Principles, Practices, and Positions in Neuropsychiatric Research: Proceedings of a Conference Held in June 1970 at the Walter Reed Army Institute of Research, Washington, D.C., in Tribute to Dr. David Mckenzie Rioch upon His Retirement as Director of the Neuropsychiatry Division of That Institute

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THE PROBLEM OF THE FRONTAL LOBE: A REINTERPRETATION

WALLE J.H. NAUTA,     Department of Psychology, Massachusetts Institute of Technology, Cambridge, Mass.

Publisher Summary

This chapter discusses the problem of the frontal lobe. As a result of the complexity of frontal lobe, the concepts concerning the function of man’s frontal lobes range between two widely separate extremes. On the one hand, there is the notion that this part of the brain is crucially involved in man’s highest mental faculties and on the other extreme, there is the conclusion that the only defects objectively demonstrable in frontal-lobe patients are of a perceptual nature. The wide divergence between these two views may be attributable in part at least to the common difficulty of determining clinically the precise extent and location of the cerebral tissue damage in human patients. The problems encountered in exploring these modality specific cortical fields are likely to be multiplied many times over in regions such as the frontal cortex, which are certain to be associated with more than one sensory modality. The problem of identifying the natural stimuli consistently capable of eliciting responses by a sufficiently large number of cortical units in such regions might prove quite elusive.

INTRODUCTION

THE FRONTAL lobe, despite decades of intensive research by physiologists, anatomists and clinicians, has remained the most mystifying of the major subdivisions of the cerebral cortex. Unlike any other of the great cerebral promontories, the frontal lobe appears not to contain a single sub-field that could be identified with any particular sensory modality, and its entire expanse must accordingly be considered association cortex. It should, perhaps, not be surprising in view of this circumstance alone that loss of frontal cortex, in primate forms in particular, leads to a complex functional deficit, the fundamental nature of which continues to elude laboratory investigators and clinicians alike. The purpose of this paper is, to review some aspects of this deficit in animals and man, and to inquire to what extent the consequences of frontal-lobe lesion can be evaluated in neurological terms.

It is unfortunate that the search for neural substrata of the frontal lobe syndrome is hampered by a nearly complete absence of data obtained by modern neurophysiological methods. As a consequence, no entirely satisfactory hypothesis concerning the neural mechanisms of the frontal lobe would seem attainable at present. On the other hand, largely as a result of several excellent anatomical studies reported within the past 5 years, the neural associations of the frontal lobe, in particular those with other regions of the cerebral cortex, have come into sharper focus, and it is on the basis of these anatomical findings that an attempt could be made to formulate a general and preliminary notion of the major neural mechanisms in which the frontal lobe is involved. Needless to say, no concept so exclusively based upon neuroanatomical data can be stated in any but very general terms, for the value of anatomical studies lies largely in the identification of specific questions that can be explored by physiological methods.

FUNCTIONAL CONSIDERATIONS

1 Observations in animals

Monkeys subjected to extensive bilateral ablation of granular frontal cortex have long been noted to exhibit hypermotility and hyperreactivity to external stimuli. Little further information concerning their functional impairment was obtained until in 1935 JACOBSEN¹ reported his now classical observation that primates deprived of their prefrontal cortex perform little better than at the level of chance in the so-called delayed-response test. In this simple task, that is quickly mastered by intact chimpanzees, monkeys, cats and dogs, the animal is shown under which one of two or more identical covers food is placed, but it is forced to postpone retrieval of the food for a short period (usually ½–2 min) during which the scene of the choice is hidden from its view by an opaque screen. The initial impression that the ‘frontal animal’ suffers from a memory loss, and while waiting for the screen to go up ‘forgets’ where he saw the food being hidden, has been effectively refuted, and it now seems certain that frontal-lobe ablation affects a response-guidance other than memory in the customary sense. In this test, as also in the somewhat related delayed-alternation (alternative baiting of the left and right one of an identical pair of containers) and multiple-choice tests (all covers marked by a differently-shaped object, one of which serves as the clue for bait in one block of trials, another one in a contiguous trial-block, and so on), ‘frontal’ animals exhibit a characteristic tendency to perseverate a particular choice, despite the obviously poor reward average. It has been suggested that this ‘rigidity of central sets’ actually constitutes the fundamental deficit² but KONORSKI and LAWICKA,³ on the basis of a remarkable series of experiments in dogs and cats, arrived at a somewhat different interpretation according to which the conditioning signal (e.g. the being shown which box contains bait) undergoes an abnormally rapid decay during the delay, and is thus overcome by the essentially unguided release response triggered by the actual presentation of the choice. Perseveration, according to Konorski and Lawicka, is a relatively unspecific phenomenon that is encountered in a variety of functional impairments (often, for example, in aphasia). As an alternative hypothesis, Konorski and Lawicka suggest an abnormally strong release-response overriding a normal signal trace, a suggestion which would appear compatible with another observation made in ‘frontal’ monkeys⁴,⁵ in the so-called go-no go tests. In this testing procedure the animal must learn not only to respond to a particular signal (either auditory or visual) but also, to withhold response to another signal that randomly alternates with the first. Under such conditions, monkeys deprived of their frontal cortex score more errors of commission than do normal monkeys. It must be remarked, however, that it still appears uncertain to what extent this deficiency is due to an actual perceptual impairment rather than to the nature of the go-no go test proper.

