Value dynamics affect choice preparation during decision-making.

During decision-making, neurons in the orbitofrontal cortex (OFC) sequentially represent the value of each option in turn, but it is unclear how these dynamics are translated into a choice response. One brain region that may be implicated in this process is the anterior cingulate cortex (ACC), which strongly connects with OFC and contains many neurons that encode the choice response. We investigated how OFC value signals interacted with ACC neurons encoding the choice response by performing simultaneous high-channel count recordings from the two areas in nonhuman primates. ACC neurons encoding the choice response steadily increased their firing rate throughout the decision-making process, peaking shortly before the time of the choice response. Furthermore, the value dynamics in OFC affected ACC ramping-when OFC represented the more valuable option, ACC ramping accelerated. Because OFC tended to represent the more valuable option more frequently and for a longer duration, this interaction could explain how ACC selects the more valuable response.

Fast and slow contributions to decision-making in corticostriatal circuits.

We make complex decisions using both fast judgments and slower, more deliberative reasoning. For example, during value-based decision-making, animals make rapid value-guided orienting eye movements after stimulus presentation that bias the upcoming decision. The neural mechanisms underlying these processes remain unclear. To address this, we recorded from the caudate nucleus and orbitofrontal cortex while animals made value-guided decisions. Using population-level decoding, we found a rapid, phasic signal in caudate that predicted the choice response and closely aligned with animals' initial orienting eye movements. In contrast, the dynamics in orbitofrontal cortex were more consistent with a deliberative system serially representing the value of each available option. The phasic caudate value signal and the deliberative orbitofrontal value signal were largely independent from each other, consistent with value-guided orienting and value-guided decision-making being independent processes.

Taking stock of value in the orbitofrontal cortex.

People with damage to the orbitofrontal cortex (OFC) have specific problems making decisions, whereas their other cognitive functions are spared. Neurophysiological studies have shown that OFC neurons fire in proportion to the value of anticipated outcomes. Thus, a central role of the OFC is to guide optimal decision-making by signalling values associated with different choices. Until recently, this view of OFC function dominated the field. New data, however, suggest that the OFC may have a much broader role in cognition by representing cognitive maps that can be used to guide behaviour and that value is just one of many variables that are important for behavioural control. In this Review, we critically evaluate these two alternative accounts of OFC function and examine how they might be reconciled.

Hippocampal neurons construct a map of an abstract value space.

The hippocampus is thought to encode a "cognitive map," a structural organization of knowledge about relationships in the world. Place cells, spatially selective hippocampal neurons that have been extensively studied in rodents, are one component of this map, describing the relative position of environmental features. However, whether this map extends to abstract, cognitive information remains unknown. Using the relative reward value of cues to define continuous "paths" through an abstract value space, we show that single neurons in primate hippocampus encode this space through value place fields, much like a rodent's place neurons encode paths through physical space. Value place fields remapped when cues changed but also became increasingly correlated across contexts, allowing maps to become generalized. Our findings help explain the critical contribution of the hippocampus to value-based decision-making, providing a mechanism by which knowledge of relationships in the world can be incorporated into reward predictions for guiding decisions.

Closed-Loop Theta Stimulation in the Orbitofrontal Cortex Prevents Reward-Based Learning.

Neuronal oscillations in the frontal cortex have been hypothesized to play a role in the organization of high-level cognition. Within the orbitofrontal cortex (OFC), there is a prominent oscillation in the theta frequency (4-8 Hz) during reward-guided behavior, but it is unclear whether this oscillation has causal significance. One methodological challenge is that it is difficult to manipulate theta without affecting other neural signals, such as single-neuron firing rates. A potential solution is to use closed-loop control to record theta in real time and use this signal to control the application of electrical microstimulation to the OFC. Using this method, we show that theta oscillations in the OFC are critically important for reward-guided learning and that they are driven by theta oscillations in the hippocampus (HPC). The ability to disrupt OFC computations via spatially localized and temporally precise stimulation could lead to novel treatment strategies for neuropsychiatric disorders involving OFC dysfunction.

Evolution of neural processing for visual perception in vertebrates.

Visual perception requires both visual information and attention. This review compares, across classes of vertebrates, the functional and anatomical characteristics of (a) the neural pathways that process visual information about objects, and (b) stimulus selection pathways that determine the objects to which an animal attends. Early in the evolution of vertebrate species, visual perception was dominated by information transmitted via the midbrain (retinotectal) visual pathway, and attention was probably controlled primarily by a selection network in the midbrain. In contrast, in primates, visual perception is dominated by information transmitted via the forebrain (retinogeniculate) visual pathway, and attention is mediated largely by networks in the forebrain. In birds and nonprimate mammals, both the retinotectal and retinogeniculate pathways contribute critically to visual information processing, and both midbrain and forebrain networks play important roles in controlling attention. The computations and processing strategies in birds and mammals share some strikingly similar characteristics despite over 300 million years of independent evolution and being implemented by distinct brain architectures. The similarity of these functional characteristics suggests that they provide valuable advantages to visual perception in advanced visual systems. A schema is proposed that describes the evolution of the pathways and computations that enable visual perception in vertebrate species.

A model-based approach for targeted neurophysiology in the behaving non-human primate.

Acute neurophysiology in the behaving primate typically relies on traditional manufacturing approaches for the instrumentation necessary for recording. For example, our previous approach consisted of distributing single microelectrodes in a fixed plane situated over a circular patch of frontal cortex using conventionally-milled recording grids. With the advent of robust, multisite linear probes, and the introduction of commercially-available, high-resolution rapid prototyping systems, we have been able to improve upon traditional approaches. Here, we report our methodology for producing flexible, MR-informed recording platforms that allow us to precisely target brain structures of interest, including those that would be unreachable using previous methods. We have increased our single-session recording yields by an order of magnitude and recorded neural activity from widely-distributed regions using only a single recording chamber. This approach both speeds data collection, reduces the damage done to neural tissue over the course of a single experiment, and reduces the number of surgical procedures experienced by the animal.

Neural Circuits That Mediate Selective Attention: A Comparative Perspective.

Selective attention is central to cognition. Dramatic advances have been made in understanding the neural circuits that mediate selective attention. Forebrain networks, most elaborated in primates, control all forms of attention based on task demands and the physical salience of stimuli. These networks contain circuits that distribute top-down signals to sensory processing areas and enhance information processing in those areas. A midbrain network, most elaborated in birds, controls spatial attention. It contains circuits that continuously compute the highest priority stimulus location and route sensory information from the selected location to forebrain networks that make cognitive decisions. The identification of these circuits, their functions and mechanisms represent a major advance in our understanding of how the vertebrate brain mediates selective attention.

Disentangling the relationship between gender and work-family conflict: An integration of theoretical perspectives using meta-analytic methods.

Implicit in many discussions of work-family issues is the idea that managing the work-family interface is more challenging for women than men. We address whether this intuition is supported by the empirical data via a meta-analysis of gender differences in work-family conflict (WFC) based on more than 350 independent samples (N > 250,000 workers). Challenging lay perceptions, our results demonstrate that men and women generally do not differ on their reports of WFC, though there were some modest moderating effects of dual-earner status, parental status, type of WFC (i.e., time-, strain-, vs. behavior-based), and when limiting samples to men and women who held the same job. To better understand the relationship between gender and WFC, we engaged in theory-testing of mediating mechanisms based on commonly invoked theoretical perspectives. We found evidence in support of the rational view, no support for the sensitization and male segmentation perspectives, and partial support for the asymmetrical domain permeability model. Finally, we build theory by seeking to identify omitted mediators that explain the relationship between gender and work-interference-with-family, given evidence that existing theoretically specified mechanisms are insufficient to explain this relationship. Overall, we find more evidence for similarity rather than difference in the degree of WFC experienced by men and women. (PsycINFO Database Record

Space-Specific Deficits in Visual Orientation Discrimination Caused by Lesions in the Midbrain Stimulus Selection Network.

