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Prefrontal cortex and diverse functions
Keiji Tanaka
The prefrontal cortex (PFC) occupies the anterior part of the frontal lobe. Its proportion in the
brain has largely increased in the primate along the evolution. PFC receives converging
information of sensory inputs and motor plans via cortico-cortical and cortico-thalamocortical projections with the mediodorsal nucleus as the major thalamic relay site. PFC also
receives internal information from the limbic and subcortical structures, including the
hippocampus, amygdala, hypothalamus and diffusely projecting modulatory systems. Because
all these connections are reciprocal, PFC can, in turn, influence on activities and information
processing in other parts of the brain through the connections. In addition, PFC
undirectionally projects to the basal ganglia, which projects to the brain stem motor nuclei as
well as back to the cortical areas.
Neuropsychological and imaging studies on humans and neuropsychological and single-cell
recording studies on monkeys have provided the data on which our current ideas about the
functions of PFC are based. The most established concept is the working memory. Patients
with PFC damages have difficulties in the n-back task. The monkeys with dorsolateral PFC
lesion show difficulties in the delay tasks including the delayed alternation and delayed
matching to sample tasks. Single-cell recordings from the monkeys performing the delay
tasks (delayed alternation, oculomotor delayed-response and delayed matching to sample
tasks) showed that cells in the dorsolateral PFC maintain differential discharges during the
delay period. Cells in the temporal and parietal areas also show differential delay discharges,
but their discharges loose the information required by the task after presentation of
interrupting stimuli.
Patients with PFC damages show a wide range of problems. They are more impulsive in that
they tend to show imitation behavior and forced tool-use. It appears that the capability to
inhibit reflective actions for the sake of a longer-term goal is weak in these patients. They also
have problems in planning (e.g., in the tower of London task) and in reasoning (e.g., in the
Raven’s progressive matrices test). Because the planning and reasoning require working
memory, the problems in planning and reasoning may be due to their weaker working
memory capacity. Patients with damage in the ventromedial part of PFC tend to have a unique
type of problems in daily life by showing socially inappropriate behavior. The Iowa gambling
task has made an insight into their problems and the function of the ventromedial PFC (the
somatic marker hypothesis).
Single-cell recordings from monkeys have shown various types of non-sensory non-motor
representations by using tasks that are simpler than those used in human neuropsychology.
Responses of many PFC cells, which are time-locked to sensory cue presentation or
maintained during the delay, represent the action to be done later or the type of reward
expected to come later. Many cells in the lateral PFC represent the categories of stimuli
(object categories and numbers) and the behavioral rule to be used in the trial. These activities
may be building blocks to generate appropriate actions in the given condition.
The lecturer’s group has combined neuropsychological and single-cell recording studies in
monkeys by using an analog of the Wisconsin Card Sorting Test (WCST). In complicated
situations, the application of previously learned behavioral rules beyond simple stimulusresponse or outcome-response associations is often necessary, and the currently relevant rule
is often not directly indicated by sensory cues. The Wisconsin Card Sorting Test (WCST)
mimics such a situation. We have developed an animal version of WCST and trained monkeys
with the task. The monkey selected one of the three test stimuli by matching it with the
sample stimulus in color or in shape. The matching rule was constant within a block of trials,
but changed between blocks without giving any notice to the monkey. There was no cue to
indicate the currently relevant rule: the monkey had to determine the rule based on the reward
given for correct responses. Lesioning of the principal sulcus region (PS), the orbitofrontal
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region (OFC) and the anterior cingulated sulcus region (ACCs) resulted in significant
degradation of the overall performance of the monkeys. Further analyses of the monkeys’
performance in the task and in other probe tests showed that the reasons of the degradation
were different. Only the PS lesion impaired maintenance of abstract rules in working
memory; only the OFC lesion impaired rapid reward-based updating of rule value; and the
ACCs lesion impaired active reference to the content of the rule working memory. Single-cell
recordings from the PS of intact monkeys have shown that many cells there show differential
discharges between shape and color blocks.
References
1)Funahashi S, Bruce CJ, Goldman-Rakic PS (1989) Mnemonic coding of visual space in the
monkey’s dorsolateral prefrontal cortex. J. Neurophysiol. 61: 331-349.
2)Thompson-Schill SL, Swick D, Farah MJ, D’Esposito M, Kan IP, Knight RT (1998) Verb
generation in patients with focal frontal lesions: a neuropsychological test of neuroimaging
findings. Proc. Natl. Acad. Sci. USA 95: 15855-15860.
3)Shallice T (1982) Specific impairments of planning. Phil. Trans. R. Soc. Lond. B 298: 199209.
4)Waltz JA, Knowlton BJ, Holyoak KJ, Boone KB, Mishkin FS, Santos MD, Thomas CR,
Miller BL (1999) A system for relational reasoning in human prefronal cortex. Psychol. Sci.
10: 119-125.
5)Bechara A, Damasio AR, Damasio H, Anderson SW (1994) Insensitivity to future
consequences following damage to human prefrontal cortex. Cognition 50: 7-15.
6)Damasio AR (1994) Descartes’ Error: Emotion, Reason, and the Human Brain. G. P.
Putnam (New York).
7)Watanabe M (1986) Prefrontal unit activity during delayed conditional Go/No-Go
discrimination in the monkey. I. relation to the stimulus. Brain Res. 382: 1-14.
8)Watanabe M (1990) Prefrontal unit activity during associative learning in the monkey. Exp.
Brain Res. 80: 296-309.
9)Freedman DJ, Riesenhuber M, Poggio T, Miller EK (2001) Categorical representation of
visual stimuli in the primate prefrontal cortex. Science 291: 312-316.
10) Minamimooto T, Saunders RC, Richmond BJ (2010) Monkeys quickly learn and
generalize visual categories without lateral prefrontal cortex. Neuron 66: 501-507.
11)Nider A, Freedman DJ, Miller EK (2002) Representation of the quantity of visual items in
the primae prefrontal cortex. Science 297: 1708-1711.
12)Wallis JD, Anderson KC, Miller EK (2001) Single neurons in prefrontal cortex encode
abstract rules. Nature 411: 953-956.
13)Mansouri FA, Tanaka K (2002) Behavioral evidence for working memory of sensory
dimension in macaque monkeys. Behav. Brain Res. 136: 415-426.
14)Mansouri F, Matsumoto K, Tanaka K (2006) Prefrontal cell activities related to monkeys’
success and failure in adapting to rule changes in a Wisconsin Card Sorting Test (WCST)
analog. J. Neurosci. 26: 2745-2756.
15)Mansouri FA, Buckley MJ, Tanaka K (2007) Mnemonic function of lateral prefrontal
cortex in conflict-induced behavioral adjustment. Science 318: 987-990.
16)Buckley MJ, Mansouri FA, Hoda H, Mahboubi M, Browning PFG, Kwok SC, Phillips A,
Tanaka K (2009) Dissociable components of rule-guided behavior depend on distinct medial
and prefrontal regions. Science 325: 52-58.
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