Abstract: BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) is an effective treatment of movement disorders and psychiatric diseases. However, this surgery is still time consuming and associated with complications, among which we aimed to identify non-stimulo-induced adverse effects. Hence, we retrospectively systematically analyzed patients operated on, at our institution, using magnetic resonance imaging (MRI) direct anatomic mapping. METHODS: One hundred and seventy-five patients (184 surgeries) were performed between 1994 and 2008, for Parkinson's disease, essential tremor, dystonia and obsessive compulsive disorder. Primary anatomic targets were the subthalamic region, the intern pallidum and the thalamus. Final electrode positioning was adjusted according to intraoperative neuron recordings and acute stimulation tests. All surgically related adverse effects were collected. Life threatening or new non-planed surgery was considered as severe adverse effects. RESULTS: Adverse effects occurred 10 times (5.4%) during MRI acquisition, 24 times (13%) with five serious (2.7%) including one1 death (0.5%) during electrodes implantation and 17 times (9.2%) with four serious (2.2%) during neuropacemaker implantation. Electrodes were repositioned in six cases (five patients, n=3.4%). CONCLUSION: DBS efficiency is recognized however the significant incidence of adverse effects should prompt us to improve the procedures.
Abstract: BACKGROUND: The ventrointermediate nucleus (Vim) of the thalamus is still considered "invisible" on current magnetic resonance imaging (MRI), requiring indirect methods based on stereotactic atlases for estimation of its location. Direct visualization of Vim is desirable to improve targeting. OBJECTIVE: To evaluate the ability of Inversion-Recovery 1.5-T MR images to produce high-resolution, anatomical depiction of the thalamus suitable for direct Vim targeting. METHODS: Twenty patients with essential tremor or tremor associated with Parkinson's disease received Vim deep brain stimulation (DBS). Fahn-Tolosa-Marin and Unified Parkinson's Disease Rating Scale (UPDRS) tremor scores were assessed pre- and postoperatively. Preoperative stereotactic 1.5-T MR images of the thalamus were acquired using a White Matter Attenuated Inversion Recovery (WAIR) sequence. Thalamic nuclei were manually contoured on the basis of spontaneous MRI contrasts; labeling relied on 3D identification from stereotactic books and in-house ex vivo 4.7-T microscopic MRI atlas. Vim was then directly probed for electrophysiological confirmation and determination of the optimal site for electrode placement. RESULTS: The shape, spatial orientation, and signal contrast of Vim as depicted on our WAIR images were similar to those observed on the Schaltenbrand and Bailey atlas, as well as in our high-field MRI atlas. These images were successfully used for pure direct Vim targeting: at the last follow-up (median = 46.3 months), the average tremor score improved from 3.80 preoperatively to 0.50 postoperatively (on stimulation; P < 0.01). CONCLUSION: 1.5-T MRI with WAIR sequence provides high-quality images of Vim suitable in DBS surgery, for accurate preoperative planning, direct targeting and anatomic analysis.
Abstract: The Clinical Global Impression scale (CGI) is frequently used in clinical research because of its face validity and ease of use but data on its reliability are scarce. Our goal was to estimate the reliability of the scale and compare reliability between face-to-face and video scoring. We analyzed 50 different video interviews recorded during 5 visits of a crossover trial to study the effect of subthalamic nucleus stimulation. Six specialized clinicians rated the CGI using these videos, providing 300 different ratings. The intraclass correlation was lower at inclusion (0.30 [0.13-0.50]) than at later visits (0.68 [0.61-0.80]). Reliability was not influenced by the patients' stimulation status. The mean of at least two independent evaluations of the video is needed to achieve an ICC greater than 0.8. The video CGI is a valid clinical outcome measure suitable for clinical trials (ClinicalTrials.gov number, NCT00169377).
