Centromedian thalamic deep brain stimulation for drug-resistant epilepsy: single-center experience.

OBJECTIVE: Neuromodulation of the centromedian nucleus of the thalamus (CM) has unclear effectiveness in the treatment of drug-resistant epilepsy. Prior reports suggest that it may be more effective in the generalized epilepsies such as Lennox-Gastaut syndrome (LGS). The objective of this study was to determine the outcome of CM deep brain stimulation (DBS) at the authors' institution. METHODS: Retrospective chart review was performed for all patients who underwent CM DBS at Emory University, which occurred between December 2018 and May 2021. CM DBS electrodes were implanted using three different surgical methods, including frame-based, robot-assisted, and direct MRI-guided. Seizure frequency, stimulation parameters, and adverse events were recorded from subsequent clinical follow-up visits. RESULTS: Fourteen patients underwent CM DBS: 9 had symptomatic generalized epilepsy (including 5 with LGS), 3 had primary or idiopathic generalized epilepsy, and 2 had bifrontal focal epilepsy. At last follow-up (mean [± SEM] 19 ± 5 months, range 4.1-33 months, ≥ 6 months in 11 patients), the median seizure frequency reduction was 91%. Twelve patients (86%) were considered responders (≥ 50% decrease in seizure frequency), including 10 of 12 with generalized epilepsy and both patients with bifrontal epilepsy. Surgical adverse events were rare and included 1 patient with hardware breakage, 1 with a postoperative aspiration event, and 1 with a nonclinically significant intracranial hemorrhage. CONCLUSIONS: CM DBS was an effective treatment for drug-resistant generalized and bifrontal epilepsies. Additional studies and analyses may investigate whether CM DBS is best suited for specific epilepsy types, and the relationship of lead location to outcome in different epilepsies.

Neuroanatomical considerations for optimizing thalamic deep brain stimulation in Tourette syndrome.

OBJECTIVE: Deep brain stimulation (DBS) of the centromedian thalamic nucleus has been reportedly used to treat severe Tourette syndrome, yielding promising outcomes. However, it remains unclear how DBS electrode position and stimulation parameters modulate the specific area and related networks. The authors aimed to evaluate the relationships between the anatomical location of stimulation fields and clinical responses, including therapeutic and side effects. METHODS: The authors collected data from 8 patients with Tourette syndrome who were treated with DBS. The authors selected the active contact following threshold tests of acute side effects and gradually increased the stimulation intensity within the therapeutic window such that acute and chronic side effects could be avoided at each programming session. The patients were carefully interviewed, and stimulation-induced side effects were recorded. Clinical outcomes were evaluated using the Yale Global Tic Severity Scale, the Yale-Brown Obsessive-Compulsive Scale, and the Hamilton Depression Rating Scale. The DBS lead location was evaluated in the normalized brain space by using a 3D atlas. The volume of tissue activated was determined, and the associated normative connective analyses were performed to link the stimulation field with the therapeutic and side effects. RESULTS: The mean follow-up period was 10.9 ± 3.9 months. All clinical scales showed significant improvement. Whereas the volume of tissue activated associated with therapeutic effects covers the centromedian and ventrolateral nuclei and showed an association with motor networks, those associated with paresthesia and dizziness were associated with stimulation of the ventralis caudalis and red nucleus, respectively. Depressed mood was associated with the spread of stimulation current to the mediodorsal nucleus and showed an association with limbic networks. CONCLUSIONS: This study addresses the importance of accurate implantation of DBS electrodes for obtaining standardized clinical outcomes and suggests that meticulous programming with careful monitoring of clinical symptoms may improve outcomes.

Minimally invasive trans-sulcal parafascicular surgical resection of cerebral tumors: translating anatomy to early clinical experience.

