Browsing by Author "Platt, Michael L"

Making decisions is fundamental to everything we do, yet it can be impaired in various disorders and conditions. While research into the neural basis of decision-making has flourished in recent years, many questions remain about how decisions are instantiated in the brain. Here we explored how primates make abstract decisions and decisions in social contexts, as well as one way to non-invasively modulate the brain circuits underlying decision-making. We used rhesus macaques as our model organism. First we probed numerical decision-making, a form of abstract decision-making. We demonstrated that monkeys are able to compare discrete ratios, choosing an array with a greater ratio of positive to negative stimuli, even when this array does not have a greater absolute number of positive stimuli. Monkeys’ performance in this task adhered to Weber’s law, indicating that monkeys—like humans—treat proportions as analog magnitudes. Next we showed that monkeys’ ordinal decisions are influenced by spatial associations; when trained to select the fourth stimulus from the bottom in a vertical array, they subsequently selected the fourth stimulus from the left—and not from the right—in a horizontal array. In other words, they begin enumerating from one side of space and not the other, mirroring the human tendency to associate numbers with space. These and other studies confirmed that monkeys’ numerical decision-making follows similar patterns to that of humans, making them a good model for investigations of the neurobiological basis of numerical decision-making.

We sought to develop a system for exploring the neuronal basis of the cognitive and behavioral effects observed following transcranial magnetic stimulation, a relatively new, non-invasive method of brain stimulation that may be used to treat clinical disorders. We completed a set of pilot studies applying offline low-frequency repetitive transcranial magnetic stimulation to the macaque posterior parietal cortex, which has been implicated in numerical processing, while subjects performed a numerical comparison and control color comparison task, and while electrophysiological activity was recorded from the stimulated region of cortex. We found tentative evidence in one paradigm that stimulation did selectively impair performance in the number task, causally implicating the posterior parietal cortex in numerical decisions. In another paradigm, however, we manipulated the subject’s reaching behavior but not her number or color comparison performance. We also found that stimulation produced variable changes in neuronal firing and local field potentials. Together these findings lay the groundwork for detailed investigations into how different parameters of transcranial magnetic stimulation can interact with cortical architecture to produce various cognitive and behavioral changes.

Finally, we explored how monkeys decide how to behave in competitive social interactions. In a zero-sum computer game in which two monkeys played as a shooter or a goalie during a hockey-like “penalty shot” scenario, we found that shooters developed complex movement trajectories so as to conceal their intentions from the goalies. Additionally, we found that neurons in the dorsolateral and dorsomedial prefrontal cortex played a role in generating this “deceptive” behavior. We conclude that these regions of prefrontal cortex form part of a circuit that guides decisions to make an individual less predictable to an opponent.

The visual world is full of potentially important information, but only a subset of the world can be evaluated at any time. An essential function of the central nervous system is to rapidly and adaptively select which stimuli warrant attention. Much of the time, attention is directed towards stimuli that are relevant for current goals. However, things that have proven important in an organisms' personal or evolutionary past effectively compete with goal-relevant targets for attention. In humans, one example of this attentional superset is faces: faces attract attention even when they are in competition with immediate goals. Using a combination of behavioral, pharmacological, and electrophysiological techniques in the rhesus macaque, I investigated the physiological, neurobiological, and evolutionary determinants of the attentional capture of faces. First, I show that the prioritization of faces is evolutionarily conserved in primates. Face distractors also capture attention in rhesus macaques, a species of old world monkey, successfully competing with task goals for limited attentional resources. Importantly, the same classes of faces have the greatest attentional effects in both monkeys and humans. Further, I describe behavioral evidence that subcortical systems contribute to the attentional salience of faces in this species, proving an initial characterization of the neural mechanisms that may mediate this effect. Next, I examine the interaction between pupil size and vigilance for faces. A focal increase in luminance has long been known to provoke pupil constriction, but here I show that the pupil response to a flashed distractor is proportional to the allocation of attention to that image. Pupil constriction may provide a novel implicit metric of stimulus attention. In particular, face images provoked greater pupil constriction than non-face images. Moreover, I also find that baseline pupil size is a strong predictor of distractor interference, suggesting that arousal may modulate social vigilance. Therefore, I next examined the activity of single neurons within dorsal anterior cingulate cortex (dACC), a region implicated in task performance across a wide variety of tasks, but which also has strong connections to subcortical neuromodulatory centers responsible for regulating arousal. I find that the dACC discriminates between social and nonsocial distractors, scales with distractor attention, and predicts adjustments in arousal and vigilance state on upcoming trials. This is consistent with a model in which dACC supports task performance through regulating arousal. Finally, I turn to oxytocin (OT), a neuromodulatory hormone released during affiliative social interactions that is also implicated in regulating arousal. Though typically thought to generally enhance social attention, I report multiple circumstances in which OT suppresses, rather than enhances, vigilance for faces. This suggests a mechanism through which affiliative social interactions can reduce social vigilance, permitting more relaxed social interactions. Together, these results highlight an evolutionarily conserved neural circuit important for the adaptive, contextual modulation of reflexive face attention, a behavior that is compromised in both anxiety disorders and autism.

