Schmahmann Lab for Neuroanatomy & Cerebellar Neurobiology
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My primary interest focuses on the anatomical substrates of cognition and emotion. In my Laboratory for Neuroanatomy and Cerebellar Neurobiology, we use the methods of systems neuroscience, and we uphold the mission of Massachusetts General Hospital by incorporating patient care and teaching into our research program.
My work pioneered the role of the cerebellum in cognition and emotion, and together with my collaborators I continue to evaluate the clinical features and neuroanatomical and functional substrates of the cerebellar cognitive affective syndrome. Our methods include tract tracing studies in animals of the pathways that link the cerebellum with the cerebral cortex; neurological and neuropsychological studies of cognition and emotion in patients with cerebellar diseases; and structural (MRI) and functional imaging (PET and fMRI) of the cerebellum to better understand the organization of the human cerebellum and the consequences of cerebellar damage on higher order behaviors.
In addition to cerebellar connections with cerebral cortex, we are interested in the connections of different cortical association areas with each other; with subcortical structures such as thalamus and basal ganglia; and the organization of the white matter tracts that link different brain regions.
Our tract tracing studies in animals provided new insights into cerebral white matter pathways, and we are using new MRI approaches (diffusion spectrum imaging – DSI) to study these pathways and connections in the whole brain – in animals and humans.
This work has potential to shed new light on cerebral and cerebellar systems affected by many diseases, from the ataxias to autism, schizophrenia and depression. We complement these anatomical investigations by studying patients with lesions in these areas (thalamus, pons, and cerebral white matter, as well as cerebellum) to better understand these presentations, and to facilitate improved diagnosis, management, and counseling.
The Mass General Ataxia Unit is the clinical arm of the Laboratory for Neuroanatomy and Cerebellar Neurobiology. It is widely recognized as a premier center in the country for the evaluation and management of patients with cerebellar disorders, including spinocerebellar ataxias, Friedreich’s ataxia, multiple system atrophy - cerebellar type, sporadic ataxia, and cerebellar malformations resulting in motor and cognitive developmental delay.
Clinical and translational research programs are directed at better diagnosing, understanding and treating patients with cerebellar disorders, and collaborations with local and national investigators help advance these goals.
Our collaborators play an essential role in fulfilling our mission. At the Mass General these include investigators and clinicians in the following areas:
- Athinoula Martinos Center for Biomedical Imaging
- Center for Morphometric Analysis
- Psychology Assessment Center
- Cognitive/Behavioral Neurology Unit
- Pediatric Neurogenetics Laboratory
- Department of Neuropathology
- Stroke Service
- Clinical Trials Unit
- MassGeneral Institute for Neurodegenerative Disease (MIND)
- The Broad Institute
- Drug Discovery program of Mass General and Harvard Medical School
- Physical Medicine and Rehabilitation (Physical therapy, occupational therapy, speech therapy)
- Neuro-otology and Vestibular Clinical Laboratories
We also collaborate closely with neuroscientists in the Boston University Laboratory for Anatomy and Neurobiology, the New England Regional Primate Center, the Beth Israel Deaconess Medical Center for Non-Invasive Brain Stimulation, the University of Lausanne, Switzerland, and previously with the McConnell Brain Imaging Center at the Montreal Neurological Institute and the Laboratory for Neuroimaging at UCLA.
Education is central to our mission. The clinical insights and results of our research efforts are shared in teaching sessions with medical students who rotate through Mass General wards on the neurology clerkships, as well as with undergraduate and graduate students locally and nationally.
Patient outreach is a central part of our clinical mission, and a driving force in our research efforts. Dr. Schmahmann is a member of the Medical Advisory Board of the National Ataxia Foundation, and the Medical Advisor to its New England Ataxia Support Group.
The Laboratory has been funded by the National Institutes of Health for the development of the MRI Cerebellar Atlas, anatomical studies of the corticopontine projections in animals, and studies of motor and cognitive effects of cerebellar strokes in patients; by the McDonnell-Pew Foundations for behavioral and anatomical studies in animals; the Birmingham Foundation; the Mass General Executive Committee on Research for anatomical as well as clinical studies; and philanthropic gifts from patients and their families.
