Neurop&hologia, Vol. 17, pp. 393 to 400. Pergamon Press Ltd 1979. Printed in Great Britain.
RELATIVE STEREOTYPY OF WATER-INGESTIVE BEHAVIOR INDUCED BY FRONTAL CORTICAL LESIONS IN THE RAT LOWELL
T. CROWand LAWRENCE S. MCWILLIAMS
Department of Psychology, Western Washington University, Bellingham, WA 98225, U.S.A. (Received 5 October 1978) Abstract-The variability of water-reinforced barpressing rate and duration was observed in rats in the progression of thirst to satiety, under CRF and extinction conditions, after electrolytic lesions of the frontal cortex. Although there was an ultimate recovery of mean rate and duration, frontal animals continued to display a lower variance of response rate and duration than controls under CRF thirst conditions. Additional indications of a relative response stereotypy as a result of the lesions are presented, and the data are discussed in terms of brain mechanisms of the initiation and cessation of thirst-motivated behavior in the rat.
ALTHOUGH of undoubted significance in the understanding of higher nervous activity the precise mechanisms of the frontal areas in behavior remain unclear. Several studies have indicated that frontal lesions result in deficits which might be described as a diminished response variability. Perseverative or stereotyped behavioral patterns as a result of frontal lesions have been noted in monkeys [ 1,2], in cats [3], and in human patients suffering from tumor of the frontal lobes [4]. In establishing what the frontal deficits are not, several studies have found subtle changes in lesioned animals which have provided a basis upon which to specify precise characteristics of the behavioral changes accompanying such brain damage. Using a fixed interval 2 min food reinforcement schedule, PRIBRAM [5] showed that neither starvation nor satiation altered the behavioral changes resulting from frontal damage. A computation of the distribution of responses across the 2 min intervals revealed that lesioned monkeys, although producing the same response rate, differed in the distribution of their responses so that a more constant rate was maintained within each interval. The “scallop” characteristic of the fixed interval schedule was not seen in frontal animals and no difference in change of rate was seen when compared with control subjects. In addition extinction of the leverpressing response was found to be much slower in frontal monkeys, a finding in keeping with the general conclusion that the surgery had reduced the effectiveness of the reinforcement to guide behavior [5, 61. By successively lengthening the interval in a DRL (differential reinforcement at low rates) schedule, STAMM[7,8] demonstrated that timing behavior was not adversely affected by frontal lesions in monkeys. It was noted that frontal animals gave fewer multiple presses (two or more responses in rapid succession) following nonrewarded leverpresses than controls. For timing responses (those other than multiple responses) normal animals displayed more very short and very long interresponse times than lesioned monkeys, this being true even though the mean interresponse times did not differ among groups. These 393
LOWELLT. CROW and LAWRENCES. MCWILLIAMS
394
data were considered in the context of an increased threshold for frustrative responses after lesions of the prefrontal and cingulate cortex. No systematic behavioral differences were found between prefrontal lobectomized and cingulectomized monkeys [8]. In varying degrees such frontal impairments have been seen in rats as well as cats and monkeys [9, IO]. TASSIN et al. [I I] have described a behavioral syndrome characterized by locomotor hyperactivity and a reduction of attentional capacities as a reult of interference with the fronto-cortical dopaminergic system in the rat. The behavioral syndrome, induced by mesencephalic lesions, included a lack of extinction in an alimentary conditioned task [12]. The present study was undertaken to look at operant behavioral variability per se as it might be influenced by frontal lesions in the rat, and to compare any such effects to previously obtained data on the barpressing variability changes occasioned by satiety as well as extinction of behavior [13]. METHODS Subjects Sixteen female rats from the Western
perimentally
Washington
University colony were used. The animals were ex-
naive.
