psychosurgery: Overviews and techniques

1. Dr. Shahnawaz Alam
MCh-Neurosurgery
Surgery for Psychiatric
Disorders
Moderated by:
Dr. V. C. Jha
HOD, Dept. of Neurosurgery

2. History of Psychosurgery
• Gottlieb Burckhardt (1836-1907), a Swiss psychiatrist, was the first to perform
surgery on the brain for psychiatric indications.
• A subsequent attempt at the surgical treatment of mental illness was
undertaken in 1910 by Puusepp, an Estonian neurosurgeon, who surgically
disrupted fibers between frontal and parietal cortices in three manic-depressive
patients.
• Egas Moniz, a Portuguese neurologist and the inventor of cerebral angiography,
and Walter Freeman, an American neurologist.
• Moniz and his neurosurgical colleague Almeida Lima therefore performed the
first prefrontal leucotomy at the Santa Marta Hospital in Lisbon in 1935,
launching psychosurgery into an era when experimental surgery was the
hallmark of this specialty (ethanol injection into the centrum semiovale
through a lateral trepanation in the skull).

3. Moniz was awarded the Nobel
Prize in 1949 for his work, and he
coined the term psychosurgery
to describe this new form of
surgical intervention.

4. • Only a year after Moniz reported his initial experience with prefrontal
lobotomy, Papez published his seminal paper on the hypothesis that a
reverberating circuit in the human brain might be responsible for emotion,
anxiety, and memory.
• The components of this system included the hypothalamus, septal nuclei,
hippocampi, mammillary bodies, anterior thalamic nuclei, cingulate gyri,
and their various connections.
• In 1952, Macleanexpanded it to include paralimbic structures such as
orbitofrontal, insular, and anterior temporal cortices; the amygdala; and
dorso- medial thalamic nuclei.
• Even today, many of the most effective surgical treatments are directed
toward some component of the limbic system, and therefore the term
limbic system surgery has been proposed as an alternative to
psychosurgery.

5. CONVENTIONAL OPEN PSYCHOSURGERY
• By the late 1940s, more precise open surgical procedures were described,
including prefrontal leucotomy, bimedial frontal leucotomy, orbital gyrus
undercutting, cerebral topectomies, and anterior cingulectomies.
• Open cingulectomy through an interhemispheric approach was first proposed
by Le Beau, who reported good results with minimal morbidity.
STEREOTACTIC SURGERY
• In 1947, Speigel and Wycis introduced stereotactic surgery, allowing the
placement of more precise lesions in deep parts of the brain with the use of a
Cartesian coordinates system of surgical planning.
• In the subsequent decade, Leksell described his experience with anterior
capsulotomy, and Kelly reported limbic leucotomy (combined subcaudate
tractotomy and cingulotomy) in 1973.

6. • Anterior cingulotomy has been the surgical procedure of choice; It involves the
placement of lesions in the anterior limb of the internal capsule, disrupting
pathways to the orbitofrontal cortex from the thalamus.
• The early results of anterior capsulotomy suggested that 48% of the patients
with major depression and 50% of those with OCD responded very positively to
the intervention.
• Geoffrey Knight championed subcaudate tractotomy for use in psychiatric
disorders. He created lesions in the posterior orbitofrontal cortex bilaterally using
radioactive yttrium seeds and reported good results in 68% of patients with OCD
and 50% of those with major depression.

7. THE DECLINE OF PSYCHOSURGERY
• In 1954, chlorpromazine, the first clinically useful psychotropic drug, received
approval from the U.S.FDA, and its introduction spelled the beginning of the end
of the era of leucotomies. It was described by Freeman as a “chemical
lobotomy,”.

8. THE PUBLIC, LEGISLATION, AND ETHICS
• In the 1970s, legislation was passed in the United States emphasised the
importance of ethical boards in the selection of functional neurosurgery
patients.
• The Commission’s conclusions clearly argued against the public perception that
psychosurgery was dangerous, ineffective, and experimental.
• The WHO today defines psychosurgery as “the selective surgical removal or
destruction of nerve pathways for the purposes of influencing behavior,” although
this needs to be modified to include the various techniques of DBS and other
neuromodulation treatments.
• Ethical responsibility lies with neurosurgeons along with expert multidisciplinary
groups of specialists in the safe and scientific application of all current forms of
psychosurgery.

9. MODERN ABLATIVE PSYCHOSURGERY
• At present, only patients with severe, chronic, disabling, and treatment-refractory
psychiatric illness should be considered for surgical intervention.
• The major psychiatric diagnostic groups, as defined by the Diagnostic and
Statistical Manual of Mental Disorders, 5the.
• In many instances, patients present with mixed disorders combining symptoms of
anxiety, depression, and OCD, and these patients remain candidates for surgery.
• Schizophrenia is not currently considered an indication for surgery. A history of
personality disorder or substance abuse is often a relative contraindication to
surgery.

10. • Cingulotomy, anterior capsulotomy, and limbic leucotomy remain the ablative
psychosurgical procedures still employed today.
• Modern results of cingulotomy suggest that nearly 70% of patients with OCD
will have a positive response to surgery and that about 75% of patients with
major depression will respond positively at long-term follow-up of more than 5
years.
• Anterior capsulotomy is most commonly performed today with the Gamma
Knife.
• Modern limbic leucotomy has generally been limited to be used as a salvage
procedure in patients who have failed to respond adequately to initial
cingulotomy.

