentation of 18F-FET PET brain images of patients with different gliomas using a U-Net CNN architecture.

Effects of tooth loss on brain structure: a voxel-based morphometry study

PurposeOne of the most prominent issues in a super-aging society is the rapid increase in dementia patients. Cross-sectional studies in dentistry have indicated that patients with dementia have worse oral health compared to healthy people. The purpose of this study was to clarify the influence of tooth loss on brain structure by comparing the volumes of gray matter (GM) and white matter (WM) between edentulous and dentulous subjects. MethodsSubjects were recruited from the Denture Clinic at Iwate Medical University Hospital Dental Center. Experiments were performed on edentulous (5 males, 8 females, 81.8±1.24years) and dentulous subjects (4 males, 7 females, 77.1±4.25years). Patients with dementia were excluded from this study. Brain volumes of GM and WM in edentulous and dentulous subjects were compared using intracranial volume, age, gender and history of hypertension as covariates. Analyzed brain areas were identified by transforming the Montreal Neurological Institute coordinate into the anatomical coordinate in edentulous subjects. ResultsThe analysis of WM structural images found no morphological differences between dentulous and edentulous subjects. However, significant atrophy of GM was observed in the hippocampus, caudate nucleus and temporal pole of the right hemisphere in edentulous subjects. ConclusionsThe results of this study suggest that tooth loss was a causal factor for volume reduction in brain areas related to memory, learning and cognition.

Epilepsy and Neurosurgery: Historical Highlights.

Epilepsy has been known since antiquity and trepanation has been documented as a therapeutic option. The Greek born physician Aretaeus of Cappadocia (2nd century BC) was the first to recommend trepanation for the treatment of refractory epilepsy to drugs, pointing out the efficacy of the method (Fig. 1). Trepanation was practiced throughout the Middle Ages, as it is proved by the book of "Quattuor Magistri" and during Renaissance as well. In 19th century, Sir Victor Alexander Horsley (1857-1916), combining analysis of clinical presentation with cortical stimulation, performed a series of craniotomies for the treatment of epilepsy Fig. 2. In the following years the advent of electrophysiology and neurosurgery provided a fertile ground for further progress in epilepsy surgery such as the preoperative use of electroencephalography (EEG) to determine the epileptogenic zone by Otfrid Foerster (1873-1941); the research of Wilder Graves Penfield (1891-1976) in Montreal Neurological Institute and the use of stereoelectroencephalography (SEEG) by the neurosurgeon Jean Talairach (1911-2007) and the neurologist Jean Bancaud (1921-1994)) Fig. 3. Nowadays, epilepsy surgery remains a valuable therapeutic option in cases of drug resistant epilepsy.

Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders.

Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

Early abnormal transient hyperemic response test can predict delayed ischemic neurologic deficit in subarachnoid hemorrhage

BackgroundEarly detection of vasospasm is crucial to prevent significant delayed ischemic neurological deficit post subarachnoid hemorrhage. The standard methods of detection, including cerebral angiogram and computed tomography are invasive and not safe to be repeated, as is very often indicated clinically. Transient hyperemic response test has been previously used to predict autoregulation failure in traumatic brain injury and subarachnoid hemorrhage.AimsWe investigate the usability of transient hyperemic response test as a predictor of clinical vasospasm in a cohort of patients with aneurismal subarachnoid hemorrhage.MethodsA retrospective review of all THRT examinations done between January 2011 and July 2012 conducted at Montreal Neurological Institute and Hospital and the Montreal General Hospital. Patients diagnosed with aSAH in which the THRT was performed within the first 24–48 h of admission were included in the study. Two-dimensional transcranial Doppler images were obtained and velocities were recorded. A positive response was one in which the velocity was increased by more than 9% of the baseline systolic velocity, indicating an intact cerebral autoregulation. Lindegaard ratio > 3 is considered abnormal and in the context of elevated systolic velocity of the MCA, is highly suggestive of DIND.ResultsFifteen patients met the inclusion criteria. A total of 6 patients developed clinical and radiological vasospasm. Out of these 6 patients, 5 (83%) had an abnormal THRT in the initial TCD assessment (p = 0.0406). We found that abnormal transient hyperemic response test readings are predictive of subsequent vasospasm development.ConclusionsThe results of this small retrospective study support the notion that transient hyperemic response test has predictive value in vasospasm development and may prove useful in patient monitoring and successful clinical management.

Chapter 21 - Parietal lobe epilepsy

There are few reports of patients with parietal lobe epilepsy. One of the largest series, from the Montreal Neurological Institute (MNI), reported that patients with epileptogenic areas in the parietal cortex behind the postcentral gyrus comprised 6% of patients with refractory focal epilepsy treated surgically at the MNI between 1929 and 1988. Since then several other institutions have reported their experience with the evaluation and treatment of patients with parietal lobe epilepsy. This chapter reviews the functional anatomy of the parietal lobe, electroclinical manifestations and surgical outcome of parietal lobe epilepsy, and recent advances in the evaluation of patients with refractory focal epilepsy.