The minimally invasive port-based trans-sulcal parafascicular surgical corridor (TPSC) has incrementally evolved to provide a safe, feasible, and effective alternative to access subcortical and intraventricular pathologies. A detailed anatomical foundation is important in mitigating cortical and white matter tract injury with this corridor. Thus, the aims of this study are (1) to provide a detailed anatomical construct and overview of TPSCs and (2) to translate an anatomical framework to early clinical experience. Based on regional anatomical constraints, suitable parafascicular entry points were identified and described. Fiber tracts at both minimal and increased risks for each corridor were analyzed. TPSC-managed cases for metastatic or primary brain tumors were retrospectively reviewed. Adult patients 18 years or older with Karnofsky Performance Status (KPS) ≥ 70 were included. Subcortical brain metastases between 2 and 6 cm or primary brain tumors between 2 and 5 cm were included. Patient-specific corridors and trajectories were determined using MRI-tractography. Anatomy: The following TPSCs were described and translated to clinical practice: superior frontal, inferior frontal, inferior temporal, intraparietal, and postcentral sulci. Clinical: Eleven patients (5 males, 6 females) were included (mean age = 52 years). Seven tumors were metastatic, and 4 were primary. Gross total, near total, and subtotal resection was achieved in 7, 3, and 1 patient(s), respectively. Three patients developed intraoperative complications; all recovered from their intraoperative deficits and returned to baseline in 30 days. A detailed TPSC anatomical framework is critical in conducting safe and effective port-based surgical access. This review may represent one of the few early translational TPSC studies bridging anatomical data to clinical subcortical and intraventricular surgical practice.

Deep Brain Stimulation for Refractory Tourette Syndrome: Electrode Position and Clinical Outcome.

The efficacy of deep brain stimulation (DBS) for refractory Tourette syndrome (TS) is accepted, but whether the efficacy of DBS treatment in the Japanese population is equivalent to those reported internationally and whether adverse effects are comparable are not yet known. This study evaluated the clinical practice and outcome of DBS for TS in a Japanese institution. This study included 25 consecutive patients with refractory TS treated with thalamic centromedian-parafascicular nucleus DBS. The severity of tics was evaluated with the Yale Global Tic Severity Scale (YGTSS) before surgery, at 1 year after surgery, and at the last follow-up of 3 years or more after surgery. The occurrence of adverse events, active contact locations, and stimulation conditions were also evaluated. YGTSS tic severity score decreased by average 45.2% at 1 year, and by 56.6% at the last follow-up. The reduction was significant for all aspects of the scores including motor tics, phonic tics, and impairment. The mean coordinates of active contacts were 7.62 mm lateral to the midline, 3.28 mm posterior to the midcommissural point, and 3.41 mm above anterior commissure-posterior commissure plane. Efficacy and stimulation conditions were equivalent to international reports. The stimulation-induced side effects included dysarthria (32.0%) and paresthesia (12.0%). Device infection occurred in three patients (12.0%) as a surgical complication. The DBS device was removed because of infection in two patients. DBS is an effective treatment for refractory TS, although careful indication is necessary because of the surgical risks and unknown long-term outcome.

Lead Repositioning Guided by Both Physiology and Atlas Based Targeting in Tourette Deep Brain Stimulation.

Background: The centromedian (CM) region of the thalamus is a common target for deep brain stimulation (DBS) treatment for Tourette Syndrome (TS). However, there are currently no standard microelectrode recording or macrostimulation methods to differentiate CM thalamus from other nearby structures and nuclei. Case Report: Here we present a case of failed conventional stereotactic targeting in TS DBS. Postoperative local field potential recordings (LFPs) showed features including beta power desynchronization during voluntary movement and thalamo-cortical phase amplitude coupling at rest. These findings suggested that the DBS lead was suboptimally placed in the ventral intermediate (VIM) nucleus of the thalamus rather than the intended CM region. Due to a lack of clinical improvement in tic severity scales three months following the initial surgery, the patient underwent lead revision surgery. Slight repositioning of the DBS leads resulted in a remarkably different clinical outcome. Afterwards, LFPs revealed less beta desynchronization and disappearance of the thalamo-cortical phase amplitude coupling. Follow-up clinical visits documented improvement of the patient's global tic scores. Discussion: This case provides preliminary evidence that combining physiology with atlas based targeting may possibly enhance outcomes in some cases of Tourette DBS. A larger prospective study will be required to confirm these findings. Highlight: This report demonstrates a case of failed centromedian nucleus region deep brain stimulation (DBS). We observed suboptimal tic improvement several months following DBS surgery and subsequent lead revision improved the outcome. The neurophysiology provided an important clue suggesting the possibility of suboptimally placed DBS leads. Repeat LFPs during lead revision revealed less beta desynchronization and disappearance of the thalamo-cortical phase amplitude coupling. There was improvement in tic outcome following slight repositioning during bilateral DBS lead revision. This case provides preliminary evidence supporting the use of physiology to augment the atlas based targeting of Tourette DBS cases.

