The cortical connectome of primate lateral prefrontal cortex.

The lateral prefrontal cortex (LPFC) of primates plays an important role in executive control, but how it interacts with the rest of the cortex remains unclear. To address this, we densely mapped the cortical connectome of LPFC, using electrical microstimulation combined with functional MRI (EM-fMRI). We found isomorphic mappings between LPFC and five major processing domains composing most of the cerebral cortex except early sensory and motor areas. An LPFC grid of ∼200 stimulation sites topographically mapped to separate grids of activation sites in the five domains, coarsely resembling how the visual cortex maps the retina. The temporal and parietal maps largely overlapped in LPFC, suggesting topographically organized convergence of the ventral and dorsal streams, and the other maps overlapped at least partially. Thus, the LPFC contains overlapping, millimeter-scale maps that mirror the organization of major cortical processing domains, supporting LPFC's role in coordinating activity within and across these domains.

The role of prefrontal cortex in the control of feature attention in area V4.

When searching for an object in a cluttered scene, we can use our memory of the target object features to guide our search, and the responses of neurons in multiple cortical visual areas are enhanced when their receptive field contains a stimulus sharing target object features. Here we tested the role of the ventral prearcuate region (VPA) of prefrontal cortex in the control of feature attention in cortical visual area V4. VPA was unilaterally inactivated in monkeys performing a free-viewing visual search for a target stimulus in an array of stimuli, impairing monkeys' ability to find the target in the array in the affected hemifield, but leaving intact their ability to make saccades to targets presented alone. Simultaneous recordings in V4 revealed that the effects of feature attention on V4 responses were eliminated or greatly reduced while leaving the effects of spatial attention on responses intact. Altogether, the results suggest that feedback from VPA modulates processing in visual cortex during attention to object features.

A Source for Feature-Based Attention in the Prefrontal Cortex.

In cluttered scenes, we can use feature-based attention to quickly locate a target object. To understand how feature attention is used to find and select objects for action, we focused on the ventral prearcuate (VPA) region of prefrontal cortex. In a visual search task, VPA cells responded selectively to search cues, maintained their feature selectivity throughout the delay and subsequent saccades, and discriminated the search target in their receptive fields with a time course earlier than in FEF or IT cortex. Inactivation of VPA impaired the animals' ability to find targets, and simultaneous recordings in FEF revealed that the effects of feature attention were eliminated while leaving the effects of spatial attention in FEF intact. Altogether, the results suggest that VPA neurons compute the locations of objects with the features sought and send this information to FEF to guide eye movements to those relevant stimuli.

Custom-fit radiolucent cranial implants for neurophysiological recording and stimulation.

BACKGROUND: Recording and manipulating neural activity in awake behaving animal models requires long-term implantation of cranial implants that must address a variety of design considerations, which include preventing infection, minimizing tissue damage, mechanical strength of the implant, and MRI compatibility. NEW METHOD: Here we address these issues by designing legless, custom-fit cranial implants using structural MRI-based reconstruction of the skull and that are made from carbon-reinforced PEEK. RESULTS: We report several novel custom-fit radiolucent implant designs, which include a legless recording chamber, a legless stimulation chamber, a multi-channel microdrive and a head post. The fit to the skull was excellent in all cases, with no visible gaps between the base of the implants and the skull. The wound margin was minimal in size and showed no sign of infection or skin recession. COMPARISON WITH EXISTING METHODS: Cranial implants used for neurophysiological investigation in awake behaving animals often employ methyl methacrylate (MMA) to serve as a bonding agent to secure the implant to the skull. Other designs rely on radially extending legs to secure the implant. Both of these methods have significant drawbacks. MMA is toxic to bone and frequently leads to infection while radially extending legs cause the skin to recede away from the implant, ultimately exposing bone and proliferating granulation tissue. CONCLUSIONS: These radiolucent implants constitute a set of technologies suitable for reliable long-term recording, which minimize infection and tissue damage.

Stimulation of the nucleus accumbens as behavioral reward in awake behaving monkeys.

It has been known that monkeys will repeatedly press a bar for electrical stimulation in several different brain structures. We explored the possibility of using electrical stimulation in one such structure, the nucleus accumbens, as a substitute for liquid reward in animals performing a complex task, namely visual search. The animals had full access to water in the cage at all times on days when stimulation was used to motivate them. Electrical stimulation was delivered bilaterally at mirror locations in and around the accumbens, and the animals' motivation to work for electrical stimulation was quantified by the number of trials they performed correctly per unit of time. Acute mapping revealed that stimulation over a large area successfully supported behavioral performance during the task. Performance improved with increasing currents until it reached an asymptotic, theoretically maximal level. Moreover, stimulation with chronically implanted electrodes showed that an animal's motivation to work for electrical stimulation was at least equivalent to, and often better than, when it worked for liquid reward while on water control. These results suggest that electrical stimulation in the accumbens is a viable method of reward in complex tasks. Because this method of reward does not necessitate control over water or food intake, it may offer an alternative to the traditional liquid or food rewards in monkeys, depending on the goals and requirements of the particular research project.