The ability to monitor, learn from, and respond to social information is essential for many highly social animals, including humans. Deficits to this capacity are associated with numerous psychopathologies, including autism spectrum disorders, social anxiety disorder, and schizophrenia. To understand the neural mechanisms supporting social information seeking behavior requires understanding this behavior in its natural context, and presenting animals with species-appropriate stimuli that will elicit the behavior in the laboratory. In this dissertation, I describe a novel behavioral paradigm I developed for investigating social information seeking behavior in rhesus macaques in a laboratory setting, with the use of naturalistic videos of freely-behaving conspecifics as stimuli. I recorded neural activity in the orbitofrontal and lateral prefrontal cortex of monkeys as they engaged in this task, and found evidence for a rich but sparse representation of natural behaviors in both areas, particularly in the orbitofrontal cortex. This sparse encoding of conspecifics' behaviors represents the raw material for social information foraging decisions.

An animal's ability to make adaptive choices is key to its fitness. Thus, the process of determining options, making a decision, evaluating outcomes, and learning from those outcomes to adjust future behavior is a central function of our nervous system. Determining the neural mechanisms of these cognitive processes is a crucial goal. One brain region, the posterior cingulate cortex (CGp), a central hub within the default mode network, is prominently dysregulated in Alzheimer's Disease and schizophrenia. Despite its clinical importance, the posterior cingulate cortex remains an enigmatic nexus of attention, memory, and motivation, all pointing to a role in decision-making. This dissertation is concerned with the role of this brain region in the learning and valuation processes involved in making adaptive choices. Specifically, I used rhesus macaques (Macaca mulatta) to examine the neural activity in posterior cingulate associated with specific learning and valuation -related variables. In the first experiment, I showed that posterior cingulate neurons track decision salience--the degree to which an option differs from a standard--but not the subjective value of a decision. To do this, I recorded the spiking activity of CGp neurons in monkeys choosing between options varying in reward-related risk, delay to reward, and social outcomes, each of which varied in level of decision salience. Firing rates were higher when monkeys chose the risky option, consistent with their risk-seeking preferences, but were also higher when monkeys chose the delayed and social options, contradicting their preferences. Thus, across decision contexts, neuronal activity was uncorrelated with how much monkeys valued a given option, as inferred from choice. Instead, neuronal activity signaled the deviation of the chosen option from the standard, independently of how it differed. The observed decision salience signals suggest a role for CGp in the flexible allocation of neural resources to motivationally significant information, akin to the role of attention in selective processing of sensory inputs. This pointed to a role for CGp in learning rather than subjective value signaling, and the second set of experiments aimed to test the role of CGp in associative learning. I recorded from single CGp neurons in monkeys performing a simple conditional motor association task while varying stimulus familiarity and motivation. CGp neurons responded phasically following commission of errors, and this error signal was modulated by motivation and stimulus novelty. Moreover, slow variations in firing rates tracked variations in learning rate over the course of sessions. Silencing these signals with muscimol impaired learning in low motivational states but spared learning in high motivational states, and spared recall of familiar associations as well. These findings endorse a role for CGp in performance and environment monitoring to regulate learning rate. Collectively, these experiments reshape our understanding of the role of posterior cingulate cortex in cognition, integrate default mode and value-based theories of CGp function, and provide a potential foundation for a circuit-level explication of Alzheimer's Disease and schizophrenia.

To solicit the attention or determine the intentions of another, we use our eyes. While many animals appear to use eyes as an important behavioral cue, for humans, these cues are especially critical. The power of the eyes to attract and direct attention shapes human behavior from an early age and likely serves as a foundation for social skill acquisition, ranging from simple, friendly eye contact to complex, spoken language, even to our almost mystical ability to empathize and "see the world through another's eyes". Humans have transformed our environment through our economic alliances and military competitions, and our individual successes and failures depend critically on social skills built on a foundation of shared attention. When these abilities break down, as in autism, pervasive social awkwardness can challenge the close relationship of individuals with their friends, family, and community. Nonetheless, we know almost nothing about the brain mechanisms that have evolved to process social cues and convert them into a rich experience of shared attention. To investigate this process, we explored the ability of human and nonhuman primates to follow the attention of other individuals. First, we characterized natural gaze-following behavior using a novel telemetric device in socially-interacting prosimian primates, and later in monkeys and humans responding to gaze cues in the lab. Finally, we examined the neuronal responses to gaze cues in a macaque posterior parietal area implicated in attention control--the lateral intraparietal area, LIP. Our findings suggest that gaze-following abilities may be widespread in social primates, relying on conserved, homologous brain pathways; and that they may not be informationally-encapsulated reflexes, but rather are densely interwoven with diverse social processes. Indeed, we found gaze cues influenced neurons in LIP, part of the dorsal frontoparietal attention network. Finally, we report that "mirror" neurons in parietal areas may thus play a role not only in representing perceived bodily actions, but also perceived mental states such as observed attention.