Perceptual decisions require both analysis of sensory information and selective routing of relevant information to decision networks. This study explores the contribution of a midbrain network to visual perception in chickens. Analysis of visual orientation information in birds takes place in the forebrain sensory area called the Wulst, as it does in the primary visual cortex (V1) of mammals. In contrast, the midbrain, which receives parallel retinal input, encodes orientation poorly, if at all. We discovered, however, that small electrolytic lesions in the midbrain severely impair a chicken's ability to discriminate orientations. Focal lesions were placed in the optic tectum (OT) and in the nucleus isthmi pars parvocellularis (Ipc)-key nodes in the midbrain stimulus selection network-in chickens trained to perform an orientation discrimination task. A lesion in the OT caused a severe impairment in orientation discrimination specifically for targets at the location in space represented by the lesioned location. Distracting stimuli increased the deficit. A lesion in the Ipc produced similar but more transient effects. We discuss the possibilities that performance deficits were caused by interference with orientation information processing (sensory deficit) versus with the routing of information in the forebrain (agnosia). The data support the proposal that the OT transmits a space-specific signal that is required to gate orientation information from the Wulst into networks that mediate behavioral decisions, analogous to the role of ascending signals from the superior colliculus (SC) in monkeys. Furthermore, our results indicate a critical role for the cholinergic Ipc in this gating process.

Does the Superior Colliculus Control Perceptual Sensitivity or Choice Bias during Attention? Evidence from a Multialternative Decision Framework.

Distinct networks in the forebrain and the midbrain coordinate to control spatial attention. The critical involvement of the superior colliculus (SC)-the central structure in the midbrain network-in visuospatial attention has been shown by four seminal, published studies in monkeys (Macaca mulatta) performing multialternative tasks. However, due to the lack of a mechanistic framework for interpreting behavioral data in such tasks, the nature of the SC's contribution to attention remains unclear. Here we present and validate a novel decision framework for analyzing behavioral data in multialternative attention tasks. We apply this framework to re-examine the behavioral evidence from these published studies. Our model is a multidimensional extension to signal detection theory that distinguishes between two major classes of attentional mechanisms: those that alter the quality of sensory information or "sensitivity," and those that alter the selective gating of sensory information or "choice bias." Model-based simulations and model-based analyses of data from these published studies revealed a converging pattern of results that indicated that choice-bias changes, rather than sensitivity changes, were the primary outcome of SC manipulation. Our results suggest that the SC contributes to attentional performance predominantly by generating a spatial choice bias for stimuli at a selected location, and that this bias operates downstream of forebrain mechanisms that enhance sensitivity. The findings lead to a testable mechanistic framework of how the midbrain and forebrain networks interact to control spatial attention. SIGNIFICANCE STATEMENT: Attention involves the selection of the most relevant information for differential sensory processing and decision making. While the mechanisms by which attention alters sensory encoding (sensitivity control) are well studied, the mechanisms by which attention alters decisional weighting of sensory evidence (choice-bias control) are poorly understood. Here, we introduce a model of multialternative decision making that distinguishes bias from sensitivity effects in attention tasks. With our model, we simulate experimental data from four seminal studies that microstimulated or inactivated a key attention-related midbrain structure, the superior colliculus (SC). We demonstrate that the experimental effects of SC manipulation are entirely consistent with the SC controlling attention by changing choice bias, thereby shedding new light on how the brain mediates attention.

Restoration of Hindlimb Movements after Complete Spinal Cord Injury Using Brain-Controlled Functional Electrical Stimulation.

Single neuron and local field potential signals recorded in the primary motor cortex have been repeatedly demonstrated as viable control signals for multi-degree-of-freedom actuators. Although the primary source of these signals has been fore/upper limb motor regions, recent evidence suggests that neural adaptation underlying neuroprosthetic control is generalizable across cortex, including hindlimb sensorimotor cortex. Here, adult rats underwent a longitudinal study that included a hindlimb pedal press task in response to cues for specific durations, followed by brain machine interface (BMI) tasks in healthy rats, after rats received a complete spinal transection and after the BMI signal controls epidural stimulation (BMI-FES). Over the course of the transition from learned behavior to BMI task, fewer neurons were responsive after the cue, the proportion of neurons selective for press duration increased and these neurons carried more information. After a complete, mid-thoracic spinal lesion that completely severed both ascending and descending connections to the lower limbs, there was a reduction in task-responsive neurons followed by a reacquisition of task selectivity in recorded populations. This occurred due to a change in pattern of neuronal responses not simple changes in firing rate. Finally, during BMI-FES, additional information about the intended press duration was produced. This information was not dependent on the stimulation, which was the same for short and long duration presses during the early phase of stimulation, but instead was likely due to sensory feedback to sensorimotor cortex in response to movement along the trunk during the restored pedal press. This post-cue signal could be used as an error signal in a continuous decoder providing information about the position of the limb to optimally control a neuroprosthetic device.

