Fumi Katsuki

Early involvement of prefrontal cortex in visual bottom-up attention

Visual attention is guided to stimuli either on the basis of their intrinsic saliency against their background (bottom-up factors) or through willful search of known targets (top-down factors). Posterior parietal cortex (PPC) is thought to be important for the guidance of visual bottom-up attention, whereas dorsolateral prefrontal cortex is thought to represent top-down factors. Contrary to this established view, we found that, when monkeys were tested in a task requiring detection of a salient stimulus defined purely by bottom-up factors and whose identity was unknown before the presentation of a visual display, prefrontal neurons represented the salient stimulus no later than those in the PPC. This was true even though visual response latency was shorter in parietal than in prefrontal cortex. These results suggest an early involvement of the prefrontal cortex in the bottom-up guidance of visual attention.

Comparison of neural activity related to working memory in primate dorsolateral prefrontal and posterior parietal cortex.

Neurons in a distributed network of cortical and subcortical areas continue to discharge after the presentation and disappearance of stimuli, providing a neural correlate for working memory. While it is thought that the prefrontal cortex plays a central role in this network, the relative contributions of other brain areas are not as well understood. In order to compare the contributions of the dorsolateral prefrontal and posterior parietal cortex, we recorded neurophysiological activity in monkeys trained to perform two different visuo-spatial working memory tasks: a Match/Nonmatch task, and a Spatial Delayed-Match-to-Sample Task. Neurons in both areas exhibited discharges in the delay periods of the tasks that could be classified in two forms. Sustained discharges persisted after the presentation of a stimulus in the receptive field with a constant or declining rate. Anticipatory responses increased in rate during the delay period, often appearing after presentation of a stimulus out of the receptive field. Despite similarities, we uncovered distinct differences between patterns of delay period in each brain area. Only in the prefrontal cortex sustained responses related to the original stimulus survived presentation of a second stimulus, in the context of the Match/Nonmatch task. Our results provide insights on the nature of processing in two areas active during working memory, and on the unique role of the prefrontal cortex in memory maintenance.

Unique and shared roles of the posterior parietal and dorsolateral prefrontal cortex in cognitive functions

The dorsolateral prefrontal cortex (PFC) and posterior parietal cortex (PPC) are two parts of a broader brain network involved in the control of cognitive functions such as working-memory, spatial attention, and decision-making. The two areas share many functional properties and exhibit similar patterns of activation during the execution of mental operations. However, neurophysiological experiments in non-human primates have also documented subtle differences, revealing functional specialization within the fronto-parietal network. These differences include the ability of the PFC to influence memory performance, attention allocation, and motor responses to a greater extent, and to resist interference by distracting stimuli. In recent years, distinct cellular and anatomical differences have been identified, offering insights into how functional specialization is achieved. This article reviews the common functions and functional differences between the PFC and PPC, and their underlying mechanisms.

Bottom-Up and Top-Down Attention Different Processes and Overlapping Neural Systems

The brain is limited in its capacity to process all sensory stimuli present in the physical world at any point in time and relies instead on the cognitive process of attention to focus neural resources according to the contingencies of the moment. Attention can be categorized into two distinct functions: bottom-up attention, referring to attentional guidance purely by externally driven factors to stimuli that are salient because of their inherent properties relative to the background; and top-down attention, referring to internal guidance of attention based on prior knowledge, willful plans, and current goals. Over the past few years, insights on the neural circuits and mechanisms of bottom-up and top-down attention have been gained through neurophysiological experiments. Attention affects the mean neuronal firing rate as well as its variability and correlation across neurons. Although distinct processes mediate the guidance of attention based on bottom-up and top-down factors, a common neural apparatus, the frontoparietal network, is essential in both types of attentional processes.

Neurons with inverted tuning during the delay periods of working memory tasks in the dorsal prefrontal and posterior parietal cortex

The dorsolateral prefrontal and posterior parietal cortices are two interconnected brain areas that are coactivated in tasks involving functions such as spatial attention and working memory. The response properties of neurons in the two areas are in many respects indistinguishable, yet only prefrontal neurons are able to resist interference by distracting stimuli when subjects are required to remember an initial stimulus. Several mechanisms have been proposed that could account for this functional difference, including the existence of specialized interneuron types, specific to the prefrontal cortex. Although such neurons with inverted tuning during the delay period of a working memory task have been described in the prefrontal cortex, no comparative data exist from other cortical areas that would establish a unique prefrontal role. To test this hypothesis, we analyzed a large database of recordings obtained in the dorsolateral prefrontal and posterior parietal cortex of the same monkeys as they performed working memory tasks. We found that in the prefrontal cortex, neurons with inverted tuning were more numerous and manifested unique properties. Our results give credence to the idea that a division of labor exists between separate neuron types in the prefrontal cortex and that this represents a functional specialization that is not present in its cortical afferents.