Negotiating the complex decisions that we encounter daily requires coordinated neu-

ronal activity. The enormous variety of decisions we make, the intrinsic complexity

of the situations we encounter, and the extraordinary flexibility of our behaviors

suggest the existence of intricate neural mechanisms for negotiating contexts and

making choices. Further evidence for this prediction comes from the behavioral al-

terations observed in illness and after injury. Both clinical and scientific evidence

suggest that decision signals are carried by electrical neuronal activity and influenced

by neuromodulatory chemicals. This dissertation addresses the function of two puta-

tive contributors to decision-making: neuronal activity in posterior cingulate cortex

and modulatory effects of serotonin. I found that posterior cingulate neurons respond

phasically to salient events (informative cues; intentional saccades; and reward deliv-

ery) across multiple contexts. In addition, these neurons signal heuristically guided

choices across contexts in a gambling task. These observations suggest that posterior

cingulate neurons contribute to the detection and integration of salient information

necessary to transform event detection to expressed decisions. I also found that

lowering levels of the neuromodulator serotonin increased the probability of making

risky decisions in both monkeys and mice, suggesting that this neurotransmitter con-

tributes to preference formation across species. These results suggest that posterior

cingulate cortex and serotonin each contribute to decision formation. In addition, the

unique serotonergic pro jections to posterior cingulate cortex, as well as the frequent

implication of altered serotonergic and posterior cingulate function in psychiatric dis-

orders, suggest that the confluence of cingulate and serotonergic activity may offer

key insights into normal and pathological mechanisms of decision making.

People are frequently forced to make decisions in social contexts, taking into account not only the social perceptual aspects of their environment, but also the effects of their actions; what will happen to themselves and what will happen to other individuals. These decisions involve consideration of potential outcomes and choosing what best suits the decision maker’s own needs, sometimes at a cost, and sometimes at a benefit, of others. Yet, the brain mechanisms that acquire and evaluate social information to subsequently form social decisions remain poorly understood. Thus, it is imperative to better understand the computations underlying social decision-making. Across three independent studies, I focus on the neural basis of making decisions in a social context. In the first study (Chapter 2), I used a relatively novel combination of restricted spatial independent component analysis and multiple regression techniques to demonstrate that distinct regions encode making decisions for other people, relative to making decisions for oneself. In the second study (Chapter 3), I investigated how large-scale functional networks shape behavior in social contexts, and examined how broad, goal-oriented networks couple with specific cortical sites to orchestrate social motivation. In my last study (Chapter 4), I examined the relationship between social perception and social decision-making at the single-neuron level in the monkey superior temporal sulcus, a region known for social perceptual processing. Here, I demonstrated that this classically social perceptual region additionally responds to social decision-making processes, and that neurons in this region multiplex both types of information. Collectively, this research points to specific regions in the brain that encode multiple aspects of social behavior and decision-making, and the interaction between perception and goal-oriented cognition process that drive complex social behavior. Lastly, this body of research also highlights the importance of examining the neural mechanisms of social behavior both at the larger systems and network levels, as well as at the single-neuron level.

The ability to enumerate approximately without counting is an evolutionarily ancient and developmentally early core cognitive ability known as the "number sense". We use the number sense when we estimate a number without counting individual items, as when we guess the number of people in a crowded room. The number sense is theorized to form an instinctual building block upon which we create the conceptual structures of mathematics. This dissertation addresses three research questions regarding the number sense.

The first is the question of whether the number sense is malleable, and if so, what are the neural correlates of malleability. In Chapter 2 we gave adults number sense training, which we found improved the accuracy of numerical estimation. In Chapter 4 we recorded from single neurons in monkeys while they viewed arrays of items on a computer screen. Similar recordings have been made previously, but usually using monkeys that were trained to discriminate sets based on number. Recordings in trained animals demonstrated that individual neurons in the monkey's brain track the number of items in a set. We reasoned that if the neural correlates of the number sense were altered by the training experience, then we would get different results in untrained monkeys. We did find neurons encoding numerical information in untrained monkeys, but at lower rates than described previously. Thus, we demonstrated that the number sense can improve with experience, and our data suggest that changes in the proportion of neurons encoding number may subserve this improvement.

