O.A. van den Heuvel

Emotion regulation before and after transcranial magnetic stimulation in obsessive compulsive disorder

BACKGROUND Impaired emotion regulation may underlie exaggerated emotional reactivity in patients with obsessive compulsive disorder (OCD), yet instructed emotion regulation has never been studied in the disorder. METHOD This study aimed to assess the neural correlates of emotion processing and regulation in 43 medication-free OCD patients and 38 matched healthy controls, and additionally test if these can be modulated by stimulatory (patients) and inhibitory (controls) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (dlPFC). Participants performed an emotion regulation task during functional magnetic resonance imaging before and after a single session of randomly assigned real or sham rTMS. Effect of group and rTMS were assessed on self-reported distress ratings and brain activity in frontal-limbic regions of interest. RESULTS Patients had higher distress ratings than controls during emotion provocation, but similar rates of distress reduction after voluntary emotion regulation. OCD patients compared with controls showed altered amygdala responsiveness during symptom provocation and diminished left dlPFC activity and frontal-amygdala connectivity during emotion regulation. Real v. sham dlPFC stimulation differentially modulated frontal-amygdala connectivity during emotion regulation in OCD patients. CONCLUSIONS We propose that the increased emotional reactivity in OCD may be due to a deficit in emotion regulation caused by a failure of cognitive control exerted by the dorsal frontal cortex. Modulatory rTMS over the left dlPFC may influence automatic emotion regulation capabilities by influencing frontal-limbic connectivity.

rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis.

Objective To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) on working memory performance, while measuring task-related brain activation and task-related brain connectivity in patients with multiple sclerosis (MS). Methods 17 patients with MS and 11 healthy controls (HCs) underwent 3 experimental sessions (baseline, real-rTMS, sham-rTMS), all including an N-back task (3 task loads: N1, N2, N3; control condition: N0) inside the MR scanner. Prior to imaging, real-rTMS (10 Hz) was applied to the right DLPFC. The stimulation site was defined based on individually assessed N-back task activation at baseline and located using neuronavigation. Changes in whole brain functional activation and functional connectivity with the right DLPFC were calculated. Results N-back task accuracy (N2 and N3) improved after real-rTMS (and not after sham-rTMS) compared with baseline (p=0.029 and p=0.015, respectively), only in patients. At baseline, patients with MS, compared with HCs, showed higher task-related frontal activation (left DLPFC, N2>N0), which disappeared after real-rTMS. Task-related (N1>N0) functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para)cingulate gyrus increased in patients after real-rTMS when compared with sham stimulation. Conclusions In patients with MS, N-back accuracy improved while frontal hyperactivation (seen at baseline relative to HCs) disappeared after real-rTMS. Together with the changes in functional connectivity after real-rTMS in patients, these findings may represent an rTMS-induced change in network efficiency in patients with MS, shifting patients’ brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS.

Obsessieve-compulsieve stoornis.

Obsessief-compulsieve stoornis (OCS; ook bekend als OCD [obsessive-compulsive disorder]) wordt gerekend tot de angststoornissen en kan zich op elke leeftijd openbaren maar doorgaans gebeurt dit tijdens de adolescentie.Deze aandoening kan leiden tot ernstige invaliditeit: kinderen kunnen hun schoolopleiding staken en ouderen komen soms hun huis niet meer uit. De WHO rekent OCS tot de 20 meest invaliderende aandoeningen. De prevalentie is ongeveer 0,8% bij volwassenen en 0,25% bij kinderen in de leeftijd van 5-15 jaar. Het is echter goed mogelijk dat in beide groepen de prevalentie aanmerkelijk hoger is. Veel patienten zoeken pas na lange tijd (gemiddeld 17 jaar!) behandeling en dan vaak bij andere artsen en niet bij psychiaters. Om deze reden stellen de schrijvers van dit overzichtsartikel dat ook andere artsen dan psychiaters bedacht moeten zijn op deze aandoening.Wat zijn de symptomen? Obsessies zijn ongewilde ideeen, beelden of opwellingen die herhaaldelijk in de gedachten van iemand opkomen. Hoewel zij door de patientworden herkend als komende uit zichzelf worden zij ervaren als ‘egodystoon’ (niet bij het karakter passend, ongewild en beangstigend).

Risk prediction and treatment monitoring are crucial for prevention and management of compulsive dopamine use in Parkinson's disease

PARKINSON’S DISEASE (PD) PATIENTS WITH SEVERE RESPONSE FLUCTUATIONS NEED PROTECTION FROM CAREGIVERS, PREVENTING COMPLICATIONS FROM THE PSYCHOSTIMULANT FEATURES OF DOPAMINE REPLACEMENT THERAPY (DRT) Despite its positive effects in the treatment for motor symptoms in PD, DRT leads to a number of motor and non-motor side effects. Non-motor side effects include dopamine dysregulation syndrome (DDS) occurring in 3% to 4% of PD patients taking DRT. DDS is characterised by compulsive DRT seeking and hoarding, selfmedication and withdrawal symptoms. DDS has devastating consequences for daily functioning and is challenging to manage. Important insights into this condition are offered in the paper by Cilia and colleagues, reporting on a retrospective naturalistic longitudinal study on the demographic and clinical risk factors for DDS and the factors related to positive treatment outcome. Logistic regression analysis revealed that a positive family history of PD, a (family) history of depression, severity of motor fluctuations (mainly motor difference between ‘on’ and ‘off ’) and severity of neuropsychiatric symptoms (ie, depression, disinhibition, irritability and delusions) were independent predictors of DDS. Regarding the course of DDS at follow-up, duodenal levodopa infusion and, less consistently, deep brain stimulation (DBS) of the subthalamic nucleus (STN) were treatment options associated with resolution of nonmotor fluctuations and addictive symptoms. This is in accordance with two recent studies showing that STN DBS reduces compulsive use of DRT, 4 probably related to reduced motor fluctuations, reduction of DRT dosage and invigorated treatment monitoring. Even more interesting, and clinically relevant, was the finding that effective caregiving, contributing to monitoring of drug compliance, plays a key role in long-term outcome of DDS. This result underlines the need for intensive monitoring of medication intake in DDS and optimal support of the patient during ‘off ’ moments. DRT abuse in response to severe motor fluctuations may be regarded as a form of self-treatment for wearingoff–related anxiety and anticipation aimed to avoid any ‘off ’ states during the day. Pharmacological treatment of neuropsychiatric symptoms, co-occurring with DDS, did not show a strong added value to the long-term outcome of DDS. However, the retrospective nature of this study and the limited sample size hamper optimal interpretation of the effects of mood and psychosis management. There is a great need for prospective longitudinal designs following de novo (unmedicated) patients during treatment for advanced stage. This enables the identification of features related to susceptibility to DDS, allowing the development of preventive strategies and detection and management of symptoms at an early stage, based on better understanding of the underlying mechanisms. The pathophysiology of impulse control disorders and DDS in PD is still poorly understood. One possible neurobiological candidate for susceptibility to DDS is premorbid, possibly genetically determined, striatal dopaminergic denervation resulting in lower availability of the dopamine transporter (DaT) and denervation-induced postsynaptic receptor hypersensitivity. DDS shares some core behavioural features of psychostimulant addiction, suggesting that DRTcan acquire psychostimulant-like properties in PD patients with severe dopaminergic denervation. This hypothesis is recently supported by the results from an α-synuclein rat model. A clinically relevant question is now whether DaT single-photon emission computed tomography scans can contribute to the prediction of DDS in individual PD patients in order to limit potential harm, using prevention strategies in at-risk patients.