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Since cholinergic neurotransmission plays a major role in cognition, stimulation of the nicotinic acetylcholine receptor may be a target for cognitive enhancement. While nicotine improves performance on several cognitive domains, results of individual studies vary. A possible explanation for these findings is that the effect of nicotine administration may be dependent on baseline cognitive function, where subjects with a suboptimal cognitive performance may benefit from nicotine, while subjects who already perform optimally may show a decline in performance after nicotinic stimulation. We conducted a double-blind randomised placebo-controlled crossover trial, examining the effects of placebo, 1, and 2mg of nicotine on cognition in young (n=16, age 18-30 years) and healthy elderly (n=16, age 60-75 years) subjects. We hypothesised that the elderly would benefit more from nicotine compared to young subjects, as normal ageing is associated with decreases in cognitive function. Attention, working memory, visual memory, information-processing speed, psychomotor function, stereotypy, and emotion recognition were assessed. Compared to the young volunteers, the elderly performed significantly worse on psychomotor function and emotion recognition in the placebo condition. Nicotine had no effect in the young volunteers and decreased performance on working memory and visual memory in the elderly. Contrary to our hypothesis, the effect of nicotine was dependent on baseline performance in both the groups, with subjects with lower baseline performance benefiting from nicotine administration, while those with higher baseline performance performed worse after nicotine administration. This suggests that subjects with lower cognitive performance, irrespective of age, may benefit from nicotine., (Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.)

Introduction: Action monitoring has been reported to be disturbed in Major Depressive Disorder (MDD). Well-known markers for this action monitoring process are the error negativity/error-related negativity (Ne/ERN) and error positivity (Pe), both event-related potentials (ERP) generated in the anterior cingulate cortex. This study aims to explore the impact of symptom severity reduction on the Ne/ERN and Pe in MDD., Methods: Behavioural and ERP measurements were obtained in 15 MDD patients during performance on a speeded flankers task during the early stages of a depressive episode and compared with those recorded after 7 weeks of treatment. The same schedule was used in 15 healthy controls., Results: Whereas overall Ne/ERN and Pe peak amplitudes did not improve from sessions 1 to 2 in the patients, positive correlations emerged between between-session changes in symptom severity and Ne/ERN amplitudes. No such correlations were observed for the Pe. ERP amplitudes in the controls also remained unchanged between both sessions. Significant group differences were observed between MDD patients and controls for the Pe, but not for the Ne/ERN., Conclusions: Whereas a clear association was observed between the level of symptom reduction and the level of improvement in Ne/ERN amplitudes in a MDD sample, no overall Ne/ERN enhancements were observed during symptom remission. Subsequent research is needed to further investigate the possible impact of depressive symptom reduction on the action monitoring in MDD. Several factors that might explain the absence of Ne/ERN group differences between patients and healthy controls in the current sample will also be discussed.

Major depressive disorder (MDD) is characterized by disturbances of mood and affect, but also by a distinct pattern of psychomotor and cognitive deficits such as motor retardation and impaired executive functioning. An important aspect of executive functioning is performance monitoring, i.e., a continuous checking whether intended action goals have been reached and whether correction of the applied strategy is necessary. A well-known marker for action monitoring is the error negativity (Ne) or error-related negativity (ERN), an event-related potential (ERP) component generated in the anterior cingulate cortex (ACC) following erroneous responses. To date, Ne/ERN amplitudes have been investigated in moderately depressed patients only. The present study is the first to investigate action monitoring in severely depressed patients (mean Hamilton score=28.4). In addition, the patients' psychomotor performance was assessed to see whether there is a relationship between action monitoring and psychomotor retardation. Behavioural and ERP measurements were obtained during performance on a speeded two-choice reaction task in 26 patients with MDD and 25 healthy, matched controls. Psychomotor performance measures were speed of simple movements in various psychomotor tasks and the score on the Salpêtrière retardation rating scale (SRRS). Relative to the controls, the patients' behavioural results revealed a similar, but slower performance pattern. Overall between-group differences were demonstrated for the error positivity (Pe) amplitudes, but not for the Ne/ERN amplitudes. However, correlations of the Ne/ERN amplitude with several psychomotor variables were strong. In the depressed patients taking benzodiazepines an additional attenuation of Ne/ERN amplitudes was observed. Only severely depressed patients manifesting retardation showed impeded action monitoring. The correlations between action monitoring and psychomotor performance indicate that in MDD these two processes are highly interdependent, both being deregulated. Moreover, the same network of brain regions is likely to be implicated in both processes.

