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Biomedical subjects

Michael L Platt

Publications and source records attributed to Michael L Platt.

At least 19 recordsLinked to original sources
PubMed2026

Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques.

Age and early life adversity (ELA) are key determinants of health, but whether they affect similar physiological mechanisms across tissues is unknown. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free-ranging rhesus macaques with naturally occurring ELA. Age-associated DNAm was predominantly tissue dependent, yet tissue-specific epigenetic clocks showed that epigenetic aging was relatively consistent within individuals. ELA effects were adversity dependent, but each ELA exerted coordinated effects across tissues. Although ELA targeted many of the same loci as age, the directions of effects differed, which indicates that ELA does not uniformly increase epigenetic age. Instead, ELA leaves a coordinated, cross-tissue epigenetic signature that is distinct from-yet intertwined with-age-related differences, which advances our understanding of how early environments sculpt the molecular foundations of aging and disease.

Animals↗
PubMed2007

Temporal discounting predicts risk sensitivity in rhesus macaques.

Humans and animals tend both to avoid uncertainty and to prefer immediate over future rewards. The comorbidity of psychiatric disorders such as impulsivity, problem gambling, and addiction suggests that a common mechanism may underlie risk sensitivity and temporal discounting. Nonetheless, the precise relationship between these two traits remains largely unknown. To examine whether risk sensitivity and temporal discounting reflect a common process, we recorded choices made by two rhesus macaques in a visual gambling task while we varied the delay between trials. We found that preference for the risky option declined with increasing delay between sequential choices in the task, even when all other task parameters were held constant. These results were quantitatively predicted by a model that assumed that the subjective expected utility of the risky option is evaluated based on the expected time of the larger payoff. The importance of the larger payoff in this model suggests that the salience of larger payoffs played a critical role in determining the value of risky options. These data suggest that risk sensitivity may be a product of other cognitive processes, and specifically that myopia for the future and the salience of jackpots control the propensity to take a gamble.

Animals↗
PubMed2006

Nonverbal representation of time and number in adults.

A wealth of human and animal research supports common neural processing of numerical and temporal information. Here we test whether adult humans spontaneously encode number and time in a paradigm similar to those previously used to test the mode-control model in animals. Subjects were trained to classify visual stimuli that varied in both number and duration as few/short or many/long. Subsequently subjects were tested with novel stimuli that varied time and held number constant (eight flashes in 0.8-3.2s) or varied number and held time constant (4-16 flashes in 1.6s). Adult humans classified novel stimuli as many/long as monotonic functions of both number and duration, consistent with simultaneous, nonverbal, analog encoding. Numerical sensitivity, however, was finer than temporal sensitivity, suggesting differential salience of time and number. These results support the notion that adults simultaneously represent the number and duration of stimuli but suggest a possible asymmetry in their representations.

Adult↗
PubMed2006

Neural correlates of reward and attention in macaque area LIP.

Saccade reaction times decrease and the frequency of target choices increases with the size of rewards delivered for orienting to a particular visual target. Similarly, increasing rewards for orienting to a visual target enhances neuronal responses in the macaque lateral intraparietal area (LIP), as well as other brain areas. These observations raise several questions. First, are reward-related modulations in neuronal activity in LIP, as well as other areas, spatially specific or more global in nature? Second, to what extent does reward modulation of neuronal activity in area LIP reflect changes in visual rather than motor processing? And third, to what degree are reward-related modulations in LIP activity independent of performance-related modulations thought to reflect changes in attention? Here we show that increasing the size of fluid rewards in blocks reduced saccade reaction times and improved performance in monkeys performing a peripherally-cued saccade task. LIP neurons responded to visual cues spatially segregated from the saccade target, and for many neurons visual responses were systematically modulated by expected reward size. Neuronal responses also were positively correlated with reaction times independent of reward size, consistent with re-orienting of attention to the saccade target. These observations suggest that motivation and attention independently contribute to the strength of sustained visual responses in LIP. Our data thus implicate LIP in the integration of the sensory, motor, and motivational variables that guide orienting.

Action Potentials↗
PubMed2006

Neural signatures of economic preferences for risk and ambiguity.

People often prefer the known over the unknown, sometimes sacrificing potential rewards for the sake of surety. Overcoming impulsive preferences for certainty in order to exploit uncertain but potentially lucrative options may require specialized neural mechanisms. Here, we demonstrate by functional magnetic resonance imaging (fMRI) that individuals' preferences for risk (uncertainty with known probabilities) and ambiguity (uncertainty with unknown probabilities) predict brain activation associated with decision making. Activation within the lateral prefrontal cortex was predicted by ambiguity preference and was also negatively correlated with an independent clinical measure of behavioral impulsiveness, suggesting that this region implements contextual analysis and inhibits impulsive responses. In contrast, activation of the posterior parietal cortex was predicted by risk preference. Together, this novel double dissociation indicates that decision making under ambiguity does not represent a special, more complex case of risky decision making; instead, these two forms of uncertainty are supported by distinct mechanisms.

