Showing papers by "Rob Knight published in 2000"

Neural representations of skilled movement.

Abstract: The frontal and parietal cortex are intimately involved in the representation of goal-directed movements, but the crucial neuroanatomical sites are not well established in humans. In order to identify these sites more precisely, we studied stroke patients who had the classic syndrome of ideomotor limb apraxia, which disrupts goal-directed movements, such as writing or brushing teeth. Patients with and without limb apraxia were identified by assessing errors imitating gestures and specifying a cut-off for apraxia relative to a normal control group. We then used MRI or CT for lesion localization and compared areas of overlap in those patients with and without limb apraxia. Patients with ideomotor limb apraxia had damage lateralized to a left hemispheric network involving the middle frontal gyrus and intraparietal sulcus region. Thus, the results revealed that discrete areas in the left hemisphere of humans are critical for control of complex goal-directed movements.

An amphioxus Krox gene: insights into vertebrate hindbrain evolution.

Abstract: The transcription factor Krox-20 has roles in the maintenance of segmentation and specification of segment identity in the vertebrate hindbrain Overt hindbrain segmentation is a vertebrate novelty, and is not seen in invertebrate chordates such as amphioxus and tunicates To test if the roles of Krox-20 are also derived, we cloned a Krox-20 related gene, AmphiKrox, from amphioxus AmphiKrox is related to a small family of vertebrate Krox genes and is expressed in the most anterior region of the amphioxus brain and in the club shaped gland, a secretory organ that develops in the anterior pharynx Neither expression domain overlaps with the expression of AmphiHox-1, -2, -3 or -4, suggesting that the roles of Krox-20 in hindbrain segmentation and in Hox gene regulation were acquired concomitant with the duplication of Krox genes in vertebrate evolution

Neural mechanisms of attention: the northern California years.

Abstract: Simon Brailowsky is best known for his contributions to brain plasticity. Yet, it was a longstanding fascination with the neural mechanisms of attention that occupied the brunt of his scientific inquiries during his three years in California, from 1983 to 1985. Simon arrived at the University of California-Davis ostensibly to finish his Ph.D. from the University of Paris. He didn’t have a firm plan in mind but, in Simon’s typical world and scientific view, he knew that something interesting would emerge. We immediately became friends and collaborators and decided to develop an animal model of hemispatial neglect that we could use to assess the behavioral, neuropharmacological, and electrophysiological underpinnings of attention. In retrospect, we may have been a bit overambitious. Nevertheless, and perhaps more important, Simon wanted any rat attention model to be easily transferable to the understanding of human attention dysfunction. Several groups, led by the work of Hillyard and colleagues at the University of California San Diego, had shown that evoked potentials could be used to monitor attention-related neural activity in behaving humans. Simon reasoned that instead of employing single-unit recording in animals, we should develop a rat evoked-potential attention model so that the work would be more easily comparable to the human data. This innate drive to do research that is immediately relevant to human behavior became a central theme of virtually all of Simon’s professional work in epilepsy, stroke, and plasticity. A rat attention model necessitated two parallel lines of research. The first problem was how to induce and measure neglect in animals. Simon came up with the brilliant idea of inducing a reversible behavioral syndrome by the microinfusion of GABA into the putative brain regions of interest. His initial studies in acute cats showed that regional GABA application reliably and reversibly suppressed sensoryevoked potentials from primary sensory cortices, and he reasoned that a similar effect would occur in the motor cortex (Brailowsky & Knight, 1984; Knight & Brailowsky, 1990). A small digression provides some insight into the problems and joys of our early acute animal endeavors. We were performing an acute animal experiment on the effects of GABA on the auditory cortex of a cat who was being ventilated by the standard. Harvard Pump. At about 2 o’clock in the morning, after about 9 to 10 h of preparation and initial experimental manipula-tions, the pump froze, along with the hearts of both investigators. Without much discussion, I began disassembling the pump, trying to unfreeze the mechanism. I will never forget Simon sitting there blowing into the tracheostomy tube, keeping the animal ventilated, and intermittently yelling to me in his typical fashion, \"Come on man, hurry it up.\" This went on for seemingly hours but in reality for only a few hilarious minutes before large amounts of oil and brute force unfroze the pump and put us back on track. The then recent development of the ALZA minipump afforded a possible 7-d GABA infusion period, which could be used to examine the time course of local cortical inactivation. The likely target sites were either parietal or prefrontal regions, on the basis of the extant animal and human neglect literature. We decided, however, that we should first examine motor performance, reasoning that this would be more amenable to