Quantifying Apathy in Late-Life Depression: Unraveling Neurobehavioral Links through Daily Activity Patterns and Brain Connectivity Analysis.

BACKGROUND: Better understanding apathy in late-life depression (LLD) would help predicting poor prognosis of the disease such as dementia. Actimetry provides an objective and ecological measure of apathy from patients' daily motor activity. We aimed to determine if patterns of motor activity were associated with apathy and brain connectivity in networks underlying goal-directed behaviors. METHODS: Resting-state functional MRI and diffusion MRI were collected from 38 non-demented LLD subjects. Apathy was evaluated using the diagnostic criteria for apathy, the apathy evaluation scale (AES) and the apathy motivation index (AMI). Functional principal components (fPC) of motor activity were derived from actimetry recordings of 72 hours. Associations between fPC and apathy were estimated by linear regression. Subnetworks whose connectivity was significantly associated with fPC were identified via the threshold-free network-based statistics. The relationship between apathy and microstructure metrics was estimated along fibers by diffusion tensor imaging and a multicompartment model called neurite orientation dispersion and density imaging via tractometry. RESULTS: We found two fPC associated with apathy: mean diurnal activity, negatively associated with AES, and an early chronotype, negatively associated with AMI. Mean diurnal activity was associated with increased connectivity in the default-mode, the cingulo-opercular and the frontoparietal networks, while chronotype was associated with a more heterogenous connectivity pattern in the same networks. We did not find significant associations between microstructural metrics and fPCs. CONCLUSION: Our findings suggest that mean diurnal activity and chronotype could provide indirect ambulatory measures of apathy in LLD, associated with modified functional connectivity of brain networks underlying goal-directed behaviors.

Prospective acceptability of digital therapy for major depressive disorder in France: multicentric real-life study.

BACKGROUND: Major depressive disorder is one of the leading causes of disability worldwide. Recently, the WHO has highlighted the negative impact of recent crises (COVID-19 pandemic, war in Ukraine, economic crisis). Although most international guidelines recommend psychological and psychosocial interventions as a first-line treatment for mild to moderate depression, access remains limited in France due to limited availability of trained clinicians, high costs for patients in a context of non-reimbursement and fear of stigmatisation. Therefore, online blended psychological treatment such as deprexis® could improve access to care for people with depression. It has several advantages such as easy access, scalability and is supported by evidence. OBJECTIVE: This study aims to evaluate the real-life acceptability of a deprexis® for people with depression in France, outside of a reimbursement pathway. METHODS: DARE was designed as a multicentre cross-sectional study in which deprexis® was offered to any patient meeting the inclusion criteria during the fixed inclusion period June 2022-March 2023. Inclusion criteria were: 1/ depression, 2/ age between 18 and 65 years, 3/ sufficient French language skills, 4/ access to internet with a device to connect to the deprexis® platform. Exclusion criteria were previous or current diagnosis of bipolar disorder, psychotic symptoms and/or suicidal thoughts during the current episode. The primary objective is to measure the prospective acceptability of deprexis®, a new digital therapy. Secondary objectives are to examine differences in acceptability according to patient and clinician characteristics and to identify reasons for refusal. All investigators received video-based training on deprexis® prior to enrolment to ensure that they all had the same level of information and understanding of the programme. RESULTS: 245 patients were eligible (56.3% women and 56.3% single). Mean age 40.7+-14.1 years. 78% had moderate to severe depression (according to PHQ-9). More than half of the population had another psychiatric comorbidity (excluding bipolar disorder, psychotic disorders and suicidal ideation). 33.9% of patients accepted the idea of using deprexis® and the main reason for refusal was financial, at 83.3%. Multivariate logistic regression identified factors that might favour acceptability of deprexis®. Among these, being in a couple, being treated with an antidepressant or having a low severity level favoured acceptance of deprexis®. CONCLUSIONS: DARE is the first French study aiming at evaluating prospective acceptability of a Digital therapy in the treatment of depression. The main reason for refusal of deprexis® was financial. DARE will allow a better identification of factors influencing it in a natural setting. This study highlights the importance of investigating factors that may be associated with the acceptability of digital interventions, such as marital status, medication use and severity of depression.

Structural Brain Connectivity and Treatment Improvement in Mood Disorder.

Background: The treatment of depressive episodes is well established, with clearly demonstrated effectiveness of antidepressants and psychotherapies. However, more than one-third of depressed patients do not respond to treatment. Identifying the brain structural basis of treatment-resistant depression could prevent useless pharmacological prescriptions, adverse events, and lost therapeutic opportunities. Methods: Using diffusion magnetic resonance imaging, we performed structural connectivity analyses on a cohort of 154 patients with mood disorder (MD) and 77 sex- and age-matched healthy control (HC) participants. To assess illness improvement, the patients with MD went through two clinical interviews at baseline and at 6-month follow-up and were classified based on the Clinical Global Impression-Improvement score into improved or not-improved (NI). First, the threshold-free network-based statistics (NBS) was conducted to measure the differences in regional network architecture. Second, nonparametric permutations tests were performed on topological metrics based on graph theory to examine differences in connectome organization. Results: The threshold-free NBS revealed impaired connections involving regions of the basal ganglia in patients with MD compared with HC. Significant increase of local efficiency and clustering coefficient was found in the lingual gyrus, insula, and amygdala in the MD group. Compared with the NI, the improved displayed significantly reduced network integration and segregation, predominately in the default-mode regions, including the precuneus, middle temporal lobe, and rostral anterior cingulate. Conclusions: This study highlights the involvement of regions belonging to the basal ganglia, the fronto-limbic network, and the default mode network, leading to a better understanding of MD disease and its unfavorable outcome.

Connectivity patterns of the core resting-state networks associated with apathy in late-life depression.

BACKGROUND: Apathy is associated with reduced antidepressant response and dementia in late-life depression (LLD). However, the functional cerebral basis of apathy is understudied in LLD. We investigated the functional connectivity of 5 resting-state networks (RSN) hypothesized to underlie apathy in LLD. METHODS: Resting-state functional MRI data were collected from individuals with LLD who did not have dementia as well as healthy older adults between October 2019 and April 2022. Apathy was evaluated using the diagnostic criteria for apathy (DCA), the Apathy Evaluation Scale (AES) and the Apathy Motivation Index (AMI). Subnetworks whose connectivity was significantly associated with each apathy measure were identified via the threshold-free network-based statistics. Regions that were consistently associated with apathy across the measures were reported as robust findings. RESULTS: Our sample included 39 individuals with LLD who did not have dementia and 26 healthy older adults. Compared with healthy controls, individuals with LLD had an altered intra-RSN and inter-RNS connectivity in the default mode, the cingulo-opercular and the frontoparietal networks. All 3 apathy measurements showed associations with modified intra-RSN connectivity in these networks, except for the DCA in the cingulo-opercular network. The AMI scores showed stronger associations with the cingulo-opercular and frontoparietal networks, whereas the AES had stronger associations with the default mode network and the goal-oriented behaviour network. LIMITATIONS: The study was limited by the small number of participants without apathy according to the DCA, which may have reduced the statistical power of between-group comparisons. Additionally, the reliance on specific apathy measures may have influenced the observed overlap in brain regions. CONCLUSION: Our findings indicate that apathy in LLD is consistently associated with changes in both intra-RSN and inter-RSN connectivity of brain regions implicated in goal-oriented behaviours. These results corroborate previous findings of altered functional RSN connectivity in severe LLD.

Understanding the potential of digital therapies in implementing the standard of care for depression in Europe.

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

Chloroplast ATP synthase biogenesis requires peripheral stalk subunits AtpF and ATPG and stabilization of atpE mRNA by OPR protein MDE1.

