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Bilateral cingulotomy

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Bilateral cingulotomy is a form of psychosurgery, introduced in 1952 as an alternative to lobotomy. Today, it is mainly used as a last resort for the treatment of obsessive-compulsive disorder and chronic pain. The objective of this surgical procedure is the severing of the supracallosal fibres of the cingulum bundle, which pass through the anterior cingulate gyrus [1].

Target

Bilateral Cingulotomy targets the anterior cingulate cortex, which is a part of the limbic system. This system is responsible for the integration of feelings and emotion in the human cortex. It consists of the cingulate gyrus, parahippocampal gyrus and the hippocampal formation [2].

Studies in patients that were a subject to bilateral cingulotomy, that involved fMRI analyses, showed that the anterior cingulate cortex has a key role in cognitive 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 [3].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 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 [4].

These findings have also been confirmed by stereotactic microelectrode analysis of single cortical neurons in a study, which involved nine patients undergoing bilateral cingulotomy [3]. The study investigated the effect of performing attention demanding tasks on the activity of 36 neurons located in the anterior cingulate cortex. Upon analyzing of the results of the study it was concluded that the anterior cingulate cortex is indeed involved in the modification of cognitive 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 [3].

Neuroimaging also uncovered different sub-regions in the anterior cingulate cortex itself based on their function. It was proven that the caudal part of the anterior cingulate cortex plays a more important function in cognitive activities that involve attention, salience, interference and response competition [4]. These results combined with electrophysiological 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 part of the anterior cingulate cortex. Thus, theoretically if bilateral cingulotomy is performed in such patient in the rostral anterior cingulate cortex, better results should be obtained [4] , [3].

Moreover, OCD has been associated with a malformation of the basal ganglia [5]. 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 sonsorimotor, motor, oculomotor as well as the cognitive processes that are manifested by the limbic system f [6]. This pathway involves GABAergic inhibitory projections that serve as one of the means of communication between the different structures involved [5], [6]. It has been hypothesized that some forms of OCD are a result of disinhibition of a one or several of the circuits that operate in the CSTC [6]. This is also indicated by a finding that showed a significant decrease in intracortical inhibition in OCD patients [7]. Thus, lesions in the anterior cingulate cortex might contribute to the lessening of the disinhibition effect. This theory has been confirmed by another study which assessed the inhibitory and excitatory mechanisms in cortical inhibitory and excitatory mechanisms in OCD [7]. The study measured the excitability of motor cortex, as well as intracortical inhibition in OCD patients and a control of healthy individuals [7]. The results showed a significant decrease in intracortical inhibition, which resulted in a slowdown of interstimulus intervals by 3msec [7]. In addition to its proximity to and association with the limbic system and the amygdala in particular, which plays a key role in emotional experience, the anterior cingulate cortex shares afferent and efferent pathways with a number of thalamic nucleias well as the posterior cingulate and part of some parietal, frontal and supplementary motor cortex [8]. All these underline the high likelihood that the anterior cingulate cortex must be linked to OCD.

Functional MRI analyses of the anterior cingulate cortex have also led to the introduction of bilateral cingulotomy for the treatment of chronic pain. Such application was introduced since the anterior cingulate cortexhas been found to be related to the processing 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 f [9], [10].

Procedure

In most cases the procedure starts with the medical team taking a number of CT scan X-ray images of the brain of the patient. This step ensures that the exact target, the cingulate cortex is mapped out, so that the surgeon can identify it. Then burr holes are created into the patient’s skull using a drill. Lesions at the targeted tissue are made with the help of fine electrodes inserted very carefully at the right angle into the subject’s brain based on plotting charts and making sure important arteries and blood vessels are intact. The electrode is placed in a probe, or a holder, with only its tip projecting. Upon the correct insertion of the holder into the brain tissue, air is injected and more scan images are taken. Then, after the medical team has made sure they are on the right track, the tip of the electrode is advanced to the plain of the cingulate where it is heated to 75-90 C. Once the first lesion is created it serves as a center around which several other lesions are created. In order to confirm whether lesions are made at the right place, scan images are taken postoperatively and analyzed [11].

Recent technological advances, however, have made bilateral cingulotomy a more precise operation. For example, nowadays a neurosurgical team that has to perform the procedure can use an MRI to identify the location of the anterior and posterior commisures. This approach allows neurosurgeons to obtain a number of coronal images, which are then used to calculate the stereotactic coordinates of the place in the anterior cingulate cortex, where lesions need to be created. Moreover the MRI enables to differentiate more precisely the cell composition, and thus easily identify the gray matter in that region. This can then be further confirmed with the help of microelectrode recordings [12].