Adolescent↗
PubMed2006

Allocentric spatial referencing of neuronal activity in macaque posterior cingulate cortex.

Neuronal activity in posterior cingulate cortex (CGp) is modulated by visual stimulation, saccades, and eye position, suggesting a role for this area in visuospatial transformations. The goal of this study was to determine whether neuronal responses in CGp are anchored to the eyes, head, or outside the body (allocentrically). To discriminate retinocentric from nonretinocentric spatial referencing, the activity of single CGp neurons was recorded while monkeys (Macaca mulatta) performed delayed-saccade trials initiated randomly from three different starting positions to a linear array of targets passing through the neuronal response field. For most neurons, tuning curves, segregated by fixation point, aligned more closely when plotted with respect to the display than when plotted with respect to the eye, suggesting a nonretinocentric frame of reference. A second experiment differentiated between spatial referencing in coordinates anchored to the head or body and allocentric spatial referencing. Monkeys shifted gaze from a central fixation point to the array of previously used targets both before and after whole-body rotation with respect to the display. For most neurons, tuning curves, segregated by fixation position, aligned more closely when plotted as a function of target position in the room than when plotted as a function of target position with respect to the monkey. These data indicate that a population of CGp neurons encodes visuospatial events in allocentric coordinates.

Animals↗
PubMed2006

Noninvasive telemetric gaze tracking in freely moving socially housed prosimian primates.

Behavioral and neurophysiological studies strongly suggest that visual orienting reflects the integration of sensory, motor, and motivational variables. Relatively little is known, however, regarding the goals that govern visual orienting of animals in their natural environments. Field observations suggest that most nonhuman primates orient to features of their natural environments whose salience is dictated by the visual demands of foraging, locomotion, and social interaction. This hypothesis is difficult to test quantitatively, however, in part because accurate gaze-tracking technology has not been employed in field studies. We here report the implementation of a new, telemetric, infrared-video gaze-tracker to measure visual orienting in freely moving, socially housed prosimian primates (Lemur catta). Two male lemurs tolerated the system at approximately 1/4 body weight, permitting successful measurements of gaze behavior during spontaneous locomotion through both terrestrial and arboreal landscapes, and in both social and asocial environments.

Animals↗
PubMed2005

Risk-sensitive neurons in macaque posterior cingulate cortex.

People and animals often demonstrate strong attraction or aversion to options with uncertain or risky rewards, yet the neural substrate of subjective risk preferences has rarely been investigated. Here we show that monkeys systematically preferred the risky target in a visual gambling task in which they chose between two targets offering the same mean reward but differing in reward uncertainty. Neuronal activity in posterior cingulate cortex (CGp), a brain area linked to visual orienting and reward processing, increased when monkeys made risky choices and scaled with the degree of risk. CGp activation was better predicted by the subjective salience of a chosen target than by its actual value. These data suggest that CGp signals the subjective preferences that guide visual orienting.

Action Potentials↗
PubMed2005

Monkeys pay per view: adaptive valuation of social images by rhesus macaques.

Individuals value information that improves decision making. When social interactions complicate the decision process, acquiring information about others should be particularly valuable. In primate societies, kinship, dominance, and reproductive status regulate social interactions and should therefore systematically influence the value of social information, but this has never been demonstrated. Here, we show that monkeys differentially value the opportunity to acquire visual information about particular classes of social images. Male rhesus macaques sacrificed fluid for the opportunity to view female perinea and the faces of high-status monkeys but required fluid overpayment to view the faces of low-status monkeys. Social value was highly consistent across subjects, independent of particular images displayed, and only partially predictive of how long subjects chose to view each image. These data demonstrate that visual orienting decisions reflect the specific social content of visual information and provide the first experimental evidence that monkeys spontaneously discriminate images of others based on social status.

Animals↗
PubMed2005

Effects of isosexual pair-housing on biomedical implants and study participation in male macaques.

