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.

[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.

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.

[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.

Reproducibility of TMS-Evoked EEG responses.

Navigated transcranial magnetic stimulation combined with electroencephalography (nTMS-EEG), allows noninvasive studies of cortical excitability and connectivity in humans. We investigated the reproducibility of nTMS-EEG in seven healthy subjects by repeating left motor and prefrontal cortical stimulation with a 1-week interval. TMS was applied at three intensities: 90, 100, and 110% of subjects' motor threshold (MT). The TMS-compatible neuronavigation system guaranteed precise repositioning of the stimulation coil. The responses were recorded by a 60-channel whole head TMS-compatible EEG amplifier. A high overall reproducibility (r > 0.80) was evident in nTMS-EEG responses over both hemispheres for both motor and prefrontal cortical stimulation. The results suggest that nTMS-EEG is a reliable tool for studies investigating cortical excitability changes in the test-retest designs.

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.

The effect of methylphenidate on auditory information processing in healthy volunteers: a combined EEG/MEG study.

INTRODUCTION: The psychomotor stimulant methylphenidate (MPH) has been shown to improve attentional processes, reflected in behavioural measures such as vigilance, reaction time and visual attention tasks. The neural mechanisms of MPH action on sensory information processing, however, remain poorly understood. To the authors' knowledge, this present study is the first to investigate whether a single dose of MPH affects neural substrates of passive attention in healthy adults studied with simultaneous whole-head magnetoencephalography (MEG) and electroencephalography (EEG). METHODS: Monaural left-ear auditory stimuli were presented in an oddball paradigm with infrequent deviant tones differing in frequency and duration. Neuronal activity was recorded with simultaneous whole-head MEG and EEG in 13 healthy subjects (five females; aged 27 +/- 5 years) after oral administration of 40 mg MPH or placebo in a randomised, double-blind, cross-over design. We analysed both electric and magnetic N100, P200 and mismatch negativity (MMN) components. RESULTS: MPH increased arousal levels in visual analogue scales. MPH had no effect on the dipole strength of MMN or MMNm in either frequency or duration deviations. MPH did, however, reduce P200 amplitudes in EEG. CONCLUSIONS: The lack of effect of MPH on either MMN or MMNm suggests no association between catecholaminergic activities and MMN generation. However, our findings imply that MPH may change the neural bases of auditory information processing such as the early stimulus evaluation reflected in the P200 component. Dopamine and noradrenaline neurotransmitter systems could be responsible for the modulation of these processes. The exclusive effect of MPH on the P200 component could have a clinical application.

Effects of verapamil, an antagonist of L-type calcium channels, on cardiovascular symptoms in alcohol withdrawal.

AIMS: We studied whether verapamil, a Ca2+ channel blocker, affects cardiovascular symptoms in alcohol withdrawal. METHODS: Cardiovascular effects of verapamil (5 mg intravenously) were compared in 20 alcohol-dependent subjects during alcohol withdrawal (n = 10) on days 1, 2 and 10 and during early recovery (n = 10; duration 45 +/- 4.1 days). The heart rate was obtained from the electrocardiogram. Systolic and diastolic blood pressures were measured with a sphygmomanometer by Korotkoff. Stroke volume was studied by impedance cardiography. RESULTS: Significant differences in verapamil effects on systolic and diastolic blood pressure and stroke volume and total peripheral resistance were observed in patients with withdrawal when compared with those in early recovery. CONCLUSION: L-type Ca2+ channels may modify vascular tone in alcohol withdrawal.

Excitation threshold of the motor cortex estimated with transcranial magnetic stimulation electroencephalography.

The excitation threshold of the human motor cortex was estimated on the basis of electroencephalographic responses evoked by transcranial magnetic stimulation. The hand area of the primary motor cortex was stimulated at 10 intensities, for seven healthy individuals. The four dominant peaks of the overall brain response could be reliably determined when stimulation was intense enough to induce a cortical electric field of approximately 33-44 mV/mm. This may be estimated as the threshold for evoking measurable brain activity by motor-cortex transcranial magnetic stimulation. The remarkably low threshold reflects the excellent sensitivity of the combination of transcranial magnetic stimulation and electroencephalography for the study of neuronal function of the cortex.

Opioid withdrawal results in an increased local and remote functional connectivity at EEG alpha and beta frequency bands.

