Inhibitory Processes Research Articles

Metabolic Diaschisis in Mild Traumatic Brain Injury.

Neurophysiological diaschisis presents in traumatic brain injury (TBI) as functional impairment distant to the lesion site caused by axonal neuroexcitation and deafferentation. Diaschisis studies in TBI models have evaluated acute phase functional and microstructural changes. Here, in vivo biochemical changes and cerebral blood flow (CBF) dynamics following TBI are studied with magnetic resonance. Behavioral assessments, magnetic resonance spectroscopy (MRS), and CBF measurements on rats followed cortical impact TBI. Data were acquired pre-TBI and 1-3 h, 2-days, 7-days, and 14-days post-TBI. MRS was performed on the ipsilateral and contralateral sides in the cortex, striatum, and thalamus. Metabolites measured by MRS included N-acetyl aspartate (NAA), aspartate (Asp), lactate (Lac), glutathione (GSH), and glutamate (Glu). Lesion volume expanded for 2 days post-TBI and then decreased. Ipsilateral CBF dropped acutely versus baseline on both sides (-62% ipsilateral, -48% contralateral, p < 0.05) but then recovered in cortex, with similar changes in ipsilateral striatum. Metabolic changes versus baseline included increased Asp (+640% by Day 7 post-TBI, p < 0.05) and Lac (+140% on Day 2 post-TBI, p < 0.05) in ipsilateral cortex, while GSH (-67% acutely, p < 0.05) and NAA decreased (-50% on Day 2, p < 0.05). In contralateral cortex Lac decreased (-73% acutely, p < 0.05). Analysis of variance showed significance for Side (p < 0.05), Time after TBI (p < 0.05), and interactions (p < 0.005) for Asp, GSH, Lac, and NAA. Transient decreases of GSH (-30%, p < 0.05, acutely) and NAA (-23% on Day 2, p < 0.05) occurred in ipsilateral striatum with reduced GSH (-42%, p < 0.005, acutely) in the contralateral striatum. GSH was decreased in ipsilateral thalamus (-59% ipsilateral on Day 2, p < 0.05). Delayed increases of total choline were seen in the contralateral thalamus were noted as well (+21% on Day 7 post-TBI, p < 0.05). Both CBF and neurometabolite concentration changes occurred remotely from the TBI site, both ipsilaterally and contralaterally. Decreased Lac levels on the contralateral cortex following TBI may be indicative of reduced anaerobic metabolism during the acute phase. The timing and locations of the changes suggest excitatory and inhibitory signaling processes are affecting post-TBI metabolic fluctuations.

Deciphering the Enigma of Neuron-Glial Interactions in Neurological Disorders.

Innate lymphocytes, including microglial cells, astrocytes, and oligodendrocytes, play a crucial role in initiating neuroinflammatory reactions inside the central nervous system (CNS). The prime focus of this paper is on the involvement and interplay of neurons and glial cells in neurological disorders such as Alzheimer's Disease (AD), Autism Spectrum Disorder (ASD), epilepsy, and multiple sclerosis (MS). In this review, we explore the specific contributions of microglia and astrocytes and analyzes multiple pathways implicated in neuroinflammation and disturbances in excitatory and inhibitory processes. Firstly, we elucidate the mechanisms through which toxic protein accumulation in AD results in synaptic dysfunction and deregulation of the immune system and examines the roles of microglia, astrocytes, and hereditary factors in the pathogenesis of the disease. Secondly, we focus on ASD and the involvement of glial cells in the development of the nervous system and the formation of connections between neurons and investigates the genetic connections associated with these processes. Lastly, we also address the participation of glial cells in epilepsy and MS, providing insights into their pivotal functions in both conditions. We also tried to give an overview of seven different pathways like toll-like receptor signalling pathway, MyD88-dependent and independent pathway, etc and its relevance in the context with these neurological disorders. In this review, we also explore the role of activated glial cells in AD, ASD, epilepsy, and MS which lead to neuroinflammation. Even we focus on excitatory and inhibitory imbalance in all four neurological disorders as imbalance affect the proper functioning of neuronal circuits. Finally, this review concludes that there is necessity for additional investigation on glial cells and their involvement in neurological illnesses.

Neurochemical Predictors of Generalized Learning Induced by Brain Stimulation and Training.

Methods of cognitive enhancement for humans are most impactful when they generalize across tasks. However, the extent to which such "transfer" is possible via interventions is widely debated. In addition, the contribution of excitatory and inhibitory processes to such transfer is unknown. Here, in a large-scale neuroimaging individual differences study with humans (both sexes), we paired multitasking training and noninvasive brain stimulation (transcranial direct current stimulation, tDCS) over multiple days and assessed performance across a range of paradigms. In addition, we varied tDCS dosage (1.0 and 2.0 mA), electrode montage (left or right prefrontal regions), and training task (multitasking vs a control task) and assessed GABA and glutamate concentrations via ultrahigh field 7T magnetic resonance spectroscopy. Generalized benefits were observed in spatial attention, indexed by visual search performance, when multitasking training was combined with 1.0 mA stimulation targeting either the left or right prefrontal cortex (PFC). This transfer effect persisted for ∼30 d post intervention. Critically, the transferred benefits associated with right prefrontal tDCS were predicted by pretraining concentrations of glutamate in the PFC. Thus, the effects of this combined stimulation and training protocol appear to be linked predominantly to excitatory brain processes.

Focal changes in alpha oscillations during short-term memorization of pain: a high-density electroencephalogram study with source localization.

Memories of painful events constitute the basis for assessing patients' pain. This study explores the brain oscillatory activity during short-term memorization of a nociceptive stimulus. High-density EEG activity (128 electrodes) was recorded in 13 healthy subjects during a match-to-sample sensory discrimination task, whereby participants compared the intensity of a thumb-located electric shock (S2) with a prior stimulus to the same location (S1) delivered 8-10s earlier. Stimuli were above or below the individual nociceptive threshold. EEG activity with intracortical source localization via LORETA source reconstruction was analysed during the inter-stimuli period and contrasted with a non-memory-related control task. The inter-stimulus memorization phase was characterized by a focal alpha-activity enhancement, significant during the nociceptive condition only, which progressed from bilateral occipital regions (cuneus and mid-occipital gyri) during the first encoding-memorization phase towards the right-superior and right mid-temporal gyri during the 2-4s immediately preceding S2. Initial alpha enhancement in occipital areas/cuneus is consistent with rapid non-specific inhibition of task-irrelevant visual processing during initial stimulus encoding. Its transfer to the right-temporal regions was concomitant to the temporary upholding of the stimulus perceptual representation, previous to receiving S2, and suggests an active and local blockade of external interferences while these regions actively maintain internal information. These results add to a growing field indicating that alpha oscillations, while indicating local inhibitory processes, can also indirectly reveal active stimulus handling, including maintenance in short-term memory buffers, by objectivizing the filtering out of irrelevant and potentially disrupting inputs in brain regions engaged in internally driven operations.

Inhibitory Control Training for Anxiety and Math Achievement in Primary School Children: Protocol for a Proof-of-Concept Study.

Cognitive control training (CCT) has shown potential to reduce emotional vulnerability in adults and adolescents. However, there is scant literature testing the efficacy of CCT for the reduction of anxiety and transferring the effects to educational outcomes in children. Building on the evidence that a greater ability to suppress a prepotent response (inhibitory control) is associated with higher math achievement in children, it is plausible that training inhibitory processes using a CCT paradigm may be beneficial for reducing anxiety, improving inhibitory control, and in turn increasing math achievement. This proof-of-concept study aims to investigate the efficacy of 15 sessions of inhibitory control training for reduction in anxiety and improvement in math achievement in primary school children. We will use a 2 (group: CCT, adaptive Go/No-Go vs active control, low-load task) multiplied by 4 (time: pre- vs posttraining vs 1-month vs 3-month follow-up) randomized design in a nonselected sample of 100 children aged 8-10 years. Both groups will complete 10 minutes of daily training for 3 weeks at school. The dependent variables will be anxiety and correlates (Spence Children's Anxiety Scale, Penn State Worry Questionnaire for Children, Revised Children's Anxiety and Depression Scale, Child Response Style Questionnaire, and Modified Abbreviated Math Anxiety Scale), inhibitory control (Go/No-Go task), shifting (color-shape shifting task), updating (n-back task), and math achievement (Applied Problems, Calculation, and Math Facts Fluency subtests from the Woodcock-Johnson IV Tests of Achievement). We opened enrollment in September 2023. The initial results are expected to be published in late 2024. We predict that children in the CCT group will show a reduction in emotional symptoms; improvements in inhibition, shifting, and updating performance; and advances in math achievement from pre- to posttraining, and that these effects will be maintained at 1- and 3-month follow-ups, compared to children in the active control group. The CCT paradigm used in our study will provide a greater understanding of the emotional and cognitive transfer effects on children and inform future work. Specifically, the findings will advance the knowledge of deploying inhibitory control training with children and provide valuable insights into its use for reducing anxiety and advancing math achievement. Open Science Framework ofs.io/de2qa; https://doi.org/10.17605/OSF.IO/DE2QA. PRR1-10.2196/52929.