Abstract: Functional and connectivity changes in corticostriatal systems have been reported in the
brains of patients with obsessive-compulsive disorder (OCD) but the relationship between
basal ganglia activity and OCD severity has never been adequately established. We recently
showed that deep brain stimulation of the subthalamic nucleus (STN),
a central basal ganglia
nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12
OCD patients, in relation to the severity of obsessions and compulsions, and compared to that
obtained in 12 patients with Parkinson’s disease. STN neurons in OCD patients had lower
discharge frequency than in PD patients, with a similar proportion of burst-type activity (69%
vs 67%). Oscillatory activity was present in 46% and 68% of neurons in OCD and PD
patients respectively, predominately in the low frequency band (1-8 Hz). In OCD patients, the
bursty and oscillatory subthalamic neuronal activity was mainly located in the associativelimbic
part. Both OCD severity and clinical improvement following STN stimulation were
related to the STN neuronal activity. In patients with the most severe OCD, STN neurons
exhibited bursts with shorter duration and interburst interval but higher intraburst frequency,
and more oscillations in the low frequency bands. In patients with best clinical outcome with
STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst
frequencies, and lower interburst interval. These findings are consistent with the hypothesis of
a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD’s
pathophysiology.
Abstract: BACKGROUND: High-frequency bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is a promising treatment in refractory obsessive-compulsive disorder (OCD). METHOD: Using the crossover, randomized, and double-blind procedure adopted by the STOC study, 10 patients treated with high-frequency bilateral STN DBS underwent am 18-fluorodeoxyglucose positron emission tomography (PET) investigation to highlight the neural substratum of this therapeutic approach. RESULTS: The median Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores for all 10 patients were 31 (minimum = 18, maximum = 36) with "Off-Stimulation" status and 19 (minimum = 0, maximum = 30) with "On-Stimulation" status (p = .05). The OCD patients in Off-Stimulation status showed a hypermetabolism in the right frontal middle and superior gyri, right parietal lobe, postcentral gyrus, and bilateral putamen compared with healthy control subjects. A significant decrease in cerebral metabolism was observed in the left cingulate gyrus and the left frontal medial gyrus in On-Stimulation conditions compared with Off-Stimulation conditions. In addition, the improvement assessed by Y-BOCS scores during the On-Stimulation conditions was positively correlated with PET signal changes at the boundary of the orbitofrontal cortex and the medial prefrontal cortex, between PET signal changes and the Y-BOCS scores modifications in On-Stimulation status. CONCLUSION: This study suggests that the therapeutic effect of STN DBS is related to a decrease in prefrontal cortex metabolism.
Abstract: The subthalamic nucleus (STN) is the main target for deep brain stimulation in Parkinson’s disease. We analyzed the relationships between MRI anatomy and spontaneous neuronal activity to confirm the potential of microelectrode recordings to assist in determining the optimal surgical target.
Ten bilateral surgeries were performed after 1.5-T (T2-weighted) anatomical MRI identification of the STN, zona incerta (ZI), Forel’s field H2 and substantia nigra (SN). Spontaneous neuronal activity was recorded simultaneously along the distal 10 mm on a central track (optimally covering the STN) and a 2 mm anterior track. We calculated off line mean firing rate and burst frequency on 248 neurons clustered according to anatomic structure. Subjective visual analysis of signal was also realized on line, during surgery, to classify patterns of activity.
Mean firing rate and burst frequency increased from H2-ZI to SN. Mean firing rate was higher in SN only using paired comparison (SN versus its neighbours). Burst frequency was lower in H2 than in SN; using comparison with neighbours, it was lower in H2 and ZI. An irregular high activity (type 2C) was more often detected in STN and SN than in H2 and ZI.
Anatomical boundaries and unitary recordings appear to be linked, supporting the ability of MRI to provide a detailed anatomy. Electrophysiological mapping combined with MRI is a useful tool for precise targeting in the subthalamic region.
