Demographic and clinical factors associated with impaired facial emotion recognition in Parkinson’s disease

Objective: Parkinson’s disease is a progressive neurodegenerative disorder characterized by the presence of motor symptoms and a variety of non-motor symptoms. The ability to recognize facial emotion expressions, a skill of great importance for non-verbal communication and social interaction, has been reported to be impaired in Parkinson’s disease, yet, previous studies showed inconsistent findings. The orbitofrontal cortex, the anterior cingulate, the amygdala, the basal ganglia, temporoparietal areas and visual processing areas seem to constitute crucial neural substrates of the ability to recognize facial emotions. The aim of this study was to further investigate facial emotion recognition in Parkinson’s disease patients and its’ association with demographic and clinical parameters (including motor and non-motor symptoms). As facial emotion recognition and olfaction, a known non-motor symptom of the disease, could share common neural substrates, we tested whether there is an association of facial emotion recognition and olfaction. Patients and methods: Thirty-four non-demented Parkinson’s disease patients and 24 frequency age- and sex-matched healthy controls underwent clinical neurological and neuropsychological assessment including the Beck Depression Inventory, the Apathy Evaluation Scale, the Rapid Eye Movement sleep Behavior Disorder Screening Questionnaire, the Parkinson neuropsychometric dementia assessment instrument and the cognitive estimation test, standardized olfactory testing with Sniffin’ sticks and the Ekman 60 Faces Emotion Recognition Test. The groups did not differ with respect to mini mental state examination score and education. Results: Parkinson’s disease patients had a significantly lower score on the total facial emotion recognition task in comparison with healthy controls (F=8.030, p=0.006), even after controlling for the potential confounding factors depression and apathy. The Parkinson’s disease group had a specific impairment in the recognition of surprise (F=7.885, p=0.007). The recognition of anger approached statistical significance (p=0.07). The emotion more accurately recognized by both groups was happiness while fear was less accurate recognized also by both groups. The most common misattributions of emotions in both groups were: happiness as surprise, sadness as fear, fear as surprise, disgust as anger and surprise as fear. Increasing chronological age (β=-0.294, p=0.001, CI 95% -0.462, -0.126) and age at disease onset (β=-0.194, p=0.012, CI 95% -0.342, -0.046) were associated with worse performance on the facial emotion recognition task in Parkinson’s disease patients. Worse olfactory function along with Parkinson’s disease diagnosis predicted worse facial emotion recognition performance within all study participants. Facial emotion recognition was not associated with patients’ characteristics like gender and education or disease characteristics like disease disability, motor impairment, disease duration, disease severity, disease most affected body side, type of Parkinson’s disease, hypomimia, freezing of gait, postural instability, orthostatic dysregulation and Rapid Eye Movement sleep behavior disorder. In addition, facial emotion recognition was not also predicted by global cognitive performance, executive functions like performance on the cognitive estimation task, depression or apathy. Conclusion: Facial emotion recognition and especially the recognition of surprise are significantly impaired in Parkinson’s patients compared with age- and sex-matched healthy control individuals. The association of facial emotion recognition with age (chronological age and age at disease onset) and olfactory function is endorsed by common structures that undergo neurodegeneration in Parkinson’s disease. Impaired facial emotion recognition in Parkinson’s disease may rely on anatomical connections of the basal ganglia, which appear to play a role in recognizing emotions from facial cues, as part of a distributed network of cortical and subcortical structures or may reflect a dysfunction of the cortical-basal ganglia-thalamic-cortical functional loops. The relevance of facial emotion recognition in social interaction stresses the clinical relevance and the need for further investigation in this field. Future studies should also determine whether impaired facial emotion recognition is already present in premotor stages of Parkinson’s disease. It seems necessary to integrate tasks accessing facial emotion recognition in clinical practice in order to evaluate this non-motor aspect of the disease that can affect patients’ social behavior in order to appreciate the full extent of deficits of patients and to provide an adequate treatment in Parkinson’s disease.Demographische und klinische Faktoren assoziiert mit gestörter Gesichtsemotionserkennung in M. Parkinson Einleitung: Morbus Parkinson ist eine progressive neurodegenerative Erkrankung, die durch das Vorliegen von motorischen und nicht-motorischen Symptomen gekennzeichnet wird. Die Fähigkeit Emotionen in Gesichtern zu erkennen, eine Fertigkeit von großer Bedeutung für die non-verbale Kommunikation und soziale Interaktion scheint beim Morbus Parkinson gestört zu sein, vorherige Studien haben diesbezüglich allerdings widersprüchliche Ergebnisse gezeigt. Der orbitofrontale Kortex, der anterioriore cinguläre Kortex, die Amygdala, die Basalganglien, temporoparietale und visuell verarbeitende Areale stellen die neuronalen Substraten der Emotionserkennung in Gesichtern dar. Das Ziel der Studie war die Emotionserkennung in Gesichtern in Patienten mit Morbus Parkinson weiter zu erforschen und mögliche Assoziationen mit demographischen und klinischen Faktoren (motorischen und nicht motorischen Symptomen) zu evaluieren. Da die Emotionserkennung und der Geruchssinn, ein bekanntes nicht-motorisches Merkmal der Krankheit, in denselben neuronalen Substraten angesiedelt sind, haben wir auch untersucht, ob eine Assoziation zwischen Emotionserkennung und Geruchssinn besteht. Matherial und Methodik: Vierunddreißig Patienten mit Morbus Parkinson und 24 gematchte gesunde Personen wurden klinisch, neurologisch und neuropsychologisch mit Hilfe des Beck Depression Inventars, der Apathie Evaluation Skala, dem Rapid Eye Movement-Schlaf-Verhaltensstörung Fragebogen, dem Parkinson neuropsychometric dementia assessment Test, dem Test zum kognitiven Schätzen, eines standarisierten Geruchtstest Sniffin’ sticks und des Ekman 60 Faces Tests zur Emotionserkennung untersucht. Es gab keine Abweichungen zwischen den beiden Gruppen bezüglich des mini-mental Status und Ausbildungsstatus. Ergebnisse: Patienten mit Morbus Parkinson hatten eine signifikant niedrigere Leistung im Emotionserkennungtest (F=8.030, p=0.006) im Vergleich zu den gesunden Personen, auch nach Berücksichtigung der potentiellen Störfaktoren Depression und Apathie. Die Parkinson Patienten wiesen eine gestörte Emotionserkennung der Emotion Überraschung auf (F=7.885, p=0.007). Die Erkennung der Emotion Wut näherte sich der statistische Signifikanz an (p=0.07). Die Emotion, die am häufigsten richtig erkannt wurde, war Freude, während Furcht von beiden Gruppen am schlechtesten erkannt wurde. Die in beiden Gruppen am häufigsten vorkommende Fehlzuschreibung von Emotionen waren: Freude als Überraschung, Traurigkeit als Furcht, Furcht als Überraschung, Ekel als Wut und Überraschung als Furcht. Zunehmendes Alter (β=-0.294, p=0.001, CI 95% -0.462, -0.126) und Alter des Patienten bei Beginn der Erkrankung (β=-0.194, p=0.012, CI 95% -0.342, -0.046) waren mit einer schlechteren Leistung der Emotionserkennung bei Parkinson Patienten assoziiert. Verminderter Geruchssinn einhergehend mit der Diagnose eines Morbus Parkinson konnten eine schlechtere Leistung zwischen allen Studie Teilnehmern voraussagen. Die Emotionserkennung war nicht assoziiert mit Eigenschaften der Patienten wie Geschlecht und Ausbildung oder mit Eigenschaften der Erkrankung wie krankheitsbedingte Behinderung, motorische Einschränkungen, Dauer der Erkrankung, der am stärksten betroffenen Körperseite, Parkinson Typ, Hypomimie, Freezing beim Gehen, posturale Instabilität, orthostatische Dysregulation und Rapid Eye Movement-Schlaf-Verhaltensstörung. Ferner konnte die Emotionserkennung mit der globalen kognitiven Leistung, exekutiven Funktionen wie kognitives Schätzen, Depression oder Apathie nicht assoziiert werden. Schlussfolgerungen: Emotionserkennung in Gesichtern und besonders die Erkennung der Emotion Überraschung sind bei den Parkinson Patienten signifikant gestört im Vergleich zu alters- und geschlechts- gematchten gesunden Personen. Der Zusammenhang der Emotionserkennung und des Alters und Alters des Beginns der Erkrankung sowie der Emotionserkennung und des Geruchssinns ist durch gemeinsame Strukturen, die eine Neurodegeneration in der Parkinson Krankheit durchmachen, zu erklären. Die gestörte Emotionserkennung beim Morbus Parkinson könnte von anatomischen Verbindungen der Basalganglien abhängen, die vermutlich eine Rolle bei der Emotionserkennung von Gesichtermerkmalen spielen, als Teil von einem verbreiteten Netzwerk von kortikalen und subkortikalen Strukturen. Des Weiteren könnte sie eine Funktionsstörung der kortiko-Basalganglien-thalamische-kortikalen funktionellen Schleifen widerspiegeln. Die Bedeutung der Erkennung von Emotionen in Gesichtern bei den sozialen Interaktionen betont die klinische Bedeutung dieser Funktion und den Bedarf an weiterer Forschung in diesem Bereich. Zukünftige Studien könnten untersuchen, ob eine gestörte Emotionserkennung sogar in den prämotorischen Stadien der Erkrankung vorhanden ist. Es ist notwendig, dass Emotionserkennungsaufgaben im klinischen Alltag integriert werden, um diesen nicht-motorischen Aspekt der Erkrankung, der das soziale Verhalten des Patienten beeinflussen kann, evaluieren zu können und eine adäquate Behandlung der Patienten mit Morbus Parkinson leisten zu können