11. NEUROMODULATION
• Vagal nerve stimulation (VNS) has been explored in the treatment of depression
and anxiety disorders because of the observation that a percentage of intractable
epilepsy patients in whom the device were implanted noted improvement in their
depressive symptoms whether or not their seizures were controlled.
• DBS has received much recent attention as an alternative technique in
psychosurgery because it is reversible, is adjustable, and can be performed
bilaterally in many of the same brain targets used in ablative surgery.

12.  Surgery for Tourette’s Syndrome (TS)
 Obsessive-compulsive disorder (OCD)
 Major depressive disorder (MDD)
 Anorexia nervosa (AN)
OVERVIEW

13. Surgery for Tourette’s Syndrome
• An idiopathic neuropsychiatric disorder; Diagnosis is based on the childhood
onset of chronic involuntary motor and phonic tics that are not attributable to
drugs or known medical causes and persist for no less than 1 cumulative year.
• It is a developmental disorder & highly hereditable.
• The frequency and severity of tic expression follows a waxing and waning
pattern, which is noteworthy when considering therapeutic strategies. Mean
onset of symptoms occurs at age 5 to 7 years and peaks at age 10.
• By late adolescence to early adulthood, symptoms either stabilize or remit in
approximately two thirds of the population; 4 to 5 times more prevalent in
boys than girls.

14. • Tics are sudden, repetitive, and purposeless and can be classified as either
simple or complex. Simple tics involve one muscle group and can be tonic,
dystonic, and/or clonic.
• Common examples are the following: (1) tonic-isometric contractions such as
tensing of the abdominal muscles; (2) dystonic-shoulder rotation and oculogyric
deviation; and (3) clonic-rapid movements such as eye blinking, facial twitching,
and head, neck, or limb jerking.
• Phonically, these are manifest as throat clearing, coughing, or grunting.
• Complex tics involve the coordination of several muscle groups and often
appear purposeful. Examples of these include gesturing, hopping, and body
jerking (motoric) and humming, making animal sounds, and coprolalia (phonic).

15. • Associated comorbidities are ADHD and OCD, each of which may be seen in up
to 80% of TS patients. Anxiety disorders, learning disabilities, and affective
disorders are also commonly observed.
• Although TS is generally self-limiting, a portion of the patient population may
experience tic burden that is persistent, severe, and medically refractory.

16. PATHOPHYSIOLOGY
• Anatomic and physiologic evidence suggests that TS results from dysfunction in
the recurrent loops of the cortico-basal ganglia-thalamocortical pathway.
• Pathologic behaviour in this network has also been implicated in ADHD and
OCD. This circuit is essential for action gating as well as the conversion of goal-
directed behaviour to automated behaviours.
• Important regions in this pathogenetic network include the motor and limbic
cortices, striatum (caudate and putamen), globus pallidus internus (GPi) and
externus (GPe), substantia nigra pars reticulata and pars compacta, nucleus
accumbens (NAcc), subthalamic nucleus, and thalamus. The pedunculopontine
nuclei and cerebellum provide extrinsic connections, which may also be
important.

17. • The cortico-basal ganglia-thalamocortical network consists of direct and indirect
pathways that are topographically organized and can be differentiated
histologically.
• It has been proposed that dopamine and γ-aminobutyric acid are the key
neurotransmitters involved in the dysfunction of transmission between the
cortex and subcortical structures, although glutamate, histamine, serotonin,
acetylcholine, and cyclic adenosine monophosphate have also been suggested
to play important modulatory roles.
• Dopamine dysregulation, as presented in the tonic-phasic model, is the most
widely accepted neurobiologic theory of TS, a theory that is supported by the
clinical observations that dopamine2 receptor antagonists effectively reduce tic
severity whereas dopamimetic drugs exacerbate symptoms of TS.

18. TREATMENT
• Because there is no cure for TS, treatment is targeted toward relieving tic
severity and frequency and the disruptive symptoms presented by
comorbidities.
• Therapeutic strategies should seek to decrease symptoms beginning with
puberty. In cases in which tics persist, behavioural, pharmacologic, and/or
surgical options are available.

19. Comprehensive Behavioural Intervention for Tics and
Pharmacologic Treatment
• Behavioural therapy may be recommended as a first-line intervention for
children and milder cases of TS.
• If medical treatment is indicated in milder cases of TS, α2- adrenergic
agonists may be effective, particularly in patients with comorbid ADHD.
• In moderate to severe cases neuroleptics may effectively relieve tic burden,
most likely through their anti-dopaminergic effects.
• The most effective of the antipsychotic agents approved by the U.S.FDA are
pimozide, haloperidol, and risperidone.

20. • Although effective, dopamine blocking agents may induce significant side
effects, including extrapyramidal symptoms, sedation, and weight gain.
• Aripiprazole, a partial agonist and antagonist that is reported to be an effective
tic suppressant with a lower incidence of severe side effects, is emerging as the
medical treatment of choice for TS.
• In patients with significant comorbidities, psychostimulants (e.g.,
methylphenidate) or SSRI may be used for the treatment of ADHD and OCD,
respectively.
• For isolated motor tics, botulinum neurotoxin injections are effective and well
tolerated.

