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OBJECTIVESince the first clinical application of the incisionless magnetic resonance–guided focused ultrasound (MRgFUS) technology only small series of patients have been reported, and thus only extrapolations of the procedure-related risks could be offered. In this study, the authors analyze side-effects and targeting accuracy in 180 consecutive treatments with MRgFUS for chronic therapy-resistant idiopathic Parkinson’s disease (PD), essential tremor (ET), cerebellar tremor (CT), and neuropathic pain (NP), all performed in their dedicated center.METHODSA total of 180 treatments with MRgFUS for chronic therapy-resistant idiopathic PD, ET, CT, and NP were prospectively assessed for side-effects and targeting accuracy. Monitoring for later side-effects was continued for at least 3 months after the procedure in all but 1 case (0.6%); in that single case, the patient was lost to follow-up after an uneventful early postoperative course. The surgical targets were the pallidothalamic tract (pallidothalamic tractotomy, n = 105), the cerebellothalamic tract (cerebellothalamic tractotomy, n = 50), the central lateral nucleus (central lateral thalamotomy, n = 84), the centrum medianum (centrum medianum thalamotomy, n = 12), and the globus pallidus (pallidotomy, n = 2). Cognitive testing was performed before, 1–2 days after, and 1 year after the procedure. The Mini–Mental State Examination (MMSE) was used for the first 29 cases and was then replaced by the Montreal Cognitive Assessment (MoCA). Lesion reconstruction and measurement of targeting accuracy were done on 2-day posttreatment MR images for each performed target. To determine targeting accuracy measurement, 234 out of the 253 lesions depicted in the 2-day postoperative MR examination could be 3D-reconstructed.RESULTSThe mean MoCA score was slightly improved 2 days postoperatively (p = 0.002) and remained stable at 1-year follow-up (p = 0.03). The mean MMSE score was also slightly improved 2 days postoperatively and at 1-year follow-up, but the improvement was not statistically significant (p = 0.06 and p = 0.2, respectively). The mean (± SD) accuracy was 0.32 ± 0.29 mm, 0.29 ± 0.28 mm, and 0.44 ± 0.39 mm for the mediolateral, anteroposterior, and dorsoventral dimensions, respectively. The mean 3D accuracy was 0.73 ± 0.39 mm. As to side-effects, 14 events over 180 treatments were documented. They were classified into procedure-related (n = 4, 2.2%), effect on neighboring structures (n = 3, 1.7%), and disease-related (n = 7, 3.9%). There was no bleeding.CONCLUSIONSThe incisionless transcranial MRgFUS technology demonstrates a higher targeting accuracy and a lower side-effect profile than techniques requiring cerebral penetration. In the absence of penetration brain shift, this technique avoids the placement of a thermolesion away from the chosen target, thus suppressing the need for reversible therapeutic energy application. With the use of proper physiopathology-based targets, definitive therapeutic effects can be coupled with sparing of sensory, motor, and paralimbic/multimodal thalamocortical functions. Clinical efficacy, not analyzed in this investigation, will ultimately rest in proper target selection and optimized thermolesional coverage of the target.

Objective: Bilateral stereotactic neurosurgery for advanced Parkinson's disease (PD) has a long history beginning in the late 1940s. In view of improved lesioning accuracy and reduced bleeding risk and in spite of long-standing caveats about bilateral approaches, there is a need to investigate bilateral MR-guided focused ultrasound (MRgFUS) interventions. We hereby present the clinical results of bilateral pallidothalamic tractotomy (PTT), i.e., targeting of pallidal efferent fibers below the thalamus at the level of Forel's field H1, followed for 1 year after operation of the second side. Methods: Ten patients suffering from chronic and therapy-resistant PD having received bilateral PTT were followed for 1 year after operation of the second side. The primary endpoints included the Unified Parkinson's Disease Rating Scale (UPDRS) scores in on- and off-medication states, dyskinesias, dystonia, sleep disturbances, pain, reduction in drug intake, and assessment by the patient of her/his global symptom relief as well as tremor control. Results: The time frame between baseline UPDRS score and 1 year after the second side was 36 ± 15 months. The total UPDRS score off-medication at 1 year after the second PTT was reduced by 52% compared to that at baseline on-medication (p < 0.007). Percentage reductions of the mean scores comparing 1 year off- with baseline on-medication examinations were 91% for tremor (p = 0.006), 67% for distal rigidity (p = 0.006), and 54% for distal hypobradykinesia (p = 0.01). Gait and postural instability were globally unchanged to baseline (13% improvement of the mean, p = 0.67, and 5.3% mean reduction, p = 0.83). Speech difficulties, namely, hypophonia, tachyphemia, and initiation of speech, were increased by 58% (p = 0.06). Dyskinesias were suppressed in four over four, dystonia in four over five, and sleep disorders in three over four patients. There was 89% pain reduction. Mean L-Dopa intake was reduced from 690 ± 250 to 110 ± 190. Conclusions: Our results suggest an efficiency of bilateral PTT in controlling tremor, distal rigidity, distal hypobradykinesia, dyskinesias, dystonia, and pain when compared to best medical treatment at baseline. Larger series are of course needed., Frontiers in Neurology, 12, ISSN:1664-2295

Background: There is a long history, beginning in the 1940s, of ablative neurosurgery on the pallidal efferent fibers to treat patients suffering from Parkinson's disease (PD). Since the early 1990s, we undertook a re-actualization of the approach to the subthalamic region, and proposed, on a histological basis, to target specifically the pallidothalamic tract at the level of Forel's field H1. This intervention, the pallidothalamic tractotomy (PTT), has been performed since 2011 using the MR-guided focused ultrasound (MRgFUS) technique. A reappraisal of the histology of the pallidothalamic tract was combined recently with an optimization of our lesioning strategy using thermal dose control. Objective: This study was aimed at demonstrating the efficacy and risk profile of MRgFUS PTT against chronic therapy-resistant PD. Methods: This consecutive case series reflects our current treatment routine and was collected between 2017 and 2018. Fifty-two interventions in 47 patients were included. Fifteen patients received bilateral PTT. The median follow-up was 12 months. Results: The Unified Parkinson's Disease Rating Scale (UPDRS) off-medication postoperative score was compared to the baseline on-medication score and revealed percentage reductions of the mean of 84% for tremor, 70% for rigidity, and 73% for distal hypobradykinesia, all values given for the treated side. Axial items (for voice, trunk and gait) were not significantly improved. PTT achieved 100% suppression of on-medication dyskinesias as well as reduction in pain (p < 0.001), dystonia (p < 0.001) and REM sleep disorders (p < 0.01). Reduction of the mean L-Dopa intake was 55%. Patients reported an 88% mean tremor relief and 82% mean global symptom relief on the operated side and 69% mean global symptom improvement for the whole body. There was no significant change of cognitive functions. The small group of bilateral PTTs at 1 year follow-up shows similar results as compared to unilateral PTTs but does not allow to draw firm conclusions at this point. Conclusion: MRgFUS PTT was shown to be a safe and effective intervention for PD patients, addressing all symptoms, with varying effectiveness. We discuss the need to integrate the preoperative state of the thalamocortical network as well as the psycho-emotional dimension., Frontiers in Surgery, 6, ISSN:2296-875X

Background: Trigeminal neuralgia (TN) is a recognized pain condition the treatment of which can be very challenging. Various surgical interventions can be applied in cases of therapy-resistance to drug treatments. The central lateral thalamotomy (CLT) against neurogenic (or neuropathic) pain is based on multiarchitectonic histological as well as physiopathological studies, and integrates the nucleus in a large thalamocortical (TC) and corticocortical network responsible for the sensory, cognitive and affective/emotional components of pain. The advent of the magnetic resonance imaging guided high intensity focused ultrasound (MRgFUS) brought a strong reduction in morbidity and increase in accuracy compared to penetration techniques. Objective: This study was aimed at analyzing the outcome of bilateral MRgFUS CLT for chronic therapy-resistant trigeminal pain, all performed in one single center. Methods: Patients were categorized in Classical, Idiopathic and Secondary TN. By definition, paroxysms lasted for seconds up to 2 min. All patients were screened for trigeminal neurovascular conflict. In case of classical TN, microvascular decompression was proposed. Therapy-resistance and thus indication for MRgFUS CLT was based on the lack of efficacy and/or side effects of antiepileptic and antidepressant drugs. Good outcome was defined by a pain relief ≥50%. Results: Eight patients suffering from chronic therapy-resistant trigeminal neuralgia were treated. All suffered from pain with paroxysmal character. Six patients reported additionally continuous pain. Mean follow-up was 53 months (range: 12-92, median: 60 months). The mean pain relief assessed by patients was 51% (median: 58%, range: 0-90%) at 3 months, 71% (median: 65%, range: 40-100%) at 1 year and 78% (median: 75%, range: 50-100%) at their longest follow-up. This represents 63% good outcomes at 3 months, 88% at 1 year and 100% at last follow-up. Frequency of the mean pain paroxysms decreased from 84 per day preoperative to 3.9 at 1 year postoperatively. There were no serious adverse events in this series. Conclusion: Our study provides preliminary support for the safety and efficacy of MRgFUS CLT, a histologically and pathophysiologically based medial thalamotomy against chronic therapy-resistant trigeminal neuralgia.

