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Electrophysiological recordings during ketamine anesthesia have revealed a slow alternating pattern of high- and low-frequency activity (a "gamma-burst" pattern) that develops along with the onset of general anesthesia. We examine the role of NMDA receptor antagonism in generating the gamma-burst pattern and the link between gamma-bursts and dissociative anesthesia by comparing the effects of ketamine with those of the highly selective NMDA receptor antagonist CGS 19755 on multi-site intracranial electrophysiology and behavior in rhesus macaques. The data show NMDA antagonism alone drives gamma-burst activity, and that it can do so without causing anesthesia. This underscores the involvement of mechanisms other than NMDA antagonism in the anesthetic effects of ketamine.

Decision-making is a deliberate process that seemingly evolves under our own volition. Yet, research on embodied cognition has demonstrated that higher-order cognitive processes may be influenced, in unexpected ways, by properties of motor and sensory systems. Here we tested whether and how simple decisions are influenced by handedness and by asymmetries in the auditory system. Right- and left-handed participants performed an auditory decision task. In the task, subjects decided whether they heard more click sounds in the right ear or in the left ear, and pressed a key with either their right or left index finger, according to an instructed stimulus-key assignment (congruent or reversed). On some trials, there was no stimulus and subjects could choose either of the responses freely. When subjects chose freely, their choices were substantially governed by their handedness: Left-handed subjects were significantly biased to make the leftward choice, whereas right-handed subjects showed a substantial rightward bias. When the choice was governed by the sensory stimulus, subjects showed a rightward choice bias under the congruent key assignment, but this effect reversed to a leftward choice bias under the reversed key assignment. This result indicates a bias towards deciding that there were more clicks presented to the right ear. Together, our findings demonstrate that human choices can be considerably influenced by properties of motor and sensory systems., Competing Interests: The authors declare no competing conflict of interest.

Many studies infer the role of neurons by asking what information can be decoded from their activity or by observing the consequences of perturbing their activity. An alternative approach is to consider information flow between neurons. We applied this approach to the parietal reach region (PRR) and the lateral intraparietal area (LIP) in posterior parietal cortex. Two complementary methods imply that across a range of reaching tasks, information flows primarily from PRR to LIP. This indicates that during a coordinated reach task, LIP has minimal influence on PRR and rules out the idea that LIP forms a general purpose spatial processing hub for action and cognition. Instead, we conclude that PRR and LIP operate in parallel to plan arm and eye movements, respectively, with asymmetric interactions that likely support eye-hand coordination. Similar methods can be applied to other areas to infer their functional relationships based on inferred information flow., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Individual differences in the spatial organization of resting state networks have received increased attention in recent years. Measures of individual-specific spatial organization of brain networks and overlapping network organization have been linked to important behavioral and clinical traits and are therefore potential biomarker targets for personalized psychiatry approaches. To better understand individual-specific spatial brain organization, this paper addressed three key goals. First, we determined whether it is possible to reliably estimate weighted (non-binarized) resting state network maps using data from only a single individual, while also maintaining maximum spatial correspondence across individuals. Second, we determined the degree of spatial overlap between distinct networks, using test-retest and twin data. Third, we systematically tested multiple hypotheses (spatial mixing, temporal switching, and coupling) as candidate explanations for why networks overlap spatially. To estimate weighted network organization, we adopt the Probabilistic Functional Modes (PROFUMO) algorithm, which implements a Bayesian framework with hemodynamic and connectivity priors to supplement optimization for spatial sparsity/independence. Our findings showed that replicable individual-specific estimates of weighted resting state networks can be derived using high quality fMRI data within individual subjects. Network organization estimates using only data from each individual subject closely resembled group-informed network estimates (which was not explicitly modeled in our individual-specific analyses), suggesting that cross-subject correspondence was largely maintained. Furthermore, our results confirmed the presence of spatial overlap in network organization, which was replicable across sessions within individuals and in monozygotic twin pairs. Intriguingly, our findings provide evidence that network overlap is indicative of linear additive coupling. These results suggest that regions of network overlap concurrently process information from all contributing networks, potentially pointing to the role of overlapping network organization in the integration of information across multiple brain systems., Competing Interests: Declaration of Competing Interests The authors declare no competing interests.

Though much research has characterized both the behavior and electrophysiology of spatial memory for single targets in non-human primates, we know much less about how multiple memoranda are handled. Multiple memoranda may interact in the brain, affecting the underlying representations. Mnemonic resources are famously limited, so items may compete for "space" in memory or may be encoded cooperatively or in a combined fashion. Understanding the mode of interaction will inform future neural studies. As a first step, we quantified interactions during a multi-item spatial memory task. Two monkeys were shown 1-4 target locations. After a delay, the targets reappeared with a novel target and the animal was rewarded for fixating the novel target. Targets could appear either all at once (simultaneous) or with intervening delays (sequential). We quantified the degree of interaction with memory rate correlations. We found that simultaneously presented targets were stored cooperatively while sequentially presented targets were stored independently. These findings demonstrate how interaction between concurrently memorized items depends on task context. Future studies of multi-item memory would be served by designing experiments to either control or measure the mode of this interaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Holmes, Ching and Snyder.)

