SEEG electrode shaft affects amplitude and latency of potentials evoked with single pulse electrical stimulation.

BACKGROUND: Long and thin shaft electrodes are implanted intracerebrally for stereoelectroencephalography (SEEG) in patients with pharmacoresistant focal epilepsies. Two adjacent contacts of one of such electrodes can deliver a train of single pulse electrical stimulations (SPES), and evoked potentials (EPs) are recorded on other contacts. In this study we assess if stimulating and recording on the same shaft, as opposed to different shafts, has an impact on common EP features. NEW METHOD: We leverage the large volume of SEEG data gathered in the F-TRACT database and analyze data from nearly one thousand SEEG implantations in order to verify whether stimulation and recording from the same shaft influence the EP pattern. RESULTS: We found that when the stimulated and the recording contacts were located on the same shaft, the mean and median amplitudes of an EP are greater, and its mean and median latencies are smaller than when the contacts were located on different shafts. This effect is small (Cohen's d ∼ 0.1), but robust (p-value < 10-3) across the SEEG database. COMPARISON WITH EXISTING METHOD(S): Our study is the first one to address this question. Due to the choice of commonly used EP features, our method is congruent with other studies. CONCLUSIONS: The magnitude of the reported effect does not obligate all standard analyses to correct for it, unless they aim at high precision. The source of the effect is not clear. Manufacturers of SEEG electrodes could examine it and potentially minimize the effect in their future products.

Cholinergic and Nadph-δ neurons in the pedunculopontine and laterodorsal tegmental nuclei of human and nonhuman primates.

The brainstem pedunculopontine (PPN) and laterodorsal tegmental (LDTg) nuclei are involved in multifarious activities, including motor control. Yet, their exact cytoarchitectural boundaries are still uncertain. We therefore initiated a comparative study of the topographical and neurochemical organization of the PPN and LDTg in cynomolgus monkeys (Macaca fascicularis) and humans. The distribution and morphological characteristics of neurons expressing choline acetyltransferase (ChAT) and/or nicotinamide adenine dinucleotide phosphate diaphorase (Nadph-δ) were documented. The number and density of the labeled neurons were obtained by stringent stereological methods, whereas their topographical distribution was reported upon corresponding magnetic resonance imaging (MRI) planes. In both human and nonhuman primates, the PPN and LDTg are populated by three neurochemically distinct types of neurons (ChAT-/Nadph-δ+, ChAT+/Nadph-δ-, and ChAT+/Nadph-δ+), which are distributed according to a complex spatial interplay. Three-dimensional reconstructions reveal that ChAT+ neurons in the PPN and LDTg form a continuum with some overlaps with pigmented neurons of the locus coeruleus, dorsally, and of the substantia nigra (SN) complex, ventrally. The ChAT+ neurons in the PPN and LDTg are -two to three times more numerous in humans than in monkeys but their density is -three to five times higher in monkeys than in humans. Neurons expressing both ChAT and Nadph-δ have a larger cell body and a longer primary dendritic arbor than singly labeled neurons. Stereological quantification reveals that 25.6% of ChAT+ neurons in the monkey PPN are devoid of Nadph-δ staining, a finding that questions the reliability of Nadph-δ as a marker for cholinergic neurons in primate brainstem.

Variability of Single Pulse Electrical Stimulation Responses Recorded with Intracranial Electroencephalography in Epileptic Patients.

Cohort studies of brain stimulations performed with stereo-electroencephalographic (SEEG) electrodes in epileptic patients allow to derive large scale functional connectivity. It is known, however, that brain responses to electrical or magnetic stimulation techniques are not always reproducible. Here, we study variability of responses to single pulse SEEG electrical stimulation. We introduce a second-order probability analysis, i.e. we extend estimation of connection probabilities, defined as the proportion of responses trespassing a statistical threshold (determined in terms of Z-score with respect to spontaneous neuronal activity before stimulation) over all responses and derived from a number of individual measurements, to an analysis of pairs of measurements.Data from 445 patients were processed. We found that variability between two equivalent measurements is substantial in particular conditions. For long ( > ~ 90 mm) distances between stimulating and recording sites, and threshold value Z = 3, correlation between measurements drops almost to zero. In general, it remains below 0.5 when the threshold is smaller than Z = 4 or the stimulating current intensity is 1 mA. It grows with an increase of either of these factors. Variability is independent of interictal spiking rates in the stimulating and recording sites.We conclude that responses to SEEG stimulation in the human brain are variable, i.e. in a subject at rest, two stimulation trains performed at the same electrode contacts and with the same protocol can give discrepant results. Our findings highlight an advantage of probabilistic interpretation of such results even in the context of a single individual.

