From self-induced to perceived errors – A generalized over-monitoring activity in obsessive–compulsive disorder

Well-functioning error monitoring of the inner and outer environments is essential for adaptively altering behavior, while malfunction characterizes conditions such as obsessive–compulsive disorder (OCD). The underlying brain processing is manifested as Error-Related Negativity (ERN) signal elicited following error comission, and Perceived Error Related Theta Activity (PERTA) signal elicited following detection of discrepancy in the environment. Yet, while enhanced ERN was repeatedly demonstrated in OCD patients and was found to be potentiated among their unaffected first degree relatives, no comparable observations were reported with regard to PERTA. We recorded EEG activity while OCD patients, OCD patients’ siblings (Family), and healthy controls (HC) performed computerized tasks. For the examination of ERN we used the Stroop task and for the examination of PERTA we presented correct and incorrect mathematical equations. Increased ERN (0–120 ms post response) was observed in both the OCD and Family groups, but only the OCD patients’ signal significantly differed from that of HC's. Similarly, modified PERTA activity was observed in both the OCD and Family groups in the N1 peak (65–125 ms post perceived error), but only for the OCD group this activity significantly differed from that of HC. Both ERN and PERTA's N1 are fast occurring peaks, which suggests that OCD is associate with a constantly over-activated detection system that monitors the inner and outer environment and reacts promptly following detection of a mistake. Furthermore, the modified but non-significantly different activity of the Family group suggests that the pathological condition evolves in vulnerable individuals with neuronal predisposition.     

Mapping scores onto stages: mini-mental state examination and clinical dementia rating.

OBJECTIVE: Although the clinical course of Alzheimer disease (AD) is gradual, it is useful for a number of reasons to distinguish between different levels of severity. The Clinical Dementia Rating (CDR) has demonstrated high validity and reliability for this purpose, but it requires a considerable amount of data to be collected both from the patient and from an informant. In the present study, the authors mapped Mini-Mental State Examination (MMSE) scores onto CDR categories to determine how well the MMSE performs as a surrogate of the CDR as a timesaving method of staging dementia. METHOD: Eight hundred sixty-three probands, including 524 patients with probable AD, 92 patients with questionable dementia, and 247 with memory complaints but no objective cognitive impairment, were included. Cutoff scores were identified on one-half of the sample using a receiver operating characteristic analysis. The cutoff values were then applied to the other half of the sample, and the agreement between MMSE score ranges and CDR stages was determined by calculating Cohen's kappa. RESULTS: The MMSE discriminated well between CDR stages 0.5, 1, 2, and 3 but performed poorly in the separation between CDR stages zero and 0.5. The MMSE ranges were 30 for no, 26-29 for questionable, 21-25 for mild, 11-20 for moderate, and 0-10 for severe dementia. Substantial agreement between the two instruments was obtained for the categories mild (kappa=0.62, p<0.001, N=115), moderate (kappa=0.69, p<0.001, N=114), and severe dementia (kappa=0.76, p<0.001, N=39), whereas the agreement was moderate for no (kappa=0.44, p<0.001, N=120) and only fair for questionable dementia (kappa=0.28, p<0.001, N=42). CONCLUSION: The MMSE can be used as a surrogate measure for the CDR for the staging of dementia in AD.     

The rationale for continuous dopaminergic stimulation in advanced Parkinson's disease

Control of movement depends on the continuous release of dopamine by neurons in the basal ganglia of the brain. The degeneration of these neurons in Parkinson's disease (PD) interferes with the flow of dopamine, leading to classic motor symptoms. In early PD, enough dopaminergic neurons remain to store dopamine provided by periodic dosing with oral levodopa and relatively normal, tonic levels of dopamine release are maintained. PD progression leads to degeneration of remaining dopaminergic terminals and loss of buffering capacity for exogenous levodopa. As a result, there are supraphysiological levels of dopamine after dosing and troughs when the available dopamine has been depleted. These divergent levels are associated with dyskinesia and ‘off’ states, respectively. Treatment strategies that provide a continuous flow of dopamine and can thus mimic normal physiological dopamine stimulation have potential to improve motor control for patients with advanced PD.     

