[Neural networks and clinical efficacy of transcranial brain stimulation in psychiatry]. / Neurale netwerken en klinische effecti­vi­teit van transcraniële hersenstimulatie in de psychiatrie.

BACKGROUND: Non-invasive forms of brain stimulation, including transcranial magnetic stimulation and direct current stimulation, are increasingly being considered by clinicians as a somatic treatment option for psychiatric disorders. AIM: Review article on the history, efficacy transcranial brain stimulation in psychiatric disorders and the role of neural networks for improving clinical efficacy. METHOD: Review of scientific literature. RESULTS: Transcranial magnetic stimulation has been proven effective for the treatment of depression, but treatment efficacy varies widely for other psychiatric disorders. Transcranial direct current stimulation is still at an experimental stage, but results suggest that using weak currents can have positive effects. Neuroscience research provides tools for improving therapeutic outcomes based on neural network approaches. CONCLUSION: Transcranial brain stimulation grafted on network information appears to be a promising approach for enhancing therapeutic outcome in psychiatric disorders.

[Electroencephalography and connectivity in delirium]. / Eeg en innovatieve behandeling van verminderde hersenconnectiviteit bij delirium.

BACKGROUND: Delirium is associated with neurophysiological changes that can be identified with quantitative EEG analysis techniques (qEEG). AIM: To provide an overview of studies on neurophysiological changes in delirium using various qEEG analysis techniques. METHOD: Literature review. RESULTS: In delirium, there is an increase in delta and theta activity but a decrease in activity in the alpha frequency band. Additionally, there is a decrease in functional connectivity and efficiency of the brain network in the alpha frequency band. CONCLUSION: Delirium is characterized by diffuse slowing of the EEG, reduced functional connectivity, and decreased efficiency of the brain network. Improved functional connectivity could be a new approach to treat delirium.

New Horizons on Non-invasive Brain Stimulation of the Social and Affective Cerebellum.

The cerebellum is increasingly attracting scientists interested in basic and clinical research of neuromodulation. Here, we review available studies that used either transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) to examine the role of the posterior cerebellum in different aspects of social and affective cognition, from mood regulation to emotion discrimination, and from the ability to identify biological motion to higher-level social inferences (mentalizing). We discuss how at the functional level the role of the posterior cerebellum in these different processes may be explained by a generic prediction mechanism and how the posterior cerebellum may exert this function within different cortico-cerebellar and cerebellar limbic networks involved in social cognition. Furthermore, we suggest to deepen our understanding of the cerebro-cerebellar circuits involved in different aspects of social cognition by employing promising stimulation approaches that have so far been primarily used to study cortical functions and networks, such as paired-pulse TMS, frequency-tuned stimulation, state-dependent protocols, and chronometric TMS. The ability to modulate cerebro-cerebellar connectivity opens up possible clinical applications for improving impairments in social and affective skills associated with cerebellar abnormalities.

NMDA Receptor-Mediated Motor Cortex Plasticity After 20 Hz Transcranial Alternating Current Stimulation.

Transcranial alternating current stimulation (tACS) has been shown to modulate neural oscillations and excitability levels in the primary motor cortex (M1). These effects can last for more than an hour and an involvement of N-methyl-d-aspartate receptor (NMDAR) mediated synaptic plasticity has been suggested. However, to date the cortical mechanisms underlying tACS after-effects have not been explored. Here, we applied 20 Hz beta tACS to M1 while participants received either the NMDAR antagonist dextromethorphan or a placebo and the effects on cortical beta oscillations and excitability were explored. When a placebo medication was administered, beta tACS was found to increase cortical excitability and beta oscillations for at least 60 min, whereas when dextromethorphan was administered, these effects were completely abolished. These results provide the first direct evidence that tACS can induce NMDAR-mediated plasticity in the motor cortex, which contributes to our understanding of tACS-induced influences on human motor cortex physiology.

[Consensus statement on the application of rTMS in depression in the Netherlands and Belgium]. / Consensusverklaring voor de toepassing van rTMS bij depressie in Nederland en België.

BACKGROUND: Since 2017, repetitive transcranial magnetic stimulation (rTMS) has become eligible for reimbursement for the treatment of therapy-resistant depression in the Dutch healthcare system.
AIM: To initiate a guideline in the Netherlands and Belgium for the safe and effective application of rTMS for the treatment of depression.
METHOD: Based on literature review, existing guidelines and consensus among Dutch rTMS experts, recommendations were developed regarding the implementation of rTMS as a treatment of depression. All available evidence was weighed and discussed among all co-authors and recommendations were reached by consensus among the group.
RESULTS: rTMS targeting the dorsolateral prefrontal cortex (DLPFC) should be seen as a first choice in the treatment of depression using high-frequency rTMS (left) or, as an alternative, low-frequency rTMS (right). Stimulation protocols should use more than 1000 pulses per session for an average of 20-30 sessions, offered in 2-5 sessions per week. Contraindications for rTMS include epilepsy, intracranial presence of (magnetisable) metals, pacemaker and cochlear implant.
CONCLUSION: rTMS, performed by competent professionals is an effective and safe treatment for depression.