Abstract: Subthalamic nucleus (STN) targeting is classically performed based on the probabilistic STN position relatively to ventricular landmarks, i.e. anterior commissure (AC) and posterior commissure (PC). Nevertheless, MRI allows direct STN visualization and targeting, without reference to the AC-PC. This study aimed to compare STN position localized on MR images against standard stereotactic images.
Material and methods
The right and left STN were manually contoured on native images of pre-operative coronal MR images of 22 Parkinsonian patients; boundaries were simplified in a schematic polygonal form. Front and lateral stereotactic images were constructed according to Talairach & Benabid. We compared x, y (from the mid-commissural point, MidP) and z coordinates of the center of gravity of MRI-based polygons and stereotactic images (Wilcoxon matched-pairs tests).
Results
There was significant discordance between MRI-based polygons and AC-PC-based images for x, y and z coordinates. The mean coordinates of centre of gravity of MRI-based polygons in Talairach and Benabid’s stereotactic spaces were, respectively: x = 9.04±1.33 mm, y = 2.82±0.99 mm, z on lateral view = -3.19±1.01 mm and z on front view = -2.97±0.97 mm; x = 9.14±1.3 mm, y = 2.56±0.96 mm, z on lateral view = -3.4±0.93 mm and z on front view = -3.18±0.97 mm. We propose a 2D-graphic representation of a probabilistic STN based on MRI-based polygons
Abstract: Background: Groups performing deep brain stimulation consider postoperative imaging (MRI/ CT) to analyse the position of each electrode contact. The artefact of the electrode Activa 3389 has been described for MR imaging but not for CT. We present the electrode artefact analysis from CT imaging in order to provide information on the artefact dimensions and on the related electrode contact positions.
Methods: The electrode was fixed on a phantom in a defined position and six acquisitions were performed (in-vitro study). The artefacts were compared to the real electrode position. Ten postoperative acquisitions were analyzed (in-vivo analysis). We measured: H (Height of the lateral black artefact), D (Distance between the beginning of the white and the lateral black artefacts) and W (maximal artefact width), representing respectively the lengths of the four contacts and of the electrode tip and the width of the contact zone. A student t-test compared the results: in-vivo versus in-vitro; coronal versus sagittal reconstructions along the electrode.
Findings: The limits of the lateral black artefact around the electrode contacts corresponded to the final electrode position. No significant difference existed for D (in-vivo, 1.1 ± 0.1 mm; in-vitro, 1.2 ± 0.2 mm; p=0.213) while W and H slightly differed (in-vivo, W=3.3 ± 0.2 mm, H=7.7 ± 0.2 mm; in-vitro, W=3.1 ± 0.1 mm, H=7.5 ± 0.2 mm). Results obtained with sagittal and coronal reconstructions were similar (p>0.6).
Conclusions: Precise 3D localization of the 4-contact zone of the electrode is provided by CT identification of the limits of the lateral black artefact. The relative position of the four contacts is deduced given the size of the contacts and the inter contact distance. Sagittal and coronal reconstructions along the electrode direction should be considered for the identification of the four electrode contacts. CT represents an interesting alternative to postoperative MRI.
Abstract: BACKGROUND: Severe, refractory obsessive-compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option. METHODS: In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests. RESULTS: After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [+/-SD], 19+/-8 vs. 28+/-7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56+/-14 vs. 43+/-8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events. CONCLUSIONS: These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.)
