Biperiden selectively induces memory impairment in healthy volunteers: no interaction with citalopram.

RATIONALE: Traditionally, the non-selective muscarinic antagonist scopolamine has been used to induce episodic memory impairments as found in Alzheimer's disease (AD). However, it also impairs attention and induces drowsiness. Muscarinic antagonists more selective for the M1 receptor might, therefore, be preferred. OBJECTIVES: We examined the effects of the M1 antagonist biperiden on cognitive functions in order to test the specificity of this drug on memory performance. Additionally, we assessed whether the selective serotonin re-uptake inhibitor citalopram can reverse a possible biperiden-induced impairment. METHODS: The study was conducted according to a double-blind, placebo-controlled, four-way cross-over design. Sixteen volunteers received biperiden (2 mg), citalopram (20 mg), a combination of the two, or a placebo in counterbalanced order with a washout of at least 4 days. Cognitive tests (verbal memory, continuous recognition memory, spatial memory, choice reaction) were performed 4 and 1 h after treatment with citalopram and biperiden, respectively. RESULTS: Biperiden impaired memory performance in the verbal learning task, the continuous recognition memory test, and the spatial memory task. Effects on attention and side effects, as measured using the choice reaction time test and questionnaires respectively, could be neglected. Citalopram did not affect any of the memory or attention measures taken. Most importantly, citalopram was also unable to reverse the biperiden-induced memory impairments. CONCLUSIONS: Our results, thus, show that the M1 antagonist biperiden may serve as a translational model to induce episodic memory deficits as seen in AD. However, the interactive influence of acetylcholine and serotonin on memory could not be confirmed.

The neural basis of sublexical speech and corresponding nonspeech processing: a combined EEG-MEG study.

We addressed the neural organization of speech versus nonspeech sound processing by investigating preattentive cortical auditory processing of changes in five features of a consonant-vowel syllable (consonant, vowel, sound duration, frequency, and intensity) and their acoustically matched nonspeech counterparts in a simultaneous EEG-MEG recording of mismatch negativity (MMN/MMNm). Overall, speech-sound processing was enhanced compared to nonspeech sound processing. This effect was strongest for changes which affect word meaning (consonant, vowel, and vowel duration) in the left and for the vowel identity change in the right hemisphere also. Furthermore, in the right hemisphere, speech-sound frequency and intensity changes were processed faster than their nonspeech counterparts, and there was a trend for speech-enhancement in frequency processing. In summary, the results support the proposed existence of long-term memory traces for speech sounds in the auditory cortices, and indicate at least partly distinct neural substrates for speech and nonspeech sound processing.

Postural control in restless legs syndrome with medication intervention using pramipexole.

Central dopamine regulation is involved in postural control and in the pathophysiology of restless legs syndrome (RLS) and Parkinson's disease (PD). Postural control abnormalities have been detected in PD, but there are no earlier studies with regard to RLS and postural control. Computerized force platform posturography was applied to measure the shift and the velocity (CPFV) of center point of forces (CPF) with eyes open (EO) and eyes closed (EC) in controls (n = 12) and prior and after a single day intervention with pramipexole in RLS subjects (n = 12). CPFV (EO) was significantly lower in the RLS group (p < 0.05) than in controls. After pramipexole intake, the difference disappeared and the subjective symptom severity diminished. Pramipexole did not significantly influence CPFV (EC) or CPF shift direction. Subjects with RLS used extensively visual mechanisms to control vestibule-spinal reflexes to improve or compensate the postural stability. Further research is needed to clarify altered feedback in the central nervous system and involvement of dopamine and vision in the postural control in RLS.

Disrupted central inhibition after transcranial magnetic stimulation of motor cortex in schizophrenia with long-term antipsychotic treatment.

Aims. Schizophrenia is a neuropsychiatric disorder associated with mental and motor disturbances. We aimed to investigate motor control, especially central silent period (CSP) in subjects with schizophrenia (n = 11) on long-term antipsychotic treatment compared to healthy controls (n = 9). Methods. Latency and duration of motor evoked potentials (MEPs) and CSPs were measured with the help of single pulse transcranial magnetic stimulation (TMS) and intramuscular electrodes. After stimulation of the dominant and nondominant motor cortex of abductor digiti minimi (ADM) and tibialis anterior (TA) muscle areas, respective responses were measured on the contralateral side. Results. MEPs did not differ significantly between the groups. Multiple CSPs were found predominantly in subjects with schizophrenia, which showed a higher number of CSPs in the dominant ADM and the longest summarized duration of CSPs in the nondominant ADM (P < 0.05) compared to controls. Conclusions. There were multiple CSPs predominantly in the upper extremities and in the dominant body side in subjects with schizophrenia. Behind multiple CSPs may lie an impaired regulation of excitatory or inhibitory neurotransmitter systems in central motor pathways. Further research is needed to clarify the role of the intramuscular recording methods and the effect of antipsychotics on the results.