Individual features of the temporal dynamics of inhibitory processes in visual short-term memory depending on the content of stimuli and memorization training

Introduction. Age-related changes in cognitive functions are caused by various processes: degrading inhibitory control, decrease in the volume of working memory, or a slowdown in the speed of thought processes. However, there is no unanimous opinion on the dynamics of these processes and their interactions yet. Based on this, our research goal became finding the temporal dynamics and individual relationship of the effects of proactive interference (Retrival-Induced Forgeting (RIF)) and learning to remember (Retrieval-Based Learning (RBL)) depending on the content of the presented stimuli as well as the age-related specifics of memorization when training the short-term visual memory. Materials and methods. Memory training was carried out in a mode independently organized by the study participants using a computerized memorization program in a proactive interference model, including five sessions of visual presentation of stimuli. University students participated in the first part of the study, aimed at clarifying the meaning of the content of two different sets of stimuli, (220 people, 20.4 ± 1.9 years old), whereas second part aimed to determine the age-related characteristics of visual short-term memory training in a group of students, (70 subjects, 21.7±2.5 years) and a group of elderly women (25 subjects, 64.4±6.3 years). Research results. The results of the memory trace retrieval analysis showed that the RIF effect dominates over the RBL effect regardless of the content of the stimuli, but at different rates of its development depending on the set of stimuli used. With significant individual diversity in the combination of memory strategies, the RIF effect dominated at the initial stage of stimulus presentation (67.6% of cases) and gradually replaced by RBL (56.2% in the fifth run of the experiment). Analysis of age-related characteristics of the effectiveness of short-term visual memory training showed that when it is independently organized, maintaining activity is observed in 32% of university students and 50% in the elderly group. Along with this. Only average of ten approaches to complete this task accompanied by a further decrease in the number of training participants. Comparison of the results of the first three training sessions revealed a significant increase in the memory index in both groups compared to the initial value and the presence of a RIF effect with a further more rapid increase in the efficiency of memorization in students. Conclusion. Proactive interference while memorization of visual stimuli repeatedly presented in five sessions, appears regardless of their content, age of the subjects and memorization training. The efficiency of memorization due to training grows faster in the group of students and accompanied by the combination of the RIF and RBL effects that is characterized by individual diversity without a significant effect on the final result of the memory retrieval.

Disambiguating vision with sound

An important task for the visual system is to identify and segregate objects from background. Figure-ground illusions, such as Edgar Rubin's bistable 'vase-faces illusion'1, make the point clearly: we see either a central vase or lateral faces, alternating spontaneously, but never both images simultaneously. The border is perceptually assigned to either faces or vase, which become figure, the other shapeless background2. The stochastic alternation between figure and ground probably reflects mutual inhibitory processes that ensure a single perceptual outcome3. Which shape dominates perception depends on many factors, such as size, symmetry, convexity, enclosure, and so on, as well as attention and intention4. Here we show that the assignment of the visual border can be strongly influenced by auditory input, far more than is possible by voluntary intention. VIDEO ABSTRACT.

Machine Learning Classification of Event-Related Brain Potentials during a Visual Go/NoGo Task.

