BRIT. J. SURG., 1964, Vol. 51, No. 2, FEBRUARY

THE ORBITAL CORTEX AS AN OBJECTIVE IN THE SURGICAL TREATMENT OF MENTAL ILLNESS*

THE RESULTS OF 450 CASES OF OPEN OPERATION AND THE DEVELOPMENT OF THE STEREOTACTIC APPROACH

BY GEOFFREY KNIGHT, LONDON

IN the philosophy of John Hunter every surgical operation forms a potential experiment in human physiology. This concept finds expression in the surgical treatment of mental illness which has re- vealed evidence concerning the function of the frontal lobes in man. This form of therapy produces its effect through the medium of the thalamofrontal and frontohypothalamic connexions, the pathways of emotional appreciation and reaction. The benefits result from an alteration in the intensity of a patient’s emotional feeling or reaction, leading to relief of distress and improvement in intellectual activity from diminished distraction. Yet the optimum ob- jective to which treatment should be directed has not been identified, as indicated by the variety of measures employed and the uncertainty still existing as to whether division of any one group of fibres is of greater importance than another.

Since Moniz, in 1936, injected alcohol into the frontal lobes in an attempt to cure delusions, but obtained instead an improvement in emotional stability, many procedures have been devised to interrupt the connexions of the frontal cortex. Early operations merely destroyed the central core of white matter without precise objective, and frequently missed the lower and inner portions of the lobe which are now known to be extremely important in treatment.

The standard leucotomy of Freeman and Watts (1942) was a destructive procedure in which a leuco- tome introduced bilaterally divided the central white matter in front of the anterior horn of the ventricle. I t was assumed that emotional changes resulted from division of the thalamofrontal radiation and the de- generation that ensued in the dorsal median nucleus of the thalamus, but the incision inflicted an exten- sive bilateral frontal lesion causing a serious blemish of personality, and total division of the pathway con- cerned in emotion produced a diminution in capacity for the enjoyment of work or leisure, to which Strom- Olsen and Tow (1949) have drawn attention.

Numerous inaccuracies complicated this blind procedure. Owing to the variable relationship between the shape of skull and brain, the site of the incision might vary by as much as z cm. The use of a blunt instrument might merely distort the brain tempor- arily without cutting it, or, more seriously, the lesion might extend beyond the planned site owing to con- cealed haemorrhage which could not be seen and checked at operation. Even the restricted lower segment operation, which omitted the upper portion

* Hunterian Lecture delivered at the Royal College of Surgeons, England, on 9 May, 1963.

of the Freeman cut, was subject to the inaccuracies of blind procedures in general and at times produced euphoria, overactivity, extroversion, and aggression, as Reitman (1946) has shown.

There can be no doubt that the damage inflicted by standard leucotomy has left an impression which has had an inhibitory effect on the employment of surgery. I n some clinics, surgical treatment has been abandoned entirely or never adopted. It is un- fortunate that this reaction should exist, for modern operations can relieve important symptoms without any blemish to intellect or personality. Indications undoubtedly exist for the far earlier employment of surgery in selected cases to cut short years of un- necessary illness, particularly in recurrent and re- sistant depressions and suicidal depressions, in whom drug treatment often fails to produce the remarkable control that was once expected of it.

Depression in its various manifestations consti- tutes a large proportion of psychiatric practice and in serious cases, where recognized psychiatric measures fail, persistent or recurrent symptoms remain despite continuous drug treatment, repeated E.C.T.s, and mental hospital admissions. In 1957, 3 out of every IOO patients admitted to hospital with depres- sion had been previously admitted over seven times before, a figure which takes no account of out- patient treatment and support outside mental hospital. Suicide is, then, an ever-present risk, re- peated heavy sedation producing at best a partial health in which symptoms partially suppressed are never far below the surface-in marked contrast to the complete relief, with freedom from both drugs and doctors, which surgery can at times achieve (Fig. I).

In 1948, Le Gros Clark’s demonstration of the distribution of the thalamofrontal relay provided an objective for accurate operations on limited cortical areas. Fibres from the anteroposterior axis of the dorsomedial nucleus project in serial order to the cingulate convexity and orbital cortex. Compara- tively few ascending fibres enter the extreme posterior orbital region. Since these fibres relay impulses originating in the hypothalamus in the circuit hippo- campus-fornix-mamillary body-thalamus, which Papez (1937) regards as the anatomical substratum of the emotions, a large part of the frontal cortex acts as an afferent projection area for fibres con- cerned in emotional integration. Each of the areas receiving these fibres gives rise to efferent fibres passing towards the hypothalamus, which constitute pathways of emotional reaction, an important pro- jection arising from that part of the posterior orbital cortex which receives few ascending fibres.

