Bilateral cingulotomy is a form of

psychosurgery Psychosurgery, also called neurosurgery for mental disorder (NMD), is the neurosurgical treatment of mental disorder. Psychosurgery has always been a controversial medical field. The modern history of psychosurgery begins in the 1880s under th ...

, introduced in 1948 as an alternative to lobotomy. Today, it is mainly used in the treatment of depression and obsessive-compulsive disorder. In the early years of the twenty-first century, it was used in Russia to treat

addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...

.A. Carter and W. Hall 2012 ''Addiction neuroethics: the promises and perils of neuroscience research on addiction''. Cambridge University Press: 188-9. It is also used in the treatment of chronic pain. The objective of this procedure is the severing of the supracallosal fibres of the cingulum bundle, which pass through the anterior cingulate gyrus.

History

Cingulotomy was introduced in the 1940s as an alternative to standard pre-frontal leucotomy/lobotomy in the hope of alleviating symptoms of mental illness whilst reducing the undesirable effects of the standard operation (personality changes, etc.). It was suggested by American physiologist John Farquhar Fulton who, at a meeting of the Society of British Neurosurgeons in 1947, said "were it feasible, cingulectomy in man would seem an appropriate place for limited leucotomy". This was derived from the hypothesis of

James Papez James Wenceslas Papez (;Livingston, Kenneth E. '. U.S. National Library of Medicine, 1981 1883–1958) was an American neuroanatomist, most famous for his 1937 description of the Papez circuit, a neural pathway in the brain thought to be invo ...

who thought that the cingulum was a major component of an anatomic circuit believed to play a significant role in emotion.S Corkin (1980) A prospective study of cingulotomy. In ES Valenstein (ed) ''The psychosurgery debate: scientific, legal, and ethical perspectives''. San Francisco, WH Freeman and Co: 164-204 The first reports of the use of cingulotomy on psychiatric patients came from J le Beau in Paris, Hugh Cairns in Oxford, and Kenneth Livingston in Oregon.

Target

Bilateral cingulotomy targets the

anterior cingulate cortex In the human brain, the anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex that resembles a "collar" surrounding the frontal part of the corpus callosum. It consists of Brodmann areas 24, 32, and 33. It is involved ...

, which is a part of the

limbic system The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''Ps ...

. This system is responsible for the integration of feelings and emotion in the human cortex. It consists of the cingulate gyrus,

parahippocampal gyrus The parahippocampal gyrus (or hippocampal gyrus') is a grey matter cortical region of the brain that surrounds the hippocampus and is part of the limbic system. The region plays an important role in memory encoding and retrieval. It has been inv ...

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...

and the hippocampal formation.Kandel E., Schwartz J., Jessel T., .. (2000). Principles of Neural Science.4th edition, McGraw-Hill, New York, 853-857. Studies in patients who were subject to bilateral cingulotomy, involving

fMRI Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area o ...

analyses, showed that the

has a key role in

cognitive Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

control and is highly likely to be involved in the control of attentional response, whereas the dorsal part of that region of the brain was not identified to be involved in such a process, although this is still under dispute. The function of the dorsal part of the cingulate cortex was connected to the sorting out and processing of conflicting information signals. In addition,

neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incre ...

studies also indicated that the anterior cingulate cortex participates in the modulation of cortical regions that are of higher order, as well as sensory processing areas. These findings have also been confirmed by stereotactic microelectrode analysis of single cortical

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

in a study, which involved nine patients undergoing bilateral cingulotomy. The study investigated the effect of performing attention demanding tasks on the activity of 36 neurons located in the

. Upon analyzing the results of the study, it was concluded that the anterior cingulate cortex is indeed involved in the modification of

tasks that require attention, based on the fact that there was a change in the basal firing rate of neurons in that region during simulation of such tasks. Neuroimaging also uncovered different sub-regions in the

itself, based on their function. These studies showed that the

caudal Caudal may refer to: Anatomy * Caudal (anatomical term) (from Latin ''cauda''; tail), used to describe how close something is to the trailing end of an organism * Caudal artery, the portion of the dorsal aorta of a vertebrate that passes into the ...

part of the anterior cingulate cortex plays a more important function in cognitive activities that involve attention, salience, interference and response competition. These results, combined with

electrophysiological Electrophysiology (from Greek , ''ēlektron'', "amber" etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , ''-logia'') is the branch of physiology that studies the electrical properties of bi ...

investigation of the function of neurons in the anterior cingulate cortex, have provided insights that can be used in the improvement of cingulotomy performed on patients treated for OCD. The basis behind this idea is the fact that a variation of certain tasks, Emotional Stroop tasks (ES), which have been particularly identified as exerting effects in OCD patients, activate neurons in the more

rostral Rostral may refer to: Anatomy * Rostral (anatomical term), situated toward the oral or nasal region * Rostral bone, in ceratopsian dinosaurs * Rostral organ, of certain fish * Rostral scale, in snakes and scaled reptiles Other uses * Rostral colu ...

part of the anterior cingulate cortex. Thus, theoretically, if bilateral cingulotomy is performed in such a patient in the rostral anterior cingulate cortex, better results should be obtained. Moreover, OCD has been associated with a malformation of the

basal ganglia The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...

