Emotional experience in patients with clinically isolated syndrome and early multiple sclerosis

Background and purpose: Evidence suggests that there are changes in the processing of emotional information (EP) in people with multiple sclerosis (MS). It is unclear which functional domains of EP are affected, whether these changes are secondary to other MS-related neuropsychological or psychiatric symptoms and if EP changes are present in early MS. The aim of the study was to investigate EP in patients with early MS (clinically isolated syndrome and early relapsing/remitting MS) and healthy controls (HCs). Methods: A total of 29 patients without neuropsychological or psychiatric deficits and 29 matched HCs were presented with pictures from the International Affective Picture System with negative, positive or neutral content. Participants rated the induced emotion regarding valence and arousal using nine-level Likert scales. A speeded recognition test assessed memory for the emotional stimuli and for the emotional modulation of response time. A subgroup of participants was tested during a magnetic resonance imaging (MRI) session. Results: Patients in the MRI subgroup rated the experience induced by pictures with positive or negative emotional content significantly more weakly than HCs. Further, these patients were significantly less aroused when watching the pictures from the International Affective Picture System. There were no effects in the non-MRI subgroup or effects on emotional memory or response times. Conclusions: Emotional processing changes may be present in early MS in the form of flattened emotional experience on both the valence and arousal dimensions. These changes do not appear to be secondary to neuropsychological or psychiatric deficits. The fact that emotional flattening was only found in the MRI setting suggests that EP changes may be unmasked within stressful environments and points to the potential yet underestimated impact of the MRI setting on behavioral outcomes

neuropsychological and psychiatric effects in Parkinson's disease

Die in dieser Schrift vorgestellten Studien belegen, dass der neuropsychologische und psychiatrische Status von Patienten mit IPS nicht zuletzt von Nebenwirkungen der etablierten Behandlung motorischer Symptome durch Dopaminersatztherapie und tiefe Hirnstimulation abhängt. Durch den Nachweis der hier teils erstmals beschriebenen Phänomene erweitern sie das Verständnis der Rolle der dopaminergen Neurotransmission und des Nucleus subthalamicus für ausgewählte kognitive, affektive und behaviorale Funktionen. Die Ergebnisse der Experimente zur dopaminergen Modulation der Verarbeitung emotionaler Information deuten darauf hin, dass Dopamin emotionale Gedächtnisprozesse über die Dimension emotionaler Valenz und Aufmerksamkeitsprozesse über die Dimension emotionaler Aktivierung vermittelt. Sie zeigen außerdem, dass bestimmte emotionale Defizite beim IPS therapieinduziert sind. In Untersuchungen zu den Auswirkungen der dopaminergen Behandlung auf eine breite Palette kognitiver, insbesondere frontal-exekutiver Funktionen wurde belegt, dass die therapeutische dopaminerge Stimulation bei Patienten mit fortgeschrittenem IPS weitgehend neutral und also kognitiv gut verträglich ist. In Experimenten zu den Effekten der tiefen Hirnstimulation wurden erstmals Hinweise für eine Beteiligung des Nucleus subthalamicus an der Realisierung prozeduraler kognitiver Lernprozesse vorgelegt. Gegenläufige Effekte der Stimulation auf prozedurales und deklaratives Gedächtnis legen ferner eine Beteiligung des Nucleus subthalamicus bei der Aktivierung unterschiedlicher Gedächtnissysteme nahe. In einer prospektiven Querschnittsstudie wurden Hinweise für erhöhte Impulsivität bei Patienten mit tiefer Hirnstimulation des Nucleus subthalamicus gefunden. Dies bestätigt die Annahme, dass dem Nucleus subthalamicus, möglicherweise durch die Regulierung der Entscheidungsschwelle, eine Rolle bei der Impulskontrolle zukommt.The studies presented here demonstrate that the established treatment modalities of dopamine replacement therapy and deep brain stimulation have an impact on neuropsychological and psychiatric state in patients with Parkinson’s disease. They extend current knowledge on the role of dopaminergic neurotransmission and of the subthalamic nucleus for specific cognitive, affective and behavioral functions. The results of the experimental studies on the dopaminergic modulation of emotional processing suggest that dopamine mediates emotional memory via the emotional valence dimension and attention via emotional arousal. They furthermore show that certain emotional changes in Parkinson’s disease are induced by dopaminergic treatment. Studies on the effects of dopamine replacement therapy on a wide range of cognitive and particularly frontal-executive functions suggest that therapeutic dopaminergic stimulation does not affect cognition in non-demented patients with Parkinson’s disease. Experiments on the effects of subthalamic deep brain stimulation on memory suggest that the subthalamic nucleus might be implicated in non-declarative memory. Antagonistic stimulation effects on non-declarative and declarative memory performance are compatible with a specific role of the subthalamic nucleus in the activation of both memory systems. A prospective cross-sectional study provided evidence for increased impulsivity in patients with Parkinsons disease treated with subthalamic deep brain stimulation. This is compatible with an implication of the subthalamic nucleus in the regulation of impulse control possibly via adjustment of the response threshold

Effects of dopaminergic and subthalamic stimulation on musical performance.

Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson's disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision

Programming parameters of subthalamic deep brain stimulators in Parkinson's disease from a controlled trial.

BACKGROUND Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. METHODS Stimulation parameters were systematically documented at 1, 5, 12, and 24 month in the cohort of 114 patients who had bilateral STN-DBS at 24 month. We investigated the influence of atypical programming, changes of stimulated electrode contacts and stimulation energy delivered. Outcomes were the Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL-subscores, health-related quality of life (PDQ-39) summary index and mobility- and ADL-subscores. RESULTS At 1/5/12/24 months follow up, mean amplitude (1.8/2.5/2.6/2.8 V), impedance (1107/1286/1229/1189 Ω) and TEED (33.7/69.0/84.4/93.0 V2*μs*Hz/Ω) mainly increased in the first 5 months, while mean pulse width (60.0/62.5/65.1/65.8 μs), frequency (130/137.7/139.1/142.7 Hz) remained relatively stable. Typical programming (single monopolar electrode contact) was used in 80.7% of electrodes. Double monopolar (11/114) and bipolar (2/114) stimulation was only rarely required. There was no significant difference in clinical outcomes between the patient groups requiring contact changes (n = 32/28.1%) nor between typical (n = 83/72.8%) versus non-typical programming. Energy used for STN-DBS was higher for the dominant side of PD. CONCLUSION In the first 5 months an increase in amplitude is required to compensate for various factors. Monopolar stimulation is sufficient in 80% of patients at 24 months. Homogeneous stimulation strategies can account for the favorable outcomes reported in the Earlystim study

Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial

Background Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. Methods We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1: 1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only. Findings Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363.3 mg/day [SE 41.8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245.8 mg/day [40.4]) in those assigned medical therapy alone (p<0.0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0.65 points [SE 0.15]) and did not change with medical therapy alone (-0.02 points [0.15]); the between-group difference in change from baseline was significant (p=0.0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1.26 points [SE 0.35]) and had increased with medical therapy alone (1.12 points [0.35]); the between-group difference was significant (p<0.0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide. Interpretation In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications