Differential neuronal responsiveness in primate perirhinal cortex and hippocampal formation during performance of a conditional visual discrimination task

Neuronal responses in the hippocampal formation, including the entorhinal cortex, have been compared with those in the inferior temporal cortex, including the perirhinal cortex, during performance by monkeys of a visual conditional discrimination task. In the task, the arrangement of three geometric shapes determined the correctness of either a left or right behavioural response according to a conditional rule. Neurons that responded differently to different types of trial were common (50% of the visually responsive neurons) in the entorhinal cortex, perirhinal cortex and area TE of the inferior temporal cortex, but significantly less common in the hippocampus (13%). This differential incidence suggests a more important role for the rhinal cortices and area TE than for the hippocampus in this task. Based on the neuronal responses, arguments are advanced that the animals probably solved the task by a strategy that did not require spatial or hippocampal processing. Thus, of the differential responses, those that would allow the animals to solve the task by using a conditional rule and so avoid spatial processing were twice as common (37%) as those allowing solution to be by selection of a particular spatially directed response to each arrangement of shapes (19%). Moreover, the differential latencies of responses that allowed the task to be solved by a conditional rule were shorter (< approximately 165 ms), and hence processing was faster, than those that provided information about particular individual types of trial ( approximately 195 ms). Even so, hippocampal responsiveness in the conditional task was differentially enhanced when compared with that during a recognition memory task, and the neuronal responses potentially allow the animal to employ a second, alternative strategy that might be expected to depend on hippocampal processing.     

Anticipatory activity in rat medial prefrontal cortex during a working memory task

Objective Working memory is a key cognitive function in which the prefrontal cortex plays a crucial role. This study aimed to show the firing patterns of a neuronal population in the prefrontal cortex of the rat in a working memory task and to explore how a neuronal ensemble encodes a working memory event.Methods Sprague-Dawley rats were trained in a Y-maze until they reached an 80%correct rate in a working memory task.Then a 16-channel microelectrode array was implanted in the prefrontal cortex.After recovery,neuronal population activity was recorded during the task, using the Cerebus data-acquisition system.Spatio-temporal trains of action potentials were obtained from the original neuronal population signals.Results During the Y-maze working memory task,some neurons showed significantly increased firing rates and evident neuronal ensemble activity.Moreover,the anticipatory activity was associated with the delayed alternate choice of the upcoming movement.In correct trials,the averaged pre-event firing rate(10.86±1.82 spikes/ bin) was higher than the post-event rate(8.17±1.15 spikes/bin)(P <0.05).However,in incorrect trials,the rates did not differ.Conclusion The results indicate that the anticipatory activity of a neuronal ensemble in the prefrontal cortex may play a role in encoding working memory events.     

Functional interactions between inferotemporal and prefrontal cortex in a cognitive task

Monkeys were trained to perform a visual short-term memory task (delayed matching to sample). In some of the animals, cooling probes were implanted over dorsolateral prefrontal cortex, covering sulcus principalis and adjacent areas; microelectrode pedestals were implanted over inferotemporal cortex. Other animals were fitted with converse implants: cooling probes over a portion of the inferotemporal cortical convexity and microelectrode pedestals over prefrontal cortex. In the awake and behaving monkeys, bilateral cooling of either the prefrontal or the inferotemporal region (to 20 °C) induced, in the other region, reversible changes of spontaneous and task-related cell discharge. In the two cortices remote cooling induced augmentations and diminutions of cell reaction to the color samples which the animal had to retain for correct performance of the task. The same was true for cell discharge during the delay, the retention period which followed each sample. However, a net effect of remote cooling was, in both cortices, a diminution of color-dependent differences in the reactions and delay-discharge of some cells. Concomitantly, errors of task-performance increased. Cells that as a result of remote cortical cooling showed changes of reaction to the color samples were found more commonly in supragranular than infragranular layers. The results are interpreted as evidence of mutual influences between inferotemporal and prefrontal areas probably mediated by corticocortical connections. The single-cell data, together with the behavioral data, suggest that those influences are functionally important for visual discrimination and short-term memory.     