Abstract: Windup is a progressive, frequency-dependent increase in the excitability of trigeminal and spinal dorsal horn wide dynamic range (WDR) nociceptive neurons to repetitive stimulation of primary afferent nociceptive C-fibers. Superficial dorsal horn neurokinin 1 receptor (NK1R)-expressing neurons were recently shown to regulate sensitization of WDR nociceptive neurons through activation of a defined spino-bulbo-spinal loop. However, the windup of WDR nociceptive neurons was not regulated through this loop. In the present study, we sought to identify the alternative circuit activated by dorsal horn NK1Rs that mediates WDR neuron windup. As a model we used the rat spinal trigeminal nucleus, in which the subnucleus oralis (Sp5O) contains a pool of WDR neurons that receive their nociceptive C-input indirectly via interneurons located in the medullary dorsal horn (MDH). First, we found that intravenous injection of NK1R antagonists (SR140333 and RP67580) produced a reversible inhibition of Sp5O WDR neuron windup. Second, we anatomically identified in the MDH lamina III a subpopulation of NK1R-expressing local interneurons that relay nociceptive information from the MDH to downstream Sp5O neurons. Third, using microinjections of NK1R antagonists during in vivo electrophysiological recordings from Sp5O WDR neurons, we showed that WDR neuron windup depends on activation of NK1Rs located in the MDH laminae I-III. We conclude that, in contrast to central sensitization that is controlled by a spino-bulbo-spinal loop, Sp5O WDR neuron windup is regulated through a local circuit activated by MDH lamina III NK1Rs.
Abstract: Object In deep brain stimulation, the anatomic positions of electrode contact centers are used as the basis for analysis. We propose a new semi-quantitative approach (contact membership concept) considering patient’s individual anatomy, contact size, and extent of involvement of STN and neighboring structures.
Materials and methods In ten bilaterally operated and improved Parkinsonian patients, effective contact positions (contacts used for monopolar stimulation) were analyzed. The position of the contact center (classical binary approach: each center assigned, 1, or not, 0, to a given structure) and of the contact in its dimension (contact membership concept: membership degree, ordinal values from 0 to 1, assigned to each anatomic structure according to extent of involvement) were compared for the whole patient group and, individually, for each patient.
Results The membership concept revealed that for 13 out of 20 contacts, more than one structure was involved, where the classical binary approach assigned only one structure. For both approaches lateral STN, zona incerta and H1 (Forel’s Field) were the main structures involved, but their frequencies of appearance differed.
Conclusion The membership concept allows detailed analysis of the anatomic contact position. In the future this approach could assist in correlating anatomy and clinical results for all electrode contacts (effective ones and clinically less efficient ones).
Abstract: Wind-up is a progressive, frequency-dependent increase in the excitability of trigeminal and spinal dorsal horn wide dynamic range (WDR) nociceptive neurons evoked by repetitive stimulation of primary afferent nociceptive C-fibres. The correlate of wind-up in humans is temporal summation, which is an increase in pain perception to repetitive constant nociceptive stimulation. Although wind-up is widely used as a tool for studying the processing of nociceptive information, including central sensitization, its actual role is still unknown. Here, we recorded from trigeminal WDR neurons using in vivo electrophysiological techniques in rats and assessed the wind-up phenomenon in response to stimuli of different intensities and frequencies. First, we found that the amplitude of C-evoked responses of WDR neurons to repetitive stimulation increased progressively to reach a peak, then consistently showed a stable or slightly decreasing plateau phase. Only the first phase of this time course fitted in with the wind-up description. Therefore, to assess wind-up, we measured a limited number of initial responses. Second, we showed that wind-up, i.e. the slope of the frequency-dependent increase in the response to C-fibre stimulation, was linearly correlated to the stimulus intensity. Intensities of brief C-fibre inputs were thus coded into frequencies of action potentials by second-order neurons through frequency-dependent potentiation of the evoked responses. Third, wind-up also occurred at stimulation intensities below the threshold for C-evoked responses in WDR neurons, suggesting that wind-up can amplify subthreshold C-fibre inputs to WDR neurons. This might account for the observation that sparse, subliminal, neuronal activity in nociceptors can become painful via central integration of neural responses. Altogether, the present results show that wind-up can provide trigeminal WDR neurons with the capability to encode the intensity of short-duration orofacial nociceptive stimuli and to detect subthreshold nociceptive input. Thus, not only may wind-up play a physiological role in trigeminal sensory processing, but its enhancement may also underlie the pathophysiology of chronic orofacial pain conditions.