Chloroplast ATP synthase contains subunits of plastid and nuclear genetic origin. To investigate the coordinated biogenesis of this complex, we isolated novel ATP synthase mutants in the green alga Chlamydomonas reinhardtii by screening for high light sensitivity. We report here the characterization of mutants affecting the two peripheral stalk subunits b and b', encoded respectively by the atpF and ATPG genes, and of three independent mutants which identify the nuclear factor MDE1, required to stabilize the chloroplast-encoded atpE mRNA. Whole-genome sequencing revealed a transposon insertion in the 3'UTR of ATPG while mass spectrometry shows a small accumulation of functional ATP synthase in this knock-down ATPG mutant. In contrast, knock-out ATPG mutants, obtained by CRISPR-Cas9 gene editing, fully prevent ATP synthase function and accumulation, as also observed in an atpF frame-shift mutant. Crossing ATP synthase mutants with the ftsh1-1 mutant of the major thylakoid protease identifies AtpH as an FTSH substrate, and shows that FTSH significantly contributes to the concerted accumulation of ATP synthase subunits. In mde1 mutants, the absence of atpE transcript fully prevents ATP synthase biogenesis and photosynthesis. Using chimeric atpE genes to rescue atpE transcript accumulation, we demonstrate that MDE1, a novel octotricopeptide repeat (OPR) protein, genetically targets the atpE 5'UTR. In the perspective of the primary endosymbiosis (~1.5 Gy), the recruitment of MDE1 to its atpE target exemplifies a nucleus/chloroplast interplay that evolved rather recently, in the ancestor of the CS clade of Chlorophyceae, ~300 My ago.

[Functional neurological disorders and forensic medicine: Clinical and practical characteristics]. / Troubles neurologiques fonctionnels et expertise médico-légale : aspects cliniques et pratiques.

Functional neurological disorders (FND) have long been a challenge for medicine, both on clinical and psychodynamic point of view. The medico-legal issue is often relegated to the background in medicine, and FND patients also suffer from such neglected topic. Nonetheless, despite the difficulty to properly diagnose FND and the numerous associated organic and/or psychiatric comorbidities, FND patients report a significant level of deficiency and a high alteration of quality of life when compared to other well-recognized chronic disorders such as Parkinson's disease or epilepsy. Whether it is for the estimation of a personal injury, a prejudice, after-effects following a medical accident or certain legal contexts requiring the elimination of a factitious disorder or a simulation, the uncertainty and imprecision in the medico-legal assessment can imply notable consequences on the patient. In this article, we propose to define the different medico-legal contexts in which FND can occur that of the legal expert, that of the consulting physician, that of the so-called recourse physician and finally that of the attending physician who can provide detailed medical files to the patient in order to help him/her in his/her procedures. We then explain how to use standardized objective evaluation tools validated by the learned societies and how to encourage multidisciplinary cross-evaluation. Finally, we specify how to differentiate FND from historically FND-associated disorders (factitious and simulated disorders), through the clinical criteria, considering the difficulties linked to the uncertainty in the clinical examination of these disorders in a medico-legal context. In addition to the rigorous completion of expertise missions, we aim to reduce two damaging consequences characterizing FND: diagnostic delay and the patients' suffering through stigma.

[Understanding functional neurological disorders: From biological markers to pathophysiological models]. / Étiopathogénie des troubles neurologiques fonctionnels : marqueurs biologiques et modèles théoriques.

