Research Topics

Objectives

Our long term goal has been to contribute to the discovery of principles underlying cortical processing, perception, higher brain functions and the "neural code" used by neuronal assemblies.

Background

A precondition to deciphering the neocortical “neural code” is to determine the functional architecture of cortex. Clearly one must first understand what is the basic function(s) actually performed by a given neuronal group(s) before one can hope to understand the strategy they employ. Next, one should define how these group s of neurons are organized in space. Subsequently, spatio-temporal patterns of electrical activity should be monitored and only then can the code in these tangled communication networks be deciphered. Long-standing questions related to sensory information processing, perception and higher cognitive functions can be finally resolved by direct visualization of the architecture and function of mammalian cortex in unprecedented detail.

This advance has been accomplished with the aid of two optical imaging techniques one based on voltage sensitive dyes (1-3) and one on intrinsic signals (4-6). Utilizing these techniques one can "directly see" how the brain functions. Our explorations are combined with traditional neuroanatomical and neurophysiological techniques and are guided by computational theories and modeling. The combination of real time optical imaging and single unit recording have facilitated the direct visualization of neuronal assemblies . Recently, a number of imaging techniques such as PET, EEG, MEG f-MRI and optical imaging have made feasible many experiments which were considered neuroscientists' “fantasy” only a decade ago. Among these imaging techniques, optical imaging stands out because it is the only imaging technique offering the temporal and spatial resolutions required to study the functional organization and the dynamics of neuronal assemblies

Recent Findings

These include establishing the pinwheel- like organization of orientation domains in primary visual cortex responsible for shape perception (7); description of the cortical point spread function implying that cortical processing is far more distributed than previously estimated (8); discovery of the functional organization for direction selectivity and its spatial relation to orientation columns in visual areas MT and 18; discovery of two subsystem of spatio-temporal frequency columns; discovery of the relationships between various functional domains in monkey primary visual cortex (9) and in cat visual cortex, underlying visual perception (see illustration); visualization of neuronal assemblies and discovery of the dynamic organization of coherent on going activity (10); discovery that on going activity of a single neuron is a reflection of the on-going activity in the related functional architecture, rather than stochastic activity (11-12); demonstration of cortical correlates of a visual illusion in early visual areas (13), implementation of chronic VSDI for the behaving monkey, for a period longer than a year. (14) discovery of the relationship between electrical activity and the responses of the microcirculation and its implication for improving of the spatial resolution of f-MRI (15-17). Clinical applications of optical imaging for neurosurgery (18) and ophthalmology (19-20) were pursued in local and foreign hospitals.

Mapping of the geometrical relationships between various processing modules underlying visual perception in primary visual cortices of monkeys (the cube) and cats (the ellipse) by Intrinsic optical imaging. (The “ice cube” model was first put forward by Hubel and Wiesel and Livingstone, and then revised based on optical imaging findings; see ref 7). Intrinsic optical imaging can be combined with anatomical methods such as biocytin labeling of single neurons thus elucidating the relationship between neuronal structure and function (bottom left square). To explore cortical dynamics, intrinsic optical imaging can be combined also with optical imaging based on voltage sensitive dyeselectrophysiological recording and microstimulation (3). Figure courtesy of Amiram Grinvald and Tobias Bonhoeffer (“Imaging Neurons” book cover, CSHL Press 1999).

Acknowledgement

Our work is supported by grants from NIH, MDA, PVA, BSF, ISF, EMBO, GIF, The Joint German Israeli Research Program, The Jewish agency, March of Dimes, USA Air force, The Jewish agency, the Center for Psychobiology and by grants from the Klingestein, Ms. Enoch, Riklis, Schilling, Minerva, The Goldsmith Foundation, The Grodetsky Center, Wolfson, and Bat Sheva de Rothschild Foundations and DuPont Corporations.

A. Grinvald is The Helen and Norman Asher Professorial Chair of Brain Research, and the director of the Grodetsky Center for the Research of Higher Brain Functions.

