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The growth hormone and hypotensive responses to clonidine have been measured in six drug free severely depressed patients before, and at two weeks after, the surgical procedure of stereotactic sub-caudate tractotomy. The responses were unaltered two weeks after operation, by which time a small clinical improvement was evident. These findings are discussed in relation to central alpha adrenoceptor functions in depression, and the effect upon this of antidepressant treatment.

Psychiatric patients undergoing the psychosurgical operation of stereotactic subcaudate tractotomy were infused intravenously with either saline or L-tryptophan (15 mg/kg/h). Plasma, lumbar cerebrospinal fluid (CSF), ventricular CSF and a specimen of frontal cortex were collected. The relationships of plasma concentrations of substances claimed to influence brain tryptophan concentration (total tryptophan, free tryptophan, large neutral amino acids) with the concentration of tryptophan in the cortex and CSF were investigated. Tryptophan infusion resulted in plasma tryptophan values comparable to those found after oral doses used in treating depression or insomnia, and about sixfold increases of tryptophan in the cerebral cortex. Increased brain 5-hydroxytryptamine synthesis was indicated by significant rises of CSF 5-hydroxyindoleacetic acid. The concentration of plasma free tryptophan was a better predictor than plasma total tryptophan of cortex tryptophan concentration. As all correlation coefficients of plasma versus brain or plasma versus ventricular CSF tryptophan concentrations were decreased when allowance was made for differences of concentration of large neutral amino acids, the results suggest that the role of these substances within their physiological range as inhibitors of tryptophan transport to the brain may previously have been overemphasised.

The concentrations of 3 putative neurotransmitters (glutamate, aspartate and gamma-aminobutyrate), 4 related amino acids and 5 non-transmitter-related amino acids have been measured in neurosurgical samples (frontal cortex) from patients with intractable depression and controls. In addition, the glutamate receptor agonist 2-amino-4-sulpho-butanoic acid (homocysteic acid) has been identified in human brain and measured in these samples. There were no changes in the concentrations of amino acids in depressed patients compared to control with the exception of aspartic and homocysteic acids which were elevated in a sub-group of patients with depression compared to control. The Ca2+-dependent release (K+-stimulated) of putative neurotransmitters has been demonstrated for the first time from brain tissue of depressed patients. Glutamate release was unaltered from the control value. Aspartate values showed unexplained variability but it's release and that of gamma-aminobutyrate were elevated in some depressed subjects. These results do not support the hypothesis of reduced amino acid function in depressive illness.

Plasma, cerebrospinal fluid and brain tissue amino acid levels were measured in 14 patients with affective illness and generally confirm previous findings. There was no correlation between these values and age, sex, family history and levels of anxiety. GABA levels measured in cortex tissue were negatively correlated with depressive mood (P less than 0.05), supporting a possible involvement of GABA in depressive illness.

Between 1979 and 1986 the number of psychosurgical operations carried out in Britain fell from 70 to 15 procedures annually. There are a number of possible reasons for this change of which increased experience with new regimes of psychotropic medication is perhaps the most important. The new Mental Health Act (1983) which brought psychosurgery under the direct jurisdiction of the law was followed by a sudden reduction in the number of patients treated but referals are now increasing. In current psychiatric practice, classification relies largely on description of syndromes, each characterised by a set of core symptoms. Schizophrenia and affective psychoses (endogenous depression, mania and obsessional illness of late onset) are characterised by disturbances of mood, thinking and perception often so profound as to impair the patient's contact with reality. In contrast, neuroses produce symptoms which are quantitatively, rather than qualitatively different from normal experience and psychosurgery has no place in their treatment. Following the introduction of phenothiazines in the early 1950's schizophrenia ceased to be an indication for psychosurgery. For a small group of severely disabled and distressed people suffering from endogenous depressive and obsessional illnesses, when other treatments have failed or ceased to be effective, psychosurgery remains an appropriate treatment. Just over half the patients treated at the Geoffrey Knight Unit are relieved to the extent that they are either free of symptoms or such symptoms that remain do not significantly impair social function. Following operation recovery is slow and progressive and a programme of rehabilitation is usually necessary. Personality which is often severely damaged by the effects of long illness returns towards normal. Neuropsychiatric evaluation has consistently failed to demonstrate adverse cognitive effects. Evaluation and selection of patients for operation should be done by a psychiatrist and neurosurgeon working in partnership. Stereotactic techniques have made it possible to produce precisely located lesions of consistent size, virtually eliminating side effects and reducing the epileptic risk to between two and three percent. The Mental Health Act, contrary to early expectations, has allowed that psychosurgery retains a place in the treatment of a small highly selected group of patients.