To study action monitoring in anorexia nervosa, behavioral and EEG measures were obtained in underweight anorexia nervosa patients (n=17) and matched healthy controls (n=19) while performing a speeded choice-reaction task. Our main measures of interest were questionnaire outcomes, reaction times, error rates, and the error-related negativity ERP component. Questionnaire and behavioral results indicated increased perfectionism in patients with anorexia nervosa. In line with their perfectionism and controlled response style patients made significantly less errors than controls. However, when controlling for this difference in error rates, the EEG results demonstrated a reduced error-related negativity in the patient group. These seemingly contradictory outcomes of improved performance and reduced error monitoring are discussed in relation with indications of anterior cingulate cortex hypoactivity in anorexia nervosa patients.

Humans need to monitor their actions continuously to detect errors as fast as possible and to adjust their performance to prevent future errors. This process of action monitoring can be investigated by measuring the error-related negativity (ERN), an ERP component elicited immediately after an error. In the current study, we investigated action monitoring after administration of the classic antipsychotic haloperidol (2.5 mg), the atypical antipsychotic olanzapine (10 mg), and the antidepressant paroxetine (20 mg), a selective serotonin reuptake inhibitor. Healthy volunteers (N = 14) were administered the three compounds and placebo in a randomized, double-blind, single-dose, four-way cross-over design. All participants performed a speeded two-choice reaction task, while event-related potentials and behavioral measurements were obtained. Both haloperidol and olanzapine significantly reduced ERN amplitudes. After paroxetine, the ERN was not different from placebo. N2 congruency effects were not affected by treatment condition. Only olanzapine demonstrated behavioral effects, namely a slowing of responses, an increase in error rates, and the absence of performance adjustments. The attenuated ERNs after the dopamine antagonist haloperidol are in line with the presumed role of dopamine in action monitoring. Haloperidol is thought to block dopaminergic signaling, thus reducing ERN amplitudes. On the other hand, the effects of olanzapine are mainly caused by its sedative side effects, leading to a decline in motivation and appraisal of errors. Finally, the absence of any effects after paroxetine suggests that serotonin transmission does not play a direct role in regulating mechanisms related to action monitoring.

Objectives: A vast amount of studies demonstrates the presence of psychomotor slowing in schizophrenia. The objective of the present study was to investigate whether this overall psychomotor slowing can be divided into distinct processes that differentially affect cognitive functioning in schizophrenia., Methods: The pen-tip movements of 30 schizophrenic inpatients and 30 matched controls were digitally recorded during performance of the Symbol Digit Substitution Test (SDST) and analysed to differentiate matching time and writing time, representing the cognitive and sensorimotor component of slowing, respectively. In addition, the results were compared to each other and to the scores of traditional neuropsychological tests that assess domains such as memory and attention., Results: Both matching time and writing time were longer in the schizophrenic patients relative to the controls but did not correlate. Only matching time correlated significantly with the conventional neuropsychological test results., Conclusions: Although schizophrenic patients display both sensorimotor and cognitive slowing, the two processes are unrelated. Furthermore, only the cognitive component was associated with most of the cognitive deficits as measured by traditional neuropsychological tests.

