Psychosurgery .pptx

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, Maclean expanded 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, 5 th e . 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 Conformite ́ 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.

52. 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.

53. 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.

54. 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.

55. 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.

56. 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 .

57. 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.

58. 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.

59. 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.

60. ≥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: 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). Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month. Insomnia or hypersomnia nearly every day. Psychomotor agitation or retardation nearly every day. Fatigue or loss of energy nearly every day. Feelings of worthlessness or excessive or inappropriate guilt. Diminished ability to think or concentrate, or indecisiveness, nearly every day. 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

61. 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.

62. 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.

63. 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.

64. 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.

65. 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 .

66. 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.

67. 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.

68. 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 .

69. 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.

70. 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.

71. 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.

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

73. 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.

74. 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.

75. 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.

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