The canonical view of motor control is that distal musculature is controlled primarily by the contralateral cerebral hemisphere; unilateral brain lesions typically affect contralateral but not ipsilateral musculature. Contralateral-only limb deficits following a unilateral lesion suggest but do not prove that control is strictly contralateral: the loss of a contribution of the lesioned hemisphere to the control of the ipsilesional limb could be masked by the intact contralateral drive from the nonlesioned hemisphere. To distinguish between these possibilities, we serially inactivated the parietal reach region, comprising the posterior portion of medial intraparietal area, the anterior portion of V6a, and portions of the lateral occipital parietal area, in each hemisphere of 2 monkeys (23 experimental sessions, 46 injections total) to evaluate parietal reach region's contribution to the contralateral reaching deficits observed following lateralized brain lesions. Following unilateral inactivation, reach reaction times with the contralesional limb were slowed compared with matched blocks of control behavioral data; there was no effect of unilateral inactivation on the reaction time of either ipsilesional limb reaches or saccadic eye movements. Following bilateral inactivation, reaching was slowed in both limbs, with an effect size in each no different from that produced by unilateral inactivation. These findings indicate contralateral organization of reach preparation in posterior parietal cortex. SIGNIFICANCE STATEMENT Unilateral brain lesions typically affect contralateral but not ipsilateral musculature. Contralateral-only limb deficits following a unilateral lesion suggest but do not prove that control is strictly contralateral: the loss of a contribution of the lesioned hemisphere to the control of the ipsilesional limb could be masked by the intact contralateral drive from the nonlesioned hemisphere. Unilateral lesions cannot distinguish between contralateral and bilateral control, but bilateral lesions can. Here we show similar movement initiation deficits after combined unilateral and bilateral inactivation of the parietal reach region, indicating contralateral organization of reach preparation., (Copyright © 2022 the authors.)

Resting-state functional MRI (rsfMRI) provides a view of human brain organization based on correlation patterns of blood oxygen level dependent (BOLD) signals recorded across the whole brain. The neural basis of resting-state BOLD fluctuations and their correlation remains poorly understood. We simultaneously recorded oxygen level, spikes, and local field potential (LFP) at multiple sites in awake, resting monkeys. Following a spike, the average local oxygen and LFP voltage responses each resemble a task-driven BOLD response, with LFP preceding oxygen by 0.5 s. Between sites, features of the long-range correlation patterns of oxygen, LFP, and spikes are similar to features seen in rsfMRI. Most of the variance shared between sites lies in the infraslow frequency band (0.01-0.1 Hz) and in the infraslow envelope of higher-frequency bands (e.g. gamma LFP). While gamma LFP and infraslow LFP are both strong correlates of local oxygen, infraslow LFP explains significantly more of the variance shared between correlated oxygen signals than any other electrophysiological signal. Together these findings are consistent with a causal relationship between infraslow LFP and long-range oxygen correlations in the resting state., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Functional connectivity, which reflects the spatial and temporal organization of intrinsic activity throughout the brain, is one of the most studied measures in human neuroimaging research. The noninvasive acquisition of resting state functional magnetic resonance imaging (rs-fMRI) allows the characterization of features designated as functional networks, functional connectivity gradients, and time-varying activity patterns that provide insight into the intrinsic functional organization of the brain and potential alterations related to brain dysfunction. Functional connectivity, hence, captures dimensions of the brain's activity that have enormous potential for both clinical and preclinical research. However, the mechanisms underlying functional connectivity have yet to be fully characterized, hindering interpretation of rs-fMRI studies. As in other branches of neuroscience, the identification of the neurophysiological processes that contribute to functional connectivity largely depends on research conducted on laboratory animals, which provide a platform where specific, multi-dimensional investigations that involve invasive measurements can be carried out. These highly controlled experiments facilitate the interpretation of the temporal correlations observed across the brain. Indeed, information obtained from animal experimentation to date is the basis for our current understanding of the underlying basis for functional brain connectivity. This review presents a compendium of some of the most critical advances in the field based on the efforts made by the animal neuroimaging community., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Working memory, the ability to maintain and transform information, is critical for cognition. Spatial working memory is particularly well studied. The premier model for spatial memory is the continuous attractor network, which posits that cells maintain constant activity over memory periods. Alternative models propose complex dynamics that result in a variety of cell activity time courses. We recorded from neurons in the frontal eye fields and dorsolateral prefrontal cortex of 2 macaques during long (5-15 s) memory periods. We found that memory cells turn on early after stimulus presentation, sustain activity for distinct and fixed lengths of time, then turn off and stay off for the remainder of the memory period. These dynamics are more complex than the dynamics of a canonical bump attractor network model (either decaying or nondecaying) but more constrained than the dynamics of fully heterogeneous memory models. We speculate that memory may be supported by multiple attractor networks working in parallel, with each network having its own characteristic mean turn-off time such that mnemonic resources are gradually freed up over time., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Primates use their arms in complex ways that frequently require coordination between the two arms. Yet the planning of bimanual movements has not been well-studied. We recorded spikes and local field potentials (LFP) from the parietal reach region (PRR) in both hemispheres simultaneously while monkeys planned and executed unimanual and bimanual reaches. From analyses of interhemispheric LFP-LFP and spike-LFP coherence, we found that task-specific information is shared across hemispheres in a frequency-specific manner. This shared information could arise from common input or from direct communication. The population average unit activity in PRR, representing PRR output, encodes only planned contralateral arm movements while beta-band LFP power, a putative PRR input, reflects the pattern of planned bimanual movement. A parsimonious interpretation of these data is that PRR integrates information about the movement of the left and right limbs, perhaps in service of bimanual coordination.