Machine learning (ML) methods are increasingly being applied to analyze biological signals. For example, ML methods have been successfully applied to the human electroencephalogram (EEG) to classify neural signals as pathological or non-pathological and to predict working memory performance in healthy and psychiatric patients. ML approaches can quickly process large volumes of data to reveal patterns that may be missed by humans. This study investigated the accuracy of ML methods at classifying the brain's electrical activity to cognitive events, i.e., event-related brain potentials (ERPs). ERPs are extracted from the ongoing EEG and represent electrical potentials in response to specific events. ERPs were evoked during a visual Go/NoGo task. The Go/NoGo task requires a button press on Go trials and response withholding on NoGo trials. NoGo trials elicit neural activity associated with inhibitory control processes. We compared the accuracy of six ML algorithms at classifying the ERPs associated with each trial type. The raw electrical signals were fed to all ML algorithms to build predictive models. The same raw data were then truncated in length and fitted to multiple dynamic state space models of order nx using a continuous-time subspace-based system identification algorithm. The 4nx numerator and denominator parameters of the transfer function of the state space model were then used as substitutes for the data. Dimensionality reduction simplifies classification, reduces noise, and may ultimately improve the predictive power of ML models. Our findings revealed that all ML methods correctly classified the electrical signal associated with each trial type with a high degree of accuracy, and accuracy remained high after parameterization was applied. We discuss the models and the usefulness of the parameterization.

Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

Fast and Stable Responses during Decision Making Require Strong Inhibitory Processes in Soccer Players.

Quick decision making is a vital factor for a successful pass in soccer games. Many previous studies of decision making in soccer focused on motor execution, but inhibitory processing has remained unclear. This study aimed to clarify the differences in motor execution and inhibitory among Japanese collegiate soccer players with different skill levels. We evaluated the behavioral data and event-related potentials in the high-skilled, low-skilled, and novice groups during the Go/No-go and pass choice reaction tasks. The reaction time (RT) was significantly shorter in the high group than in the novice group, and RT variability was small in the high group. The amplitude of the N2 component was significantly larger in the high group than in the low and novice groups, and the latency of the P3 component was significantly shorter in the high and low groups than in the novice group during the pass choice reaction task. The subtracted No-go N2 amplitude was also significantly larger in the high and low groups than in the novice group, and correlations existed between the RT, RT variability, and the subtracted No-go N2 amplitude during these tasks. These data indicate that soccer players' behavioral responses and inhibition processing decision-making activities are associated with skill levels.

Insights into anaerobic digestion of microalgal biomass for enhanced energy recovery

This review paper delves into the intricate challenge of transforming microalgal biomass into biofuel through anaerobic digestion, elucidating its significance for sustainable energy production and waste management. Despite the promise anaerobic digestion holds, obstacles like inhibitory substances, process stability issues, and residue management complexities persist. Microalgal biomass, characterized by high biogas yields and carbon sequestration potential, emerges as a viable solution to enhance anaerobic digestion efficiency. Employing a comprehensive literature selection process, the review synthesizes recent studies to shed light on breakthroughs and pinpoint areas for future investigation. Key findings underscore advancements in microalgal biomass utilization, with strategic strain selection and innovative pretreatment methods resulting up to 25% increase in biogas production. Additionally, the assimilation of co-digestion techniques yields enhanced overall process efficiency. Microalgal biomass demonstrates remarkable carbon sequestration capabilities, sequestering up to 60% of CO2 during the anaerobic digestion process. Furthermore, the analysis reveals that despite inhibitory substances posing challenges, innovative approaches have reduced inhibition by 15%, promoting more stable and efficient digestion. Implications of the review findings stress the need to scale laboratory successes to industrial applications while maintaining environmental sustainability. Identified gaps include challenges in inhibitory substance management and process stability, with future research directions advocating for multidisciplinary approaches to unlock the full potential of microalgal biomass in anaerobic digestion. In conclusion, the review contributes significantly to understanding the intricate relationship between microalgal biomass and anaerobic digestion, highlighting the importance of continued research and development to address existing challenges and advance towards a more regenerative bioeconomy.

Distinct neuronal circuits mediate cortical hyperexcitability in amyotrophic lateral sclerosis.