Social housing has been shown to contribute to the psychological well-being and physical health of captive primates, and this factor has led to United States Department of Agriculture guidelines requiring facilities to address the social needs of primate species known to live socially in nature as long as doing so does not endanger the animals or interfere with research goals. Although pair-housing is the best way to provide social enrichment, many researchers and facilities are hesitant to implement it, particularly in biomedical research contexts where implanted devices or behavioral performance might be compromised. In order to study the effects of pair-housing on biomedical implants and study participation, we collected data from a group of isosexually pair-housed male macaques (adult and subadult) with 1) cranial and eye implants and 2) controlled access to water as means of motivating subjects to participate in psychophysical studies. Implants, study participation, and weight gain were not adversely affected by pair-housing. Our results support the use of pair-housing as social enrichment for macaques with biomedical implants and controlled access to water.

Animals↗
PubMed2004

Expectations and outcomes: decision-making in the primate brain.

Success in a constantly changing environment requires that decision-making strategies be updated as reward contingencies change. How this is accomplished by the nervous system has, until recently, remained a profound mystery. New studies coupling economic theory with neurophysiological techniques have revealed the explicit representation of behavioral value. Specifically, when fluid reinforcement is paired with visually-guided eye movements, neurons in parietal cortex, prefrontal cortex, the basal ganglia, and superior colliculus-all nodes in a network linking visual stimulation with the generation of oculomotor behavior-encode the expected value of targets lying within their response fields. Other brain areas have been implicated in the processing of reward-related information in the abstract: midbrain dopaminergic neurons, for instance, signal an error in reward prediction. Still other brain areas link information about reward to the selection and performance of specific actions in order for behavior to adapt to changing environmental exigencies. Neurons in posterior cingulate cortex have been shown to carry signals related to both reward outcomes and oculomotor behavior, suggesting that they participate in updating estimates of orienting value.

Action Potentials↗
PubMed2004

Visual and saccade-related activity in macaque posterior cingulate cortex.

Previous neurophysiological studies have reported that neurons in posterior cingulate cortex (PCC) respond after eye movements, and that these responses may vary with ambient illumination. In monkeys, PCC neurons also respond after the illumination of large visual patterns but not after the illumination of small visual targets on either reflexive saccade tasks or peripheral attention tasks. These observations suggest that neuronal activity in PCC is modulated by behavioral context, which varies with the timing and spatial distribution of visual and oculomotor events. To test this hypothesis, we measured the spatial and temporal response properties of single PCC neurons in monkeys performing saccades in which target location and movement timing varied unpredictably. Specifically, an unsignaled delay between target onset and movement onset permitted us to temporally dissociate changes in PCC activity associated with either event. Response fields constructed from these data demonstrated that many PCC neurons were activated after the illumination of small contralateral visual targets, as well as after the onset of contraversive saccades guided by those targets. In addition, the PCC population maintained selectivity for small contralateral targets during delays of up to 600 ms. Overall, PCC activation was highly variable trial to trial and selective for a broad range of directions and amplitudes. Planar functions described response fields nearly as well as broadly tuned 2-dimensional Gaussian functions. Additionally, the overall responsiveness of PCC neurons decreased during delays when both a fixation stimulus and a saccade target were visible, suggesting a modulation by divided attention. Finally, the strength of the neuronal response after target onset was correlated with saccade accuracy on delayed-saccade trials. Thus PCC neurons may signal salient visual and oculomotor events, consistent with a role in visual orienting and attention.

Animals↗
PubMed2003

Saccade reward signals in posterior cingulate cortex.

Movement selection depends on the outcome of prior behavior. Posterior cingulate cortex (CGp) is strongly connected with both limbic and oculomotor circuitry, and CGp neurons respond following saccades, suggesting a role in signaling the motivational outcome of gaze shifts. To test this hypothesis, single CGp neurons were studied in monkeys while they shifted gaze to visual targets for liquid rewards that varied in size or were delivered probabilistically. CGp neurons responded following saccades as well as following reward delivery, and these responses were correlated with reward size. CGp neurons also responded following the omission of predicted rewards. The timing of CGp activation and its modulation by reward could provide signals useful for updating representations of expected saccade value.

Animals↗
PubMed2003

Reflexive social attention in monkeys and humans.

For humans, social cues often guide the focus of attention. Although many nonhuman primates, like humans, live in large, complex social groups, the extent to which human and nonhuman primates share fundamental mechanisms of social attention remains unexplored. Here, we show that, when viewing a rhesus macaque looking in a particular direction, both rhesus macaques and humans reflexively and covertly orient their attention in the same direction. Specifically, when performing a peripheral visual target detection task, viewing a monkey with either its eyes alone or with both its head and eyes averted to one side facilitated the detection of peripheral targets when they randomly appeared on the same side. Moreover, viewing images of a monkey with averted gaze evoked small but systematic shifts in eye position in the direction of gaze in the image. The similar magnitude and temporal dynamics of response facilitation and eye deviation in monkeys and humans suggest shared neural circuitry mediating social attention.

Animals↗