The Effects of a Voice Treatment on Facial Emotional Expression in Parkinson\u27s Disease: Expressivity, Experience, and Gender

Individuals with Parkinson’s disease (PD) suffer from decreased ability to express emotion through facial expression, in what has been termed “masked facies” or hypomimia. Facial emotional expression is necessary for the accurate communication of needs, to obtain or maintain empathy from care-givers, and to be perceived by others in a way that matches the way that one feels. The current study provides a review of the deficits seen in Parkinson’s disease, an overview of the neurobehavioral disparity of spontaneous versus posed facial expression of emotion, and factors that influence the perception of emotion, such as gender and clinical variables. The relationship between the experience and expression of emotion is also discussed. Further, theorized neural mechanisms underlying a current treatment strategy for Parkinson’s disease (i.e., The Lee Silverman Voice Treatment – Loud [LSVT – LOUD®; Ramig et al., 2001]) is described. Finally, the neurobiological correlates between vocal production and facial expression were examined. The current study had three aims. The first one was to explore whether LSVT-LOUD® affects spontaneous facial emotional expression in PD compared to healthy control groups. Second, we examined whether the internal emotional experience of individuals with PD was related to their expression of facial emotion. The third aim was to explore whether there were gender differences in how men and women evaluated same- and opposite-gendered facial expressions of emotion. Eighty-two individuals comprised the “the poser participants” (i.e., the participant groups of this study), which included PDs receiving the experimental treatment related to voice amplitude (LSVT-LOUD®; Ramig et al., 2001), PDs receiving a control therapy involving articulation (LSVT-ARTIC®; Ramig et al., 2015), PDs not receiving any therapeutic treatment (PD-untrx), and demographically-matched healthy controls (HCs). Using procedures from the New York Emotion Battery (Borod, Cicero, et al., 1998; Borod, Welkowitz, & Obler, 1992), all participants, while being videotaped, were asked to recall a previously experienced emotional event that was happy, sad, or angry, as well as a neutral non-emotional event. Participants’ self-reported experience of each emotion was also recorded. Twenty-fourundergraduate-student rater participants, naïve to the hypotheses of the study, viewed 15-second silent video clips of posers as they recalled the previously experienced emotional or non-emotional events. The “raters” evaluated each video on a 7-point Likert scale, from 1 (“very little”) to 7 (“extreme amount”), for facial emotional expressivity, in terms of emotional frequency, emotional intensity, and emotional variability, as well as social engagement and facial mobility (a non-emotional measure). Our results indicated that the PDs in our sample demonstrated impaired facial expressivity relative to HCs. Contrary to our expectation, we did not find an effect of LSVT-LOUD® treatment on PDs’ spontaneous facial emotional expressions. Second, when exploring whether PDs and HCs experience monologue emotions similarly, we found no differences between the two participant groups. Finally, when viewing same- and opposite-gender facial expressions of emotion, male raters rated all posers as more facially expressive than did female raters. Female raters rated female posers as significantly more facially expressive than did male posers. The results of the current study further characterize the emotional deficits seen in PD and are discussed in terms of clinical implications

