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Biomedical subjects

R W Doty

Publications and source records attributed to R W Doty.

12 recordsLinked to original sources

Bi-versus monohemispheric performance in split-brain and partially split-brain macaques.

Experiments comparing binocular with monocular abilities of monkeys working on visual mnemonic tasks were performed. First, it was shown that even in split-brain monkeys performance was more accurate when both hemispheres were utilized than when the task was performed with only the single (better) hemisphere. Some form of noncommissural integration is thus possible. However, when the forebrain commissures are present, as in four other animals (with only optic chiasm transected) it was shown that integration occurs via callosal mechanisms as well. This was demonstrated by the fact that here, too, binocular performance was normally more accurate than monocular performance, but when different images to be remembered were presented concurrently to the two eyes, the binocular advantage was lost. Finally, in three monkeys with only the anterior commissure allowing interhemispheric communication the superiority of binocular assessment remained even when the two hemispheres simultaneously received such differing images.

Animals

Schizophrenia: a disease of interhemispheric processes at forebrain and brainstem levels?

The evidence is convincing that each human cerebral hemisphere is capable of human mental activity. This being so, every normal human thought and action demands either a consensus between the two hemispheres, or a dominance of one over the other, in any event integrated into a unity of conscious mentation. How this is achieved remains wholly mysterious, but anatomical and behavioral data suggest that the two hemispheres, and their respective bilateral, anatomical-functional components, maintain a dynamic equilibrium through neural competition. While the forebrain commissures must contribute substantially to this competitive process, it is emphasized in this review that the serotonergic raphé nuclei of pons and mesencephalon are also participants in interhemispheric events. Each side of the raphé projects heavily to both sides of the forebrain, and each is in receipt of bilateral input from the forebrain and the habenulo-interpeduncular system. A multifarious loop thus exists between the two hemispheres, comprised of both forebrain commissural and brainstem paths. There are many reasons for believing that perturbation of this loop, by a variety of pathogenic agents or processes, probably including severe mental stress in susceptible individuals, underlies the extraordinarily diverse symptomatology of schizophrenia. Abnormality of features reflecting interhemispheric processes is common in schizophrenic patients; and the 'first rank' symptoms of delusions or hallucinations are prototypical of what might be expected were the two hemispheres unable to integrate their potentially independent thoughts. Furthermore, additional evidence suggests that the disorder lies within, or is focused primarily through, the raphé serotonergic system, that plays such a fundamental role in consciousness, in dreaming, in response to psychotomimetic drugs, and probably in movement, and even the trophic state of the neocortex. This system is also well situated to control the dopaminergic neurons of the ventral tegmental area, thus relating to the prominence of dopaminergic features in schizophrenia; and the lipofuscin loading and intimate relation with blood vessels and ependyma may make neurons of the raphé uniquely vulnerable to deleterious agents.

Brain Stem

Disturbance of delayed match-to-sample in macaques by tetanization of anterior commissure versus limbic system or basal ganglia.

Three pig-tailed macaques were trained to select ("match") from a pair of colored images that which they had seen ("sample") and responded to 5--15 s previously. The anterior commissure (AC) and/or its radiation, various loci in basal ganglia, hippocampal formation and "control" areas, (splenium of corpus callosum, precentral gyrus, insular cortex), totalling 40 loci, were each tetanized for 4 s during presentation of the "sample" image, during the delay period, or when the monkey was required to select the "matching" image. For several loci in the hippocampal formation tetanization at any phase of the task reduced "matching" to chance levels and gave evidence of electrical after-discharge; but other comparable hippocampal loci had little or no effect. Response to "sample" or "match" stimuli were absent during tetanization of basal ganglia or anterior commissure. When finally made, upon cessation of tetanization, responses were equally correct for basal ganglia and "control" sites, but for AC were at chance levels.

Animals

Luxotonic responses of units in macaque striate cortex.

1. Single units in striate cortex were studied in alert macaques while they viewed a ganzfeld. Of the 385 well-isolated units studied for 10 min to 2 h, 24% gave "luxotonic" responses, i.e., their rate of discharge for 1 min or more in diffuse, featureless, wideangle illumination (20-450 cd/m2) was at least double that during a comparable period in darkness, or vice versa, and not attributable to eye movements of blinking. Those discharging faster in the light, "photergic" units, outnumber those responding to darkness, "scotergic" units 1 by 4:1. 2. In the lateral geniculate nucleus, on the other hand, among 46 units studied, 28% were luxotonic, but scotergic units were the more common. Both types were present in both magno- and parvocellular laminae. 3. For striate cortex two-thirds of the luxotonic units were binocular. Some showed highly similar response for either eye alone, and essentially no summation binocularly; others had grossly differing responses from each eye, and complex binocular interaction. 4. Many units of all types at striate cortex showed significant modulation of their activity consequent to saccadic eye movements made in darkness, whereas comparable modulation was not observed at the lateral geniculate nucleus. 5. On the basis of these and other findings it is concluded that luxotonic cortical activity is prominent probably only in alert primates, and that this is a consequence of the fact that all retinal ganglion cells in primates synapse in the lateral geniculate nucleus (Ref. 9). Possible functions range from mere trophic input to providing a veridical image or a scaling factor for maintenance of perceptual constancy in the face of varying levels of general illumination.

Adaptation, Physiological

Tonic retinal influences in primates.