KNIGHT : SURGERY OF ORBITAL CORTEX

These are the fibres described by Le Gros Clark and Meyer (1950) which pass from Area 13 to the hypothalamus. All descending fibres converge to a point of concentration over the posterior orbital cortex in an area adjacent to the hypothalamus, where they may possibly be interrupted at a point somewhat posterior to the ascending thalamofrontal radiation.

METHOD In 1950, at the instigation of Strom-Olsen, we

adopted a restricted modification of the technique of orbital undercutting described by Scoville (1949). Rylander’s (1939) clinical observations had indicated

(Fulton, 1951). These indicated a sharp division of function between the lateral and medial surfaces. Lesions in the granular and transitional cortex of the lateral surface produced an intellectual deficit, with little change in emotional behaviour, whereas lesions in the primitive agranular areas of the medial surface led to reduction of emotional response without im- pairment of intellectual function. A relationship between the incision and the agranular cortex is therefore important, and it is significant that inferiorly this incision overlies the older portions of the frontal lobes which are represented in the posterior orbital region in the primitive agranular cortex of Area 13.

A B C

picture; 6, 3 weeks after operation; C, 18 months after operation. FIG. I.-A patient suffering from obsessional illness of 10 years’ duration, with depression and suicidal tendencies. A, Preoperative

that orbital lesions produced change in emotional tone rather than intellectual activity. Ablation of the orbital region had produced quiescence and increased tameness in higher animals (Livingston, Fulton, Delgardo, Sachs, Brindler, and Davis, 1948): It appeared possible that orbital incisions might diminish the intensity of harmful emotions, such as agitation or tension, whilst leaving the greater part of the brain undisturbed (Fig. 2).

We modified Scoville’s incision. Instead of under- cutting the entire orbital cortex, we employed a narrow incision, 2 cm. wide, passing back in the inner aspect of the lobe, lying I cm. from the midline and I cm. above the orbital roof, extending to a distance of 6 cm. from the frontal pole (Fig. z B) to a point beneath the caudate nucleus and anterior limb of the internal capsule, to divide fibres descending from the thalamofrontal radiation at that point. We have described elsewhere (Knight and Tredgold, 1955) our objective in avoiding apparently needless damage to the lateral portions of the lobe. This narrow incision has been found to accomplish all that the full incision can effect.

An orientation towards the mesial aspect later received support from the results of ablation experi- ments in monkeys carried out in Fulton’s laboratory

A B FIG. z.-A, Orbital aspect of left frontal lobe, showing Area 13

in cross hatch and Area 14 in stipple. 6, Orbital aspect of rlght frontal lobe, showing,site of incision employed, 1.8 cm. wide, situated I cm. from midline, extendmg to 6 cm. from the frontal pole. The last 2 cm. corresponds to Area 13 (see A).

Sir Wilfred Le Gros Clark has kindly discussel- this incision and has pointed out that its posterior portion would undercut areas of the human cortex corresponding to Areas 13 and 14, more particularly the former, as described by Earl Walker (1940) in the monkey. Elizabeth Beck (1949) has shown that in man the change to agranular cortex of Area 13 takes place at the middle and posterior thirds of the orbital cortex. Demarcation is not sharp, a zone of

116 BRIT. J. SURG., 1964, Vol. 51, No. 2, FEBRUARY

15

disgranular cortex being encountered before the true agranular cortex starts, 4 cm. from the frontal pole, and thereafter extends posteriorly to a point 6.3 cm. from the tip of the pole. Internal to this there is another Area 14 whose function is at present unknown (Fig. 2 A). Hence the posterior 2 cm. of a 6-cm. incision situated I cm. from the midline will accurately overlie Area 13, an area from which autonomic responses can be obtained, and which may possibly represent a site at which reactions to primitive emotions are subserved.

OPERATIVE TECHNIQUE The operative technique has been described else-

where (Knight, 1959, 1960). Only certain points require mention.

A transverse scalp incision is concealed within the hairline or a butterfly incision follows the edge of the

Table Z.-REPEAT UNDERCUTTING OPERATIONS WITH IMPROVEMENT OF POSTERIOR PORTION OF THE INCISION

z Obsessional 4 z Schizophrenic 4 Chronic depression 3 Chronic anxiety state -

I 1

No FURTHER IMPROVEMENT IMPROVED No. OF

CASES

PREVIOUS OPERATION

3 Prefrontals

2 Prefrontals

I Prefrontal

Trans o r b i t a I

Rostral ant. closed

Rostral ant. opened

Grantham

Total

N,oa: I M P R O ~ D FAILED MORTALITY

I I, Obsessional

4 I, Obsessional I, Obsessional ~ - _ _ _ _ _

I, Schizophrenic I, Schizophrenic

3, Obsessional 3, Schizophrenic 3. Schizophrenic I, Hypertensive I

-__ 12 I, Depressive

__ - -_ I I, Agitated

4 I, Obsessional

I I, Obsessional

I I, Obsessional

depression -- 2, Depressive I, Anxiety state

~~ ~ _ _ _ - --___-

24 I5 S I

remaining hair in balding patients. The scalp flap and a flap of epicranium are reflected forward, and large trephine circles are fashioned to within I cm. of the midline, as low down as possible. The dura is opened and a transverse incision 24cm. wide is made in the cortex. A 2-cm. cleft is then opened in the white matter which is divided with a fine suction tube, as spatula forceps are introduced and the incision deepened. Puncture with a ventricular needle ensures that the cut is kept I cm. above the

