Age-related deficits in speech production: From phonological planning to motor implementation.

Speaking is one of the most complex motor actions that humans can perform, requiring the coordination between linguistic, cognitive, affective and sensorimotor systems. Perhaps counter-intuitively, it is also one of the easiest acts that humans perform, on a daily basis, from a very early age till the end of life, without even thinking about it. With age, however, spoken language production undergoes significant changes, with potential impacts on interpersonal communication and social participation. Unfortunately, the neurobiological mechanisms involved are unclear, which impedes efforts towards the development of clinical interventions, differential diagnosis strategies and even prevention strategies for this population. In the present study, we examined age differences in speech production using a simple diadochokinetic rates task in which phonological and sequential complexity were manipulated. 85 cognitively healthy adults (20-93 years) were recruited from the general population. Cognitive level, hearing and depression symptoms were measured. Participants produced short and long sequences of simple and complex syllables aloud as quickly, steadily and accurately as possible. Performance was assessed in terms of articulation rate, articulation rate stability and accuracy. Results show that, controlling for cognition, hearing and depression, articulation rate stability and accuracy declined significantly with age. The phonological manipulation had more impact on performance than the sequential manipulation. These findings were interpreted as reflecting age-related central disruptions at the level of phonological and motor planning, which provides important new cues into underlying neurobiological mechanisms.

Sleep habits in middle-aged, non-hospitalized men and women with schizophrenia: a comparison with healthy controls.

Patients with schizophrenia may have sleep disorders even when clinically stable under antipsychotic treatments. To better understand this issue, we measured sleep characteristics between 1999 and 2003 in 150 outpatients diagnosed with Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) schizophrenia or schizoaffective disorder and 80 healthy controls using a sleep habits questionnaire. Comparisons between both groups were performed and multiple comparisons were Bonferroni corrected. Compared to healthy controls, patients with schizophrenia reported significantly increased sleep latency, time in bed, total sleep time and frequency of naps during weekdays and weekends along with normal sleep efficiency, sleep satisfaction, and feeling of restfulness in the morning. In conclusion, sleep-onset insomnia is a major, enduring disorder in middle-aged, non-hospitalized patients with schizophrenia that are otherwise clinically stable under antipsychotic and adjuvant medications. Noteworthy, these patients do not complain of sleep-maintenance insomnia but report increased sleep propensity and normal sleep satisfaction. These results may reflect circadian disturbances in schizophrenia, but objective laboratory investigations are needed to confirm subjective sleep reports.

REM sleep EEG spectral analysis in patients with first-episode schizophrenia.

The pathophysiology of schizophrenia includes abnormalities in subcortical-cortical transfer of information that can be studied using REM sleep EEG spectral analysis, a measure that reflects spontaneous and endogenous thalamocortical activity. We recorded 10 patients with first-episode schizophrenia and 30 healthy controls for two consecutive nights in a sleep laboratory, using a 10-electrode EEG montage. Sixty seconds of REM sleep EEG without artifact were analyzed using FFT spectral analysis. Absolute and relative spectral amplitudes of five frequency bands (delta, theta, alpha, beta1 and beta2) were extracted and compared between the two groups. Frequency bands with significant differences were correlated with BPRS positive and negative symptoms scores. Patients with schizophrenia showed lower relative alpha and higher relative beta2 spectral amplitudes compared to healthy controls over the averaged total scalp. Analysis using cortical regions showed lower relative alpha over frontal, central and temporal regions and higher relative beta2 over the occipital region. Absolute spectral amplitude was not different between groups for any given EEG band. However, absolute alpha activity correlated negatively with BPRS positive symptoms scores and correlated positively with negative symptoms scores. Since similar results have been reported following EEG spectral analysis during the waking state, we conclude that abnormalities of subcortical-cortical transfer of information in schizophrenia could be generated by mechanisms common to REM sleep and waking.

Rivastigmine treatment as an add-on to antipsychotics in patients with schizophrenia and cognitive deficits.

OBJECTIVE: Although new atypical antipsychotic agents have been found to improve overall cognitive function in patients with schizophrenia (SZ), some aspects of memory, attention and executive functions still remain impaired. Acetylcholinesterase (AChE) inhibitors, such as rivastigmine, have been shown to improve cognition in other disorders, particularly Alzheimer's disease. Dysfunctions in cholinergic systems, especially in the prefrontal cortex, have been identified in SZ, suggesting that cholinesterase inhibitors may be effective in treating cognitive deficits in this disease. RESEARCH DESIGN AND METHODS: Using a randomized crossover design, we assessed SZ patients with stable symptoms and poor cognitive functioning. Fifty-eight patients with memory deficits, according to subjective complaints or based on clinicians' observations, were assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS). Only 24 of these subjects met the inclusion criteria. Twenty patients took part in the study (four dropped out). All subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for SZ were maintained on their current antipsychotic medication (18 atypicals and two typicals) and were randomly assigned to treatment with rivastigmine. Dosage was a function of tolerability, beginning at 3 mg/day and progressively increasing to 9 mg/day. Subjects were given the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and 3 and 6 months. RESULTS: The results revealed no significant improvement in any of the cognitive variables investigated following rivastigmine treatment and symptom severity scores remained unchanged over all recorded time periods. CONCLUSION: Rivastigmine treatment did not appear to enhance cognition in SZ patients with important cognitive impairments. This finding needs to be interpreted with care and requires substantiation with larger sample size studies with patients treated with cognitive enhancer for longer periods.

