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David T Blake

Publications and source records attributed to David T Blake.

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Experience-dependent adult cortical plasticity requires cognitive association between sensation and reward.

We tested the involvement of cognition in adult experience-dependent neuroplasticity using primate cortical implants. In a prior study, learning an operant sensory discrimination increased cortical excitability and target selectivity. Here, the prior task was separated into three behavioral phases. First, naive animals were exposed to stimulus-reward pairings from the prior study. These yoked animals did not have to discriminate to be rewarded and did not learn the discrimination. The plasticity observed in the prior study did not occur. Second, the animals were classically conditioned to discriminate the same stimuli in a simplified format. Learning was accompanied by increased sensory response strength and an increased range of sensory inputs eliciting responses. The third study recreated the original operant discrimination, and selectivity for task targets increased. These studies demonstrate that cognitive association between sensory stimuli and reinforcers accompanies adult experience-dependent cortical plasticity and suggest that selectivity in representation and action are linked.

Acoustic Stimulation↗

Experience-dependent plasticity in S1 caused by noncoincident inputs.

Prior work has shown that coincident inputs became co-represented in somatic sensory cortex. In this study, the hypothesis that the co-representation of digits required synchronous inputs was tested, and the daily development of two-digit receptive fields was observed with cortical implants. Two adult primates detected temporal differences in tap pairs delivered to two adjacent digits. With stimulus onset asynchronies of > or = 100 ms, representations changed to include two-digit receptive fields across the first 4 wk of training. In addition, receptive fields at sites responsive to the taps enlarged more than twofold, and receptive fields at sites not responsive to the taps had no significant areal change. Further training did not increase the expression of two-digit receptive fields. Cortical responses to the taps were not dependent on the interval length. Stimuli preceding a hit, miss, false positives, and true negatives differed in the ongoing cortical rate from 50 to 100 ms after the stimulus but did not differ in the initial, principal, response to the taps. Response latencies to the emergent responses averaged 4.3 ms longer than old responses, which occurs if plasticity is cortical in origin. New response correlations developed in parallel with the new receptive fields. These data show co-representation can be caused by presentation of stimuli across a longer time window than predicted by spike-timing-dependent plasticity and suggest that increased cortical excitability accompanies new task learning.

Action Potentials↗

Associative learning shapes the neural code for stimulus magnitude in primary auditory cortex.

Since the dawn of experimental psychology, researchers have sought an understanding of the fundamental relationship between the amplitude of sensory stimuli and the magnitudes of their perceptual representations. Contemporary theories support the view that magnitude is encoded by a linear increase in firing rate established in the primary afferent pathways. In the present study, we have investigated sound intensity coding in the rat primary auditory cortex (AI) and describe its plasticity by following paired stimulus reinforcement and instrumental conditioning paradigms. In trained animals, population-response strengths in AI became more strongly nonlinear with increasing stimulus intensity. Individual AI responses became selective to more restricted ranges of sound intensities and, as a population, represented a broader range of preferred sound levels. These experiments demonstrate that the representation of stimulus magnitude can be powerfully reshaped by associative learning processes and suggest that the code for sound intensity within AI can be derived from intensity-tuned neurons that change, rather than simply increase, their firing rates in proportion to increases in sound intensity.

Acoustic Stimulation↗

Representation of the hand in the cerebral cortex.

In this brief review, the body of work on hand use and cortical plasticity is reviewed. The hand movements and sensory inputs are represented in the mammalian primary motor cortex and the anterior parietal strip. The dominant organizational rules are that representational area is proportional to peripheral innervation, and that cortical architecture is columnar with limited horizontal spread. The representational area and columnar structure can be shaped by behavior and other input manipulations. The central core systems, and especially cholinergic inputs, act as teachers of the cerebral cortex by marking behavioral reinforcers with the release of acetylcholine. This marking is both necessary and sufficient for plasticity to occur in sensory cortex. As a result of this temporal marking of reinforcing events, nearly coincident inputs over restricted sensory, or motor, segments form coherent representations in primary sensory or motor cortex. Focal dystonia is a problem in which overuse of the hand leads to a lack of motor control, and especially inappropriate use of sensory feedback for motor control. Receptive field size, and columnar architecture, are highly abnormal in this disorder. The deficiencies in focal dystonia, and their appropriate treatment, can be understood by applying the principles of cortical plasticity to the behavioural manipulations that cause focal dystonia.

