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127
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Introduction
Additional affiliations
January 2010 - present
Center for Ultrasound Functional Neurosurgery
Position
- CEO / Medical Direction SoniModul
January 2001 - October 2009
October 1993 - October 2009
University Hospital Zurich
Position
- Leitender Arzt
Publications
Publications (127)
Objective:
Medial thalamotomies were introduced in the late 1940s. Pain relief was shown to be achieved for all body locations. With some exceptions, these early relatively small series showed frequent, more or less complete recurrence of the original pain. The posterior part of the central lateral nucleus in the human medial thalamus was identifi...
BACKGROUND
The authors reported the case of a 66-year-old male patient with a 14-year history of right-sided severe episodic and therapy-resistant cluster headache (CH) who underwent bilateral central lateral thalamotomy (CLT) using incisionless transcranial magnetic resonance imaging–guided focused ultrasound (MRgFUS).
OBSERVATIONS
The patient ex...
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) interve...
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 ph...
OBJECTIVE
In 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 a...
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 pallidoth...
Background: MR-guided focused ultrasound (MRgFUS) offers the possibility of safe and accurate lesioning inside the brain. Until now, most MRgFUS thermal applications have been based on temperature or energy protocols. Experimental studies support however an approach centered on thermal dose control.
Objective: To show the technical feasibility and...
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 tr...
Background
After 60 years of history in the field of functional neurosurgery, the issue of target coverage remains primordial and sub-optimally addressed and solved. The possibility of intraoperative visualization and monitoring of a selected target heated with MR-guided high intensity focused ultrasound (MRgFUS) offers new perspectives for safe an...
OBJECTIVE
Since 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...
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...
Les récentes avancées de la technologie des ultrasons focalisés permettent depuis 2008 la réalisation de lésions cérébrales thérapeutiques sans incision avec une précision et une sécurité jamais atteintes par les techniques stéréotaxiques avec pénétration cérébrale. Elle permet actuellement de proposer aux patients atteints de tremblement essentiel...
Die neuen Entwicklungen der intrakraniellen fokussierten Ultraschalltechnologie erlauben seit 2008 die Durchführung von therapeutischen, inzisionslosen Eingriffen am Gehirn mit einer Präzision und Sicherheit, die durch stereotaktische Methoden mit Penetration des Gehirns niemals erreicht werden konnten. Sie bietet Patienten, die unter chronischen u...
La technologie des ultrasons focalisés guidés par IRM permet la réalisation de lésions cérébrales thérapeutiques sans incision avec une précision et une sécu-rité jamais atteintes par les techniques stéréotaxiques avec pénétration. Elle permet actuellement de proposer aux patients atteints de tremblement essen-tiel, de la maladie de Parkinson ou de...
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 pat...
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 initia...
The authors would like to highlight the overlap in the Background, Methods and Discussions sections between their article in the Journal of Therapeutic Ultrasound [1] and their previous publication in Neurosurgical Focus [2], published and copyrighted by the American Association of Neurosurgeons. The novel aspects of this article [1] are the demons...
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...
Background
The purpose of this study was to describe targeting accuracy in functional neurosurgery using incisionless transcranial magnetic resonance (MR)-guided focused ultrasound technology.
Methods
MR examinations were performed before and 2 days after the ultrasound functional neurosurgical treatment to visualize the targets on T2-weighted ima...
Several recent studies report the presence of a specific EEG pattern named Thalamocortical Dysrhythmia (TCD) in patients with severe chronic neurogenic pain. This is of major interest since so far no neuroscientific indicator of chronic pain could be identified. We investigated whether a TCD-like pattern could be found in patients with moderate chr...
CONSORT checklist.
(DOC)
Clinical description of all patients.
(DOC)
Trial Protocol.
(PDF)
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...
The object of this study was to describe a method of measuring targeting accuracy in functional neurosurgery using MR imaging and the Stereotactic Atlas of the Human Thalamus and Basal Ganglia. This method should be useful for any functional procedure using these tools or similar ones, and is described here in the specific context of focused ultras...
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 latera...
The concept of consciousness is omnipresent in the fields of neuroscience, quantum physics, philosophy and spirituality. In
neuroscience, it represents the highest and least understandable component of brain function, unescapable but difficult to
describe, its mechanism(s) remaining until today elusive. The dominant view in this field is that consc...
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...
Greater low frequency power (<8 Hz) in the electroencephalogram (EEG) at rest is normal in the immature developing brain of children when compared to adults. Children with epilepsy also have greater low frequency interictal resting EEG activity. Whether these power elevations reflect brain immaturity due to a developmental lag or the underlying epi...
Functional stereotactic lesions in the central lateral nucleus of the medial thalamus have proved to be an effective treatment of neurogenic pain and other neurological disorders associated with thalamocortical dysrhythmia. The mechanisms underlying patient recovery after surgery are currently being explored using quantitative electroencephalograph...