Object decoding with attention in inferior temporal cortex.

Recognizing objects in cluttered scenes requires attentional mechanisms to filter out distracting information. Previous studies have found several physiological correlates of attention in visual cortex, including larger responses for attended objects. However, it has been unclear whether these attention-related changes have a large impact on information about objects at the neural population level. To address this question, we trained monkeys to covertly deploy their visual attention from a central fixation point to one of three objects displayed in the periphery, and we decoded information about the identity and position of the objects from populations of ∼ 200 neurons from the inferior temporal cortex using a pattern classifier. The results show that before attention was deployed, information about the identity and position of each object was greatly reduced relative to when these objects were shown in isolation. However, when a monkey attended to an object, the pattern of neural activity, represented as a vector with dimensionality equal to the size of the neural population, was restored toward the vector representing the isolated object. Despite this nearly exclusive representation of the attended object, an increase in the salience of nonattended objects caused "bottom-up" mechanisms to override these "top-down" attentional enhancements. The method described here can be used to assess which attention-related physiological changes are directly related to object recognition, and should be helpful in assessing the role of additional physiological changes in the future.

Top down attentional deficits in macaques with lesions of lateral prefrontal cortex.

Brain imaging, electrical stimulation, and neurophysiological studies have all implicated the prefrontal cortex (PFC) in the top-down control of attention. Specifically, feedback from PFC has been proposed to bias activity in visual cortex in favor of attended stimuli over irrelevant distracters. To identify which attentional functions are critically dependent on PFC, we removed PFC unilaterally in combination with transection of the corpus callosum and anterior commissure in two macaques. In such a preparation, the ipsilesional hemisphere is deprived of top-down feedback from PFC to visual cortex, and the contralesional hemisphere can serve as an intact normal control. Monkeys were trained to fixate a central cue and discriminate the orientation of a colored target grating presented among colored distracter gratings in either the hemifield affected by the PFC lesion or the normal control hemifield. Locations of the targets and distracters were varied, and the color of the central cue specified the color of the target on each trial. The behavioral response was a bar release, and thus attentional impairments could be distinguished from impaired oculomotor control. When the cue was held constant for many trials, task performance in the affected hemifield was nearly normal. However, the monkeys were severely impaired when the cue was switched frequently across trials. The monkeys were unimpaired in a pop-out task with changing targets that did not require top-down attentional control. The PFC thus appears to play a critical role in the ability to flexibly reallocate attention on the basis of changing task demands.

Finding a face in the crowd: parallel and serial neural mechanisms of visual selection.

At any given moment, our visual system is confronted with more information than it can process. Thus, attention is needed to select behaviorally relevant information in a visual scene for further processing. Behavioral studies of attention during visual search have led to the distinction between serial and parallel mechanisms of selection. To find a target object in a crowded scene, for example a "face in a crowd", the visual system might turn on and off the neural representation of each object in a serial fashion, testing each representation against a template of the target object. Alternatively, it might allow the processing of all objects in parallel, but bias activity in favor of those neurons representing critical features of the target, until the target emerges from the background. Recent neurophysiological evidence shows that both serial and parallel selections take place in neurons of the ventral "object-recognition pathway" during visual search tasks in which monkeys freely scan complex displays to find a target object. Furthermore, attentional selection appears to be mediated by changes in the synchrony of responses of neuronal populations in addition to the modulation of the firing rate of individual neurons.

Somatosensory areas S2 and PV project to the superior colliculus of a prosimian primate, Galago garnetti.

As part of an effort to describe the connections of the somatosensory system in Galago garnetti, a small prosimian primate, injections of tracers into cortex revealed that two somatosensory areas, the second somatosensory area (S2) and the parietal ventral somatosensory area (PV), project densely to the ipsilateral superior colliculus, while the primary somatosensory area (S1 or area 3b) does not. The three cortical areas were defined in microelectrode mapping experiments and recordings were used to identify appropriate injection sites in the same cases. Injections of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) were placed in S1 in different mediolateral locations representing body regions from toes to face in five galagos, and none of these injections labeled projections to the superior colliculus. In contrast, each of the two injections in the face representation of S2 in two galagos and three injections in face and forelimb representations of PV in three galagos produced dense patches of labeled terminations and axons in the intermediate gray (layer IV) over the full extent of the superior colliculus. The results suggest that the higher-order somatosensory areas, PV and S2, are directly involved in the visuomotor functions of the superior colliculus in prosimian primates, while S1 is not. The somatosensory inputs appear to be too widespread to contribute to a detailed somatotopic representation in the superior colliculus, but they may be a source of somatosensory modulation of retinotopically guided oculomotor instructions.

Parallel and serial neural mechanisms for visual search in macaque area V4.

