Florence Le Jeune

Predictive Value of 18F-FDG PET and Somatostatin Receptor Scintigraphy in Patients with Metastatic Endocrine Tumors

The treatment of metastatic neuroendocrine tumors depends on the aggressiveness of the disease. We wanted to know whether 18F-FDG PET and somatostatin receptor scintigraphy (SRS) can predict early disease progression and patient survival. Methods: We undertook a prospective study of patients with metastatic neuroendocrine tumor diagnosed between September 2003 and January 2006. After obtaining signed informed consent from the patients, we performed CT, SRS, and 18F-FDG PET and reviewed histologic data. CT was repeated every 3 mo to assess the risk of early progressive disease (first 6 mo), progression-free survival, and overall survival. Results: Thirty-eight patients (mean age, 60 ± 15 y) were included. Histologically, 4 patients had a high-grade and 34 a low-grade tumor. The results of 18F-FDG PET and SRS were positive in 15 and 27 patients. The 2-y overall survival and progression-free survival were 73% and 45%; 16 patients had early progressive disease. Most 18F-FDG PET–positive patients had early progressive disease (14/15, vs. 2/23 18F-FDG PET–negative patients), and most SRS-negative patients had early progressive disease (9/11, vs. 7/27 SRS-positive patients); 18F-FDG PET gave excellent negative and positive predictive values of 91% and 93%; 18F-FDG PET results correlated with progression-free survival (P < 0.001) and overall survival (P < 0.001) even when only low-grade tumors were considered. SRS was associated with progression-free survival (P < 0.001) and overall survival (P < 0.03). At multivariate analysis, only 18F-FDG PET was predictive of progression-free survival. Conclusion: 18F-FDG PET exhibits excellent predictive values for early tumor progression. 18F-FDG PET and SRS results correlate with progression-free survival and overall survival even for histologically low-grade tumors. These explorations could be included in the initial work-up for metastatic neuroendocrine tumor.

Emotional Processing in Parkinson’s Disease: A Systematic Review

Parkinsons disease provides a useful model for studying the neural substrates of emotional processing. The striato‐thalamo‐cortical circuits, like the mesolimbic dopamine system that modulates their function, are thought to be involved in emotional processing. As Parkinsons disease is histopathologically characterized by the selective, progressive, and chronic degeneration of the nigrostriatal and mesocorticolimbic dopamine systems, it can therefore serve as a model for assessing the functional role of these circuits in humans. In the present review, we begin by providing a synopsis of the emotional disturbances observed in Parkinsons disease. We then discuss the functional roles of the striato‐thalamo‐cortical and mesolimbic circuits, ending with the conclusion that both these pathways are indeed involved in emotional processing.

Apathy in patients with Parkinson disease without dementia or depression: A PET study

Objective: We sought to identify apathy metabolic bases in Parkinson disease (PD). Methods: A total of 45 patients with PD who were not clinically depressed (Montgomery-Åsberg Depression Rating Scale [MADRS] <21) and had no dementia (Mattis Dementia Rating Scale [MDRS] >130) were assessed with the Apathy Evaluation Scale (AES) and underwent a resting-state F-18 fluorodeoxyglucose PET (FDG-PET) scan. A motor assessment comprising the Unified Parkinsons Disease Rating Scale Part III (UPDRS-III) was conducted and total levodopa equivalent daily dose (LEDD) was calculated. Imaging data were analyzed with statistical parametric mapping. Age, LEDD, and MDRS scores were introduced as covariates. Results: Positive correlations were observed between the AES score and cerebral metabolism in the right inferior frontal gyrus (Brodmann area [BA] 47), right middle frontal gyrus (BA 10), right cuneus (BA 18), and right anterior insula (BA 13). Negative correlations were observed between the AES score and cerebellar metabolism in the semilunar lobules bilaterally, within the posterior lobe. Using an AES score equal to or above 42 to define clinical apathy, prevalence in our patient group was 17.8%. The AES score was negatively correlated with the MDRS score and positively correlated with the “retardation” subscore of the MADRS. It was not correlated with either UPDRS III or LEDD. Conclusions: Results indicate that the frontal, temporal, and cerebellar areas known to be involved in reward, emotion, and cognition are also implicated in apathy in patients with PD without dementia or depression. Their roles in the etiopathology of apathy are discussed.

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

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.

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

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.

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

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.

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

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.

Apathy and impaired emotional facial recognition networks overlap in Parkinson's disease: a PET study with conjunction analyses

Apathy is a disabling non-motor symptom that is frequently observed in Parkinsons disease (PD). Its description and physiopathology suggest that it is partially mediated by emotional impairment, but this research issue has never been addressed at a clinical and metabolic level. We therefore conducted a metabolic study using 18fluorodeoxyglucose positron emission tomography (18FDG PET) in 36 PD patients without depression and dementia. Apathy was assessed on the Apathy Evaluation Scale (AES), and emotional facial recognition (EFR) performances (ie, percentage of correct responses) were calculated for each patient. Confounding factors such as age, antiparkinsonian and antidepressant medication, global cognitive functions and depressive symptoms were controlled for. We found a significant negative correlation between AES scores and performances on the EFR task. The apathy network was characterised by increased metabolism within the left posterior cingulate (PC) cortex (Brodmann area (BA) 31). The impaired EFR network was characterised by decreased metabolism within the bilateral PC gyrus (BA 31), right superior frontal gyrus (BAs 10, 9 and 6) and left superior frontal gyrus (BA 10 and 11). By applying conjunction analyses to both networks, we identified the right premotor cortex (BA 6), right orbitofrontal cortex (BA 10), left middle frontal gyrus (BA 8) and left posterior cingulate gyrus (BA 31) as the structures supporting the association between apathy and impaired EFR. These results confirm that apathy in PD is partially mediated by impaired EFR, opening up new prospects for alleviating apathy in PD, such as emotional rehabilitation.

Preoperative factors of apathy in subthalamic stimulated Parkinson disease: A PET study

Objective: The current literature provides discrepant results regarding preoperative sociodemographic and clinical factors, and no information about preoperative cerebral metabolic patterns associated with apathy after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. Methods: To resolve this issue, we set out to identify preoperative metabolic patterns and sociodemographic and clinical factors associated with increased apathy after STN-DBS. Forty-four patients with Parkinson disease were enrolled in this study. They all underwent STN-DBS. Metabolic activity was assessed with F-18 fluorodeoxyglucose PET 3 months before surgery. Apathy was assessed on the Apathy Evaluation Scale 3 months before and after STN-DBS. We controlled for preoperative age, levodopa therapy, and overall cognitive functions. Results: Increased apathy after STN-DBS was significantly associated with reduced preoperative metabolism within the right ventral striatum. None of the sociodemographic and clinical variables tested were associated with apathy after STN-DBS. Conclusions: Preoperative PET, but not sociodemographic or clinical factors, is associated with apathy after STN-DBS.

Obsessive Compulsive Disorder Networks: Positron Emission Tomography and Neuropsychology Provide New Insights

Background Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. Methods and Findings This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state 18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. Conclusion As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes.