Jean-François Houvenaghel

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.

Does Facial Amimia Impact the Recognition of Facial Emotions? An EMG Study in Parkinson’s Disease

According to embodied simulation theory, understanding other people’s emotions is fostered by facial mimicry. However, studies assessing the effect of facial mimicry on the recognition of emotion are still controversial. In Parkinson’s disease (PD), one of the most distinctive clinical features is facial amimia, a reduction in facial expressiveness, but patients also show emotional disturbances. The present study used the pathological model of PD to examine the role of facial mimicry on emotion recognition by investigating EMG responses in PD patients during a facial emotion recognition task (anger, joy, neutral). Our results evidenced a significant decrease in facial mimicry for joy in PD, essentially linked to the absence of reaction of the zygomaticus major and the orbicularis oculi muscles in response to happy avatars, whereas facial mimicry for expressions of anger was relatively preserved. We also confirmed that PD patients were less accurate in recognizing positive and neutral facial expressions and highlighted a beneficial effect of facial mimicry on the recognition of emotion. We thus provide additional arguments for embodied simulation theory suggesting that facial mimicry is a potential lever for therapeutic actions in PD even if it seems not to be necessarily required in recognizing emotion as such.

Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit?

Objective The decrease in verbal fluency in patients with Parkinson’s disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS) is usually assumed to reflect a frontal lobe-related cognitive dysfunction, although evidence for this is lacking. Methods To explore its underlying mechanisms, we combined neuropsychological, psychiatric and motor assessments with an examination of brain metabolism using F-18 fluorodeoxyglucose positron emission tomography, in 26 patients with PD, 3 months before and after surgery. We divided these patients into two groups, depending on whether or not they exhibited a postoperative deterioration in either phonemic (10 patients) or semantic (8 patients) fluency. We then compared the STN-DBS groups with and without verbal deterioration on changes in clinical measures and brain metabolism. Results We did not find any neuropsychological change supporting the presence of an executive dysfunction in patients with a deficit in either phonemic or semantic fluency. Similarly, a comparison of patients with or without impaired fluency on brain metabolism failed to highlight any frontal areas involved in cognitive functions. However, greater changes in cognitive slowdown and apathy were observed in patients with a postoperative decrease in verbal fluency. Conclusions These results suggest that frontal lobe-related cognitive dysfunction could play only a minor role in the postoperative impairment of phonemic or semantic fluency, and that cognitive slowdown and apathy could have a more decisive influence. Furthermore, the phonemic and semantic impairments appeared to result from the disturbance of distinct mechanisms.

Weight gain following subthalamic nucleus deep brain stimulation: a PET study.

Several hypotheses have been put forward to explain weight gain after deep brain stimulation (DBS), but none provides a fully satisfactory account of this adverse effect. We analyzed the correlation between changes in brain metabolism (using positron emission tomography [PET] imaging) and weight gain after bilateral subthalamic nucleus DBS in patients with Parkinsons disease. Body mass index was calculated and brain activity prospectively measured using 2‐deoxy‐2[18F]fluoro‐D‐glucose 3 months before and 4 months after the start of subthalamic nucleus deep brain stimulation in 23 patients with Parkinsons disease. Motor complications (United Parkinsons Disease Rating Scale [UPDRS]‐IV scores) and dopaminergic medication were included in the analysis to control for their possible influence on brain metabolism. Mean ± standard deviation (SD) body mass index increased significantly by 0.8 ± 1.5 kg/m2 (P = 0.03). Correlations were found between weight gain and changes in brain metabolism in limbic and associative areas, including the orbitofrontal cortex (Brodmann areas [BAs] 10 and 11), lateral and medial parts of the temporal lobe (BAs 20, 21, 22,39 and 42), anterior cingulate cortex (BA 32), and retrosplenial cortex (BA 30). However, we found no correlation between weight gain and metabolic changes in sensorimotor areas. These findings suggest that changes in associative and limbic processes contribute to weight gain after subthalamic nucleus DBS in Parkinsons disease.

Vocal emotion decoding in the subthalamic nucleus: An intracranial ERP study in Parkinson’s disease

&NA; Using intracranial local field potential (LFP) recordings in patients with Parkinsons disease (PD) undergoing deep brain stimulation (DBS), we explored the electrophysiological activity of the subthalamic nucleus (STN) in response to emotional stimuli in the auditory modality. Previous studies focused on the influence of visual stimuli. To this end, we recorded LFPs within the STN in response to angry, happy, and neutral prosodies in 13 patients with PD who had just undergone implantation of DBS electrodes. We observed specific modulation of the right STN in response to anger and happiness, as opposed to neutral prosody, occurring at around 200–300 ms post‐onset, and later at around 850–950 ms post‐onset for anger and at around 3250–3350 ms post‐onset for happiness. Taken together with previous reports of modulated STN activity in response to emotional visual stimuli, the present results appear to confirm that the STN is involved in emotion processing irrespective of stimulus valence and sensory modality. Graphical abstract Figure. No caption available. HighlightsWe explored the STNs electrophysiological activity in response to auditory emotions.We recorded LFPs in 13 patients with Parkinsons disease who had undergone DBS.We observed a specific activity of the right STN in response to angry and happy voices.STN is involved in human emotion, irrespective of valence and sensory modality.