OBJECTIVEIn addition to the well-recognized ventral intermediate nucleus (Vim) thalamotomy for the treatment of chronic therapy-resistant essential tremor (ET), an alternative approach targeting the posterior part of the subthalamus was proposed in the 1960s and early 1970s and then was reactualized as cerebellothalamic tractotomy (CTT) with the advent of MR-guided focused ultrasound (MRgFUS) surgery. The goal of this study was to improve target coverage and thus efficacy (i.e., tremor control and its consistency). The authors undertook a histological reappraisal of the CTT target and proposed a targeting strategy of the MRgFUS CTT based on 1) the MR visualization of the center of the red nucleus and 2) the application of preplanned target subunits realized with short sonications under thermal dose control. This study was aimed at demonstrating the efficacy and risk profile of this approach against chronic therapy-resistant ET.METHODSTen consecutive patients suffering from chronic therapy-resistant ET benefited from a unilateral MRgFUS CTT and were followed over the course of 1 year. Primary endpoints were subjective tremor relief, Clinical Rating Scale for Tremor (CRST) score, activities of daily living (ADL) score, and the hand function (HF) scores HF16 and HF32. Histological reappraisal of the target led the authors to propose a standardized targeting protocol for MRgFUS CTT. Thermal doses for 18 and 240 cumulative equivalent minutes at 43°C were calculated and correlated with intraoperative and 2 days postoperative T2-weighted MR images.RESULTSThe mean ± SD for the baseline CRST score was 48 ± 12; the score was 16 ± 7 at 3 months, and 17 ± 8 at 1 year. The mean tremor relief rated by the patients for the operated side was 95% after 2 days, 96% at 3 months, and 93% at 1 year. The mean HF16 was 11.0 ± 2.1 at baseline, 0.7 ± 0.7 at 3 months, and 0.8 ± 0.9 at 1 year (93% mean reduction). The minimum reduction for the HF16 at 1 year was 78%. There was a 51% reduction of the mean ADL score at 1 year. There was no bleeding or infection. Gait difficulties, only detectable on tandem gait, were increased in 3 patients and reduced in 2 patients at 1 year. There was no dysarthria.CONCLUSIONSThe authors’ results suggest that MRgFUS CTT is a very effective treatment option for therapy-resistant ET.

Background: MR-guided focused ultrasound (MRgFUS) offers new perspectives for safe and efficient lesioning inside the brain. The issue of target coverage remains primordial and sub-optimally addressed or solved in the field of functional neurosurgery. Objective: To provide an optimized planning and operative strategy to perform a pallidothalamic tractotomy (PTT) in chronic therapy-resistant Parkinson's disease (PD) with the technology of MRgFUS. Methods and results: Histological sections and maps from 6 human brain hemispheres were analyzed and outlines of the pallidothalamic tract on Myelin-stained sections were drawn and superimposed. We determined a standardized PTT target coverage characterized by 5 to 7 preplanned target lesion sub-units of 1.5 × 1.5 × 3.0 mm, which were placed using focal point displacements and shortest possible times, under thermal dose control. Conclusion: We hereby present our current approach to the MRgFUS PTT on the basis of a histological reappraisal and optimized heat application to the pallidothalamic tract in the H1 field of Forel., Frontiers in Surgery, 6, ISSN:2296-875X

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. © 2011 Springer Science+Business Media LLC.

Background: Subthalamic stereotactic interventions have recently caught renewed interest as a treatment for essential tremor (ET). However, it is not clear whether these interventions are associated with neurocognitive, mood or personality changes. Objective: To investigate neurocognition, neuropsychiatric functions and personality variables in patients with ET and to explore the neurocognitive and neuropsychiatric effects of cerebellothalamic tractotomy (CTT), a form of subthalamotomy. Methods: In our study, we investigated cognitive functions, frontal functions, mood and personality variables in 5 patients with intractable ET. Patients were tested before and 3 months after surgery using neuropsychological tests, clinical scales for depression, anxiety, anger regulation and a personality test. Results: Before surgery, ET patients showed normal neurocognitive function, a slightly elevated frontal lobe score in the dimensions mental control and memory, without being indicative of a frontal lesion, and no elevated depression or anxiety scores compared to norm values. After surgery, there was no change in neurocognitive function and no increase in depression or anxiety scores. Conclusion: In this exploratory study on 5 ET patients, CTT was not associated with alterations of mood or neurocognitive functions.

To study the mechanisms of chronic neurogenic pain, we compared the power spectra of the resting EEG of patients (n = 15, 38-75 years, median 64 years, 6 women) and healthy controls (n = 15, 41-71 years, median 60 years, 8 women). On an average, the patient group exhibited higher spectral power over the frequency range of 2-25 Hz, and the dominant peak was shifted towards lower frequencies. Maximal differences appeared in the 7-9 Hz band in all electrodes. Frontal electrodes contributed most to this difference in the 13-15 Hz band. Bicoherence analysis suggests an enhanced coupling between theta (4-9 Hz) and beta (12-25 Hz) frequencies in patients. The subgroup of six patients free from centrally acting medication showed higher spectral power in the 2-18 Hz frequency range. On an individual basis, the combination of peak height and peak frequency discriminated between patient and control groups: discriminant analysis classified 87% of all subjects correctly. After a therapeutic lesion in the thalamus (central lateral thalamotomy, CLT) we carried out follow-up for a subgroup of seven patients. Median pain relief was 70 and 95% after 3 and 12 months, respectively. The average EEG power of all seven patients gradually decreased in the theta band and approached normal values only after 12 months. The excess theta EEG power in patients and its decrease after thalamic surgery suggests that both EEG and neurogenic pain are determined by tightly coupled thalamocortical loops. The small therapeutic CLT lesion is thought to initiate a progressive normalization in the affected thalamocortical system, which is reflected in both decrease of EEG power and pain relief.

Bungener, P. & D. Jeanmonod (2019). The Brothers Soleirol, a centuries-long history of a confusion on a collector in Corsica. Candollea 74: 209–216. In French, English & French abstracts.Soleirol is a famous botanical collector well known for his plant collections in Corsica in the 1820's. Many scientific names of taxa have been dedicated to him. Although his herbarium specimens and letters have been signed by his surname alone and without his first name, the botanical tradition has given him the surname of Joseph-Francois (1781–1863). Our investigation shows that this botanist is in fact Henri-Augustin (1792–1860), the younger brother of Joseph-Francois. That conclusion is drawn on the analysis of his herbarium specimens, botanical literature, correspondence and biographical accounts. The Brothers Soleirol have followed a similar career in the French Army and had the same interests for art and botany. These similar ways of life have subsequently caused the confusion of their surnames. Our research shows that Henry-Augustin was the only one who collected plants in Corsica between 1820 and 1823 and visited about sixty localities from Cap Corse to Bonifacio through the large mountain ranges. As an important plant collector for Corsica, Soleirol has collected more than 5000 specimens that he has distributed or exchanged with other botanists. This paper highlights the activity of an amateur botanist at the beginning of the XIXth century. It honors Henry Augustin for his work after more than one century of confusion with his brother.