Neuronal activity in the monkey dorsolateral prefrontal cortex during a discrimination task with delay

Ninety-nine single neuron activities of the dorsolateral prefrontal cortex of 3 monkeys were recorded during performance of a Konorski task. Green or red lights were presented successively with a separation of fixed delay interval. The monkey responded as soon as the second stimulus was presented. If the two stimuli were color-matched, the ‘YES’ lever press was rewarded; if the two stimuli were not, the ‘NO’ lever press was rewarded. In the second task, after paired color stimuli, a tone pip was presented as the ‘GO’ signal for lever presses. During sample and matching periods 50 neurons increased their discharge rates and 10 decreased. In 86% of increasing type neurons rate increase occurred during both periods. During auditory GO periods, 27 neurons increased their rates and 11 decreased. Discharge peak was before or at the moment of hold key release. In 60% of these neurons were also observed the rate changes to sample and matching stimuli. Differential activations between left and right levers were found in 20%. It was suggested that the prefrontal cortex is related to a sensorial attention mechanism to the visual stimulus which enables correct choice of the behavior to be rewarded.     

Spatial and temporal distribution of visual information coding in lateral prefrontal cortex

Prefrontal neurons code many kinds of behaviourally relevant visual information. In behaving monkeys, we used a cued target detection task to address coding of objects, behavioural categories and spatial locations, examining the temporal evolution of neural activity across dorsal and ventral regions of the lateral prefrontal cortex (encompassing parts of areas 9, 46, 45A and 8A), and across the two cerebral hemispheres. Within each hemisphere there was little evidence for regional specialisation, with neurons in dorsal and ventral regions showing closely similar patterns of selectivity for objects, categories and locations. For a stimulus in either visual field, however, there was a strong and temporally specific difference in response in the two cerebral hemispheres. In the first part of the visual response (50–250 ms from stimulus onset), processing in each hemisphere was largely restricted to contralateral stimuli, with strong responses to such stimuli, and selectivity for both object and category. Later (300–500 ms), responses to ipsilateral stimuli also appeared, many cells now responding more strongly to ipsilateral than to contralateral stimuli, and many showing selectivity for category. Activity on error trials showed that late activity in both hemispheres reflected the animal's final decision. As information is processed towards a behavioural decision, its encoding spreads to encompass large, bilateral regions of prefrontal cortex.     

Rule-dependent shifting of sensorimotor representation in the primate prefrontal cortex

When we react to the outer world, perceived sensory information is frequently memorized over a temporal interval then transformed into a motor command based on a behavioural rule. In this type of memory-based sensorimotor transformation, working memory is considered to play an important role. It has been suggested that the lateral prefrontal cortex is involved in the process of the working memory. However, the neuronal mechanism for guiding a motor command from the working memory has not been established. To examine how visuospatial working memory is linked with a forthcoming saccade direction, we used an antisaccade paradigm for monkeys in which a behavioural rule was presented in the middle of a delay period. In this task, the subjects were required to maintain cue location and to select a response based on a behavioural rule. We found that a subset of mnemonic neurons in the lateral prefrontal cortex changed their representation from cue to saccade direction. Furthermore, the discriminability for saccade direction of these neurons tended to appear soon after the behavioural rule presentation, indicating their significant dependency on the behavioural rule. These results suggest that a subset of mnemonic neurons in the lateral prefrontal cortex change their activity depending on a behavioural rule to guide a prospective motor command.     