Targeting the centromedian thalamic nucleus for deep brain stimulation.

OBJECTIVES: Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by: (1) developing a structural MRI approach for CM visualisation, (2) identifying the CM's neurophysiological characteristics using microelectrode recordings (MERs) and (3) mapping connectivity from CM-DBS sites using functional MRI (fMRI). METHODS: 19 patients with LGS (mean age=28 years) underwent presurgical 3T MRI using magnetisation-prepared 2 rapid acquisition gradient-echoes (MP2RAGE) and fMRI sequences; 16 patients proceeded to bilateral CM-DBS implantation and intraoperative thalamic MERs. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE using Sobel edge detection. Mixed-effects analysis compared two MER features (spike firing rate and background noise) between ventrolateral, CM and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions of interest. RESULTS: The CM appeared as a hyperintense region bordering the comparatively hypointense pulvinar, mediodorsal and parafasicular nuclei. At the group level, reduced spike firing and background noise distinguished CM from the ventrolateral nucleus; however, these trends were not found in 20%-25% of individual MER trajectories. Areas of fMRI connectivity included basal ganglia, brainstem, cerebellum, sensorimotor/premotor and limbic cortex. CONCLUSIONS: In the largest clinical trial of DBS undertaken in patients with LGS to date, we show that accurate targeting of the CM is achievable using 3T MP2RAGE MRI. Intraoperative MERs may provide additional localising features in some cases; however, their utility is limited by interpatient variability. Therapeutic effects of CM-DBS may be mediated via connectivity with brain networks that support diverse arousal, cognitive and sensorimotor processes.

Clinical Outcome of Patients with Deep Brain Stimulation of the Centromedian Thalamic Nucleus for Refractory Epilepsy and Location of the Active Contacts.

OBJECTIVES: To investigate the clinical outcome of patients treated with chronic deep brain stimulation (DBS) of the centromedian nucleus (CM) for refractory epilepsy and to determine the location of active contacts. METHODS: The outcome of CM stimulation was evaluated as percent seizure reduction compared to the baseline 3 months. To establish the location of active contacts, 27 leads were studied in 14 patients with refractory epilepsy. An analysis was conducted to reveal whether any coordinates of the center of the active contacts predicted percent seizure reduction. RESULTS: With an average follow-up of 18.2 ± 5.6 months, the mean percent seizure reduction (n = 14) was 68 ± 22.4% (25-100%). Eleven of the 14 patients (78.6%) achieved >50% improvement in seizure frequency. Specifically, all 4 patients (100%) with generalized epilepsy (Lennox-Gastaut syndrome) and 7 of 10 patients (70%) with multilobar epilepsy showed >50% reduction in seizure frequency. The mean coordinates of the center of the active contact were located in the superior part of the anterior ventrolateral CM. The calculated coordinates of laterality from midline (x), anterior-posterior (y) and height (z) from the posterior commissure did not correlate with seizure outcome measured by percent seizure reduction. However, the locations of active contacts used during chronic CM stimulation in multilobar epilepsy were identified more dorsal to those used in generalized epilepsy. CONCLUSIONS: Chronic CM stimulation is a safe and effective means in the treatment of refractory epilepsy.

Characterising the Analgesic Effect of Different Targets for Deep Brain Stimulation in Trigeminal Anaesthesia Dolorosa.

BACKGROUND: Several deep brain stimulation (DBS) targets have been explored for the alleviation of trigeminal anaesthesia dolorosa. We aimed to characterise the analgesia produced from the periaqueductal grey (PAG) and centromedian-parafascicular (CmPf) nucleus using a within-subject design. METHOD: We report a case series of 3 subjects implanted with PAG and CmPf DBS systems for the treatment of anaesthesia dolorosa. At follow-up, testing of onset and offset times, magnitude, and thermal and mechanical sensitivity was performed. RESULTS: The mean pain score of the cohort was acutely reduced by 56% (p < 0.05) with PAG and 67% (p < 0.01) with CmPf stimulation at mean time intervals of 38 and 16 min, respectively. The onset time was 12.5 min (p < 0.05) for PAG stimulation and 2.5 min (p < 0.01) for CmPf. The offset time was 2.5 min (p < 0.05) for PAG and 12.5 min (p < 0.01) for CmPf. The two targets were effective at different stimulation frequencies and were not antagonistic in effect. CONCLUSION: The mechanisms by which stimulation at these two targets produces analgesia are likely to be different. Certain pain qualities may respond more favourably to specific targets. Knowledge of onset and offset times for the targets can guide optimisation of stimulation settings. The use of more than one stimulation target may be beneficial and should be considered in anaesthesia dolorosa patients.

