Investigator Assoc Prof (M) Athinoula A. Martinos Center for Biomedical Imaging, Mass General Research Institute

Associate Professor of Radiology Harvard Medical School

autism; autism spectrum disorder; brain imaging; diffusion tensor imaging; electroencephalography; eye contact; face; facial expression; fear; fmri; fusiform face area; human visual cortex; magnetoencephalography; migraine; migraine disorders; migraine with aura; pattern recognition visual; positron emission tomography; visual cortex

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, including eye-tracking, 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. 

The neurolimbic system is interestingly at the core of these two conditions, namely migraine and autism.

In migraine, it is involved in the perception of pain and in the sensitization of the cortex over time, which can lead to the progression from episodic to chronic migraine, and may be connected with some of the co-morbidities associated with migraine, including mood and anxiety disorders; in autism, we know since the pioneering work from Bauman and Kemper (1985) that there are anatomical abnormalities in the amygdala, and dysfuntions of the limbic system are participating to the social and emotional difficulties encountered by individuals with 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 1300 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, and examining the role of neuroinflammation in migraine. 

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 64 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. However, we have also demonstrated that so-called affective empathy is intact in autism, that is, mirroring of other people's pain is not affected, therefore demonstrating that mirror mechanisms are not simply broken in autism, but that difficulties may perttain to specific type of stimuli.

Our current work is dedicated to understand the neural bases of the difficulties with eye contact in autism, and consider them as one indication of the consequence of an abnormal balance between the inhibitory and the excitatory systems in early development, a hypothesis that we are testing with a series of new protocols.