Background Already in the late 1960s and early 1970s, targeting of the “posterior subthalamic area (PSA)” was explored by different functional neurosurgical groups applying the radiofrequency (RF) technique to treat patients suffering from essential tremor (ET). Recent advances in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) technology offer the possibility to perform thermocoagulation of the cerebellothalamic fiber tract in the PSA without brain penetration, allowing a strong reduction of the procedure-related risks and increased accuracy. We describe here the first results of the MRgFUS cerebellothalamic tractotomy (CTT). Methods Twenty-one consecutive patients suffering from chronic (mean disease duration 29.9 years), therapy-resistant ET were treated with MRgFUS CTT. Three patients received bilateral treatment with a 1-year interval. Primary relief assessment indicators were the Essential Tremor Rating Scale (Fahn, Tolosa, and Marin) (ETRS) taken at follow-up (3 months to 2 years) with accent on the hand function subscores (HF16 for treated hand and HF32 for both hands) and handwriting. The evolution of seven patients with HF32 above 28 points over 32 (group 1) differentiated itself from the others’ (group 2) and was analyzed separately. Global tremor relief estimations were provided by the patients. Lesion reconstruction and measurement of targeting accuracy were done on 2-day post-treatment MR pictures for each CTT lesion. Results The mean ETRS score for all patients was 57.6 ± 13.2 at baseline and 25.8 ± 17.6 at 1 year (n = 10). The HF16 score reduction was 92 % in group 2 at 3 months and stayed stable at 1 year (90 %). Group 1 showed only an improvement of 41 % at 3 months and 40 % at 1 year. Nevertheless, two patients of group 1 treated bilaterally had an HF16 score reduction of 75 and 88 % for the dominant hand at 1 year after the second side. The mean patient estimation of global tremor relief after CTT was 92 % at 2 days and 77 % at 1-year follow-up. Conclusions CTT with MRgFUS was shown to be an effective and safe approach for patients with therapy-refractory essential tremor, combining neurological function sparing with precise targeting and the possibility to treat patients bilaterally.

Object Recent technological developments open the field of therapeutic application of focused ultrasound to the brain through the intact cranium. The goal of this study was to apply the new transcranial magnetic resonance imaging–guided focused ultrasound (tcMRgFUS) technology to perform noninvasive central lateral thalamotomies (CLTs) as a treatment for chronic neuropathic pain. Methods In 12 patients suffering from chronic therapy-resistant neuropathic pain, tcMRgFUS CLT was proposed. In 11 patients, precisely localized thermal ablations of 3–4 mm in diameter were produced in the posterior part of the central lateral thalamic nucleus at peak temperatures between 51°C and 64°C with the aid of real-time patient monitoring and MR imaging and MR thermometry guidance. The treated neuropathic pain syndromes had peripheral (5 patients) or central (6 patients) origins and covered all body parts (face, arm, leg, trunk, and hemibody). Results Patients experienced mean pain relief of 49% at the 3-month follow-up (9 patients) and 57% at the 1-year follow-up (8 patients). Mean improvement according to the visual analog scale amounted to 42% at 3 months and 41% at 1 year. Six patients experienced immediate and persisting somatosensory improvements. Somatosensory and vestibular clinical manifestations were always observed during sonication time because of ultrasound-based neuronal activation and/or initial therapeutic effects. Quantitative electroencephalography (EEG) showed a significant reduction in EEG spectral overactivities. Thermal ablation sites showed sharply delineated ellipsoidal thermolesions surrounded by short-lived vasogenic edema. Lesion reconstructions (18 lesions in 9 patients) demonstrated targeting precision within a millimeter for all 3 coordinates. There was 1 complication, a bleed in the target with ischemia in the motor thalamus, which led to the introduction of 2 safety measures, that is, the detection of a potential cavitation by a cavitation detector and the maintenance of sonication temperatures below 60°C. Conclusions The authors assert that tcMRgFUS represents a noninvasive, precise, and radiation-free neurosurgical technique for the treatment of neuropathic pain. The procedure avoids mechanical brain tissue shift and eliminates the risk of infection. The possibility of applying sonication thermal spots free from trajectory restrictions should allow one to optimize target coverage. The real-time continuous MR imaging and MR thermometry monitoring of targeting accuracy and thermal effects are major factors in optimizing precision, safety, and efficacy in an outpatient context.

During stereotactic functional neurosurgery, stimulation procedure to control for proper target localization provides a unique opportunity to investigate pathophysiological phenomena that cannot be addressed in experimental setups. Here we report on the distribution of response modalities to 487 intraoperative thalamic stimulations performed in 24 neurogenic pain (NP), 17 parkinsonian (PD) and 10 neuropsychiatric (Npsy) patients. Threshold responses were subdivided into somatosensory, motor and affective, and compared between medial (central lateral nucleus) and lateral (ventral anterior, ventral lateral and ventral medial) thalamic nuclei and between patients groups. Major findings were as follows: in the medial thalamus, evoked responses were for a large majority (95%) somatosensory in NP patients, 47% were motor in PD patients, and 54% affective in Npsy patients. In the lateral thalamus, a much higher proportion of somatosensory (83%) than motor responses (5%) was evoked in NP patients, while the proportion was reversed in PD patients (69% motor vs. 21% somatosensory). These results provide the first evidence for functional cross-modal changes in lateral and medial thalamic nuclei in response to intraoperative stimulations in different functional disorders. This extensive functional reorganization sheds new light on wide-range plasticity in the adult human thalamocortical system.

Accurate knowledge of the morphology of the human brain is required for minimally or non-invasive surgical interventions. On the (sub-)cellular level, brain tissue is generally characterized using optical microscopy, which allows extracting morphological features with a wide spectrum of staining procedures. The preparation of the histological slices, however, often leads to artifacts resulting in imperfect morphological data. In addition, the generation of 3D data is time-consuming. Therefore, we propose synchrotron radiation-based micro computed tomography (SRmicroCT) avoiding preparation artifacts and giving rise to the 3D morphology of features such as gray and white matter on the micrometer level. One can differentiate between white and gray matter without any staining procedure because of different X-ray absorption values. At the photon energy of 10keV, the white matter exhibits the absorption of 5.08 cm(-1), whereby the value for the gray matter corresponds to 5.25 cm(-1). The tomography data allow quantifying the local strains in the histological images using registration algorithms. The deformation of histological slices compared to the SRmicroCT in a 2D-2D registration leads to values of up to 6.3%. Mean deformation values for the Nissl-stained slices are determined to about 1%, whereas the myelin-stained slices yield slightly higher values than 2%.

Patients with severe and chronic neurogenic pain are known to exhibit excess EEG oscillations in the 4- to 9-Hz theta frequency band in comparison with healthy controls. The generators of these excess EEG oscillations are localized in the cortical pain matrix. Since cortex and thalamus are tightly interconnected anatomically, we asked how thalamic activity and EEG are functionally related in these patients. During the surgical intervention in ten patients with neurogenic pain, local field potentials were recorded from the posterior part of the central lateral nucleus (CL). The highest thalamocortical coherence was found in the 4- to 9-Hz theta frequency band (median 7.7 Hz). The magnitude of thalamocortical theta coherence was comparable to the magnitude of EEG coherence between scalp electrode pairs. Median thalamocortical theta coherence was 27%, reached up to 68% and was maximal with frontal midline scalp sites. The observed high thalamocortical coherence underlines the importance of the thalamus for the synchronization of scalp EEG. We discuss the pathophysiology within the framework of a dysrhythmic thalamocortical interplay, which has important consequences for the choice of therapeutic strategy in patients with chronic and severe forms of neurogenic pain.