Cortical hyperexcitability is an important pathophysiological mechanism in amyotrophic lateral sclerosis (ALS), reflecting a complex interaction of inhibitory and facilitatory interneuronal processes that evolves in the degenerating brain. The advances in physiological techniques have made it possible to interrogate progressive changes in the motor cortex. Specifically, the direction of transcranial magnetic stimulation (TMS) stimulus within the primary motor cortex can be utilized to influence descending corticospinal volleys and to thereby provide information about distinct interneuronal circuits. Cortical motor function and cognition was assessed in 29 ALS patients with results compared to healthy volunteers. Cortical dysfunction was assessed using threshold-tracking TMS to explore alterations in short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), the index of excitation and stimulus response curves using a figure-of-eight coil with the coil oriented relative to the primary motor cortex in a posterior-anterior, lateral-medial and anterior-posterior direction. Mean SICI, between interstimulus interval of 1-7 ms, was significantly reduced in ALS patients compared to healthy controls when assessed with the coil oriented in posterior-anterior (P = 0.044) and lateral-medial (P = 0.005) but not the anterior-posterior (P = 0.08) directions. A significant correlation between mean SICI oriented in a posterior-anterior direction and the total Edinburgh Cognitive and Behavioural ALS Screen score (Rho = 0.389, P = 0.037) was evident. In addition, the mean SICF, between interstimulus interval 1-5 ms, was significantly increased in ALS patients when recorded with TMS coil oriented in posterior-anterior (P = 0.035) and lateral-medial (P < 0.001) directions. In contrast, SICF recorded with TMS coil oriented in the anterior-posterior direction was comparable between ALS and controls (P = 0.482). The index of excitation was significantly increased in ALS patients when recorded with the TMS coil oriented in posterior-anterior (P = 0.041) and lateral-medial (P = 0.003) directions. In ALS patients, a significant increase in the stimulus response curve gradient was evident compared to controls when recorded with TMS coil oriented in posterior-anterior (P < 0.001), lateral-medial (P < 0.001) and anterior-posterior (P = 0.002) directions. The present study has established that dysfunction of distinct interneuronal circuits mediates the development of cortical hyperexcitability in ALS. Specifically, complex interplay between inhibitory circuits and facilitatory interneuronal populations, that are preferentially activated by stimulation in posterior-to-anterior or lateral-to-medial directions, promotes cortical hyperexcitability in ALS. Mechanisms that underlie dysfunction of these specific cortical neuronal circuits will enhance understanding of the pathophysiological processes in ALS, with the potential to uncover focussed therapeutic targets.

Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited association of the experimental data with the pathophysiological condition in humans. The use of Fmr1 KO rats offers additional translational validity in this regard. Therefore, we employed a multi-level approach to study the behavioral profile and the glutamatergic and GABAergic neurotransmission status in pathophysiology-associated brain structures of Fmr1 KO rats, including the recordings of evoked and spontaneous field potentials from hippocampal slices, paralleled with next-generation RNA sequencing (RNA-seq). We found that these rats exhibit hyperactivity and cognitive deficits, along with characteristic bidirectional glutamatergic and GABAergic alterations in the prefrontal cortex and the hippocampus. These results are coupled to affected excitability and local inhibitory processes in the hippocampus, along with a specific transcriptional profile, highlighting dysregulated hippocampal network activity in KO rats. Overall, our data provide novel insights concerning the biobehavioral profile of FmR1 KO rats and translationally upscales our understanding on pathophysiology and symptomatology of FXS syndrome.

Improved subjective sleep quality after three months of balance learning in older adults

Improved subjective sleep quality after three months of balance learning in older adults

Repetitive magnetic stimuli over the motor cortex impair long-term consolidation of a balance task by suppressing up-regulation of intracortical inhibition