Transcranial magnetic stimulation-electroencephalography responses in recovered and symptomatic mild traumatic brain injury.

Mild traumatic brain injury (mTBI) may cause diffuse damage to the brain, especially to the frontal areas, that may lead to persistent symptoms. We studied participants with past mTBI by means of navigated transcranial magnetic stimulation (nTMS) combined with electroencephalography (EEG). Eleven symptomatic and 8 recovered participants with a history of single mTBI and 9 healthy controls participated. Average time from injury to testing was 5 years. The participants did not have abnormalities or signs of injury on brain magnetic resonance imaging, and they did not use any centrally acting medication. Left primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) were stimulated with nTMS and evoked potentials measured from the corresponding areas of both hemispheres. Delayed ipsilateral P30 and contralateral N45 peak latencies to left DLPFC nTMS were found in the symptomatic group, along with higher DLPFC N100 amplitudes compared with the control or recovered group. The recovered group had shorter P200 latencies in left DLPFC nTMS compared with the other groups. Both mTBI groups had higher motor thresholds compared with the control group. In left M1 nTMS, the mTBI groups showed less P30 amplitude increase, and the symptomatic group showed longer P60 interhemispheric latency difference with higher stimulation intensities. The results suggest altered brain reactivity and connectivity in mTBI. Some of the observed differences may be related to compensatory mechanisms of recovery. nTMS-EEG is a potentially useful tool for studying the effects of mTBI.

Recurrent CSPs after Transcranial Magnetic Stimulation of Motor Cortex in Restless Legs Syndrome.

Aims. The aim of this study was to investigate the motor control and central silent period (CSP) in restless legs syndrome (RLS). Methods. Transcranial magnetic stimulation was focused on the dominant and nondominant hemispheric areas of motor cortex in six subjects with RLS and six controls. The responses were recorded on the contralateral abductor digiti minimi (ADM) and tibialis anterior (TA) muscles with intramuscular needle electrodes. Results. No significant differences were found in the motor conduction or central motor conduction time, in the latency, or in the duration of the CSPs between or within the groups, but multiple CSPs were observed in both groups. The number of the CSPs was significantly higher in both ADMs and in the dominant TA (P ≤ 0.01) in the RLS group compared to the controls. Conclusion. Descending motor pathways functioned correctly in both groups. The occurrence of the recurrent CSPs predominantly in the RLS group could be a sign of a change of function in the inhibitory control system. Further research is needed to clarify the role of the intramuscular recording technique and especially the role of the subcortical generators in the feedback regulation of the central nervous system in RLS.

Validation of head movement correction and spatiotemporal signal space separation in magnetoencephalography.

OBJECTIVE: Our aim was to assess the effectiveness and reliability of spatiotemporal signal space separation (tSSS) and movement correction (MC) in magnetoencephalography (MEG) recordings disturbed by head movements and magnetized material on the head. METHODS: We recorded MEG from 20 healthy adults in stationary (reference) head position and during controlled head movements. Nearby magnetic interference sources were simulated by attaching magnetized particles on the subject's head. Auditory and somatosensory stimuli were presented. MC, tSSS and averaging were performed to obtain auditory (AEF) and somatosensory (SEF) evoked fields. Neuronal sources were modeled as equivalent current dipoles. MC was also validated by reconstructing signals generated by current dipoles in a phantom. RESULTS: After MC, the AEF and SEF responses recorded during intermittent head movements were similar in amplitude to the reference recordings and differed by 5-7mm in source location. The tSSS method removed artifacts due to the attached magnetized particles but did not affect the reference data. CONCLUSIONS: The methods are able to reliably recover MEG responses contaminated by movements and magnetic artifacts on the head. SIGNIFICANCE: The combination of tSSS and MC methods is especially useful in clinical measurements, where movements and magnetic disturbances are commonly present.

[Internet-based cognitive-behavioral therapy in the treatment of psychiatric disorders]. / Kognitiivinen verkkoterapia psykiatristen häiriöiden hoidossa.

Recent years have seen the development of Internet-based cognitive-behavioral therapy, i.e. psychological self-help program mediated via the Internet, the patient being in contact via e-mail with the support person directing the therapy. Internet-based cognitive-behavioral therapy usually consists of psychoeducation, exercises and prevention of the recurrence of symptoms. Modules of the network program are thus the cornerstones of "live" cognitive-behavioral therapy. Self-help provided by Internet-based cognitive-behavioral therapy therapy has been found to be effective especially in the treatment of panic disorder, social phobia and depression, providing an opportunity to extend therapeutic services also to persons beyond the reach of traditional therapy.

How human electrophysiology informs psychopharmacology: from bottom-up driven processing to top-down control.