Abstract: In this article, we briefly review the concept of brain mapping in stereotactic surgery taking into account recent advances in stereotactic imaging. The gold standard continues to rely on probabilistic and indirect targeting, relative to a stereotactic reference, i.e., mostly the anterior (AC) and the posterior (PC) commissures. The theoretical position of a target defined on an atlas is transposed into the stereotactic space of a patient's brain; final positioning depends on electrophysiological analysis. The method is also used to analyze final electrode or lesion position for a patient or group of patients, by projection on an atlas. Limitations are precision of definition of the AC-PC line, probabilistic location and reliability of the electrophysiological guidance. Advances in MR imaging, as from 1.5-T machines, make stereotactic references no longer mandatory and allow an anatomic mapping based on an individual patient's brain. Direct targeting is enabled by high-quality images, an advanced anatomic knowledge and dedicated surgical software. Labeling associated with manual segmentation can help for the position analysis along non-conventional, interpolated planes. Analysis of final electrode or lesion position, for a patient or group of patients, could benefit from the concept of membership, the attribution of a weighted membership degree to a contact or a structure according to its level of involvement. In the future, more powerful MRI machines, diffusion tensor imaging, tractography and computational modeling will further the understanding of anatomy and deep brain stimulation effects.
Abstract: Object Relationships between clinical effects, anatomy, and electrophysiology are not fully understood in DBS of the subthalamic region in Parkinson’s disease. We proposed an anatomic study based on direct image-guided stereotactic surgery with a multiple source data analysis.
Materials and Methods A manual anatomic mapping was realized on coronal 1.5-Tesla MRI of 15 patients. Biological data were collected under local anesthesia: the spontaneous neuron activities and the clinical efficiency and the appearance of adverse effects. They were related to relevant current values (mA), the benefit threshold (bt, minimal current leading an clear efficiency), the adverse effect threshold (at, minimal current leading an adverse effect) and the stimulation margin (sm = at − bt); they were matched with anatomy.
Results We found consistent relationships between anatomy and biological data. The optimal stimulation parameters (low bt + high sm) were noted in the dorsolateral STN. The highest spontaneous neuron activity was found in the ventromedial STN. Dorsolateral (sensorimotor) STN seems the main DBS effector. The highest spontaneous neuron activity seems related to the anterior (rostral) ventromedial (limbic) STN.
Conclusion 1.5 Tesla images provide sufficiently detailed subthalamic anatomy for image-guided stereotactic surgery and may aid in understanding DBS mechanisms.
Abstract: The subthalamic nucleus (STN) is the main target of deep brain stimulation (DBS) treatment for severe idiopathic Parkinson's disease. But there is still no clear information on the location of the effective contacts (used during the chronic phase of stimulation). Our aim was to assess the anatomical structures of the subthalamic area (STA) involved during chronic DBS. Ten patients successfully treated were included. The surgical procedure was based on direct STN targeting (stereotactic MRI based) pondered by the acute effects of intraoperative stimulation. We used a formaldehyde-fixed human specimen to compare by matching MRI images obtained at 1.5 Tesla (performed in clinical stereotactic conditions) and at very high field at 4.7 Tesla. This allowed accurate analysis of the anatomy of the STA and retrospective precision of the location of the center of effective contacts which were located within the STN in 4 patients, at the interface between the STN and the ZI and/or FF in 13, at the interface between ZI and FF in 2 and between the STN and the substantia nigra in one. These results were consistent with the literature, revealing the implication of neighboring structures, especially the zona incerta and Forel's Field, in the clinical benefit.