from the falx. Unless this point is checked, the weight of the spatula handles may cause right lateral deviation with the result that the incision misses its objective and passes laterally to Area 13, on the right, an event which will entirely vitiate the result,

FIG. 3.-Diagrammatic representatlon of the effect of the weight of the spatula handles in causing right lateral deviation of the tips of the spatula blades unless care is taken to ensure that the inner tip of the blade i s kept at I cm. from the midline.

as shown later by the difference in effect between unilateral and bilateral stereotaxic implants (Fig. 3).

There is evidence that the maximum benefit is derived from the posterior 2 cm. of the incision. We

orbital roof, the incision being kept on this descend- ing plane as it passes below the head of the caudate nucleus (Fig. 4). Direct observation confirms that the inner tip of the spatula blade is kept I cm.

have re-operated in 10 early cases when a first opera- tion with a s-cm. cut had failed; a second operation extending the cut posteriorly for a further centimetre produced success in 6 cases. In various types of

KNIGHT: SURGERY OF ORBITAL CORTEX

failed leucotomy the formation of this incision behind the plane of the leucotomy scar, encountered at points up to 4 cm. from the frontal pole, has produced numerous successes. We have performed 15 repeat undercutting operations and, by improving the posterior portion of the incision, have obtained success in I I cases (Tables I, ZZ).

In a variety of failed leucotomies improvement has been obtained in patients who have had 2 or 3 pre- frontal operations and in 7 out of 12 failed single prefrontal operations, as well as in examples of trans- orbital, rostral, and Grantham operations, a total of 15 out of 24 cases being improved.

There therefore appears to be a concentration of fibres in the last 2 cm. of this narrow incision, division of which produces adequate relief of symptoms (Fig. 4). Whether these are descending fibres passing down from the frontal cortex through the substantia in- nominata towards the hypothalamus, or whether these are directly connected with the primitive agranular cortex of Area 13, cannot be stated, but we regard this area of the substantia innominata, lying beneath the head of the caudate nucleus and overlying Area 13, as an important objective in treatment. Vertical incisions which enter this area, however, produce serious damage, as a result of which this area was for long regarded as t2boo.

In 1943 (Knight, 1943) we demonstrated that posterior vertical incisions should never be employed, an observation amply confirmed by Meyer and Beck (1945), Zeigler and Osgood (1945), and others. Beck, Meyer, and McClardy (1948) conclude that the agranular and the disgranular areas should not be impinged upon by vertical incisions, their general conclusion being that all cases showing restlessness or autonomic disturbance exhibited bilateral damage to the posterior orbital region or striatum, or both. However, it must be the additional effect of the lesion in the striatum which produces these harmful effects. In a balanced mechanism which involves rhinencephalic and cortical areas, the effects pro- duced by a cortical lesion are entirely altered if the

Table III.-MORTAI.ITY Total cases at Earlv ooerative mortalitv

Dec., 1962 463 I , HypeGen'sive. Status ep.- I, Hypertensive. Hemiplegia.

Second operation 15 I, F.F.L. scar. i.v. haemorrhage

Total operations 478

Delayed operative mortality I, Coronary thrombosis first day I, Cerebral thrombosis seventh day I, Bronchopneumonia twelfth day

3

-

Total mortality 6 (1.24 per cent)

rhinencephalon is subjected to concomitant damage (Bard and Mountcastle, 1948). Numerous animal ex- periments illustrate this principle, contrasting effects being produced in different species by species differ- ence. In the human the difference between the damag- ing effect produced by incisions which enter the posterior orbital regions on a vertical plane, compared with the beneficial effects of a horizontal incision, can be explained on this basis.

PROGNOSIS By December, 1962,463 cases had been treated by

restricted orbital undercutting. All had previously received psychiatric treatment by various means without relief, sometimes for as long as 12-15 years in patients who responded satisfactorily. In general, a better prognosis attaches to patients who are

FIG. 4.-Sagittal section of left frontal lobe showing the situation of the 6-cm. incision, and A-A the last 2 cm. of that incision in the substantia innominata. The underlying cortical Area 13 lies behind and below the ascending thalamofrontal radiation, which passes between the caudate nucleus ( 5 ) and putamen (6 ) . The posterior vertical incision is seen t o cross the corpus striatum before entering the posterior orbital region. (Figs. 4, 6 reproduced by kind permission of Professor Srelmasiak and the Polish State Medical Publishers from ' The Anatomical Atlas of the Human Brain and Spinal Cord'.)

operated on at an earlier date. Age is not a deter- mining factor. I n the absence of hypertension and other physical abnormalities, success may be ob- tained in the 70-80-year age-group.