Spatially precise visual gain control mediated by a cholinergic circuit in the midbrain attention network.

A primary function of the midbrain stimulus selection network is to compute the highest-priority location for attention and gaze. Here we report the contribution of a specific cholinergic circuit to this computation. We functionally disconnected the tegmental cholinergic nucleus isthmi pars parvocellularis (Ipc) from the optic tectum (OT) in barn owls by reversibly blocking excitatory transmission in the Ipc. Focal blockade in the Ipc decreases the gain and spatial discrimination of OT units specifically for the locations represented by the visual receptive fields (VRFs) of the disconnected Ipc units, and causes OT VRFs to shift away from that location. The results demonstrate mechanisms by which this cholinergic circuit controls bottom-up stimulus competition and by which top-down signals can bias this competition, and they establish causal linkages between a particular circuit, gain control and dynamic shifts of VRFs. This circuit may perform the same function in all vertebrate species.

Interactive Effects Between Exercise and Serotonergic Pharmacotherapy on Cortical Reorganization After Spinal Cord Injury.

BACKGROUND: In rat models of spinal cord injury, at least 3 different strategies can be used to promote long-term cortical reorganization: (1) active exercise above the level of the lesion; (2) passive exercise below the level of the lesion; and (3) serotonergic pharmacotherapy. Whether and how these potential therapeutic strategies-and their underlying mechanisms of action-interact remains unknown. Methods In spinally transected adult rats, we compared the effects of active exercise above the level of the lesion (treadmill), passive exercise below the level of the lesion (bike), serotonergic pharmacotherapy (quipazine), and combinations of the above therapies (bike+quipazine, treadmill+quipazine, bike+treadmill+quipazine) on long-term cortical reorganization (9 weeks after the spinal transection). Cortical reorganization was measured as the percentage of cells recorded in the deafferented hindlimb cortex that responded to tactile stimulation of the contralateral forelimb. Results Bike and quipazine are "competing" therapies for cortical reorganization, in the sense that quipazine limits the cortical reorganization induced by bike, whereas treadmill and quipazine are "collaborative" therapies, in the sense that the reorganization induced by quipazine combined with treadmill is greater than the reorganization induced by either quipazine or treadmill. CONCLUSIONS: These results uncover the interactive effects between active/passive exercise and serotonergic pharmacotherapy on cortical reorganization after spinal cord injury, emphasizing the importance of understanding the effects of therapeutic strategies in spinal cord injury (and in other forms of deafferentation) from an integrated system-level approach.

Cholinergic control of gamma power in the midbrain spatial attention network.

The modulation of gamma power (25-90 Hz) is associated with attention and has been observed across species and brain areas. However, mechanisms that control these modulations are poorly understood. The midbrain spatial attention network in birds generates high-amplitude gamma oscillations in the local field potential that are thought to represent the highest priority location for attention. Here we explore, in midbrain slices from chickens, mechanisms that regulate the power of these oscillations, using high-resolution techniques including intracellular recordings from neurons targeted by calcium imaging. The results identify a specific subtype of neuron, expressing non-α7 nicotinic acetylcholine receptors, that directly drives inhibition in the gamma-generating circuit and switches the network into a primed state capable of producing high-amplitude oscillations. The special properties of this mechanism enable rapid, persistent changes in gamma power. The brain may employ this mechanism wherever rapid modulations of gamma power are critical to information processing.

Gamma oscillations in the midbrain spatial attention network: linking circuits to function.