Test-Retest Reproducibility for the Tau PET Imaging Agent Flortaucipir F 18.

Alzheimer disease (AD) is characterized by β-amyloid (Aβ) plaques and tau neurofibrillary tangles. There are several PET imaging biomarkers for Aβ including 11C-PiB and 18F-florbetapir. Recently, PET tracers for tau neurofibrillary tangles have become available and have shown utility in detection and monitoring of neurofibrillary pathology over time. Flortaucipir F 18 is one such tracer. Initial clinical studies indicated greater tau binding in AD and mild cognitive impairment patients than in controls in a pattern consistent with tau pathology observed at autopsy. However, little is known about the reproducibility of such findings. To our knowledge, this study reports the first data regarding test-retest reproducibility of flortaucipir F 18 PET. Methods: Twenty-one subjects who completed the study (5 healthy controls, 6 mild cognitive impairment, and 10 AD) received 370 MBq of flortaucipir F 18 and were imaged for 20 min beginning 80 min after injection and again at 110 min after injection. Follow-up (retest) imaging occurred between 48 h and 4 wk after initial imaging. Images were spatially normalized to Montreal Neurological Institute template space. SUVRs were calculated using AAL (Automated Anatomical Labeling atlas) volumes of interest (VOIs) for parietal, temporal, occipital, anterior, and posterior hippocampal, parahippocampal, and fusiform regions, as well as a posterior neocortical VOI composed of average values from parietal, temporal, and occipital areas. Further, a VOI derived by discriminant analysis that maximally separated diagnostic groups (multiblock barycentric discriminant analysis [MUBADA]) was used. All VOIs were referenced to a subsection of cerebellar gray matter (cere-crus) as well as a parametrically derived white matter-based reference region (parametric estimate of reference signal intensity [PERSI]). t test, correlation analyses, and intraclass correlation coefficient were used to explore test-retest performance. Results: Test-retest analyses demonstrated low variability in flortaucipir F 18 SUVR. The SD of mean percentage change between test and retest using the PERSI reference region was 2.22% for a large posterior neocortical VOI, 1.84% for MUBADA, 1.46% for frontal, 1.98% for temporal, 2.28% for parietal, and 3.27% for occipital VOIs. Further, significant correlations (R2 > 0.85; P < 0.001) were observed for all regions, and intraclass correlation coefficient values (test-retest consistency) were greater than 0.92 for all regions. Conclusion: Significant test-retest reproducibility for flortaucipir F 18 was found across neocortical and mesial temporal lobe structures. These preliminary data suggest that flortaucipir F 18 tau imaging could be used to examine changes in tau burden over time.

Evaluation of the "non-epileptic" patient in a tertiary center epilepsy clinic

PurposeThe epilepsy clinic at the Montreal Neurological Institute receives a high volume of referrals. Despite most patients assessed in the clinic eventually being diagnosed with epilepsy, other disorders causing alteration of consciousness or paroxystic symptoms that could be misdiagnosed as seizures are seen frequently. The incidence and clinical characteristics of such patients have not yet been determined. We aimed to determine the proportion and clinical characteristics of patients referred to our epilepsy clinic who had a final diagnosis other than epilepsy. MethodsWe performed a retrospective chart analysis of consecutive patient referrals to the epilepsy clinic from January 2013 to January 2015, inclusively. ResultsFour hundred four patient referrals were evaluated, 106 (or 26%) had a final diagnosis other than epilepsy. Referrals came primarily from general practitioners and nonneurology specialists. Although most patients had a normal routine electroencephalography (EEG) prior to the clinic visit, sleep-deprived EEG and cardiac investigations were rarely performed. Patients received a final diagnosis other than epilepsy after 1 to 2 visits in 92% of cases and with minimal paraclinical investigations. Prolonged video-EEG recording was required in 27% of patients. The most common diagnoses were syncope (33%), psychiatric symptoms (20%), followed by migraine (10%), and psychogenic nonepileptic seizures (9%). ConclusionsA significant proportion of patients seen in our tertiary care epilepsy clinic is in fact, not patients with epilepsy. Enhanced knowledge of these differential diagnosis and important anamnesis components to rule out seizures will help improve guidelines for referral to Epilepsy clinic and cost-effectively optimize the use of paraclinical investigations.

Wilder Penfield, Sir Arthur Currie, and the Montreal Neurological Institute.

Wilder Penfield and the Montreal Neurological Institute (MNI) are inextricably linked. It was Penfield's unique idea to create a building with an academic atmosphere wherein basic neuroscience and clinical care of neurological patients would benefit from interaction and mutual support. It is clear that without Penfield that there would be no MNI; however, the role of another Canadian icon, Sir Arthur Currie, in the development of the MNI has heretofore been barely mentioned. The thesis of this paper is that Currie had a critical role in the gestation of the MNI that has generally been ignored.