Electrophysiological recordings have established that GABAergic interneurons regulate excitability, plasticity, and computational function within local neural circuits. Importantly, GABAergic inhibition is focally disrupted around sites of brain injury. However, it remains unclear whether focal imbalances in inhibition/excitation lead to widespread changes in brain activity. Here, we test the hypothesis that focal perturbations in excitability disrupt large-scale brain network dynamics. We used viral chemogenetics in mice to reversibly manipulate parvalbumin interneuron (PV-IN) activity levels in whisker barrel somatosensory cortex. We then assessed how this imbalance affects cortical network activity in awake mice using wide-field optical neuroimaging of pyramidal neuron GCaMP dynamics as well as local field potential recordings. We report 1) that local changes in excitability can cause remote, network-wide effects, 2) that these effects propagate differentially through intra- and interhemispheric connections, and 3) that chemogenetic constructs can induce plasticity in cortical excitability and functional connectivity. These findings may help to explain how focal activity changes following injury lead to widespread network dysfunction., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Within the domain of motor performance, eye-hand coordination centers on close relationships between visuo-perceptual, ocular and appendicular motor systems. This coordination is critically dependent on a cycle of feedforward predictions and feedback-based corrective mechanisms. While intrinsic feedback harnesses naturally available movement-dependent sensory channels to modify movement errors, extrinsic feedback may be provided synthetically by a third party for further supplementation. Extrinsic feedback has been robustly explored in hand-focused, motor control studies, such as through computer-based visual displays, highlighting the spatial errors of reaches. Similar attempts have never been tested for spatial errors related to eye movements, despite the potential to alter ocular motor performance. Stroke creates motor planning deficits, resulting in the inability to generate predictions of motor performance. In this study involving visually guided pointing, we use an interactive computer display to provide extrinsic feedback of hand endpoint errors in an initial baseline experiment (pre-) and then feedback of both eye and hand errors in a second experiment (post-) to chronic stroke participants following each reach trial. We tested the hypothesis that extrinsic feedback of eye and hand would improve predictions and therefore feedforward control. We noted this improvement through gains in the spatial and temporal aspects of eye-hand coordination or an improvement in the decoupling noted as incoordination post-stroke in previous studies, returning performance toward healthy, control behavior. More specifically, results show that stroke participants, following the interventional feedback for eye and hand, improved both their accuracy and timing. This was evident through a temporal re-synchronization between eyes and hands, improving correlations between movement timing, as well as reducing the overall time interval (delay) between effectors. These experiments provide a strong indication that an extrinsic feedback intervention at appropriate therapeutic doses may improve eye-hand coordination during stroke rehabilitation., (© 2019 Elsevier B.V. All rights reserved.)

Working memory, the ability to maintain and manipulate information in the brain, is critical for cognition. During the memory period of spatial memory tasks, neurons in the prefrontal cortex code for memorized locations via persistent, spatially tuned increases in activity. Local field potentials (LFPs) are understood to reflect summed synaptic activity of local neuron populations and may offer a window into network-level processing. We recorded LFPs from areas 8A and 9/46 while two male cynomolgus macaques ( Macaca fascicularis ) performed a long duration (5.1-15.6 s) memory-guided saccade task. Greater than ∼16 Hz, LFP power was contralaterally tuned throughout the memory period. Yet power for both contralateral and ipsilateral targets fell gradually after the first second of the memory period, dropping below baseline after a few seconds. Our results dissociate absolute LFP power from mnemonic tuning and are consistent with modeling work that suggests that decreasing synchronization within a network may improve the stability of memory coding. SIGNIFICANCE STATEMENT The frontal cortex is an important site for working memory. There, individual neurons reflect memorized information with selective increases in activity, but how collections of neurons work together to achieve memory is not well understood. In this work, we examined rhythmic electrical activity surrounding these neurons, which may reflect the operation of recurrent circuitry that could underlie memory. This rhythmic activity was spatially tuned with respect to memorized locations as long as memory was tested (∼7.5 s). Surprisingly, however, the overall magnitude of rhythmic activity decreased steadily over this period, dropping below baseline levels after a few seconds. These findings suggest that collections of neurons may actively desynchronize to promote stability in memory circuitry., (Copyright © 2018 the authors 0270-6474/18/388177-10$15.00/0.)

Bimanual coordination is critical for a broad array of behaviors. Drummers, for example, must carefully coordinate movements of their 2 arms, sometimes beating on the same drum and sometimes on different ones. While coordinated behavior is well-studied, the early stages of planning are not well understood. In the parietal reach region (PRR) of the posterior parietal cortex (PPC), the presence of neurons that modulate when either arm moves by itself has been taken as evidence for a role in bimanual coordination. To test this notion, we recorded neurons during both unilateral and bimanual movements. We find that the activity that precedes an ipsilateral arm movement is primarily a sensory response to a target in the neuron's visual receptive field and not a plan to move the ipsilateral arm. In contrast, the activity that precedes a contralateral arm movement is the sum of a movement plan plus a sensory response. Despite not coding ipsilateral arm movements, about half of neurons discriminate between different patterns of bimanual movements. These results provide direct evidence that PRR neurons represent bimanual reach plans, and suggest that bimanual coordination originates in the sensory-to-motor processing stream prior to the motor cortex, within the PPC.