Oscillatory and coherent EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions. We aimed to study deviations from the norm of different resting EEG parameters in Parkinson's disease (PD) patients. We compared spectral parameters of the resting EEG of PD patients (n=24, median age 67 years) to those of healthy controls (n=34, median age 62 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz, and the dominant peak was shifted towards lower frequencies. Maximal differences appeared in the 6-9 Hz theta band in all electrodes. Frontal electrodes contributed most to this difference in the 4-6 Hz theta, 12-18 Hz beta and 30-45 Hz gamma bands. On an individual basis, the combination of six spectral power band parameters discriminated between patient and control groups and 72% of all subjects were classified correctly. Using LORETA source analysis, the generators of this power difference were localized to fronto-insulo-temporal cortical areas in the theta and beta bands, and to interhemispheric frontal (supplementary motor area, SMA) and cingulate areas in the 30-45 Hz gamma band. We calculated spectral coherence between electrode pairs in a frontal, central and parietal region of interest (ROI). In the frontal ROI, coherence was enhanced significantly in the patient group in the theta, high beta and gamma bands. In the parietal ROI, patients showed lower coherence around 10 Hz. We demonstrate a deviation from the norm of different resting EEG parameters in PD patients. This evidence can be integrated in the context of a pathophysiological chain reaction initiated in the substantia nigra and resulting in a cortical aberrant dynamics rooted in enhanced dysrhythmic thalamocortical interactions.

Functional brain imaging of pain over the last years has provided insight into a distributed anatomical matrix involved in pain processing which includes multiple cortical areas. EEG/MEG-based imaging studies have mostly relied on settings of evoked nociception. We report here the spontaneous presence of enhanced activations in the pain matrix of the patient group on the basis of continuous EEG and functional Low Resolution Electromagnetic Tomography (LORETA) from 16 chronic neurogenic pain patients and 16 healthy controls. These overactivations occurred predominantly within the high theta (6-9 Hz) and low beta frequency ranges (12-16 Hz). Theta and beta overactivations were localized to multiple pain-associated areas, primarily to insular (IC), anterior cingulate (ACC), prefrontal, and inferior posterior parietal cortices, as well as to primary (S1), secondary (S2), and supplementary somatosensory (SSA) cortices. After a therapeutic lesion in the thalamus (central lateral thalamotomy, CLT), we followed a subgroup of 6 patients. Twelve months after surgery, activation in cingulate and insular cortices was significantly reduced. The presence of rhythmic processes in multiple, partially overlapping areas of the cortical pain matrix concur with the concept of thalamocortical dysrhythmia (TCD) that predicts increased thalamocortical low and high frequency oscillations ensuing from thalamic desactivation. These spontaneous, ongoing, frequency-specific overactivations may therefore serve as an anatomo-physiological hallmark of the processes underlying chronic neurogenic pain.

The premotor cortex of macaque monkeys is currently subdivided into at least six different subareas on the basis of structural, hodological and physiological criteria. To determine the degree of divergence/convergence of thalamocortical projections to mesial [supplementary motor area (SMA)-proper and pre-SMA] and lateral (PMd-c, PMd-r, PMv-c and PMv-r) premotor (PM) subareas, quantitative analyses were performed on the distribution of retrograde labelling after multiple tracer injections in the same animal. The results demonstrate that all PM and SMA subareas receive common inputs from several thalamic nuclei, but the relative contribution of these nuclei to thalamocortical projections differs. The largest difference occurs between subareas of SMA, with much greater contribution from the mediodorsal (MD) and area X, and a smaller contribution from the ventral lateral anterior (VLa) and ventral part of the ventral lateral posterior (VLpv) to pre-SMA than to SMA-proper. In PM, differences between subareas are less pronounced; in particular, all receive a significant contribution from MD, the ventral anterior (VApc) and area X. However, there are clear gradients, such as increasing projections from MD to rostral, from VLa and VLpv to caudal, and from dorsal VLp (VLpd) to dorsal premotor subareas. Intralaminar nuclei provide widespread projections to all premotor subareas. The degree of overlap between thalamocortical projections varies among different PM and SMA subareas and different sectors of the thalamus. These variations, which correspond to different origin and topography of thalamocortical projections, are discussed in relation to functional organizations at thalamic and cortical levels.

Background Radiofrequency (RF) subthalamotomies have been proposed since the 1960s to treat patients suffering from Parkinson's disease (PD). Recently, the magnetic resonance (MR)-guided focused ultrasound technology (MRgFUS) offers the possibility to perform subthalamic thermocoagulations with reduced risks and optimized accuracy. We describe here the initial results of the MRgFUS pallidothalamic tractotomy (PTT), an anatomical and physiological update of the earlier subthalamotomies. Methods Thirteen consecutive patients suffering from chronic (mean disease duration 9.7 years) and therapy-resistant PD were treated unilaterally with an MRgFUS PTT. Primary relief assessment indicators were the score reduction of the Unified Parkinson Disease Rating Scale (UPDRS) and the patient estimation of global symptom relief (GSR) taken at 3 months follow-up. Final temperatures at target were between 52°C and 59°C. The MR examinations were performed before the treatment, 2 days and 3 months after it. The accuracy of the targeting was calculated on 2 days post-treatment MR pictures for each PTT lesion. Results The first four patients received a PTT using the lesional parameters applied for thalamotomies. They experienced clear-cut recurrences at 3 months (mean UPDRS relief 7.6%, mean GSR 22.5%), and their MR showed no sign of thermal lesion in T2-weighted (T2w) images. As a consequence, the treatment protocol was adapted for the following nine patients by applying repetition of the final temperatures 4 to 5 times. That produced thermocoagulations of larger volumes (172 mm3 against 83 mm3 for the first four patients), which remained visible at 3 months on T2w images. These nine patients enjoyed a mean UPDRS reduction of 60.9% and a GSR of 56.7%, very close to the results obtained with radiofrequency lesioning. The targeting accuracy for the whole patient group was 0.5, 0.5, and 0.6 mm for the anteroposterior (AP), mediolateral (ML), and dorsoventral (DV) dimensions, respectively. Conclusions This study demonstrated the feasibility, safety, and accuracy of the MRgFUS PTT. To obtain similar results as the ones of RF PTT, it was necessary to integrate the fact that white matter, in this case, the pallidothalamic tract, requires repeated thermal exposition to achieve full lesioning and thus full therapeutic effect.

Stereotactic neurosurgery aims at placing therapeutic lesions or chronic stimulating electrodes at very precise locations within the brain. Microelectrode recording and macrostimulation are used in addition to anatomoradiological techniques to optimize targeting. Recently, the usefulness of electrophysiological procedures has been questioned. Based on more than 500 therapeutic stereotactic lesions in the last 10 years at the thalamic and subthalamic levels, we evaluate here retrospectively the utility of the two electrophysiological procedures. In two of the three stereotactic targets considered in this study, intraoperative electrophysiological confirmation is mandatory because of the target size with respect to interindividual anatomical variations and of the more or less close vicinity of eloquent structures.

Following earlier stereotactic experiences, we re-explored the possibilities of a therapeutic lesion of the pallidothalamic tract in the fields H1 and H2 of Forel in patients with parkinsonian signs. The physiopathological rationale of the pallidothalamic tractotomy (PTT) is based on the presence in the parkinsonian brain of a state of thalamic overinhibition due to an increased output of the internal pallidum. This causes the development of a thalamocortical dysrhythmia characterized by increased low frequencies in the relevant thalamic and frontal cortical areas. The fields of Forel are strategically placed to control this thalamic overinhibition, as they give passage to the majority of the pallidothalamic fibres. Magnetic resonance- and microelectrode-guided stereotactic PTT was proposed to 21 parkinsonian patients (mean age: 60 ± 10 years; mean Hoehn and Yahr in on-condition: 3.5 ± 1; mean disease duration: 11 ± 5 years). At a follow-up of 14 ± 6 months and in on-medication condition, a significant (P < 0.001) postoperative improvement of the motor part of the UPDRS (64.6%) and of the activities of daily living (ADL; 75.8%) was observed. Rest tremor, on-chorea and rigidity were reduced by 77.9, 92.2 and 82.3%, respectively. Distal and axial hypobradykinesias showed an improvement of 72.9 and 64%, respectively. Gait and postural stability also improved (57.5 and 66%, respectively) but at a lower level of significance (P < 0.005). Voice was not statistically influenced. L-dopa intake was decreased by 52.2% (P < 0.001) and 33% of the patients could be freed from treatment. In conclusion, PTT is an effective treatment for chronic therapy-resistant Parkinson's disease, improving symptoms in both on- and off-conditions.