Age-dependent changes in prefrontal intrinsic connectivity

Significance The prefrontal cortex, the brain area associated with higher cognitive operations such as working memory and executive function, undergoes a protracted period of development. How the activity of prefrontal neurons changes during peri- and postpubertal cortical maturation is largely unknown. To address this question, we recorded neuronal activity from the prefrontal cortex of peripubertal and adult monkeys and compared the functional connectivity between pairs of neurons in each group. The magnitude of connectivity measured between neurons was lower overall in the prefrontal cortex of peripubertal monkeys compared with adults, as inhibitory interactions were generally stronger in young animals. Our results identify changes in intrinsic connectivity between prefrontal neurons as a possible substrate for peri- and postpubertal cognitive maturation. The prefrontal cortex continues to mature after puberty and into early adulthood, mirroring the time course of maturation of cognitive abilities. However, the way in which prefrontal activity changes during peri- and postpubertal cortical maturation is largely unknown. To address this question, we evaluated the developmental stage of peripubertal rhesus monkeys with a series of morphometric, hormonal, and radiographic measures, and conducted behavioral and neurophysiological tests as the monkeys performed working memory tasks. We compared firing rate and the strength of intrinsic functional connectivity between neurons in peripubertal vs. adult monkeys. Notably, analyses of spike train cross-correlations demonstrated that the average magnitude of functional connections measured between neurons was lower overall in the prefrontal cortex of peripubertal monkeys compared with adults. The difference resulted because negative functional connections (indicative of inhibitory interactions) were stronger and more prevalent in peripubertal compared with adult monkeys, whereas the positive connections showed similar distributions in the two groups. Our results identify changes in the intrinsic connectivity of prefrontal neurons, particularly that mediated by inhibition, as a possible substrate for peri- and postpubertal advances in cognitive capacity.

Differences in Intrinsic Functional Organization Between Dorsolateral Prefrontal and Posterior Parietal Cortex

The dorsolateral prefrontal and posterior parietal cortex are 2 components of the cortical network controlling attention, working memory, and executive function. Little is known about how the anatomical organization of the 2 areas accounts for their functional specialization. In order to address this question, we examined the strength of intrinsic functional connectivity between neurons sampled in each area by means of cross-correlation analyses of simultaneous recordings from monkeys trained to perform working memory tasks. In both areas, effective connectivity declined as a function of distance between neurons. However, the strength of effective connectivity was higher overall and more localized over short distances in the posterior parietal than the prefrontal cortex. The difference in connectivity strength between the 2 areas could not be explained by differences in firing rate or selectivity for the stimuli and task events, it was present when the fixation period alone was analyzed, and according to simulation results, was consistent with a systematic difference either in the strength or in the relative numbers of shared inputs between neurons. Our results indicate that the 2 areas are characterized by unique intrinsic functional organization, consistent with known differences in their response patterns during working memory.

Influence of monkey dorsolateral prefrontal and posterior parietal activity on behavioral choice during attention tasks.

The dorsolateral prefrontal and the posterior parietal cortex have both been implicated in the guidance of visual attention. Traditionally, posterior parietal cortex has been thought to guide visual bottom‐up attention and prefrontal cortex to bias attention through top‐down information. More recent studies suggest a parallel time course of activation of the two areas in bottom‐up attention tasks, suggesting a common involvement, though these results do not necessarily imply identical roles. To address the specific roles of the two areas, we examined the influence of neuronal activity recorded from the prefrontal and parietal cortex of monkeys as they performed attention tasks based on choice probability and on correlation between reaction time and neuronal activity. The results revealed that posterior parietal but not dorsolateral prefrontal activity correlated with behavioral choice during the fixation period, prior to the appearance of the stimulus, resembling a bias factor. This preferential influence of posterior parietal activity on behavior was transient, so that dorsolateral prefrontal activity predicted choice after the appearance of the stimulus. Additionally, reaction time was better predicted by posterior parietal activity. These findings confirm the involvement of both dorsolateral prefrontal and posterior parietal cortex in the bottom‐up guidance of visual attention, but indicate different roles of the two areas in the guidance of attention and a dynamic time course of their effects, influencing behavior at different stages of the task.

Time Course of Functional Connectivity in Primate Dorsolateral Prefrontal and Posterior Parietal Cortex during Working Memory

The dorsolateral prefrontal and posterior parietal cortex play critical roles in mediating attention, working memory, and executive function. Despite proposed dynamic modulation of connectivity strength within each area according to task demands, scant empirical data exist about the time course of the strength of effective connectivity, particularly in tasks requiring information to be sustained in working memory. We investigated this question by performing time-resolved cross-correlation analysis for pairs of neurons recorded simultaneously at distances of 0.2–1.5 mm apart of each other while monkeys were engaged in working memory tasks. The strength of effective connectivity determined in this manner was higher throughout the trial in the posterior parietal cortex than the dorsolateral prefrontal cortex. Significantly higher levels of parietal effective connectivity were observed specifically during the delay period of the task. These differences could not be accounted for by differences in firing rate, or electrode distance in the samples recorded in the posterior parietal and prefrontal cortex. Differences were present when we restricted our analysis to only neurons with significant delay period activity and overlapping receptive fields. Our results indicate that dynamic changes in connectivity strength are present but area-specific intrinsic organization is the predominant factor that determines the strength of connections between neurons in each of the two areas.