Abstract: Activation of afferent nociceptive pathways is subject to activity-dependent plasticity, which may manifest as windup, a progressive increase in the response of dorsal horn nociceptive neurons to repeated stimuli. At the cellular level, N-methyl-d-aspartate (NMDA) receptor activation by glutamate released from nociceptive C-afferent terminals is currently thought to generate windup. Most of the wide dynamic range nociceptive neurons that display windup, however, do not receive direct C-fibre input. It is thus unknown where the NMDA mechanisms for windup operate. Here, using the Sprague-Dawley rat trigeminal system as a model, we anatomically identify a subpopulation of interneurons that relay nociceptive information from the superficial dorsal horn where C-fibres terminate, to downstream wide dynamic range nociceptive neurons. Using in vivo electrophysiological recordings, we show that at the end of this pathway, windup was reduced (24 +/- 6%, n = 7) by the NMDA receptor antagonist AP-5 (2.0 fmol) and enhanced (62 +/- 19%, n = 12) by NMDA (1 nmol). In contrast, microinjections of AP-5 (1.0 fmol) within the superficial laminae increased windup (83 +/- 44%, n = 9), whereas NMDA dose dependently decreased windup (n = 19).These results indicate that NMDA receptor function at the segmental level depends on their precise location in nociceptive neural networks. While some NMDA receptors actually amplify pain information, the new evidence for NMDA dependent inhibition of windup we show here indicates that, simultaneously, others act in the opposite direction. Working together, the two mechanisms may provide a fine tuning of gain in pain.
Abstract: We have developed a new phosphorescent probe, PdTCPPNa(4), whose luminescence properties are affected by local variations of intracellular oxygen tension (PO(2)). Spectrofluorometric measurements on living human umbilical venous endothelial cells loaded with this molecule show that a decrease in extracellular oxygen tension induces a decrease of PO(2), illustrating the phenomenon of oxygen diffusion and validating the use of this probe in living cells. Moreover, KCN- or 2,4-dinitrophenol-induced modifications of respiration do not lead to detectable PO(2) variations, probably because O(2) diffusion is sufficient to allow oxygen supply. On the contrary, activation by acetylcholine or endothelial nitric oxide synthase (eNOS), which produces NO while consuming oxygen, induces a significant decrease in PO(2), whose amplitude is dependent on the acetylcholine dose, i.e., the eNOS activity level. Hence, activated cytosolic enzymes could consume high levels of oxygen which cannot be supplied by diffusion, leading to PO(2) decrease. Other cell physiology mechanisms leading to PO(2) variations can now be studied in living cells with this probe.
Abstract: OBJECTIVE: To characterise subthalamic neuronal activity in OCD patients, in comparison to patients with Parkinson's disease (PD), and its relationship to the severity of obsessions and compulsions. BACKGROUND: Modifications in the function and connectivity of the brain's corticostriatal systems have been reported in patients with obsessive-compulsive disorder (OCD). However, changes in the basal ganglia neuronal activity in relation to the severity of OCD have never been adequately elucidated. DESIGN/METHODS: Twelve patients with OCD and 12 patients with PD operated for subthalamic stimulation were included. Resting-state subthalamic single-unit neuronal activity was recorded during surgery. Recorded neurons were located with precision and mapped according to the motor, associative and limbic subdivisions of the subthalamic nucleus. Discharge frequency, pattern, bursting and oscillatory activities were characterized for each recorded neuron and compared between OCD and PD patients. Correlations with the severity of symptoms in OCD patients were explored. RESULTS: One hundred and thirty-seven subthalamic neurons were isolated and recorded in OCD patients and 173 subthalamic neurons in PD patients. Between groups, OCD patients had lower STN neuronal discharge frequency, with a similar fraction of subthalamic neurons exhibiting burst-type activity. Significant oscillatory activity was present in 46% and 68% of neurons in OCD and PD patients, respectively; predominantly in the low frequency band (1-8 Hz). In OCD patients, abnormal subthalamic neuronal activity was mainly observed in the associative-limbic part of the subthalamic nucleus. Additionally, OCD patients with more severe symptoms exhibited subthalamic neuronal activity with a higher proportion of bursts, intraburst frequency, proportion of low frequency oscillatory activity. CONCLUSIONS: Heightened burst and low frequency oscillatory activities in the associative limbic subthalamic subdivision demonstrate its involvement in the pathophysiology of OCD. Supported by: Grants Assistance-Publique Hpitaux de Paris (APHP, P030422); Fondation pour la Recherche sur le Cerveau (FRC 2008), Agence Nationale pour la Recherche (N ANR-06-NEURO-006-01, BG EMO/PATH 2006-2010).
