Excitation/inhibition balance in the aMCC influences resting state activity in the CEN

Introduction: Excitation/inhibition balance can be used as a predictor not only for the functional regional response in the task-based functional magnetic resonance imaging (fMRI) but also for functional connectivity (FC) strength measured within and between networks [1]. Previous studies reported that both Glutamate (Glu) and γ-Aminobutyric acid (GABA) levels can predict within network connectivity patterns [2,3]. However, the results were inconsistent and they were mainly focused on the default mode network confirming that there is a need for more robust and extensive measurements. Therefore, we investigated whole brain associations between the main excitatory – Glu – and inhibitory neurotransmitter – GABA – with the FC of the anterior mid cingulate cortex (aMCC), a node of the salience network (SN), with a particular focus on regions of the central executive network (CEN). We additionally explored how these metabolites influence basic neuronal measurements such as fractional amplitude of low frequency fluctuations (fALFF). Methods: 106 subjects (age = 27.09 ± 6.72, 44 females) completed a research paradigm that included a resting-state fMRI and a magnetic resonance spectroscopy (MRS) session in 7T. An MRS voxel was placed in the aMCC, and Glu, GABA and Creatine (Cr) levels were acquired using a stimulated-echo acquisition mode (STEAM) sequence. A regression analysis was conducted in SPM8 between metabolites and aMCC voxel–seed FC maps with age, sex and grey matter ratio as covariates of nuisance. Additionally, the same regression analysis was performed for fALFF. Results are reported on FWE < 0.05 cluster level significance with an initial threshold of p < 0.001, uncorrected. Results: Glu/Cr and aMCC voxel FC showed a strong negative association in the left posterior frontal gyrus and several nodes of the visual cortex. A regionally converging positive correlation was found between fALFF and GABA/Cr in the left posterior frontal gyrus. Conclusions: Both GABA and Glu levels measured in the aMCC predict the strength and the basal activity of the posterior frontal gyrus, which is a node of the CEN

Effects of Neurexan® on brain responses to deviant stimuli during an auditory oddball task

Introduction: Neurexan®, a medicinal product sold over the counter (OTC), is composed of four plant and mineral ingredients; passionflower, oats, coffee and zinc valerianate. Neurexan® has been investigated in patients with symptoms related to acute stress, nervousness/restlessness, and insomnia. The previous research suggested an attenuated neuroendocrine stress response in healthy volunteers induced by Neurexan® (Doering et al. 2016). This study further explores the effects of Neurexan® on cognitive performance and attention. It is generally recognized that stress is associated with cognitive impairments. Expecting that Neurexan® reduces the stress level, we hypothesized that the subjects in the placebo group would be more susceptible to distraction compared to treatment group. Material and Methods: In a randomized, placebo-controlled, double-blind, two-period crossover trial, brain responses of 39 healthy, moderate stressed males were measured during an unattended auditory oddball paradigm via 64-channel electroencephalogram (EEG) after intake of Neurexan® and placebo. The paradigm consisted of 80 standard tones and two types of deviant tones (10 frequency deviant; 10 duration deviant), presented in a pseudo-randomized order. The standard tone was composed of eight equally loud sinusoidal tones (fundamental frequency 330 Hz and seven harmonic partials) and had a duration of 100 ms. The deviants were either 40 ms shorter (duration deviant) or 1.25 semitones higher (frequency deviant). Results: Here we present the results about the effect of Neurexan treatment on both mismatch negativity (MMN) and latency of the peaks when assessing EEG responses (ERPs) to deviant tones (frequency and duration deviant) compared to placebo. Discussion: Our findings suggest that Neurexan® also leads to subtle primary processing changes additionally to its postulated top down effects

Effects of Neurexan® on emotional brain response

Introduction: Neurexan®, a natural pharmaceutical product sold over the counter (OTC), is composed of four diluted plant and mineral components: Passiflora incarnata (passionflower), Avena sativa (oats), Coffea arabica (coffee) and Zincum isovalerianicum (zinc valerianate). Neurexan® has been so far investigated in patients with symptoms related to acute stress, nervousness or restlessness and insomnia. Acute stress response is modulated via the hypothalamic–pituitary–adrenal (HPA) axis, which interacts both with limbic and cortical areas in the brain. One of the prominent regions affected by stress is the amygdala. The amygdala is involved in the development of fear and emotional behavior and acute stress sensitizes the amygdala. It increases vigilance and anxiety levels, which in turn further promote the stress response (van Marle et al., 2009). Amygdala reactivity to negative stimuli is considered a reliable phenotype that closely associates with the stress regulation (Swartz et al., 2015) and can be assessed with the Hariri paradigm, a task measuring response to emotional facial expression of fear, happiness or anger (Hariri et al., 2003). A linkage between an increased level of stress hormones and increased emotional response to angry faces has been shown in patients with social phobia (van Peer et al., 2009), further associating stress and emotion processing via the amygdala. Previous investigation suggested an attenuated neuroendocrine stress response in healthy volunteers induced by Neurexan® (Doering et al., 2016). Thus, the aim of this study was to explore possible effects of Neurexan® on lower emotional brain response to negative faces in the amygdala. Material and Methods: 39 healthy male subjects (age= 43.7± 9.8) participated in a randomized, placebo- controlled, double- blind, two- period crossover trial study. Participants were scanned in a 3 Tesla functional magnetic resonance (fMR). After a single dose of Neurexan® or placebo, to challenge their stress response, subjects firstly underwent a moderate stress task, after which an emotional Hariri paradigm was measured. Data were preprocessed and analyzed in SPM12. Amygdala was anatomically defined by the AAL (Automated Anatomical Labelling Atlas) and a difference between responses of placebo and Neurexan® for negative faces was calculated with a paired t-test, peak level FWE corrected for multiple comparisons within the search volume. Results: Hariri task was firstly validated for emotional negative faces response. Significant (peak level FWE corrected) bilateral activations of fusiform gyri, amygdalae and prefrontal cortex as well as unilateral activation in right thalamus were confirmed as previously reported (Hariri et al., 2003). Additionally, significant activations in the visual area and cerebellum were observed. Paired t-test showed a drug effect (p< 0.05) in the left amygdala, with stronger activations in placebo than in Neurexan® condition. Right amygdala did not show significant effect. Discussion: We found a significant reduction of BOLD response to negative faces in the left amygdala during the Neurexan® session compared to the placebo session. Neurexan® reduced the emotional brain response to negative stimuli, possibly interacting with the HPA axis