OBJECTIVES: Functional neurological disorders have witnessed intense research activity in the fields of structural and functional neuroimaging for more than twenty years. Thus, we propose a synthesis of recent research findings and etiological hypotheses that have been proposed so far. This work should help clinicians to better understand the nature of the mechanisms involved, but also help patients to increase their knowledge about the biological features underlying their functional symptoms. METHODS: We carried out a narrative review of international publications dealing with neuroimaging and biology of functional neurological disorders, from 1997 to 2023. RESULTS: Several brain networks underlie functional neurological symptoms. These networks play a role in the management of cognitive resources, in attentional control, emotion regulation, in agency and in the processing of interoceptive signals. The mechanisms of the stress response are also associated with the symptoms. The biopsychosocial model helps to better understand predisposing, precipitating, and perpetuating factors involved. The functional neurological phenotype results from the interaction between: i) a specific pre-existing vulnerability resulting from biological background and epigenetic modifications, and ii) exposure to stress factors, according to the stress-diathesis model. This interaction causes emotional disturbances including hypervigilance, lack of integration of sensations and affects, and emotional dysregulation. These characteristics in turn impact the cognitive, motor and affective control processes related with the functional neurological symptoms. CONCLUSIONS: A better knowledge of the biopsychosocial determinants of brain network dysfunctions is necessary. Understanding them would help developing targeted treatments, but is also critical for patients care.

Motor Symptom Asymmetry Predicts Cognitive and Neuropsychiatric Profile Following Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: a 5-Year Longitudinal Study.

INTRODUCTION: Risk factors (e.g., motor symptom asymmetry) for short- and long-term cognitive and neuropsychiatric symptoms following deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease have yet to be fully identified. The objectives of the present study were to determine whether motor symptom asymmetry in Parkinson's disease is one such risk factor and to identify predictors of subnormal cognitive decline. METHODS: A total of 26 patients receiving STN-DBS (13 with left-sided motor symptoms and 13 with right-sided ones) underwent follow-up neuropsychological, depression and apathy assessments over a 5-year period. Nonparametric intergroup comparisons were performed on raw scores, as well as Cox regression analyses on standardized Mattis Dementia Rating Scale scores. RESULTS: Compared with patients who had predominantly left-sided symptoms, right-sided patients scored higher on both apathy (at 3 months and 36 months) and depressive symptoms (at 6 months and 12 months) and scored lower on global cognitive efficiency (at 36 months and 60 months). Survival analyses revealed that only right-sided patients had subnormal standardized dementia scores, which were negatively associated with the number of perseverations in the Wisconsin Card Scoring Test. CONCLUSION: Right-sided motor symptoms are a risk factor for more severe short- and long-term cognitive and neuropsychiatric symptoms following STN-DBS, confirming literature findings on left hemispheric vulnerability.

Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study.

BACKGROUND: Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19. METHODS: This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis. RESULTS: In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9-59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. CONCLUSION: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.

Place of the partial dopamine receptor agonist aripiprazole in the management of schizophrenia in adults: a Delphi consensus study.

BACKGROUND: Aripiprazole is a second-generation antipsychotic, efficacious in patients with schizophrenia during acute episodes. Due to its pharmacological profile, aripiprazole may be of interest in patients with specific clinical profiles who have not been studied extensively in randomised clinical trials. OBJECTIVES: To capture experience with aripiprazole in everyday psychiatric practice using the Delphi method in order to inform decision-making on the use of aripiprazole for the treatment of patients with schizophrenia in clinical situations where robust evidence from clinical trials is lacking. METHODS: The scope of the survey was defined as the management of schizophrenia in adults. A systematic literature review was performed to identify the different clinical situations in which aripiprazole has been studied, and to describe the level of clinical evidence. Clinical profiles to include in the Delphi survey were selected if there was a clear interest in terms of medical need but uncertainty over the efficacy of aripiprazole. For each clinical profile retained, five to seven specific statements were generated and included in a questionnaire. The final 41-item questionnaire was proposed to a panel of 406 French psychiatrists with experience in the treatment of schizophrenia. Panellists rated their level of agreement using a Likert scale. A second round of voting on eleven items was organised to clarify points for which a consensus was not obtained in the first round. RESULTS: Five clinical profiles were identified in the literature review (persistent negative symptoms, pregnancy, cognitive dysfunction, addictive comorbidity and clozapine resistance). Sixty-two psychiatrists participated in the first round of the Delphi survey and 33 in the second round. A consensus was obtained for 11 out of 41 items in the first round and for 9/11 items in the second round. According to the panellists' clinical experience, aripiprazole can be used as maintenance treatment for pregnant women, is relevant to preserve cognitive function and can be considered an option in patients with a comorbid addictive disorder or with persistent negative symptoms. CONCLUSION: These findings may help physicians in choosing relevant ways to use aripiprazole and highlight areas where more research is needed to widen the evidence base.

