Testosterone modulates preattentive sensory processing and involuntary attention switches to emotional voices

Testosterone is capable of altering facial threat processing. Voices, similar to faces, convey social information. We hypothesized that administering a single dose of testosterone would change voice perception in humans. In a placebo-controlled, randomly assigned, double-blind crossover design, we administered a single dose of testosterone or placebo to 18 healthy female volunteers and used a passive auditory oddball paradigm. The mismatch negativity (MMN) and P3a in responses to fearfully, happily, and neutrally spoken syllables dada and acoustically matched nonvocal sounds were analyzed, indicating preattentive sensory processing and involuntary attention switches. Results showed that testosterone administration had a trend to shorten the peak latencies of happy MMN and significantly enhanced the amplitudes of happy and fearful P3a, whereas the happy- and fearful-derived nonvocal MMN and P3a remained unaffected. These findings demonstrated acute effect of testosterone on the neural dynamics of voice perception. Administering a single dose of testosterone modulates preattentive sensory processing and involuntary attention switches in response to emotional voices.

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Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor function

10.1101/2021.03.18.435979 ◽

2021 ◽

Author(s):

Lilian A. Weber ◽

Sara Tomiello ◽

Dario Schöbi ◽

Katharina V. Wellstein ◽

Daniel Müller ◽

...

Keyword(s):

Receptor Antagonist ◽

Muscarinic Acetylcholine Receptor ◽

Differential Sensitivity ◽

Oddball Paradigm ◽

Individual Treatment ◽

Receptor Function ◽

Double Blind ◽

Muscarinic Acetylcholine ◽

Auditory Oddball ◽

Drug Plasma Levels

AbstractThe auditory mismatch negativity (MMN) has been proposed as a biomarker of NMDA receptor (NMDAR) dysfunction in schizophrenia. Pathophysiological theories suggest that such dysfunction might be partially caused by aberrant interactions of different modulatory neurotransmitters with NMDARs, which could explain heterogeneity among patients with schizophrenia and their treatment response. Understanding the differential impact of different neuromodulators on readouts of NMDAR function is therefore of high clinical relevance.Here, we report results from two studies (N=81 each) which systematically tested whether the MMN is sensitive to diminishing and enhancing cholinergic vs. dopaminergic function. Both studies used a double-blind, placebo-controlled between-subject design and monitored individual drug plasma levels. Using a novel variant of the auditory oddball paradigm, we contrasted phases with stable versus volatile probabilities of tone switches. In the first study, we found that the muscarinic acetylcholine receptor antagonist biperiden reduced mismatch responses, particularly during stable phases of the experiment, whereas this effect was absent for amisulpride, a dopamine D2/D3 receptor antagonist. The direct comparison between biperiden and amisulpride indicated a significant drug × mismatch interaction. In the second study, neither elevating acetylcholine nor dopamine levels via administration of galantamine and levodopa, respectively, exerted significant effects on MMN.Overall, our results indicate differential sensitivity of the MMN to changes in cholinergic (muscarinic) versus dopaminergic receptor function. This finding may prove useful for developments of future tools for predicting individual treatment responses in disorders that show abnormal MMN, such as schizophrenia.

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A Single Dose of Beetroot Gel Rich in Nitrate Does Not Improve Performance but Lowers Blood Glucose in Physically Active Individuals

Journal of Nutrition and Metabolism ◽

10.1155/2017/7853034 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Julia Vasconcellos ◽

Diego Henrique Silvestre ◽

Diego dos Santos Baião ◽

João Pedro Werneck-de-Castro ◽

Thiago Silveira Alvares ◽

...

Keyword(s):

