The need to create new knowledge and new treatments is enormous. Your gift in support of research at the McGovern Institute can have a direct impact on our understanding of the brain diseases and disorders that cause millions to suffer.

Alzheimer's Disease

Institute Professor and McGovern faculty member Emilio Bizzi investigates among other areas the underlying neuropsychology of Alzheimer's patients, with the hope of developing new neuropsychological tests that better predict the disease's onset and progress. Alzheimer's Disease (AD) is a type of dementia that currently afflicts an estimated 4.5 million Americans; a number expected to rise to between 11-16 million by 2050. Prior to the onset of dementia an individual goes through a pre-dementia phase in which measurable memory deficits do exist, but the symptoms of dementia are not yet present. This condition is known as mild cognitive impairment (MCI). Many people with MCI go on to develop AD, while others develop other types of dementia, and others still do not develop dementia at all. Knowing which individuals with MCI are likely to develop AD is a crucial part of identifying the disease in its pre-clinical phases.

Funds are needed to support psychomotor testing on three subject groups — those with mild AD, those with MCI, and normal healthy subjects — with the hope of developing new neuropsychological tests that better predict the onset and progress of Alzheimer's disease.

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Parkinson's Disease

McGovern faculty member and Medal of Science recipient Ann Graybiel, and fellow McGovern faculty member Christopher Moore are collaborating on a research project designed to determine whether they can identify functional compartments in the primate striatum using new fMRI methods. The striatum is known to be affected in Parkinson's disease, and Drs. Graybiel and Moore propose using fMRI methods to explore the relationship between neural activity in the striatum and some of the anatomical substructures in the striatum previously identified in Dr. Graybiel's seminal work concerning the striatum and more generally the basal ganglia.

Funds are needed to support experiments in which the Graybiel and Moore laboratories will combine expertise to examine the modality of the cortico-striatal system of primates in fMRI studies.

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Schizophrenia

Christopher Moore is also investigating neuronal dynamics - the way rapid changes in brain organization contribute to our ability to switch quickly between different tasks and interact in varying environments. For example, shifts in attention between different voices at a party or between specific parts of a landscape or movie, likely benefit from these dynamics. Evidence suggests that individuals suffering from schizophrenia have a selective deficit in this kind of rapid perceptual processing and recent studies have shown that a specific class of inhibitory neuron in the mammalian neocortex is found to be deficient in neurotransmitter synthesis in these schizophrenic patients.

Funds are needed to support a full scale initiative to investigate whether and how this specific class of neurons contributes to perceptual neural dynamics and to see whether a link can be made to perceptual processing in schizophrenia.

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Brain development, plasticity, evolution and neurological diseases

McGovern faculty members H. Robert Horvitz (2002 Nobel Prize winner) and Martha Constantine-Paton are interested in pursuing the area of microRNAs and the brain. MicroRNAs are a new class of tiny regulatory RNAs found in nematodes, plants, insects and mammals and thought to act as post-transcriptional modulators of gene expression. In invertebrates microRNAs have been implicated as regulators of developmental timing, neuronal differentiation, cell proliferation, programmed cell death and fat metabolism. However, little is known about the role of microRNAs in mammals and, in particular, in the mammalian brain.

Funds are needed to expand recent development of microarray technology that can be used to analyze the expression of microRNAs and of other small RNAs. MicroRNA microarrays offer a new tool that should facilitate studies of the biological roles of microRNAs in brain function, development and aging and in human neurologic disease.

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Autism and Schizophrenia

In addition to her work with Dr. Horvitz on MicroRNAs, Martha Constantine-Paton's research focuses on neural activity-dependent brain development, specifically with respect to N-methyl-D-aspartate glutamate receptors (NRs), which have been implicated in neurological diseases with initiating events in perinatal periods when glutamate networks are developing. Two relevant dysfunctions of this type are autism spectrum disorders and schizophrenia. For both autism and schizophrenia, genetic linkage analyses have identified molecules that are known to function downstream of NR signaling. However, tying them to a specific function in circuit formation requires an understanding of changes in NR function with age.

Funds are needed to initiate a new program in Dr. Constantine-Paton's research focused on forebrain regions involved in autism and schizophrenia. The funding will allow molecular and electrophysiological studies on 2 protein subunits of the NR complex that change during development and are involved in either stabilizing or destabilizing young neuron contacts (synapses) on the basis of the electrical signals the receptors transmit. The lab has built chimeric subunits composed of the extracellular and membrane-pore region of one subunit and the intracellular tail of the other. These can be expressed in developing neurons and will allow dissociation of each subunits's contribution to NR intracellular chemical signaling versus NR ion current influx during early activity-dependent circuit formation. How molecules genetically linked to autism and schizophrenia interact with NR signaling and NR dependent circuit refinement can be understood in this way. The research will potentially identify new drug targets or treatments that can mitigate or eliminate these devastating diseases. It could also inform normal childrearing and pediatrics.

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Dyslexia

In the laboratory of McGovern faculty member Tomaso Poggio researcher Gadi Geiger is engaged in an ongoing study to determine whether in the early stages of learning to read increased activities in novel hand-eye coordination tasks will reduce the number of children with reading difficulties. This research is based on a previous discovery that dyslexics differ from ordinary readers not only in reading, but also in their strategies of visual perception. For the last two years, Geiger and his colleagues have tested their hypothesis with children from kindergarten, first and second grades and found that daily arts and crafts practice by the students reduced by at least one third their likelihood for being at risk for reading difficulties.

Funds are needed to enlarge the sample of students, to determine which activities are more efficient, which are the critical ages for optimal practice, which time of day is the most effective, and how best to educate teachers and parents for awareness of reading problems and dyslexia, as well as possible remedial and preventive practices.

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Perception and Learning

Dr. Poggio is also a leading expert in visual recognition by animals and machines. His highly collaborative research (including Dr. Dicarlo and Dr. Bizzi) seeks to answer an age-old question in neuroscience "How does the brain works?" and, in particular, "How does visual cortex work?" Dr. Poggio's research suggests that the answer to this question is that the brain relies on a general mechanism — a cortical microcircuit repeated in different cortical areas — using it to learn to recognize many different types of objects. Similar learning modules may be used by other parts of cortex, including the motor system.

Funds are needed to investigate how the brain works and how to make machines that learn from experience like our brain does.

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Macular Degeneration

McGovern faculty member Nancy Kanwisher and postdoctoral associate Chris Baker, in collaboration with Professor Eli Peli of the Schepens Eye Institute and Harvard Medical School, have discovered the first evidence that brain reorganization occurs in people suffering from the progressive visual disorder Macular Degeneration, which afflicts over 1.7 million people in the United States and tens of millions worldwide.

Funds are needed to explore whether this newly discovered brain reorganization enables people with Macular Degeneration to see better with peripheral vision than normally-sighted people and to identify the conditions that lead to these changes in the brain.

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