We often orient to where we are about to reach. Spatial and temporal correlations in eye and arm movements may depend on the posterior parietal cortex (PPC). Spatial representations of saccade and reach goals preferentially activate cells in the lateral intraparietal area (LIP) and the parietal reach region (PRR), respectively. With unimanual reaches, eye and arm movement patterns are highly stereotyped. This makes it difficult to study the neural circuits involved in coordination. Here, we employ bimanual reaching to two different targets. Animals naturally make a saccade first to one target and then the other, resulting in different patterns of limb-gaze coordination on different trials. Remarkably, neither LIP nor PRR cells code which target the eyes will move to first. These results suggest that the parietal cortex plays at best only a permissive role in some aspects of eye-hand coordination and makes the role of LIP in saccade generation unclear., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Previous memoranda interfere with working memory. For example, spatial memories are biased toward locations memorized on the previous trial. We predicted, based on attractor network models of memory, that activity in the frontal eye fields (FEFs) encoding a previous target location can persist into the subsequent trial and that this ghost will then bias the readout of the current target. Contrary to this prediction, we find that FEF memory representations appear biased away from (not toward) the previous target location. The behavioral and neural data can be reconciled by a model in which receptive fields of memory neurons converge toward remembered locations, much as receptive fields converge toward attended locations. Convergence increases the resources available to encode the relevant memoranda and decreases overall error in the network, but the residual convergence from the previous trial can give rise to an attractive behavioral bias on the next trial., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Behavior is guided by previous experience. Good, positive outcomes drive a repetition of a previous behavior or choice, whereas poor or bad outcomes lead to an avoidance. How these basic drives are implemented by the brain has been of primary interest to psychology and neuroscience. We engaged animals in a choice task in which the size of a reward outcome strongly governed the animals' subsequent decision whether to repeat or switch the previous choice. We recorded the discharge activity of neurons implicated in reward-based choice in 2 regions of parietal cortex. We found that the tendency to retain previous choice following a large (small) reward was paralleled by a marked decrease (increase) in the activity of parietal neurons. This neural effect is independent of, and of sign opposite to, value-based modulations reported in parietal cortex previously. This effect shares the same basic properties with signals previously reported in the limbic system that detect the size of the recently obtained reward to mediate proper repeat-switch decisions. We conclude that the size of the obtained reward is a decision variable that guides the decision between retaining a choice or switching, and neurons in parietal cortex strongly respond to this novel decision variable., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Given an instruction regarding which effector to move and what location to move to, simply adding the effector and spatial signals together will not lead to movement selection. For this, a nonlinearity is required. Thresholds, for example, can be used to select a particular response and reject others. Here we consider another useful nonlinearity, a supralinear multiplicative interaction. To help select a motor plan, spatial and effector signals could multiply and thereby amplify each other. Such an amplification could constitute one step within a distributed network involved in response selection, effectively boosting one response while suppressing others. We therefore asked whether effector and spatial signals sum supralinearly for planning eye versus arm movements from the parietal reach region (PRR), the lateral intraparietal area (LIP), the frontal eye field (FEF), and a portion of area 5 (A5) lying just anterior to PRR. Unlike LIP neurons, PRR, FEF, and, to a lesser extent, A5 neurons show a supralinear interaction. Our results suggest that selecting visually guided eye versus arm movements is likely to be mediated by PRR and FEF but not LIP., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these "task-negative" BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

When we make a decision, we experience a degree of confidence that our choice may lead to a desirable outcome. Recent studies in animals have probed the subjective aspects of the choice confidence using confidence-reporting tasks. These studies showed that estimates of the choice confidence substantially modulate neural activity in multiple regions of the brain. Building on these findings, we investigated the neural representation of the confidence in a choice in humans who explicitly reported the confidence in their choice. Subjects performed a perceptual decision task in which they decided between choosing a button press or a saccade while we recorded EEG activity. Following each choice, subjects indicated whether they were sure or unsure about the choice. We found that alpha activity strongly encodes a subject's confidence level in a forthcoming button press choice. The neural effect of the subjects' confidence was independent of the reaction time and independent of the sensory input modeled as a decision variable. Furthermore, the effect is not due to a general cognitive state, such as reward expectation, because the effect was specifically observed during button press choices and not during saccade choices. The neural effect of the confidence in the ensuing button press choice was strong enough that we could predict, from independent single trial neural signals, whether a subject was going to be sure or unsure of an ensuing button press choice. In sum, alpha activity in human cortex provides a window into the commitment to make a hand movement.

Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.

When faced with a choice, humans and animals commonly distribute their behavior in proportion to the frequency of payoff of each option. Such behavior is referred to as matching and has been captured by the matching law. However, matching is not a general law of economic choice. Matching in its strict sense seems to be specifically observed in tasks whose properties make matching an optimal or a near-optimal strategy. We engaged monkeys in a foraging task in which matching was not the optimal strategy. Over-matching the proportions of the mean offered reward magnitudes that would yield more reward than matching, yet, surprisingly, the animals almost exactly matched them. To gain insight into this phenomenon, we modeled the animals' decision-making using a mechanistic model. The model accounted for the animals' macroscopic and microscopic choice behavior. When the models' three parameters were not constrained to mimic the monkeys' behavior, the model over-matched the reward proportions and in doing so, harvested substantially more reward than the monkeys. This optimized model revealed a marked bottleneck in the monkeys' choice function that compares the value of the two options. The model featured a very steep value comparison function relative to that of the monkeys. The steepness of the value comparison function had a profound effect on the earned reward and on the level of matching. We implemented this value comparison function through responses of simulated biological neurons. We found that due to the presence of neural noise, steepening the value comparison requires an exponential increase in the number of value-coding neurons. Matching may be a compromise between harvesting satisfactory reward and the high demands placed by neural noise on optimal neural computation.

When faced with a choice, humans and animals commonly distribute their behavior in proportion to the frequency of payoff of each option. Such behavior is referred to as matching and has been captured by the matching law. However, matching is not a general law of economic choice. Matching in its strict sense seems to be specifically observed in tasks whose properties make matching an optimal or a near-optimal strategy. We engaged monkeys in a foraging task in which matching was not the optimal strategy. Over-matching the proportions of the mean offered reward magnitudes would yield more reward than matching, yet, surprisingly, the animals almost exactly matched them. To gain insight into this phenomenon, we modeled the animals' decision-making using a mechanistic model. The model accounted for the animals' macroscopic and microscopic choice behavior. When the models' three parameters were not constrained to mimic the monkeys' behavior, the model over-matched the reward proportions and in doing so, harvested substantially more reward than the monkeys. This optimized model revealed a marked bottleneck in the monkeys' choice function that compares the value of the two options. The model featured a very steep value comparison function relative to that of the monkeys. The steepness of the value comparison function had a profound effect on the earned reward and on the level of matching. We implemented this value comparison function through responses of simulated biological neurons. We found that due to the presence of neural noise, steepening the value comparison requires an exponential increase in the number of value-coding neurons. Matching may be a compromise between harvesting satisfactory reward and the high demands placed by neural noise on optimal neural computation.

