Motor learning and performance in schizophrenia and aging: two different patterns of decline.

Psychomotor slowing has consistently been observed in schizophrenia, however research on motor learning in schizophrenia is limited. Additionally, motor learning in schizophrenia has never been compared with the waning of motor learning abilities in the elderly. Therefore, in an extensive study, 30 individuals with schizophrenia, 30 healthy age-matched controls and 30 elderly participants were compared on sensorimotor learning tasks including sequence learning and adaptation (both explicit and implicit), as well as tracking and aiming. This paper presents new findings on an explicit motor sequence learning task, an explicit verbal learning task and a simple aiming task and summarizes all previously published findings of this large investigation. Individuals with schizophrenia and elderly had slower Movement Time (MT)s compared with controls in all tasks, however both groups improved over time. Elderly participants learned slower on tracking and explicit sequence learning while individuals with schizophrenia adapted slower and to a lesser extent to movement perturbations in adaptation tasks and performed less well on cognitive tests including the verbal learning task. Results suggest that motor slowing is present in schizophrenia and the elderly, however both groups show significant but different motor skill learning. Cognitive deficits seem to interfere with motor learning and performance in schizophrenia while task complexity and decreased movement precision interferes with motor learning in the elderly, reflecting different underlying patterns of decline in these conditions. In addition, evidence for motor slowing together with impaired implicit adaptation supports the influence of cerebellum and the cerebello-thalamo-cortical-cerebellar (CTCC) circuits in schizophrenia, important for further understanding the pathophysiology of the disorder.

Impaired Sensorimotor Adaption in Schizophrenia in Comparison to Age-Matched and Elderly Controls.

BACKGROUND: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum. OBJECTIVES: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls. METHODS: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°. RESULTS: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects. CONCLUSIONS: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks.

Systematic review of cognitive event related potentials in euthymic bipolar disorder.

Cognitive deficits are critical features of bipolar disorder (BD), greatly impacting quality of life. The aim is to systematically review and critically evaluate underlying event related potential (ERP) features in euthymic BD relating to differences in sensory processes, attention, inhibition and conflict monitoring compared with healthy controls. 911 unique articles were identified using the PubMed database and 14 studies met the inclusion criteria. Individuals with BD in a euthymic state have reduced P50 sensory gating and reduced P100 amplitudes compared with healthy controls. Many studies demonstrated reduced P300 amplitudes and normal P300 latencies in BD. In addition, reduced NoGo N2 and abnormal NoGo P3 activity were observed in BD. Finally, there is some evidence of reduced error-related negativity amplitudes in BD. Importantly, ERP modulations vary with stimulus factors and clinical profile. The functional significance of these findings and clinical implications are discussed. ERP differences in BD arise at various stages of cognitive processing, specifically in early auditory and visual processing, attention allocation, context updating, inhibition and conflict monitoring. Treating these deficits and their underlying neurobiological disturbances corresponding to abnormal performance on cognitive tasks may aid functional remission. This knowledge might enable personalized treatment interventions targeting specific cognitive deficits.

An overview of pharmacotherapy for bipolar I disorder.

INTRODUCTION: Bipolar I disorder (BD I) is complex with a chronic course that significantly impacts a sufferer's quality of life. As of right now, there are many available treatments that aim to rapidly treat manic or depressive episodes and stabilize mood. The purpose of this report is to provide an up-to-date comprehensive review of the available evidence-based trials of pharmacotherapy for the treatment of BD I. AREAS COVERED: This paper reviews randomized active comparator-controlled or placebo-controlled trials evaluating the use of current pharmacotherapy in adults with BD I from phase III to clinical practice. Monotherapy and combination therapy for acute and long-term treatment were reviewed for this purpose. EXPERT OPINION: There are many treatments available for BD mania; however, the depressive and stabilization phases of the illness remain a clinical challenge. Unfortunately, randomized controlled trials do not represent 'real world' patients, as their strict inclusion and exclusion criteria do not allow for different features sometimes present in patients to be considered. Research efforts must also focus on treating cognitive deficits, which adds to lower functional outcome. The authors believe that there is dire need for new, more targeted treatments in BD I, with a critical view of the side effects.

Implicit motor sequence learning in schizophrenia and in old age: reduced performance only in the third session.

Although there still is conflicting evidence whether schizophrenia is a neurodegenerative disease, cognitive changes in schizophrenia resemble those observed during normal aging. In contrast to extensively demonstrated deficits in explicit learning, it remains unclear whether implicit sequence learning is impaired in schizophrenia and normal aging. Implicit sequence learning was investigated using a computerized drawing task, the 'implicit pattern learning task (IPLT)' in 30 stable patients with schizophrenia, 30 age-matched controls and 30 elderly subjects on two consecutive days and after 1 week (sessions 1, 2 and 3). Fixed sequence trials were intermixed with random trials, and sequence learning was assessed by subtraction of the response time in fixed sequence trials from random trials. Separate analyses of response times and movement accuracy (i.e., directional errors) were performed. Explicit sequence knowledge was assessed using three different awareness tasks. All groups learned equally during sessions 1 and 2. In session 3, control subjects showed significantly larger learning scores than patients with schizophrenia (p = .012) and elderly subjects (p = .021). This group difference is mainly expressed in movement time and directional errors. Patients with schizophrenia demonstrated less subjective sequence awareness, and both patients with schizophrenia and elderly subjects had less explicit sequence recall. Explicit recall was positively correlated with task performance in all groups. After a short 24 h interval, all subjects showed similar improvements in implicit sequence learning. However, no benefit of prior task exposure 1 week later was observed in patients with schizophrenia and elderly subjects compared to controls. As patients with schizophrenia and elderly both display less explicit sequence recall, the control group superiority after 1 week could be explained by an explicit learning component. The few patients with schizophrenia and elderly subjects who had some sequence recall could possibly utilize this explicit knowledge to improve their task performance but did this by distinct mechanisms.