To find a target object in a crowded scene, a face in a crowd for example, the visual system might turn the neural representation of each object on and off in a serial fashion, testing each representation against a template of the target item. Alternatively, it might allow the processing of all objects in parallel but bias activity in favor of those neurons that represent critical features of the target, until the target emerges from the background. To test these possibilities, we recorded neurons in area V4 of monkeys freely scanning a complex array to find a target defined by color, shape, or both. Throughout the period of searching, neurons gave enhanced responses and synchronized their activity in the gamma range whenever a preferred stimulus in their receptive field matched a feature of the target, as predicted by parallel models. Neurons also gave enhanced responses to candidate targets that were selected for saccades, or foveation, reflecting a serial component of visual search. Thus, serial and parallel mechanisms of response enhancement and neural synchrony work together to identify objects in a scene. To find a target object in a crowded scene, a face in a crowd for example, the visual system might turn the neural representation of each object on and off in a serial fashion, testing each representation against a template of the target item. Alternatively, it might allow the processing of all objects in parallel but bias activity in favor of those neurons that represent critical features of the target, until the target emerges from the background. To test these possibilities, we recorded neurons in area V4 of monkeys freely scanning a complex array to find a target defined by color, shape, or both. Throughout the period of searching, neurons gave enhanced responses and synchronized their activity in the gamma range whenever a preferred stimulus in their receptive field matched a feature of the target, as predicted by parallel models. Neurons also gave enhanced responses to candidate targets that were selected for saccades, or foveation, reflecting a serial component of visual search. Thus, serial and parallel mechanisms of response enhancement and neural synchrony work together to identify objects in a scene.

Frontal eye field activity before visual search errors reveals the integration of bottom-up and top-down salience.

We investigated the saccade decision process by examining activity recorded in the frontal eye field (FEF) of monkeys performing 2 separate visual search experiments in which there were errors in saccade target choice. In the first experiment, the difficulty of a singleton search task was manipulated by varying the similarity between the target and distractors; errors were made more often when the distractors were similar to the target. On catch trials in which the target was absent the monkeys occasionally made false alarm errors by shifting gaze to one of the distractors. The second experiment was a popout color visual search task in which the target and distractor colors switched unpredictably across trials. Errors occurred most frequently on the first trial after the switch and less often on subsequent trials. In both experiments, FEF neurons selected the saccade goal on error trials, not the singleton target of the search array. Although saccades were made to the same stimulus locations, presaccadic activation and the magnitude of selection differed across trial conditions. The variation in presaccadic selective activity was accounted for by the variation in saccade probability across the stimulus-response conditions, but not by variations in saccade metrics. These results suggest that FEF serves as a saccade probability map derived from the combination of bottom-up and top-down influences. Peaks on this map represent the behavioral relevance of each item in the visual field rather than just reflecting saccade preparation. This map in FEF may correspond to the theoretical salience map of many models of attention and saccade target selection.

A visual salience map in the primate frontal eye field.

Models of attention and saccade target selection propose that within the brain there is a topographic map of visual salience that combines bottom-up and top-down influences to identify locations for further processing. The results of a series of experiments with monkeys performing visual search tasks have identified a population of frontal eye field (FEF) visually responsive neurons that exhibit all of the characteristics of a visual salience map. The activity of these FEF neurons is not sensitive to specific features of visual stimuli; but instead, their activity evolves over time to select the target of the search array. This selective activation reflects both the bottom-up intrinsic conspicuousness of the stimuli and the top-down knowledge and goals of the viewer. The peak response within FEF specifies the target for the overt gaze shift. However, the selective activity in FEF is not in itself a motor command because the magnitude of activation reflects the relative behavioral significance of the different stimuli in the visual scene and occurs even when no saccade is made. Identifying a visual salience map in FEF validates the theoretical concept of a salience map in many models of attention. In addition, it strengthens the emerging view that FEF is not only involved in producing overt gaze shifts, but is also important for directing covert spatial attention.

Priming in macaque frontal cortex during popout visual search: feature-based facilitation and location-based inhibition of return.

In popout search, humans and monkeys are affected by trial-to-trial changes in stimulus features and target location. The neuronal mechanisms underlying such sequential effects have not been examined. Single neurons were recorded in the frontal eye field (FEF) of monkeys performing a popout search during which stimulus features and target position changed unpredictably across trials. Like previous studies, repetition of stimulus features improved performance. This feature-based facilitation of return was manifested in the target discrimination process in FEF: neurons discriminated the target from distractors earlier and better with repetition of stimulus features, corresponding to improvements in saccade latency and accuracy, respectively. The neuronal target selection was mediated by both target enhancement and distractor suppression. In contrast to the repetition of features, repetition of target position increased saccade latency. This location-based inhibition of return was reflected in the neuronal discrimination process but not in the baseline activity in FEF. These results show adjustments of the target selection process in FEF corresponding to and therefore possibly contributing to changes in performance across trials caused by sequential regularities in display properties.