Behavior rests on the experience of reinforcement and punishment. It has been unclear whether reinforcement and punishment act as oppositely valenced components of a single behavioral factor, or whether these two kinds of outcomes play fundamentally distinct behavioral roles. To this end, we varied the magnitude of a reward or a penalty experienced following a choice using monetary tokens. The outcome of each trial was independent of the outcome of the previous trial, which enabled us to isolate and study the effect on behavior of each outcome magnitude in single trials. We found that a reward led to a repetition of the previous choice, whereas a penalty led to an avoidance of the previous choice. Surprisingly, the effects of the reward magnitude and the penalty magnitude revealed a pronounced asymmetry. The choice repetition effect of a reward scaled with the magnitude of the reward. In a marked contrast, the avoidance effect of a penalty was flat, not influenced by the magnitude of the penalty. These effects were mechanistically described using a reinforcement learning model after the model was updated to account for the penalty-based asymmetry. The asymmetry in the effects of the reward magnitude and the punishment magnitude was so striking that it is difficult to conceive that one factor is just a weighted or transformed form of the other factor. Instead, the data suggest that rewards and penalties are fundamentally distinct factors in governing behavior., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The mechanism underlying temporal correlations among blood oxygen level-dependent signals is unclear. We used oxygen polarography to better characterize oxygen fluctuations and their correlation and to gain insight into the driving mechanism. The power spectrum of local oxygen fluctuations is inversely proportional to frequency raised to a power (1/f) raised to the beta, with an additional positive band-limited component centered at 0.06 Hz. In contrast, the power of the correlated oxygen signal is band limited from ∼ 0.01 Hz to 0.4 Hz with a peak at 0.06 Hz. These results suggest that there is a band-limited mechanism (or mechanisms) driving interregional oxygen correlation that is distinct from the mechanism(s) driving local (1/f) oxygen fluctuations. Candidates for driving interregional oxygen correlation include rhythmic or pseudo-oscillatory mechanisms.

Parietal cortex is central to spatial cognition. Lesions of parietal cortex often lead to hemispatial neglect, an impairment of choices of targets in space. It has been unclear whether parietal cortex implements target choice at the general cognitive level, or whether parietal cortex subserves the choice of targets of particular actions. To address this question, monkeys engaged in choice tasks in two distinct action contexts--eye movements and arm movements. We placed focused reversible lesions into specific parietal circuits using the GABAA receptor agonist muscimol and validated the lesion placement using MRI. We found that lesions on the lateral bank of the intraparietal sulcus [lateral intraparietal area (LIP)] specifically biased choices made using eye movements, whereas lesions on the medial bank of the intraparietal sulcus [parietal reach region (PRR)] specifically biased choices made using arm movements. This double dissociation suggests that target choice is implemented in dedicated parietal circuits in the context of specific actions. This finding emphasizes a motor role of parietal cortex in spatial choice making and contributes to our understanding of hemispatial neglect.

Recordings in the lateral intraparietal area (LIP) reveal that parietal cortex encodes variables related to spatial decision-making, the selection of desirable targets in space. It has been unclear whether parietal cortex is involved in spatial decision-making in general, or whether specific parietal compartments subserve decisions made using specific actions. To test this, we engaged monkeys (Macaca mulatta) in a reward-based decision task in which they selected a target based on its desirability. The animals' choice behavior in this task followed the molar matching law, and in each trial was governed by the desirability of the choice targets. Critically, animals were instructed to make the choice using one of two actions: eye movements (saccades) and arm movements (reaches). We recorded the discharge activity of neurons in area LIP and the parietal reach region (PRR) of the parietal cortex. In line with previous studies, we found that both LIP and PRR encode a reward-based decision variable, the target desirability. Crucially, the target desirability was encoded in LIP at least twice as strongly when choices were made using saccades compared with reaches. In contrast, PRR encoded target desirability only for reaches and not for saccades. These data suggest that decisions can evolve in dedicated parietal circuits in the context of specific actions. This finding supports the hypothesis of an intentional representation of developing decisions in parietal cortex. Furthermore, the close link between the cognitive (decision-related) and bodily (action-related) processes presents a neural contribution to the theories of embodied cognition., (Copyright © 2015 the authors 0270-6474/15/354869-13$15.00/0.)

Previous memoranda can interfere with the memorization or storage of new information, a concept known as proactive interference. Studies of proactive interference typically use categorical memoranda and match-to-sample tasks with categorical measures such as the proportion of correct to incorrect responses. In this study we instead train five macaques in a spatial memory task with continuous memoranda and responses, allowing us to more finely probe working memory circuits. We first ask whether the memoranda from the previous trial result in proactive interference in an oculomotor delayed response task. We then characterize the spatial and temporal profile of this interference and ask whether this profile can be predicted by an attractor network model of working memory. We find that memory in the current trial shows a bias toward the location of the memorandum of the previous trial. The magnitude of this bias increases with the duration of the memory period within which it is measured. Our simulations using standard attractor network models of working memory show that these models easily replicate the spatial profile of the bias. However, unlike the behavioral findings, these attractor models show an increase in bias with the duration of the previous rather than the current memory period. To model a bias that increases with current trial duration we posit two separate memory stores, a rapidly decaying visual store that resists proactive interference effects and a sustained memory store that is susceptible to proactive interference., (Copyright © 2015 the American Physiological Society.)

