1) Spinal reflex facilitating brain stem stimulation in the anesthetized cat when stimulated in the conscious cat led to positive behavior (purring, cuddling etc); spinal reflect inhibitory brain stem stimulation when anesthetized led to rage and attack in the conscious cat (1956)
(2) Amygdale stimulation in electrode implanted humans doubled circulating corticoids, hippocampal stimulation markedly re duced plasma corticoids (1966)
(3) We discovered a methylation, hallucinogen (DMT and bufotenin) forming enzyme in the frontal lobes of humans (1972-73)
(4) The plasma level corticoids were increased by injections of ACTH, the rate limiting liver enzyme in the tryptophan pathway was induced such that most of the tryptophan was used for energy metabolism leading to decreases in the tryptophan needed to form brain serotonin. Depression increased corticoids which induced liver tryptophan pyrolase making via the serotonin decreases, bad matters worse.1964-1968) Book: Psychochemical Research Strategies in Man, Academic Press, N.Y. 1969.
(5) Rapid eye movement sleep episodes are associated with release of high levels of anti-diuretic hormone, ADH, with complete arrest of urine formation (in humans). When REM periods ended there was a compensatory diuresis (1967). Correlated changes in urinary steroids.
(6) We described the first allosterically modulated brain enzyme, tyrosine hydroxylase (1972-77) and drug effects on these systems. Allosteric modulation is finally a focus of the drug with two start ups in the last couple of years dedicated to finding Book: Neurobiological Mechanisms of Adaptation and Behavior, Raven, N.Y. 1975.
(7) Demonstrated modulation of serotonin and dopamine synthesis and receptor sensitivity by peptides ligands, ions such as calcium and lithium, far from equilibrium cofactor concentrations, amine feedback regulation of mixed fundtion oxygenases, substrate uptake dynamics in a coordinated, multiple characteristic time global dynamic (1968-1978) Books: New Concepts in Neurotransmitter Regulation, Plenum, N.Y. 1973; Biochemistry of Mental Disorders, New Vistas, (with E. Usdin) Marcel Dekker, N.Y. 1978.
(8) First application of fluctuation analysis to rate limiting enzyme activity manifesting bifurcations, power law scaling, fractal dynamics, Levy statistics, ergodic measure theory (1981-1987)
(9) Documented, for the first time, the routine use of super doses of amphetamine (up to 150 mg within two or three hours to induce paranoid rage in NFL football players. Systematic interview with >200 NFL players demonstrated systematicrelationships between position, “personality” and typical dose ranges of amphetamine.(1969-1978) Book: Nightmare Season, Random House, 1976
(10) Eigendecomposition followed by wavelet transformation of proteins as series of variously hydrophobic amino acid discriminated among several classes of proteins (blind) AND indicated hydrophobic sequence patterns (hydrophobic eigenmodes) that we used in peptide design that actually worked on the target receptors, modulated proteins allosterically and changed behavior. Peptides are made in d amino acid form so resist hydrolysis. (1995-2008) Book: Perspectives in Biological Dynamics and Theoretical Medicine (with S.H. Koslow and M.F. Shlesinger) Vol 504; New York Academy of Sciences. 1987
(11) Cardiac interbeat interval (and other physiological time series) demonstrates decreases in variously measured entropy in pathological states (1980). "Lost entropy" as a pathophysiological dynamical state (1982)Similar findings of entropy deficiency in dynamnics of multiple pathological states including desensitization, aging gaits, interictal epileptic states, fetal motion, Parkinsonism, (1982-2005)
(12) MEG symmetric sensor difference series revealed individually different power laws, entropy reduction in schizophrenics and non-seizing epileptics, and the presence of intermittent scale free helicity we call strudels (2007). Development of a Multiple measures, MEG-ssds Measure Suite as “open source”. 2006-2010. Measures quantitatively describe brain MEG and EEG global dynamical systems, emphasis on time not space. A global dimension of dynamics: “From intermittency to transitivity in neuropsychobiological flows” describes smooth transitions from diffusive randomness to bursting as a general dynamical property of EEG and MEG brain systems.
1958: Borden Research Prize in Medicine
1963-1965: Career Teacher Award of the National Institutes of Mental Health
1962 A.E. Bennet Award for Research in Biological Psychiatry
1968-1978 Founding Chairman and Professor Emeritus, Department of Psychiatry (Neuroscience, Mathematics) UCSD.
1976-1977: President, Society of Biological Psychiatry
1979: Foundations Fund Research Prize of the American Psychiatric Association
1980-1982: Grass Foundation Visiting Scientist Award, Society for Neuroscience
1984-1989: The John D. and Catherine T. MacArthur Foundation Prize Fellowship in Mathematical and Theoretical Neuroscience
1991-1995: Traveling Lecturer of Mathematical Association of America
1994: Senior United States Scientist Prize Fellowship, Humboldt Foundation,
Institute of Nonlinear Science, Bremen, Germany