Abstract: Objective: Study the subthalamic (STN) neuronal activity in
patients with Obsessive Compulsive Disorders (OCD).
Background: Dysfunction in the basal ganglia circuitry has been
implicated in obsessive and compulsive disorder (OCD). In a recent
clinical research program, high frequency electrical stimulation of the
STN has proved to be efficient in alleviating obsessions and compulsions in OCD patients and permitted to study neuronal activity in
this disorder (Mallet et al, 2008).
Methods: Unit neuronal activity of STN neurons were recorded in
awake OCD patients at rest and compared to data obtained in
patients with Parkinson’s disease (PD). The mean firing rate and
interspike intervals were calculated for each cell. The firing pattern
was classified as regular, irregular or bursting (Kaneoke and Vitek,
1996). Neuronal activity was also sampled for each period and
epochs of elevated discharge rate were classified as burst using a
Poisson surprise analysis. Spike trains with S ‡ 3 were considered to
be bursts. Percentages of action potentials and duration with S ‡ 3
and mean S value were calculated for each cell. The precise localization
of neuronal activity recordings was performed using a 3-D deformable
basal ganglia atlas with a particular reference to STN subterritories.
Results: 156 STN neurons were isolated in 11 OCD patients and
113 neurons in 10 PD patients. In comparison to PD, the mean discharge
frequency of STN neurons was lower in OCD patient (24.1 6
14.1 Hz vs 32.16 17.7 Hz, P<10-3) with a higher burst type activity
(p<0.03). The mean S value was higher in OCD patients (7.0 6 3.5
vs 5.9 6 1.9, P<10-2) with a higher mean percentage of action
potentials (39.0 6 13.5 vs 32.8 6 14.4 %, P<10-3) and duration
with S ‡ 3 (17.7 6 4.7 vs 14.9 6 5.6 %, P<10-4).
Conclusions: In OCD patients, the subthalamic neuronal activity
seems abnormal with an increase in the bursting type activity. This is
in line with the hypothesis of the role of basal ganglia, and the subthalamic
nucleus, in the physiopathology of this disorder. Mallet
et al, N Engl J Med, 2008 Nov 13;359:2121-34. Kaneoke and Vitek,
J Neurosci Methods, 1996 Oct;68:211-23.
Abstract: Objective: To study the role of the subthalamic nucleus (STN) in
the processing of cognitive information during checking behaviour in
patients with obsessive compulsive behaviour (OCD).
Background: Human behavior depends on complex interactions
between cognition and emotion. How does the brain combine these
two dimensions to make a decision and elaborate a goal-directed
action remains unclear. One hypothesis is that such an integrative
process might occur owing to the convergence of information
through the basal ganglia. Recently, the associative and limbic STN
have been proposed as potential targets for deep brain stimulation in
patients with medically-resistant form of OCD1. We took the opportunity
of the last study to investigate the role of STN neurons in the
processing of cognitive information.
Methods: We used an instrumental task (CT), adapted from a
matching to sample-task, that specifically offered the opportunity to
verify once one subject has made a choice2. Single unit neuronal activity
was recorded in the STN whereas patients with obsessive compulsive
disorders (OCD) performed the CT.
Results: Among 125 single neurons recorded during task performance,
45 (36%) were task-related. Modifications of activity were
observed in relation with: visual information during the study phase
(28%), the choice phase (22%), or the checking phase (20%), movement execution during the choice phase (37%), or the checking phase
(35%) and during the evaluation phase at the end of the task (56%).
We found that STN neurons frequently responded in a polymodal
manner to cognitive, premotor and emotional events. Moreover, discharge
frequency was influenced by checking behavior.