Studies of visually guided unimanual reaching have established that a saccade usually precedes each reach and that the reaction times (RTs) for the saccade and reach are highly correlated. The correlation of eye and hand RT is commonly taken as a measure of eye-hand coordination and is thought to assist visuospatial guidance of the hand. We asked what happens during a bimanual reach task. As with a unimanual reach, a saccade was executed first. Although latencies were fastest on unimanual trials, eye and hand RT correlation was identical whether just one or both hands reached to a single target. The average correlation was significantly reduced, however, when each hand reached simultaneously to a different target. We considered three factors that might explain the drop. We found that correlation strength depended on which hand reached first and on which hand reached to the same target as the saccade. Surprisingly, these two factors were largely independent, and the identity of the hand, left or right, had little effect. Eye-hand correlation was similar to that seen with unimanual reaching only when the hand that moved to the same target as the saccade was also the first hand to move. Thus both timing as well as spatial pattern are important in determining eye-hand coordination., (Copyright © 2014 the American Physiological Society.)

The neurons comprising many cortical areas have long been known to be arranged topographically such that nearby neurons have receptive fields at nearby locations in the world. Although this type of organization may be universal in primary sensory and motor cortex, in this review we demonstrate that associative cortical areas may not represent the external world in a complete and continuous fashion. After reviewing evidence for novel principles of topographic organization in macaque lateral intraparietal area (LIP) - one of the most-studied associative areas in the parietal cortex - we explore the implications of these new principles for brain function., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Primates frequently reach toward visual targets. Neurons in early visual areas respond to stimuli in the contralateral visual hemifield and without regard to which limb will be used to reach toward that target. In contrast, neurons in motor areas typically respond when reaches are performed using the contralateral limb and with minimal regard to the visuospatial location of the target. The parietal reach region (PRR) is located early in the visuomotor processing hierarchy. PRR neurons are significantly modulated when targets for either limb or eye movement appear, similar to early sensory areas; however, they respond to targets in either visual field, similar to motor areas. The activity could reflect the subject's attentional locus, movement of a specific effector, or a related function, such as coordinating eye-arm movements. To examine the role of PRR in the visuomotor pathway, we reversibly inactivated PRR. Inactivation effects were specific to contralateral limb movements, leaving ipsilateral limb and saccadic movements intact. Neither visual hemifield bias nor visual attention deficits were observed. Thus our results are consistent with a motoric rather than visual organization in PRR, despite its early location in the visuomotor pathway. We found no effects on the temporal coupling of coordinated saccades and reaches, suggesting that this mechanism lies downstream of PRR. In sum, this study clarifies the role of PRR in the visuomotor hierarchy: despite its early position, it is a limb-specific area influencing reach planning and is positioned upstream from an active eye-hand coordination-coupling mechanism.

We often make decisions based on sensory evidence that is accumulated over a period of time. How the evidence for such decisions is represented in the brain and how such a neural representation is used to guide a subsequent action are questions of considerable interest to decision sciences. The neural correlates of developing perceptual decisions have been thoroughly investigated in the oculomotor system of macaques who communicated their decisions using an eye movement. It has been found that the evidence informing a decision to make an eye movement is in part accumulated within the same oculomotor circuits that signal the upcoming eye movement. Recent evidence suggests that the somatomotor system may exhibit an analogous property for choices made using a hand movement. To investigate this possibility, we engaged humans in a decision task in which they integrated discrete quanta of sensory information over a period of time and signaled their decision using a hand movement or an eye movement. The discrete form of the sensory evidence allowed us to infer the decision variable on which subjects base their decision on each trial and to assess the neural processes related to each quantum of the incoming decision evidence. We found that a low-frequency electrophysiological signal recorded over centroparietal regions strongly encodes the decision variable inferred in this task, and that it does so specifically for hand movement choices. The signal ramps up with a rate that is proportional to the decision variable, remains graded by the decision variable throughout the delay period, reaches a common peak shortly before a hand movement, and falls off shortly after the hand movement. Furthermore, the signal encodes the polarity of each evidence quantum, with a short latency, and retains the response level over time. Thus, this neural signal shows properties of evidence accumulation. These findings suggest that the decision-related effects observed in the oculomotor system of the monkey during eye movement choices may share the same basic properties with the decision-related effects in the somatomotor system of humans during hand movement choices., (© 2013 Elsevier Inc. All rights reserved.)

We often look at and sometimes reach for visible targets. Looking at a target is fast and relatively easy. By comparison, reaching for an object is slower and is associated with a larger cost. We hypothesized that, as a result of these differences, abrupt visual onsets may drive the circuits involved in saccade planning more directly and with less intermediate regulation than the circuits involved in reach planning. To test this hypothesis, we recorded discharge activity of neurons in the parietal oculomotor system (area LIP) and in the parietal somatomotor system (area PRR) while monkeys performed a visually guided movement task and a choice task. We found that in the visually guided movement task LIP neurons show a prominent transient response to target onset. PRR neurons also show a transient response, although this response is reduced in amplitude, is delayed, and has a slower rise time compared with LIP. A more striking difference is observed in the choice task. The transient response of PRR neurons is almost completely abolished and replaced with a slow buildup of activity, while the LIP response is merely delayed and reduced in amplitude. Our findings suggest that the oculomotor system is more closely and obligatorily coupled to the visual system, whereas the somatomotor system operates in a more discriminating manner.

The circuits that drive visually guided eye and arm movements transform generic visual inputs into effector-specific motor commands. As part of the effort to elucidate these circuits, the primate lateral intraparietal area (LIP) has been interpreted as a priority map for saccades (oculomotor-specific) or a salience map of space (not effector-specific). It has also been proposed as a locus for eye-hand coordination. We reversibly inactivated LIP while monkeys performed memory-guided saccades and reaches. Coordinated saccade and reach reaction times were similarly impaired, consistent with a nonspecific role. However, reaches made without an accompanying saccade remained intact, and the relative temporal coupling of saccades and reaches was unchanged. These results suggest that LIP contributes to saccade planning but not to reach planning. Coordinated reaches are delayed as a result of an eye-hand coordination mechanism, located outside of LIP, that actively delays reaches until shortly after the onset of an associated saccade. We conclude with a discussion of how to reconcile specificity for saccades with a possible role in directing attention.