Illustration of the steps performed for the load dependent EEG-BOLD signal analysis. The first step (panels on the top) is the calculation of the BOLD signal contrast ss5-ss2 (p<0.005, FDR corrected). The second step is the extraction of the contrast estimates for the different frequency bands and load conditions in the activated region (some areas...
(A) EEG-BOLD signal correlations (group results, p<0.001, uncorrected) for the RMS and electrodes Afz, C3 and O2. Blue areas indicating negative EEG-BOLD signal correlations, red areas indicating positive EEG-BOLD signal correlations. (B) Statistical differences between the RMS and the single electrode approach (paired t-tests, k>15 voxel). For exa...
Group averaged grey- and white matter beta2-BOLD (A) and gamma-BOLD (B) signal correlations (p<0.005, uncorrected). Red areas indicating positive EEG-BOLD signal correlations.
(1.92 MB EPS)
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 alp...
Table S1. Patient clinical details. Symptom laterality: BL (bilateral), R (right), L (left). Quality of Life: QL. Intensity scaling for anxiety, depression, frustration, hyperacusis and reduction of QL: 0 is for normal, 1 for slight, 2 for moderate, 3 for strong and 4 for severe. VAS: visual analogue scale (0-100). NA: not available.
Grand average of the normalized power spectrum for EC condition in tinnitus and healthy control groups. Normalized EEG power spectrum for the group of patients (red) was enhanced with respect to the group of healthy controls (green).
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 p...
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...
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...
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...
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...
Head and Holmes postulated in 1911 the existence of an “essential medial thalamic centre,” localized medial to a pain-generating lesion in the thalamic ventroposterior (VP) nucleus, and responsible for the pathogenesis of central pain [1]. This centre was thought to be exposed to a decreased inhibitory influence from thalamo-cortico-thalamic loops....
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 cli...
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 h...
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 slice...
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 electrode...
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...
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 stereotact...
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 int...
The dense and reciprocal connections between thalamus and cortical areas provide anatomical evidence for the importance of thalamocortical interactions in brain function. We studied the thalamocortical interplay in patients with neurogenic pain during therapeutic neurosurgical interventions by recording simultaneously single cell activity in the th...
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 gm thick. Consequently, the three-dimensional dataset, generated out of the two-dimensional...
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 t...
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...
Defined more than one century ago, the concept of positive symptoms has become obsolete, except in the psychiatric domain. However, its relevance remains intact today when considering such pathophysiologies as neuropathic (phantom) pain, movement disorders, tinnitus, epilepsy, and psychiatric disorders. Beside their very different clinical characte...
Neurophysiological studies at the cellular level (microelectrode unit activity recordings and local field potentials) as well as electro- and magnetoencephalographic recordings provide converging evidence for a thalamocortical dysregulation at the source of chronic neurogenic pain of both peripheral and central origin. These indicate an increase of...
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 dysrhythm...
The over-inhibition of thalamic relay cells by hyperactivity of the internal part of the globus pallidus is a cornerstone of the parkinsonian pathophysiology that leads to a distortion of the thalamocortical dynamics called thalamocortical dysrhythmia (TCD). Here, we present the results of the stereotactic pallidothalamic tractotomy (PTT), which in...
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 PM...
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...
Clearly, more clinical experience must be amassed to define in detail the possibilities of this surgical approach in disabling neuropsychiatric disorders. We propose, however, that the evidence for benign and efficient surgical intervention against the neuropsychiatric TCD syndrome is already compelling. The potential appearance of strong postopera...
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 neurop...
The distribution of the calcium-binding proteins calbindin-D28K (CB), parvalbumin (PV) and calretinin (CR), and of the nonphosphorylated neurofilament protein (with SMI-32) was investigated in the human basal ganglia to identify anatomofunctional territories. In the striatum, gradients of neuropil immunostaining define four major territories: The f...
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 volitiona...
Thalamic and cortical neurons are richly and reciprocally interconnected and support recurrent functional loops in the intact brain, but the role of this circuitry is still poorly understood. Here, we present evidence—from cellular and from functional neuroimaging in control and clinical domains—that thalamocortical resonance is not only a prerequi...
Thalamic and cortical neurons are richly and reciprocally interconnected and support recurrent functional loops in the intact brain, but the role of this circuitry is still poorly understood. Here, we present evidence—from cellular and from functional neuroimaging in control and clinical domains—that thalamocortical resonance is not only a prerequi...
The companion paper (Llinás et al., 2001) presents evidence, at both cellular and network levels, for the role of resonant oscillatory thalamocortical properties in normal and pathological brain function. Here we present confirmatory single cell electrophysiology from the thalami of thalamocortical dysrhythmia (TCD) patients and review our surgical...