Introduction&#x0D; Recent findings have demonstrated that low-frequency repetitive magnetic stimulations (rTMS) over the primary motor cortex (M1) impaired short-term consolidation of a balance task, underscoring the causal connection between M1 and the consolidation of balancing skills (Egger et al., 2023). However, the underlying neural mechanisms induced by rTMS and whether these adaptations endure over an extended period, encompassing multiple acquisition sessions, remain insufficiently elucidated (Censor &amp; Cohen, 2011). So far, its is widely acknowledged that GABAergic processes play an important role for consolidation (Sanes &amp; Donoghue, 2000), at the same time, are affected by learning balance skills (Mouthon &amp; Taube, 2019; Taube et al., 2020). Therefore, the present study aimed to investigate the impact of rTMS on GABA-mediated short-interval intracortical inhibition (SICI) and to explore the role of M1 in the long-term consolidation of a balance task (i.e., across multiple acquisition sessions).&#x0D; Methods&#x0D; Thirty-one volunteers underwent six balance acquisition sessions on a rocker-board, each followed by either rTMS or sham rTMS based on group affiliation. During the first and last training session, SICI was measured twice; before the balance acquisition and after the application of rTMS or sham-rTMS to investigate potential short- and long-term adaptations in intracortical inhibition. Adaptations were assessed during the execution of the learned balance task and in a non-learning postural control task (i.e., stable upright stance).&#x0D; Results&#x0D; Regardless of group affiliation, all participants achieved comparable improvements within the balance acquisition sessions. However, consolidation varied between groups. In particular, between the third and the fourth acquisition session, as Tukey corrected post-hoc tests showed a significant decline in performance for the rTMS group (p = 0.006). Both short- (p = 0.014) and long-term (p = 0.038) adaptations in SICI were affected by rTMS: while the sham rTMS group upregulated SICI, rTMS led to reduced levels of inhibition. No neurophysiological effects were observed in the non-learning control task (upright stance).&#x0D; Discussion/Conclusion&#x0D; The interfering effect of rTMS on balance consolidation and on upregulation of SICI indicates that increased intracortical inhibition is an important mechanism to protect and engrave newly acquired motor memory. Importantly, adaptations in SICI were only apparent during the execution of the learned task.&#x0D; References&#x0D; Censor, N., &amp; Cohen, L. G. (2011). Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory. The Journal of Physiology, 589(1), 21-28. https://doi.org/10.1113/jphysiol.2010.198077&#x0D; Egger, S., Wälchli, M., Rüeger, E., &amp; Taube, W. (2023). Short-term balance consolidation relies on the primary motor cortex: A rTMS study. Scientific Reports, 13, Article 5169. https://doi.org/10.1038/s41598-023-32065-x&#x0D; Mouthon, A., &amp; Taube, W. (2019). Intracortical inhibition increases during postural task execution in response to balance training. Neuroscience, 401, 35-42. https://doi.org/10.1016/j.neuroscience.2019.01.007&#x0D; Sanes, J. N., &amp; Donoghue, J. P. (2000). Plasticity and primary motor cortex. Annual Review of Neuroscience, 23, 393-415. https://doi.org/10.1146/annurev.neuro.23.1.393&#x0D; Taube, W., Gollhofer, A., &amp; Lauber, B. (2020). Training-, muscle- and task-specific up- and downregulation of cortical inhibitory processes. The European Journal of Neuroscience, 51(6), 1428-1440. https://doi.org/10.1111/ejn.14538

Neuronal correlates of intensification and acceptance of symptoms during exposure therapy in patients with obsessive-compulsive disorder.

Cognitive behaviour therapy with exposure and response prevention is efficient in treating patients with obsessive-compulsive disorder (OCD). Nevertheless, it would be helpful for many patients to complement the therapeutic treatment with acceptance strategies to further increase the therapeutic benefit. The aim of the present study was to examine neurobiological responses to acceptance and intensification strategies during symptom provocation alongside the psychotherapeutic process. A total of 23 patients diagnosed with OCD (subtype: washing/contamination fear) was instructed to utilise either an acceptance strategy (ACS) or an intensification strategy (INS) to cope with their emotional and cognitive reactions to personalised symptom-triggering and neutral pictures. Fourteen patients participated twice: at the beginning [T1] and at the end [T2] of an inpatient multimodal treatment including cognitive behaviour therapy with response prevention to assess functional variations. For the contrast of T1 and T2, ACS showed increased brain activity in the left inferior frontal gyrus (IFG), left caudate body, and posterior cingulate gyrus (PCC). They also showed decreased activity in the left anterior insula. INS showed decreased activation in right lingual gyrus and right caudate body. At T2, ACS showed increased activation compared to INS in the left cerebrum: IFG, caudate nucleus, middle and superior temporal gyrus, and PCC/cuneus. For the comparison of T1 and T2, the ACS revealed increased brain activity in the left IFG, left caudate body, and right inferior parietal lobe. It showed decreased activity in the left anterior insula. The INS revealed decreased activity in right lingual gyrus and right caudate body.The psychometric questionnaires suggested that patients were able to reduce obsession, compulsion, and depression symptoms. Furthermore, patients rated the ACS as more useful for themselves compared with the INS. The increased left IFG activity using ACS (T1 vs. T2) could be interpreted as a better inhibitory top-down process, while the increased PCC response might be due to a better reappraisal strategy after therapy. ACS seems to mobilise neuronal activations under therapy, especially in the left hemisphere. Both strategies showed reductions in emotional networks as a neuronal correlate of therapy success. Overall, ACS may be more efficient than INS, as rated by the patients and as in accordance with neurobiological findings.

