Sensorimotor faculties bias perceptual decision-making.

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.

Functional organization of posterior parietal cortex circuitry based on inferred information flow.

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.

Heterogeneous Forgetting Rates and Greedy Allocation in Slot-Based Memory Networks Promotes Signal Retention.

A key question in the neuroscience of memory encoding pertains to the mechanisms by which afferent stimuli are allocated within memory networks. This issue is especially pronounced in the domain of working memory, where capacity is finite. Presumably the brain must embed some "policy" by which to allocate these mnemonic resources in an online manner in order to maximally represent and store afferent information for as long as possible and without interference from subsequent stimuli. Here, we engage this question through a top-down theoretical modeling framework. We formally optimize a gating mechanism that projects afferent stimuli onto a finite number of memory slots within a recurrent network architecture. In the absence of external input, the activity in each slot attenuates over time (i.e., a process of gradual forgetting). It turns out that the optimal gating policy consists of a direct projection from sensory activity to memory slots, alongside an activity-dependent lateral inhibition. Interestingly, allocating resources myopically (greedily with respect to the current stimulus) leads to efficient utilization of slots over time. In other words, later-arriving stimuli are distributed across slots in such a way that the network state is minimally shifted and so prior signals are minimally "overwritten." Further, networks with heterogeneity in the timescales of their forgetting rates retain stimuli better than those that are more homogeneous. Our results suggest how online, recurrent networks working on temporally localized objectives without high-level supervision can nonetheless implement efficient allocation of memory resources over time.

Evaluating functional brain organization in individuals and identifying contributions to network overlap.

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.

The most prominent electrophysiological effect of ketamine is not sufficient to cause anesthesia.

NMDA receptor inhibition has been identified as a key functional property of numerous psychoactive drugs, anesthetics, and analgesics including alcohol, nitrous oxide, dextromethorphan, phencyclidine, and ketamine. This report investigates the role of NMDA receptor inhibition in ketamine-induced anesthesia by comparing the effects of systemic injections of ketamine and the highly selective NMDA receptor antagonist CGS 19755 on intracortical electrophysiological activity and behavior in rhesus macaques. Changes in cortical electrophysiology following sub-anesthetic doses of CGS 19755 resemble the "gamma-burst" activity caused by anesthetic doses of ketamine, while the behavioral effects of the two drugs differ considerably. This shows that while NMDA antagonism is sufficient to cause a key neural correlate of ketamine anesthesia, it is not sufficient on its own to cause anesthesia. These findings shed light on a previously unappreciated effect of systemic NMDA antagonism, and clarify the relationship between electrophysiological changes caused by ketamine and ketamine's anesthetic mechanisms.

Primates chunk simultaneously-presented memoranda.

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.

Contralateral Limb Specificity for Movement Preparation in the Parietal Reach Region.

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.

Relationships between correlated spikes, oxygen and LFP in the resting-state primate.

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.

Contribution of animal models toward understanding resting state functional connectivity.

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.

Local field potentials in the parietal reach region reveal mechanisms of bimanual coordination.

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.

Primate Spatial Memory Cells Become Tuned Early and Lose Tuning at Cell-Specific Times.

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.

Local Perturbations of Cortical Excitability Propagate Differentially Through Large-Scale Functional Networks.

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.

Eye-hand re-coordination: A pilot investigation of gaze and reach biofeedback in chronic stroke.

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.

Dissociation of LFP Power and Tuning in the Frontal Cortex during Memory.

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.

Spatial eye-hand coordination during bimanual reaching is not systematically coded in either LIP or PRR.

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.

Spontaneous Infra-slow Brain Activity Has Unique Spatiotemporal Dynamics and Laminar Structure.

Systems-level organization in spontaneous infra-slow (<0.1Hz) brain activity, measured using blood oxygen signals in fMRI and optical imaging, has become a major theme in the study of neural function in both humans and animal models. Yet the neurophysiological basis of infra-slow activity (ISA) remains unresolved. In particular, is ISA a distinct physiological process, or is it a low-frequency analog of faster neural activity? Here, using whole-cortex calcium/hemoglobin imaging in mice, we show that ISA in each of these modalities travels through the cortex along stereotypical spatiotemporal trajectories that are state dependent (wake versus anesthesia) and distinct from trajectories in delta (1-4 Hz) activity. Moreover, mouse laminar electrophysiology reveals that ISA travels through specific cortical layers and is organized into unique cross-laminar temporal dynamics that are different from higher frequency local field potential activity. These findings suggest that ISA is a distinct neurophysiological process that is reflected in fMRI blood oxygen signals.

Single Units in the Posterior Parietal Cortex Encode Patterns of Bimanual Coordination.

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.

Reward Size Informs Repeat-Switch Decisions and Strongly Modulates the Activity of Neurons in Parietal Cortex.

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.

Ghosts in the Machine II: Neural Correlates of Memory Interference from the Previous Trial.

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.