Transcranial alternating current stimulation (tACS) is a unique form of non-invasive brain stimulation. Sinusoidal alternating electric currents are delivered to the scalp to affect mostly cortical ...neurons. tACS is supposed to modulate brain function and, in turn, cognitive processes by entraining brain oscillations and inducing long-term synaptic plasticity. Therefore, tACS has been investigated in cognitive neuroscience, but only recently, it has been also introduced in psychiatric clinical trials. This review describes current concepts and first findings of applying tACS as a potential therapeutic tool in the field of psychiatry. The current understanding of its mechanisms of action is explained, bridging cellular neuronal activity and the brain network mechanism. Revisiting the relevance of altered brain oscillations found in six major psychiatric disorders, putative targets for the management of mental disorders using tACS are discussed. A systematic literature search on PubMed was conducted to report findings of the clinical studies applying tACS in patients with psychiatric conditions. In conclusion, the initial results may support the feasibility of tACS in clinical psychiatric populations without serious adverse events. Moreover, these results showed the ability of tACS to reset disturbed brain oscillations, and thus to improve behavioural outcomes. In addition to its potential therapeutic role, the reactivity of the brain circuits to tACS could serve as a possible tool to determine the diagnosis, classification or prognosis of psychiatric disorders. Future double-blind randomised controlled trials are necessary to answer currently unresolved questions. They may aim to detect response predictors and control for various confounding factors.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In the last decade, there has been growing evidence that an interaction exists between inflammation and the kynurenine pathway in schizophrenia. Additionally, many authors found microglial activation ...in cases of schizophrenia due to inflammatory mechanisms related mostly to an increase of pro-inflammatory cytokines. In order to gain new insights into the pathophysiology of schizophrenia, it is important to incorporate the latest published evidence concerning inflammatory mechanisms and kynurenine metabolism. This systematic review aims to collect reliable recent findings within the last decade supporting such a theory.
A structured search of electronic databases was conducted for publications between 2008 and 2018 to identify eligible studies investigating patients with schizophrenia/psychosis and the relationship between inflammation and kynurenine pathway. Applicable studies were systematically scored using the NIH Quality Assessment Tools. Two researchers independently extracted data on diagnosis (psychosis/schizophrenia), inflammation, and kynurenine/tryptophan metabolites.
Ten eligible articles were identified where seven studies assessed blood samples and three assessed cerebrospinal fluid in schizophrenic patients. Of these articles: Four investigated the relationship between immunoglobulins and the kynurenine pathway and found correlations between IgA-mediated responses and levels of tryptophan metabolites (i.e., kynurenine pathway).Five examined the correlation between cytokines and kynurenine metabolites where three showed a relationship between elevated IL-6, TNF-α concentrations, and the kynurenine pathway.Only one study discovered correlations between IL-8 and the kynurenine pathway.Two studies showed correlations with lower concentrations of IL-4 and the kynurenine pathway.Moreover, this systematic review did not find a significant correlation between CRP (n = 1 study), IFN-γ (n = 3 studies), and the kynurenine pathway in schizophrenia.
These results emphasize how different inflammatory markers can unbalance the tryptophan/kynurenine pathway in schizophrenia. Several tryptophan/kynurenine pathway metabolites are produced which can, in turn, underlie different psychotic and cognitive symptoms via neurotransmission modulation. However, due to heterogeneity and the shortage of eligible articles, they do not robustly converge to the same findings. Hence, we recommend further studies with larger sample sizes to elucidate the possible interactions between the various markers, their blood vs. CSF ratios, and their correlation with schizophrenia symptoms.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neurochemistry of Visual Attention Lockhofen, Denise Elfriede Liesa; Mulert, Christoph
Frontiers in neuroscience,
05/2021, Volume:
15
Journal Article
Peer reviewed
Open access
Visual attention is the cognitive process that mediates the selection of important information from the environment. This selection is usually controlled by bottom-up and top-down attentional ...biasing. Since for most humans vision is the dominant sense, visual attention is critically important for higher-order cognitive functions and related deficits are a core symptom of many neuropsychiatric and neurological disorders. Here, we summarize the importance and relative contributions of different neuromodulators and neurotransmitters to the neural mechanisms of top-down and bottom-up attentional control. We will not only review the roles of widely accepted neuromodulators, such as acetylcholine, dopamine and noradrenaline, but also the contributions of other modulatory substances. In doing so, we hope to shed some light on the current understanding of the role of neurochemistry in shaping neuron properties contributing to the allocation of attention in the visual field.