21. Ablative Surgery
• Surgical intervention may be indicated for patients with TS that is severe and
medically refractory.
• In 1962, Baker published the first paper describing ablation for TS, reporting the
results of a bimedial leucotomy in a young male suffering from vocal and motor
tics, with concomitant obsessive-compulsive symptoms.
• After this, many other groups attempted diverse neurosurgical ablative
approaches that included lesioning of the frontal lobes (bimedial frontal
leucotomies and prefrontal lobotomies), the thalamus (medial, intralaminar, and
ventrolateral nuclei), the limbic system (anterior cingulotomy and limbic
leucotomy), the zona incerta, and the cerebellum, as well as combinations of
these targets.

22. Deep Brain Stimulation
• Benabid et al. first described thalamic DBS in 1987 as a treatment for medically
refractory tremor; however, the reversibility and dynamic adjustability of DBS
offered the possibility of revolutionizing the treatment of multiple functional brain
disorders, including TS.
• Today, DBS is both FDA approved and Conformité Européenne (CE) marked for the
treatment of Parkinson’s disease, primary dystonia, essential tremor, and OCD.
• The majority of reported cases involve DBS at four brain areas: the medial
thalamus, GPi, GPe, and internal capsule/nucleus accumbens (IC/NAcc).

23. Thalamus
• The specific target was the convergence of the centromedian nucleus, the
substantia periventricularis, and the nucleus ventro-oralis internus.
Globus Pallidus Internus
• GPi-DBS in TS: posteroventrolateral segment/ anteromedial or limbic segment;
Anteromedial Gpi-stimulated patients improved more than the
posteroventrolateral Gpi-stimulated patients, with tic reductions of 54% and
37%, respectively.
Internal Capsule and Nucleus Accumbens
• DBS of the anterior limb of the IC/NAcc, as part of the ventral striatum, is an
established CE-approved therapy for patients suffering from refractory TS &
OCD.

24. Inclusion Criteria
• < 18 Yrs of age; Motor and vocal tics should be chronic, severe, and the main
source of disability; Refractory to pharmacologic and behavioural therapy.
• If the patient presents comorbid psychiatric or neurological symptoms, he or
she should be under treatment and considered stable over the course of 6
months.
• The candidate must have a stable social environment with adequate support. In
addition, the cognitive and psychological profile of the patient must
demonstrate a capacity to cope with the demand of the procedure and the
requested therapeutic recommendations.

25. Exclusion Criteria
• Presence of suicidal or homicidal ideation within 6 months of the planned
procedure; Recent depressive moods or substance abuse should be under
treatment and considered a contraindication if they persist.
• Evidence or suspicion of a factitious disorder or the presence of psychogenic
tics; Medical or neurological condition that could compromise the success of
the procedure or the postoperative care and recovery.
• Structural brain lesions found on MRI, and severe cardiovascular, pulmonary,
or hematologic abnormalities.

26. • In contrast to DBS for tremor or Parkinson’s disease, for which the procedure is
mostly performed under LA so that one may perform intraoperative test
stimulation, DBS in TS cannot be performed under LA because of the
hyperkinetic nature of the disease.
• Instead, the stimulating leads are implanted under GA. If the patient is considered
a good candidate for sedation, this can be carried out with either a combination
of lormetazepam (or lorazepam) and clonidine or with a propofol infusion.

27. Obsessive-compulsive disorder (OCD)
• A chronic and severe anxiety disorder; 2% to 3% of the population;
Characterized by persistent obsessions with intrusive thoughts leading to severe
generalized anxiety or compulsions in the form of repetitive tasks to relieve this
distress.
• These compulsions are severe and long enough (>1 hr/day) to interfere with
one’s routine activities, performance at work, and family and social
interactions.
• In addition to these symptoms, patients with OCD are twice as likely to report
suicide attempts as those with other psychiatric disorders.

28. • Pharmacotherapy SSRIs] and cognitive behaviour therapy (CBT) are the first-line
treatment option for patients with OCD.
• These therapeutic measures provide a 40% to 60% reduction in OCD symptoms in
50% of patients.
• Surgical management is a consideration for this subset of patients with medically
refractory OCD.
• Neurostimulation is presently considered superior to ablation when treating
psychiatric disorders.
• Both the minimally invasive nature of DBS surgery and its excellent safety profile
make it a favourable technique for treating functional brain disorders.

29. NEURAL CIRCUITS AND PATHOPHYSIOLOGY
• In contrast to movement disorders, there is no one neural “circuit” or “target”
that is implicated in the pathophysiology of OCD.
• Instead, the symptoms of OCD are caused by abnormalities in multiple
interweaved neural circuits or targets that form a complex network controlling
mood and anxiety.
• Alexander et al. identified multiple parallel basal ganglia-thalamocortical loops
(cortical-striatal-pallidal-thalamic-cortical loops) that process cortical inputs
from the motor, oculomotor, dorsolateral prefrontal, lateral orbitofrontal, and
anterior cingulate regions.
• Each of these circuits includes functionally and anatomically discrete regions of
the striatum, globus pallidus and substantia nigra, thalamus, and cortex.

30. Schematic representation of neural
circuits involved in the basic
pathophysiology of obsessive-compulsive
disorder. Red dots indicate different
surgical targets for deep brain
stimulation therapy. Ant, anterior; DM,
dorsomedial.
• In the motor loop, motor and
somatosensory cortical areas send
partially overlapping projections to a
specific region of the striatum.
• The striatum then sends projections
that further converge at the level of
the globus pallidus. From the globus
pallidus, fully converged fibers
project to a specific location in the
thalamus.