Nitric Oxide ◽

Single Dose ◽

Serum Cortisol ◽

Acute Effect ◽

Peak Oxygen Consumption ◽

Controlled Study ◽

Nitrate Content ◽

Nitric Oxide Synthesis ◽

Double Blind ◽

Physically Active

Background. Beetroot consumption has been proposed to improve exercise performance, since the nitrate content of this food is able to stimulate the synthesis of nitric oxide.Objective. The acute effect of 100 g of a beetroot gel containing ~10 mmol of nitrate was tested on the nitric oxide synthesis, on metabolic and biochemical parameters, and on performance in physically active individuals.Methods. Through a double blind, crossover, placebo-controlled study, 25 healthy runners ingested a single dose of beetroot and placebo gels. Participants performed an aerobic exercise protocol on a treadmill (3 min warm-up of 40% peak oxygen consumption, 4 min at 90% of gas exchange threshold I and 70% (Δ) maximal end speed until volitional fatigue).Results. Urinary levels of nitrite and nitrate increased after 90 min of beetroot gel ingestion. Plasma glucose concentrations lowered after the exercise and the decrease was maintained for 20 min. Systolic and diastolic blood pressures, serum cortisol, and blood lactate were not altered after the beetroot gel ingestion compared to a placebo gel.Conclusion. The single dose of beetroot gel provoked an increase of nitric oxide synthesis although no improvement on the physical performance of athletes during aerobic submaximal exercise was observed.

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NMDA receptor blockade causes selective prefrontal disinhibition in a roving auditory oddball paradigm

10.1101/133371 ◽

2017 ◽

Cited By ~ 1

Author(s):

Richard E Rosch ◽

Ryszard Auksztulewicz ◽

Pui Duen Leung ◽

Karl J Friston ◽

Torsten Baldeweg

Keyword(s):

Auditory Processing ◽

Human Subjects ◽

Network Models ◽

Inhibitory Interneuron ◽

Controlled Study ◽

Oddball Paradigm ◽

Double Blind ◽

Auditory Oddball ◽

Specific Effects ◽

Auditory Oddball Paradigm

N-methyl-D-aspartate receptors (NMDARs) are expressed widely throughout the human cortex. Yet disturbances in NMDAR transmission - as implicated in patients with schizophrenia or pharmacologically induced - can cause a regionally specific set of electrophysiological effects. Here, we present a double-blind placebo-controlled study of the effects of the NMDAR blocker ketamine in human volunteers. We employ a marker of auditory learning and putative synaptic plasticity - the mismatch negativity - in a roving auditory oddball paradigm. Using recent advances in Bayesian modelling of group effects in dynamic causal modelling, we fit biophysically plausible network models of the auditory processing hierarchy to whole-scalp evoked response potential recordings. This allowed us to identify the regionally specific effects of ketamine in a distributed network of interacting cortical sources. Under placebo, our analysis replicated previous findings regarding the effects of stimulus repetition and deviance on connectivity within the auditory hierarchy. Crucially, we show that the effect of ketamine is best explained as a selective change in intrinsic inhibition, with a pronounced ketamine-induced reduction of inhibitory interneuron connectivity in frontal sources. These results are consistent with findings from invasive recordings in animal models exposed to NMDAR blockers, and provide evidence that inhibitory-interneuron specific NMDAR dysfunction may be sufficient to explain electrophysiological abnormalities of sensory learning induced by ketamine in human subjects.

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One-week escitalopram intake shifts excitation-inhibition balance in the healthy female brain

10.1101/2021.07.09.451806 ◽

2021 ◽

Author(s):

Rachel G. Zsido ◽

Eóin N. Molloy ◽

Elena Cesnaite ◽

Gergana Zheleva ◽

Nathalie Beinhölzl ◽

...

Keyword(s):

Single Dose ◽

Steady State ◽

Selective Serotonin Reuptake Inhibitors ◽

Double Blind Study ◽

Healthy Human ◽

Double Blind ◽

Female Brain ◽

Healthy Female ◽

Cortical Excitation ◽

Relationship Of

Background: Neural health relies on cortical excitation-inhibition balance (EIB), with disrupted EIB underlying circuit dysfunction in several neuropsychiatric disorders. Previous research suggests links between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear. To this end, we assessed changes in EIB following longitudinal escitalopram-intake. Methods: In a randomized, double-blind study protocol, a sample of 59 healthy female individuals on oral contraceptives underwent three resting-state electroencephalography recordings after daily administration of 20 mg escitalopram (n = 28) or placebo (n = 31) at baseline, after single dose, and after 1 week (steady state).We assessed 1/f slope of the power spectrum, a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Results: Escitalopram-intake associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after single dose of escitalopram predicted 1/f slope at steady state. Higher plasma escitalopram levels at single dose associated with better maintenance of these EIB changes throughout the drug administration week. Conclusions: Characterizing changes in 1/f slope during longitudinal SSRI-intake in healthy female individuals, we show that escitalopram shifted EIB in favor of excitation. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the neuroimaging lens by testing an interventional psychopharmacological design in a clearly-defined endocrinological state.

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