This review surveys human event-related brain potential (ERP) and event-related magnetic field (ERF) approaches to psychopharmacology and psychopathology, and the way in which they complement behavioral studies and other neuroimaging modalities. The major paradigms involving ERP/ERF are P50 suppression, loudness-dependent auditory evoked potential (LDAEP), mismatch negativity (MMN), P300, mental chronometry, inhibitory control, and conflict processing (eg, error-related negativity (ERN)). Together these paradigms cover a range of more bottom-up driven to more top-down controlled processes. A number of relationships between the major neurotransmitter systems and electrocortical mechanisms are highlighted. These include the role of dopamine in conflict processing, and perceptual processing vs motor preparation; the role of serotonin in P50 suppression, LDAEP, and MMN; glutamate/NMDA and MMN; and the role of acetylcholine in P300 generation and memory-related processes. A preliminary taxonomy for these relationships is provided, which should be helpful in attuning possible new treatments or new applications of existing treatments to various disorders.

Effects of alcohol withdrawal on cardiovascular system.

Alcohol withdrawal syndrome (AWS) develops after cessation of alcohol intake in alcoholic patients characterizing psychiatric symptoms and changes in autonomous nervous systems. We studied cardiovascular changes during different phases of AWS (1, 2, 3 and 10 days after admission for detoxification; n=34) and compared them with those in early recovery (at least 1 month of abstinence; n=30). The results study showed that cardiovascular system underwent significant changes during AWS characterizing the decrease of heart rate, systolic and diastolic blood pressures, and total peripheral resistance. Stroke index was lower during AWS than in early recovery. As the decreased stroke index was compensated by increased heart rate, cardiac index did not differ during AWS from that in early recovery. Increased functioning of noradrenaline (along with other central and peripheral regulating mechanisms) may be an important factor associated with cardiovascular changes in AWS. Normalization of this function after AWS leads to returning of cardiovascular parameters to baseline levels.

[Treatment of obsessive-compulsive disorder in an adult]. / Aikuisten pakko-oireisen häiriön hoito.

Obsessive-compulsive disorder is a common, chronic and functionally incapacitating psychiatric disorder characterized by obsessive thoughts and compulsive acts. First-line drug therapy utilizes serotonin reuptake inhibitors at dosages that are usually higher and yield slower responses than those used in the treatment of major depression. Second generation antipsychotics or haloperidol may also be beneficial. Merely behavioral and/or cognitive psychotherapy may be applied in mild and moderate cases, whereas a combination of different forms of therapy is the most effective treatment in severe forms.

Effect of visual information on postural control in patients with schizophrenia.

Lateralized motor and attentional abnormalities contribute to schizophrenia, but little is known about possible abnormalities in neural machinery involved in postural control. We examined postural stability of 22 patients with schizophrenia taking medication and 14 healthy control participants using computerized force platform posturography. The shift in the center point of pressure in the condition of eyes open versus eyes closed characterizes the effect of visual information on body posture. Closing the eyes had less of an effect on the center point of velocity (velocity sm/s) in the patients with schizophrenia than in the control group (median change, 36% vs. 70%, p = 0.0006). Change in the body position during eye closure tended to be directed rightwards in the control group but leftwards in the group with schizophrenia (p = 0.025). The results show that visual component had less dominance in the balance control of these patients with schizophrenia. The lateralized effect of visual information on posture was also impaired.

[Brief psychotherapy of persons who have attempted suicide]. / Itsemurhaa yrittäneiden kognitiivinen lyhytpsykoterapia.

A brief psychotherapeutic regime aiming to prevent future attempts has been developed for persons who have attempted suicide. According to the cognitive-behavioral framework, the patients' injurious automatic thoughts and basic delusions make the problem situations subjectively impossible. After an assessment of suicide risk, a safety plan shall be devised. Conceptualization, a description of the actual suicidal crisis, constitutes the cornerstone of therapy. Application of measures supporting survival, adoption of problem-solving skills and a functional contact with a social support network will decrease the likelihood of self-destructive actions.

Cerebral measurements and their correlation with the onset age and the duration of opioid abuse.

