Berenson-Allen Center for Noninvasive Brain Stimulation (CNBS)
Optimizing and applying noninvasive brain stimulation to health care and research

Faculty

Amir Amedi, PhD
Research Faculty

I was born in Jerusalem (Israel) and studied in the Interdisciplinary Center for Neural Computation (ICNC) in the Hebrew University of Jerusalem, doing research on multisensory processing and plasticity in humans using fMRI. I joined the CNBS in 2004 after being exposed to TMS in a research project conducted at the National Institute of Health (NINDS / NIH). I am currently a postdoctoral research investigator in the center and also serves as an Instructor of Neurology at Beth Isreal Medical Center / Harvard Medical School . I am holding a long-term fellowship from the Human Frontiers Science Program to study brain plasticity, sensory substitution and their possible relevance to vision research and vision restoration.

Research Interests / Research Focus

Restoration of sight in a blind person imposes great clinical and scientific challenges. Despite intensive efforts, restoration of truly functional vision using neuroprostheses has not been achieved, possibly due to limited knowledge about how to communicate with the massive reorganization in the visual cortex of blind (e.g. Amedi, Raz et. al., Nature Neuroscience 2003). As our life experience is a rich multisensory process, I believe that studying how information from the different senses is integrated, is important to our understanding how the brain functions (Amedi et al. Nature Neuroscience 2001; Cerebral Cortex 2002) and how it reorganizes after injury or insult. The brain undergoes plastic changes constantly, and in understanding brain mechanisms of plasticity, the challenge is learning enough in order to be able to modify them in need (Pascual-Leone, Amedi et al., Annual Reviews in Neuroscience 2005).

I use advanced neuroimaging and neurophysiological techniques combined or correlated with psychophysical behavioral testing. Specifically, fMRI is used to identify brain areas or networks that are devoted to a given function. Repetitive TMS is then used as a ‘virtual lesion tool’ to evaluate the functional significance of these brain regions by assessing the behavioral consequences of their transient disruption (e.g. Amedi, Floel et. al., Nature Neuroscience 2004). Single-pulse TMS can potentially reveal spatio-temporal patterns of information flow between the different areas of the network (e.g. Pascual-Leone, Amedi et al., Annual Reviews in Neuroscience 2005). Finally, real-time combination of TMS with neuroimaging (fMRI) is used to investigate the neural basis and effective connectivity for any given function that can be modified or elicited by TMS. We have recently made some progress in this line of work, solving some technical challenges, and currently studying various aspects of perception, visual awareness and plasticity.

One line of research during my post-doctoral fellowship, involves studying sensory substitution devices (SSDs). In SSD, visual information captured by an artificial receptor is delivered to the brain of a blind person using non-visual sensory information (e.g. auditory soundscapes) via a human-machine interface. Preliminary data, (Amedi et al. CNS 2005; Amedi and Meijer, 2005; IMRF conference paper presentation) suggests that the neural basis of using auditory-to-visual SSD in proficient blind users includes recruitment of ventral and dorsal visual cortex to process form and space in a specific manner. This led us to propose that sensory substitution devices (SSD) may play a major role in ‘guiding’ the visual cortex to interpret visual information arriving from a retinal prosthesis (Merabet et al. Nature Reviews in Neuroscience, 2005; Pascual-Leone, Amedi et al., Annual Reviews in Neuroscience 2005; ). The project have two main general aims: 1) Studying the learning process of using SSD in order to speed it up and help increasing the efficiency of using such SSDs for blind in daily life activities. 2) Closing the gap between visual neuroprostheses and functional restoration of vision. These two aims of the project has fundamental applications in visual and cognitive neuroscience as well as a potential practical significance for the quality of life of millions of blind people worldwide.

Using SSDs, blind individuals are able to represent and recognize ‘visual’ input using a different sensory modality. As a corollary, we studied a case of a completely blind individual able to paint and draw using his touch sense only, with exquisite detail despite having no sight experiences or visual recollections. We have studied his ability to recognize, mentally represent in his “mind’s eye” and then draw objects in a way that can be easily understood by a sighted person (including concepts such as vantage point and perspective). His remarkable abilities are mirrored by a corresponding unique pattern of plasticity within his ‘visual’ cortex (Amedi et al. HBM 2005 abstract). We also found atypical pattern of activity during mental imagery, which led us to further study mental imagery versus visual perception in sighted.