Unraveling psychomotor slowing in bipolar disorder.

BACKGROUND/AIMS: In addition to affective and cognitive symptomatology, psychomotor deficits are known to be present in bipolar disorder (BD). Psychomotor functioning includes all of the processes necessary for completing a movement, from planning to initiation and execution. While these psychomotor symptoms have been studied extensively in schizophrenia and major depressive disorder, only simple measures have been conducted in BD. The present study examines psychomotor functioning in BD. METHODS: Twenty-two euthymic BD patients and 21 healthy controls performed three computerized copying tasks varying in cognitive load. Movement times (MT), reflecting fine motor processing, and initiation times (IT), reflecting cognitive processing of visual-spatial information, were separately measured in each group. RESULTS: The BD patients had longer IT but not MT in the simplest task and the opposite pattern of longer MT but not IT in the complex task. However, when controlling for residual mood symptoms, the MT were no longer significantly slower in the BD group. CONCLUSIONS: The longer MT and IT in BD reflect overall psychomotor slowing. Specifically, the results provide evidence for cognitive slowing in BD. In addition, the longer MT in the complex task reflect a slowed motor component of movement when the cognitive load is high and when depressive symptoms are present. These findings extend the current knowledge of the nature of psychomotor slowing in BD and may have important prognostic implications for patients.

Electrophysiological (EEG) evidence for reduced performance monitoring in euthymic bipolar disorder.

OBJECTIVES: Apart from mood episodes, many cognitive deficits are present in bipolar disorder (BD). Performance monitoring is an important aspect of executive functioning and involves continuous monitoring of behavior and making subsequent changes when an error is made. On a neurophysiological level, the error-related negativity (ERN), an event-related brain potential (ERP) generated in the anterior cingulate cortex (ACC), reflects this process of performance monitoring. Abnormal ERN amplitudes have been observed in many major psychiatric disorders. However, despite conflicting evidence regarding the role of the ACC in BD, no studies to date have investigated performance monitoring as reflected in the ERN in BD. METHODS: Sixteen patients with BD in a euthymic state and 14 matched healthy controls performed a speeded two-choice reaction-time paradigm (Flankers Task) while electroencephalogram (EEG) measures were obtained. Behavioral and ERP measurements were analyzed for the two groups. RESULTS: The patients with BD, although euthymic, scored higher on depressive symptoms than healthy controls. While no behavioral group differences were found, patients with BD displayed lower ERN amplitudes than healthy controls when controlling for effects of residual mood. CONCLUSIONS: The lower ERN amplitudes in the BD group reflect reduced performance monitoring and extend current knowledge of executive functioning in BD. Importantly, these findings go a long way to resolving the contradictory results regarding ACC involvement in BD by showing that taking into account residual mood may greatly influence error-related ACC activations and is critically important in understanding cognitive deficits in BD.

The nature of the relationship of psychomotor slowing with negative symptomatology in schizophrenia.

INTRODUCTION: Psychomotor slowing is an important feature of schizophrenia and the relation with negative symptoms is not fully understood. This study aims, first, to investigate the association between negative symptoms and psychomotor slowing. Second, we want to investigate whether fine motor slowing reflects clinically observable gross motor slowing. METHODS: In 53 stabilised adult patients with schizophrenia, negative symptoms were assessed using the Positive and Negative Syndrome Scale negative subscale (PANSS-N) with two calculated factors entering the analysis: an expressivity factor and a volitional factor. Psychomotor slowing was assessed by using a modified version of the Salpêtrière Retardation Rating Scale, the Finger Tapping Test, and a writing task measuring fine psychomotor slowing. RESULTS: Negative symptomatology is associated with difficulties in the initiation of fine motor movements, r=.334, p<.05, whilst planning and execution are not. The volitional factor, r=-.407, p=.005, but not the expressivity factor, r=.060, p=.689, is significantly associated with psychomotor slowing. No associations between fine and clinically observable gross psychomotor functioning were found. CONCLUSIONS: These findings indicate that higher values of negative symptomatology-more specifically the volitional deficit cluster-affect motor initiation, indicating a heterogeneity in the PANSS-N factorial structure, and that gross and fine psychomotor functioning are affected independently.

Longitudinal evaluation of the psychomotor syndrome in schizophrenia.

Little is known about the longitudinal course of psychomotor signs and symptoms after illness onset in schizophrenia. Therefore, a 1-year follow-up study was conducted in which patients with schizophrenia were assessed three times with an extensive battery of psychomotor rating scales and tests. The syndromic structure of psychomotor symptoms was also studied. In accordance with a neurodevelopmental view on schizophrenia, psychomotor functioning was found to remain stable or improve slightly. Prospective studies with longer follow-up periods are needed to rule out the possibility of neurodegeneration in subgroups of patients and to evaluate possible covariation in the course of psychomotor symptoms.