[rTMS for treatment resistant depression - proposal for a treatment protocol]. / Repetitieve transcraniële magnetische stimulatie bij therapieresistente depressie; voorstel voor een behandelprotocol.

BACKGROUND: At present, the use of repetitive transcranial magnetic stimulation (rtms) for treatment-resistant depression is sufficiently substantiated to be applied in clinical practice. In the Netherlands, it will be reimbursed when offered in combination with cognitive behavior therapy.
AIM: Proposal for a clinical treatment protocol for rtms in The Netherlands.
METHOD: A study of the literature and a critical appraisal of available international guidelines for rtms.
RESULTS: rtms is a safe treatment for patients suffering from a moderate to severe depressive disorder that is relatively treatment-resistant. The duration of the effect is still unknown. It is advised to stimulate the left dorsolateral prefrontal cortex using an intensity of 120% of the resting motor threshold, with a frequency of 10 Hz and using 3000 pulses per session during a total of 20-30 sessions.
CONCLUSION: The proposed treatment protocol is favored based on the available evidence when rtms is used as a treatment aimed to acutely decrease the severity of depressive symptoms. It is further proposed to systematically collect technical and outcome data on treatment with rtms to further improve treatment with rtms in clinical practice.

[Minimally invasive brain stimulation for unipolar depression]. / Minimaal invasieve hersenstimulatie bij unipolaire depressie.

BACKGROUND: Unipolar depression is one of the most prevalent psychiatric disorders and has a high impact at individual and societal level. Commonly used treatments such as antidepressants and psychotherapy are often not effective. AIM: To determine the efficacy of repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS) as minimally invasive forms of treatment for unipolar depression. METHOD: We searched the literature. RESULTS: rTMS is effective in treating unipolar depression and is comparable to existing forms of medication and behavioural therapy. The effects of tDCS are promising, but more research is needed. CONCLUSION: rTMS is a useful addition to the existing arsenal of treatment for unipolar depression.

Empathy and prosocial behavior in response to sadness and distress in 6- to 7-year olds diagnosed with disruptive behavior disorder and attention-deficit hyperactivity disorder.

Empathy has been associated with decreased antisocial and increased prosocial behavior. This study examined empathy and prosocial behavior in response to sadness and distress in disruptive behavior disorder (DBD) and attention-deficit hyperactivity disorder (ADHD). Six- and 7-year-old children with DBD (with and without ADHD) (n = 67) and with ADHD only (n = 27) were compared to typically developing children (TD) (n = 37). Parents and teachers rated affective empathy in response to sadness and distress on the Griffith Empathy Measure. Children reported affective empathic ability in response to sad story vignettes. Empathy-induced prosocial behavior in response to sadness and distress was assessed with a computer task, the Interpersonal Response Task (IRT). Compared to TD, children with DBD (with and without ADHD) and those with ADHD only were rated as less empathic by their teachers, but not by their parents. No differences between groups were observed in children who reported affect correspondence. Children with DBD (with and without ADHD) showed less prosocial behavior in response to sadness and distress compared to TD. Children with ADHD only did not differ from TD. An additional analysis comparing all children with a diagnosis to the TD group revealed that the difference in prosocial behavior remained after controlling for ADHD symptoms, but not after controlling for DBD symptoms. These findings of impaired empathy-induced prosocial behavior in response to sadness and distress in young children with DBD suggest that interventions to ameliorate peer relationships may benefit from targeting on increasing prosocial behavior in these children.

[Ethical considerations regarding the use of transcranial magnetic stimulation in the treatment of depression]. / Ethische overwegingen bij transcraniële magnetische stimulatie in de behandeling van depressie.