Side Effects

Patients usually recover from this operation over a period of 4 days. However, there are cases of subjects 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, vomiting, and headaches. However, in some cases patients exhibit seizures that sometimes appear up to two months after the surgical intervention. There is the discussion as to whether this is relevant and can be account to cingulotomy because such seizures were observed in patients that already had a history of this condition [13].

Case Studies

A recent study conducted at the Massachusetts General Hospital 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 6 months, 2) how many cingulotomies had a patient undergone before the examination of the effectiveness of the procedure, 3) did the patient show any significant change after the most recent procedure and 4) what were the side effects related to the procedure [13].

The follow up of the patients produced contradictory results, which indicated that bilateral cingulotomy is not the optimal treatment for OCD as of today [13]. From the 44 patients only 32% could be classified as responders and showed significant improvement compared to the other subjects. Another 14% exhibited some signs of improvement. Multiple cingultomies lead to the increase in responders by 6% and to partial responders by 11%. However, the side effects associated with the procedure were numerous. Among the complaints that patients had after the surgery were deficits in memory and apathy although these were rarely observed. In addition, some of the subjects complained from some form of urinary disturbance ranging from urinary retention to incontinence. Hydrocephalus (2%) and seizures (2%) were also observed [13].

Another clinical study investigated the effect of bilateral cingulotomy for the treatment of refractory chronic pain [14]. In this case 23 patients that 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 social and family relations of the participants in the study. Based on the data obtained, cingulatomy 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 aspects [14].

Future Research and Application

Bilateral cingulotomy is a method that can be used with care in patients with mental disorders that are not susceptible to any other form of treatment. However, further investigations that aim to more clearly identify the emotions connected with specific anatomical features of the limbic system should provide a better insight into how the effect of cingulotomy can be maximized. In addition, a clear set of guidelines of cases in which the procedure should be applied is necessary. This is currently done by the Massachusetts General Hospital, but this process should be standardized.

References

  1. Christmas et al.. (2004). Neurosurgery for mental disorders. Advances in Psychiatric Treatment, 10, 189-199.
  2. Kandel E., Schwartz J., Jessel T., .. (2000). Principles of Neural Science.4th edition, McGraw-Hill, New York, 853-857.
  3. 3.0 3.1 3.2 3.3 Davis et al.. (2000). Human anterior cingulate cortex neurons modulated by attention-demanding tasks. Journal of Neurophysiology , 83(6), 3575-2577.
  4. 4.0 4.1 4.2 Crottaz-Herbette S., Menon V.. (2006). Where and when the anterior cingulate cortex modulates attentional response: combined fMRI and ERP evidence. Journal of Cognitive Neuroscience, 18(5), 766-780.
  5. 5.0 5.1 Kandel E., Schwartz J., Jessel T., .. (2000). Principles of Neural Science.4th edition, McGraw-Hill, New York, 1223-1224.
  6. 6.0 6.1 6.2 Leckman. (2000). Tic Disorder. Neuropsychopharmacology: The Fifth Generation of Progress
  7. 7.0 7.1 7.2 7.3 Greenberg.(2000).Altered Cortical excitability in obsessive-compulsive disorder. Neurology, (54), 142
  8. Cohen et al. (1999). Alteration of Intention and Self-Initiated Action Associated With Bilateral Anterior Cingulotomy. J Neuropsychiatry Clin Neurosci, (11), 444-453142
  9. Lenz et al. (1998). Painful stimuli evoke potentials recorded from parasylvian cortex in humans. Journal of Neurophysiology , 80(4), 2077-2078
  10. Rolls et al. (2003). Representations of Pleasant and Painful Touch in the Human Orbitofrontal and Cingulate Cortices. Cerebral Cortex, 13(3), 308-317
  11. Joann Rodgers. (1992).Psychosurgery: Damaging the Brain to Save the Mind , HarperCollins, New York, 350-378, ISBN 0060164050
  12. Richter et al. (2004). Cingulotomy for Psychiatric Disease: Microelectrode Guidance, a Callosal Reference System for Documenting Lesion Location, and Clinical Results, 54(3), 622-630
  13. 13.0 13.1 13.2 13.3 Dougherty et al. (2002). Prospective Long-Term Follow-Up of 44 Patients Who Received Cingulotomy for Treatment-Refractory Obsessive-Compulsive Disorder, 159(2), 269-275
  14. 14.0 14.1 Wilkinson et al. (2000). Bilateral anterior cingulotomy for chronic noncancer pain, 46(6), 1535-1536
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