Prefrontal Cortex and Memory in Primates
PREFRONTAL CORTEX AND MEMORY IN PRIMATES
A primate needs its prefrontal cortex for behavior based on information accumulated before the moment of action. The prefrontal cortex is especially important if the information is new to the organism or conflicts with prior cues or memories that call for different actions. Whether the information is new or old, it must be retained in memory until the moment it can inform an act. It is the prefrontal cortex that supports this short-term memory (also called working memory) that subserves behavior.
Prefrontal memory is a matter not of content or duration but of context, the context of action. Short-term memory is not the only function of the prefrontal cortex, nor is it exclusively the role of the prefrontal cortex. But, insofar as action requires short-term memory, it also needs the prefrontal cortex. It follows that this part of the cortex is essential for the construction of sequential behaviors, especially if they are novel or require choices. It is needed for the syntax of the action, including, of course, the syntax of the spoken language, particularly creative speech.
The prefrontal cortex is the cortex of the pole of the frontal lobe. It is that part of the cerebral cortex to which the nucleus mediodorsalis of the thalamus projects. Phylogenetically, it is the neocortical region that undergoes the greatest and latest expansion (see Figure 1). It reaches maximum development in the brain of the human, where it occupies almost one-third of the totality of the neocortex. In the course of evolution, its dorsolateral aspect, that is, the cortex of the external convexity of the frontal lobe, develops relatively more than its medial and inferior aspects. This is an important consideration because the dorsolateral prefrontal cortex supports mainly cognitive functions, whereas the orbitomedial prefrontal cortex mostly pertains to emotional and visceral functions.
Cytoarchitectonically, the prefrontal cortex of the primate (area FD of Von Bonin and Bailey, 1947) includes areas 9, 10, 11, 12, and 13 of Brodmann (1909). It is one of the best-connected of all neocortical regions; it is directly and reciprocally connected to the anterior and dorsal thalamus, the hypothalamus, and limbic structures, especially the amygdala and the hippocampus. It sends profuse efferent fibers to the basal ganglia. Dorsolateral prefrontal areas have rich reciprocal connections with many other neocortical areas of the frontal lobe and of the temporal and parietal lobes. The first clear indication of the involvement of the prefrontal cortex in short-term memory was provided by Jacobsen in the early 1930s (Jacobsen, 1935). He showed that monkeys with lesions of the dorsolateral prefrontal cortex are impaired in the learning and performance of delayed response (DR) and delayed alternation (DA) tasks. These tasks fall within a general category of behavioral tasks—delay tasks—that demand from the animal the performance of motor acts in accord with sensory information presented a few seconds or minutes earlier. In other words, delay tasks demand short-term memory for the logical and consequent bridging of temporal gaps between perception and action, the mediation of cross-temporal contingencies of behavior. Primates deprived of substantial portions of dorsolateral prefrontal cortex cannot properly perform delay tasks, regardless of the nature of the sensory information that guides them, especially if after a long delay between sensory cue and motor response.
There appears, however, to be some specificity of prefrontal areas with regard to the type of sensory information they help retain. Lesions of the cortex of the sulcus principalis are most detrimental to performance of delay tasks with spatially defined sensory cues, such as DR and DA. However, time seems to override space on this matter. Those spatial tasks are impaired only when a delay occurs between cue and response. The critical factor is the time during which the cue must be retained. Furthermore, dorsolateral prefrontal lesions also impair performance of delay tasks in which the sensory cue is not spatially defined, a correlation that has been demonstrated by local cortical cooling. The cryogenic depression of a large portion of dorsolateral cortex (area 9), including the sulcus principalis, induces a reversible deficit in performance of delay tasks, whether the cue is visual and spatially defined (as in DR) or not (as in delayed matching to sample). Furthermore, the cryogenic deficit also affects delayed matching tasks in which the cue (sample) is perceived by active touch (haptically).
Humans with dorsolateral prefrontal lesions also show impairments in delay tasks. Tasks in which the material to be retained can be verbally encoded are affected more by lesions of the left than of the right prefrontal cortex. They are impaired most of all by bilateral lesions. The human prefrontal syndrome usually involves disorders of attention, planning, and language. Prefrontal patients have difficulty maintaining attention on internal cues or short-term retention of mental material. Their planning is poor for both the short and the long term; it is as if they lacked "memory of the future" in addition to memory of the recent past. Both retrospective and prospective representations are needed for the sequential construction not only of external motor action but also of "internal action," such as sequential logical thinking—hence the trouble the patients have in this kind of activity, whether expressed in spoken language or not. Speech is most impaired if it requires the bridging of long intervals (cross-temporal contingencies) between subjects and verbs, subjects and predicates, or logically interdependent sentences. The trouble is extreme in lesions of Broca's area, which is a part of the prefrontal cortex specialized in the most elementary aspects of linguistic syntax. Animal and human neuropsychology thus suggests that the prefrontal cortex is essential for bridging cross-temporal contingencies of behavior, and that this is so at least in part because of its role in short-term memory.
Microelectrode recording in the monkey has corroborated the role of the prefrontal cortex in short-term memory. Prefrontal neurons show sustained activation of firing during the delay periods of delay tasks (see Figure 2). Statistical analysis and control experiments indicate that this activation is
- a result of learning the task;
- dependent on the presence of a cross-temporal contingency between cue and motor response;
- related in some cells to the property of the cue on which the response depends;
- related in some cells to the response that the animal has to execute at the end of the delay;
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- directly related to the efficacy with which the animal performs the task.
All these indications are consistent with the assumption that prefrontal neurons participate in cortical networks that, by their sustained activation, retain sensory information as long as needed for prospective action.
The analysis of single-unit discharge in other areas of association cortex (inferotemporal and posterior parietal) during visual and haptic delay tasks has revealed sustained neuronal activations in those areas. This observation, in addition to the study of the effects of local cortical cooling on remote cortical cell discharge and delay-task performance, has led to the following inference: The prefrontal cortex exerts its role in short-term memory and preparation for action through close functional interplay with areas of posterior association cortex with which it is intimately and reciprocally connected. Thus, the activated cortical network that retains sensory information during behavior has several components in short-term memory. Posterior areas are involved in the network inasmuch as the information falls within their special modality (vision, audition, somesthesis, and so on). The prefrontal cortex is involved inasmuch as the information calls for prospective goal-directed action. The maintenance of activity in the network is assured by the continuous circulation of excitatory impulses within and between all contributing areas, including the prefrontal cortex if the outcome is to be a goal-directed action in accord with the sensory information.
The prefrontal cortex of the primate is a large and phylogenetically new part of the cerebral cortex that performs a critical function in short-term memory that subserves action. Thus, it is critically important for sequential behaviors with cross-temporal contingencies. In the human, such behaviors include the spoken language and logical thought, which is a form of sequential "inner action." The memory function of the prefrontal cortex is one of several functions that this cortex supports in cooperation with other associative cortical areas. These functions are essential for the syntax of action—for organization of behavior in the time domain.
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