Cognitive reserve predicts episodic memory enhancement induced by transcranial direct current stimulation in healthy older adults.

Episodic memory shows the largest degree of age-related decline. Anodal transcranial Direct Current Stimulation (tDCS) can enhance episodic memory in aging but there is also evidence of response variability even when using identical stimulation parameters. To explore which inter-individual factors (i.e. age, education, encoding performance, cognitive reserve, tDCS group and timing of tDCS application) may directly and/or indirectly modulate verbal memory recall, we used data from our previous tDCS studies that showed enhanced episodic memory recall in 80 healthy older adults. In these studies we used the same paradigm and stimulation parameters but tDCS was applied during different memory stages. Memory recall was tested 48 hours and 30 days after encoding. Univariate regression models showed that tDCS group (Anodal vs. Sham) predicted memory recall, indicating higher scores in the Anodal group than in the Sham group. Encoding performance predicted memory recall in both tDCS groups. Multiple regression models revealed that cognitive reserve, measured with a life experience questionnaire, predicted memory recall only for the Anodal group. Higher cognitive reserve was linked to better memory recall. Accounting for individual differences in cognitive reserve at baseline helps to explain tDCS responsiveness. This knowledge may contribute to optimize its use in older adults.

A polyphasic molecular approach to characterize a collection of grapevine endophytic bacteria with bioprotective potential.

AIMS: The work presented here was conducted to characterize the biodiversity of a collection of bacterial isolates, mainly wood endophytes, as part of a research project focused on exploring their bioprotective potential for postharvest biological control of fruits. METHODS AND RESULTS: This work was the basis for the development of a tailored method combining 16S rDNA sequencing and Rep-PCR to differentiate the isolates and identify them to genus level or below. More than one hundred isolates obtained from wood and roots of different grapevine genotypes were cultured on appropriate growth media and then subjected to the specified multistep molecular identification. CONCLUSIONS: We have obtained good dereplication for grapevine-endophytic bacteria, together with reliable genetic identification. Both are essential prerequisites to properly characterize a biome bank and, at the same time, beneficial prerequisites to subsequently perform a correct bioprotection assessment.

Left Prefrontal tDCS during Learning Does Not Enhance Subsequent Verbal Episodic Memory in Young Adults: Results from Two Double-Blind and Sham-Controlled Experiments.

Recent studies suggest that transcranial direct current stimulation (tDCS) applied over the prefrontal cortex (PFaC) may enhance episodic memory ability. As such, there is ongoing interest in the therapeutic potential of this technique in age-related memory decline. At the same time, the findings are not yet conclusive regarding the magnitude of this effect, and assumptions regarding underlying brain mechanisms of stimulation-induced changes in behaviour are yet to be tested in detail. Here, we evaluated the effect of tDCS over left PFC on verbal episodic memory in young adults. Two separate randomized, double-blind, sham-controlled experiments were carried out using (1) incidental learning followed by a recognition test and (2) intentional learning followed by a free recall. In both studies, participants performed a learning task with active or sham tDCS during the encoding period, followed by retrieval tasks on the same day and the next day. The results suggest that, contrary to expectations, active tDCS did not enhance memory performance relative to sham tDCS. Possible reasons behind the lack of enhancement effects are discussed, including the possibility that memory enhancement effects of tDCS may be smaller than first thought. Scientific practices that could improve estimation accuracy in the field are also discussed.

Breeding toward improved ecological plant-microbiome interactions.

Domestication processes, amplified by breeding programs, have allowed the selection of more productive genotypes and more suitable crop lines capable of coping with the changing climate. Notwithstanding these advancements, the impact of plant breeding on the ecology of plant-microbiome interactions has not been adequately considered yet. This includes the possible exploitation of beneficial plant-microbe interactions to develop crops with improved performance and better adaptability to any environmental scenario. Here we discuss the exploitation of customized synthetic microbial communities in agricultural systems to develop more sustainable breeding strategies based on the implementation of multiple interactions between plants and their beneficial associated microorganisms.

tDCS-Induced Memory Reconsolidation Effects: Analysis of Prominent Predicting Factors.

