Historical development of neurosurgery for psychiatric disorders

The trajectory of neurosurgery for mental illness differs markedly from that of movement disorders. Although Swiss psychiatrist Gottlieb Burckhardt performed the earliest psychosurgical operations in 1888, the field came to be dominated decades later by the frontal lobotomy, introduced by Egas Moniz and popularised by Walter Freeman, neither of whom was a trained neurosurgeon. These procedures were anatomically imprecise, widely destructive and associated with substantial adverse effects and disability, leaving lasting ethical and professional concerns about psychosurgery.

As with large resections in movement disorders, frontal lobotomy for mental disorders was rightly abandoned in favour of stereotactic neurosurgery. Procedures such as anterior cingulotomy and anterior capsulotomy now targeted symptoms of obsessive–compulsive disorder (OCD), anxiety and depression with greater anatomical precision, aiming to minimise the cognitive and personality side-effects that had plagued lobotomy.

The Geoffrey Knight psychosurgical unit represented one example of a stereotactic ablation service that remained active in the UK into the late 20th century. However, as with movement disorders, this activity declined following the increasing reliance on, and preference for, pharmacological treatments, together with an understandable revulsion at the history of neurosurgical treatments for mental health conditions in an era when the biological roots of mental illness were less well understood. The renaissance of neurosurgery for medically refractory movement disorders has not been replicated in the field of psychiatry for individuals with treatment-refractory mental health conditions.

In a similar way to movement disorders such as Parkinson disease or tremor, the symptoms of OCD and depression can be conceptualised as arising from abnormal circuit activity, making the underlying networks plausible targets for neuromodulation. This framework has supported renewed academic and clinical interest in neurosurgical approaches for psychiatric disorders, particularly following the success of DBS in neurological conditions. Researchers have subsequently explored the application of DBS to Gilles de la Tourette syndrome, OCD and depression.

Gilles de la Tourette syndrome

Gilles de la Tourette syndrome is a disorder that bridges the artificial divide between neurology and psychiatry. Severe symptoms can be profoundly disabling, with motor and vocal tics, social and occupational impairment, self-injury and elevated suicide risk. For individuals who do not respond to behavioural and pharmacological treatments, DBS has shown encouraging results in both observational studies and randomised trials. Common targets include thalamic nuclei and the globus pallidus internus, with evidence of sustained reductions in tic severity in selected patients. ^{Reference Johnson, Fletcher, Servello, Bona, Porta and Ostrem1}

OCD

Among psychiatric conditions, functional neurosurgery has the strongest evidence for efficacy in OCD. Although many individuals improve with cognitive behavioural therapy and serotonin reuptake inhibitors, a significant minority remain severely symptomatic, experiencing an often extremely disabling and lifelong burden of illness.

Stereotactic anterior capsulotomy and anterior cingulotomy aim to interrupt abnormal activity driving OCD symptoms while having minimal effects on personality and neurocognitive functioning. Evidence includes randomised trial data for gamma-knife capsulotomy, as well as a substantial body of open-label studies with approximately two-thirds of patients experiencing clinically meaningful improvement. ^{Reference Lopes, Greenberg, Canteras, Batistuzzo, Hoexter and Gentil2}

DBS has also been investigated for OCD, particularly targeting the ventral anterior limb of the internal capsule (ALIC) and the anteromedial subthalamic nucleus (amSTN). ^{Reference Luyten, Hendrickx, Raymaekers, Gabriëls and Nuttin3,Reference Mallet, Polosan, Jaafari, Baup, Welter and Fontaine4} Randomised controlled trials have demonstrated clinically meaningful reductions in Yale–Brown Obsessive–Compulsive Scale scores. A key study directly comparing these two targets found that they produced similar large symptom reductions, but with some target-specific differences: amSTN stimulation improved cognitive flexibility whereas ALIC stimulation had a stronger positive effect on mood. ^{Reference Tyagi, Apergis-Schoute, Akram, Foltynie, Limousin and Drummond5} This supports the idea that different anatomical targets modulate different but interconnected circuits.

There are currently no head-to-head randomised comparisons between DBS and ablation for OCD, but multiple literature reviews suggest that stereotactic ablation may be at least as effective, and possibly more beneficial than DBS, for severe OCD. ^{Reference Pepper, Hariz and Zrinzo6} For severe or extreme OCD, capsulotomy may produce higher remission rates whereas DBS carries device-related risks such as infection and hardware malfunction.

Treatment-refractory depression

Depression is a leading cause of global disability and mortality and, like OCD, is increasingly understood as involving dysfunction in specific brain circuits. Although most patients respond to psychotherapy, medication or electroconvulsive therapy, a small group will not.

Compared with OCD, the evidence for neurosurgery in treatment-refractory depression (TRD) is more limited. Ablative procedures such as anterior capsulotomy and anterior cingulotomy have been evaluated primarily in open-label studies. One systematic review suggested that over half of patients responded to surgery, with up to a third reaching symptomatic remission. ^{Reference Joyce, Matthews, Christmas and Zrinzo7} Importantly, neurocognitive and personality testing do not show significant negative effects at follow-up, but the absence of randomised controlled trials and the potential for selection and expectation biases should be acknowledged and addressed in future research.

DBS has also been investigated in TRD, targeting the subcallosal cingulate cortex, ventral capsule/ventral striatum and medial forebrain bundle. Although early open-label studies were promising, results from sham-controlled trials are mixed, highlighting the complexity of this condition and the challenges of conducting neuromodulation research in psychiatry.

Focused ultrasound (FUS)

Magnetic resonance-guided FUS represents a major development in stereotactic surgery. It enables incisionless ablation with real-time imaging and thermal monitoring, and more readily accommodates sham procedures for blinded trial designs. FUS has been validated in essential tremor and is being explored in OCD and TRD, with early studies suggesting potential benefit, particularly in the former. ^{Reference Hamani, Davidson, Rabin, Goubran, Boone and Hynynen8} However, current technology cannot penetrate around a third of skulls and, even among eligible individuals, roughly a quarter of attempted procedures fail to produce an adequate lesion. Ongoing and future randomised controlled trials will determine its clinical role.

Deep brain stimulation (DBS) versus ablation

DBS is often perceived as a preferable approach because of reversibility and adjustability, whereas ablation produces permanent changes. However, this distinction can be misleading and should be considered alongside other factors, including complications inherent in the ongoing requirement for implanted hardware. In psychiatric indications, ablation in commonly used anatomical targets has not been associated with the same rate of complications seen in historical movement disorder procedures. A recent systematic review with meta-analysis comparing the neuropsychological side-effects associated with ablative neurosurgery for psychiatric disorders found the risks comparable to those observed in neuro-oncological, neurovascular and epilepsy surgeries. ^{Reference Vilela-Filho, Bannach, Lino-Filho, Hamani, Nuttin and Hariz9} These insights challenge misconceptions about the safety and consequences of stereotactic ablation that may represent an unjustified barrier to its broader use in psychiatry.

DBS, although adjustable, is expensive, involves implanted hardware and requires ongoing specialist programming and maintenance. If the device malfunctions or needs to be removed due to infection, severe symptom rebound can occur. In addition, factors such as insertion-related effects, delayed clinical response and placebo influences may complicate the interpretation of trial outcomes.

At present there is insufficient evidence to conclude that one approach is superior – both DBS and stereotactic ablation have strengths and limitations and both deserve further investigation.

Clinical governance and timely referrals

Each country has its own approach to the ethical aspects of neurosurgery for psychiatric disorders. In the UK, DBS for mental health disorders is limited to research settings whereas stereotactic ablation is supported by professional psychiatric guidance and is available on the National Health Service within a strict governance framework. Given the vulnerability of these patients, procedures require rigorous consent processes, multidisciplinary review and oversight under relevant mental health legislation.

Modern practice rests on three principles: rigorous assessment to detect subtle cognitive disturbance; genuine equipoise regarding the long-term risks of irreversible ablation versus hardware-dependent DBS; and multidisciplinary oversight across psychiatry, neurosurgery and neuropsychology – safeguards often absent in the field’s early era.

Neurosurgery should be considered only after all other established treatments have been exhausted, but it should not be delayed unnecessarily. If a patient receives surgical benefit after a decade or more of severe illness, that delay itself represents lost life opportunities.

Why referrals are still rare

One of the most important points is the mismatch between disease burden and referral patterns. Far fewer patients with severe OCD and depression are referred for neurosurgical assessment than might be expected. Several factors may contribute:

1. (a) the enduring association of modern psychosurgery with historic lobotomy;

2. (b) limited awareness among psychiatrists of modern techniques and their safety profiles;

3. (c) separation between psychiatry and neurosurgery training and services;

4. (d) ethical concerns regarding the use of interventions in vulnerable patients.

Although these concerns are understandable, they may contribute to the inequity of access to effective treatment. In other neurological conditions, referral for surgical evaluation is often considered part of routine pathways when standard treatments fail – even when the procedures are more extensive, invasive and high-risk than stereotactic functional neurosurgery. A similar assessment-focused approach should be considered in selected psychiatric cases when quality of life is severely impaired, suffering is significant with raised risk of self-harm or suicide and all other treatment approaches have failed.

Modern functional neurosurgery is fundamentally different from historical psychosurgery, relying on stereotactic targeting, MRI guidance and adjustable or minimally invasive methods. However, this distinction is often not appreciated by clinicians, patients or the public.