BACKGROUND: Opioid-dependent patients have been shown to have structural brain alterations. This study focuses on magnetic resonance imaging (MRI) measurements of brain and their correlation with the onset age and the duration of opioid abuse. METHODS: Brain MRI was obtained from 17 opioid-dependent patients (mean age 34 years, SD 7 years) and 17 controls. Compulsive opioid use had begun between ages 15 and 31 (mean 20) and had continued from 5 to 26 years. All patients were tobacco smokers, six had also abused amphetamines and 11 benzodiazepines. Relative volumes of cerebral white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) spaces were measured. In addition, Sylvian fissure ratio (SFR), bifrontal ratio, and midsagittal cerebellar vermian area were correlated with the onset age and the duration of opioid abuse. RESULTS: The total volume (GM + WM + CSF) of the cerebrum was significantly smaller in patients than in controls (Mann-Whitney U-test, p = 0.026) as well as the absolute volumes of GM and WM (p = 0.014 and p = 0.007, respectively). There was no significant difference in GM and WM volumes normalized with total cerebral volume. In contrast, the absolute volume of CSF did not significantly differ between the groups, but the relative volume of CSF was significantly higher in opioid dependents (p = 0.029). SFR and bifrontal ratio were larger in opioid dependents than in controls (p = 0.005 and p = 0.013). The SFR correlated negatively (p = 0.017, r = - 0.569) and the area of vermis cerebelli correlated positively (p = 0.043, r = 0.496) with the onset age of opioid abuse. The length of opioid abuse and the area of vermis cerebellum had a negative correlation (p = 0.038, r = - 0.523) even though the areas of cerebellar vermis did not significantly differ between opioid dependents and controls. The authors speculate that the onset of substance abuse in adolescence or early adulthood may have in part disturbed the late brain maturation process, as in normal development, the dorsolateral frontal cortex and superior parts of the temporal lobes are the last to maturate. Also, the cerebellar vermis may be affected by early onset substance abuse. It is possible that the brain is more vulnerable to substance abuse at a young age than later in life.

Methadone restores local and remote EEG functional connectivity in opioid-dependent patients.

Currently it has been proposed that normal brain function is critically dependent upon a dynamical balance between functions of local neuronal assemblies and global integrative processes. A loss of such metastable balance in favor of either independent or hyper-ordered processing is considered as the reflection of a brain disease. It has been shown that opioid dependence can be characterized as a disease of brain metastable balance, wherein local functional connectivity (synchronicity within neuronal assemblies) increased and remote functional connectivity (synchronicity between neuronal assemblies) decreased. Since methadone may be used as a maintenance treatment for opioid-dependent patients, the aim of this research was to study how methadone would influence the temporal and metastable cortical organization through the measures of local and remote electroencephalogram (EEG) functional connectivity in six opioid-depended patients who manage to complete at least six-month methadone treatment. The present study demonstrated that average parameters of temporal and metastable organization of the cortical dynamics (indexed by local and remote EEG functional connectivity) in such opioid-dependent patients did not differ from normal values of healthy subjects. We interpret these findings as a capability of the methadone to restore a normal temporal and metastable structure of brain activity in opioid-dependent patients after many months of methadone treatment. To our knowledge, present preliminary study is the first where the influence of methadone on temporal and metastable structure of EEG activity is demonstrated.

[Cognitive psychotherapy of social phobia and generalized anxiety disorder]. / Sosiaalisten tilanteiden pelon ja yleistyneen ahdistuneisuushäiriön kognitiivinen psykoterapia.

Recent years have seen a better understanding of the psychological changes underlying social phobia and generalized anxiety disorder, and successful methods of cognitive psychotherapy have been developed. Exposure to social situations causing anxiety and cognitive restructuring has diminished social anxiety. An underlying factor in generalized anxiety disorder is, among other things, a difficulty to deal with and tolerate uncertainty. Adaptation of distressing dysfunctional metacognitions has recently emerged alongside conventional cognitive-behavioral treatment modalities.

Central auditory dysfunction in schizophrenia as revealed by the mismatch negativity (MMN) and its magnetic equivalent MMNm: a review.

Since the early 1990s, the auditory change-detection response, mismatch negativity (MMN) and its magnetoencephalographic (MEG) equivalent MMNm have been applied in a large number of studies on schizophrenia. These studies have enhanced our understanding of the central auditory dysfunction underlying schizophrenia. The attenuation of the MMN amplitude is a systematic and robust neurophysiological finding in these patients. The gradual attenuation of the MMN amplitude resulting from frequency change reflects the progress of the disease, particularly the impairment occurring as a function of illness duration, whereas the MMN deficiency for duration change may be more closely linked to the genetic aspect of the illness. Electroencephalographic (EEG) and magnetoencephalographic (MEG) studies, together, suggest that both the temporal and frontal cortices contributing to MMN generation are affected in schizophrenia patients. Furthermore, abnormalities in auditory perception and discrimination revealed by a deficient temporal MMN generator process might be associated with patients' positive symptoms, whereas the dampened frontal attention-switching function, suggested by the attenuated responses of the frontal MMN generator, might contribute to the negative symptoms such as social withdrawal. In addition, gradual MMN amplitude reduction, in particular that for frequency change, reflects cognitive and functional impairment occurring as a function of illness duration. Finally, as MMN can be detected even in animals such as the mouse, it might provide a useful biomarker for assessing the effects of the drugs developed to fight the cognitive and functional impairments in schizophrenia patients.