Attention and non-REM sleep in neuroleptic-naive persons with schizophrenia and control participants.

The relationship between sleep architecture and attentional performance was evaluated in neuroleptic-naive patients with schizophrenia and healthy controls. Participants were recorded in a sleep laboratory for two consecutive nights after which selective and sustained attention performance was tested. In both groups of participants, Spearman's rho statistics revealed a negative correlation between reaction time on the selective attention task and sleep spindle density. Only control participants showed a negative correlation between reaction time and duration of stage 2 sleep and a positive correlation between reaction time and duration of stage 1 ("light") sleep. Only persons with schizophrenia showed a negative correlation between reaction time and duration of stage 4 ("deep") sleep. In the sustained attention task, we found no correlation between reaction time and sleep for control participants while persons with schizophrenia showed a negative correlation between reaction time and duration of stage 4 sleep. It is proposed that EEG sleep spindle activity is associated with automatic attentional processing, while stage 2 sleep continuity in healthy individuals and percentage of stage 4 in patients with schizophrenia are associated with voluntary processes. These results support the existence of a relationship between non-rapid-eye-movement sleep and cognitive performance in healthy individuals as well as in persons with schizophrenia.

Are cholinergic enhancers beneficial for memory in schizophrenia? An event-related potentials (ERPs) study of rivastigmine add-on therapy in a crossover trial.

Studies have reported beneficial effects of cholinergic enhancers, e.g., rivastigmine, on memory in schizophrenia but others have not. Possibly, these discrepancies are related to the lack of specificity of the tests used. This study investigated the effect of rivastigmine on memory in schizophrenia using event-related potentials (ERPs). Eighteen patients treated with atypical antipsychotic received rivastigmine adjuvant therapy in a randomized, crossover design. They were assessed at baseline (T1) and on two subsequent occasions (T2 and T3), where one half of the subjects were taken rivastigmine and the other half not. ERPs were recorded during a recognition memory task on each session. Behavioral and ERP data were analyzed using mixed ANOVA models first at T1 to detect potential group differences and for the trial (T1-T2) to determine the influence of rivastigmine, i.e., sessionxgroup interactions. The results showed no group difference at T1 except a trend for one group to be less efficient than the other on RT measures. When controlling for this difference the results on the trial data showed a trend for a benefit of rivastigmine on the RT memory effect. ERP analysis revealed that rivastigmine affects the amplitudes of two components elicited within 150-300 ms over posterior (reduced N2b) and frontal sites (enhanced P2a). It also enhances the magnitude of the memory (old/new) effect on two later components over posterior (N400) and frontal sites (F-N400). These results suggest that rivastigmine improves selective attention by enhancing interference inhibition processes (P2a) and lowering the reactivity to incoming stimulus (N2b). It also improves the integration of information with knowledge (N400) and with its context (F-N400). Generally, this study showed that the beneficial effect of rivastigmine on memory is not unitary but rather comes from its action at different time points within information processing cascade.

Sleep in untreated patients with schizophrenia: a meta-analysis.

The present meta-analysis investigated the characteristics of sleep in patients with schizophrenia without neuroleptic treatment at the time of sleep recording. The 20 selected studies included 652 participants (321 patients with schizophrenia and 331 healthy subjects). Effect sizes were evaluated using d values for the following sleep variables: sleep latency (SL), total sleep time (TST), sleep efficiency index (SEI), total awake time (TAT), stage 2 percentage (S2%), stage 4 percentage, slow-wave-sleep percentage, rapid-eye-movement (REM) percentage, and REM latency. The initial meta-analysis revealed that patients with schizophrenia have the following sleep disorders: increased SL, decreased TST, and decreased SEI. A moderator analysis revealed that these sleep disorders were worse for the neuroleptic-withdrawal group relative to the never-treated group. However, only never-treated patients showed significantly increased TAT and diminished S2%. These results confirm that patients with schizophrenia have sleep disorders that are not necessarily a consequence of neuroleptic treatments, suggesting that sleep disorders are an intrinsic feature of schizophrenia. However, it must be noted that some sleep disorders may be amplified by residual effects of neuroleptic withdrawal, while others appear to be dampened by neuroleptic treatment.

Sleep architecture and its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia.

The goal of the present study was to characterize sleep organization in first episode and neuroleptic-naive patients with schizophrenia and to evaluate relationships between those sleep parameters and clinical symptoms. Eleven patients with acute schizophrenia never treated with neuroleptics were compared to 11 healthy controls. Sleep stages and phasic events (sleep spindles and rapid-eye-movements during REM sleep (REMs) were visually identified. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Compared to controls, patients with schizophrenia had difficulty initiating sleep, decreased stage 4 duration, reduced rapid eye movement (REM) sleep latency, and normal sleep spindles and REMs densities. Positive symptoms correlated negatively with REM sleep latency. The BPRS total score correlated negatively with REM sleep duration and REMs density. The present results indicate that first episode and neuroleptic-naive patients with schizophrenia have difficulties initiating, but not maintaining, sleep. These results also confirm that the duration of stage 4 and REM sleep latency are reduced in first episode and neuroleptic-naive patients with schizophrenia. The fact that measures of REM sleep correlate with clinical scales of schizophrenia suggests that REM sleep physiology shares common substrates with symptoms of this disease.