A type of unit discharge, termed "luxotonic," has been found in the striate cortex of unanesthetized squirrel monkeys and macaques.6, 21 The firing frequency of these units shows relatively little adaptation, continues indefinitely (hours), and reflects the level of diffuse illumination of the eye. The more numerous "photergic" units discharge more rapidly in the light, whereas "scotergic" units fire fastest in the dark (or at luminance levels below threshold for cones). Luxotonic activity is abolished by anesthesia and has not been described for striate cortex of other species. Primates also display a profound alteration in the EEG of striate cortex following elimination of all retinal input.32 Since this change is far more drastic than that produced by blindness in other species, it is natural to inquire whether it is related to the loss of the normally prominent luxotonic activity. When the blind monkey sleeps, the bizarre EEG is replaced by patterns wholly normal in appearance,32 indicating that some nonvisual system has extensive access to striate cortex in this state.

Animals

Deleterious effects of prolonged electrical excitation of striate cortex in macaques.

Macaques were trained to respond to electrical excitation applied through electrodes permanently implanted within or upon striate cortex. Threshold current for the animal to detect this stimulation was highly consistent from day to day and, in the absence of tissue encapsulation of the electrodes or deliberately inflicted damage, remained stable indefinitely, 38 months in the longest case so far. Stimulating continuously for 1-8h, however, produces an elevation of threshold, which may be permanent or temporary, depending upon a variety of conditions. A major cause of such injury is the hydrolysis commonly occurring consequent to passage of low-level currents between solutions and metal electrodes. Even when the hydrolytic reaction is eliminated by restricting the level of electrode polarization or by using capacitative stimulation with tantalum pentoxide electrodes, a rise in threshold often still occurs with protracted stimulation. With proper control in some instances, however, effective stimulation at 2-10 times the threshold level could be maintained indefinitely without apparent injury, e.g. in a blind monkey having a threshold of 290 muA that could respond immediately to an 80-muA diminution in 580-muA, 0.2-msec stimulus pulses which had been applied steadily for 1 h at 50 Hz.

Animals

Influence of saccadic eye movements on geniculostriate excitability in normal monkeys.

Using permanently implanted electrodes in squirrel monkeys and macaques, transmission through the lateral geniculate nucleus (LGN) was assayed from the amplitude of potentials evoked in optic radiation by and electrical pulse applied to optic tract. Averaging of either individually or machine selected potentials, elicited at 0.3, 1.0, 20 or 50 HZ, in all cases showed a decrease in transmission ranging from 5-60% in the period after saccadic eye movements made ad libitum. The suppression was greater in a patterned visual environment than in diffuse illumination, which in turn was greater than that occurring following saccades in the dark. Demonstration of the effect in darkness always required data averaging and never exceeded 20%. The effect was consistently greater in the magnocellular than parvocellular component. Suppresion was often abruptly terminated and replaced by a facilitation of 5-15% about 100 msec after saccade detection. Comparable effects were observed for excitability of striate cortex tested by a stimulus pulse applied to optic radiation. In addition, sharply demarcated potentials inherently arising in LGN and striate cortex were found in association with saccades made even in total darkness. Neglecting a possible but dubious contribution from eye muscle proprioceptors, the experiments establish the existence of a centrally originating modulation of visual processing at both LGN and striate cortex in ralation to saccadic eye movement in primates. This modulation may partially underlie the phenomenon of "saccadic suppression" and hasten the acquistion of a meaningful visualsample immediately following an ocular saccade. It remains uncertain as to how it may relate to similar or greater effects accompanying changes in alertness, or to fluctuations of unknown origin occurring sometimes semirhythmically at 0.05-0.03 HZ (Fig 7).

Animals

EEG of striate cortex in blind monkeys: effects of eye movements and sleep.

After control studies, using electrodes permanently implanted in the central visual system, squirrel monkeys and macaques were in most instances blinded by acute glaucoma. This permitted subsequent observation of eye movements. Ocular nystagmus developed in all cases. Beginning immediately upon recovery from anesthesia, and persisting for at least 1 year, the EEG of the striate cortex was characterized by totally flat periods up to several seconds in duration which were ended abruptly by a sharp "spike" trailed in turn by a ragged high voltage, slow pattern for another second or two. The great majority of these "spikes" from the blind striate cortex occurred within 60-200 msec after a saccadic eye movement, made either in nystagmus or attempted fixation. They were not dependent upon proprioception from the extraocular muscles. It is suggested that they represent a "corollary discharge" for movement of the eyes. The blind striate cortex was judged to be hyperexcitable on the basis of these saccade-associated "spikes", not often observable in intact monkeys, and from the increase both in response evoked by electrical stimulation of optic radiation and amplitude of the EEG in sleep.

Animals

Consciousness from neurons.

Consciousness derives from a neural process that requires unceasing metabolic support, and probably involves only a select population of neocortical elements. The essential process must operate for roughly more than 100 ms for sensorial registration (Libet). It is highly unlikely that the essence of the process lies in its computational logic and hence it can never be produced by inanimate machines. Since the process is thus unique to neurons, and since the consciousness of the left hemisphere normally communicates with that of the right (and probably vice versa) via the forebrain cornmissures, at least some portion of the nerve impulse traffic across the commissures must possess a wholly mysterious property enabling its transcendent compilation into a unified conscious experience. Comprehending the nature of this property which couples ionic fluxions into mentality is the quintessential problem of science. The forebrain commissures may ultimately provide the clues for its solution.

Animals