The mortality is low (Table ZZZ). Six patients died out of 478 operations, or 1.24 per cent; but 2 were hypertensive. The operation should not be per- formed in the presence of gross hypertension. If these cases were excluded the irreducible mortality of 4 would represent a fraction of I per cent. The quality of recovery is high. Psychological tests usually reveal an improved score. Unlike the leuco- tomized case, the patients who are improved remain warm and normal emotionally and fully capable of enjoying both work and leisure.

Tredgold (1963), in an analysis of 350 cases, has shown that the symptoms most effectively relieved are anxiety and depression, but that obsessions, insomnia, delusions, hallucinations, hypochondriacal preoccupation, and lack of confidence all improve in over 50 per cent of cases. Relief may be apparent immediately, or a gradual improvement may con- tinue for as long as 3 years. During the early stages, postoperative psychiatric management, support at home, and work opportunity can determine the level of success that a patient will achieve. Release phenomena of outspokenness and aggression, and the phase of laziness and over-relaxation seen in the early weeks, respond well to firm management, but may persist as a permanent personality blemish if support is lacking. Each case presents an individual problem in which the prognosis will depend not only on the nature of the psychiatric illness but on the personality of the patient, and the environment to which he must return, which may represent a

118 BRIT. J. SURG., 1964, Vol. 51, No. 2, FEBRUARY

31 I 45

W.R. 3

___ W.R. 2

_____I__---

W.R. I 22

continuing source of stress. When symptoms have been removed by operation the underlying personal- ity becomes more clearly revealed: hence a well- preserved personality recovers well; the hysteric, the psychopath, the schizophrenic, or inadequate person, relieved of their distress, may remain, by their nature, a continuing psychiatric problem.

A reduction of tension and agitation benefits un- differentiated tension states and anxiety neurosis.

A young girl, referred as a query schizophrenic, had made several suicidal attempts, and more than one spirited attempt to strangle her medical superintendent; under the influence of lysergic acid she literally bit and tore. An excellent relief of tension was obtained, and after patient rehabilitation, despite a difficult environment, she is now working steadily, 8 years after operation.

Mr. X had lived, since 1945, in constant fear of meeting people and was afraid of falling in the street; the mere thought of going anywhere made him perspire and tremble. He had not worked for years, his family lived on National Assistance, and his wife's health deteriorated from frustration. After operation he leads a full and active life and enjoys both work and leisure.

T h e operation is extremely effective in depression, melancholia, and depressive stupor. Examples include a woman who sawed off her right arm as a gesture of despair, another who threw herself from a cliff, sustaining a fractured skull-both of whom are fully recovered-and a woman who had remained i n a stuporose state for many years.

The latter sat huddled in a chair without spontaneous speech, and if spoken to would only answer, 'I don't know. What is the use? I am dead.' She was convinced she had practised witchcraft and that she had died in 1953. She was unable to remember where she lived or how many children she had. Following operation in the summer, on the recommendation of Dr. Strom-Olsen, she succeeded in running Christmas for her husband and family, who regarded her recovery as IOO per cent, and in the following year resumed full activities, playing in tennis matches for her club, and enjoying an active holiday in the south of France.

10 Slightly incapacitated. Regular part-time employment

Unfit for regular employment. Regular household work

120 Grossly incapacitated. Sits about. Occasional chores

___- 43 Considerably incapacitated.

_-

--

In schizophrenia, severely agitated or disturbed patients whose personality is well preserved may respond well, and, with the reduction in emotional tension, delusional patterns and hallucinations may fade. Poverty of emotion is sometimes seen post- operatively as a feature of the schizophrenic person- ality, in contrast to the normal emotion of other postoperative states.

A patient from South Africa, who had been confined in Pietermaritzburg for 7 years, often completely intractable and vividly hallucinated, flew back to South Africa unaccompanied 5 months after operation. She obtained a post in a Government office which she has held satisfac- torily at a time when others have been discharged for redundancy. Her father states that aparr from a certain tendency to desire her own way her recovery is complete.

T h e effect of operation on working capacity is shown in Tredgold's analysis of 177 cases (Table I V ) .

Table IV.-WORK RATINGS (W.R.) IN 177 CASES (R. TREDGOLD)

PREOPERATIVE POSTOPERATIVE W.R. 4 I 79 lk7zzzz7 -

No. OF CASES PREOPERATIVE DISABLEMENT

No SLIGHT SYMPTOMS.