Transcranial direct current stimulation (tDCS) has been proposed for experimental and therapeutic modulation of regional brain function. Specifically, anodal tDCS of the dorsolateral prefrontal ...cortex (DLPFC) together with cathodal tDCS of the supraorbital region have been associated with improvement of cognition and mood, and have been suggested for the treatment of several neurological and psychiatric disorders. Although modeled mathematically, the distribution, direction, and extent of tDCS-mediated effects on brain physiology are not well understood. The current study investigates whether tDCS of the human prefrontal cortex modulates resting-state network (RSN) connectivity measured by functional magnetic resonance imaging (fMRI). Thirteen healthy subjects underwent real and sham tDCS in random order on separate days. tDCS was applied for 20 min at 2 mA with the anode positioned over the left DLPFC and the cathode over the right supraorbital region. Patterns of resting-state brain connectivity were assessed before and after tDCS with 3 T fMRI, and changes were analyzed for relevant networks related to the stimulation-electrode localizations. At baseline, four RSNs were detected, corresponding to the default mode network (DMN), the left and right frontal-parietal networks (FPNs) and the self-referential network. After real tDCS and compared with sham tDCS, significant changes of regional brain connectivity were found for the DMN and the FPNs both close to the primary stimulation site and in connected brain regions. These findings show that prefrontal tDCS modulates resting-state functional connectivity in distinct functional networks of the human brain.
•We researched glycine's effect on ketamine-induced EEG changes.•Ketamine-induced gamma changes correlate with negative symptoms.•Glycine-pretreatment attenuates these gamma impairments.•A sizable ...EEG response is associated with attenuated symptoms.
Although a substantial number of studies suggests some clinical benefit concerning negative symptoms in schizophrenia through the modulation of NMDA-receptor function, none of these approaches achieved clinical approval. Given the large body of evidence concerning glutamatergic dysfunction in a subgroup of patients, biomarkers to identify those with a relevant clinical benefit through glutamatergic modulation are urgently needed. A similar reduction of the early auditory evoked gamma-band response (aeGBR) as found in schizophrenia patients can be observed in healthy subjects following the application of an NMDA-receptor antagonist in the ketamine-model, which addresses the excitation / inhibition (E/I) imbalance of the disease. Moreover, this oscillatory change can be related to the emergence of negative symptoms. Accordingly, this study investigated whether glycine-related increases of the aeGBR, through NMDA-receptor co-agonism, accompany an improvement concerning negative symptoms in the ketamine-model. The impact of subanesthetic ketamine doses and the pretreatment with glycine was examined in twenty-four healthy male participants while performing a cognitively demanding aeGBR paradigm with 64-channel electroencephalography. Negative Symptoms were assessed through the PANSS. S-Ketamine alone caused a reduction of the aeGBR amplitude associated with more pronounced negative symptoms compared to placebo. Pretreatment with glycine attenuated both, the ketamine-induced alterations of the aeGBR amplitude and the increased PANSS negative scores in glycine-responders, classified based on relative aeGBR increase. Thus, we propose that the aeGBR represents a possible biomarker for negative symptoms in schizophrenia related to insufficient glutamatergic neurotransmission. This would allow to identify patients with negative symptoms, who might benefit from glutamatergic treatment.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Auditory verbal hallucinations (AVH) occur in psychotic disorders, but also as a symptom of other conditions and even in healthy people. Several current theories on the origin of AVH converge, with ...neuroimaging studies suggesting that the language, auditory and memory/limbic networks are of particular relevance. However, reconciliation of these theories with experimental evidence is missing. We review 50 studies investigating functional (EEG and fMRI) and anatomic (diffusion tensor imaging) connectivity in these networks, and explore the evidence supporting abnormal connectivity in these networks associated with AVH. We distinguish between functional connectivity during an actual hallucination experience (symptom capture) and functional connectivity during either the resting state or a task comparing individuals who hallucinate with those who do not (symptom association studies). Symptom capture studies clearly reveal a pattern of increased coupling among the auditory, language and striatal regions. Anatomical and symptom association functional studies suggest that the interhemispheric connectivity between posterior auditory regions may depend on the phase of illness, with increases in non-psychotic individuals and first episode patients and decreases in chronic patients. Leading hypotheses involving concepts as unstable memories, source monitoring, top-down attention, and hybrid models of hallucinations are supported in part by the published connectivity data, although several caveats and inconsistencies remain. Specifically, possible changes in fronto-temporal connectivity are still under debate. Precise hypotheses concerning the directionality of connections deduced from current theoretical approaches should be tested using experimental approaches that allow for discrimination of competing hypotheses.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Neural oscillations are fundamental mechanisms of the human brain that enable coordinated activity of different brain regions during perceptual and cognitive processes. A frontotemporal network ...generated by means of gamma oscillations and comprising the auditory cortex (AC) and the anterior cingulate cortex (ACC) has been shown to be involved in the cognitively demanding auditory information processing. This study aims to reveal patterns of functional and effective connectivity within this network in healthy subjects by means of simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI).