Accurate eye-position signals are critically important for localizing targets in space when the eyes move. In this issue of Neuron, Xu et al. (2012) provide evidence that eye-position gain fields in area LIP remain spatially inaccurate for some time after a saccade, indicating they are not updated rapidly enough to play a role in the computation of target locations for upcoming saccades., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Comparing cognitive functions between humans and nonhuman primates is helpful for understanding human tool use. We comment on the latest insights from comparative research on executive control functions. Based on our own work, we discuss how even a mental function in which non-human primates outperform humans might have played a key role in the development of tool use.

Successful decision making involves combining observations of the external world with prior knowledge. Recent studies suggest that neural activity in macaque lateral intraparietal area (LIP) provides a useful window into this process. This study examines how rapidly changing prior knowledge about an upcoming sensory stimulus influences the computations that convert sensory signals into plans for action. Two monkeys performed a cued direction discrimination task, in which an arrow cue presented at the start of each trial communicated the prior probability of the direction of stimulus motion. We hypothesized that the cue would either shift the initial level of LIP activity before sensory evidence arrived, or it would scale sensory responses according to the prior probability of each stimulus, manifesting as a change in slope of LIP firing rates. Neural recordings demonstrated a clear shift in the activity level of LIP neurons following the arrow cue, which persisted into the presentation of the motion stimulus. No significant change in slope of responses was observed, suggesting that sensory gain was not strongly modulated. To confirm the latter observation, middle temporal area (MT) neurons were recorded during a version of the cued direction discrimination task, and we found no change in MT responses resulting from the presentation of the directional cue. These results suggest that information about an immediately upcoming stimulus does not scale the sensory response, but rather changes the amount of evidence that must be accumulated to reach a decision in areas that are involved in planning action.

Neurons in the parietal reach region (PRR) have been implicated in the sensory-to-motor transformation required for reaching toward visually defined targets. The neurons in each cortical hemisphere might be specifically involved in planning movements of just one limb, or the PRR might code reach endpoints generically, independent of which limb will actually move. Previous work has shown that the preferred directions of PRR neurons are similar for right and left limb movements but that the amplitude of modulation may vary greatly. We now test the hypothesis that frames of reference and eye and hand gain field modulations will, like preferred directions, be independent of which hand moves. This was not the case. Many neurons show clear differences in both the frame of reference as well as in direction and strength of gain field modulations, depending on which hand is used to reach. The results suggest that the information that is conveyed from the PRR to areas closer to the motor output (the readout from the PRR) is different for each limb and that individual PRR neurons contribute either to controlling the contralateral-limb or else bimanual-limb control.

Although the parietal cortex is traditionally associated with spatial attention and sensorimotor integration, recent evidence also implicates it in higher order cognitive functions. We review relevant results from neuron recording studies showing that inferior parietal neurons integrate information regarding target location with a variety of non-spatial signals. Some of these signals are modulatory and alter a stimulus-evoked response according to the action, category, or reward associated with the stimulus. Other non-spatial inputs act independently, encoding the context or rules of a task even before the presentation of a specific target. Despite the ubiquity of non-spatial information in individual neurons, reversible inactivation of the parietal lobe affects only spatial orienting of attention and gaze, but not non-spatial aspects of performance. This suggests that non-spatial signals contribute to an underlying spatial computation, possibly allowing the brain to determine which targets are worthy of attention or action in a given task context., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The sensorimotor transformations for visually guided reaching were originally thought to take place in a series of discrete transitions from one systematic frame of reference to the next with neurons coding location relative to the fixation position (gaze-centered) in occipital and posterior parietal areas, relative to the shoulder in dorsal premotor cortex, and in muscle- or joint-based coordinates in motor output neurons. Recent empirical and theoretical work has suggested that spatial encodings that use a range of idiosyncratic representations may increase computational power and flexibility. We now show that neurons in the parietal reach region use nonuniform and idiosyncratic frames of reference. We also show that these nonsystematic reference frames coexist with a systematic compound gain field that modulates activity proportional to the distance between the eyes and the hand. Thus, systematic and idiosyncratic signals may coexist within individual neurons.

Establishing the circuitry underlying attentional and oculomotor control is a long-standing goal of systems neuroscience. The macaque lateral intraparietal area (LIP) has been implicated in both processes, but numerous studies have produced contradictory findings. Anatomically, LIP consists of a dorsal and ventral subdivision, but the functional importance of this division remains unclear. We injected muscimol, a GABA(A) agonist, and manganese, a magnetic resonance imaging lucent paramagnetic ion, into different portions of LIP, examined the effects of the resulting reversible inactivation on saccade planning and attention, and visualized each injection using anatomical magnetic resonance imaging. We found that dorsal LIP (LIPd) is primarily involved in oculomotor planning, whereas ventral LIP (LIPv) contributes to both attentional and oculomotor processes. Additional testing revealed that the two functions were dissociable, even in LIPv. Using our technique, we found a clear structure-function relationship that distinguishes LIPv from LIPd and found dissociable circuits for attention and eye movements in the posterior parietal cortex.

