Julie Anne Peron

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

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.

Subthalamic nucleus stimulation in Parkinson disease induces apathy A PET study

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.

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.

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

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.

Subthalamic nucleus: A key structure for emotional component synchronization in humans

Affective neuroscience is concerned with identifying the neural bases of emotion. For historical and methodological reasons, models describing the brain architecture that supports emotional processes in humans have tended to neglect the basal ganglia, focusing instead on cortical and amygdalar mechanisms. Now, however, deep brain stimulation (DBS) of the subthalamic nucleus (STN), a neurosurgical treatment for Parkinsons disease and obsessive-compulsive disorder, is helping researchers explore the possible functional role of this particular basal ganglion in emotional processes. After reviewing studies that have used DBS in this way, we propose a model in which the STN plays a crucial role in producing temporally organized neural co-activation patterns at the cortical and subcortical levels that are essential for generating emotions and related feelings.

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.

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

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.

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.

Major depressive disorder skews the recognition of emotional prosody.

OBJECTIVE Major depressive disorder (MDD) is associated with abnormalities in the recognition of emotional stimuli. MDD patients ascribe more negative emotion but also less positive emotion to facial expressions, suggesting blunted responsiveness to positive emotional stimuli. To ascertain whether these emotional biases are modality-specific, we examined the effects of MDD on the recognition of emotions from voices using a paradigm designed to capture subtle effects of biases. METHODS Twenty-one MDD patients and 21 healthy controls (HC) underwent clinical and neuropsychological assessments, followed by a paradigm featuring pseudowords spoken by actors in five types of emotional prosody, rated on continuous scales. RESULTS Overall, MDD patients performed more poorly than HC, displaying significantly impaired recognition of fear, happiness and sadness. Compared with HC, they rated fear significantly more highly when listening to anger stimuli. They also displayed a bias toward surprise, rating it far higher when they heard sad or fearful utterances. Furthermore, for happiness stimuli, MDD patients gave higher ratings for negative emotions (fear and sadness). A multiple regression model on recognition of emotional prosody in MDD patients showed that the best fit was achieved using the executive functioning (categorical fluency, number of errors in the MCST, and TMT B-A) and the total score of the Montgomery-Asberg Depression Rating Scale. CONCLUSIONS Impaired recognition of emotions would appear not to be specific to the visual modality but to be present also when emotions are expressed vocally, this impairment being related to depression severity and dysexecutive syndrome. MDD seems to skew the recognition of emotional prosody toward negative emotional stimuli and the blunting of positive emotion appears not to be restricted to the visual modality.

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.