Apparatus The apparatus and duration.
consisted
of four water-delivery
operant chambers
equipped
to measure response
rate
Procedure All animals were adapted to a 23 + hr deprivation schedule and trained in a 30 min daily session of CRF barpressing for water. Eight of the animals were then subjected to ether anesthesia and stereotaxically placed D.C. anodal lesions at DeGroot coordinates, A9.5 and 10.5, bilaterally 1 mm at A9.5, 1 and 2 mm at A10.5. A current of 3 mA was passed through the electrode for 20 sec. The electrodes were steel orthodontic arch wire, 0.01 in. in diameter, insulated except at the tip with Epoxylite 6001-M insulator. Due to the nature of the general variability hypothesis involved [14], control animals were not subjected to any aspect of the surgery, but otherwise were treated identically to the experimental animals. Fig. 1 shows the location and general extent of the lesions. It may be seen that the damage involved the midline sulcal cortical regions as well as the frontal and dorsolateral area, Leonard [15] having shown that the primary projection fields of the mediodorsal nucleus of the thalamus is for the rat, unlike many higher mammals, confined to the sulcal and medial cortex. All animals were maintained on the water deprivation and operant schedule throughout the study, but critical measures were not taken until each lesioned animal recovered the prelesion response rate (approximately two weeks). After recovery from surgery, measures were made of the number of responses and average response duration for each minute of the daily 30 min operant drinking period. Extinction data were then taken by extinguishing three 1 min segments of the total 30 min session on each day until all of the 30 min data for each animal were collected. The minute segments for a given day were chosen to represent the initial, middle, and concluding aspects of the session on any day. Also measures were made on alternate days so a full 30 min of reinforcement always followed the days on which extinction data were taken. The extinction part of the study thus required 20 days.
RESULTS The postrecovery I-min data segments throughout the 30 min operant drinking session consisted of number of responses per minutes and average response duration per minutes in seconds. The total number of responses in CRF conditions did not differ between the lesion and control group (Table 1), but the variance was lower for the frontal animals. Figure 2 shows the nature of the variance change as a result of the lesions. The rate of change of response rate is lower as a consequence of the lesion, that is, the deceleration of rate was diminished. For example, in the first 15 min the control group decreased its mean response
FRONTAL
CORTICAL
LESIONS IN THE RAT
FIG. 1. D.C. anodal lesions involved frontal lobe and sulcal regions. Animal above suffered largest frontal pole damage.
395
397
Tr(ONTALCORTICALLESIONS~THERAT
rate by 0.62 responses/min/min, while the lesioned group in the same period decreased its rate by 0.25 responses/min/min (P = 0.010). In keeping with these CRF rate data the percentage of 1 min intervals in which responding occurred was greater for the lesioned group (Table 1). Table 1. Changes in mean and variability of various response measures as a result of frontal lesions. Probabilities derived from Mann-Whitney U tests Measure Response Rate (CRF) Variance of Rate (CRF) Per cent 1 min intervals in which responding occurred (CRF) Number of responses in extinction Per cent 1 min intervals in which responding occurred (Ext.) Response Duration (CRF) Variance of response duration in first 5 min (CRF) Variance of response duration in first 5 min (Ext.) Variance of response duration in last 5 min (CRF) Variance of response duration in last 5 min (Ext.)
Mean (control) 3.4O/min 0.52 65 112.75
Mean (lesion) 3.74/min 0.29 81 190.38
Probability 0.263 0.032 0.025 0.001
57 0.524 set
77 0.529 set
0.003 0.480
0.0054 sec.
0.0927 set
0.041
0.1502 set
0.0567 set
0.052
0.3791 set
0.3006 set
0.480
0.4271 set
0.3235 set
0.139
UNOPERATED CONTROL
MINUTES
FIG. 2. Mean number of responses per minute for lesioned (N = 8) and unoperated
control
(A’ = 8) groups.