Despite several attempts to define retinotopic maps in the macaque lateral intraparietal area (LIP) using histological, electrophysiological, and neuroimaging methods, the degree to which this area is topographically organized remains controversial. We recorded blood oxygenation level-dependent signals with functional MRI from two macaques performing a difficult visual search task on stimuli presented at the fovea or in the periphery of the visual field. The results revealed the presence of a single topographic representation of the contralateral hemifield in the ventral subdivision of the LIP (LIPv) in both hemispheres of both monkeys. Also, a foveal representation was localized in rostral LIPv rather than in dorsal LIP (LIPd) as previous experiments had suggested. Finally, both LIPd and LIPv responded only to contralateral stimuli. In contrast, human studies have reported multiple topographic maps in intraparietal cortex and robust responses to ipsilateral stimuli. These blood oxygenation level-dependent functional MRI results provide clear evidence for the topographic organization of macaque LIP that complements the results of previous electrophysiology studies, and also reveal some unexpected characteristics of this organization that have eluded these previous studies. The results also delineate organizational differences between LIPv and LIPd, providing support for these two histologically defined areas may subserve different visuospatial functions. Finally, these findings point to potential evolutionary differences in functional organization with human posterior parietal cortex.

Neural responses are typically characterized by computing the mean firing rate, but response variability can exist across trials. Many studies have examined the effect of a stimulus on the mean response, but few have examined the effect on response variability. We measured neural variability in 13 extracellularly recorded datasets and one intracellularly recorded dataset from seven areas spanning the four cortical lobes in monkeys and cats. In every case, stimulus onset caused a decline in neural variability. This occurred even when the stimulus produced little change in mean firing rate. The variability decline was observed in membrane potential recordings, in the spiking of individual neurons and in correlated spiking variability measured with implanted 96-electrode arrays. The variability decline was observed for all stimuli tested, regardless of whether the animal was awake, behaving or anaesthetized. This widespread variability decline suggests a rather general property of cortex, that its state is stabilized by an input.

A gain field, the scaling of a tuned neuronal response by a postural signal, may help support neuronal computation. Here, we characterize eye and hand position gain fields in the parietal reach region (PRR). Eye and hand gain fields in individual PRR neurons are similar in magnitude but opposite in sign to one another. This systematic arrangement produces a compound gain field that is proportional to the distance between gaze location and initial hand position. As a result, the visual response to a target for an upcoming reach is scaled by the initial gaze-to-hand distance. Such a scaling is similar to what would be predicted in a neural network that mediates between eye- and hand-centered representations of target location. This systematic arrangement supports a role of PRR in visually guided reaching and provides strong evidence that gain fields are used for neural computations.

The vestibular system helps maintain equilibrium and clear vision through reflexes, but it also contributes to spatial perception. In recent years, research in the vestibular field has expanded to higher-level processing involving the cortex. Vestibular contributions to spatial cognition have been difficult to study because the circuits involved are inherently multisensory. Computational methods and the application of Bayes theorem are used to form hypotheses about how information from different sensory modalities is combined together with expectations based on past experience in order to obtain optimal estimates of cognitive variables like current spatial orientation. To test these hypotheses, neuronal populations are being recorded during active tasks in which subjects make decisions based on vestibular and visual or somatosensory information. This review highlights what is currently known about the role of vestibular information in these processes, the computations necessary to obtain the appropriate signals, and the benefits that have emerged thus far.

Previous research suggests that visually responsive neurons in the frontal eye field (FEF) respond to visual targets even when they are not the goal of a saccadic eye movement. These results raise the possibility that these neurons respond to visual targets independent of the effector that is to be used to acquire the target locations. In the present study, we examined whether a plan to execute a saccade or a reach to a visual target influenced the response to and the representation of targets in the FEF. We recorded single unit responses to the onset of the target, during the delay period, and around the time of the movement, on interleaved saccade and reach trials of a delayed-response task. We found that the responses of approximately equal percentages of visual, visuomovement, and movement neurons (50%, 58%, and 58%, respectively) were greater on saccade trials than on reach trials in at least one interval of the delayed-response task. Converse biases, in favor of reaches, were much less frequent (13%, 10%, and 19%, in visual, visuomovement, and movement neurons respectively). Thus, although visual neurons may not be directly involved in triggering saccadic eye movements, they are nonetheless highly saccade-biased, with percentages comparable to neurons that are directly involved in triggering saccadic eye movements.

Executive control functions (ECFs) have become an important topic in the cognitive sciences in the past 40 years. The number of publications has steadily increased, and in the last decade, studies have been conducted in one of the best models of human cognition: the old-world macaque monkey. Here, we review recent studies in the monkey that have contributed to our understanding of the neuronal implementation of ECFs, with a focus on task-switching paradigms. These paradigms have revealed that ECFs are distributed across both the parietal and frontal lobes.

Previous single-unit recordings in monkeys showed that essential information regarding a decision is available earlier to posterior parietal cortex than expected based on simultaneously measured behavioral response times (RTs). We propose that this observation reflects a tendency of the brain to reduce RT variability in repetitive response sequences. To test this, we studied the effects of experimentally introduced variability in trial duration on RTs in humans. We found that humans adapt timing based on the timing of surrounding trials, essentially reducing RT variability in trial sequences. This implies that RTs do not always reflect the minimal time it takes to make a decision. Implications for the interpretation of behavioral data are discussed.

To reach for something we see, the brain must integrate the target location with the limb to be used for reaching. Neuronal activity in the parietal reach region (PRR) located in the posterior parietal cortex represents targets for reaching. Does this representation depend on the limb to be used? We found a continuum of limb-dependent and limb-independent responses: some neurons represented targets for movements of either limb, whereas others represented only contralateral-limb targets. Only a few cells represented ipsilateral-limb targets. Furthermore, these representations were not dependent on preferred direction. Additional experiments provide evidence that the PRR is specifically involved in contralateral-limb movements: firing rates are correlated with contralateral- but not ipsilateral-limb reaction times. The current study therefore provides novel evidence that the PRR operates as a limb-dependent stage that lies further along the sensory-motor transformation for visually guided reaching than previously expected.