Acetylcholine↗

Neural correlates of instrumental learning in primary auditory cortex.

In instrumental learning, Thorndike's law of effect states that stimulus-response relations are strengthened if they occur prior to positive reinforcement and weakened if they occur prior to negative reinforcement. In this study, we demonstrate that neural correlates of Thorndike's law may be observed in the primary auditory cortex, A1. Adult owl monkeys learned to discriminate tones higher than a standard frequency. Responses recorded from implanted microelectrodes initially exhibited broad spectral selectivity over a four-to-five octave range. With training, frequency discrimination thresholds changed from close to one octave to about 1/12 octave. Physiological recordings during the week in which the monkey came under behavioral control signaled by a drop in measured threshold had stronger responses to all frequencies. During the same week, A1 neural responses to target stimuli increased relative to standard and nontarget stimuli. This emergent difference in responsiveness persisted throughout the subsequent weeks of behavioral training. These data suggest that behavioral responses to stimuli modulate responsiveness in primary cortical areas.

Animals↗

Sensory representation abnormalities that parallel focal hand dystonia in a primate model.

In our hypothesis of focal dystonia, attended repetitive behaviors generate aberrant sensory representations. Those aberrant representations interfere with motor control. Abnormal motor control strengthens sensory abnormalities. The positive feedback loop reinforces the dystonic condition. Previous studies of primates with focal hand dystonia have demonstrated multi-digit or hairy-glabrous responses at single sites in area 3b, receptive fields that average ten times larger than normal, and high receptive field overlap as a function of horizontal distance. In this study, we strengthen and elaborate these findings. One animal was implanted with an array of microelectrodes that spanned the border between the face and digits. After the animal developed hand dystonia, responses in the initial hand representation increasingly responded to low threshold stimulation of the face in a columnar substitution. The hand-face border that is normally sharp became patchy and smeared over 1 mm of cortex within 6 weeks. Two more trained animals developed a focal hand dystonia variable in severity across the hand. Receptive field size, presence of multi-digit or hairy-glabrous receptive fields, and columnar overlap covaried with the animal's ability to use specific digits. A fourth animal performed the same behaviors without developing dystonia. Many of its physiological measures were similar to the dystonic animals, but receptive field overlap functions were minimally abnormal, and no sites shared response properties that are normally segregated such as hairy-glabrous combined fields, or multi-digit fields. Thalamic mapping demonstrated proportionate levels of abnormality in thalamic representations as were found in cortical representations.

Animals↗

Changes of AI receptive fields with sound density.

Primates engage in auditory behaviors under a broad range of signal-to-noise conditions. In this study, optimal linear receptive fields were measured in alert primate primary auditory cortex (A1) in response to stimuli that vary in spectrotemporal density. As density increased, A1 excitatory receptive fields systematically changed. Receptive field sensitivity, expressed as the expected change in firing rate after a tone pip onset, decreased by an order of magnitude. Spectral selectivity more than doubled. Inhibitory subfields, which were rarely recorded at low sound densities, emerged at higher sound densities. The ratio of excitatory to inhibitory population strength changed from 14.4:1 to 1.4:1. At low sound densities, the sound associated with the evocation of an action potential from an A1 neuron was broad in spectrum and time. At high sound densities, a spike-evoking sound was more likely to be a spectral or temporal edge and was narrower in time and frequency range. Receptive fields were used to predict responses to a novel high-noise-density stimulus. The predictions were highly correlated with the actual responses to the 2-s complex sound excerpt. The structure of prediction failures revealed that neurons with prominent inhibitory fields had relatively poor linear predictions. Further, the finding that stochastic variance is limiting in prediction even after averaging 150 repetitions means that high-fidelity representations of simple sounds in A1 must be distributed over at least hundreds of neurons. Auditory context alters A1 responses across multiple parameter spaces; this presents a challenge for reconstructing neural codes.

Acoustic Stimulation↗