SYMPTOMS " " ~ ~ ~ ~ ~ " ' s o ~ ~ & ~ ~ ~ M s UNC-ANCID DETERIORATED TREATMENT Free from medical care

Whereas IZO were grossly incapacitated prior to operation and only 4 were in regular employment, after operation gross incapacity was reduced to 2 2 ; 79 were in full employment and 45 were in part-time employment. These results were obtained in a mixed

2 . Socially disabled, i.e., out of hospital

I . Totallv disabled, i.e., in mental

Total

but unable to work

hospital

Table V.-~LASSIFICATION OF 450 RESULTS ACCORDING TO PREOPERATIVE DISABLEMENT AND POSTOPERATIVE RESULTS I I I I I I

I12 31 31 38 I 1 I

228 57 63 67 39 2

450 I18 123 I34 70 5

~ ___ _ _ _ ~ _ _ ____-___- ~

- -~ 3. Psychiatrically disabled, i.e., out of

mental hospital but in need of con- stant psychiatric help and treatment including drugs and E.C.T. 1 I 1 0 1 30 I 29 1 29 I 20 1 2

Relief has been obtained i n drug addiction and alcoholism when the cause of this addiction has been an escape from a depressive illness, the patient seek- ing sedation by this means. In hysterics, useful results can be obtained when the patient is genuinely distressed, but great care is required i n the selection; everything depends upon the amount of tension present, and the genuine fear and concern that the patient feels for his imagined ill health.

series, certain of whom might now be regarded as unsuitable on account of their psychiatric syndrome or personality, but who were originally included in this series for research purposes.

W e have classified 450 cases according to pre- operative disablement and postoperative state (Table V) . Preoperative disablement is expressed in three categories :-

I. Totally disabled-in mental hospital.

1 I9 KNIGHT: SURGERY OF ORBITAL CORTEX

No SLIGHT SYMPTOMS.

Free from medical care

No TREATMENT TYPE REQUIRED

2. Socially disabled-out of mental hospital but unable to work.

3. Psychiatrically disabled-out of mental hospital -working part- or full-time-in need of constant psychiatric help and treatment.

Postoperative results are expressed in five grades :- Group ~.-NO symptoms. Group 2.-Slight symptoms. No treatment

Patients in both these groups were free from

Group 3.--Improved, still some symptoms re-

In Group 3, certain patients were still receiving treatment only for such conditions as headaches, insomnia, or epilepsy, whereas their previous psychiatric syndrome had improved to a greater or lesser degree.

required.

medical care.

quiring treatment.

Group 4.-Unchanged. Group 5.-Worse.

Of a total of 450 cases 241 were free of medical care and 134 are improved. Of 228 patients previously in mental hospitals, 120 are free of medical care and 67 are improved.

Results analysed in relation to type of psychiatric illness (Table VZ) show that the greater number of successes are among the depressions. Fewer anxiety states reach the highest grades. Obsessional compul- sive states, although responding well, do not do as well as depressives.

I n schizophrenia a far smaller proportion of patients with good personalities are benefited. Patients of poor personality, the hysterics, the

s O ~ ~ ~ ~ ~ ~ M s UNCHANGED DETERIORATED TREATMENT

So much for the benefit. There is a loss (Table VZZZ): 10 per cent of patients show an occasional epileptic fit; 50 patients exhibited seizures; 4 were epileptic before operation; 46 developed seizures postoperatively. I n 2 the diagnosis was very doubt- ful; 3 had a single seizure, which was definitely precipitated by the use of tranquillizers. Twenty

Hysteria ~- Obsessional compulsive states

Anxiety states

Devressions __-

[RECURRENT NPRESSIOH 1 HOSPIIAL AOYISSIOYS

SIYIE wriaiinw H O S P l I A l AOHlSSlONS

BtlORI O?tllhllOil

I . . I . .I

I 2 4 6 I

13 15 24 I 2 I

-___ -

8 26 20 4

91 64 52 I1 3

FIG. 5.-Diagram of the influence of operation on recurring mental hospital admissions in recurrent endogenous depression, showing the number of admissions in 5-year periods before and after operation. The iength of hospitalization, antedating the 5-year preoperative period, is recorded on the left.

Table VZ.-POSTOPERATIVE RESULTS ANALYSED IN RELATION TO TYPE OF PSYCHIATRIC ILLNESS

Schizophrenia 25

Hypochondriasis. Chronic pain. Mixed syndrome, including psychopathy

I I , ,

psychopaths, and hypochondriacs do not do so well, although some improvement can be obtained by careful selection.