Flexible spatial learning requires both the dorsal and ventral hippocampus and their functional interactions with the prefrontal cortex

When faced with changing contingencies, animals can use memory to flexibly guide actions, engaging both frontal and temporal lobe brain structures. Damage to the hippocampus (HPC) impairs episodic memory, and damage to the prefrontal cortex (PFC) impairs cognitive flexibility, but the circuit mechanisms by which these areas support flexible memory processing remain unclear. The present study investigated these mechanisms by temporarily inactivating the medial PFC (mPFC), the dorsal HPC (dHPC), and the ventral HPC (vHPC), individually and in combination, as rats learned spatial discriminations and reversals in a plus maze. Bilateral inactivation of either the dHPC or vHPC profoundly impaired spatial learning and memory, whereas bilateral mPFC inactivation primarily impaired reversal versus discrimination learning. Inactivation of unilateral mPFC together with the contralateral dHPC or vHPC impaired spatial discrimination and reversal learning, whereas ipsilateral inactivation did not. Flexible spatial learning thus depends on both the dHPC and vHPC and their functional interactions with the mPFC.     

Acute cocaine administration increases NO efflux in the rat prefrontal cortex via a neuronal NOS-dependent mechanism

An understanding of the neurochemical changes occurring following exposure to psychostimulants such as cocaine is critical for the development of novel pharmacotherapies aimed at disrupting the addictive cycle. It is well established that the acute effects of cocaine associated with drug-induced blockade of dopamine (DA) reuptake processes occur in reward-related areas of the brain including the medial prefrontal cortex (mPFC). Considerable evidence has accumulated indicating that the interaction between DA, glutamate, and nitric oxide (NO) is likely to play a critical role in the neuroplastic changes associated with psychostimulant exposure. However, the potential impact of cocaine on NO synthase (NOS) activity in the mPFC has not been examined. In this study, NO efflux was measured in the mPFC of anesthetized male rats using a NO-selective electrochemical microsensor. Acute systemic administration of cocaine significantly increased NO efflux in the mPFC in a time-dependent manner. Similar injections using vehicle did not affect NO efflux. The facilitatory effect of cocaine on NO efflux was transient and reproducible. The signal was derived from neuronal sources of NO, because it was attenuated by systemic administration of the neuronal NO synthase inhibitor 7-nitroindazole. These studies support a role for prefrontal cortical NO signaling in cocaine-induced changes in neurotransmission in reward-related circuits involved in addiction.     

Time discrimination with positional responses after selective prefrontal lesions in monkeys

Monkeys with ablations of the cortex in the principal sulcus who were impaired on a spatial delayed reaction test were unimpaired on a time discrimination test in which length of time since the last trial signalled the spatial position of the correct foodwell. The finding undermines the view that the classical delayed reaction deficit after lateral prefrontal lesions reflects the loss of temporal structuring of the stream of sensory input. The result is consistent instead with the alternative view that the classical deficit reflects a spatial memory disorder. Monkeys with inferior prefrontal ablations were impaired on both spatial tasks, and on object discrimination reversal as well; analysis of their deficits indicated that they were instances of perseverative interference. Finally, monkeys with ablations of the cortex in the arcuate sulcus were not consistently impaired on any of the tasks. There is no evidence from these results that prefrontal cortex plays any role in time perception.     

Ventrolateral prefrontal cortex is required for performance of a strategy implementation task but not reinforcer devaluation effects in rhesus monkeys

The ability to apply behavioral strategies to obtain rewards efficiently and make choices based on changes in the value of rewards is fundamental to the adaptive control of behavior. The extent to which different regions of the prefrontal cortex are required for specific kinds of decisions is not well understood. We tested rhesus monkeys with bilateral ablations of the ventrolateral prefrontal cortex on tasks that required the use of behavioral strategies to optimize the rate with which rewards were accumulated, or to modify choice behavior in response to changes in the value of particular rewards. Monkeys with ventrolateral prefrontal lesions were impaired in performing the strategy-based task, but not on value-based decision-making. In contrast, orbital prefrontal ablations produced the opposite impairments in the same tasks. These findings support the conclusion that independent neural systems within the prefrontal cortex are necessary for control of choice behavior based on strategies or on stimulus value.     