A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials.

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.

Relationship between direct cortical stimulation and induced high-frequency activity for language mapping during SEEG recording.

OBJECTIVE: The authors assessed the clinical relevance of preoperative task-induced high-frequency activity (HFA) for language mapping in patients with refractory epilepsy during stereoelectroencephalography recording. Although HFA evaluation was described as a putative biomarker of cognition, its clinical relevance for mapping language networks was assessed predominantly by studies using electrocorticography (ECOG). METHODS: Forty-two patients with epilepsy who underwent intracranial electrode implantation during both task-induced HFA and direct cortical stimulation (DCS) language mapping were evaluated. The spatial and functional relevance of each method in terms of specificity and sensitivity were evaluated. RESULTS: The results showed that the two methods were able to map classic language regions, and a large and bilateral language network was obtained with induced HFA. At a regional level, differences were observed between methods for parietal and temporal lobes: HFA recruited a larger number of cortical parietal sites, while DCS involved more cortical temporal sites. Importantly, the results showed that HFA predicts language interference induced by DCS with high specificity (92.4%; negative predictive value 95.9%) and very low sensitivity (8.9%; positive predictive value 4.8%). CONCLUSIONS: DCS language mapping appears to be more appropriate for an extensive temporal mapping than induced HFA mapping. Furthermore, induced HFA should be used as a complement to DCS to preselect the number of stimulated sites during DCS, by omitting those reported as HFA-. This may be a considerable advantage because it allows a reduction in the duration of the stimulation procedure. Several parameters to be used for each method are discussed and the results are interpreted in relation to previous results reported in ECOG studies.

Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease.

The pedunculopontine nucleus (PPN) included in the caudal mesencephalic reticular formation (cMRF) plays a key role in the control of locomotion and wake state. Regarding its involvement in the neurodegenerative process observed in Parkinson disease (PD), deep brain stimulation of the PPN was proposed to treat levodopa-resistant gait disorders. However, the precise role of the cMRF in the pathophysiology of PD, particularly in freezing of gait and other non-motor symptoms is still not clear. Here, using micro electrode recording (MER) in 2 primates, we show that dopamine depletion did not alter the mean firing rate of the overall cMRF neurons, particularly the putative non-cholinergic ones, but only a decreased activity of the regular neurons sub-group (though to be the cholinergic PPN neurons). Interestingly, a significant increase in the relative proportion of cMRF neurons with a burst pattern discharge was observed after MPTP intoxication. The present results question the hypothesis of an over-inhibition of the CMRF by the basal ganglia output structures in PD. The decreased activity observed in the regular neurons could explain some non-motor symptoms in PD regarding the strong involvement of the cholinergic neurons on the modulation of the thalamo-cortical system. The increased burst activity under dopamine depletion confirms that this specific spike discharge pattern activity also observed in other basal ganglia nuclei and in different pathologies could play a mojor role in the pathophysiology of the disease and could explain several symptoms of PD including the freezing of gait. The present data will have to be replicated in a larger number of animals and will have to investigate more in details how the modification of the spike discharge of the cMRF neurons in the parkinsonian state could alter functions such as locomotion and attentional state. This will ultimely allow a better comprehension of the pathophysiology of freezing of gait.

Deep Brain Stimulation of the Pedunculopontine Nucleus Area in Parkinson Disease: MRI-Based Anatomoclinical Correlations and Optimal Target.