BACKGROUND: Transcranial magnetic stimulation (TMS) has proved effective in the treatment of depression. However, the step that was needed to progress from positive research results to the actual use of TMS to treat patients has raised a number of ethical concerns. The concerns extend beyond matters such as the safety of the technique, the patient's right of access to therapy and the patient's informed consent; ethics are involved because the new treatment can be mind-bending and can interfere with the patient's autonomy and decision-making capacity. AIM: To discuss ethical issues raised by the use of TMS in the treatment of depression. METHOD: We reviewed the relevant scientific literature. RESULTS: The effects of the treatment on the patient's genuine wishes and on his or her views on the efficacy of the treatment are technique-related ethical issues that have not yet been adequately addressed. Furthermore, the effects of TMS on the patient's autonomy and mental capacity and the 'last resort' argument in relation to the effectiveness of the therapy are context-related considerations that warrant further discussion. CONCLUSION: There will have to be more research and discussion among researchers and clinicians about specific ethical questions before TMS can take its rightful place in clinical practice.

Individual differences in the effects of salience and reward on impulse control and action selection.

Impulse control and adequate decision making are vital functions when it comes to detection and adherence to personal goals and societal rules. In the current study we tested the hypothesis that increasing the salience of environmental cues would be most effective in improving impulse control, as assessed by a stop-signal task, in subjects with low environmental susceptibility as indexed by low pre-stimulus EEG alpha power. In addition, we anticipated that an external-reward manipulation improves performance during a Go/No go task, especially in individuals with low task-induced motivation as indexed by low theta/beta power ratios. High salience of stop signals enhanced stopping performance but there was no difference in responsivity to the salience manipulation between participants with high and low EEG alpha power. Individuals with low theta/beta power ratios responded more accurately when rewards were involved. Together these results suggest that increasing the salience of external cues may help impulse control in general, whereas the effectiveness of external-reward manipulations is higher in individuals with low task-induced motivation.

Lower cerebello-cortical functional connectivity in veterans with reactive aggression symptoms: A pilot study.

A significant number of veterans experience irritability and aggression symptoms as a result of being exposed to extremely stressful and life-threatening situations. In addition to the well-established involvement of the brain's cortico-subcortical circuit in aggression-related behaviours, a role of the deep cerebellar nuclei (DCN) in reactive aggression has been suggested. In the present study, seed-based resting-state functional connectivity between the DCN and cortico-subcortical areas was explored in veterans with and without reactive aggression symptoms. Nineteen male veterans with reactive aggression symptoms and twenty-two control veterans without reactive aggression symptoms underwent 3T resting-state functional MRI scans. Region-of-interest (ROI) analyses that included the amygdala, hypothalamus and periaqueductal grey as ROIs did not yield significant group-related differences in resting-state functional connectivity with the DCN. However, exploratory whole-brain analysis showed that veterans with reactive aggression symptoms exhibited lower functional connectivity between the DCN and the orbitofrontal cortex compared to control veterans. Our findings provide preliminary evidence for the possible involvement of a cerebello-prefrontal pathway in reactive aggression in male veterans.

[Transcranial magnetic stimulation as a treatment for depression]. / Transcraniële magnetische stimulatie als behandelingsvorm voor depressie.

BACKGROUND: The high incidence of depressive disorder in the Netherlands calls for additional forms of therapy. Transcranial magnetic stimulation (TMS) is a form of non-invasive brain stimulation that has been investigated in the last 15 years in order to find out whether this form of stimulation is effective in the treatment of depression. AIM: To discover whether TMS has proved effective in the treatment of depressed patients. RESULTS: Results show that tms treatment is safe when applied to the frontal lobes of the cerebral cortex and that the therapeutic effect is comparable to the effect of psychotherapy and antidepressants. Future studies should concentrate on an increase in efficiency by providing more insight into the working mechanisms and the effect of individual differences. Follow-up studies are needed to investigate the duration of the antidepressive effect. CONCLUSION: TMS seems to be a promising tool for the treatment of depressive disorders. However, there are many questions and uncertainties about the efficiency and applicability of TMS.

Quantitative review of the efficacy of slow-frequency magnetic brain stimulation in major depressive disorder.

BACKGROUND: Slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the frontal cortex has been suggested as a safer and better tolerable alternative to fast-frequency rTMS in the treatment of major depressive disorder (MDD). The aim of the present study was to examine the efficacy of slow-frequency rTMS to the frontal cortex in MDD. METHOD: A literature search was carried out in the databases PubMed and Web of Science in the period between January 1994 and July 2009 with the search terms 'depression' and 'transcranial magnetic stimulation'. Nine double-blind sham-controlled parallel intention-to-treat studies (252 patients) fulfilled inclusion criteria and were entered in a random-effects meta-analysis. RESULTS: The test for heterogeneity was not significant (QT=9.63, p=0.38). An overall weighted moderate mean effect size (d=0.63, 95% confidence interval=0.03-1.24) for active treatment was observed. CONCLUSIONS: The findings suggest that slow-frequency rTMS to the frontal cortex is more effective than sham treatment and may be equally effective as fast-frequency rTMS in the treatment of MDD.