Selected Publications

  1. Grinvald A., B.M. Salzberg and L.B. Cohen. Simultaneous recording from several neurons in an invertebrate central nervous system. Nature 268:140, (1977).
  2. Shoham, D., D .E. Glaser, A. Arieli, Tal Kenet, R. Hildesheim, and A. Grinvald. Imaging cortical architecture and dynamics at high spatial and temporal resolution with new voltage-sensitive dyes. Neuron, 24: 1-12, (1999).
  3. Grinvald A. and Hildesheim R. VSDI, a new era in functional brain imaging of cortical dynamics. Nature Review Neuroscience, 5: 873-884, (2004).
  4. Grinvald A., E. Lieke, R. Frostig, C.D. Gilbert and T.N. Wiesel. Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature, 324: 361-364, (1986).
  5. Frostig R.D., E. Lieke, D.Y. Ts'o and A. Grinvald. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo  high resolution optical imaging of intrinsic signals in cat and monkey visual cortex. Proc. Natl. Acad. Sci. USA,  87: 6082-6086, (1990).
  6. Ts'o D.Y., R.D. Frostig. E. Lieke and A. Grinvald. Functional architecture of primate visual cortex revealed by high resolution optical imaging. Science, 249: 417-420, (1990).
  7. Bonhoeffer T. and A. Grinvald. Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns. Nature, 353: 429-431, (1991).
  8. Grinvald A., E. Lieke, R.D. Frostig and R. Hildesheim. Cortical point images and long-range lateral interaction in primary visual cortex of Macaque monkey. J. Neurosci.,  14: 2545-2568, (1994).
  9. Bartfeld E. and A. Grinvald. Architecture of the orientation, ocularity and color processing-modules in primate striate cortex. Proc. Natl. Acad. Sci. USA, 89: 11905-11909, (1992).
  10. Arieli A., D. Shoham, R. Hildesheim and A. Grinvald. Coherent spatio-temporal pattern of on-going activity revealed by real-time optical imaging coupled with single unit recording in the cat visual cortex. J. Neurophysiol., 73: 2072-2093, (1995).
  11. Tsodyks M., T. Kenet, A. Grinvald and A. Arieli. The spontaneous activity of single cortical neuron depends the underlying global functional architecture. Science, 286: 1943-1946, (1999).
  12. Kenet, T., A. Grinvald, M. Tsodyks, A. Arieli. Spontaneously occurring cortical representations of visual attributes. Nature , 425: 954-956, (2003).
  13. Jancke Dirk Chavane Frédéric Naaman Shmuel , and Amiram Grinvald. Imaging cortical correlates of a visual illusion. Nature, 428: 424-42, (2004).
  14. Slovin, H., A. Arieli , R. Hildesheim, and A. Grinvald. Long-term voltage-sensitive dye imaging of cortical dynamics in the behaving monkey . J. Neurophys.  88: 342-3438, (2002).
  15. Malonek D. and A. Grinvald. Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy; implications for functional brain imaging. Science,  272: 551-554, (1996).
  16. Vanzetta I., and A. Grinvald. Cortical activity-dependent oxidative metabolism revealed by direct oxygen tension measurements; implications for functional brain imaging. Science, 286: 1555-1558, (1999).
  17. Vanzetta Ivo, Slovin Hamutal and Omer Didi -Baklash Grinvald Amiram. Columnar resolution of blood volume and oximetry functional maps in the behaving monkey; implications for FMRI. Neuron, 42: 843-54, (2004).
  18. Shoham D., A. Grinvald A.  The Cortical Representative of the hand in Macaque and Human Area S-I: High Resolution Optical Imaging. J. Neuroscience, 21(17): 6820-6835 (2001).
  19. Grinvald, A. Bonhoeffer, T. Pollack, A. Aloni, E. Ofri, R. and Nelson, D.. High Resolution Functional Optical Imaging; From the Neocortex to the Eye. Ophthalmol. Clin. N Am., 17: 53-67, (2004).
  20. Nelson, DA. S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, R. Mordechai, and A. Grinvald. Noninvasive Multi-parameter Functional Optical Imaging of the Eye. Ophthalmic Surgery, Lasers and Imaging, 36(1):57-66, (2005).