A neural network underlying cognitive strategies related to eating, weight and body image concerns.

Concerns about food intake, weight and body shape can trigger negatively loaded emotions, which may prompt the use of cognitive strategies to regulate these emotional states. A novel fMRI task was developed to assess the neurobehavioral correlates of cognitive strategies related to eating, weight and body image concerns, such as self-criticism, avoidance, rumination, and self-reassurance. Fourteen healthy females were presented audio sentences referring to these conditions and instructed to repeat these internally while engaging their thoughts with the content of food or body images. Participants were asked to report the elicited emotion and rate their performance. All cognitive strategies recruited a network including the inferior and superior frontal gyri, orbitofrontal and anterior cingulate cortex, insula, and dorsal striatum. These brain regions are involved in emotional, reward and inhibitory control processing. Representational similarity analysis revealed distinct patterns of neural responses for each cognitive strategy. Additionally, self-report measures showed that self-criticism was positively associated with superior frontal gyrus (SFG) activation. Self-compassion scores were negatively correlated with activations in the insula and right putamen, while self-reassurance scores were negatively associated with activity in the orbitofrontal cortex. These findings identify a neural network underlying cognitive strategies related to eating, weight and body image concerns, where neurobehavioral correlation patterns depend on the cognitive strategy.

No Evidence of Cross-Orientation Suppression Differences in Migraine with Aura Compared to Healthy Controls.

It has been suggested that there may be an imbalance of excitation and inhibitory processes in the visual areas of the brain in people with migraine aura (MA). One idea is thalamocortical dysrhythmia, characterized by disordered oscillations, and thus disordered communication between the lateral geniculate nucleus and the cortex. Cross-orientation suppression is a visual task thought to rely on inhibitory processing, possibly originating in the lateral geniculate nucleus. We measured both resting-state oscillations and cross-orientation suppression using EEG over occipital areas in people with MA and healthy volunteers. We found evidence of cross-orientation suppression in the SSVEP responses, but no evidence of any group difference. Therefore, inhibitory processes related to cross-orientation suppression do not appear to be impaired in MA.

Extractive fermentation as a strategy to increase the co-production of H2 and carboxylates in dark fermentation

Ion exchange resins were used to remove carboxylates from a dark fermentation batch reactor to enhance hydrogen (H2) and carboxylate production. Three anion exchange resins were tested. The A110 resin (macroporous, primary amine functionalized) was selected as suitable for carboxylates removal due to its total exchange capacity (1.25 ± 0.12 mmol/g) and affinity towards butyrate. The extractive fermentation system included a column packed with the A110 resin which was connected to a batch-stirred tank H2 reactor. This setup achieved 3762.9 ± 229.1 NmL H2/L of total accumulated H2 volume, equivalent to a 15.2 % increase compared with the control experiment (3288.6 ± 279.0 NmL H2/L). Also, the molar yields of acetate (0.81 ± 0.11 mol/mol hexose) and butyrate (1.01 ± 0.21 mol/mol hexose) increased by 62.7 % and 71.3 %, respectively. The extractive fermentation system could dampen the inhibitory processes by product accumulation and possibly favor a change in the metabolism of dark fermentation microbial communities that enhanced the production of butyrate and H2 from lactate and acetate. Future studies might guarantee molecular analysis of the microbial communities in extractive fermentation as well testing different extraction systems.

Tanshinone IIA alleviates bleomycin-induced pulmonary fibrosis by inhibiting Zbtb16

Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased. HE and Masson staining revealed that pathological symptoms of lung histopathology were relieved after Zbtb16 knockdown. Protein expressions of α-SMA, Collagen I and Fibronectin were significantly decreased after Zbtb16 knockdown in vivo and in vitro. Meanwhile, the protein content of TGF-β1 and the phosphorylation of Smad2/3 were inhibited by Zbtb16 knockdown. Conversely, under the treatment of Tan IIA and TGF-β1, overexpression of Zbtb16 improved cell viability, increased the expression of fibrosis-related proteins, and promoted the phosphorylation of Smad 2/3. All above demonstrates that Zbtb16 inhibition ameliorates pulmonary fibrosis and suppresses the TGF-β/Smad pathway. Furthermore, Zbtb16 mediates the inhibitory process of Tan IIA on pulmonary fibrosis. This study provides a novel candidate therapeutic target for pulmonary fibrosis.