Conclusions: These results suggest that STN neurons process multiple
sources of information in accordance with the model of information
convergence within the basal ganglia. They also demonstrate
that the STN play a part in the physiology of doubt, a critical feature
of OCD pathophysiology. 1. Mallet L, et al. STOC Study Group. N
Engl J Med. 2008 Nov 13;359(20):2121-34. 2. Rotge JY, et al., Acta
Psychiatr Scand. 2008 Jun;117(6):465-73.
Abstract: Objective. A somatotopy inside the human globus pallidus (GP),
based on intraoperative microelectrode-recordings during passive
or active movement, and on clinical results of deep brain stimulation
(DBS) in movement disorders, has been reported. We aimed to
report a GP somatotopy, observed in one parkinsonian patient
based on dystonic motor side effect assessment during acute stimulation,
and related to MRI anatomy.
Methods. A 68 year old parkinsonian (female, 16-year history;
suffering mainly from limb and trunk dyskinesia) underwent bilateral
stereotactic DBS surgery in internal GP (GPi) based on
LVIII D. A. Bosch et al.
direct MRI targeting. We identified the different GP parts on T2-
weighted coronal slices: external GP (GPe) and lateral and medial
subdivisions of GPi (GPil, GPim). Controlateral dystonic movements
were noted during acute intraoperative stimulation under
local anaesthesia (1 or 2mm step; mean current 0.97 +/- 0.14mA)
along the distal 10mm on 3 parallel tracts (2mm distant; left
hemisphere: central, lateral and medial; right hemisphere: central,
anterior and lateral). On the 6 tracts (45 GP checkpoints), the
involved body parts (face, upper and lower limbs) were matched
with the anatomic structures. Postoperatively, chronic DBS dramatically
improved dyskinesia (electrodes implanted on the central
tracks).
Results. GPe, GPil and GPim seemed to be characterized by
a segregated body map. We found inside each structure a rostrocaudal
organisation: face, superior part; upper limb, intermediate
part; lower limb, inferior part.
Conclusions. Motor side effect analysis is an interesting tool for
somatotopic investigations. The GP somatotopy related to these
clinical conditions has to be confirmed.
Abstract: Objective. In the subthalamic area, the subthalamic nucleus (STN)
is the main target for deep brain stimulation (DBS) in idiopathic
VI D. A. Bosch et al.
Parkinson’s disease (PD). We aimed at analysing relationships
between the MRI anatomy and spontaneous neuronal activity in
order to confirm the potential of microelectrode recording to assist
in the determination of the optimal surgical target.
Methods. Thirty trajectories were analysed. Procedures (8 bilateral
surgeries) were performed under local anaesthesia after identification
on 1.5T MRI (T2 weighted) of anatomical structures, STN,
above STN (zona incerta, forel’s fields) and substantia nigra (SN).
Spontaneous neuronal activity was recorded (30 seconds, 0.5mm
step), simultaneously along the distal 10mm on a central (covering
optimally STN) and on a 2mm anterior track. Intra operative
X-Ray controls checked that the exploration tracts followed the
planed trajectories. Chronic DBS (on central tract 14 times out
of 16) dramatically improved PD. We calculated cell numbers and
mean firing rates (MFR, average firing on 30 seconds) on 276 isolated
neurons (after threshold and principal component analysis)
regrouped according to anatomical structures. MFR were compared
with a non parametric statistical test.
Results. 60% of spontaneously active cells were in the dorsal
and lateral STN. MFR increased entering STN and SN (p<0.03):
5.88 +/- 1.06 spike.sec-1 above STN; 9.23 +/- 1.22 spike.sec-1 in
STN; 14.46 +/- 2.32 spike.sec-1 in SN.
Conclusions. Anatomical boundaries and unitary recordings
seem to be linked. We found a maximum number of spontaneously
active neurons in the dorsal and lateral STN which is also known
as a good surgical target for DBS in severe PD.