31. • To close the loop, the thalamus projects back to a cortical area that feeds into
the circuit; these circuits are anatomically and functionally segregated, there is
connectivity between them so that limbic, cognitive, and motor pathways are
integrated.
• The basal ganglia-thalamocortical loop implicated in the pathophysiology of
OCD originates in the prefrontal cortex and orbitofrontal cortex (OFC).
• Fibers originating from the prefrontal and orbitofrontal cortices project to the
ventral striatum through the ventral internal capsule. Specifically, these fibers
reach the ventral aspect of the caudate and the nucleus accumbens (NAcc) and
are excitatory in nature by means of glutamate and aspartate.
• This area also receives inhibitory serotonergic input from the dorsal raphe
nucleus of the midbrain. From the ventral striatum, the fibers then project to
the ventral pallidum and are mediated by substance P, enkephalin, and γ-
aminobutyric acid (GABA).

32. • Inhibitory projections then reach the mediodorsal aspect of the thalamus.
Finally, the thalamus projects fibers back to the OFC. The overall output of this
pathway is inhibitory in nature and seeks to dampen the input to the cortex.
• There also exists a parallel circuit originating in the anterior cingulate cortex
(ACC), with projections to the ventral striatum and pallidum and termination in
the mediodorsal aspect of the thalamus.
• This loop then projects back to the ACC. The anterior cingulate loop is believed to
underlay the anxiety component of OCD, whereas the circuit originating in the
OFC is thought to mediate the core symptoms of OCD.
• Moreover, although the basal ganglia−thalamocortical loop originating in the
OFC is inhibitory in nature, the cortical-thalamic-cortical circuit originating in the
orbitofrontal and prefrontal cortices is excitatory in nature. These loops are also
referred to as the direct and inhibitory pathways, respectively.

33. • In a normal state, this excitatory pathway is dampened by the net inhibitory
output of the aforementioned basal ganglia-thalamocortical loop.
• It is believed that OCD symptoms arise when the equilibrium between these
finely tuned pathways is lost.
• An additional loop involving the limbic and Papez circuits underlies the
emotional aspects of OCD.
• Obsessive-compulsive symptoms are caused by either decreased activity in
the basal ganglia-thalamocortical (striatal-pallidal-thalamic- cortical) loops or
increased activity in the cortical-thalamic- cortical (orbital-frontal-thalamic)
loops.
• Therefore modulating either of these pathways and Papez circuit could
possibly ameliorate the obsessive-compulsive, anxiety, and emotional
symptoms associated with OCD.

34. Schematic representation of motor (A), associative (B), and limbic (C) circuits of the
cortical- striatal-pallidal-thalamic-cortical loops implicated in the pathophysiology of
movement and psychiatric disorders.
Cn, caudate nucleus; GPe, globus pallidus externus; GPi, globus pallidus internus; Put,
putamen; STN, subthalamic nucleus.

35. • Functional neuroimaging (PET and fMRI) studies report abnormally increased
metabolic activity of the prefrontal cortex, ACC, OFC, caudate, and thalamus in
OCD patients in both neutral and provoked states as compared to healthy
individuals.
• Studies have also reported decreased levels of N-acetyl aspartate (a marker of
neuronal density) in the medial prefrontal cortex and its correlation with
symptom severity in patients with OCD as compared to healthy controls.
• A decrease in metabolic activity in the pathologic cortical-subcortical loop
(OFC, bilateral caudate, and cingulate gyri) has been shown in patients with OCD
after successful treatment with either medications (SSRIs) or behaviour therapy.
• These neuroimaging, anatomic, and physiologic studies provide insight into the
pathophysiology of OCD that may identify new nodes for surgical intervention.

36. SURGICAL MANAGEMENT OF OBSESSIVE COMPULSIVE DISORDER
• The advent of stereotaxy made it possible to target subcortical structures with
submillimetric accuracy, thereby increasing surgical safety while maintaining the
efficacy of earlier surgical procedures for OCD.
• All of the procedures employed tend to modulate activity within the OFC, dorsolateral
frontal cortex, and ACC and their interactions with the basal ganglia and thalamus.
Surgical procedures such as DBS, stereotactic ablation, and vagus nerve stimulation
(VNS) have been shown to ameliorate OCD symptoms.
Stereotactic Ablation Procedures
• With the advent of stereotaxis, procedures such as anterior cingulotomy,
capsulotomy, subcaudate tractotomy, and limbic leucotomy were developed to help
patients with severe and refractory psychiatric disorders.
• These procedures tend to modulate activity in the cortical-striatal-pallidal-thalamic-
cortical loops through targeted ablation, ameliorating OCD symptoms.
• These ablative procedures are irreversible and therefore demand precise placement
to avoid adverse neurological events.

37. Acute postoperative axial MRI demonstrating lesion location in anterior capsulotomy
(A), cingulotomy (B), and subcaudate tractotomy (C).

38. Stereotactic Cingulotomy
• This surgical technique involves interrupting the connections between the
dorsal ACC, OFC, amygdala, and hippocampus, thereby modulating the
cortical-striatal-thalamic-cortical (CSTC) loops.
• Cingulotomy for anxiety-like states was first reported by neurologist Walter
Freeman and neurosurgeon James Watts in 1942.
• Anterior cingulotomy is a safe procedure with an incidence of complications
similar to that of other stereotactic procedures.
• Stereotactic cingulotomy is the most widely performed surgical procedure for
medically refractory OCD.