Rostral Intralaminar Thalamic Deep Brain Stimulation Triggered Cortical and Hippocampal Structural Plasticity and Enhanced Spatial Memory.

BACKGROUND/AIMS: Rostral intralaminar thalamic nucleus (ILN) has been shown to modulate cognition through indirect connection with the hippocampus and prefrontal cortex. We explored the effects of deep brain stimulation (DBS) to the rostral ILN on spatial memory acquisition, brain neuronal activation and cortical and hippocampal synaptic changes in rats. METHODS: The Morris water maze (MWM) task was used to evaluate the spatial memory of the rats. The expression of c-fos, an immediate early gene, was used to identify neural activation in the cerebral cortex and hippocampus. Synaptic changes in the somatosensory cortical and hippocampal neurons were explored with dendritic spine analysis following Golgi-Cox staining. RESULTS: Our results showed that a barrage of DBS to the rostral ILN of normal rats significantly shortened their escape latency in MWM compared with sham-stimulated and untreated control rats. Rats with enhanced spatial memory had more c-fos immunoreactive cells in layer IV of the somatosensory cortex. Layer III cortical and CA1 hippocampal pyramidal neurons showed over 50% increase of dendritic spines, while only the proximal apical dendrites of layer V cortical pyramidal neurons had more dendritic spines. CONCLUSIONS: Rostral ILN-DBS activated neurons in the cerebral cortex and triggered cortical and hippocampal structural plasticity in association with spatial memory enhancement.

Correlations between EEG and clinical outcome in chronic neuropathic pain: surgical effects and treatment resistance.

Chronic neuropathic pain may require a neurosurgical treatment, but for reasons that have not been fully explored yet, a significant number of patients do not benefit from the intervention. We compared the resting EEG of 15 healthy controls to the EEG of 23 chronic neuropathic pain patients before and 12 months after treatment by the central lateral thalamotomy (CLT). A patient subgroup had a high (n = 14, pain relief (PR) ≥ 50%) and another subgroup a low (n = 9, PR < 50%) postoperative PR. EEG spectral power and source localization of the high PR patients were normalized postoperatively. In contrast, low PR patients showed postoperative maintenance of insular, cingulate and prefrontal overactivities, and their frustration values were positively correlated with cingulate and prefrontal activity. These findings demonstrate a normalizing effect of CLT on cortical activity and suggest that treatment resistance is associated with a frustration-based dynamics.

Delineation of the nucleus centre median by proton density weighted magnetic resonance imaging at 3 T.

OBJECTIVE: To demonstrate that proton density weighted magnetic resonance imaging (MRI) at 3 T accomplishes delineation of the centre median (CM) complex from surrounding thalamic tissue and may improve targeting accuracy in stereotactic neurosurgery. METHODS: Five healthy subjects (1 man, 4 women; age range 22-35 years) underwent high-resolution MRI at 3 T with different imaging parameters in order to optimize the direct visualization of the CM. RESULTS: In healthy subjects, the CM complex of the thalamus can be reliably contrasted on axially oriented slices by means of proton density weighted turbo-spin-echo MRI. An in-plane resolution of at least 0.6 x 0.6 mm2 is crucial at a slice thickness between 2 and 3 mm. Effective suppression of head motion is essential. CONCLUSION: MRI-based delineation of the CM could have therapeutic potential to facilitate target determination for neuromodulation in stereotactic neurosurgery.

Clinical review of DBS for Tourette Syndrome.

Deep brain stimulation for Tourette Syndrome is an emerging therapy for patients with severe, disabling tics. The complexity of symptoms associated with TS present challenges for electrode target selection and evaluation of outcome that distinguish it from other disorders for which DBS has been studied. Accumulating data have been sufficiently promising to justify further study. Yet, many questions remain. Systematic, controlled, collaborative studies are required to answer the many questions that remain.

