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Featured researches published by Claire Haegelen.


Journal of Neurology | 2006

Does subthalamic nucleus stimulation induce apathy in Parkinson’s disease?

Dominique Drapier; Sophie Drapier; Paul Sauleau; Claire Haegelen; Sylvie Raoul; Isabelle Biseul; Julie Anne Peron; François Lallement; I. Rivier; Jean-Michel Reymann; G. Edan; Marc Vérin; Bruno Millet

BackgroundSubthalamic Nucleus Deep Brain Stimulation (STN-DBS) has been shown to significantly improve motor symptoms in advanced Parkinson’s disease (PD). Only few studies, however, have focused on the non-motor effects of DBS.MethodsA consecutive series of 15 patients was assessed three months before (M-3), then three months (M3) and six months (M6) after surgery. Mean (± SD) age at surgery was 59.7 (7.6). Mean disease duration at surgery was 12.2 (2.8) years. The Mini International Neuropsychiatric Inventory was used to assess psychiatric disorders three months before surgery. Depression was evaluated using Montgomery and Asberg Rating Scale (MADRS). Anxiety was evaluated using the AMDP system (Association for Methodology and Documentation in Psychiatry). Apathy was particularly evaluated using the Apathy Evaluation Scale (AES) and the Starkstein Scale. All these scales were performed at every evaluation.ResultsApathy worsened at M3 and M6 after STN-DBS in comparison with the preoperative evaluation: the AES mean score was significantly impaired between the preoperative (38.4±7.1) and both the postoperative M3 (44.6±9.5, p = 0.003) and M6 scores (46.0±10.9, p = 0.013). Significant worsening of apathy was confirmed using the Starkstein scale. There was no evidence of depression: the mean MADRS score did not differ before surgery (9.1±7.4) and at both M3 (8.6±8.2) and M6 (9.9±7.7) after STN-DBS. The anxiety level did not change between preoperative (9.4±9.2) and both M3 (5.5±4.5) and M6 (6.6±4.6) postoperative states.ConclusionAlthough STN-DBS constitutes a therapeutic advance for severely disabled patients with Parkinson’s disease, we should keep in mind that this surgical procedure may contribute to the inducing of apathy. Our observation raises the issue of the direct influence of STN- DBS on the limbic system by diffusion of stimulus to the medial limbic compartment of STN.


Neurology | 2009

Subthalamic nucleus stimulation in Parkinson disease induces apathy A PET study

F. Le Jeune; Dominique Drapier; Aurélie Bourguignon; Julie Anne Peron; H. Mesbah; Sophie Drapier; Paul Sauleau; Claire Haegelen; David Travers; E. Garin; C.-H. Malbert; Bruno Millet; Marc Vérin

Objective: Apathy may be induced by subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease (PD). We therefore wished to test the hypothesis that apathy induced by STN-DBS correlates with changes in glucose metabolism, using 18FDG-PET. Methods: Twelve patients with PD were assessed 3 months before (M−3) and 3 months after (M+3) STN-DBS with 18FDG-PET and the Apathy Evaluation Scale. Results: Apathy had significantly worsened at M+3 after STN-DBS. Positive correlations were observed between this variation in apathy scores and changes in glucose metabolism, especially in the right frontal middle gyrus (Brodmann area [BA] 10) and right inferior frontal gyrus (BA 46 and BA 47). Negative correlations between the two were observed in the right posterior cingulate gyrus (BA 31) and left medial frontal lobe (BA 9). Conclusion: These preliminary results confirm the role of the subthalamic nucleus in associative and limbic circuitry in humans and suggest that it is a key basal ganglia structure in motivation circuitry.


Neuropsychologia | 2005

Fear recognition is impaired by subthalamic nucleus stimulation in Parkinson's disease.

Isabelle Biseul; Paul Sauleau; Claire Haegelen; Pascale Trebon; Dominique Drapier; Sylvie Raoul; Sophie Drapier; François Lallement; Isabelle Rivier; Youenn Lajat; Marc Vérin

Behavioural disturbances such as disorders of mood, apathy or indifference are often observed in Parkinsons disease (PD) patients with chronic high frequency deep brain stimulation of subthalamic nucleus (STN DBS). Neuropsychological modifications causing these adverse events induced by STN DBS remain unknown, even if limbic disturbances are hypothesised. The limbic system supports neural circuits processing emotional information. The aim of this work is to evaluate changes of emotional recognition in PD patients induced by STN DBS. Thirty PD patients were assessed using a computerised paradigm of recognition of emotional facial expressions [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto, CA: Consulting Psychologists Press], 15 before STN DBS and 15 after. The two patients groups were compared to a group of 15 healthy control subjects. One series of 55 pictures of emotional facial expressions was presented to each patient. Patients had to classify the pictures according to seven basic emotions (happiness, sadness, fear, surprise, disgust, anger and no emotion). The intact ability to percept faces was firstly assured using the Benton Recognition Test. Recognition of fear expressions was significantly and selectively reduced in the post-operative group in comparison to both pre-operative and control groups. Our results demonstrate for the first time a selective reduction of recognition of facial expressions of fear by STN DBS. This impairment could be the first neuropsychological marker of a more general limbic dysfunction, thought to be responsible for the behavioural disorders reported after STN DBS.


Brain | 2008

Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a pet study

F. Le Jeune; Julie Anne Peron; Isabelle Biseul; S. Fournier; Paul Sauleau; Sophie Drapier; Claire Haegelen; Dominique Drapier; Bruno Millet; E. Garin; J.-Y. Herry; C.-H. Malbert; Marc Vérin

Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) in Parkinsons disease is thought to produce adverse events such as emotional disorders, and in a recent study, we found fear recognition to be impaired as a result. These changes have been attributed to disturbance of the STNs limbic territory and would appear to confirm that the negative emotion recognition network passes through the STN. In addition, it is now widely acknowledged that damage to the orbitofrontal cortex (OFC), especially the right side, can result in impaired recognition of facial emotions (RFE). In this context, we hypothesized that this reduced recognition of fear is correlated with modifications in the cerebral glucose metabolism of the right OFC. The objective of the present study was first, to reinforce our previous results by demonstrating reduced fear recognition in our Parkinsons disease patient group following STN DBS and, second, to correlate these emotional performances with glucose metabolism using 18FDG-PET. The 18FDG-PET and RFE tasks were both performed by a cohort of 13 Parkinsons disease patients 3 months before and 3 months after surgery for STN DBS. As predicted, we observed a significant reduction in fear recognition following surgery and obtained a positive correlation between these neuropsychological results and changes in glucose metabolism, especially in the right OFC. These results confirm the role of the STN as a key basal ganglia structure in limbic circuits.


Neuropsychologia | 2008

Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson's disease have separate neural substrates

Dominique Drapier; Julie Anne Peron; Emmanuelle Leray; Paul Sauleau; Isabelle Biseul; Sophie Drapier; F. Le Jeune; David Travers; Aurélie Bourguignon; Claire Haegelen; Bruno Millet; Marc Vérin

OBJECTIVE To test the hypothesis that emotion recognition and apathy share the same functional circuit involving the subthalamic nucleus (STN). METHODS A consecutive series of 17 patients with advanced Parkinsons disease (PD) was assessed 3 months before (M-3) and 3 months (M+3) after STN deep brain stimulation (DBS). Mean (+/-S.D.) age at surgery was 56.9 (8.7) years. Mean disease duration at surgery was 11.8 (2.6) years. Apathy was measured using the Apathy Evaluation Scale (AES) at both M-3 and M3. Patients were also assessed using a computerised paradigm of facial emotion recognition [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto: Consulting Psychologist Press] before and after STN DBS. Prior to this, the Benton Facial Recognition Test was used to check that the ability to perceive faces was intact. RESULTS Apathy had significantly worsened at M3 (42.5+/-8.9, p=0.006) after STN-DBS, in relation to the preoperative assessment (37.2+/-5.5). There was also a significant reduction in recognition percentages for facial expressions of fear (43.1%+/-22.9 vs. 61.6%+/-21.4, p=0.022) and sadness (52.7%+/-19.1 vs. 67.6%+/-22.8, p=0.031) after STN DBS. However, the postoperative worsening of apathy and emotion recognition impairment were not correlated. CONCLUSIONS Our results confirm that the STN is involved in both the apathy and emotion recognition networks. However, the absence of any correlation between apathy and emotion recognition impairment suggests that the worsening of apathy following surgery could not be explained by a lack of facial emotion recognition and that its behavioural and cognitive components should therefore also be taken into consideration.


Lancet Neurology | 2015

Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study

Lars Timmermann; Roshini Jain; Lilly Chen; Mohamed Maarouf; Michael T. Barbe; Niels Allert; Thomas Brücke; Iris Kaiser; Sebastian Beirer; Fernando Sejio; Esther Suarez; Beatriz Lozano; Claire Haegelen; Marc Vérin; Mauro Porta; Domenico Servello; Steven S. Gill; Alan L Whone; Nic Van Dyck; François Alesch

BACKGROUND High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinsons disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinsons disease. METHODS We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinsons disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinsons disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. FINDINGS Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure. 125 adverse events were reported, the most frequent of which were dystonia, speech disorder, and apathy. 18 serious adverse events were recorded, three of which were attributed to the device or procedure (one case each of infection, migration, and respiratory depression). All serious adverse events resolved without residual effects and stimulation remained on during the study. INTERPRETATION The multiple-source, constant-current, eight-contact DBS system suppressed motor symptoms effectively in patients with Parkinsons disease, with an acceptable safety profile. Future trials are needed to investigate systematically the potential benefits of this system on postoperative outcome and its side-effects. FUNDING Boston Scientific.