Withdrawal may be a natural model to study craving and compulsive drug seeking, since craving can be viewed as a conditioned dysphoric state. It has been suggested that functional connectivity between brain areas may be of major value in explaining excessive craving and compulsive drug seeking by providing essential link between psychological and biological processes. Considering that withdrawal initiates a widespread activation of cortical regions responsible for compulsive drug seeking and desire for the drug, we predict that withdrawal would result in a significant increase in functional cortical connectivity. We applied the novel operational architectonics approach that enables us to estimate both local and remote functional cortical connectivity by means of EEG structural synchrony measure. In 13 withdrawal opioid-dependent patients we found the evidence that local and remote cortical functional connectivity was indeed significantly enhanced (for both alpha and beta frequency oscillations). Additionally, statistical relationship between functional connectivity and the severity of opioid withdrawal has been found.

Effects of alcohol on TMS-evoked N100 responses.

TMS combined with simultaneous EEG is a novel brain imaging tool allowing investigation local excitability of human cortex. As alcohol acts through increasing function of A-type gamma-aminobutyric acid receptors and attenuating the function of glutaminergic NMDA-receptors-related excitation, we tested whether TMS-evoked N100 response which is thought to reflect cortical inhibitory processes, might be affected by alcohol. Ten healthy subjects ingested alcohol (0.8 g/kg) and EEG responses from 60 channels before and after alcohol ingestion were recorded after left motor-cortex stimulation. Alcohol almost abolished TMS-evoked N100 response. Control experiments with a piece of plastic placed between the head and coil to exclude auditory artefacts were conducted. Alcohol effects were similar when EEG responses from control experiments were subtracted from real-TMS. Alcohol-induced decrease was similar at ipsilateral, contralateral and frontal EEG sites suggesting that alcohol may change cortico-cortical connectivity of motor cortex. Alternative explanation is that alcohol has overall suppression effect on motor cortex. N100 may provide a useful marker of neural inhibition of human cortex for drug research.

Nitric oxide mediates cardiovascular symptoms in alcohol withdrawal.

We studied whether nitric oxide is involved in cardiovascular symptoms in alcohol withdrawal. Cardiovascular effects of isosorbide dinitrate (ISDN; 20 mg sublingually), a nitric oxide donor were compared in 21 alcohol-dependent subjects during alcohol withdrawal (n=11) on days 1, 2, 3, and 10 to those during remission (n=10; duration=60.7+/-10.5 days). Cardiovascular parameters were measured non-invasively. The levels of systolic and diastolic blood pressure, total peripheral resistance were significantly higher in patients with withdrawal than in remission. Same cardiovascular parameters showed different response to ISDN during withdrawal when compared to remission. The differences were largest during the initial phase (1-2 days) of withdrawal. Nitric oxide may mediate at least some cardiovascular symptoms in withdrawal.

Impaired pre-attentive auditory processing in opioid dependence with and without benzodiazepine co-dependence revealed by combined magnetoencephalography and electroencephalography.

Cognitive dysfunctions may be a significant factor in drug-seeking behavior, reducing the efficiency of rehabilitation in opioid dependence. Neurophysiological basis of these dysfunctions is poorly understood. 21 opioid-dependent patients and 15 healthy controls with no experience of illicit drugs were studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Among opioid dependents 15 were benzodiazepine co-dependent. In a passive oddball paradigm, a train of 700-Hz standard tones (80%), presented to the left ear, was occasionally interrupted by infrequent deviants, which were either 600-Hz or 400-Hz pure tones or complex novel sounds. The auditory evoked potentials (AEP) and fields (AEF) were analyzed. The strength of the N1m dipoles was enhanced in patients with benzodiazepine co-dependence, but the latency of the response or the source location was not changed. A delay of mismatch negativity (MMN) response of novel tones in EEG, and delay of P3am response on the contralateral hemisphere to stimulated ear in MEG in opioid-dependent patients were observed. There were no differences in source locations or strengths of the dipoles for P1m, MMNm, and P3am determined using equivalent current dipoles. There were no group differences in EEG amplitude measures. In conclusion, our results suggest delayed pre-attentive auditory processing of novel information in opioid dependence. Benzodiazepine co-dependence modulated N1m response.

Effects of NMDA receptor antagonist memantine on mismatch negativity.

Mismatch negativity (MMN) and its magnetic counterpart (MMNm) have been shown to be altered in patients with various psychiatric and neurological disorders, e.g. Alzheimer's disease and schizophrenia, indicating deficits in involuntary attention. N-Methyl-D-aspartate (NMDA) receptor-mediated glutamate dysfunction is suggested to underlie these deficits. However, the role of NMDA receptors in involuntary attention is poorly understood. Memantine is an NMDA receptor antagonist that has been demonstrated to be effective in the treatment of patients with Alzheimer's disease. We aimed to investigate whether a single dose of memantine would affect MMN/MMNm in healthy subjects studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Monaural left-ear auditory stimuli were presented in a passive oddball paradigm with infrequent deviant tones differing in frequency and duration. Neuronal activity was recorded in 13 healthy subjects after oral administration of 30mg of memantine or placebo in a randomized, double-blind, cross-over design. MMNm was analyzed using equivalent current dipoles. MMN was evaluated from frontocentral electrodes. Memantine lowered subjects' arousal level as measured by visual analog scales, and enhanced the amplitude of MMN in EEG. No differences in MMN latency were observed in MEG or EEG. Memantine did not affect the location, strength, amplitude or latency of MMNm, P1m, and N1m components. No changes in amplitude or latency were observed for P1 and N1 peaks. These results indicate that memantine affects involuntary attention without otherwise changing auditory processing of the stimuli. As memantine-induced changes in MMN were detected only in EEG, we suggest that the effect is mostly related to the frontal cortex.

