Since 1993, I have employed neuroanatomy, histology, Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), Diffusion Tensor Imaging (DTI), electroencephalography (EEG), magnetoencephalography (MEG) as well as behavioral methods to study the normal and the diseased brain.
My MD thesis was focused on anatomical studies of the human visual cortex, examining the callosal connections between different visual regions of the human brain. As a postdoctoral fellow at the Karolinska Institute, Stockholm, Sweden, I used PET to study crossmodal matching between touch and vision, and was able to show for the first time communication between modality specific areas through the claustrum.
In my research at the MGH-Martinos Center, I have been using different methods of brain imaging (fMRI, EEG, MEG) to better characterize the different functional components of our visual system. Using fMRI, I discovered and characterized the area of the brain that is responsible for color vision. Using this extensive base of knowledge of the functional organization of the brain, I extended the scope of my research beyond the visual system, in the broader context of neurological diseases such as brain damage following focal lesions, migraine, and developmental disorders such as autism.
Migraine is a very common yet poorly understood phenomenon. In about a third of patients, the headache is preceded by a visual phenomenon called the aura. For the first time, our group was able to show that the aura of migraine was a phenomenon similar cortical spreading depression, invalidating the old vascular theory of migraine and opening new perspectives in the treatment of this common and debilitating disorder. This work has been cited more than 500 times and referenced in a review article in Nature Neuroscience as being “the most thorough investigation of changes in neuronal activity during migraine aura”. Presently, our group is working on extending our understanding of the pathophysiology of migraine, and examining the long-term consequences of this disease on the brain, including in the perception of pain.
Neurological syndromes following focal lesions provide a way to better understand the functional organization of the brain. We have been using this approach to investigate the network of areas involved in face recognition. Examining the responses of lesioned brains to stimuli characterized in normal controls can cast light on the potential plasticity and help identify appropriate strategies to adopt for rehabilitation.
Autism is a neurodevelopmental disease that affects one in 88 children. The etiology of this syndrome is still not well understood, and the links between behavioral deficits in autism and their biological substrate are just starting to emerge. Based on my extensive knowledge of the organization of the visual system, our group was able to demonstrate that "low level" visual processing is normal in individuals with autism, ruling out a bottom-up deficit. Moreover, we were the first to provide data disproving a popular theory stating that individuals with autism are lacking the brain area devoted to face identification (the “fusiform face area”, or FFA), opening new hypotheses on the etiology of some of the behavioral aspects of autism potential new therapeutic strategies. Our anatomical and functional studies have demonstrated the presence of abnormalities in the so-called “mirror neuron” areas (which enable us to mimic and mentally simulate the emotions, behavior and movement of others) of young adults with high-functioning autism .These findings suggest a possible deficit that could be addressed with behavioral training. In fact, recent results indicate that imitation training, an activity that will activate the mirroring mechanisms, does significantly improve autistic behavior. Our current work is dedicated to understand the neural bases of the deficits of social instinct in ASD, and to develop neural biomarkers that will help to objectify the effect of therapeutical approaches, both behavioral and phramacological.
Emotion perception has been studied using functional imaging for several years, but to date has been concentrated primarily on processes associated with viewing facial expressions. However, from an evolutionary perspective, investigations of expressive body movements may be just as important for understanding the neurobiology of emotional behavior. We published the first functional study on the perception of body expression of emotion in normal subjects, and we are using this new and fascinating model of emotion perception to examine neurodevelopmental disorders and intend to explore this aspect of emotional cognition in autism.
Recently, I have been collaborating with a group of geneticists in a project examining the consequences of chromosome 16p11.2 copy number variant (CNV). This CNV was known to be associated with autism, and we furthered these studies publishing a paper in Nature, which reported, for the first time, an association between a CNV and obesity.