Motor symptom asymmetry predicts non-motor outcome and quality of life following STN DBS in Parkinson's disease.

Risk factors for long-term non-motor symptoms and quality of life following subthalamic nucleus deep brain stimulation (STN DBS) have not yet been fully identified. In the present study, we investigated the impact of motor symptom asymmetry in Parkinson's disease. Data were extracted for 52 patients with Parkinson's disease (half with predominantly left-sided motor symptoms and half with predominantly right-sided ones) who underwent bilateral STN and a matched healthy control group. Performances for cognitive tests, apathy and depression symptoms, as well as quality-of-life questionnaires at 12 months post-DBS were compared with a pre-DBS baseline. Results indicated a deterioration in cognitive performance post-DBS in patients with predominantly left-sided motor symptoms. Performances of patients with predominantly right-sided motor symptoms were maintained, except for a verbal executive task. These differential effects had an impact on patients' quality of life. The results highlight the existence of two distinct cognitive profiles of Parkinson's disease, depending on motor symptom asymmetry. This asymmetry is a potential risk factor for non-motor adverse effects following STN DBS.

Dynamics of cognitive action control in late-life depression during action selection.

INTRODUCTION: Late-Life Depression (LLD) is characterized by deficits in cognitive control. We investigated the effect of LLD on a subset of cognitive control functions, the Cognitive Action Control (CAC), distinguishing on-line and adaptive control. METHODS: We compared LLD subjects (n = 31) and Healthy Controls (HC, n = 31) on their performance in a Simon task. The online congruency effect and adaptive effect were compared for reaction times (RT) and accuracy rates between the groups using mixed models. We applied distributional analyses of RT to differentiate the strength of impulsive action selection and the proficiency of selective action suppression. Finally, we measured correlations between the performances on the task and clinical scores of the LLD group. RESULTS: LLD had increased error rates in congruent trials compared to HC. Conversely, the adaptive CAC was equivalent between the groups. Distributional analyses showed that the fastest actions were less led by pertinent information in LLD. This phenomenon was found exclusively for congruent trials preceded by non-congruent trials. On the other hand, LLD patients, when they take time, were better than HC to suppress selectively non-relevant information. No difference was observed for adaptation to the preceding condition. No association between behavioral measurements and clinical scores were found. CONCLUSION: Our results suggest that LLD participants have a specific cognitive disturbance of CAC, showing less facilitation than HC in congruent situations. We propose that this originates in a difficulty in LLD patients in disengaging their attention from conflict situations, which is consistent with a biased CAC to aversive stimuli in depression.

Multimodal brain imaging connectivity analyses of emotional and motivational deficits in depression among women.

BACKGROUND: Major depressive disorder (MDD) is characterized by impaired cortical-subcortical functional connectivity. Apathy adds to functional impairment, but its cerebral basis in MDD remains unknown. Our objective was to describe impairments in functional connectivity during emotional processing in MDD (with varying levels of congruency and attention), and to determine their correlation with apathy. METHODS: We used the Variable Attention Affective Task during functional MRI, followed by diffusion-weighted MRI, to assess 55 right-handed women (30 with MDD and 25 healthy controls) between September 2012 and February 2015. We estimated functional connectivity using generalized psychophysiologic interaction and anatomic connectivity with tract-based spatial statistics. We measured apathy using the Apathy Evaluation Scale. RESULTS: We found decreased functional connectivity between the left amygdala and the left anterior cingulate cortex (ACC) during negative stimuli in participants with MDD (t54 = 4.2; p = 0.035, family-wise error [FWE]-corrected). During high-attention stimuli, participants with MDD showed reduced functional connectivity between the right dorsolateral prefrontal cortex (dlPFC) and the right ACC (t54 = 4.06, pFWE = 0.02), but greater functional connectivity between the right dlPFC and the right amygdala (t54 = 3.35, p = 0.048). Apathy was associated with increased functional connectivity between the right dlPFC and the right ACC during high-attention stimuli (t28 = 5.2, p = 0.01) and increased fractional anisotropy in the right posterior cerebellum, the anterior and posterior cingulum and the bilateral internal capsule (all pFWE < 0.05). LIMITATIONS: Limitations included a moderate sample size, concomitant antidepressant therapy and no directed connectivity. CONCLUSION: We found that MDD was associated with impairments in cortical-subcortical functional connectivity during negative stimuli that might alter the recruitment of networks engaged in attention. Apathy-related features suggested networks similar to those observed in degenerative disorders, but possible different mechanisms.

