Brenda Milner: Pioneer of the Study of the Human Frontal Lobes

Although the behavioral effects of damage to the frontal lobes date back to at least the late 19th century even midway through the 20th century very little was known about human frontal lobe function and there was a general consensus that the frontal lobe did not play a key role in cognition. This all changed when Brenda Milner published a chapter in a 1964 volume entitled: The Frontal Granular Cortex and Behavior. Milner’s chapter, “Some effects of frontal lobectomy in man,” was the first systematic study of the effect of frontal lobe excisions on cognition in human patients. Milner had access to a unique population of frontal excision patients at the Montreal Neurological Institute that were being treated by Wilder Penfield and his associates for a wide range of neurological disorders, including intractable epilepsy. Milner and her colleagues engaged in a more than 50-year study that has had a formidable impact on our understanding of frontal lobe function. Paralleling studies of frontal lobe function in non-humans they influence on understanding the evolution and function of the prefrontal cortex of mammals. Thus, although Brenda Milner is best known for her studies of human memory, she has had an equally important contribution to our understanding of the frontal lobes.

Quantitative Susceptibility Atlas Construction in Montreal Neurological Institute Space: Towards Histological-consistent Iron-rich Deep Brain Nucleus Sub-region Identification

Iron-rich deep brain nuclei (DBN) of the human brain are involved in various motoric, emotional and cognitive brain functions. The abnormal iron alterations in the DBN are closely associated with multiple neurological and psychiatric diseases. Quantitative susceptibility mapping (QSM) provides the spatial distribution of tissue magnetic susceptibility in the human brain. Compared to traditional structural imaging, QSM has superiority for imaging the iron-rich DBN owing to the susceptibility difference existing between brain tissues. In this study, we construct a Montreal Neurological Institute (MNI) space unbiased QSM human brain atlas via group-wise registration from 100 healthy subjects aged 19-29 years. The atlas construction process is guided by hybrid images that fused from multi-modal Magnetic Resonance Images (MRI), thus named as Multi-modal-fused magnetic Susceptibility (MuSus-100) atlas. The high-quality susceptibility atlas provides extraordinary image contrast between iron-rich DBN with their surroundings. Parcellation maps of DBN and their sub-regions that are highly related to neurological and psychiatric pathology are then manually labeled based on the atlas set with the assistance of an image border-enhancement process. Especially, the bilateral thalamus is delineated into 64 detailed sub-regions referring to the Schaltenbrand and Wahren stereotactic atlas. To our best knowledge, the histological-consistent thalamic nucleus parcellation map is well defined for the first time in MNI space. Comparing with existing atlases emphasized on DBN parcellation, the newly proposed atlas outperforms on atlas-guided individual brain image DBN segmentation accuracy and robustness. Moreover, we apply the proposed DBN parcellation map to conduct detailed identification of the pathology-related iron content alterations in subcortical nuclei for Parkinson Disease (PD) patients. We envision that the MuSus-100 atlas could play a crucial role in improving the accuracy of DBN segmentation for the research of neurological and psychiatric disease progress and also be helpful for target planning in deep brain stimulation surgery

The C-BIG Repository: an Institution-Level Open Science Platform

In January 2016, the Montreal Neurological Institute-Hospital (The Neuro) declared itself an Open Science organization. This vision extends beyond efforts by individual scientists seeking to release individual datasets, software tools, or building platforms that provide for the free dissemination of such information. It involves multiple stakeholders and an infrastructure that considers governance, ethics, computational resourcing, physical design, workflows, training, education, and intra-institutional reporting structures. The C-BIG repository was built in response as The Neuro’s institutional biospecimen and clinical data repository, and collects biospecimens as well as clinical, imaging, and genetic data from patients with neurological disease and healthy controls. It is aimed at helping scientific investigators, in both academia and industry, advance our understanding of neurological diseases and accelerate the development of treatments. As many neurological diseases are quite rare, they present several challenges to researchers due to their small patient populations. Overcoming these challenges required the aggregation of datasets from various projects and locations. The C-BIG repository achieves this goal and stands as a scalable working model for institutions to collect, track, curate, archive, and disseminate multimodal data from patients. In November 2020, a Registered Access layer was made available to the wider research community at https://cbigr-open.loris.ca, and in May 2021 fully open data will be released to complement the Registered Access data. This article outlines many of the aspects of The Neuro’s transition to Open Science by describing the data to be released, C-BIG’s full capabilities, and the design aspects that were implemented for effective data sharing.

The brain function state in different phase and relation with clinical symptoms in migraine: an fMRI study based on Reho