Reactualization of the medial thalamotomy, performed since the fifties in cases of neurogenic pain, has been guided by the discovery of low threshold calcium spike bursts at frequencies in the delta–theta range in the posterior part of the central lateral (CL) nucleus. This thalamic rhythmicity is transmitted to the cortex through thalamocortical resonant properties, giving rise to the thalamocortical dysrhythmia, proposed to be the mechanism of neurogenic pain as well as other central nervous system (CNS) dysfunctions. Magnetic resonance- and microelectrode-guided stereotactic CL thalamotomy was implemented in 96 patients suffering from chronic therapy-resistant peripheral or central neurogenic pain (mean age: 56±15 years; pain duration before surgery: 7.5±8 years). At a mean follow-up of 3 years, 9 months±2 years, 9 months, 53% of the patients benefited from a relief superior to 50% (complete relief in 18.7%). Further analysis of the results demonstrated a significant difference between patients suffering from intermittent as compared with continuous pain. Patients with continuous pain showed only a mean relief of 20.4±25.8% in contrast to the 66±39.2% obtained for patients with intermittent (episodic or paroxysmal) pain manifestations. This was confirmed by the pre- and postoperative visual analogue scale scores showing a significant decrease (59.2%) only in the patient group with intermittent pain. Allodynia was suppressed in 57.3% of the patients. Parameters such as the preoperative pain duration or the site of the causal lesion did not affect the surgical outcome. In 28 patients suffering from unilateral continuous pain, the addition of an ipsilateral CL thalamotomy provided a further significant pain relief. A suppression of drug intake was observed in 31.6% of the patients. Complications occurred in 11.5% of the patients and led to a long term significant disability in only one case. In conclusion, CL thalamotomy is a safe neurosurgical option for neurogenic pain, especially for patients suffering from intermittent pain or allodynia. Its limitation in cases of continuous pain indicates the necessity to explore other stereotactic targets outside of the medial thalamus.

In 1997, Morel, Magnin, and Jeanmonod presented a microscopic stereotactic atlas of the human thalamus. Parcellations of thalamic nuclei did not only use cyto- and myeloarchitectonic criteria, but were additionally corroborated by staining for calcium-binding proteins, which bears functional significance. The atlas complies with the Anglosaxon nomenclature elaborated by Jones and the data were sampled in three orthogonal planes in the AC-PC reference space. We report on the generation of three-dimensional digital models of the thalamus based on the three sets of sections (sagittal, horizontal, and frontal). Spatial differences between the three anatomical specimens were evaluated using the centers of gravity of 13 selected nuclei as landmarks. Subsequent linear regression analysis yielded equations, which were used to normalize the frontal and horizontal digital models to the sagittal one. The outcome is an internally consistent Canonical Model of Morel's atlas, which minimizes the linear component of the variability between the three sectioned anatomical specimens. In addition, we demonstrate the feasibility of the atlas-to-MRI registration in conjunction with on-line visualization of the trajectory in the digital models.

Objectives : Investigation of sleep and sleep EEG before and after stereotactic neurosurgery. Methods : All-night polysomnographic recordings were obtained in 3 neurogenic pain patients and 3 parkinsonian patients. One subject of each group was recorded in addition 3 months after surgery. Stereotactic operations were performed in the medial thalamus and on the pallido-thalamic tract to relieve neurogenic pain and parkinsonian symptoms, respectively. Results : Sleep efficiency was little affected by the surgical intervention in neurogenic pain patients and a dramatic reduction in REM sleep occurred, which had recovered in the subject recorded after 3 months. After the surgery parkinsonian patients showed an increase in total sleep time and in sleep efficiency, and a decrease in REM sleep latency. Sleep efficiency remained elevated in the 3 months follow-up. Medial thalamotomy abolished spindle frequency activity (SFA) in the power and coherence spectra in non-REM sleep stage 2 systematically. Pallido-thalamic tractotomy attenuated SFA only to varying degrees. After 3 months SFA had reemerged. The alpha peak of the waking EEG was shifted to lower frequencies after surgery in 5 of 6 patients and had reverted to the original frequency 3 months later. Conclusions : Medial thalamotomy or pallido-thalamic tractotomy had acute and reversible effects on the EEG and long-term deleterious side effects of stereotactic surgery on sleep and sleep EEG are improbable. The results provide further evidence for the involvement of the human thalamus in the generation of sleep spindles.

Spontaneous magnetoencephalographic activity was recorded in awake, healthy human controls and in patients suffering from neurogenic pain, tinnitus, Parkinson's disease, or depression. Compared with controls, patients showed increased low-frequency θ rhythmicity, in conjunction with a widespread and marked increase of coherence among high- and low-frequency oscillations. These data indicate the presence of a thalamocortical dysrhythmia, which we propose is responsible for all the above mentioned conditions. This coherent θ activity, the result of a resonant interaction between thalamus and cortex, is due to the generation of low-threshold calcium spike bursts by thalamic cells. The presence of these bursts is directly related to thalamic cell hyperpolarization, brought about by either excess inhibition or disfacilitation. The emergence of positive clinical symptoms is viewed as resulting from ectopic γ-band activation, which we refer to as the “edge effect.” This effect is observable as increased coherence between low- and high-frequency oscillations, probably resulting from inhibitory asymmetry between high- and low-frequency thalamocortical modules at the cortical level.

Our goal was to evaluate the accuracy of stereotactic technique using MRI in thalamic functional neurosurgery. A phantom study was designed to estimate errors due to MRI distortion. Stereotactic mechanical accuracy was assessed with the Suetens-Gybels-Vandermeulen (SGV) angiographic localiser. Three-dimensional MRI reconstructions of 86 therapeutic lesions were performed. Their co-ordinates were corrected from adjustments based on peroperative electrophysiological data and compared to those planned. MR image distortion (maximum: 1 mm) and chemical shift of petroleum oil-filled localiser rods (2.2 mm) induced an anterior target displacement of 2.6 mm (at a field strength of 1.5 T, frequency encoding bandwidth of 187.7 kHz, on T1-weighted images). The average absolute error of the stereotactic material was 0.7 mm for anteroposterior (AP), 0.5 mm for mediolateral (ML) and 0.8 mm for dorsoventral (DV) co-ordinates (maximal absolute errors: 1.6 mm, 2.2 mm and 1.7 mm, respectively; mean euclidean error: 1 mm). Three-dimensional MRI reconstructions showed an average absolute error of 0.8 mm, 0.9 mm and 1.9 mm in AP, ML and DV co-ordinates, respectively (maximal absolute errors: 2.4 mm, 2.7 mm and 5.7 mm, respectively; mean euclidean error: 2.3 mm). MRI distortion and chemical-shift errors must be determined by a phantom study and then compensated for. The most likely explanation for an average absolute error of 1.9 mm in the DV plane is displacement of the brain under the pressure of the penetrating electrode. When this displacement is corrected for by microelectrode recordings and stimulation data, MRI offers a high degree of accuracy and reliability for thalamic stereotaxy.

BACKGROUND: Stereotactic central lateral thalamotomy (CLT) has been applied as a treatment for chronic intractable neuropathic pain. However, it is not clear whether this intervention influences the emotional and cognitive impairments observed in patients who have chronic neuropathic pain. OBJECTIVE: To investigate neuropsychological functions and emotional processing in patients with chronic neuropathic pain compared with healthy volunteers and to explore the neuropsychiatric effect of the CLT. METHODS: We investigated pain ratings, cognitive functions, emotional processes, and personality variables before and after surgery in 8 patients with intractable neuropathic pain. Patients were tested before and 3 months after CLT by the use of neuropsychological tests; clinical scales for depression, anxiety, anhedonia, and anger regulation; a personality test; and 2 experimental tasks testing the theory of mind as well as the ability to recognize facial emotional expressions. Nine age- and sex-matched control subjects were tested once using the same procedure. RESULTS: The comparison of the patient group before surgery with the control group evidenced significant differences on the cognitive assessments, the depression and anxiety scores, as well as on the somatic complaint subscale of the personality test. Three months after CLT, patients experienced a significant improvement in their depression scores. There were no additional postsurgical cognitive impairments. CONCLUSION: For our patients with chronic neuropathic pain, CLT provided pain relief and reduction of their depression scores without causing postsurgical cognitive impairments.

