The Schmahmann Laboratory for Neuroanatomy and Cerebellar Neurobiology focuses on two inter-related areas of investigation:
First, we explore the structure and function of the cerebellum (the little brain) in health and disease.
- We study healthy individuals using magnetic resonance brain imaging (MRI) techniques to identify what parts of cerebellum are engaged in different functions, how these cerebellar regions are linked to the cerebral hemispheres (the big brain), and what it is that cerebellum contributes to these different behaviors. We have shown that different parts of cerebellum are engaged in motor control, intellectual functions and emotional processing, and we are continuing to explore this in more detail.
- We evaluate patients who have experienced cerebellar injury including adults with stroke, children with cerebellar tumors, and those with developmental disorders of the cerebellum. This allows us to develop an understanding of the effects of cerebellar damage on motor control (cerebellar ataxia), and the relationship between cerebellar injury and disorders of intellect and mood.
- We are engaged in studies in the monkey of the anatomical circuits linking the cerebellum with other brain regions, and the cerebellar contributions to movement and cognition in behavioral studies.
- We have recently entered into collaboration with colleagues locally and nationally to:
- explore the role of cerebellar stimulation using magnetic fields (transcranial magnetic stimulation) to treat psychiatric conditions;
- study stem cells derived from patients with cerebellar diseases to explore the basic biology of those disease as a way to engage in specifically targeted treatment of these diseases;
- use MRI to develop markers of disease progression in cerebellar degeneration so that we will have valid and quantifiable measures of the effectiveness of new treatment approaches as they evolve;
- test clinical rating scales to measure the effects of new treatments on ataxia; investigate the role of mitochondria in causing cerebellar diseases; and
- further characterize the clinical features of the spinocerebellar and other ataxias.
- What is presently missing from this cerebellar research portfolio is the more active investigation of the genetic causes of as yet unexplained familial cerebellar diseases; the apparent biological link between different SCAs (such as SCA2 and SCA 17) and other more common neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases; clinical trials of new medications designed to slow down the progression of ataxia; and studies to evaluate different treatment strategies for cognitive and emotional impairments in patients with cerebellar injury. These await further research funding support.
Our second major focus is the field of connectional neuroanatomy in the human brain.
- Our work using tract tracer injections in monkeys remains the gold standard for defining nerve pathways that link different regions of the brain. The exciting new development in this field is that we now have the ability, using MRI techniques (DSI – diffusion spectrum imaging) to conduct research in the human brain, both living and deceased, to find out how the human brain is hard wired. This line of enquiry will enable us to start fulfilling the centuries old dream of studying the human brain directly – not the monkey or cat brain with extrapolation to human, but the human brain itself.
- In collaboration with MGH investigators who invented this new technology, we will analyze the wiring of brain regions that disintegrate or are abnormal in Alzheimer’s disease, epilepsy, multiple sclerosis, autism, schizophrenia, obsessive compulsive disorder, depression and many others.
- We will also continue to use this connectional approach to explore how the cerebellum is linked to the cerebral hemispheres thus allowing the cerebellum to carry out its tasks.
- This work has already led to fundamental new insights, and with the ability to study living people at different ages and the same individuals across time we are hopeful that it will shed light on the human brain in health and disease.