Objective Through regional homogeneity (ReHo) to analyze the activation of brain regions at different phase in migraineurs and to explore its relationship with clinical symptoms. Methods we analyzed resting-state Resting brain functional magnetic resonance in 19 patients with episodes and 22 patients with interictal phase,22 healthy controls. Using regional homogeneity (ReHo) method to do post-processing. All subjects were evaluated by Montreal cognitive assessment scale (MoCA), simple mental state examination (MMSE), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD). Subjects' clinical indicators (such as frequency of attack, course of disease, duration of each headache, and severity of headache) were correlated with ReHo values of brain regions. This study was approved by the ethics committee of Yangtze river shipping general hospital. Results the episodes group compared with the interictal group, Montreal Neurological Institute (MNI) (-9,42༌15)༌is that the ReHo value of bilateral anterior cingulate cortex was lower active than the interictal group; and Montreal Neurological Institute (MN) (-3༌-24༌66) ,the ReHo value of bilateral paracentrallobule was stronger active than the interictal group(P < 0.01). Compared with the control group, patients in interictal phase had lower activation in bilateral cuneus and bilateral lingual gyrus, MNI of the two are (9, -84, 36) and (0,-72,6). No significant different brain area was found between the episodes group and the control group. In episodes group, significant correlation was found between attack frequency and ReHo value of the bilateral paracentrallobule (r = 0.492; p = 0.038). Conclusion We need to observe the course of migraine as a whole. Even in the interictal, it may affect the development of the disease through the cuneus and lingual gyrus. ACC regulates different states of migraine by inducing anti-injury sensation regulation function. Paracentric lobule is not only associated with migraine attacks, but also with the frequency. it may have an effect with the outcome of subsequent migraines, whether become chronic, and the remodeling of the brain.

Understanding the human brain: A lifetime of dedicated pursuit

As a pioneer in the field of neuropsychology, Dr. Brenda Milner has contributed to many important landmark discoveries in the study of memory and temporal lobes, the lateralization of hemispheric function in language, as well as the role of frontal lobes in problem-solving. She is a fellow of the Royal Society (London) and the Royal Society of Canada, and a Foreign Associate of the National Academy of Sciences (USA). She has been recognized with numerous prestigious awards throughout her career, the latest of which include the Donald O. Hebb Distinguished Contribution Award in 2001, the Neuroscience Award from the United States National Academy of Science in 2004 and the Gairdner Award in 2005. Dr. Milner received her undergraduate degree at the University of Cambridge in 1939 and completed her PhD under the supervision of Dr. Donald Hebb at McGill University in 1952. She joined the Montreal Neurological Institute in 1950 to work with Dr. Wilder Penfield. Dr. Milner is presently the Dorothy J. Killam Professor of Psychology at the Montreal Neurological Institute and the Department of Neurology & Neurosurgery of McGill University. I spent an afternoon with Dr. Milner on May 12th, 2006, where she shared with me her thoughts on her work, her perspective on the past and future of cognitive neuroscience, as well as her advice for students beginning in research.

Wilder Penfield and the Montreal Neurological Institute: Heralding the Modern Age of Neurology and Neurosurgery

N/A

The Relationship between Neuropsychiatric Symptoms and Default-Mode Network Connectivity in Alzheimer’s Disease

Objective Neuropsychiatric symptoms of dementia are prevalent and extremely burdening for the patient and caregivers, but the underlying mechanism of these symptoms has not been investigated. This study aimed to investigate the relationship between neuropsychiatric symptoms and default-mode functional connectivity in Alzheimer’s disease.Methods Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. Functional magnetic resonance imaging was conducted on seventy patients with Alzheimer’s disease during rest. We conducted a seed-based functional connectivity analysis to identify anterior and posterior default-mode networks (DMN). Seeds were the medial prefrontal cortex (Montreal Neurological Institute 12, 51, 36; seed radius=3 mm) for the anterior DMN and the precuneus (Montreal Neurological Institute -6, -63, 27; seed radius=3 mm) for the posterior DMN We then correlated the scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective, and psychosis syndrome) with maps of connectivity in the default-mode network.Results There was a significant correlation between decreased connectivity in the medial prefrontal cortex of the anterior defaultmode network and hyperactivity (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) syndrome (p<0.05, family wise error cluster-level corrected).Conclusion Our study demonstrated that hyperactivity syndrome is related to hypoconnected default-mode network in Alzheimer’s disease. This finding suggests that specific network alterations are associated with certain neuropsychiatric syndromes.

Reintroduction to Medicine and Neurology in Montreal

This chapter describes Fisher’s reintroduction to civilian life. His refresher course was in Montreal, Canada, at the Royal Victoria Hospital and the Montreal Neurological Institute, also called the “Neuro.” The history of the Neuro and its principal figure, Dr. Wilder Penfield, are also described. Academic medicine and research were well established in Montreal by the mid-20th century. The two fields and disciplines that were to be the cornerstone of Fisher’s later career, pathology and neurology, were among the centerpieces of medicine in Montreal at the time Fisher began his retraining in 1945. It was during these early post-war years that Fisher was introduced to and became interested in neurology.

Morphology and Spatial Probability Maps of the Horizontal Ascending Ramus of the Lateral Fissure

The horizontal ascending ramus of the lateral fissure (half) is a characteristic sulcus of the ventrolateral frontal cortex that forms the morphological boundary between the pars triangularis and the pars orbitalis of the inferior frontal gyrus. The present study examined the morphology of this sulcus to provide a means of identifying it accurately with magnetic resonance imaging (MRI). Voxels within the half were labeled in 50 in vivo MRI volumes (1.5 T) that had been linearly registered to the Montreal Neurological Institute stereotaxic space and the morphology of the half was categorized based on relations with neighboring sulci. The spatial variability and extent of the half were then quantified across subjects using volumetric (MINC Toolkit) and surface (FreeSurfer) spatial probability maps. The half could be identified in 95% of hemispheres, and the main morphological patterns were classified into three categories: Types I, II, and III. There were no statistically significant interhemispheric differences in the frequency of the half or its morphological patterns. Understanding the details of the sulcal morphology of this ventrolateral region is critical for an accurate interpretation of the location of activation peaks generated in functional neuroimaging studies investigating language, working memory, and other cognitive processes.