Introduction: Few studies using objective and sensitive measuring techniques have investigated whether psychomotor retardation (PR), an important symptom of a major depressive disorder (MDD), is also present in dysthymic patients. In this study, the following questions were addressed: (1) is PR also prevalent in dysthymia? (2) If so, is the PR cognitive or motor in nature? And (3) does the nature and degree of the PR in patients with dysthymia differ from the PR in MDD patients found in earlier studies?, Methods: PR was measured by comparing the, digitally recorded, fine motor performance of 20 unmedicated dysthymic inpatients (mean age: 33) and 32 controls on copying and drawing tasks. In addition, the performance of the dysthymic patients was compared to the performance results of 32 unmedicated MDD inpatients collected in an earlier study., Results: The dysthymic patients were not slower than the controls in performing the fine motor tasks: neither initiation time (IT) nor movement time (MT) were prolonged. As expected, the MDD patients did show significantly longer ITs and MTs in all tasks compared to the controls. On the clinical Salpetriere Retardation Rating Scale (SRRS), the dysthymic patients had high scores on mainly subjective cognitive items like concentration and memory complaints., Limitations: The dysthymic patients had significantly less severe forms of depression compared to the MDD patients. As dysthymia, by definition, is a less severe form of depression we could not examine whether PR would manifest itself in severely depressed dysthymic patients, as is the case in certain MDD patients., Conclusion: In this study, no objective evidence was found for PR in dysthymic patients during fine motor tasks. PR may be used to differentiate between dysthymia and MDD.

Rationale: Action monitoring has been studied extensively by means of measuring the error-related negativity (ERN). The ERN is an event-related potential (ERP) elicited immediately after an erroneous response and is thought to originate in the anterior cingulate cortex (ACC). Although the ACC has a central role in the brain, only a few studies have been performed to investigate directly the effects of drugs on action monitoring. A recent theory argues that the mesencephalic dopamine system carries an error signal to the ACC, where it generates the ERN., Methods: ERPs and behavioral measurements were obtained from 12 healthy volunteers performing an Eriksen Flankers task. On each of the 4 test days, the stimulant D-amphetamine, the sedative lorazepam, the antidepressant mirtazapine, or a placebo was orally administered in a double-blind, four-way crossover design., Results: The indirect dopamine agonist amphetamine led to a strong enlargement of ERN amplitudes without affecting reaction times. Lorazepam and mirtazapine both showed slowing of responses, but only lorazepam led to reduced ERN amplitudes., Conclusions: Administration of amphetamine leads to stimulated action monitoring, reflected in increased ERN amplitudes. This result provides evidence for dopaminergic involvement in action monitoring and is in line with differences in ERN amplitude found in neuropsychiatric disorders also suggesting dopaminergic involvement. The different effects for lorazepam and mirtazapine are probably caused by the neurobiological characteristics of these two types of sedation. Action monitoring is suppressed after administration of lorazepam, because the GABAergic pathways directly inhibit ACC functioning, whereas the histaminergic pathways of mirtazapine do not innervate the ACC directly.

Background: The results of previous studies on psychomotor retardation (PR) in elderly depressed patients are inconsistent. The purpose of this study was (1) to try and establish whether elderly depressed patients show PR, and (2) if so, which process (cognitive/motor or both) is mainly slowed?, Methods: Twelve elderly depressed patients and healthy controls (age: 70) were compared on figure copying tasks in which the cognitive task difficulty was manipulated., Results: Both initiation time (IT) and movement time (MT) were prolonged in the patient group. The effects of the cognitive manipulations were not larger in the patient group., Limitations: The sample size was small. Furthermore, patients were not medication free., Conclusions: A cognitive and a more pronounced motor retardation was found. Clinicians should be aware of this at least additive effect of aging and depression on PR in elderly patients.

Schizophrenia and depression have an overlap in symptomatology, namely a slowing in both motor and mental activities, denoted in depression as 'psychomotor retardation' and in schizophrenia as 'psychomotor poverty'. By means of a new technique that allows the measurement of psychomotor speed and the computerized analysis of writing movements recorded during the performance of the Digit Symbol Test, it indeed proved to be possible to observe a slowing in both disorders. In addition, a different structure of slowing in the two patient groups could be identified.