Social Symptoms of Parkinson\u27s Disease

© 2020 Margaret T. M. Prenger et al. Parkinson\u27s disease (PD) is typically well recognized by its characteristic motor symptoms (e.g., bradykinesia, rigidity, and tremor). The cognitive symptoms of PD are increasingly being acknowledged by clinicians and researchers alike. However, PD also involves a host of emotional and communicative changes which can cause major disruptions to social functioning. These incude problems producing emotional facial expressions (i.e., facial masking) and emotional speech (i.e., dysarthria), as well as difficulties recognizing the verbal and nonverbal emotional cues of others. These social symptoms of PD can result in severe negative social consequences, including stigma, dehumanization, and loneliness, which might affect quality of life to an even greater extent than more well-recognized motor or cognitive symptoms. It is, therefore, imperative that researchers and clinicans become aware of these potential social symptoms and their negative effects, in order to properly investigate and manage the socioemotional aspects of PD. This narrative review provides an examination of the current research surrounding some of the most common social symptoms of PD and their related social consequences and argues that proactively and adequately addressing these issues might improve disease outcomes

Development of Markerless Systems for Automatic Analysis of Movements and Facial Expressions: Applications in Neurophysiology

This project is focused on the development of markerless methods for studying facial expressions and movements in neurology, focusing on Parkinson’s disease (PD) and disorders of consciousness (DOC). PD is a neurodegenerative illness that affects around 2% of the population over 65 years old. Impairments of voice/speech are among the main signs of PD. This set of impairments is called hypokinetic dysarthria, because of the reduced range of movements involved in speech. This reduction can be visible also in other facial muscles, leading to a hypomimia. Despite the high percentage of patients that suffer from dysarthria and hypomimia, only a few of them undergo speech therapy with the aim to improve the dynamic of articulatory/facial movements. The main reason is the lack of low cost methodologies that could be implemented at home. DOC after coma are Vegetative State (VS), characterized by the absence of self-awareness and awareness of the environment, and Minimally Conscious State (MCS), in which certain behaviors are sufficiently reproducible to be distinguished from reflex responses. The differential diagnosis between VS and MCS can be hard and prone to a high rate of misdiagnosis (~40%). This differential diagnosis is mainly based on neuro-behavioral scales. A key role to plan the rehabilitation in DOC patients is played by the first diagnosis after coma. In fact, MCS patients are more prone to a consciousness recovery than VS patients. Concerning PD the aim is the development of contactless systems that could be used to study symptoms related to speech and facial movements/expressions. The methods proposed here, based on acoustical analysis and video processing techniques could support patients during speech therapy also at home. Concerning DOC patients the project is focused on the assessment of reflex and cognitive responses to standardized stimuli. This would allow objectifying the perceptual analysis performed by clinicians

Quantification of striatal dopaminergic uptake in Parkinson's disease: a new multimodal method combining SPECT DaT and MPRAGE