We found that, during mental imagery (but not during visual perception), auditory, somatosensory and subcortical structures show dramatic deactivation. Perception of the world requires merging of multi-sensory information so that seeing is inextricably associated with processing of other sensory modalities that modify visual cortical activity and shape experience (e.g. Amedi et al., Experimental Brain Research 2005). By contrast, we suggest that pure visual imagery is the isolated activation of visual cortical areas with concurrent deactivation of sensory inputs that could disrupt the image created by our ‘mind’s eye’. Indeed, we found correlations between the magnitude of deactivation and the vividness of visual imagery across individuals. Furthermore, we found evidence (using inter-regional functional connectivity analysis), supporting the hypothesis that visual cortex is disconnected from other sensory systems during pure visual imagery (Amedi et al., Neuron 2005). The relation between behavior and brain processing as reflected by positive BOLD signals is in the heart of neuroimaging research. It seems that similar attention should be given to study the contribution of negative BOLD to behavior. I was also fortunate to collaborate with post-doctoral fellows in the lab on various topics such as the interactions between vision and emotion. This line of work led to recent publications in leading neuroimaging journals (Bermphol et al. Neuroimage, 2005; Human Brain Mapping, 2005).

My focus in the past year was work on developing cutting-edge techniques of a real-time combination of TMS with neuroimaging (in collaboration with Dr. Joan Camprodon and under the supervision of Prof. Alvaro Pascual-Leone and in collaboration with the Center for Biomedical Imaging at Boston University directed by Prof. Dae-Shik Kim). Concurrent fMRI-TMS can be used to study and collaborate on a variety of topics ranging from sensory perception, motor functions and high-level cognitive function in which TMS can have a significant behavioral effect. In parallel, it can be used to target any given cortical area and study its pattern of connectivity to all other cortical or subcortical structures simultaneously and thus can serve as a basis for any network analysis (such as chronometry, modeling of large-scale neural networks etc.). It can also be used to study the changes in connectivity between brain areas depending on the task (‘effective connectivity’) or connectivity changes following learning or plasticity processes (for instance, changes in brain connectivity in the occipital cortex of blind individuals). This can nicely complement anatomical markers approaches, which have contributed crucial insights but have limitations (laborious and slow data acquisition, applicable almost solely to animal models and limited to anatomical rather then effective connectivity). Recently, we have developed and validated an experimental protocol to record TMS-induced fMRI BOLD activity to run a study of visual awareness and connectivity. In parallel, we are collaborating with Gregor Thut’s lab in Geneva to implement similar protocol using TMS-EEG setup in order to add crucial time information. Preliminary findings of this study were presented recently (Amedi et al., Society for Neuroscience 2005).

Relevant Publications

Amedi A, Malach R, Pascual-Leone A. Negative BOLD differentiates visual imagery and perception. Neuron. 2005; Vol. 48:859-872.

Pascual-Leone A, Amedi A, Fregni F, Merabet L. The Plastic Human Brain Cortex. Annual Reviews Neuroscience. 2005; 28:377-401.

Amedi A, Floel A, Knecht S, Zohary E, Cohen, LG. Transcranial magnetic stimulation of the occipital pole interferes with verbal processing in blind subjects Nature Neuroscience 2004; 7:1266-70.

Raz N, Amedi A, Zohary E. V1 activation in congenitally blind is associated with episodic retrieval. Cerebral Cortex 2005; 15:1459-1468.

Amedi A, Raz N, Pianka P, Malach R, Zohary E. Early ‘visual’ cortex activation correlates with superior verbal-memory performance in the blind. Nature Neuroscience 2003; 6:758-66.

Amedi A, Jacobson G, Hendler T, Malach R, Zohary E. Convergence of visual and tactile shape processing in the human lateral occipital complex. Cerebral Cortex 2002; 12:1202-1212.

Amedi A, Malach R, Hendler T, Peled S, Zohary E. Visuo-haptic object-related activation in the ventral visual pathway. Nature Neuroscience 2001; 4:324-330.

Amedi A, Merabet L, Bermpohl F, Pascual-Leone A. The Occipital Cortex in the Blind: Lessons about Plasticity and Vision. Current Directions in Psychological Science. 2005.(In Press).

Amedi A, Von Kriegstein K, Van Atteveldt N, Beauchamp MS, Naumer MJ. Functional imaging of human crossmodal identification and object recognition Experimental Brain Research 2005; 166: 559-71.

Merabet L, Rizzo J, Amedi A, Somers D, Pascual-Leone A. What blindness can tell us about seeing again: Merging neuroplasticity and neuroprostheses. Nature Review Neuroscience. 2005; 6:71-77.

Bermpohl F, Pascual-Leone A, Amedi A, Merabet L, Fregni F, Gaab N, Alsop D, Schlaug G, Northoff G. Attention Modulation of Emotional Stimulus Processing-An fMRI Study Using Emotional Expectancy. Human Brain Mapping (2005) (Epub ahead of print).

Merabet L, Amedi A, Pascual-Leone A. Activation of the Primary Visual Cortex by Braille reading in Blind Subjects. In: Reprogramming the Cerebral Cortex (Eds. S. Lomber and D. Eggermont) Oxford University Press. 2005.

Bermpohl F, Pascual-Leone A, Amedi A, Merabet L, Fregni F, Gaab N, Alsop D, Schlaug G, Northoff G. Dissociable Networks for the Expectancy and Perception of Emotional Stimuli in the Human Brain. Neuroimage (2005) (Epub ahead of print).