The insula of Reil represents a large cortical territory buried in the depth of the lateral sulcus and subdivided into 3 major cytoarchitectonic domains: agranular, dysgranular, and granular. The present study aimed at reinvestigating the architectonic organization of the monkey's insula using multiple immunohistochemical stainings (parvalbumin, PV; nonphosphorylated neurofilament protein, with SMI-32; acetylcholinesterase, AChE) in addition to Nissl and myelin. According to changes in density and laminar distributions of the neurochemical markers, several zones were defined and related to 8 cytoarchitectonic subdivisions (Ia1–Ia2/Id1–Id3/Ig1–Ig2/G). Comparison of the different patterns of staining on unfolded maps of the insula revealed: 1) parallel ventral to dorsal gradients of increasing myelin, PV- and AChE- containing fibers in middle layers, and of SMI-32 pyramidal neurons in supragranular layers, with merging of dorsal and ventral high-density bands in posterior insula, 2) definition of an insula “proper” restricted to two-thirds of the “morphological” insula (as bounded by the limiting sulcus) and characterized most notably by lower PV, and 3) the insula proper is bordered along its dorsal, posterodorsal, and posteroventral margin by a strip of cortex extending beyond the limits of the morphological insula and continuous architectonically with frontoparietal and temporal opercular areas related to gustatory, somatosensory, and auditory modalities.

Microelectrode recordings in the medial thalamus of 45 neurogenic pain patients undergoing medial thalamotomy revealed that most units (316/318) did not respond to somatosensory stimuli, and that half exhibited low-threshold calcium spike bursts. After medial thalamotomy, 67% of the patients reached a 50 to 100% pain relief, without somatosensory deficits. Colocalization of bursting activities and of the most efficient therapeutic lesions in the central lateral nucleus suggests a key role of this structure in neurogenic pain. We propose that neurogenic pain is due to an imbalance between central lateral and ventroposterior nuclei, resulting in an overinhibition of both by the thalamic reticular nucleus.

Greater low frequency power (

Background The physiopathological mechanism underlying the tinnitus phenomenon is still the subject of an ongoing debate. Since oscillatory EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions, this study investigates deviations from the norm of different resting EEG parameters in patients suffering from chronic tinnitus. Results Spectral parameters of resting EEG of male tinnitus patients (n = 8, mean age 54 years) were compared to those of age-matched healthy males (n = 15, mean age 58.8 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz. Using LORETA source analysis, the generators of delta, theta, alpha and beta power increases were localized dominantly to left auditory (Brodmann Areas (BA) 41,42, 22), temporo-parietal, insular posterior, cingulate anterior and parahippocampal cortical areas. Conclusions Tinnitus patients show a deviation from the norm of different resting EEG parameters, characterized by an overproduction of resting state delta, theta and beta brain activities, providing further support for the microphysiological and magnetoencephalographic evidence pointing to a thalamocortical dysrhythmic process at the source of tinnitus. These results also provide further confirmation that reciprocal involvements of both auditory and associative/paralimbic areas are essential in the generation of tinnitus.

While the development of transcranial MR‐guided High Intensity Focused Ultrasound has been driven mainly by applications for tumor ablation this new intervention method is also very attractive for functional neurosurgery due to its non‐invasiveness, the absence of ionizing radiation and the closed‐loop intervention control by MRI. Here we provide preliminary data to demonstrate the clinical feasibility, safety and precision of non‐invasive functional neurosurgery by transcranial MR‐guided High Intensity Focused Ultrasound.

BACKGROUND: EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown. METHODOLOGY: In 16 healthy adult subjects, we first investigated EEG-BOLD signal correlations for theta (5-7 Hz), alpha1 (8-10), alpha2 (10-12 Hz), beta1 (13-20), beta2 (20-30 Hz), and gamma (30-40 Hz) during the retention period of a WM task with set size 2 and 5. Secondly, we investigated whether load sensitive brain regions are characterised by effects that relate frequency bands to BOLD signals effects. PRINCIPAL FINDINGS: We found negative theta-BOLD signal correlations in the MPFC, PPC, and cingulate cortex (ACC and PCC). For alpha1 positive correlations with the BOLD signal were found in ACC, MPFC, and PCC; negative correlations were observed in DLPFC, PPC, and inferior frontal gyrus (IFG). Negative alpha2-BOLD signal correlations were observed in parieto-occipital regions. Beta1-BOLD signal correlations were positive in ACC and negative in precentral and superior temporal gyrus. Beta2 and gamma showed only positive correlations with BOLD, e.g., in DLPFC, MPFC (gamma) and IFG (beta2/gamma). The load analysis revealed that theta and--with one exception--beta and gamma demonstrated exclusively positive load effects, while alpha1 showed only negative effects. CONCLUSIONS: We conclude that the directions of EEG-BOLD signal correlations vary across brain regions and EEG frequency bands. In addition, some brain regions show both load sensitive BOLD and frequency band effects. Our data indicate that lower as well as higher frequency brain oscillations are linked to neurovascular processes during WM.

Transcranial magnetic resonance (MR)-guided high-intensity focused ultrasound (tcMRgHIFU) implies a novel, noninvasive treatment strategy for various brain diseases. Nine patients with chronic neuropathic pain were treated with selective medial thalamotomies. Precisely located thermal ablations of 4mm in diameter were produced at peak temperatures of 51 degrees C to 60 degrees C under continuous visual MR guidance and MR thermometry. The resulting lesions are clearly visible on follow-up MR imaging. All treatments were well tolerated, without side effects or neurological deficits. This is the first report on successful clinical application of tcMRgHIFU in functional brain disorders, portraying it as safe and reliable for noninvasive neurosurgical interventions.

Functional neurosurgery relies on robust localization of the subcortical target structures, which cannot be visualized directly with current clinically available in-vivo imaging techniques. Therefore, one has still to rely on an indirect approach, by transferring detailed histological maps onto the patient's individual brain images. In contrast to macroscopic MRI atlases, which often represent the average of a population, each stack of sections, which a stereotactic atlas provides, is based on a single specimen. In addition to this bias, the anatomy is displayed with a highly anisotropic resolution, leading to topological ambiguities and limiting the accuracy of geometric reconstruction. In this work we construct an unbiased, high-resolution three-dimensional atlas of the thalamic structures, representing the average of several stereotactically oriented histological maps. We resolve the topological ambiguity by combining the information provided by histological data from different stereotactic directions. Since the stacks differ not only in geometrical detail provided, but also due to inter-individual variability, we adopt an iterative approach for reconstructing the mean model. Starting with a reconstruction from a single stack of sections, we iteratively register the current reference model onto the available data and reconstruct a refined mean three-dimensional model. The results show that integration of multiple stereotactic anatomical data to produce an unbiased, mean model of the thalamic nuclei and their subdivisions is feasible and that the integration reduces problems of atlas reconstruction inherent to histological stacks to a large extent.

Potential applications of Transcranial Magnetic Resonance guided Focused Ultrasound (TcMRgFUS) include treatment of functional brain disorders, such as Parkinson’s disease, dystonia and tremor, neurogenic pain and tinnitus, neuropsychiatric disorders and epilepsy. In this study we demonstrate the feasibility of non‐invasive TcMRgFUS ablation of clinically well established targets in the human thalamus that are currently accessed stereotactically by interventional strategies based on the concept of the thalamocortical dysrhythmia (TCD). Thermal hotspots suitable for clinical intervention were created successfully in anatomical preparations of human ex‐vivo heads under pseudo clinical conditions. The hotspots could be positioned at the target locations as needed and local energy deposition was sufficient to create tissue ablation. Numerical simulations based on these experimental data predict that the acoustic energy needed to create ablative lesions in‐vivo will be within limits that can safely applied.