39. Stereotactic Anterior Capsulotomy
• The white matter fibers in the anterior limb of the internal capsule connect the
orbitofrontal and subgenual ACCs to the medial, dorsomedial, and anterior
thalamic nuclei.
• Severing these fibers can disrupt the overactive CSTC loop and ameliorate the
OCD symptoms. Anterior capsulotomy can be performed using either Gamma
Knife or radiofrequency ablation.
• The lesion is typically produced in the area between the anterior and middle one
third of the internal capsule at the level of foramen of Monro.
• For Gamma Knife anterior capsulotomy, Kihlstrom and associates targeted the
area 10 mm in front of the anterior commissure, 8 mm above the
intercommissural line, and 17 mm lateral to the midcommissural plane in
patients with refractory OCD.

40. Stereotactic Subcaudate Tractotomy
• In 1965, Geoffrey Knight, with an experience of 550 restricted undercutting
operations for psychiatric disorders between 1950 and 1965, realized that it was
the posterior part of the incision in the subcortical white matter that was
associated with the best therapeutic effect.
• This posterior part of subcortical white matter was identified as the substantia
innominata, and this serendipitous finding led to the origin of subcaudate
tractotomy.
• The substantia innominata contains white matter fibers that connect the OFC to
the thalamus, amygdala, and subgenual ACC. Interrupting these white matter
tracts tends to modify the CSTC loops.
• The substantia innominata is located beneath the head of the caudate nucleus.
These lesions are made by placing bilateral frontal bur holes 2 cm long in the
anteroposterior plane of planum sphenoidale and 15 mm from the midline.

41. Stereotactic Limbic Leucotomy
• Limbic leucotomy involves interrupting the white matter tracts at the lower
medial quadrant of each frontal lobe (subcaudate tractotomy) and those in
the cingulum (cingulotomy).
• This procedure was first described in 1973 by Kelly and Richardson in London.
• Limbic leucotomy interrupts the frontothalamic and limbic loops and thus
modulates the CSTC loops involved in the pathophysiology of OCD. This ablative
procedure is performed using either thermocoagulative or cryogenic
techniques.

42. Deep Brain Stimulation
• In 1979, low-frequency (5-Hz) stimulation of the area near the parafascicular
complex in the intralaminar thalamic nuclei was shown to ameliorate phobia
and OCD symptoms at 1 year of follow-up.
• Similarly, stimulation of the cerebellar vermis has been shown to improve OCD
symptoms by targeting neural circuits instead of a specific target.
• The advantages of reversibility, ability to adjust the stimulation parameters
over time, and better surgical safety profile relative to ablation made DBS
surgery an attractive and favourable treatment option for patients with
refractory OCD.

43. • Hypotheses such as depolarization blockade, synaptic inhibition, synaptic
depression, and stimulation-induced modulation of pathologic network
activity have been implicated as the probable mechanisms underlying the
therapeutic efficacy of DBS.
• Of these, stimulation-induced modulation of pathologic network activity is the
most likely mechanism underlying the therapeutic benefits of DBS.
• Furthermore DBS improves the functioning of thalamocortical neurons and
potentially normalizes the imbalance in the cognitive-behavior-emotional circuit.
• Various structures such as the anterior limb of internal capsule (ALIC), ventral
capsule and ventral striatum (Vc/Vs), NAcc, subthalamic nucleus (STN), and
inferior thalamic peduncle (ITP) have been explored as potential DBS targets in
patients with refractory OCD with varied results.

44. Ventral Capsule and Ventral Striatum
• The promising results of Gamma Knife and radiofrequency thermal ventral
capsulotomy and ALIC-DBS for medically refractory OCD led investigators to
explore structures adjacent to the internal capsule as potential DBS targets.
• The ventral striatum consists of the ventral portion of the caudate nucleus and
NAcc, which are believed to be the reward centers of the brain.
• The combined ventral capsule and ventral striatum (Vc/Vs) was subsequently
explored as a potential DBS target for refractory OCD.
• Symptoms such as depression, anxiety, independent living, and self-care were
also improved.
• Adverse effects included asymptomatic hemorrhage, seizure, superficial
infection, and psychiatric symptoms such as hypomania and worsening of
depression.

45. Subthalamic Nucleus
• The STN is one of the nodal points in the dorsolateral prefrontal, orbitofrontal,
and limbic loops, and STN-DBS for Parkinson’s disease has been shown to have
neuropsychological effects, with improvements in mood, anxiety, and OCD
symptoms.
• Ventromedial portions of the STN and surrounding structures such as the lateral
hypothalamus, ventral tegmental area, substantia nigra, and zona incerta have
been implicated in the neuropsychological effects of STN stimulation.
Inferior Thalamic Peduncle
• The white fiber bundle within the inferior thalamic peduncle (ITP) connects the
thalamus to the OFC and thus plays a crucial role in the pathophysiology of OCD.

46. Surgical Technique for DBS
• DBS surgery for OCD is performed in two stages:
 Stage 1 involves stereotactically guided implantation of the DBS electrodes into
deep anatomic targets.
 Stage 2 involves connecting the free end of the lead wire to an extension cable,
which is subsequently tunneled under the scalp and skin of neck into the
subclavicular or abdominal area and connected to the pulse generator.
• The stage 2 procedure is usually performed 7 to 10 days after the stage 1
procedure as an outpatient procedure under general anesthesia.
• On the day of stage 1 surgery, the patient’s head is shaved, and a stereotactic
frame is attached to the patient’s head under sedation and local anesthesia.
• Stereotactic head computed tomography is performed, and the images are
exported to a stereotactic workstation and fused to a volumetric MRI scan.