BACKGROUND: Experimental studies led to testing of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as a new therapy to treat freezing of gait (FOG) in Parkinson disease (PD). Despite promising initial results fueling a growing interest toward that approach, several clinical studies reported heterogeneity in patient responses. Variation in the position of electrode contacts within the rostral brainstem likely contributes to such heterogeneity. OBJECTIVE: To provide anatomoclinical correlations of the effect of DBS of the caudal mesencephalic reticular formation (cMRF) including the PPN to treat FOG by comparing the normalized positions of the active contacts among a series of 11 patients at 1- and 2-yr follow-up and to provide an optimal target through an open-label study. METHODS: We defined a brainstem normalized coordinate system in relation to the pontomesencephalic junction. Clinical evaluations were based on a composite score using objective motor measurements and questionnaires allowing classification of patients as "bad responders" (2 patients), "mild responders" (1 patient) and "good responders" (6 patients). Two patients, whose long-term evaluation could not be completed, were excluded from the analysis. RESULTS: Most effective DBS electrode contacts to treat FOG in PD patients were located in the posterior part of the cMRF (encompassing the posterior PPN and cuneiform nucleus) at the level of the pontomesencephalic junction. CONCLUSION: In the present exploratory study, we performed an anatomoclinical analysis using a new coordinate system adapted to the brainstem in 9 patients who underwent PPN area DBS. We propose an optimal DBS target that allows a safe and efficient electrode implantation in the cMRF.

Probabilistic functional tractography of the human cortex revisited.

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human.

IntrAnat Electrodes: A Free Database and Visualization Software for Intracranial Electroencephalographic Data Processed for Case and Group Studies.

In some cases of pharmaco-resistant and focal epilepsies, intracranial recordings performed epidurally (electrocorticography, ECoG) and/or in depth (stereoelectroencephalography, SEEG) can be required to locate the seizure onset zone and the eloquent cortex before surgical resection. In SEEG, each electrode contact records brain's electrical activity in a spherical volume of 3 mm diameter approximately. The spatial coverage is around 1% of the brain and differs between patients because the implantation of electrodes is tailored for each case. Group studies thus need a large number of patients to reach a large spatial sampling, which can be achieved more easily using a multicentric approach such as implemented in our F-TRACT project (f-tract.eu). To facilitate group studies, we developed a software-IntrAnat Electrodes-that allows to perform virtual electrode implantation in patients' neuroanatomy and to overlay results of epileptic and functional mapping, as well as resection masks from the surgery. IntrAnat Electrodes is based on a patient database providing multiple search criteria to highlight various group features. For each patient, the anatomical processing is based on a series of software publicly available. Imaging modalities (Positron Emission Tomography (PET), anatomical MRI pre-implantation, post-implantation and post-resection, functional MRI, diffusion MRI, Computed Tomography (CT) with electrodes) are coregistered. The 3D T1 pre-implantation MRI gray/white matter is segmented and spatially normalized to obtain a series of cortical parcels using different neuroanatomical atlases. On post-implantation images, the user can position 3D models of electrodes defined by their geometry. Each electrode contact is then labeled according to its position in the anatomical atlases, to the class of tissue (gray or white matter, cerebro-spinal fluid) and to its presence inside or outside the resection mask. Users can add more functionally informed labels on contact, such as clinical responses after electrical stimulation, cortico-cortical evoked potentials, gamma band activity during cognitive tasks or epileptogenicity. IntrAnat Electrodes software thus provides a means to visualize multimodal data. The contact labels allow to search for patients in the database according to multiple criteria representing almost all available data, which is to our knowledge unique in current SEEG software. IntrAnat Electrodes will be available in the forthcoming release of BrainVisa software and tutorials can be found on the F-TRACT webpage.

Automatic bad channel detection in intracranial electroencephalographic recordings using ensemble machine learning.

OBJECTIVE: Intracranial electroencephalographic (iEEG) recordings contain "bad channels", which show non-neuronal signals. Here, we developed a new method that automatically detects iEEG bad channels using machine learning of seven signal features. METHODS: The features quantified signals' variance, spatial-temporal correlation and nonlinear properties. Because the number of bad channels is usually much lower than the number of good channels, we implemented an ensemble bagging classifier known to be optimal in terms of stability and predictive accuracy for datasets with imbalanced class distributions. This method was applied on stereo-electroencephalographic (SEEG) signals recording during low frequency stimulations performed in 206 patients from 5 clinical centers. RESULTS: We found that the classification accuracy was extremely good: It increased with the number of subjects used to train the classifier and reached a plateau at 99.77% for 110 subjects. The classification performance was thus not impacted by the multicentric nature of data. CONCLUSIONS: The proposed method to automatically detect bad channels demonstrated convincing results and can be envisaged to be used on larger datasets for automatic quality control of iEEG data. SIGNIFICANCE: This is the first method proposed to classify bad channels in iEEG and should allow to improve the data selection when reviewing iEEG signals.