Apomorphine pump in advanced Parkinson's disease: Effects on motor and nonmotor symptoms with brain metabolism correlations.

INTRODUCTION Patients with advanced Parkinsons disease (PD) and contraindications for subthalamic nucleus deep brain stimulation (DBS) could particularly benefit from subcutaneous infusion therapy with apomorphine. This original study was designed to evaluate the general efficacy of add-on apomorphine in motor and nonmotor symptoms in advanced PD, while characterizing the changes induced in brain glucose metabolism. The aim was to look at the underlying anatomical-functional pathways. METHODS 12 patients with advanced PD were assessed before and after 6months of add-on apomorphine, using resting-state 18F-fluorodeoxyglucose positron emission tomography and exhaustive clinical assessments. RESULTS After 6months of therapy, oral treatment was significantly reduced. Both motor and nonmotor scores improved, with a beneficial effect on executive functions, quality of life and apathy. Significant metabolic changes were observed, with overall increases in the right fusiform gyrus and hippocampus, alongside a decrease in the left middle frontal gyrus. Consistent correlations between significant changes in clinical scores and metabolism were established. CONCLUSION Well tolerated, add-on apomorphine appears to be an interesting option for patients with fluctuations and contra-indications for DBS. Changes in brain metabolism, with beneficial effects on motor and nonmotor symptoms were observed after 6months. These preliminary results have to be confirmed by further studies.

Weight Gain following Pallidal Deep Brain Stimulation: A PET Study.

The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson’s disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target.

Evaluating Cognitive Action Control Using Eye-Movement Analysis: An Oculomotor Adaptation of the Simon Task.

Cognitive action control has been extensively studied using conflict tasks such as the Simon task. In most recent studies, this process has been investigated in the light of the dual route hypothesis and more specifically of the activation-suppression model using distributional analyses. Some authors have suggested that cognitive action control assessment is not specific to response modes. In this study we adapted the Simon task, using oculomotor responses instead of manual responses, in order to evaluate whether the resolution of conflict induced by a two-dimensional stimulus yielded similar results to what is usually reported in tasks with manual responses. Results obtained from 43 young healthy participants revealed the typical congruence effect, with longer reaction times (RT) and lesser accuracy in the incongruent condition. Conditional accuracy functions (CAF) also revealed a higher proportion of fast errors in the incongruent condition and delta plots confirmed that conflict resolution was easier, as the time taken to respond increased. These results are very similar to what has been reported in the literature. Furthermore, our observations are in line with the assumptions of the activation-suppression model, in which automatic activation in conflict situations is captured in the fastest responses and selective inhibition of cognitive action control needs time to build up. Altogether, our results suggest that conflict resolution has core mechanisms whatever the response mode, manual or oculomotor. Using oculomotor responses in such tasks could be of interest when investigating cognitive action control in patients with severe motor disorders.

Impulsive oculomotor action selection in Parkinson's disease.

ABSTRACT The effects of Parkinsons disease (PD) on the dynamics of impulsive action selection and suppression have recently been studied using distributional analyses, but with mixed results, especially for selection. Furthermore, some authors have suggested that impulsivity, regarded as a personality trait, shares common features with behavioral tasks’ measures. The current study was designed to clarify the impact of PD on impulsive action selection and suppression, and investigate the link between cognitive action control and self‐reported impulsivity. We administered an oculomotor version of the Simon task to 32 patients with PD and 32 matched healthy controls (HC), and conducted distributional analyses in accordance with the activation‐suppression model. Patients and HC also filled out the Barratt Impulsiveness Scale (BIS) questionnaire. Results showed that patients with PD were faster overall and exhibited a greater congruence effect than HC. They also displayed enhanced impulsive action selection. By contrast, the suppression of impulsive responses was similar across both groups. Furthermore, patients had higher impulsivity scores, which were correlated with higher impulsive action selection and higher suppression. Our study yielded two interesting findings. First, PD resulted in a higher number of fast errors. The activation‐suppression model suggests that patients with PD are more susceptible to the impulsive action selection induced by the irrelevant stimulus dimension. Second, impulsive action selection and suppression were both associated with trait impulsivity, as measured by the BIS, indicating that these two aspects of impulsivity share common features. HIGHLIGHTSWe compared action selection and suppression between PD patients and controls.We investigated the link between behavioral and trait impulsivity.PD patients displayed a higher impulsive action selection than controls.Impulsive action selection and suppression were correlated with trait impulsivity.