Anatomical knowledge of the structures to be targeted and of the circuitry involved is crucial in stereotactic functional neurosurgery. The present study was undertaken in the context of surgical treatment of motor disorders such as essential tremor (ET) and Parkinson’s disease (PD) to precisely determine the course and three-dimensional stereotactic localisation of the cerebellothalamic and pallidothalamic tracts in the human brain. The course of the fibre tracts to the thalamus was traced in the subthalamic region using multiple staining procedures and their entrance into the thalamus determined according to our atlas of the human thalamus and basal ganglia [Morel (2007) Stereotactic atlas of the human thalamus and basal ganglia. Informa Healthcare Inc., New York]. Stereotactic three-dimensional coordinates were determined by sectioning thalamic and basal ganglia blocks parallel to stereotactic planes and, in two cases, by correlation with magnetic resonance images (MRI) from the same brains prior to sectioning. The major contributions of this study are to provide: (1) evidence that the bulks of the cerebellothalamic and pallidothalamic tracts are clearly separated up to their thalamic entrance, (2) stereotactic maps of the two tracts in the subthalamic region, (3) the possibility to discriminate between different subthalamic fibre tracts on the basis of immunohistochemical stainings, (4) correlations of histologically identified fibre tracts with high-resolution MRI, and (5) evaluation of the interindividual variability of the fibre systems in the subthalamic region. This study should provide an important basis for accurate stereotactic neurosurgical targeting of the subthalamic region in motor disorders such as PD and ET.

In the literature on EEG during working memory (WM) the role of alpha power (8 13 Hz) during WM retention has remained unclear. We recorded EEG while 18 subjects retained sets of consonants in memory for 3 s; setsize ( ss4 ss6 ss8) determines memory workload. Theta power (4 8 Hz) increased with workload in all subjects in middle frontal electrodes. Using ICA the increase in theta could be attributed to one component whose generators were localized by sLORETA in the medial frontal gyrus. Alpha power in parietal electrode Pz showed a mean increase during retention as compared to prestimulus fixation (event related synchronization ERS). On an individual basis alpha power increased with workload in 9 subjects (WL+ group) and decreased in 9 subjects (WL group). The alpha increased in upper alpha for the WL+ group ( mean: 10.4 Hz) and decreased in lower alpha for the WL group ( mean: 8.9 Hz). Time frequency representations show high alpha power early during retention for the WL+ group and high alpha power late during retention for the WL group. sLORETA revealed maximal contrast for the WL+ group in the cuneus and for the WL group in the precuneus. In subjects with WL+ alpha increase in the cuneus may reflect WM maintenance or active inhibition of task irrelevant areas. In subjects with WL alpha decrease in the precuneus may reflect release of inhibition associated with attentional demands. Thus alpha EEG characterizes two aspects of processing in the same WM task. (c) 2008 Elsevier Inc. All rights reserved.

Research investigating the pathophysiology of Parkinson's disease (PD) mostly focuses on basal ganglia dysfunction. However, the main output from the basal ganglia is via the thalamus, and corticothalamic feedback constitutes the primary source of synapses in the thalamus. We therefore focus on the thalamocortical interplay. During the surgical intervention in six patients, local field potentials (LFPs) were recorded from pallidal-recipient thalamic nuclei VA and VLa. Simultaneously, EEG was recorded from several sites on the scalp. The highest thalamocortical coherence was found in the theta frequency band (4–9 Hz) with a mean peak frequency of 7.5 Hz. The magnitude of thalamocortical theta coherence was comparable to the magnitude of EEG coherence between scalp electrode pairs. Thalamocortical theta coherence reached 70% and was maximal with frontal scalp sites on both hemispheres. In the 13–20 Hz β frequency band, maximal coherence was comparatively low but localized on the scalp ipsilateral to the site of thalamic LFP recording. The high thalamocortical coherence underlines the importance of thalamic function for the genesis of scalp EEG. We discuss the PD pathophysiology within the framework of dysrhythmic thalamocortical interplay, which has important consequences for the choice of therapeutic strategy in patients with severe forms of PD.

The microstructure of brain tissues becomes visible using different types of optical microscopy after the tissue sectioning. This preparation procedure introduces stress and strain in the anisotropic and inhomogeneous soft tissue slices, which are several 10 μm thick. Consequently, the three-dimensional dataset, generated out of the two-dimensional images with lateral submicrometer resolution, needs algorithms to correct the deformations, which can be significant for mellow tissue such as brain segments. The spatial resolution perpendicular to the slices is much worse with respect to the lateral sub-micrometer resolution. Therefore, we propose as complementary method the synchrotron-radiation-based micro computed tomography (SRμCT), which avoids any kind of preparation artifacts due to sectioning and histological processing and yields true micrometer resolution in the three orthogonal directions. The visualization of soft matter by the use of SRμCT, however, is often based on elaborate staining protocols, since the tissue exhibits (almost) the same x-ray absorption as the surrounding medium. Therefore, it is unexpected that human tissue from the pons and the medulla oblongata in phosphate buffer show several features such as the blood vessels and the inferior olivary nucleus without staining. The value of these tomograms lies especially in the precise non-rigid registration of the different sets of histological slices. Applications of this method to larger pieces of brain tissue, such as the human thalamus are planned in the context of stereotactic functional neurosurgery.

We simultaneously recorded the local field potential (LFP) in the thalamus and the electroencephalogram (EEG) on the scalp of 5 patients suffering from neurogenic pain, epilepsy and movement disorders. In an earlier study [], we have investigated the slowing of EEG and the high thalamocortical coherence in the framework of thalamocortical dysrhythmia, the common underlying pathophysiology. The current study focuses on the effects of different cognitive conditions. When patients rested with eyes closed, a theta peak dominated the EEG spectra. The peak height was reduced upon opening the eyes, reminiscent of the classical alpha blocking. This peak reduction also appeared in the thalamic LFP recording. When patients activated their working memory by counting backwards, the theta peak increased in scalp EEG or in the LFP recorded in thalamic nuclei VA/VL. The coherence estimates between EEG and LFP ranged between 21% and 76% for different patients and cognitive conditions (mean: 50%). The involvement of both cortex and thalamus in working memory and the high thalamocortical coherence underline, in addition to cortico-cortical interactions, the importance of thalamocortical modules in the generation of higher cognitive functions.

Neuropsychiatric surgery has had a long and complex history with examples of less than optimal surgical procedures implemented in wrong settings. Such past errors have raised important philosophical and ethical issues that remain with us for good reasons. However, the existence of enormous suffering due to chronic therapy-resistant disabling neuropsychiatric disorders compels a search for alternative surgical approaches based on a sound understanding of the underlying physiopathological mechanisms. We bring evidence, from single cell physiology and magnetoencephalography, for the existence of a set of neuropsychiatric disorders characterized by localized and protracted low frequency spontaneous recurrent activation of the thalamocortical system. This condition, labeled thalamocortical dysrhythmia, underlies certain chronic psychotic, affective, obsessive compulsive, anxiety and impulse control disorders. Considering the central role of recurrent oscillatory thalamocortical properties in the generation of normal hemispheric functions, we propose a surgical approach that provides a reestablishment of normal thalamocortical oscillations without reduction of cortical tissue and its specific thalamic connectivity. It consists of small strategically placed pallidal and medial thalamic lesions that serve to make subcritical the increased low frequency thalamocortical recurrent network activity. This result is attained via reduction of both thalamic overinhibition and low frequency oversynchronization. Thalamic disinhibition is obtained by a lesion in the anterior medial paralimbic pallidum. The medial thalamic lesion is localized in the posterior part of the central lateral nucleus, where a large majority of cells have been shown to be locked in low frequency production and to have lost their normal activation patterns. We present here our experience with 11 patients, including clinical follow ups and pre- and postsurgical magnetoencephalographic studies. The evidence speaks (1) for a benign and efficient surgical approach, and (2) for the relevance of the patient’s presurgical cognitive and social settings, making them more or less prone to postoperative psychoreactive manifestations upon rekindling of personal goals and social reentry.

We simultaneously recorded local field potentials (LFP) in the thalamus and EEG on the scalp of 17 patients suffering from neurogenic pain, epilepsy and movement disorders. The EEG of 11 patients displayed enhanced power in the theta frequency range (4–8 Hz). The thalamic LFP of 14 patients peaked in the theta range. The theta coherence between EEG and LFP was significant for 12 patients and reached strengths up to 70%. These findings suggest that enhanced theta rhythmicity occurs in tight functional thalamocortical loops and is a major element in all three diseases investigated. To investigate second-order phase-coupling between LFP frequency components, we computed the bicoherence and averaged over the group of patients. We found peaks in the theta band and the beta band (14–30 Hz), indicating phase correlations of oscillatory events in these frequency ranges with their first harmonic. A further peak indicates that phase coupling occurred also between theta and beta frequencies. This indicates a strong functional interaction between the generators of these oscillations. We also computed the cross-correlation between LFP spectral power at different frequencies. Although this measure is independent of phase, we found good agreement with the bicoherence patterns, pointing again to strong interaction between theta and beta rhythmicity. The overproduction of theta rhythms, the thalamocortical coherence and the correlation of theta with beta rhythms are key elements for the understanding of thalamocortical dysrhythmia (TCD).

Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions.

Knowledge of the organization and connections of the basal ganglia has greatly advanced in recent years, and, concurrently, understanding and neurosurgical treatment of movement disorders of basal ganglia origin, primarily Parkinson’s disease, have significantly improved. Models of basal ganglia-thalamo-cortical circuitry have been developed to account for both normal function and motor disorders (DeLong, 1990), but these rely primarily on hodological data extrapolated from experimental animals. Direct investigations of basal ganglia output connections in the human brain are rare and often impeded by lesions encroaching upon the capsule, thus rendering interpretations of the origin of degeneration difficult (Martinez, 1961; Beck and Mignami, 1968; Rye et al., 1995). Moreover, these studies were conducted in the brains of parkinsonian patients already presenting pathological features due to the disease. The present study on the distribution of axonal degeneration resulting from lesions confined to the striatum and pallidum provides additional significant information on the pallidofugal pathways in man, especially on those from the external segment, which may have particular relevance in the physiopathology of movement disorders.

Microelectrode-guided stereotactic operations performed in 29 parkinsonian patients allowed the recording of 86 cells located in the globus pallidus and 563 in thalamic nuclei. In the globus pallidus, the average firing rate was significantly higher in the internal (91±52 Hz) than in the external (60±21 Hz) subdivision. This difference was further accentuated when the average firing rate in the external subdivision was compared with that of the internal part of the internal subdivision (114±30 Hz). A rhythmic modulation in globus pallidus activities was observed in 19.7% of the cells, and this only during rest tremor episodes. In these cases, modulation frequency of unit activities was not statistically different from the rest tremor frequency (average: 4.6±0.5 vs 4.4±0.4 Hz, respectively). In the medial thalamus, four types of unit activities could be defined. A sporadic type was mainly found in the parvocellular division of the mediodorsal nucleus (96.8% of the cells recorded) and in the centre median–parafascicular complex (74.2%). Two other types of activities characterized by random or rhythmic bursts fulfilling the extracellular criteria of low-threshold calcium spike bursts were concentrated in the central lateral nucleus (62.3%) and the paralamellar division of the mediodorsal nucleus (34.1%). These activities could be recorded independently of the presence of a rest tremor. When a tremor episode occurred, the rhythmic low-threshold calcium spike bursts had an interburst frequency similar to rest tremor frequency, although they were not synchronized with it. The fourth type, the so-called tremor locked, was also characterized by rhythmic bursts which, however, did not display low-threshold calcium spike burst properties. These bursts occurred only when a rest tremor was present and was in-phase with the electromyographic bursts. All tremor-locked cells were located in the centre median–parafascicular complex. In the lateral thalamus, cells exhibiting random or rhythmic low-threshold calcium spike bursts were found preponderantly in the ventral anterior nucleus (53.4%) and in the ventral lateral anterior nucleus (52.7%). Tremor-locked units were confined to the ventral division of the ventral lateral posterior nucleus (35.4%). None of the random or rhythmic low-threshold calcium spike bursting units responded to somatosensory stimuli or voluntary movements, either in the medial or in the lateral thalamus. The presence of low-threshold calcium spike bursts at the thalamic level, together with the paucity (8%) of responses to voluntary movements compared to what is found in normal non-human primates, demonstrate a pathological state of inhibition due to the overactivity of the internal subdivision of the globus pallidus units. Activities of the thalamic cells producing low-threshold calcium spike bursts are not synchronized with each other or with the tremor. However, this does not exclude a causal role of these activities in the generation of tremor. Indeed, it has been demonstrated that even random electrical stimulations of the rolandic cortex in parkinsonian patients induce tremor episodes, probably due to the triggering of rhythmic, low-threshold calcium spike-dependent, thalamocortical activities. Similarly, low-threshold calcium spike bursts could be at the origin of rigidity and dystonia through an activation of the supplementary motor area and of akinesia when reaching the pre-supplementary motor area. We conclude that the intrinsic oscillatory properties of individual neurons, combined with the dynamic properties of the thalamocortical circuitry, are responsible for the three cardinal parkinsonian symptoms.

Objective The aim of this work was to provide a detailed description of the arterial vascularization of the temporomesial region (TMR), correlated with the definitions of the macroscopic and cytoarchitectonic subdivisions of this area. Methods Selective colored arterial injections were performed in 16 hemispheres to study their blood supply. Four hemispheres were used to illustrate the macroscopic aspect of the TMR and were then cut into thin sections and stained with Nissl's stain to study the cytoarchitectonic areas. Results The surface of the TMR is subdivided into several areas: anteriorly, the lateral olfactory gyrus is covered by prepiriform cortex; dorsomedially, the semilunar gyrus and uncus hippocampi consist, respectively, of cortical amygdaloid nucleus and hippocampal cytoarchitectonic fields; and ventrolaterally, the anterior part of the parahippocampal gyrus is covered by periamygdaloid cortex, entorhinal, and transentorhinal areas and its posterior part is covered by Fields TH and TF per Von Economo and subicular complex. Six cortical arterial groups were defined: Group I, anterosuperior parahippocampal arteries (mean, 3.9 arteries) vascularize the ambiens, semilunar, and lateral olfactory gyri (origins: middle cerebral artery, anterior choroidal artery [AChA], posterior cerebral artery [PCA], and internal carotid artery); Group II, anteroinferior parahippocampal arteries (mean, 2.8 arteries) irrigate the anterior ventrolateral region of the parahippocampal gyrus (origins: middle cerebral artery, PCA, and AChA); Group III, medial uncal arteries (mean, 1.9 arteries) supply the medial part of uncus hippocampi (origins: AChA and PCA); Group IV, lateral uncal arteries (mean, 2.9 arteries) vascularize the lateral part of the uncus hippocampi (origins: AChA and PCA); Group V, several small posterior parahippocampal arteries irrigate Fields TF and TH per Von Economo (origins: PCA and AChA); and Group VI, posterior hippocampal arteries (mean, 3.2 arteries) irrigate the posterior part of hippocampal formation (origin: PCA). Many anastomoses are found among these arteries, particularly in the ventrolateral part of the TMR. Three groups of amygdaloid arteries were defined: Group I, the anterolateral group (mean, 5.7 arteries) (origin: middle cerebral artery); Group II, the medial group (mean, 6.4 arteries) (origins: AChA, internal carotid artery, and PCA); and Group III, the posterolateral group (mean, 5 arteries) (origins: AChA and internal carotid artery). Conclusion We hope that this work will be useful for any microneurosurgical procedures on the TMR. We have clarified the macroscopic and histological definitions of the cortical and nuclear areas of the TMR and the arterial groups closely related to them. The systematic analysis of the variability of the arterial vascularization of this area was our second goal; such a goal, however, requires more observations to be exhaustive. The numerous interterritorial anastomoses found inside the TMR imply that a selective presurgical injection of short-acting barbiturates to evaluate its functions (Wada test) may well result in its diffusion to other areas of the TMR.