Research Goals & Current Projects

Rajeev D.S. Raizada, Ph.D.
Postdoctoral Fellow, University of Washington Department of Psychology

Goals

The goals of my research program are to understand, enhance and exploit cortical plasticity. The tools that will allow me to pursue these goals are functional neuroimaging, psychophysics, neuropharmacology and computation. My postdoctoral and Ph.D. training have given me a solid grounding in these tools, and my current projects are laying the foundations for this research program. Because my background spans several scientific areas, ranging from measuring children's behavioural performance to computationally simulating results from macaque neurophysiology, I believe that I have the opportunity to draw together and cross-fertilise diverse areas of research which are often isolated from each other. An example, described in more detail below, is my ongoing study of cholinergic enhancement of perceptual learning, which applies results from rat physiology, human psychophysics and Alzheimer's research towards seeking to enhance clinical treatments. In my future work, I plan to build upon and expand my current set of tools, and to use them to explore the neural mechanisms of training-induced plasticity. In particular, I am working towards finding pharmacological and behavioural techniques that can be exploited to make training, and training-based remediation, more effective.

Current projects

The main project that I am currently working on is to explore whether human cortical plasticity can be enhanced using the cholinergic drug galanthamine, which is currently used for treating Alzheimer's disease. This project draws its motivation from human clinical studies which show that training-induced cortical plasticity may be useful for remediating conditions such as stroke-induced movement disorders, dystonia and dyslexia. Animal studies have shown that acetylcholine can significantly enhance cortical plasticity, and galanthamine allows acetylcholine levels to be increased safely and reversibly in normal healthy volunteer subjects. The drug galanthamine therefore offers a novel opportunity to apply results from the animal research to human plasticity, with potential clinical applications. In this experiment, cortical plasticity is being induced by training subjects on a visual perceptual learning task. The drug's effect on cortical plasticity is being assessed in two ways: using fMRI to compare neural activation during task performance before versus after training, and also behaviourally by measuring subjects' rate of learning on the task when trained on the drug versus on placebo. I wrote and secured funding for three grants on this project: an R21 from NINDS ($250K direct costs), a pilot grant from the NSF ($50K total costs), and also a grant from Janssen Pharmaceutica ($80K total costs).

A second project, investigating audio-visual processing in dyslexic and normal subjects, asks a question that is logically prior to the types of training-based deficit-remediation that the drug-study addresses: before attempting to remediate a deficit, one must first find a deficit to remediate. The hypothesis being tested is that deficits in audio-visual cross-modal integration may partly underlie reading disability, on grounds of the fact that that learning to read is a fundamentally cross-modal process, requiring the pairing of letters and words with sounds. The task used to measure cross-modal processing ability was chosen to be as simple as possible: audio-visual simultaneity detection. The subjects in the study are dyslexic and normal children, aged 7 to 14. Their thresholds on the behavioural task are measured, and their neural activation elicited by the task is recorded using fMRI. In a companion study, the same task is being used in event-related fMRI of normal adults, with the subjects' trial-by-trial behavioural responses in the scanner used to dissociate the neural responses that correlate with perceived simultaneity from the neural responses that are driven by the physical aspects of the stimulus. I wrote and obtained funding for two grants to support this project: a Postdoctoral Fellowship from the McDonnell-Pew Program in Cognitive Neuroscience ($150K direct costs over three years) and grant from the International Dyslexia Association ($15K direct costs). This work has been presented at the conferences of the Society for Neuroscience and the Cognitive Neuroscience Society; a manuscript is in preparation.

A third project also addresses a type of processing that may be impaired in dyslexics, but in the context of seeking to move beyond the question of what types of stimuli make a brain area "light up", and to ask instead what types of computational processing an area is carrying out. This study is using a new technique called adaptation-fMRI to investigate the categorical processing of speech. This adaptation method, which has until now been confined mostly to fMRI studies of visual object invariance, exploits short-term neural plasticity to probe whether two stimuli count as the same or different for a given neuronal population. In this experiment, the stimuli consist of pairs of Klatt-synthesised phonemes drawn from a set of ten speech stimuli spread evenly along the /ba/ to /da/ continuum. If a brain area processes the pair of stimuli as speech then it will process them categorically, treating the members of the pair as different when, and only when, they fall on opposite sides of the category boundary. Because the adaptation-fMRI signal from a brain area becomes greater when that area treats a pair of stimuli as different rather than as the same, this signal therefore becomes a marker for whether the stimuli are being processed categorically, as speech, versus non-categorically, as low-level acoustic signals. A possible future application of this method is to assess the brain-wide differences in phonetic processing between dyslexic and normal subjects. This work has been presented at the Society for Neuroscience conference; a manuscript is in preparation.