The second question is how to resolve the problem of stimulus control in laboratory tests of the number sense. Typically, number sense function is assessed by presenting arrays of dots on a computer screen. In such stimuli, however, non-numerical features necessarily covary with numerical features. By counter-balancing different stimulus conditions, it is possible to determine if number and not some other feature is influencing a dependent measure. In Chapter 3, we develop a technique to go further and determine which of eleven stimulus features is influencing a dependent measure.

The third question is whether the intraparietal sulcus (IPS), a brain area known to be engaged during numerical cognition, is specialized for it. To address this question, we apply the technique developed in Chapter 3 to the neural data recorded from monkeys in Chapter 4. We show that the IPS does contain number neurons; however, it also contains neurons that encode many other features in equal proportion, indicating that it is not specialized for number. In Chapter 5, we use drugs injected into the IPS to reversibly inactivate it. We found that after IPS inactivation, performance on a numerical discrimination task was impaired but no more so than a color discrimination control task. Again, our data do not support the theory that the IPS is specialized for numerical processing.

It has been suggested that primate brains are inherently biased towards gathering and processing the social information present in the world. In fact, the neural network that mediates our engagement with the external world - the default mode network (DMN) ¬- is strongly convergent with the neural circuitry for social cognition. The posterior cingulate (PCC) is believed to be a key node in both the DMN and in social cognition. Human and non-human primate studies have demonstrated a role for the PCC in outcome monitoring: it tracks rewards, subjective values of choices, task engagement and global choice strategies. It is also implicated in social cognition. Human studies show that PCC activity varies with the recall of autobiographical memories and exposure to social stimuli. While several electrophysiological studies explicate the response of PCC neurons to non-social outcome monitoring and valuation, there is a lack of similar studies for social valuation. This thesis is concerned with characterizing the neuronal responses in the PCC to social stimuli and determining whether social valuation occurs in the PCC in a manner similar to that previously described for non-social outcomes. I recorded the single unit activity of neurons in the PCC of rhesus macaques while they performed behavioral tasks that required attending to the faces of high-status or low-status individuals. Monkeys valued the faces of high-status individuals more than low-status individuals, though they were equally likely to identity and overtly attend to faces of both social classes. This differential valuation of face stimuli was represented in the firing activity of PCC neurons, with higher neuronal activity seen in response to subordinate faces as compared to dominant ones. Cells in the PCC did not track the individual identity of the presented faces. Furthermore, neuronal activity in the PCC predominantly tracked social value, and not non-social reward delivery as previously reported. Neuronal activity also predicted task engagement, with higher firing rates being predictive of a decrease in task engagement. To summarize, the PCC is biased towards social information processing, and neuronal activity in the PCC tracks social category information and the level of task engagement.

The ultimate goal of the nervous systems of all animals is conceptually simple: Manipulate the external environment to maximize one's own survival and reproduction. The myriad means animals employ in pursuit of this goal are astoundingly complex, but constrained by common factors. For example, to ensure survival, all animals must acquire the necessary nutrients to sustain metabolism. Similarly, social interaction of some form is necessary for mating and reproduction. For some animals, the required social interaction goes far beyond that necessary for mating. Humans and many other primates exist in complex social environments, the navigation of which are essential for adaptive behavior. This dissertation is concerned with processes of transforming sensory stimuli regarding both nutritive and social information into motor commands pursuant to the goals of survival and reproduction. Specifically, this dissertation deals with these processes in the rhesus macaque. Using a task in which monkeys make decisions simultaneously weighing outcomes of fruit juices and images of familiar conspecifics, I have examined the neurophysiology of social and nutritive factors as they contribute to choice behavior; with the ultimate goal of understanding how these disparate factors are weighed against each other and combined to produce coherent motor commands that result in adaptive social interactions and the successful procurement of resources. I began my investigation in the lateral intraparietal cortex, a well-studied area of the primate brain implicated in visual attention, oculomotor planning and control, and reward processing. My findings indicate the lateral intraparietal cortex represents social and nutritive reward information in a common neural currency. That is, the summed value of social and nutritive outcomes is proportional to the firing rates of parietal neurons. I continued my investigation in the striatum, a large and functionally diverse subcortical nuclei implicated in motor processing, reward processing and learning. Here I find a different pattern of results. Striatal neurons generally encoded information about either social outcome or juice rewards, but not both, with a medial or lateral bias in the location of social or juice information encoding neurons, respectively. In further contrast to the lateral intraparietal cortex, the firing rates of striatal neurons coding social and nutritive outcome information is heterogeneous and not directly related to the value of the outcome. This dissertation represents a few incremental steps toward understanding how social information and the drive toward social interaction are incorporated with other motivators to influence behavior. Understanding this process is a necessary step for elucidating, treating, and preventing pathologies