In extinction as well the percentage of 1 min intervals in which responding occurred was greater for the lesioned group, and the number of responses was greater (greater resistance to extinction). The extinction response variance was high in both the lesioned and control groups and there was no significant difference between them. In keeping with previous analyses of response duration [13] the 30 min session was divided into the initial 5 min of responding vs the last 5 min responding period (those minutes in which responding occurred). The mean standard deviation scores for the initial and last responding periods are shown in Fig. 3. As was found previously there was an
398
LOWELLT. CROW and LAWRENCES. MCWILLIAMS
overall increase in variability as a result of both extinction (P = 0.01) and satiation (P = 0.01). In terms of the lesion effect, the frontal animals showed a lower variability than controls in the initial 5 min responding period in the CRF condition, but, although in the expected direction, the differences between the lesioned and control groups were not significant in the CRF satiety or in either of the extinction conditions (Table 1). 07 -
06 -
00'
I
I
30-S
0+5
RESPONDING
lNTERVALS(MINUTES)
FIG. 3. Response duration variability in the first and last 5 min of responding in a 30 min CRF reinforced operant session.
DISCUSSION That behavioral changes which occur as a result of frontal lobe lesions are, to some extent, characterized by a lack of changeability to correspond with changing circumstances is an attractive hypothesis. The perseverative errors in reversal tasks with monkeys [I, 21 and the continued circle drawing in frontal patients [4] appear to fit the hypothesis as do the findings of greater resistance to extinction [5] and the loss of multiple responses with the discontinuation of reward [8]. In the present study perseverative or stereotyped actions were enhanced by frontal damage in response rate to satiation, successive minutes of responding, number of responses in extinction, and in certain aspects of response duration. The lesions of the present study did not appear to affect the postrecovery water balance of the animals as the number of reinforcements per 30 min session returned to normal and bodyweight stabilized. What was affected by the lesions was the rate of change of behavior corresponding to the change from the state of thirst to the state of satiety or the change from conditions of reinforcement to conditions of extinction, the behavioral distinctions being less sharp than in the intact rat. The results seem to be in keeping with the concept of PRIBRAM et al. [6] of impairments from frontal damage in flexible noticing orders. If central programs of search for matches between permanent memories and temporary storage of specific outcomes are varied in terms of order so that a specific adaptation to
FRONTALCORTICALLESIONSIN THP.RAT
399
external (and perhaps internal) change is made more facile, then the results of the present study would be expected. Elsewhere one of the present authors has suggested that the general concept of behavioral variability may be a unifying one [14]. If a primary feature of higher neural activity is the initiation of specific kinds of behavioral variability, the cessation of a behavior cued by some internal state (e.g. gastric distention) may involve a diminished inhibition of the variability as the behavior “breaks-up” and other responses appear in its stead. Extinction may share these features with satiety as both were affected by the lesions of the present study, and the fronto-cortical system involved may be common to both categories of behavioral cessation. REFERENCES 1. PRIERAM,K. H. The intrinsic systems of the forebrain. In Handbook of Physiology: Neuropsychology. J. FIELD (Editor), Vol. 2, pp. 1223-1344. American Physiological Society, Washington, D.C., 1960. 