.Kandel E., Schwartz J., Jessel T., .. (2000). Principles of Neural Science.4th edition, McGraw-Hill, New York, 1223-1224. The function of this part of the human brain has been mapped to be composed of fiber tracks associated with numerous parallel cortico-striato-thalamocortical circuits (CSTC), which are involved in sensorimotor, motor, oculomotor as well as the

processes that are manifested by the

.Leckman. (2000). Tic Disorder. Neuropsychopharmacology: The Fifth Generation of Progress This pathway involves

GABAergic In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter GABA. For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic neuron produces GABA. A ...

inhibitory An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a Chemical synapse, postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Inc ...

projections that serve as one of the means of communication between the different structures involved. It has been hypothesized that some forms of OCD are a result of disinhibition of one or several of the circuits that operate in the CSTC. This is also indicated by a finding that showed a significant decrease in intracortical

inhibition Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

in OCD patients. Thus,

lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

in the

might contribute to the lessening of the disinhibition effect. This hypothesis has been confirmed by another study, which assessed the cortical inhibitory and excitatory mechanisms in OCD. The study measured the excitability of the motor cortex, as well as intracortical inhibition in OCD patients and a control group of healthy individuals. The results showed a significant decrease in intracortical inhibition, which resulted in a slowdown of

interstimulus interval The interstimulus interval (often abbreviated as ISI) is the temporal interval between the offset of one stimulus to the onset of another. For instance, Max Wertheimer did experiments with two stationary, flashing lights that at some interstimulus ...

s by 3 ms. In addition to its proximity to and association with the limbic system and the

in particular, which plays a key role in emotional experience, the anterior cingulate cortex shares

afferent Afferent may refer to: Anatomical structures Meaning "conveying towards a center": * Afferent arterioles, blood vessels that supply the nephrons * Afferent lymphatic vessels, lymph vessels that carry lymph to a lymph node * Afferent nerve fiber ...

and

efferent Efferent may refer to: Anatomical structures Meaning 'conveying away from a center': *Efferent arterioles, conveying blood away from the Bowman's capsule in the kidney *Efferent nerve fiber, carries nerve impulses away from the central nervous sy ...

pathways with a number of thalamic nuclei as well as the posterior cingulate and part of some parietal,

frontal Front may refer to: Arts, entertainment, and media Films * ''The Front'' (1943 film), a 1943 Soviet drama film * ''The Front'', 1976 film Music *The Front (band), an American rock band signed to Columbia Records and active in the 1980s and ea ...

and

supplementary motor cortex The supplementary motor area (SMA) is a part of the motor cortex of primates that contributes to the control of movement. It is located on the midline surface of the hemisphere just in front of (anterior to) the primary motor cortex leg representa ...

. All these underline the high likelihood that the anterior cingulate cortex must have some involvement in OCD. Functional MRI analyses of the

have also led to the introduction of bilateral cingulotomy for the treatment of chronic pain. Such application was introduced since the anterior cingulate cortex has been found to be related to the processing of nociceptive information input. In particular, the role of the anterior cingulate cortex is in the interpretation of how a stimulus affects a person rather than its actual physical intensity.

Procedure

A book published in 1992 described how the operation was carried out at that time. In most cases the procedure started with the medical team taking a number of CT scan

X-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

images of the brain of the patient. This step ensured that the exact target, the

cingulate cortex The cingulate cortex is a part of the brain situated in the medial aspect of the cerebral cortex. The cingulate cortex includes the entire cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the ci ...

was mapped out, so that the surgeon could identify it. Burr holes were then created in the patient's

skull The skull is a bone protective cavity for the brain. The skull is composed of four types of bone i.e., cranial bones, facial bones, ear ossicles and hyoid bone. However two parts are more prominent: the cranium and the mandible. In humans, the ...

using a drill.

Lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

at the targeted tissue were made with the help of fine electrodes inserted at the right angle into the subject's brain based on plotting charts and making sure important arteries and

blood vessels The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...

were intact. The electrode was placed in a probe, or a holder, with only its tip projecting. Upon the correct insertion of the holder into the brain tissue, air was injected and more scan images were taken. Then, after the medical team had made sure they were on the right track, the tip of the electrode was advanced to the plane of the

cingulate Cingulata, part of the superorder Xenarthra, is an order of armored New World placental mammals. Dasypodids and chlamyphorids, the armadillos, are the only surviving families in the order. Two groups of cingulates much larger than extant arm ...

where it was heated to 75-90 °C. Once the first lesion was created it served as a center around which several other

were created. In order to confirm whether lesions are made at the right place,

scan Scan may refer to: Acronyms * Schedules for Clinical Assessment in Neuropsychiatry (SCAN), a psychiatric diagnostic tool developed by WHO * Shared Check Authorization Network (SCAN), a database of bad check writers and collection agency for bad ...

images were taken postoperatively and analyzed.Joann Rodgers. (1992).Psychosurgery: Damaging the Brain to Save the Mind, HarperCollins, New York, 350-378, Recent technological advances, however, have made bilateral cingulotomy a more precise operation. For example, nowadays a

neurosurgical Neurosurgery or neurological surgery, known in common parlance as brain surgery, is the medical specialty concerned with the surgical treatment of disorders which affect any portion of the nervous system including the brain, spinal cord and peri ...

team that performs the procedure can use an MRI to identify the location of the

anterior Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

and posterior commissures. This approach allows neurosurgeons to obtain a number of coronal images, which are then used to calculate the stereotactic coordinates of the target in the

, where lesions need to be made. Moreover, the MRI enables more precise differentiation of the cell composition, and thus easily permits the identification of the

grey matter Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distingui ...

in that region. This can then be further confirmed with the help of microelectrode recordings.

Side effects

Patients usually recover from this operation over a period of four days. However, there are cases of subjects being released from hospital after as few as 48 hours after the operation. The mild shorter postoperative complications that are most commonly related to bilateral cingulotomy are typical of head interventions and include but are not limited to

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

, and

headaches Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result of m ...

. However, in some cases, patients exhibit

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

that sometimes appear up to two months after the surgical intervention. It has been questioned whether this is relevant and can be attributed to cingulotomy because such seizures were observed in patients who already had a history of this condition.

Case studies

A 2002 study conducted at the

Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...

analyzed the outcome of bilateral cingulotomy in 44 patients for the treatment of OCD in the period between 1965 and 1986. Patients were followed up over a long term and evaluated based on several criteria: 1) how many of them were responders after a period of six months, 2) how many cingulotomies a patient had undergone before the examination of the effectiveness of the procedure, 3) whether the patient showed any significant change after the most recent procedure, and 4) what the side effects related to the procedure were. The follow-up of the patients produced contradictory results, which indicated that bilateral cingulotomy is not the optimal treatment for OCD. Of the 44 patients, only 32% both fit the "responder" criteria and showed significant improvement compared to the other subjects. Another 14% exhibited some signs of improvement. Multiple cingulotomies correlated with a higher likelihood of continuing to respond to follow-up inquiries (6% more often fit the full "responder" criteria, 11% more often fit the partial "responder" criteria. However, the side effects associated with the procedure were numerous. Among the complaints that patients had after the surgery were

apathy Apathy is a lack of feeling, emotion, interest, or concern about something. It is a state of indifference, or the suppression of emotions such as concern, excitement, motivation, or passion. An apathetic individual has an absence of intere ...

and deficits in memory, although these were rarely reported. In addition, some subjects complained of some form of urinary disturbance, ranging from urinary retention to

incontinence Incontinence or Incontinent may refer to: *Fecal incontinence, the involuntary excretion of bowel contents *Urinary incontinence, the involuntary excretion of urine * Lack of moderation or self-control, especially related to sexual desire - see I ...

Hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...

(2%) and seizures (2%) were also observed. Bilateral cingulotomy has also been used in the treatment of chronic refractory pain. A systematic review of 11 studies encompassing 224 patients found that anterior cingulotomy led to significant pain relief in greater than 60% of patients post-operatively as well as at one year following the procedure. Of the included studies, one clinical study investigated the effect of bilateral cingulotomy for the treatment of

refractory In materials science, a refractory material or refractory is a material that is resistant to decomposition by heat, pressure, or chemical attack, and retains strength and form at high temperatures. Refractories are polycrystalline, polyphase, ...

chronic pain. In this case, 23 patients who were subject to 28 cingulotomies in total were followed up. The analyses aimed at determining how much the pain of each individual was affected after the procedure with the help of a questionnaire. In addition, the examiners tried to evaluate the impacts on social and family relations of the participants in the study. Based on the data obtained, cingulotomy for treatment of chronic pain showed promising results. 72% reported improvement in the level of pain experienced, and 50% indicated that they no longer required painkillers after cingulotomy. More than half of the patients also claimed that the surgical procedure was beneficial and contributed to the improvement of their social interactions.

Notes

References

External links

MGH Psychiatric Neurosurgery Committee
{{DEFAULTSORT:Bilateral Cingulotomy Neurosurgical procedures Treatment of depression Treatment of obsessive–compulsive disorder