Can acupuncture combined with SSRIs improve clinical symptoms and quality of life in patients with depression? Secondary outcomes of a pragmatic randomized controlled trial

ObjectivesTo explore the effects of acupuncture (manual acupuncture or electroacupuncture) combined with SSRIs for moderate to severe depression improving major clinical symptoms and life quality of the patients on secondary outcomes.DesignPragmatic, parallel, randomized controlled trial.Setting6 hospitals in China.Interventions6 weeks of manual acupuncture (MA)+selective serotonin reuptake inhibitors (SSRIs), electroacupuncture (EA)+SSRIs, and SSRIs alone.Main outcome measuresThe primary outcome was response rate of 17-item Hamilton Depression Scale (HAMD-17) total score at 6^th week. The secondary outcomes reported in this analysis were HAMD-17 factor scores at 1^st, 2^nd, 4^th, 6^th, 10^th week and WHO Quality of Life-BREF (WHOQOL-BREF) scores at 6^th week.Results477 patients were randomly assigned into MA + SSRIs (n = 161), EA + SSRIs (n = 160), or SSRIs alone (n = 156) groups. For HAMD-17 (at 6^th week), the MA + SSRIs group was significantly better than the SSRIs alone group in retardation factor (p = 0.008), while the EA+SSRIs group was significantly better than the SSRIs alone group in anxiety/somatization factor (p<0.001) and sleep disturbance factor (p = 0.002). For WHOQOL-BREF (at 6^th week), the EA + SSRIs group, compared with the SSRIs alone group, produced a more significant improvement in the overall quality of life, general health, physical health, and psychological health (p<0.05). While, the MA + SSRIs group, compared to the SSRIs alone group, showed significant advantage only in psychological health (p = 0.023).ConclusionsEither MA or EA combined SSRIs treatment could improve symptoms and quality of life for patients with moderate to severe depression. The main limitation of this trial was not using a sham control therefore the placebo effect could not be excluded.     

Functional neuroimaging and clinical features of drug naive patients with de novo Parkinson’s disease and probable RBD

IntroductionThe association between Parkinson Disease (PD) and REM sleep behavior disorder (RBD) has been related to a specific, malignant clinical phenotype. Definite RBD diagnosis requires video-polysomnography that is often unfeasible. A malignant clinical PD-RBD phenotype could be expected also in PD patients with probable RBD. Aim of this cross-sectional study was to evaluate whether a more severe neuropsychological and functional neuroimaging phenotype can be identified in PD patients with probable RBD.MethodsThirty-eight de novo, drug naïve PD patients underwent a first-line clinical assessment and a second-line multimodal assessment, including neuropsychological evaluation, ¹²³I-FP-CIT-SPECT and ¹⁸F-FDG-PET, which were compared between PD patients with (PD + RBD+) and without (PD + RBD-) probable RBD.ResultsOn first-line assessment, PD + RBD + patients had significantly more constipation (p = 0.02) and showed worse olfaction (p = 0.01) compared with PD + RBD-while the two groups were similar as for age, presence of orthostatic hypotension, UPDRS-III and MMSE scores. On second-line assessment, PD + RBD + patients showed a worse neuropsychological test profile, more severe nigro-striatal dopaminergic impairment, mainly at caudate level in the less affected hemisphere (p = 0.004) and impaired brain glucose metabolism, with relative hypometabolism in posterior cortical regions and relative hypermetabolism mainly in anterior regions of the more affected hemisphere (p = 0.015).ConclusionsPD patients with probable RBD are likely to have a more severe neuropsychological and functional brain-imaging phenotype already at the time of diagnosis.