47. Basic Procedure

48. Components of DBS
 The pacemaker consist of:
• Electrodes
• Lead wire
• Pulse generator

49. Stealth Autoguide cranial robotics guidance platform in the operating room with the StealthStation platform visible in
the background. Credit: Medtronic
StimLock burr hole cover with anchored electrode, yellow
arrow-electrode in exit slot, red arrow-base of StimLock,
blue arrow-securing mechanism of the support clip.
Neuronav Drive
(Alpha Omega,
Nazareth, Israel)

50. The quadripolar deep brain stimulation
electrode and the internal pulse
generator. (Courtesy of Medtronic, Inc.)
The electrode lead holder assembly.

51. (A) The computed tomography of the patient is fused to the MRI done at an earlier
date. (B) The Schaltenbrand- Wahren atlas is fused to the magnetic resonance
image.

53. • The target is localized using either an indirect targeting method in
reference to the coordinates of the midcommissural point or by direct
visualization of the nucleus on T2-weighted MRI.
• A safe surgical trajectory to the target that avoids the cortical sulci,
intracranial vessels, and ventricular walls is planned on the navigation
station.
• With the patient in the supine position, an incision and bur hole are
made, centered on the planned trajectory.
• The Stimloc device (Medtronic, Minneapolis, MN), which will secure
the lead and cover the bur hole, is attached to the skull with two set
screws.
• The underlying dura mater is coagulated and opened at the desired
entry point for the cannula; Then pia mater is coagulated, and a sharp
corticectomy is performed.

54. • The microelectrode is then advanced through the brain matter using a Neuronav
Drive (Alpha Omega, Nazareth, Israel) in submillimetric steps in an awake
patient.
• The neuronal activities within the target are evaluated by cognitive tasks every 1
to 2 mm along the length of the nucleus. The neuronal activity is amplified,
filtered, displayed, and recorded using a high-quality audio monitor, computer
display, and digital oscilloscopes.
• Based on the microelectrode recordings, the borders and volume of the
intended target is defined. Each neuronal structure has characteristic
electrophysiologic properties that assist in delineating the entry and exit points
through that structure.

55. Other Surgical Procedures
• VNS is an effective and adjunctive treatment in patients with chronic
refractory depression and was approved by the FDA for adult patients (>18
years of age) in 2005.
• Based on PET and single-photon emission computed tomography imaging
studies, it has been shown that VNS is associated with reduced perfusion in
the ipsilateral brainstem, cingulate, amygdala, and hippocampus, and in the
contralateral thalamus and cingulate in patients with refractory epilepsy.
• Vagus nerve fibers project to the nucleus tractus solitarius, which has been
shown to have intricate connections with the limbic system.

56. Major depressive disorder (MDD)
• A common and challenging psychiatric disorder, which is responsible for a
significant proportion of global morbidity; 12% of men and 20% of women will
experience a major depressive episode (MDE) in their lifetime (>2weeks).
• The mainstay of MDD treatment is a combination of psychotherapy (Cognitive
behaviour therapy) and pharmacotherapy.
• Up to 30% to 40% of patients remain depressed despite optimal care and are
characterized as having treatment-resistant depression (TRD).
• Patients with TRD are significantly impaired, are unable to work, and suffer from
poor personal relationships and quality of life. Up to 15% of TRD patients
commit suicide.

57. CIRCUITRY OF MOOD AND DEPRESSION
• The generation and maintenance of mood are believed to be a consequence of
cortical-subcortical circuits involved in affective and emotional processing.
• Top-down, largely cortical structures, such as the ventromedial prefrontal
cortex, interact with bottom-up, largely subcortical structures, such as the
amygdala and hippocampus, through key regulatory structures in the extended
basal ganglia.
• Several key structures, comprising important nodes in mood circuitry, have been
identified; These include the nucleus accumbens (NAcc), subcallosal cingulate
(SCC), anterior limb of the internal capsule (ALIC), and medial forebrain
bundle.

58. Nucleus Accumbens
• The NAcc is a gray matter structure located at the ventral interface of the
caudate and putamen (i.e., ventral striatum [VS]), which is intimately involved
with reward processing.
• When expecting or experiencing a reward, dopamine is released by neurons in
the ventral tegmental area (VTA) projecting to the NAcc in the VS.
• Extracellular levels of dopamine rise in the NAcc, which in turn sends
dopaminergic projections to the orbitofrontal cortex, the dorsolateral
prefrontal cortex, and other cortical areas.
• Drugs like cocaine, methamphetamine, and caffeine, as well as natural rewards
like food and sex, all increase, either directly or indirectly, dopamine release in
this mesocorticolimbic pathway.
• NAcc is also functionally related to the experience of anhedonia, which is the
abject lack of pleasure in a typically pleasurable activity. Anhedonia is a core
feature of MDD, and work by several research groups has linked NAcc activity to
anhedonia in MDD patients.