[Non-invasive brain stimulation for the treatment of depression]. / Niet-invasieve hersenstimulatie als behandeling voor depressie.

Depression is one of the most common psychiatric disorders and is a heavy burden, not only for the patient and his or her environment but also in economic and social terms. 35% of depressed patients do not recover after standard treatment with medication or psychotherapy. There is a need for more effective treatment options for depression. In recent decades, new forms of brain stimulation have been developed for the treatment of depression, the most important of which is transcranial magnetic stimulation (TMS). TMS uses magnetic pulses to influence brain activity. Meta-analyses show approximately 30-40% of patients respond to treatment with repetitive TMS. The depression goes into remission in about 20-30% of cases. Research has led to new treatment protocols and variations on the conventional TMS method. More research into the effectiveness of these developments is needed. We recommend using TMS as an add-on treatment more often when the patient has completed two steps of the treatment guideline.

A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression.

BACKGROUND: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. RESEARCH QUESTION: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? METHOD: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. RESULTS: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. CONCLUSION: "Standard" 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.

[Transcranial magnetic stimulation and cerebral physiology in psychiatric disorders]. / Transcraniale magnetische stimulatie en cerebrale fysiologische processen bij psychiatrische stoornissen.

BACKGROUND: Transcranial magnetic stimulation (tms) is a technique that is being used increasingly to investigate the biological precursors of psychiatric disorders. AIM: To survey the current knowledge about deficits in local cerebral physiologic processes, as measured with tms methods in patients with obsessive-compulsive disorder, depression, schizophrenia or attention deficit/ hyperactivity disorder. METHOD: Aspects of cortical excitability and functional connectivity between the cerebral hemispheres as measured with single and paired-pulse tms were investigated by reviewing the scientific literature. results Obsessive compulsive disorder, depression, schizophrenia and attention deficit/ hyperactivity disorder are found to be associated with aberrant cerebral excitability and impaired functional connectivity. CONCLUSION: TMS is a suitable tool for examining unique aspects of brain physiology in individuals with a psychiatric condition.

Alpha-band transcranial alternating current stimulation modulates precision, but not gain during whole-body spatial updating.

Spatial updating is essential to maintain an accurate representation of our visual environment when we move. A neural mechanism that contributes to this ability is called remapping: the transfer of visual information from neural populations that code a location before the motion to those that encode it after the motion. While there is ample evidence for neural remapping in conjunction with eye movements, only recent findings suggest a role of this mechanism for whole-body motion updating, based on the observation that alpha band (10Hz) activity is selectively reorganized during remapping. This study tested whether alpha oscillations directly contribute to whole-body motion updating using transcranial alternating current stimulation (tACS). In a double blind sham controlled design, healthy volunteers received 10Hz tACS at an intensity of 1mA over either the left or right posterior hemisphere during a whole-body motion updating task. Updating performance was assessed psychometrically and indices of gain and precision were obtained. No tACS-related effects on updating gain were found, irrespective of whether the remapping was across or within the hemispheres. In contrast, updating precision was enhanced when a target representation had to be internally remapped to the stimulated hemisphere, but not in other remapping conditions. Our observations suggest that alpha band oscillations do not directly affect the transfer of target representations during remapping, but increase the fidelity of the updated representation by attenuating interference of afferent information.

[Is there a big role for the little brain in psychiatry?]. / Is er een grote rol voor de kleine hersenen in de psychiatrie?

The cerebellum is a structure situated in the posterior cranial fossa. It has long been assumed that the cerebellum is concerned primarily with motor-related functions. However recent research has demonstrated that the cerebellum also plays a role in psychiatric disorders, including schizophrenia, autism and depression. Recent developments, described in this article, suggest that malfunctioning of the cerebellum can lead to severe emotion dysregulation and to psychopathological conditions.

Electromyographic responses to emotional facial expressions in 6-7 year olds with autism spectrum disorders.

This study aimed to examine facial mimicry in 6-7 year old children with autism spectrum disorder (ASD) and to explore whether facial mimicry was related to the severity of impairment in social responsiveness. Facial electromyographic activity in response to angry, fearful, sad and happy facial expressions was recorded in twenty 6-7 year old children with ASD and twenty-seven typically developing children. Even though results did not show differences in facial mimicry between children with ASD and typically developing children, impairment in social responsiveness was significantly associated with reduced fear mimicry in children with ASD. These findings demonstrate normal mimicry in children with ASD as compared to healthy controls, but that in children with ASD the degree of impairments in social responsiveness may be associated with reduced sensitivity to distress signals.