Parkinson's disease (PD) is a neurodegenerative disease that causes degeneration of nigral dopaminergic terminals in the caudate and the putamen regions of the striatum in the basal ganglia. According to current practice, when an unequivocal clinical diagnosis of PD cannot be made, a single-photon emission computed tomography scan using the DaTscan radionuclide (SPECT DaT scan) is ordered. However, the assessment of SPECT DaT scans in the diagnosis of PD depends on the subjective judgment of a radiologist, which can pose problems for the accuracy of the diagnosis. Furthermore, as research studies generally do not quantify SPECT DaT scans when using them, their conclusions are not based on standardized data. The aim of this paper is to propose a method of quantification for SPECT DaT scans, to be employed in diagnostic and research environments. The methodology proposed in this thesis project will eventually be used for a much larger multimodal imaging project investigating the connectivity changes in the brain related to cognitive and affective symptoms in PD patients. Each of the 4 subjects in this project underwent a SPECT DaT scan and an MPRAGE scan (Magnetization Prepared Rapid Gradient Echo), an anatomical MRI (magnetic resonance image). The SPECT DaT scans and the MPRAGEs were coregistered, and then a voxel-based quantification of the caudate and the putamen in the left and the right hemispheres was performed in every subject. First, the percentages of voxels with intensities exceeding various pericalcarine baselines were calculated. A pericalcarine baseline was used because the pericalcarine gyrus in the occipital lobe has been shown to have little to no dopaminergic activity, particularly on SPECT DaT scans. Next, asymmetry indices (AI) were calculated for two of the thresholds whereby the ratio of the percentage of voxels in the right to the left hemispheric region was taken. Wilcoxon Signed-Rank tests and bootstrapping analyses were performed on both the caudate and the putamen in all four subjects to determine the significance of any detected asymmetry. The quantification of the data and the AI values revealed asymmetries in the voxel intensities between the left and right hemispheres. This asymmetry was consistent with each subject's side of physical symptom onset. According to the bootstrapping analyses, this asymmetry was significant in five of the eight comparisons. In summary, this methodology has potential to bring greater objectivity to the use of SPECT DaT scans in the diagnosis of PD and in research through its anatomically accurate, voxel-based quantification

Dissecting the Genetic Basis of Parkinson Disease, Dystonia and Chorea

In this thesis I used of a range of genetic methodologies and strategies to unravel the genetic bases of Parkinson disease (PD), myoclonus-dystonia (M-D), and chorea. First, I detail the work I performed in PD, including (1) the screening of GBA in a cohort of early-onset PD cases, which led to the identification of the allele E326K (p.Glu365Lys) as the single most frequent, clinically relevant, risk variant for PD; (2) a detailed genetic analysis in a large cohort of PD cases who underwent deep-brain stimulation treatment and a longitudinal comparison of the phenotypic features of carriers of mutations in different genes; (3) the observation that rare GCH1 coding variants, known to be responsible for the childhood-onset disorder DOPA-responsive dystonia, are a novel risk factor for PD. Then, I describe the work I performed to identify novel causes of M-D, including (1) the discovery of the missense p.Arg145His mutation in KCTD17 as a novel cause of autosomal dominant M-D; (2) the identification of tyrosine hydroxylase deficiency as a novel treatable cause of recessive M-D; and (3) the conclusive disproof of the pathogenic role of the p.Arg1389His variant in CACNA1B as a cause of M-D. Finally, I detail my work in the field of choreic syndromes, including (1) the genetic screening of NKX2-1 in the Queen Square cohort of benign hereditary chorea (BHC) cases; (2) the identification of ADCY5 mutations, the gene thought to be responsible for the condition familial dyskinesias with facial myokymia, as an important cause of BHC; and (3) the identification of de novo mutations in PDE10A as a novel genetic cause of chorea. These findings are discussed in light of the recent literature. Following my analysis, I suggest future directions for the identification of novel genetic causes of movement disorders, in light of my recent findings and ongoing research