Cardiovascular effects of propranolol in patients with alcohol dependence during withdrawal.

The cardiovascular effects of the beta-adrenergic receptor antagonist propranolol (40 mg) were compared in 20 alcohol-dependent subjects during alcohol withdrawal syndrome (WS; n=10) on days 1, 2, 3, and 10 to those during remission (n=10; 50 +/- 7.7 days). Significant differences were observed in negative chronotropic and hypotensive effects during withdrawal compared to remission. The initial level of hemodynamics prior to propranolol administration was the most important factor modifying the drug responses. The amount of daily consumption of alcohol also predicted to some extent the effects of propranolol. The WS-related changes in peripheral and central beta-adrenergic system were most likely responsible for the differences in propranolol actions.

Composition of EEG oscillations and their temporal characteristics: methadone treatment.

In this study, we examine the composition of electroencephalographic (EEG) oscillations within a broad frequency band (0.5-30 Hz) for opioid abuse (22 patients), during withdrawal (13 patients), and after 6 months of methadone treatment (6 patients) and in 14 healthy subjects during a resting condition (closed eyes). The exact compositions of EEG oscillations and their temporal behaviour were assessed using the probability-classification analysis of short-term EEG spectral patterns. The study reveals the dynamics of particular EEG oscillations throughout the conditions of opioid dependency, withdrawal and methadone-based treatment. It was shown that methadone maintenance treatment normalized considerably the composition of EEG oscillations and their percentage ratio and restored the temporal structure of patients' EEG comparable with healthy subjects. The importance of the methadone's ability to restore a normal temporal structure of the brain's activity is discussed.

The novelty value of the combined use of electroencephalography and transcranial magnetic stimulation for neuroscience research.

Electroencephalographic (EEG) responses measured simultaneously with transcranial magnetic stimulation (TMS) have opened a new window into the human nervous system. The combined use of TMS and EEG (TMS-EEG) provides a means for the detailed study of the reactivity of any cortical region in the intact brain; also the reactivities of non-motor cortical areas related with higher-order functions are now appreciable. A recent epochal finding concerning cortical reactivity is that neuronal activation is induced with remarkably low stimulation intensities. This knowledge is significant when optimizing experimental set-ups for maximal patient safety. Stimulation of different cortical areas evokes different patterns of remote EEG activity, confirming the viability of TMS-EEG for the study of corticocortical connections. In this review, we expand on these and other notable findings related with TMS-EEG. We discuss the possibilities of the technique for the study of cortical reactivity and connectivity. We show that TMS-EEG allows the study of interhemispheric connections with high spatiotemporal specificity and the assessment of cortical reactivity with excellent sensitivity.

Breakdown of long-range temporal correlations in theta oscillations in patients with major depressive disorder.

Neuroimaging has revealed robust large-scale patterns of high neuronal activity in the human brain in the classical eyes-closed wakeful rest condition, pointing to the presence of a baseline of sustained endogenous processing in the absence of stimulus-driven neuronal activity. This baseline state has been shown to differ in major depressive disorder. More recently, several studies have documented that despite having a complex temporal structure, baseline oscillatory activity is characterized by persistent autocorrelations for tens of seconds that are highly replicable within and across subjects. The functional significance of these long-range temporal correlations has remained unknown. We recorded neuromagnetic activity in patients with a major depressive disorder and in healthy control subjects during eyes-closed wakeful rest and quantified the long-range temporal correlations in the amplitude fluctuations of different frequency bands. We found that temporal correlations in the theta-frequency band (3-7 Hz) were almost absent in the 5-100 s time range in the patients but prominent in the control subjects. The magnitude of temporal correlations over the left temporocentral region predicted the severity of depression in the patients. These data indicate that long-range temporal correlations in theta oscillations are a salient characteristic of the healthy human brain and may have diagnostic potential in psychiatric disorders. We propose a link between the abnormal temporal structure of theta oscillations in the depressive patients and the systems-level impairments of limbic-cortical networks that have been identified in recent anatomical and functional studies of patients with major depressive disorder.