The results in depressive illness are encouraging (Table V l l ) . Of 221 cases, 155 were free of medical care, 52 were improved, and 11 were unchanged. Reactive depression and endogenous depression did equally well in each group. I n the endogenous depressions recurrent endogenous depression was particularly successful, many patients reaching the highest grade (Fig. 5). I t was interesting to observe how operation cut short the regular sequenceof hospital readmissions which had characterized their course, the only patients remaining in hospital usually being those who had no home to go to after years of long- standing illness.

had a single seizure only which was rcadily con- trolled, and some of these may have been related to the use of tranquillizers, though proof was lacking. Twenty-one (approximately 5 per cent) had more than one attack despite phenobarbitone, but only 7 of these regarded the attacks as being a handicap. Many patients with single seizures forgot to men- tion them until they were asked, and the majority regarded the price as being well worth the relief they had obtained.

STEREOTACTIC OPERATION There are postoperative personality changes, some

of which are beneficial, but in Tredgold's analysis (1963) approximately 5 per cent exhibit some deteri- oration of behaviour with evidence to suggest that

I20 BRIT. J. SURG., 1964, Vol. 51, No. 2, FEBRUARY

this is not merely due to progression of their psychia- tric illness but results from damage derived from operation.

It was with the object of eliminating these features that an attempt has been made to devise a method of stereotactic operation which reduces the extent of

FIG. 6.-Coronal section showing site of an incision approximately 1.8 cm. wide in the substantia innominata. The thalamofrontal radiation is in relation to its anterior and lateral aspect between the putamen (8) and the caudate nucleus (9). The genu of the corpus callosum descends from its inner aspect.

scarring in the brain. I t was decided to explore the possibilities presented in the posterior z cm. of the incision (Fig. 4). Anatomically this zone of the substantia innominata contains fibres descending from the frontal cortex converging towards the hypo- thalamus and others derived from the amygdaloid complex (Nauta, 1961) and an important projection from Area 13 of the cortex. Area 13 receives few afferent fibres from the ascending thalamofrontal projection and, indeed, lies well below and largely behind it. It gives origin to descending tracts

tory responses may be obtained from areas which, under different conditions, yield inhibitory response.

Spencer (1894), Bailey and Sweet (1940), and Delgardo and Livingston (1948) obtained changes in

FIG. 7.-Modification of McCaul’s stereotactic device with moving vernier scale added showing the implanting needle, with collar containing millimetre screw adjustment to control depth of implantation. This collar is set with the implanting needle withdrawn to the I-cm. control mark.

Table VZI.-POSTOPERATIVE RESULTS IN DEPRESSIVE ILLNESS (Recurrent Endogenous Depression. Involutional Depression. Reactive Depression)

I I I I I I

3 171 20 I I1 I 9 I 3

which project through the genu of the corpus callosum to the venteromedial hypothalamic nuclei (Fig. 6).

Le Gros Clark and Meyer (1950) have demon- strated a massive bilateral projection (Fig. 6). Wall, Glees, and Fulton (1951) have described a similar pathway. Ward and McCullough (1947), using strychnine oscillography, have fired paraventricular and posterior hypothalamic areas from the posterior orbital cortex. Experimental stimulation yields con- flicting results, certain of which are accounted for by species difference and others by the condition of stimulation, for, as Karda (1951) has shown, excita-

respiration and blood-pressure, and gastric motility on stimulation of Area 13. Similar effects have been obtained in the human by pre-leucotomy stimulation (Livingston, Chapman, Livingston, and Kraintz, 1948). It is perhaps significant that these are accom- paniments of intense emotion. Through connexions with the ventromesial nuclei the orbital cortex may produce an influence upon brain-stem mechanisms which are executively concerned in the expression of rage. Wheatley (1944) showed that lesions which destroy these nuclei are invariably associated with savage behaviour, suggesting that inhibitory influ- ences are eventually channelled through these areas.

KNIGHT: SURGERY OF ORBITAL CORTEX I21

These observations suggest that operation in the no farther than I mm. beyond the margins and to a region of Area 13 might have a significant effect upon somewhat greater extent above and below the plane, the intensity of emotional reaction. which corresponds well enough with the softening

In 1960, experiments were begun at Hammersmith resulting from bruising on either side of a surgical Hospital with the object of isolating this area by incision. stereotaxic methods. Markers inserted into the intra- cerebral incision at open operation localized the area in relation to skull landmarks ; the posterior margin of the incision lay I cm. above the anterior clinoid

Table VIII.-TOTAL OPERATIONS, 475 50 Patients exhibited seizures 4 Epileptic before operation

46 Developed seizures postoperatively J 1 Approximately Io per cent

Diagnosis very

Single seizure only,

doubtful 2

precipitated by tranquillizers 3

Single seizure only, readily controlled by phenobarbitone 20

despite phenobarbitone 21

by patient 7

More than one attack,

Regarded as handicap

FIG. 8.-Stereotactic device in situ. The distance between

between the lower sphere and the centre of rotation of the instrument. The site of the target area is marked on the radiograph

to cross the perforated scale. If the aiming needle is now moved to this point it will he directed accurately at the target in this plane.