Functional Role of the Cerebellum in Parkinson Disease: A PET Study.

OBJECTIVES: To test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism. METHODS: We included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations. RESULTS: Severity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters. CONCLUSIONS: These results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops.

Motor symptom asymmetry in Parkinson's disease predicts emotional outcome following subthalamic nucleus deep brain stimulation.

The objective of this study was to explore the brain modifications associated with vocal emotion (i.e., emotional prosody) processing deficits in patients with Parkinson's disease after deep brain stimulation of the subthalamic nucleus, and the impact of motor asymmetry on these deficits. We therefore conducted 18-fluorodeoxyglucose positron emission tomography scans of 29 patients with left- or right-sided motor symptoms of Parkinson's disease before and after surgery, and correlated changes in their glucose metabolism with modified performances on the recognition of emotional prosody. Results were also compared with those of a matched healthy control group. Patients with more left-sided motor symptoms exhibited a deficit in vocal emotion recognition for neutral, anger, happiness and sadness in the preoperative condition that was normalized postoperatively. Patients with more right-sided motor symptoms performed comparably to controls in the preoperative condition, but differed significantly on fear postoperatively. At the metabolic level, the improvement observed among patients with left-sided motor symptoms was correlated with metabolic modifications in a right-lateralized network known to be involved in emotional prosody, while the behavioral worsening observed among patients with right-sided motor symptoms was correlated with metabolic modifications in the left parahippocampal gyrus and right cerebellum. We suggest that surgery has a differential impact on emotional processing according to motor symptom lateralization, and interpret these results as reflecting the (de)synchronization of the limbic loop in the postoperative condition.

The OPR Protein MTHI1 Controls the Expression of Two Different Subunits of ATP Synthase CFo in Chlamydomonas reinhardtii.

In the green alga Chlamydomonas (Chlamydomonas r einhardtii), chloroplast gene expression is tightly regulated posttranscriptionally by gene-specific trans-acting protein factors. Here, we report the identification of the octotricopeptide repeat protein MTHI1, which is critical for the biogenesis of chloroplast ATP synthase oligomycin-sensitive chloroplast coupling factor. Unlike most trans-acting factors characterized so far in Chlamydomonas, which control the expression of a single gene, MTHI1 targets two distinct transcripts: it is required for the accumulation and translation of atpH mRNA, encoding a subunit of the selective proton channel, but it also enhances the translation of atpI mRNA, which encodes the other subunit of the channel. MTHI1 targets the 5' untranslated regions of both the atpH and atpI genes. Coimmunoprecipitation and small RNA sequencing revealed that MTHI1 binds specifically a sequence highly conserved among Chlorophyceae and the Ulvale clade of Ulvophyceae at the 5' end of triphosphorylated atpH mRNA. A very similar sequence, located ∼60 nucleotides upstream of the atpI initiation codon, was also found in some Chlorophyceae and Ulvale algae species and is essential for atpI mRNA translation in Chlamydomonas. Such a dual-targeted trans-acting factor provides a means to coregulate the expression of the two proton hemi-channels.