Targeting the caudal intralaminar nuclei for functional neurosurgery of movement disorders.

The caudal intralaminar nuclei, in particular the Centrum-Medianum Parafascicularis (CM-Pf) nucleus complex, are involved in various functions, particularly in pain processing and in motor control, through their projections to the subthalamic nucleus and their afferents from the pallidum internus (GPi) (or entopeduncular nucleus in the rat). The nociceptive inputs received by the CM-Pf are modulated by the somato-sensory thalamus. The lateral habenula (HbL) receives noxious inputs and has an inhibitory influence on the nigral dopaminergic neurons. CM-Pf and the HbL share comparable response characteristics to noxious inputs and might play comparable, and perhaps complementary, roles in conveying the nociceptive information to the basal ganglia system, thereby modulating motor responses, such as freezing and dyskinesias. The interaction between CM-Pf, HbL, GPi, STN and SNC might provide a new template for high frequency stimulation strategies in the treatment of movement disorders.

Multi-target strategy for Parkinsonian patients: the role of deep brain stimulation in the centromedian-parafascicularis complex.

The intra-laminar (IL) thalamic complex, composed of centromedian (CM) and parafascicular (Pf) nucleus, is a strategic crossroad for the activity of the basal ganglia and is recently regaining its position has a putative neurosurgical target for Parkinsonian syndromes. The multi-target approach we have encouraged since the late nineties has allowed the combined implantation of a standard target (the subthalamic nucleus-STN or the internal pallidus-GPi) plus an innovative one (CM/Pf) in well-identified Parkinson's disease (PD) patients; hence, it is possible to study, in the same PD patients, the specific target-mediated effects on different clinical signs. Here, we focus on the potential usefulness of implanting the CM/Pf complex when required in the management of contra-lateral tremor (resistant to standard deep brain stimulation-DBS - in STN - , n=2) and disabling involuntary movements, partially responsive to GPi-DBS (n=6). When considering global UPDRS scores, CM/Pf-DBS ameliorate extra-pyramidal symptoms but not as strongly as STN (or GPi) does. Yet, CM/Pf acts very powerfully on tremor and contributes to the long-term management of l-Dopa-induced involuntary movements. The lack of cognitive deficits and psychic impairment associated with the improvement of their quality of life, in our small cohort of CM/Pf implanted patients, reinforces the notion of CM/Pf as a safe and attractive area for surgical treatment of advanced PD, possibly affecting not only motor but also associative functions.

Transsulcal approach supported by navigation-guided neurophysiological monitoring for resection of paracentral cavernomas.

OBJECTIVES: The aim of the study is to evaluate tools that can improve surgical precision and minimize surgical trauma for removal of cavernomas in the paracentral area. Moreover, the surgical strategies for the treatment of symptomatic epilepsy in cavernoma patients are discussed. PATIENTS AND METHODS: Between June 2000 and July 2007, 17 patients suffering from paracentral cavernoma underwent surgery via a transsulcal approach with the aid of neuronavigation, functional mapping and neurophysiological intraoperative monitoring. To optimize outcome for procedures in the paracentral area, the hemosiderin-stained tissue was removed entirely except for a small proportion on the side of precentral gyrus. RESULTS: All cavernomas and their adjacent sulci could be precisely located with the aid of ultrasonography-assisted neuronavigation. By combining preoperative fMRI and intraoperative neurophysiological monitoring, including SEP, MEP and cortical mapping, the motor cortex could be defined in all cases. Thus damage to the primary motor area could be avoided during resection of cavernomas. All the lesions located in the paracentral area were removed completely via transsulcal microsurgical approach without neurological deficits. No significant seizures were induced during surgery. CONCLUSIONS: The successful excision of these lesions was effected by the following four key factors: (1) the precise location of the lesion supported by intraoperative neuronavigation; (2) the preservation of the eloquent area with the aid of functional mapping; (3) a minimally invasive transsulcal microsurgical approach; and (4) the entire removal of cavernoma and hemosiderin-stained tissue.

A minimally invasive transsulcal approach to the paracentral inner lesion.