Last to be mentioned here is the observation that, in object-discrimination tests, ‘frontal’ monkeys show an increased tendency to prefer any novel object over a tried, familiar one, even if the experiment is so arranged that the choice of a novel object is never rewarded. Although this novelty-preference would at first glance seem incompatible with the choice-reiteration noted above, both could conceivably result from one and the same guidance failure in a response that in normal subjects is more stably determined by the previously experienced consequence of the choice.

2 The frontal-lobe syndrome in man

Complex and difficult of analysis as are the consequences of frontal lobe ablation in animals, the frontal lobe syndrome in man is even more bewildering. As a result of its complexity, current concepts concerning the function of man’s frontal lobes range between two widely separate extremes: on the one hand the notion that this part of the brain is crucially involved in man’s highest mental faculties;⁶,⁷ on the other extreme the conclusion that the only defects objectively demonstrable in frontal-lobe patients are of a perceptual nature, all other impairments being too variable and vague to serve as reliable characteristics of frontal-lobe dysfunction.⁸

The wide divergence between these two views may be attributable in part at least to the common difficulty of determining clinically the precise extent and location of the cerebral tissue damage in human patients. As emphasized by TEUBER,⁹ tumors of the frontal lobe are likely to have reached considerable size by the time the patient is seen by a neurologist, and in such cases it is difficult to determine whether the symptomatology may not have become complicated by a more general impairment of brain function. Penetrating traumatic lesions of the frontal lobes are only rarely explored surgically, and their result in tissue loss thus as a rule remains undetermined. In fact, the only category of patients in whom the extent of the tissue defect is usually known with reasonable accuracy are those who have been subjected to surgical ablations performed in order to alleviate epileptic disorders.

Most controversial among the symptoms of frontal-lobe disorder in man are the psychiatric signs, in particular mood changes (euphoria, irritability or its opposite: emotional indifference), and character changes (boastfulness, impetuousness, lack of initiative and other behavioral disorders). Significant and practically important though such general personality changes may be, they show much individual variation and for the present must therefore remain somewhat at the periphery of the search for common denominators in the frontal-lobe syndrome. This search is still directed largely toward an evaluation of the patient’s perceptual and motor capacities, and his strategies in performing certain relatively simple tasks. Some results of such analyses will be reviewed in the following account.

In the course of detailed studies of patients with gunshot wounds of the frontal lobe, TEUBER and his associates⁸,⁹ have identified certain perceptual impairments, notably such affecting the maintenance of the perceived vertical during passive tilt of the body, the interpretation of line drawings with ambiguous perspective, and the capacity of reversing standpoint in dealing with mirror images of the body. Their tests, in addition, disclosed in frontal-lobe patients a significant impairment in the speed and efficiency with which a visual array is scanned for detail (see also LURIA¹⁰). In discussing these functional deficits, TEUBER⁹ arrives at the important suggestion that all are attributable to the loss of a mechanism of ‘corollary discharge’, i.e. a flow of impulses from the central effector organization to central sensory structures, … presetting the latter for those predictable changes of input that will be the consequences of the particular motor output.*