- Tract tracing studies in animals of the connections between amygdala and the cerebellar system; organization of fibers in the anterior limb of the internal capsule; cortical projections to the zona incerta
- Diffusion spectrum imaging in animals and humans to study cerebral white matter pathways and connectional neuroanatomy
- Structure-function correlations of motor and cognitive effects of cerebellar stroke
- Cerebral hemisphere diaschisis identified with PET in cerebellar stroke patients
- Neurobehavioral manifestations of patients with cerebellar agenesis
- Linguistic processing in patients with cerebellar degeneration
- Further studies of the neuropsychiatric aspects of the cerebellar cognitive affective syndrome
- Transcranial Magnetic Stimulation of cerebellum in neuropsychiatric disorders
- Evaluation of the arginine-growth hormone stimulation test for the diagnosis of multiple system atrophy – cerebellar type
- Ataxia Rating Scales in cerebellar patients
- Neuropathology of cerebellar disorders
- Neuroimaging in multiple system atrophy for early diagnosis and prognosis
- Mitochondrial basis of sporadic ataxia syndromes
- Case studies and neuropathology of cerebral white matter leukodystrophy
- Translational research studies of new therapeutic options in Friedreich’s Ataxia
We are not presently hiring, but we welcome enquiries from students who are interested in volunteering in the laboratory and/or clinic on selected projects.
- Schmahmann JD, Pandya DN. Disconnection syndromes of basal ganglia, thalamus and cerebrocerebellar systems. Cortex. 2008; 44: 1037-66.
- Schmahmann JD. Vascular Syndromes of the Thalamus. Stroke 2003:34; 2264-2278.
- Schmahmann JD, Pandya DN, Wang R, Dai G, D’Arceuil HE, de Crespigny AJ, Wedeen VJ. Association fiber pathways of the brain: Parallel observations from diffusion spectrum imaging and autoradiography. Brain. 2007; 130: 630-53.
- Schmahmann JD, Pandya DN. Fiber Pathways of the Brain. New York, Oxford University Press. 2006.
- Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies. NeuroImage, 2008. http://dx.doi.org/10.1016/j.neuroimage.2008.08.039
- Schmahmann JD, Doyon J, Toga A, Evans A, Petrides M. MRI Atlas of the Human Cerebellum. San Diego, Academic Press. 2000.
- Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum – insights from the clinic. The Cerebellum. 2007; 6: 254-67.
- Schmahmann JD. Disorders of the cerebellum. Ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. Journal of Neuropsychiatry and Clinical Neurosciences. 2004; 16(3): 367-378.
- Schmahmann JD and Sherman JC. The cerebellar cognitive affective syndrome. Brain 1998; 121: 561-579.
- Schmahmann JD. ed. The Cerebellum and Cognition. International Review of Neurobiology. Volume 47. San Diego, Academic Press. 1997.
Composite Color-coded Summary Diagram
Composite color-coded summary diagram illustrating the distribution within the basilar pons of the research animal of projections derived from associative cortices in the prefrontal (purple), posterior parietal (blue), temporal (red), and parastriate and parahippocampal regions (orange), and from motor, premotor and supplementary motor areas (green). The medial (A), lateral (B) and ventral (C) surfaces of the cerebral hemisphere are shown at upper left.
The plane of section through the basilar pons is at lower left, and the rostrocaudal levels of the pons I through IX are shown on the right. Cerebral areas that have been shown to project to the pons by other investigators using either anterograde or retrograde tracers are depicted in white; those areas studied with both anterograde and retrograde studies and found to have no pontine projections are shown on the hemispheres in yellow; and those with no pontine projections according to retrograde studies by other investigators are shaded in gray.
The dashed lines in the hemisphere diagrams represent the sulcal cortices. In the pons diagrams the dashed lines represent the pontine nuclei, and the solid lines depict the traversing corticofugal fibers. The associative corticopontine projections are substantial. There is a complex mosaic of terminations in the pons, and each cerebral cortical region has preferential sites of pontine terminations. There is considerable interdigitation of the terminations from some of the different cortical sites, but almost no overlap.