The routine air ventriculograms of 66 psychiatric patients, aged from 22 to 73 years, taken during the psychosurgical operation of stereotactic subcaudate tractotomy, were studied. Ventricular size was unrelated to progressive ageing, but a minority of patients over 60 years had abnormally large ventricles, not invariably associated with cognitive impairment on testing. Enlargement was associated with a clinical diagnosis of schizoaffective illness but not with past ECT.

The results of stereotactic subcaudate tractotomy in nine patients with resistant bipolar affective disorder are presented in the form of a single case study with a summary of the other eight cases. Follow-up studies at 2-4 years showed substantial improvement in five patients and amelioration of symptoms in a further four patients, with a tendency for a greater improvement in the manic than in the depressive episodes. These preliminary results suggest that there is a place for this operation in the management of severe bipolar affective disorders which are not responding to any other treatment, although decisive recovery occurs less often than with unipolar depression.

The relationship between neurotransmitter metabolite concentrations and measurements of ventricular size on CAT scans and pneumoencephalographs was investigated in 15 patients with severe affective disorder. An association was identified between reduced levels of plasma free tryptophan and ventricular enlargement, and also between raised ventricular CSF levels of 5 HIAA and ventricular enlargement.

With its head steadied within a form-fitting mask, a macaque was first taught to signal when it detected the application of 0.2-ms electrical pulses at 50 Hz through electrodes chronically implanted within its striate cortex. Stimuli were then applied via a movable microelectrode and the threshold for the animal’s detection determined at intervals of 50-250 micrometers. With permanently implanted 130- 200-micrometers diameter electrodes such thresholds range between 50 and 250 microamperes (and are highly stable), whereas with the microelectrodes sites were encountered, estimated to be primarily within cortical layers V-VI, where the monkey could reliably detect as little as 2-4 microamperes. The threshold at most sites within striate cortex with the microelectrode, however, was 15-25 microamperes. Background unit activity recorded with the microelectrode varied greatly in different laminae and survived the microstimulation, but has so far provided no clear basis for predicting threshold. It is tentatively hypothesized that the relatively rare points where the threshold is as much as 10 times less than that in the surround arise because the giant, solitary cells of Meynert provide the exclusively effective output for the behavioral response. This hypothesis would also explain the singular uniformity of sensation (a "phosphene") evoked in human subjects by such stimuli, and the equivalence of all such stimuli in striate cortex found for the macaque.

The firing frequency of a population of 213 units in striate and circumstriate cortex of the moderately restrained rabbit was studied under the influences of alternating 1-min periods of darkness versus steady, diffuse, featureless illumination. The intent was to determine whether luxotonic responses, so prominent in striate cortex of primates, are indeed absent in rabbits. Such was the case, there being only transient occurrences in three units where the continuing rate of discharge in darkness was double that in the light. There were, however, much more modest differences in rate of continuing discharge in light versus darkness, and for 46% of the units discharging greater than 1/s this difference exceeded 10% and/or 1/s. The rate of discharge in any case did not provide a reliable index as to the characteristics of a unit's receptive field in response to patterned visual stimuli. The nature and function of luxotonic activity in primates still not being understood, it cannot be decided whether its absence in rabbits represents a true qualitative or merely a quantitative difference between species.

The records of 377 patients with head injuries admitted to the South East Thames Regional Neurosurgical Unit in the two years following the introduction of the EMI scanner (computerized tomography) were examined. Each patient was assessed on the reason for transfer, the necessity for transfer, the safety of transfer and whether immediate access to a scanner would have altered management. The results show that the majority of patients were referred because of a possible intracranial haematoma. Thirty per cent of the patients required operation, in 6 per cent transfer was unnecessary and 10 per cent arrived with inadequate resuscitation. It is suggested that with a wider deployment of head-dedicated scanners to some accident centres, the number of patients with head injuries at present being transferred to special units for assessment would be reduced substantially, with improvement of patient care.