Process ; transversely it Was placed Over the inner

of the midline. T o form the equivalent Of a flat

the two spheres on the aiming needle corresponds to the distance

and a line projected from this point through the centre of rotatio;

third of the sphenoid wing, extending to within I cm,

incision in this area, having length and breadth but little depth, it was decided to implant rows of

A FIG. 9.-A, Anteroposterior and, 6, lateral view of the yttrium seeds

four seeds of radioactive ytrrium [Yg0] within a zone 2 cm. long, 1.8 cm. wide, at a height I cm. above the orbital roof (Figs. 4, 6). The necrotic dose being empirically believed to be 30,000 rads, we used seeds yielding a total of 50,000 rads at the edge of the plane and 80,000 rads maximum between the seeds. Since the dose outside the plane falls by 50 per cent with each millimetre of distance, the necrotic dose extends

B placed in position to irradiate a plane 1.8 cm. wide by 2 cm. long.

A modification of McCaul’s (1959) apparatus has been constructed, having a moving vernier attach- ment fixed to the perforated scale (Fig. 7). The implanting needle has a millimetre screw attachment to control the depth of implantation of the deepest row and a centimetre control marker to ensure that the needle is withdrawn to this extent when the anterior row of seeds is implanted. The instrument

I 2 2 BRIT. J. SURG., 1964, Vol. 51, No. 2, FEBRUARY

is aimed by hand at the presumed target and then corrected first i n the sagittal and then in the trans- verse planes by radiographic control, and is thus set on target for the inner row of seeds. T h e implanting needle is tested for depth by radiographic control and adjusted by the millimetre screw (Fig. 8).

The deepest seed is inserted, the needle withdrawn I cm. to the control marker, and a second seed inserted. T h e needle is withdrawn, the vernier scale moved to the next site of implantation, and the process repeated until four lines are sown at regular intervals, the process being repeated on the opposite side (Fig. 9).

RESULTS In early cases we performed the implant on one

side at a time and it was interesting to observe only a minor reduction in symptoms from the unilateral

easily, and becoming markedly agitated. She developed depressive stupor, with shorter and shorter remissions following E.C.T. Leucotomy had failed in 1956, and she had remained for 4 years practically mute. Following implantation in 1961 she made steady progress. She began to talk, at first in a whisper, and is now quite cheerful, talks normally, and has not been depressed since her return to mental hospital where she is full of activity, awaiting discharge to live with a friend.

Later cases have been treated by bilateral implants in one stage. One severe hysteric was not improved but made a fair recovery following open operation, indicating perhaps that too great a refinement with elimination of reduction of affect is not advantageous in the hysteric in whom some blunting of feeling may be desirable. One anxiety state with depression, auricular fibrillation, and cardiac failure relapsed after 6 months. One other anxiety state has not

A B C FIG. IO.-A, A bedridden patient, aged 79 years, with a I6-year history of melancholia. 6, Three months after operation, showing

animated facial expression. C, SIX months after operation, visiting her friends.

operation followed by marked improvement when the second side was completed, indicating how easily failure may follow blind or open operations if one side misses the objective over Area 13. This is an experimental method designed with a view to mapping out this area. I t is hoped to determine later whether the operation can be restricted still further to the region of the genu of the corpus callosum. Initially the method was used only on patients too ill by reason of physical infirmity to stand the open operation, but the results have been sufficiently consistent to permit younger patients to be referred with a request for this operation. T w o early cases may be described.

B. G., aged 79 years, following a 16-year history of melancholia with three suicidal attempts and twelve mental hospital admissions, was severely crippled with arthritis, suffering from cardiac fibrillation and extensive bed-sores, had chewed her lip into a mass of granulations, and was mouthing, muttering, and restless. She would have died soon from hypostatic changes and inanition. After operation she was able to live at home, cheerful and composed, had no drugs by day, and slept well without tablets ; her heart, which was fibrillating before operation, was steady (Fig. 10).

F. C., aged 66 years, had suffered from melancholia for 18 years, was nervous and terrified, saying little, weeping

improved. An elderly patient aged 75 years, with marked cerebral atrophy, has had persistent enuresis since operation, which is the only evidence of bladder disturbance which we have detected. Other cases have maintained their improvement, the maximum period of review being 2 years.

A woman, aged 33 years, with continuous depression of 8 years, which had been steadily increasing, as a psychiatrist said, despite every possible form of modern chemotherapy, singly and combined, had progressed to a near-suicidal state and at one stage had sustained largactil poisoning. She is said to be vastly improved and for the first time in years relatively cheerful and normal.