We simultaneously recorded EEG and fMRI in 28 healthy subjects during the performance of a cognitively demanding auditory choice reaction task. Connectivity between the ACC and AC was analysed employing EEG and fMRI connectivity measures.
We found a significant BOLD signal correlation between the ACC and AC, a significant task-dependant increase of fMRI connectivity (gPPI) and a significant increase in functional coupling in the gamma frequency range between these regions (LPS), which was increased in top-down direction (granger analysis). EEG and fMRI connectivity measures were positively correlated.
The results of these study point to a role of a top-down influence of the ACC on the AC executed by means of gamma synchronisation. The replication of fMRI connectivity patterns in simultaneously recorded EEG data and the correlation between connectivity measures from both domains found in our study show, that brain connectivity based on the synchronisation of gamma oscillations is mirrored in fMRI connectivity patterns.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
NMDA-receptor hypofunction is increasingly considered to be an important pathomechanism in schizophrenia. However, to date, it has not been possible to identify patients with relevant NMDA-receptor ...hypofunction who would respond to glutamatergic treatments. Preclinical models, such as the ketamine model, could help identify biomarkers related to NMDA-receptor function that respond to glutamatergic modulation, for example, via activation of the glycine-binding site. We, therefore, aimed to investigate the effects of opposing modulation of the NMDA receptor on gamma activity (30-100 Hz) at rest, the genesis of which appears to be highly dependent on NMDA receptors. The effects of subanesthetic doses of S-ketamine and pretreatment with glycine on gamma activity at rest were examined in twenty-five healthy male participants using 64-channel electroencephalography. Psychometric scores were assessed using the PANSS and the 5D-ASC. While S-ketamine significantly increased psychometric scores and gamma activity at the scalp and in the source space, pretreatment with glycine did not significantly attenuate any of these effects when controlled for multiple comparisons. Our results question whether increased gamma activity at rest constitutes a suitable biomarker for the target engagement of glutamatergic drugs in the preclinical ketamine model. They might further point to a differential role of NMDA receptors in gamma activity generation.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Our understanding of the neural correlates of auditory-verbal-hallucinations (AVH) has substantially increased during the last few years, but is far from sufficient. One current hypothesis, the ...interhemispheric miscommunication theory, is based on findings from fMRI, DTI and EEG, but there is only limited evidence so far concerning underlying functional coupling mechanisms. Here we report a 64-channel EEG study using lagged phase synchronization analysis and eLORETA source estimation to examine the functional connectivity between bilateral auditory cortices in the gamma-band in 26 schizophrenia patients (13 with and 13 without AVH) and 26 matched healthy controls (HC) while performing a dichotic listening task. We found a significantly reduced right-ear-advantage (REA) in AVH but not in non-AVH patients compared to HC. The major finding was significantly stronger gamma-band connectivity between bilateral auditory cortices during conscious perception of left (versus right) ear syllables in patients with AVH compared to HC and patients without AVH. A significant positive correlation was found between this connectivity alteration and the AVH symptom score in schizophrenia patients. These findings provide further support for the interhemispheric miscommunication hypothesis of AVH pathophysiology by indicating that aberrant gamma-band coupling between auditory cortices is related to the emergence of AVH in schizophrenia.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