Among the results obtained with more complex testing procedures, the observations reported by MILNER¹¹ and LURIA¹⁰,¹² are particularly noteworthy. Milner’s findings have demonstrated a profound and characteristic inability of frontal-lobe patients to achieve normal scores in the Wisconsin modification of the Weigl card-sorting test, a test in which the patient is asked to sort 128 cards on the basis of any one of three arbitrary criteria (color, shape or number of the figures shown on the cards). The patient is given no verbal instruction as to which criterion is valid, and is required to determine the criterion pragmatically, on the basis of being told at each placement whether his choice is right or wrong. It is remarkable that frontal-lobe patients in this testing situation show no noteworthy difficulty in deducing the required strategy from the signals given by the observer. Their characteristic deficit appears when, at some point in the procedure, the observer arbitrarily changes the criterion (e.g. from color to number), thus requiring the patient to identify and follow a new ordering system. Under such conditions, frontal-lobe patients tend to perseverate the original strategy, even in the face of an ever-mounting score of errors. In the words of MILNER¹¹: … it does not seem accurate to attribute this poor test performance to a loss of abstract thought, since such patients often state spontaneously that ‘it has to be the color, the form or the number,’ although they seem unable to recognize the possibility of a change once a particular pattern of response has become established. They thus show a curious dissociation between the ability to verbalize the requirements of the test and the ability to use this verbalization (and other verbal cues) as a guide to action. Superfluous to say that the perseveration shown by frontal-lobe patients in the card-sorting test strongly recalls the high score of reiterative errors recorded for ‘frontal’ monkeys in various testing procedures.

LURIA and his colleagues¹⁰,¹² have identified a similar perseverative tendency in frontal-lobe patients. When asked to draw a sequence of simple figures, for example, a cross, two circles and a triangle, the frontal-lobe patient may simply draw four crosses. This ‘inertia’ may declare itself dramatically when the patient is asked to perform a task requiring an orderly sequence of separate steps. In such cases, he may perseverate an early phase of the action, but it is important to note that he may, instead, be side-tracked in a direction that could have been appropriate in the context of another task. LURIA and HOMSKAYA¹² note that such patients evince no dismay at their failure to achieve the required goal, and suggest … a deficit in matching of action carried out with the original intention … as a central characteristic of the frontal-lobe syndrome. Particularly interesting among Luria and Homskaya’s findings is their observation that this derailment of programmed behavior is remarkably refractory to the normally quite compelling effect of repeated verbalization of the required steps by the observer, or even by the patient himself, throughout the process. Such dissociation of the verbal signal from the subject’s action appears closely related to MILNER’S¹¹ observations in frontal-lobe patients in the card-sorting test. As an electrophysiological corollary of this behavioral disconnection, LURIA¹⁰ cites the following important observation by his co-workers Homskaya and Simernitskaya: frontal-lobe patients—but not patients with more posterior cerebral lesions—fail to show an effect that in normal subjects characteristically follows a verbal instruction to await a visual or tactile signal, namely, an enhancement of the electrical potentials evoked in the corresponding sensory area by the signal. LURIA¹⁰ concludes from this observation … that the frontal lobes play a significant part in the regulation of the active states started by a verbal instruction.

Of considerable significance among the test results reported for frontal-lobe patients appear to be MILNER’S¹¹ findings in the so-called stylus-maze test. According to Milner, the poor performance of frontal-lobe patients in this tracing task is attributable not to any form of spatial disorientation but, instead, to an apparent inability to comply reliably with the ‘rules of the game’. Such patients often seem unable to curb a propensity for taking illegal shortcuts (such as moving the stylus diagonally across the board); as in the card-sorting test, they appear aware of their mistakes (in the sense that they can verbalize these) but unable to modify their strategy accordingly.

3 Comment

It is clear even from the foregoing highly fragmentary review that the frontal-lobe disorder is characterized foremost by a derangement of behavioral programming. One of the essential functional deficits of the frontal-lobe patient appears to lie in an inability to maintain in his behavior a normal stability-in-time: his action programs, once started, are likely to fade out, to stagnate in reiteration or to become deflected away from the intended goal. The fact that even his self-admitted awareness of a mis-match between the purpose and the result of his actions fails to affect his strategy suggests an inadequate ‘internalization’ of all those error—or error-approach signals, including even self-directed verbal commands, that normally modulate the evolvement of behavioral programs. The same failure to register (i.e. to furnish a stable constraint) could be thought to be involved in his tendency to break game-rules. If this indeed be the case, it would seem probable that ‘feed-back’ of opposite sign likewise would fail to become incorporated in the mechanisms of behavioral guidance. It could be asked, for example, if the reiterative phenomena illustrated so forcefully by Luria and his co-workers could not be due in part at least to a ‘getting lost’ of a message reporting successful accomplishment of initial or intermediate stages of the program.