Correlation of FDG-PET hypometabolism and SEEG epileptogenicity mapping in patients with drug-resistant focal epilepsy.

OBJECTIVE: Interictal [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is used in the presurgical evaluation of patients with drug-resistant focal epilepsy. We aimed at clarifying its relationships with ictal high-frequency oscillations (iHFOs) shown to be a relevant marker of the seizure-onset zone. METHODS: We studied the correlation between FDG-PET and epileptogenicity maps in an unselected series of 37 successive patients having been explored with stereo-electroencephalography (SEEG). RESULTS: At the group level, we found a significant correlation between iHFOs and FDG-PET interictal hypometabolism only in cases of temporal lobe epilepsy. This correlation was found with HFOs, and the same comparison between FDG-PET and ictal SEEG power of lower frequencies during the same epochs did not show the same significance. SIGNIFICANCE: This finding suggests that interictal FDG-PET and ictal HFOs may share common underlying pathophysiologic mechanisms of ictogenesis in temporal lobe epilepsy, and combining both features may help to identify the seizure-onset zone.

Response inhibition rapidly increases single-neuron responses in the subthalamic nucleus of patients with Parkinson's disease.

The subthalamic nucleus (STN) plays a critical role during action inhibition, perhaps by acting like a fast brake on the motor system when inappropriate responses have to be rapidly suppressed. However, the mechanisms involving the STN during motor inhibition are still unclear, particularly because of a relative lack of single-cell responses reported in this structure in humans. In this study, we used extracellular microelectrode recordings during deep brain stimulation surgery in patients with Parkinson's disease (PD) to study STN neurophysiological correlates of inhibitory control during a stop signal task. We found two neuronal subpopulations responding either during motor execution (GO units) or during motor inhibition (STOP units). GO units fired selectively before patients' motor responses whereas STOP units fired selectively when patients successfully withheld their move at a latency preceding the duration of the inhibition process. These results provide electrophysiological evidence for the hypothesized role of the STN in current models of response inhibition.

The primate pedunculopontine nucleus region: towards a dual role in locomotion and waking state.

The mesencephalic reticular formation (MRF) mainly composed by the pedunculopontine and the cuneiform nuclei is involved in the control of several fundamental brain functions such as locomotion, rapid eye movement sleep and waking state. On the one hand, the role of MRF neurons in locomotion has been investigated for decades in different animal models, including in behaving nonhuman primate (NHP) using extracellular recordings. On the other hand, MRF neurons involved in the control of waking state have been consistently shown to constitute the cholinergic component of the reticular ascending system. However, a dual control of the locomotion and waking state by the same groups of neurons in NHP has never been demonstrated in NHP. Here, using microelectrode recordings in behaving NHP, we recorded 38 neurons in the MRF that were followed during transition between wakefulness (TWS) and sleep, i.e., until the emergence of sleep episodes characterized by typical cortical slow wave activity (SWA). We found that the MRF neurons, mainly located in the pedunculopontine nucleus region, modulated their activity during TWS with a decrease in firing rate during SWA. Of interest, we could follow some MRF neurons from locomotion to SWA and found that they also modulated their firing rate during locomotion and TWS. These new findings confirm the role of MRF neurons in both functions. They suggest that the MRF is an integration center that potentially allows to fine tune waking state and locomotor signals in order to establish an efficient locomotion.

On the Role of the Pedunculopontine Nucleus and Mesencephalic Reticular Formation in Locomotion in Nonhuman Primates.