Tryptophan and 5-hydroxyindoleacetic acid (precursor and metabolite respectively of 5-hydroxytryptamine) were determined in ventricular CSF of psychiatric patients undergoing stereotactic subcaudate tractotomy. Tyrosine and homovanillic acid (precursor and metabolite respectively of dopamine) were also determined. Results suggest an association between affective state and the above precursor amino acids with lower concentrations in primary depression and higher ones when anxiety or agitation predominate. This leads to lower 5-hydroxyindoleacetic acid concentrations in depression and higher concentrations in anxiety and agitation.

Neuronal responses to continuous, diffuse white light or darkness were studied in cortical visual areas 17, 18, 19 and Clare-Bishop of the unanesthetized cat. In contrast to squirrel monkeys and macaques in which about 40 or 25% of the units in striate cortex are luxotonic (response to continuous light or darkness sustained > 2.0 min), all of the visual areas in the cat had fewer than 4.0% of the units exhibiting such luxotonic activity. The functional basis of this difference may be related to differences between the two species in the quantitative balance of antagonistic receptive field properties.

An approach to evaluating the cost-effectiveness of high-technology diagnostic equipment has been devised, using the introduction of computerised axial tomography (CAT) as a model. With the advent of CAT scanning, angiography and air encephalography have a reduced, though important, role in investigating intracranial disease, and the efficient use of conventional equipment requires the centralisation of neuroradiological services, which would result in major cash savings. In contrast, the pattern of demand for CAT scanning, in addition to the acknowledged clinical efficiency of the scanner and its unique role in the head-injured patient, ephasies the need for improved access to scanners. In the interest of the patients the pattern of service must change.

Using permanently implanted electrodes in squirrel monkeys and macaques, transmission through the lateral geniculate nucleus (LGN) was assayed from the amplitude of potentials evoked in optic radiation by and electrical pulse applied to optic tract. Averaging of either individually or machine selected potentials, elicited at 0.3, 1.0, 20 or 50 HZ, in all cases showed a decrease in transmission ranging from 5-60% in the period after saccadic eye movements made ad libitum. The suppression was greater in a patterned visual environment than in diffuse illumination, which in turn was greater than that occurring following saccades in the dark. Demonstration of the effect in darkness always required data averaging and never exceeded 20%. The effect was consistently greater in the magnocellular than parvocellular component. Suppresion was often abruptly terminated and replaced by a facilitation of 5-15% about 100 msec after saccade detection. Comparable effects were observed for excitability of striate cortex tested by a stimulus pulse applied to optic radiation. In addition, sharply demarcated potentials inherently arising in LGN and striate cortex were found in association with saccades made even in total darkness. Neglecting a possible but dubious contribution from eye muscle proprioceptors, the experiments establish the existence of a centrally originating modulation of visual processing at both LGN and striate cortex in ralation to saccadic eye movement in primates. This modulation may partially underlie the phenomenon of "saccadic suppression" and hasten the acquistion of a meaningful visualsample immediately following an ocular saccade. It remains uncertain as to how it may relate to similar or greater effects accompanying changes in alertness, or to fluctuations of unknown origin occurring sometimes semirhythmically at 0.05-0.03 HZ (Fig 7).

The records of the first 571 patients to be examined with an EMI brain scanner were assessed. The patients were divided into diagnostic categories according to their clinical presentation. The intracranial investigations that would have been performed had the scanner not been available were compared with the investigations that were actually performed. As expected, the number of contrast investigations fell, but the reduction surpassed expectation. If the full clinical impact of the scanner is to be realised the patient's illness must be defined in detail and strict attention paid to radiographic detail. By reducing the number of special contrast investigations use of the scanner enables existing contrast facilities to serve a wider population; and use of the brain scanner in district general hospitals would improve the service to patients, especially those with head injuries.

The results of treating 85 patients suffering from craniopharyngioma are reviewed. The recurrence of the tumour after 20 symptom-free years after radical excision is reported. Claims for successful treatment of this illness should be reviewed in this light.