59. • The NAcc is a highly connected node within a well-defined cortical-striatal-
thalamic-cortical loop.
• The NAcc receives afferents from the anterior cingulate cortex as well as the
limbic temporal cortex, including the hippocampus, entorhinal cortex, and
amygdala.
• The NAcc sends efferent projections to the ventral (limbic) portions of the
globus pallidus externus and internus.
• The globus pallidus internus then projects to the mediodorsal nucleus of the
thalamus, which in turn projects to the anterior cingulate, completing the
circuit; this striatal circuit is responsible for the emotional memory associated
with depression.

60. Circuit diagram for mood and anxiety
disorders and deep brain stimulation
targets.
ACC, anterior cingulate cortex; dlPFC,
dorsolateral prefrontal cortex; MD, mediodorsal;
SCC, subcallosal cingulate cortex; vmPFC,
ventromedial prefrontal cortex.

61. A. ≥5 for 2-week period and represent a change from previous functioning; at
least one of the symptoms is either (1) depressed mood or (2) loss of interest
or pleasure:
1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels
sad, empty, hopeless) or observation made by others (e.g., appears tearful).
2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every
day.
3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body
weight in a month.
4. Insomnia or hypersomnia nearly every day.
5. Psychomotor agitation or retardation nearly every day.
6. Fatigue or loss of energy nearly every day.
7. Feelings of worthlessness or excessive or inappropriate guilt.
8. Diminished ability to think or concentrate, or indecisiveness, nearly every day.
9. Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt
or a specific plan for committing suicide.
 From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA:
American Psychiatric Publishing; 2013.
Diagnostic Criteria for Major Depressive Disorder

62. B. The symptoms cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
C. The episode is not attributable to the physiologic effects of a substance or to
another medical conditrion.
D. The occurrence of the major depressive episode is not better explained by
schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional
disorder, or other specified and unspecified schizophrenia spectrum and other
psychotic disorders.
E. There has never been a manic episode or a hypomanic episode.

63. Subcallosal Cingulate Cortex
• The SCC (Brodmann area [BA] 25) is a critical regulatory node in the medial
ventral frontal lobe, immediately below the genu of the corpus callosum.
• It exists at the interface of several key white matter pathways, which govern
affective regulation, emotional decision making, and basal vegetative and
autonomic functions.
• The SCC has long been postulated as a central node in circuits mediating
emotion. Early models of emotional circuits by Papez suggested the cingulate
gyrus is the “seat of dynamic vigilance” and an essential component for
emotional processing.

64. • More recently, Seminowicz et al. proposed a model of depression circuitry based
on FDG-PET across three cohorts of patients with MDD. In this model, the SCC
receives afferent projections from the hippocampus and sends efferent
projections to the lateral prefrontal cortex (BA 9).It also shares bilateral
connectivity with both the rostral cingulate (Cg24a) and the orbitofrontal cortex
(BA 11).
• Additionally, the orbitofrontal cortex has been implicated in decision making
and emotional processing.
• In particular, SCC connections to cortical structures implicated in depression
suggest that altering Cg25 activity may treat the cognitive aspects of depression:
guilt, hopelessness, and suicidal ideation.

65. Anterior Limb of the Internal Capsule
• The ALIC is a white matter pathway connecting frontal cortical structures with
subcortical, thalamic, and other basal ganglia structures.
• As a key limbic pathway, the ALIC has been postulated to be a critical
connection between top-down and bottom-up regulatory structures important
for mood and emotional processing as well as decision making.
• Imaging and anatomic tracer studies have shown that the ALIC connects the
anterior cingulate and parts of the prefrontal cortex with lower limbic
structures like the hippocampus, amygdala, and dorsomedial nucleus of the
thalamus.
Medial Forebrain Bundle
• The superolateral medial forebrain bundle (MFB) is part of a circuit that has
been associated with positive affective states.

66. THE ABLATIVE EXPERIENCE
• Four ablative procedures were developed to treat depression: anterior
cingulotomy, subcaudate tractotomy, limbic leucotomy, and anterior
capsulotomy.
Anterior Cingulotomy
• Cingulotomy involves the generation of a lesion in the anterior cingulate
gyrus, typically 1 to 2 cm posterior to the frontal horn of the lateral
ventricle.
Subcaudate Tractotomy
• In the 1950s Knight introduced the refined orbital undercut, designed to
interrupt three bundles of fibers: (1) projection fibers descending from both
the frontal cortex and BA 13 to the ventromedial nucleus of the
hypothalamus, (2) amygdala white matter, and (3) connections between BA
13 and the frontal cortex.
• These projections were thought to be important for mediating the visceral
effects of emotion, and it was believed that their division would mediate
some emotional relief in psychiatric patients.

67. Limbic Leucotomy
• Limbic leucotomy combines anterior cingulotomy with SST. Anterior
cingulotomy disrupts the circuit of Papez by ablating connections between the
anterior cingulate (BA 24) and the hippocampus.
• SST targets the substantia innominata inferior and slightly anterior to the head
of the caudate and also involves lesioning the subgenual cingulate cortex (BA
25).
• The SCC has been widely implicated in mood regulation, so the limbic
leucotomy represents a multitarget ablative technique to disrupt anterior
cingulate function.

68. Anterior Capsulotomy
• The procedure is characterized by lesions placed in the anterior third portion of
the anterior limb of the internal capsule.
• This region contains fibers that connect both the prefrontal cortex and anterior
cingulate cortex with the hippocampus, amygdala, and thalamus.
• Anterior capsulotomy may therefore have a twofold effect. The disruption of
corticothalamic fibers may disrupt somatic symptoms of depression, whereas
the ablation of fibers connecting the cingulate with the hippocampus and
amygdala may relieve depressive symptoms by disrupting the medial circuit of
Papez, known to be essential for emotion.