Clinical and functional imaging correlates in Parkinson's disease

Parkinson's disease (PD) is misdiagnosed throughout its disease course for conditions such as essential tremor, drug-induced parkinsonism, vascular pseudo-parkinsonism, Alzheimer's disease and other degenerative parkinsonian diseases. This thesis aims to verify the accuracy of dopaminergic imaging in early and uncertain parkinsonian/tremor disorders through 3 studies. The first is a prospective United Kingdom multicentre assessment of [1231] FP-CIT SPECT use in 190 patients in pre-defined diagnostic categories and with particular focus on clinical features to assess the influence of imaging in routine practice. The second is a 2 year follow-up study of 150 consecutive patients with normal SPECT, with specific attention to clinical progression and antiparkinson medication use, and includes focus on a subgroup who fulfilled PD criteria where successful antiparkinson medication withdrawal was achieved. The third is a multicentre prospective European study of the accuracy of [1231] FP-CIT SPECT in 99 patients that included serial clinical and imaging assessments. Notably, when initial diagnosis/scan mismatch cases occurred, and with awareness of the scan result, the clinician invariably changed the diagnosis in line with the scan result which confirms the considerable influence of imaging on the practising clinician. Parkinson's disease is clinically overdiagnosed early in its disease course, whereas imaging is more specific, in the vast majority of cases with normal dopaminergic imaging, there was no evidence of clinical or imaging progression which would be in keeping with degenerative parkinsonism

Gait Analysis before and after different rehabilitation treatments in Parkinson's disease

openLa presente tesi si concentra sulla valutazione dei trattamenti riabilitativi per la malattia di Parkinson, in particolare attraverso la “Gait Analysis”. Il morbo di Parkinson è una malattia neurodegenerativa che colpisce la funzione motoria, compresa l'andatura e la mobilità. Lo studio mira a valutare come due interventi riabilitativi, l'esoscheletro e la kinesiterapia fisica, possano mitigare gli effetti sulla deambulazione nei pazienti affetti da Parkinson. Le tecniche di analisi del cammino vengono utilizzate per misurare i miglioramenti di parametri quali gli spazio-tempo , la cinematica e la cinetica articolari. La fisiopatologia della malattia di Parkinson coinvolge la degenerazione dei neuroni dopaminergici, l'accumulo anomalo di proteine, la disfunzione mitocondriale, la compromissione della clearance proteica, la neuro infiammazione e i fattori genetici. I trattamenti per il Parkinson includono farmaci come la carbidopa-levodopa, gli agonisti della dopamina, gli inibitori MAOB, procedure chirurgiche come la stimolazione cerebrale profonda e trattamenti riabilitativi come la fisioterapia e la terapia assistita da esoscheletro. L'analisi del cammino è un metodo utilizzato per valutare il movimento umano durante il cammino e può essere effettuato tramite tecniche osservazionali o strumentali. L'analisi osservazionale prevede la valutazione visiva dell'andatura, mentre l'analisi strumentale utilizza apparecchiature avanzate come sistemi di analisi del movimento, piattaforme di forza ed elettromiografia di superficie per misurare varie variabili legate al movimento e all'attività muscolare. Il ciclo del passo è caratterizzato da due fai principali: appoggio e oscillazione. La fase di appoggio prevede che il piede sia a contatto con il suolo e porti il peso, mentre la fase di oscillazione vede il piede muoversi in avanti per il contatto successivo. Ogni fase ha delle sottofasi con funzioni specifiche come l'accettazione del carico, il supporto di un arto singolo e l'avanzamento dell'arto. Parametri come la lunghezza del passo, la larghezza del passo, la cadenza e la velocità sono cruciali nell'analisi del passo. Queste metriche aiutano a comprendere e diagnosticare anomalie o patologie del movimento legate alla patologia. La stereofotogrammetria è una tecnica utilizzata nell'analisi del cammino per catturare e analizzare con precisione il movimento tridimensionale. Si tratta di sistemi optoelettronici, marcatori e telecamere per tracciare il movimento e ricostruire le posizioni in modo accurato. Vari protocolli, come i protocolli Davis-Hellen Hayes, CAST e IORgait, forniscono metodi standardizzati per il posizionamento dei marcatori, la raccolta dei dati e i calcoli degli angoli articolare durante l'analisi del cammino. IORgait è il protocollo utilizzato in questo studio. Sono state osservate differenze significative tra le misurazioni T0 e T1 sia per i gruppi Fkt che per Ekso, nonché rispetto al gruppo di controllo. Queste differenze comprendevano vari parametri come gli angoli degli arti inferiori, l’attività EMG, le forze articolari, le coppie e i parametri spaziotemporali. Entrambe le terapie Ekso e Fkt hanno portato a miglioramenti significativi nei parametri dell’andatura rispetto alle misurazioni inizial