OBJECTIVE: Surgical options to remove lesions located deep in the sulcus at the paracentral area are limited. To minimize therapeutic morbidities, such as cortical injuries before the removal, a transsulcal approach was applied by taking the results of neuroimaging and functional mapping into consideration. METHODS: Four patients with paracentral inner lesions including anaplastic astrocytoma, cortical dysplasia, and cavernous angioma were operated on. All lesions were located deep in the paracentral sulci. According to the outcome of MRI and functional mapping of the cortex over the lesion, the central or the postcentral sulcus was opened toward the lesion. Immediately after complete dissection of the sulcus to remove the lesion, neurological findings were evaluated in the awake state. RESULTS: All lesions were situated beneath the hand or foot area. The transsulcal approach was successfully conducted without any neurological deficits in all cases. CONCLUSION: Microsurgical techniques based on anatomic and functional information allow surgeons to reach the lesions deep in the paracentral area safely.

Validation of a method for localised microinjection of drugs into thalamic subregions in rats for epilepsy pharmacological studies.

OBJECTIVES: To validate a method for the chronic implantation of micro-cannulae to examine the effect of drug administration to two small brain regions critical to the control of generalised seizures, the reticular nucleus of the thalamus (Rt) and the ventrobasal thalamus (VB), in a genetically epileptic rat model. METHOD: Micro-cannulae guides (length 9 mm, 26G, i.d. 0.24 mm, o.d. 0.46 mm) were implanted bilaterally into either the Rt or the VB of 11- to 13-week-old Genetic Absence Epilepsy Rats from Strasbourg (GAERS) using a stereotaxic head frame. After a seven-day recovery period the animals were injected with 0.2 microl of methylene blue. The animals were allowed to move freely in their cages for a further 90 min while a post-drug EEG recording was acquired and then brains were perfused with 4% paraformaldehyde and extracted. Twenty-micrometer slices were cut on a cryostat and the site and extent of the methylene blue staining in the brain determined. The implantation co-ordinates were adjusted accordingly, and then a validation study was performed on a further cohort of rats (n=8 Rt, n=7 VB). RESULTS: The co-ordinates that were found to most accurately localise the Rt were: AP -3mm, ML 3.6mm, DV -5.8mm (relative to Bregma). Those that accurately localised the VB were: AP -3mm, ML 2.6mm, DV -5.5mm. In the validation study, the dye staining was measured to diffuse an average radius of 520+/-120 microm from the centre of the injection site for the 0.2 microl injection in both brain hemispheres. For the VB injections the dye remained confined within the structure, however, for the smaller Rt there was spread to surrounding structures in the axial plane. The radial diffusion for the 0.5 microl injection was similar, but more of the dye was found to spread back up the cannula tract away from the target zone. CONCLUSION: These studies have validated a method for accurate and localised injection of drugs into the VB and Rt for neuropharmacological studies in a rat model of generalised epilepsy. This method allows the measurement of localised drug effects on EEG and generalised seizure activity at these sites.

Center median-parafascicular complex and pain control. Review from a neurosurgical perspective.

The center median-parafascicular (CM-Pf) complex, which constitutes the major portion of the intralaminar thalamus in man, has long been known to be involved in the processing of pain under normal and pathological conditions. Yet, these 'forgotten' nuclei with their rich connectivity to other thalamic nuclei, the basal ganglia and cortical areas have received only relatively little attention over the past two decades. With regard to the recent reinterest in functional stereotactic neurosurgery as a treatment option for chronic refractory pain, the CM-Pf complex has been reconsidered as a target. This review provides a systematic overview on the current knowledge about the anatomy and connectivity of the CM-Pf complex, neurophysiological studies, and on concepts of its role in pain processing under various conditions. We also review the previous experience with ablative surgery and deep brain stimulation of the CM-Pf complex. Studies in men and experimental animals indicate that the CM-Pf complex is part of a medial pain system, which appears to be involved primarily in affective and motivational dimensions of pain. Single-unit recordings from the CM-Pf complex have shown that the activity of CM-Pf cells is modified by painful stimuli. Under pathological conditions, bursting firing patterns and altered discharge rates were found. Thalamotomies targeting at the CM-Pf complex yielded beneficial results for chronic pain, but interpretation of the results is limited. With bifocal deep brain stimulation, short-term effects of CM-Pf stimulation were superior to those of somatosensory thalamic stimulation in neuropathic pain. There is evidence, that the CM-Pf complex might also be involved in the mediation of the beneficial effects of somatosensory thalamic stimulation and periventricular grey stimulation.