69. • Anorexia nervosa (AN) is a treatment-refractory medical psychiatric disorder
that usually begins in adolescence and is characterized by excessive dieting,
often accompanied by compulsive exercise, which results in severe weight loss
and a sustained body weight of at least 85% less than normal.
• A subgroup of affected patients also exhibits purging behaviour, with or without
binge eating. Other features include disturbed body image, heightened desire to
lose more weight, and pervasive fear of fatness.
• In affected female patients, amenorrhea also often occurs. The average
prevalence rate of AN is 0.3% to 1% among young women and approximately
one-tenth of that rate among men. Lifetime prevalence among women is 2.2%.
• Of all mental disorders, AN is associated with the highest rate of mortality; the
crude mortality rate is 5.9%, and the mortality rate per decade of life is 5.6%.
• Long-lasting malnutrition can lead to numerous severe physical complications,
including osteoporosis, gastrointestinal and cardiac complications, liver damage,
electrolyte disturbances, and eventually multiple-organ failure.

70. • Psychiatric comorbid conditions include major depressive disorder (MDD; 50%-
70% of patients with AN), anxiety disorder (>60%), and obsessive-compulsive
disorder (OCD; >40%); Personality disorders and alcohol or substance abuse
are also common (12%-27%).
• The majority of individuals with eating disorders report suicidal thoughts, and
about 22% attempt suicide.
• NONSURGICAL MANAGEMENT :Current psychotherapeutic interventions and
pharmacologic therapies for AN are far from universally effective; Selective
serotonin reuptake inhibitors (SSRIs) are the main pharmacologic treatment for
AN symptoms and weight restoration.

71. SURGICAL MANAGEMENT
• Considerable data indicate that individuals with AN exhibit disturbances in
dopamine and serotonin systems, particularly in the ACC, limbic system, and
nucleus accumbens (NAcc).
• The ACC appears to play a role in reward anticipation, decision making, impulse
control, and repetitive and ritualistic behaviors to control eating in patients with
AN.
• Serotonin might play a role in altered satiety, impulse control, and mood, whereas
dopamine is implicated in motivation, executive functions, and the aberrant
reward effects of food.
• Depletion of serotonin levels reduces anxiety in acutely ill patients and in those
recovered from AN. Starvation may reduce pathologically increased dopamine
levels that are associated with anxious temperament.

72. • Two stereotactic procedures are now used for AN: deep brain stimulation (DBS)
and ablative procedures.
• DBS for AN treatment targets the NAcc or the precallosal and subcallosal
components of the ACC, whereas ablative procedures include capsulotomy, NAcc
lesioning, and cingulotomy.
• Cingulotomy is a relatively safe procedure, and the incidence of adverse events is
lower than that with anterior capsulotomy.
• In view of the successful results of anterior cingulotomy in OCD and anxiety, this
procedure may be considered as a potential second surgery for patients with AN
who experience symptoms of OCD, depression, or anxiety after failure of the
initial bilateral anterior capsulotomy.

73. Axial view (A) and coronal view (B) of the nucleus accumbens after the
implantation of deep brain stimulation electrodes (arrows).

74. International Journal of Contemporary Medicine Surgery and Radiology Volume 3 | Issue 3 | July-
September 2018
DBS in India
Future scope and Enhancement
• Focuses on the device which automatically senses the need for increased voltage.
• Improving longevity.
• Reduction in size & cost.

75. CONCLUSION
• The field of psychosurgery has been one of the most interesting in all of medicine
and will continue to be so in the future.
• Much remains to be learned, but understanding its history will impart important
lessons to practitioners in the future.
• The future of psychosurgery will rest on the application of sound clinical and
ethical guidelines.
• Advances in technology, particularly in the fields of optogenetics,
nanotechnology, and focused ultrasound, will provide surgeons with additional
tools to target specific neural pathways with even more precision and continue to
improve our understanding of the neural circuits and pathophysiology
underlying psychiatric disorders.
• Functional neuroimaging studies are particularly useful for finding the
mechanisms of disease development and possible target areas for further
neurosurgical interventions.

76. • Potential biomarkers for TS/OCD/MDD/AN can thereby be revealed by tracking
specific neurobiological changes in dysfunctional circuits.
• Knowledge of these biomarkers and their characteristic involvement in the disease
state may allow for real-time improvements in target localization during surgery
and promote the development of next-generation technologies such as closed-
loop stimulation.
• DBS has emerged as the preferred surgical intervention for medically refractory
psychiatric disorders, owing to its enhanced safety profile.
• Nevertheless, ablative procedures using radiofrequency thermocoagulation or
Gamma Knife radiosurgery are still in use. The reversible and adjustable nature of
DBS may allow treating physicians to optimize therapy over time.
• Surgery for psychiatric disorders should be performed by a multidisciplinary team
of specialists, including psychiatrists, functional neurosurgeons, neurologists,
neuropsychologists, neuroradiologists, biomedical engineers, and bioethicists,
working within strict ethical paradigms.

77. References:
• Youmans and Winn neurological surgery 7th edition
• Ramamurthi & Tandon's textbook of neurosurgery 3rd edition
• Internet
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