Neuropsychologia | 2010

Recognition of emotional prosody is altered after subthalamic nucleus deep brain stimulation in Parkinson's disease.

Julie Anne Peron; Didier Maurice Grandjean; Florence Le Jeune; Paul Sauleau; Claire Haegelen; Dominique Drapier; Tiphaine Rouaud; Sophie Drapier; Marc Vérin

The recognition of facial emotions is impaired following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinsons disease (PD). These changes have been linked to a disturbance in the STNs limbic territory, which is thought to be involved in emotional processing. This was confirmed by a recent PET study where these emotional modifications were correlated with changes in glucose metabolism in different brain regions, including the amygdala and the orbitofrontal regions that are well known for their involvement in emotional processing. Nevertheless, the question as to whether these emotional changes induced by STN DBS in PD are modality-specific has yet to be answered. The objective of this study was therefore to examine the effects of STN DBS in PD on the recognition of emotional prosody. An original emotional prosody paradigm was administered to twenty-one post-operative PD patients, twenty-one pre-operative PD patients and twenty-one matched controls. Results showed that both the pre- and post-operative groups differed from the healthy controls. There was also a significant difference between the pre and post groups. More specifically, an analysis of their continuous judgments revealed that the performance of the post-operative group compared with that of the other two groups was characterized by a systematic emotional bias whereby they perceived emotions more strongly. These results suggest that the impaired recognition of emotions may not be specific to the visual modality but may also be present when emotions are expressed through the human voice, implying the involvement of the STN in the brain network underlying the recognition of emotional prosody.


Neuropsychology (journal) | 2010

Subthalamic nucleus stimulation affects fear and sadness recognition in Parkinson's disease.

Julie Anne Peron; Isabelle Biseul; Emmanuelle Leray; Siobhan Vicente; Florence Le Jeune; Sophie Drapier; Dominique Drapier; Paul Sauleau; Claire Haegelen; Marc Vérin

Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinsons disease (PD) can produce emotional disorders that have been linked to disturbance of the STNs limbic territory. The aim of this study was to confirm the impairment of the recognition of facial emotions (RFE) induced by STN DBS, not only ruling out the effect of the diseases natural progression in relation to the effect of DBS, but also assessing the influence of modifications in dopamine replacement therapy (DRT) following STN DBS. RFE was investigated in 24 PD patients who underwent STN DBS and 20 PD patients treated with apomorphine. They were assessed 3 months before and after treatment. The 2 patient groups were compared with a group of 30 healthy matched controls. The results showed that RFE for negative emotions (fear and sadness) was impaired in only the STN DBS group in the posttreatment condition and was unrelated to DRT. Results confirm the selective reduction of RFE induced by STN DBS, due neither to the diseases natural progression nor to modifications in DRT.


European Journal of Nuclear Medicine and Molecular Imaging | 2010

Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

Florence Le Jeune; Julie Anne Peron; Didier Maurice Grandjean; Sophie Drapier; Claire Haegelen; Etienne Garin; Bruno Millet; Marc Vérin

PurposeAlthough high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson’s disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN’s functional role and explain neuropsychological modifications following STN DBS in PD.MethodsWe studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using 18F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS.ResultsThe first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits.ConclusionThese metabolic results confirm the STN’s central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure’s functional role.


PLOS ONE | 2010

Subthalamic Nucleus Stimulation Affects Theory of Mind Network: A PET Study in Parkinson's Disease

Julie Anne Peron; Florence Le Jeune; Claire Haegelen; Thibaut Dondaine; Dominique Drapier; Paul Sauleau; Jean-Michel Reymann; Sophie Drapier; Tiphaine Rouaud; Bruno Millet; Marc Vérin

Background There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinsons disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism. Methodology/Principal Findings To this end, we conducted 18FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucose metabolism and impaired ToM in several cortical areas: the bilateral cingulate gyrus (BA 31), right middle frontal gyrus (BA 8, 9 and 10), left middle frontal gyrus (BA 6), temporal lobe (fusiform gyrus, BA 20), bilateral parietal lobe (right BA 3 and right and left BA 7) and bilateral occipital lobe (BA 19). There were also correlations between increased cerebral glucose metabolism and impaired ToM in the left superior temporal gyrus (BA 22), left inferior frontal gyrus (BA 13 and BA 47) and right inferior frontal gyrus (BA 47). All these structures overlap with the brain network that mediates ToM. Conclusion/Significance These results seem to confirm that STN DBS hinders the ability to infer the mental states of others and modulates a distributed network known to subtend ToM.

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