Excitation/inhibition balance in the aMCC influences resting state activity in the CEN

Introduction: Excitation/inhibition balance can be used as a predictor not only for the functional regional response in the task-based functional magnetic resonance imaging (fMRI) but also for functional connectivity (FC) strength measured within and between networks [1]. Previous studies reported that both Glutamate (Glu) and γ-Aminobutyric acid (GABA) levels can predict within network connectivity patterns [2,3]. However, the results were inconsistent and they were mainly focused on the default mode network confirming that there is a need for more robust and extensive measurements. Therefore, we investigated whole brain associations between the main excitatory – Glu – and inhibitory neurotransmitter – GABA – with the FC of the anterior mid cingulate cortex (aMCC), a node of the salience network (SN), with a particular focus on regions of the central executive network (CEN). We additionally explored how these metabolites influence basic neuronal measurements such as fractional amplitude of low frequency fluctuations (fALFF). Methods: 106 subjects (age = 27.09 ± 6.72, 44 females) completed a research paradigm that included a resting-state fMRI and a magnetic resonance spectroscopy (MRS) session in 7T. An MRS voxel was placed in the aMCC, and Glu, GABA and Creatine (Cr) levels were acquired using a stimulated-echo acquisition mode (STEAM) sequence. A regression analysis was conducted in SPM8 between metabolites and aMCC voxel–seed FC maps with age, sex and grey matter ratio as covariates of nuisance. Additionally, the same regression analysis was performed for fALFF. Results are reported on FWE < 0.05 cluster level significance with an initial threshold of p < 0.001, uncorrected. Results: Glu/Cr and aMCC voxel FC showed a strong negative association in the left posterior frontal gyrus and several nodes of the visual cortex. A regionally converging positive correlation was found between fALFF and GABA/Cr in the left posterior frontal gyrus. Conclusions: Both GABA and Glu levels measured in the aMCC predict the strength and the basal activity of the posterior frontal gyrus, which is a node of the CEN

Excitation/inhibition balance in the aMCC influences resting state activity in the CEN

Background: Excitation/inhibition balance can be used as a predictor not only for the functional regional response in the task-based functional magnetic resonance imaging (fMRI) but also for functional connectivity (FC) strength measured within and between networks. Previous studies reported that both Glutamate (Glu) and γ-Aminobutyric acid (GABA) levels can predict within network connectivity patterns. However, the results were inconsistent and they were mainly focused on the default mode network confirming that there is a need for more robust and extensive measurements. Therefore, we investigated whole brain associations between the main excitatory - Glu - and inhibitory neurotransmitter - GABA - with the FC of the anterior mid cingulate cortex (aMCC), a node of the salience network (SN), with a particular focus on regions of the central executive network (CEN). We additionally explored how these metabolites influence basic neuronal measurements such as fractional amplitude of low frequency fluctuation (fALFF). Methods: 78 healthy subjects (39 females, age = 26.97 ± 6.53) completed a research paradigm that included a resting-state fMRI and a magnetic resonance spectroscopy (MRS) session in 7T. An MRS voxel was placed in the aMCC, and Glu, GABA and Creatine (Cr) levels were acquired using a stimulated-echo acquisition mode (STEAM) sequence. A regression analysis was conducted in SPM8 between metabolites and aMCC voxel-seed FC maps with age, sex and grey matter ratio as covariates of nuisance. Additionally, the same regression analysis was performed for fALFF. Results are reported on FWE < 0.05 cluster level significance with an initial threshold of p < 0.001, uncorrected. Results: Glu/Cr and aMCC voxel FC showed a strong negative association in the left posterior frontal gyrus and several nodes of the visual cortex. A regionally converging positive correlation was found between fALFF and GABA/Cr in the left posterior frontal gyrus. Conclusion: Both GABA and Glu levels measured in the aMCC predict the strength and the basal activity of the posterior frontal gyrus, which is a node of the CEN