Gamma-band (25-140Hz) oscillations are ubiquitous in mammalian forebrain structures involved in sensory processing, attention, learning and memory. The optic tectum (OT) is the central structure in a midbrain network that participates critically in controlling spatial attention. In this review, we summarize recent advances in characterizing a neural circuit in this midbrain network that generates large amplitude, space-specific, gamma oscillations in the avian OT, both in vivo and in vitro. We describe key physiological and pharmacological mechanisms that produce and regulate the structure of these oscillations. The extensive similarities between midbrain gamma oscillations in birds and those in the neocortex and hippocampus of mammals, offer important insights into the functional significance of a midbrain gamma oscillatory code.

Selective disinhibition: A unified neural mechanism for predictive and post hoc attentional selection.

The natural world presents us with a rich and ever-changing sensory landscape containing diverse stimuli that constantly compete for representation in the brain. When the brain selects a stimulus as the highest priority for attention, it differentially enhances the representation of the selected, "target" stimulus and suppresses the processing of other, distracting stimuli. A stimulus may be selected for attention while it is still present in the visual scene (predictive selection) or after it has vanished (post hoc selection). We present a biologically inspired computational model that accounts for the prioritized processing of information about targets that are selected for attention either predictively or post hoc. Central to the model is the neurobiological mechanism of "selective disinhibition" - the selective suppression of inhibition of the representation of the target stimulus. We demonstrate that this mechanism explains major neurophysiological hallmarks of selective attention, including multiplicative neural gain, increased inter-trial reliability (decreased variability), and reduced noise correlations. The same mechanism also reproduces key behavioral hallmarks associated with target-distracter interactions. Selective disinhibition exhibits several distinguishing and advantageous features over alternative mechanisms for implementing target selection, and is capable of explaining the effects of selective attention over a broad range of real-world conditions, involving both predictive and post hoc biasing of sensory competition and decisions.

Dissociating movement from movement timing in the rat primary motor cortex.

Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions.

Descending control of neural bias and selectivity in a spatial attention network: rules and mechanisms.

The brain integrates stimulus-driven (exogenous) activity with internally generated (endogenous) activity to compute the highest priority stimulus for gaze and attention. Little is known about how this computation is accomplished neurally. We explored the underlying functional logic in a critical component of the spatial attention network, the optic tectum (OT, superior colliculus in mammals), in awake barn owls. We found that space-specific endogenous influences, evoked by activating descending forebrain pathways, bias competition among exogenous influences, and substantially enhance the quality of the categorical neural pointer to the highest priority stimulus. These endogenous influences operate across sensory modalities. Biologically grounded modeling revealed that the observed effects on network bias and selectivity require a simple circuit mechanism: endogenously driven gain modulation of feedback inhibition among competing channels. Our findings reveal fundamental principles by which internal and external information combine to guide selection of the next target for gaze and attention.

Distinguishing bias from sensitivity effects in multialternative detection tasks.

Studies investigating the neural bases of cognitive phenomena increasingly employ multialternative detection tasks that seek to measure the ability to detect a target stimulus or changes in some target feature (e.g., orientation or direction of motion) that could occur at one of many locations. In such tasks, it is essential to distinguish the behavioral and neural correlates of enhanced perceptual sensitivity from those of increased bias for a particular location or choice (choice bias). However, making such a distinction is not possible with established approaches. We present a new signal detection model that decouples the behavioral effects of choice bias from those of perceptual sensitivity in multialternative (change) detection tasks. By formulating the perceptual decision in a multidimensional decision space, our model quantifies the respective contributions of bias and sensitivity to multialternative behavioral choices. With a combination of analytical and numerical approaches, we demonstrate an optimal, one-to-one mapping between model parameters and choice probabilities even for tasks involving arbitrarily large numbers of alternatives. We validated the model with published data from two ternary choice experiments: a target-detection experiment and a length-discrimination experiment. The results of this validation provided novel insights into perceptual processes (sensory noise and competitive interactions) that can accurately and parsimoniously account for observers' behavior in each task. The model will find important application in identifying and interpreting the effects of behavioral manipulations (e.g., cueing attention) or neural perturbations (e.g., stimulation or inactivation) in a variety of multialternative tasks of perception, attention, and decision-making.