UNLABELLED: The mesencephalic reticular formation (MRF) is formed by the pedunculopontine and cuneiform nuclei, two neuronal structures thought to be key elements in the supraspinal control of locomotion, muscle tone, waking, and REM sleep. The role of MRF has also been advocated in modulation of state of arousal leading to transition from wakefulness to sleep and it is further considered to be a main player in the pathophysiology of gait disorders seen in Parkinson's disease. However, the existence of a mesencephalic locomotor region and of an arousal center has not yet been demonstrated in primates. Here, we provide the first extensive electrophysiological mapping of the MRF using extracellular recordings at rest and during locomotion in a nonhuman primate (NHP) (Macaca fascicularis) model of bipedal locomotion. We found different neuronal populations that discharged according to a phasic or a tonic mode in response to locomotion, supporting the existence of a locomotor neuronal circuit within these MRF in behaving primates. Altogether, these data constitute the first electrophysiological characterization of a locomotor neuronal system present within the MRF in behaving NHPs under normal conditions, in accordance with several studies done in different experimental animal models. SIGNIFICANCE STATEMENT: We provide the first extensive electrophysiological mapping of the two major components of the mesencephalic reticular formation (MRF), namely the pedunculopontine and cuneiform nuclei. We exploited a nonhuman primate (NHP) model of bipedal locomotion with extracellular recordings in behaving NHPs at rest and during locomotion. Different MRF neuronal groups were found to respond to locomotion, with phasic or tonic patterns of response. These data constitute the first electrophysiological evidences of a locomotor neuronal system within the MRF in behaving NHPs.

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease.

OBJECT: The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. METHODS: Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. RESULTS: Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. CONCLUSIONS: This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

Anatomy-preserving nonlinear registration of deep brain ROIs using confidence-based block-matching.

Brain atlases are commonly used in a number of applications such as MRI segmentation and surgery targetting. Our goal is to register a basal ganglia atlas to a subject using MR image registration. Existing registration methods are for the most part either too constrained (linear registration) or can deform deep brain ROIs into implausible anatomical shapes. We developed a block-matching registration method suitable for atlas registration, using a new confidence-based regularization of the vector field. The method was used to register a set of 17 manually segmented MRI onto one subject. Results show that basal ganglia structures were better registered than when using an affine registration method.

Modeling and detecting deep brain activity with MEG & EEG.

We introduce an anatomical and electrophysiological model of deep brain structures dedicated to magnetoencephalography (MEG) and electroencephalography (EEG) source imaging. So far, most imaging inverse models considered that MEG/EEG surface signals were predominantly produced by cortical, hence superficial, neural currents. Here we question whether crucial deep brain structures such as the basal ganglia and the hippocampus may also contribute to distant, scalp MEG and EEG measurements. We first design a realistic anatomical and electrophysiological model of these structures and subsequently run Monte-Carlo experiments to evaluate the respective sensitivity of the MEG and EEG to signals from deeper origins. Results indicate that MEG/EEG may indeed localize these deeper generators, which is confirmed here from experimental MEG data reporting on the modulation of alpha brain waves.

Retrospective cross-evaluation of an histological and deformable 3D atlas of the basal ganglia on series of Parkinsonian patients treated by deep brain stimulation.

In functional neurosurgery, there is a growing need for accurate localization of the functional targets. Since deep brain stimulation (DBS) of the Vim thalamic nucleus has been proposed for the treatment of Parkinson's disease, the target has evolved toward the globus pallidus and subthalamic nucleus (STN) and the therapeutic indications have enlarged to include psychiatric disorders such as Tourette syndrome or obsessive compulsive disorders. In these pathologies, the target has been restrained to smaller functional subterritories of the basal ganglia, requiring more refined techniques to localize smaller and smallerbrain regions, often invisible in routine clinical MRI. Different strategies have been developed to identify such deep brain targets. Direct methods can identify structures in the MRI itself, but only the larger ones. Indirect methods are based on the use of anatomical atlases. The present strategy comprised a 3D histological atlas and the MRI of the same brain specimen, and deformation methodology developped to fit the atlas toward the brain of any given patient. In this paper, this method is evaluated in the aim of being applied to further studies of anatomo-clinical correlation. The accuracy of the method is first discussed, followed by the study of short series of Parkinsonian patients treated by DBS, allowing to compare the deformed atlas with various per- and post-operative data.