Thibaut Dondaine

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 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.

Pallidal Stimulation in Advanced Parkinson's Patients with Contraindications for Subthalamic Stimulation

The aim of this study was to evaluate the efficacy and safety of bilateral pallidal (GPi) deep brain stimulation (DBS) 6 months after surgery in advanced parkinsonian patients whose dopa‐resistant axial motor signs or cognitive decline constituted contraindications for subthalamic nucleus (STN) DBS. Seventeen patients with a mean age of 59.3 ± 7.1 years (range, 45–70), mean disease duration of 12.5 ± 4.3 years (range, 7–20), and contraindications for STN DBS, underwent bilateral GPi DBS. They were evaluated before surgery and 6 months afterward, in accordance with Core Assessment Program for Intracerebral Transplantation recommendations. There were mean improvements of 41.1% in the UPDRS III motor score in the off‐dopa condition and 20.3% in the activities of daily living score. Motor fluctuations were reduced by 22.9% and dyskinesias by 68.6%. Axial motor signs improved in the off‐dopa condition by 34.2%. Neuropsychological performances remained unchanged at the 6‐month assessment. Bilateral GPi DBS is both safe and effective in advanced parkinsonian patients with untreatable motor fluctuations, for whom STN DBS is contraindicated due to dopa‐resistant axial motor signs or cognitive decline. As such, it should be regarded as a viable option for these patients.

Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive-compulsive disorder: a double-blind, crossover study

This pilot study was designed to assess the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right orbitofrontal cortex (OFC) by means of a double-cone coil in patients suffering from obsessive-compulsive disorder. We hypothesized that low-frequency stimulation of the OFC would lead to a reduction in clinical symptoms, as measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A randomized, double-blind, crossover design was implemented with two 1-week treatment periods (active stimulation versus sham stimulation) separated by a 1-month washout period. Concomitantly, a subgroup of patients underwent a positron emission tomography (PET) scan after each stimulation sequence. Statistical analyses compared the Y-BOCS scores at the end of each period. At day 7, we observed a significant decrease from baseline in the Y-BOCS scores, after both active (P<0.01) and sham stimulation (P=0.02). This decrease tended to be larger after active stimulation than after sham stimulation: −6 (−29, 0) points versus −2 (−20, 4) points (P=0.07). Active versus sham PET scan contrasts showed that stimulation was related to a bilateral decrease in the metabolism of the OFC. The OFC should definitely be regarded as a key neuroanatomical target for rTMS, as it is easier to reach than either the striatum or the subthalamic nucleus, structures favored in neurosurgical approaches.

The nucleus accumbens: a target for deep brain stimulation in resistant major depressive disorder

ObjectiveThis review aimed to investigate the therapeutic potential of Deep Brain Stimulation (DBS) for treating resistant Major Depressive Disorder (MDD). We explored the role of Nucleus accumbens (Nac) as a target for treatment.MethodWe made a systematic review of all studies examining the mechanisms of action of high frequency brain stimulation and the pathophysiology of MDD. We also reported all the studies exploring the therapeutic potential of DBS in MDD.ResultsAs a central relay-structure, the Nac seems to play a central role in MDD symptomatology. We investigated its role as a primary target for DBS in depressed patients. Anatomically the Nac is at the centre of the interactions between dopaminergic, serotoninergic and glutamatergic systems. Functionally, the Nac is involved in both normal and abnormal reward processes and in anhedonia and loss of motivation. Due to its central location between the emotional system, the cognitive system and motor control system, the Nac seems to have a central role in mood and feeling regulation.ConclusionAccording to encouraging recent studies, DBS seems to be a promising technique in resistant MDD treatment.

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.

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.

Biases in facial and vocal emotion recognition in chronic schizophrenia

There has been extensive research on impaired emotion recognition in schizophrenia in the facial and vocal modalities. The literature points to biases toward non-relevant emotions for emotional faces but few studies have examined biases in emotional recognition across different modalities (facial and vocal). In order to test emotion recognition biases, we exposed 23 patients with stabilized chronic schizophrenia and 23 healthy controls (HCs) to emotional facial and vocal tasks asking them to rate emotional intensity on visual analog scales. We showed that patients with schizophrenia provided higher intensity ratings on the non-target scales (e.g., surprise scale for fear stimuli) than HCs for the both tasks. Furthermore, with the exception of neutral vocal stimuli, they provided the same intensity ratings on the target scales as the HCs. These findings suggest that patients with chronic schizophrenia have emotional biases when judging emotional stimuli in the visual and vocal modalities. These biases may stem from a basic sensorial deficit, a high-order cognitive dysfunction, or both. The respective roles of prefrontal-subcortical circuitry and the basal ganglia are discussed.

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.