Age-related valence-based reversal in recruitment of medial prefrontal cortex on a visual search task

Previous behavioral research has revealed a positivity effect that occurs with aging, with older adults focusing more on positive information and less on negative emotional stimuli as compared to young adults. Questions have been raised as to whether this effect exists in the rapid detection of information or whether it operates only at later stages of processing. In the present study, we used eye-tracking and neuroimaging methodologies to examine whether the two age groups accomplished the detection of emotional information on a visual search task using the same mechanisms. Eye-tracking results revealed no significant age differences in detection or viewing time of emotional targets as a function of valence. Despite their general similarity in task performance, neuroimaging results revealed an age-related valence-based reversal in medial prefrontal cortex (MPFC) activity, with detection of negative compared to positive targets activating the MPFC more for younger adults, and detection of positive compared to negative targets activating the MPFC more for older adults. These results suggest that age-related valence reversals in neural activity can exist even on tasks that require only relatively automatic processing of emotional information.     

Feature to space conversion during target selection in the dorsolateral and ventrolateral prefrontal cortex of monkeys

To investigate the neuronal mechanism of the process of selection of a target from an array of stimuli, we analysed neuronal activity of the lateral prefrontal cortex during the response period of a serial probe reproduction task. During the response period of this task, monkeys were trained to select a memorized target object from an array of three objects and make a saccadic eye movement toward it. Of 611 neurons, 74 neurons showed visual response and 56 neurons showed presaccadic activity during the response period. Among visual neurons, 27 showed array‐ and target‐selectivity. All of these array‐ and target‐selective visual responses were recorded from the ventrolateral prefrontal cortex (VLPFC). Among 56 neurons with presaccadic activity, nine showed target‐selective activity, 17 showed target‐ and direction‐selective activity, and 23 showed direction‐selective activity. The target‐selective, and the target‐ and direction‐selective activities were recorded from the VLPFC, and the direction‐selective activities were recorded from VLPFC and dorsolateral prefrontal cortex (DLPFC). The starting time of the activity was earlier for the target‐selective, and target‐ and direction‐selective activities in VLPFC, intermediate for the direction‐selective activities in VLPFC, and later for the direction‐selective activities in DLPFC. These results suggest that VLPFC plays a role in the process of selection of a target object from an array of stimuli, VLPFC and DLPFC play a role in determining the location of the target in space, and DLPFC plays a role in selecting a direction and making a decision to generate a saccadic eye movement.     

Properties and distribution of auditory neurons in the dorsolateral prefrontal cortex of the alert monkey

In alert monkeys, some prefrontal neurons located in the superior dorsolateral area were activated to acoustic stimuli delivered in a restricted range of directions with respect to the animal's head. The effective direction was usually contralateral to the animal. The function of the auditory neurons in connection to that of the visual ones, which are commonly found in the prefrontal cortex, is discussed.     

Representations of visual proportions in the primate posterior parietal and prefrontal cortices

The primate prefrontal (PFC) and posterior parietal cortices (PPC) have been shown to be cardinal structures in processing abstract absolute magnitudes, such as numerosity or length. The neuronal representation of quantity relations, however, remained largely elusive. Recent functional imaging studies in humans showed that blood flow changes systematically both in the PFC and the PPC as a function of relational distance between proportions. We investigated the response properties of single neurons in the lateral PFC and the inferior parietal lobule (IPL, area 7) in rhesus monkeys performing a lengths-proportion-discrimination task. Neurons in both areas shared many characteristics and showed peaked tuning functions with preferred proportions. However, a significantly higher percentage of neurons coding proportions was found in the PFC compared with the IPL. In agreement with human studies, our study shows that proportions are represented in the fronto-parietal network that has already been implicated for absolute magnitude processing.     

Functional heterogeneity of single neuronal activity in the monkey dorsolateral prefrontal cortex

Extracellular single unit recording during high fixed ratio bar press behavior, guided by multimodal cue stimuli for food intake, revealed functional heterogeneity in the monkey dorsolateral prefrontal cortex. Cells were found significantly more often in the ventral arcuate concavity, the dorsal arcuate concavity, the principal sulcal area and the inferior convexity which responded, respectively, to visual events, auditory events, visual plus auditory events and bar press.     

Increased activity in the right prefrontal cortex measured using near-infrared spectroscopy during a flower arrangement task

Objective: Flower arrangement program (FAP) horticultural therapy promotes psychological, social and physiological wellness and recovery. Moreover, FAPs have been used to evaluate the outcomes related to visuospatial working memory; yet, most of these studies used subjective outcome measures such as behavioural observations and questionnaires. Few studies report objective evaluations of FAP effects in humans. In the present study, we measured the effects of an FAP task on frontal lobe activity in healthy participants using near-infrared spectroscopy. We quantified salivary amylase levels as an indicator of stress level during the FAP.

Methods: The FAP task involved a predetermined arrangement pattern of natural materials (flowers and leaves) that required the participants to identify where a given material should be placed and temporarily memorise the designated position to complete the flower arrangement. The FAP task was compared to the block-tapping task (BTT), which is routinely used to evaluate visuospatial working memory.

Results: Both the FAP task and BTT positively stimulated the right prefrontal cortex; however, stress was more effectively limited during the performance of the FAP task.

Conclusions: Our data suggest that FAP therapy may be useful for the rehabilitation of patients who are sensitive to stress.     

Magnetic stimulation of the dorsolateral prefrontal cortex dissociates fragile visual short-term memory from visual working memory

To guide our behavior in successful ways, we often need to rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). While VSTM is usually broken down into iconic memory (brief and high-capacity store) and visual working memory (sustained, yet limited-capacity store), recent studies have suggested the existence of an additional and intermediate form of VSTM that depends on activity in extrastriate cortex. In previous work, we have shown that this fragile form of VSTM can be dissociated from iconic memory. In the present study, we provide evidence that fragile VSTM is different from visual working memory as magnetic stimulation of the right dorsolateral prefrontal cortex (DLPFC) disrupts visual working memory, while leaving fragile VSTM intact. In addition, we observed that people with high DLPFC activity had superior working memory capacity compared to people with low DLPFC activity, and only people with high DLPFC activity really showed a reduction in working memory capacity in response to magnetic stimulation. Altogether, this study shows that VSTM consists of three stages that have clearly different characteristics and rely on different neural structures. On the methodological side, we show that it is possible to predict individual susceptibility to magnetic stimulation based on functional MRI activity.     

Delay-related activity of prefrontal neurons in rhesus monkeys performing delayed response

Activity of dorsolateral prefrontal cortical neurons was examined in rhesus monkeys while they performed a spatial delayed-response task with delays of 2, 4, 8 or 12 s interposed between cue and response. Of the 600 neurons recorded for at least 10 trials under each delay condition, 95 displayed a pattern of discharge during the delay period which was significantly different from neuronal firing before or after this period. Changes in the duration of the delay elicit two distinct patterns of activity in these neurons: some (59/95, 62%) exhibit a fixed pattern of discharge regardless of the duration of the ensuing delay; others (31/95, 33%) alter their pattern of activity in relation to the temporal changes. Although both types of delay-related neurons display a variety of discharge profiles, more than half of each class exhibit their highest activity in the early part of the delay period. A related finding concerns a small subclass of spatially selective neurons which fire significantly more when the cue is presented on the left than on the right or vice versa. A striking 80% of these spatially discriminative neurons exhibit peak activity in the first few seconds of the delay period. These findings provide cellular evidence that (1) prefrontal neurons are responsive to temporal as well as spatial features of the delayed-response task; and (2) the involvement of a subset of these is particularly critical in the first few seconds of the delay. The latter finding emphasizes that prefrontal neurons may play an important role in the registration process of spatial memory.