2. MISHKIN, M. Perseveration of central sets after frontal lesions in monkeys. In The Frontal Granular Cortex and Behavior, J. M. WARRENand K. AKERT (Editors), pp. 219-241. McGraw-Hill, New York, 1964. 3 WARREN,J. M. The behavior of carnivores and primates with lesions in the prefrontal cortex. In The Frontal Granular Cortex qndBehavior, J. M. WARRENand K. AKERT (Editors), pp. 168-191. McGrawHill, New York, 1964. 4. LURIA, A. R. and HOMSKAYA,E. D. Disturbance in the regulative role of speech with frontal lobe lesions. In The Frontal Granular Cortex and Behavior, J. M. WARREN and K. AKERT (Editors), pp. 353-371. McGraw-Hill, New York 1964. 5. PRIBRAM,K. H. A further experimental analysis of the behavioral deficit that follows injury to the primate frontal cortex. Expl Neural. 3, 432-466, 1961. 6. PRIBRAM,K. H., AHUMSDA,A. HART~~, J. and Roos, L. A progress report on the neurological process disturbed by frontal lesions in primates. In The Frontal Granular Cortex and Behavior, J. M. WARREN and K. AKERT (Editors), pp. 28-55. McGraw-Hill, New York, 1964, 7. STAMM,J. S. Function of prefrontal cortex in timing behavior of monkeys. Expl Neural. 7,87-97, 1963. 8. STAMM,J. S. Function of cingulate and prefrontal cortex in frustrative behavior. Actu. Biol. Exp. (Warsaw) 24, 27-36, 1964. 9. DIVAC, I. Frontal lobe system and spatial reversal in the rat. Neuropsychologiu 9, 175-183, 1971. 10. MARKOWITSCH,H. J. and PRITZEL, M. Comparative analysis of prefrontal learning functions in rats, cats, and monkeys. Psychol. Bull. 84, 817-837, 1977. 11. TA%IN, J., SIXNUS,L., SIMON,H., BLANC,G., THIERRY,A., LE MOAL, M., CARDO,B. and GLOWINSKI,J. Relationship between the locomotor hyperactivity induced by Alo lesions and the destruction of the frontocortical dopaminergic innervation in the rat. Brain Res. 141, 267-281, 1978. 12. LE MOAL, M., CARDO, B. and STINUS,L. Influence of ventral mesencephalic lesions on various spontaneous and conditioned behaviors in the rat. Physiol. Behav. 4, 567-573, 1969. 13. CROW, L. T. A comparison of the effects of extinction and satiety on operant response duration in the rat. Bull. Psychonom. Sot. 11, 8688, 1978. 14. CROW, L. T. Is variability a unifying behavioral concept? Psychol. Rec. 27, 783-790, 1977. 15. LEONARD,C. M. The prefrontal cortex of the rat-I. Cortical projection of the mediodorsal nucleus. II. Efferent connections. Bruin Res. 12, 321-343, 1969.
LOWEI.LT. CROW and LAWRENCES.MCWKLIAMS Resume
: On a dtudi6
d’un
levier
sous
des
frontal.
avec
CRF et
Bien
constate
qu’on
les
que
les
contr6les
une
relative
mes
cGr6braux le
des
conditions
moyens,
chez
chez
renforcement
animaux
des
stGr6otypie de
l’initiation
la
variation lors
l’eau,
d’extinction, une
montraient sous
rats par
apres
r6cupEration
une -~
variance
conditions
des
de
r6ponses. et
de
du du
des
moindre soif
de
la
la
soif
ces du
la
taut
AprSs
dur6e i
de la
pression
satiiSt6.
Blectrolytiques de
du
CRF.
cessation
et de
Idsions
terminale
On discute la
taux
passage
et
dur& de
l&ions
donnBes
comportement
la il
en
et
du du
cortex
taux
duree existait
termes
de
motiv6
par
de
rdponse aussi
mlcanisla
soi;
rat.
Deutschsprachige Zusammenfassung: Die Variabilitat der mit Trinkwasser verstarkten Hebeldruckrate und -dauer wurde bei Ratten untersucht und zwar be1 zunehmender Durststillung bis zur Sattigung, unter CRF-. und Extinktionsbedingengen nach elektrolytischen Lasionen der frontalen Hirnrinde. Obwohl sich die mittlere Rate und Dauer schlieRlich erholte, boten frontal geschadigte Tiere weiterhin eine verringerte Varianz (Streuung) der Antwortrate und -dauer als Kontrollen unter CRF-Durst-Bedingungen. Zus$tzliche Hinweise auf eine relative Antwortstereotypie als Ergebnis der Lasionen werden dargelegt und die Daten diskutiert i. S. von Hirnmechanismen fur das Ingangsetzen (initiation) und Beenden (cessation) von durstmotivierten Verhaltensweisen bei der Ratte.