A state of affairs as here suggested would amount to one in which action programs can be aimed at their intended goal, but must evolve under conditions of severely impaired functioning of some guidance mechanism associated (but not necessarily identical) with that determining the subject’s affective responses to the apparent success or failure of his approach. Depending on circumstances, the effect of such inadequate guidance could be either an abnormal inflexibility of the program or an excessive vulnerability to interfering events.

NEURAL ASSOCIATIONS OF THE FRONTAL LOBE

In view of the complex and evasive character of the frontal-lobe syndrome it is appropriate to ask what the nature might be of the neural information normally received and processed by the frontal cortex, and what efferent channels might account for its unique role in behavioral programming.

Obviously, nothing short of a comprehensive analysis of the response determinants of single cortical units can be expected to answer the question as to the informational content of neural impulses converging upon the frontal cortex. Studies of this sort (exemplified by Hubel’s contribution to this volume) recently have provided extremely valuable insights into the feature-extracting mechanisms of the visual, somatosensory and auditory fields of the cerebral cortex. However, the problems encountered in exploring these modality-specific cortical fields are likely to be multiplied many times over in regions such as the frontal cortex which are certain to be associated with more than one sensory modality. Especially the problem of identifying the natural stimuli consistently capable of eliciting responses by a sufficiently large number of cortical units in such regions might prove quite elusive. However that may be, explorations of this sort have not yet provided the data which alone could identify the nature of the information received, and the manner in which it is processed by the frontal cortex. Consequently, little more than anatomical data are currently available from which to draw inferences related to this question. This anatomical information, as the following account is intended to show, is by no means negligible.

1 Anatomical definition

The term, frontal lobe or ‘prefrontal cortex’, has come to denote the cortical field that extends forward of the ‘premotor’ area 6 and is projected upon by the mediodorsal nucleus of the thalamus. In primates and carnivores, this large cortical expanse covers the frontal pole of the hemisphere, but in the rat, and probably in other rodent species as well, the corresponding and relatively smaller region is composed of two widely separate sub-fields: one confined to the medial surface of the hemisphere, the other occupying the dorsal bank of the rhinal sulcus, and neither extending forward far enough to cover the frontal pole¹³. Apart from such differences of relative size and topography, there is another reason to believe that the prefrontal cortex reaches vastly different stages of development in different mammalian lineages: Only in primates does the larger rostral part of the field exhibit the cytoarchitectural features of a granular cortex. In the cat, dog, sheep, and rat, apparently the only non-primate species in which the prefrontal cortex has been delimited by experimental methods, the field is throughout of an agranular structure; in the rat its laminar pattern is so poorly differentiated that it is nearly indistinguishable from the anterior cingulate cortex with which its medial sub-field is caudally continuous. In fact, on cytoarchitectural grounds alone the existence of a non-primate homologue of the primate prefrontal cortex could be questioned, and it is largely the constancy of its afferent relationship with the mediodorsal nucleus of the thalamus that has allowed a prefrontal cortex to be identified in non-primate forms.

Since the anatomical account to follow is based very largely upon observations in the rhesus monkey, a brief description of the main anatomical features of the prefrontal cortex of this species would seem relevant. As shown in Fig. 1, the caudal border of the prefrontal cortex is marked by the deep arcuate sulcus which delimits it from the agranular ‘motor cortex’ of the precentrai gyrus (areas 4 and 6 of Brodmann). The only other macroscopic features of importance are: (1) the general shape of the frontal lobe which allows a fairly flat medial surface to be distinguished from a concave ventral (or orbital) aspect and a lateral convexity, and (2) the deep principal sulcus which divides the lateral convexity into a dorsal and a ventral field.

FIG. 1 Line drawing representing the lateral (lower half of figure) and medial aspect of the cerebral hemisphere of a rhesus monkey. The lateral view shows the arcuate sulcus (Arc) which marks the caudal boundary of the region here called ‘the frontal lobe’, and the principal sulcus (Pr) which divides the frontal convexity in a dorsal and ventral half. The shaded region forming the rostral bank of the arcuate sulcus represents the dysgranular area often referred to as ‘frontal eye field.’ A small rostral part of the orbital surface of the frontal lobe (O) is visible in the lateral view. The broken line in the upper half of the figure indicates the approximate position of the amygdala, a structure largely hidden from view by the overlying olfactory cortex. Other structures labelled are: Ci: cingulate gyrus; CS: central sulcus; HG: hippocampal gyrus; IP: inferior parietal lobule; IPS: intraparietal sulcus; IT: inferior temporal region; S: septum; SP: superior parietal