A man, aged 79 years, with recurrent depression of 24 years’ duration, had made four suicidal attempts in 2 years and had had six mental hospital admissions. At his last admission, having attempted suicide with an overdose of tablets the previous day, he tried to hang himself behind the door with a bandage on the day following admission. He is reported 6 months after operation to have a normal mood, to have retained his interest in sport, to be very sociable, to require no medicine, and to be eating and sleeping well.

A Methodist preacher, aged 68 years, spent his nights sitting up in bed catling on his Maker to take him, repeating the hymn, Where is the peace that once I knew’. By day he entertained strong pyrogenic feelings

KNIGHT: SURGERY OF ORBITAL CORTEX

A 6 FIG. I I.-A, Patient suffering from severe obsessional illness. Showing marked emotional tension whilst attempting to handle a shawl

prior to operation. 6, After operation. Knitting quietly. Well relaxed and composed.

towards the Church of Rome. He has now returned to preach in his own denomination, and regards others with tolerance.

A very obvious improvement (Fig. I I A, B) was obtained in a woman, aged 56 years, suffering from an obsessional ill- n e s with marked tension and depression, following the loss of her husband and son in a drowning accident. She was described as ‘polite, but grim’, and looking upon the world as ‘a vale of tears’. She was considered to be a suicidal risk, and exhibited persistent tension and a disturbed facial expression. Prior to operation she was unable to handle things and repeatedly asked for a locker to be cleared for fear that she would throw things. She was quite unable to handle anything without hurling it away. After operation she could knit steadily while conversing pleasantly. She has maintained this improvement. She says that she has received a wonderful relief although she is still slightly depressed at times, which is only natural in the circum- stances, but she is therefore only classified in Grade 3.

SUMMARY Twenty-five patients are now ready for review out

of 30 operations. One can, of course, only give a limited description i n follow-up tables, as many elderly patients are bound to exhibit symptoms other than psychiatric ones, as a result of their age and disability. We have therefore used the Groups I , 2,

STEREOTACTIC OPERATION Results of lirst 25 cases

no - RtCURRtYT OtQRISS10N 0 - OEQRtSSlOLl AYX - A U X l t l V SlAlE HVP- HVWCHQYORIASIS

00s -DBISSIOYU

I I V S - R V S X R I A 3 to express freedom from, and improvement in, psychiatric state, and need for continued treatment

FIG. ~z.-Result of first 25 cases of stereotactic operation, showing age of patient, degree of improvement in psychiatric symptoms, duration of illness in ~ years, and psychiatric state. for psychiatric symptoms only (Fig. 12).

Of 25 patients : 8 are completely relieved in Group I ; 10 are to all intents and purposes completely been achieved without mortality i n patients of relieved and require no treatment; 4 are improved advancing years and poor physical condition. Four and still require drugs; 3 are unchanged. This has patients over the age of 79 years, 3 with depressive

BRIT. J. SURG., 1964, Vol. 51, No. 2, FEBRUARY

symptoms of more than 15 years’ duration, and 4 others above the age of 59 years, some with illnesses of 10-20 years’ duration, reached Group I . Nine patients between the age of 60-70 years, and 5 with illnesses of 10-20 years’ duration, reached the second Group. Two previous failed leucotomies have been improved. One patient had a single epileptic fit in the first 24 hours after operation, which has not been repeated. These results are obviously significant and indicate that relief can be extended with little risk to geriatric patients, certain of whom suffer severely from the depressive illness of old age.

Operation in the region of Area 13 therefore has a marked effect in diminishing the intensity of depres- sive illness. I t likewise diminishes the intensity of emotional reaction in certain cases of obsessional illness and in chronic anxiety states. It has been effective in cases where the standard prefrontal leucotomies have failed. I t produces improvement in some cases of hysteria, but is insufficient in others who require the fuller operation, possibly to produce a blunting of affect.

We would suggest that it is possible that too much attention has been paid to the affective aspect of the post-leucotomy case. Perhaps we have tended to seek the origin of improvement in the effect of opera- tion upon emotional feeling, whereas the intensity of a patient’s reaction to emotional experience may be of equal or greater significance. The relaxation of an individual relieved of agitation and distress, whose emotional feeling and appreciation remain intact, may well suggest that it is the isolation of areas concerned in intense emotional reaction which has contributed to this success, and that the effect upon descending effector pathways passing towards the hypothalamus has contributed markedly to their improvement.

Acknowledgements.-I would like to acknow- ledge my debt to the many friends who have helped me in this investigation. One cannot mention them all. Particularly my psychiatric colleagues, Dr. Strom-Olsen, Dr. Tredgold, Dr. Sargant, Dr. Rice, Dr. Ainslie, Dr. Bram, and Dr. Backus; and recently, at the Postgraduate Medical School, my colleagues in the Physics Department and the Department of Radiology, who have given so much of their time and upon whose work the accuracy of the stereotaxic operation entirely depends. The results which have been obtained originate from our concerted effort, in which operations have played only a part.

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