Background: Memory impairment is among one of the greatest cognitive complaints in midlife and in old age. Considering the importance of good memory functioning in everyday life, it is crucial to study interventions that can reduce the natural decline in this cognitive function. Transcranial Magnetic Stimulation (TMS) studies have demonstrated that the lateral prefrontal cortex (PFC) plays a causal role in enhancing episodic memory recall through reconsolidation. Using a similar paradigm with transcranial direct current stimulation (tDCS) over the left lateral PFC, facilitation effects were observed in delayed memory retrieval in older adults with subjective memory complaints (SMCs) and amnestic Mild Cognitive Impairment (aMCI). However, it remains unclear which potential factors (i.e., tDCS group, cognitive reserve, education level, diagnosis and encoding performance) directly and/or indirectly modulate the tDCS-induced memory reconsolidation effects. Methods: We reanalyzed data acquired in our previous tDCS studies with 22 SMC and 18 aMCI participants from the perspective of predicting delayed memory retrieval performance. These studies included a learning session on Day 1, a reactivation by a contextual reminder followed by 15 min of tDCS session on Day 2 (24 h after Day 1), and two retrieval sessions (free recall and recognition) tested on Days 3 and 30 (48 h and 30 Days after Day 1). Results: Univariate models showed that tDCS group (sham vs. active) significantly predicted memory recognition (but not free recall), evidenced by higher scores in the active tDCS group than in sham group, confirming our previous results. Encoding performance and diagnosis (SMC vs. aMCI) significantly predicted memory retrieval, suggesting higher performances in individuals with SMC than in those with aMCI. Regarding cognitive reserve, higher leisure time activity subscores significantly predicted better memory recognition. Finally, multiple models did not show any tDCS group × predictor interaction effects, indicating that the effects of the predictors on retrieval occurred irrespective of tDCS group. Conclusion: Our results shed light on predicting factors of episodic memory retrieval in this reconsolidation paradigm in individuals with SMC and aMCI. The findings suggest that multifactorial interventions program may be most promising to slow cognitive decline and delay the onset of dementia.

Novel sustainable strategies to control Plasmopara viticola in grapevine unveil new insights on priming responses and arthropods ecology.

BACKGROUND: Reduction of fungicide consumption in agriculture is globally recognized as a priority. Government authorities are fostering research to achieve a reduction of risks associated with conventional pesticides and promoting the development of sustainable alternatives. To address these issues, in the present study, alternative protocols for the control of downy mildew infection in grapevine were compared to the standard protocol. In the first protocol, only resistance inducers were used, comprising a single formulation with Acibenzolar S-methyl, laminarin and disodium-phosphonate. The second and third protocols followed the standard protocol but substituted phosphonates with phosphorus pentoxide and Ecklonia maxima extract. RESULTS: The results showed that at veraison downy mildew incidence and severity in all tested protocols were significantly reduced compared to nontreated controls on both canopy and bunches. Expression analysis of key genes involved in plant stress response, indicated that the two protocols for phosphites substitution induced a remodulation of salicylic acid (SA) and jasmonic acid (JA), with positive impact on yields. Analysis of the first protocol revealed that the primed state induced a short delay in bunch ripening, with a shift of carbohydrate metabolism to boost the plant defences, involving an upregulation of defence related-gene, SAR response and a decreased ROS detoxification. Additionally, analysis on the arthropods populations, in parallel with the positive results achieved using alternatives to conventional fungicides, were enriched by those showing the potential of naturally occurring predators of spider mites. CONCLUSION: This study provides practical solutions to reduce the environmental impact of treatments for the control downy mildew in viticulture. © 2022 Society of Chemical Industry.

Cigarette smoking is associated with difficulties in the use of reappraisal for emotion regulation.

BACKGROUND: Negative emotions can promote smoking relapse during a quit attempt. The use of cognitive reappraisal to self-regulate these emotions may therefore aid smoking cessation. Determining whether smokers exhibit difficulties in the use of reappraisal, and which factors are associated with such difficulties, may aid smoking cessations. METHODS: 50 smokers and 50 non-smokers completed an online reappraisal task in which they either reappraised or naturally experienced emotions induced by negatively- and neutrally-valenced images that presented situations in either the 1st-person or 3rd-person perspective. Participants also completed the Difficulties in Emotion Regulation Scale (DERS). RESULTS: Compared to non-smokers, smokers were less successful in using reappraisal to self-regulate emotions elicited by negatively-valenced images (but not neutrally-valenced images). Importantly, this effect was only true for images that were presented in the 1st-person (but not 3rd-person) perspective. Contrary to predictions, there were no group differences in DERS scores. CONCLUSIONS: This study provides the first evidence that smokers experience difficulties in the use of reappraisal, particularly in situations that appear to be happening to themselves. Because the use of this regulation technique may help smokers to quit, improving smokers' abilities to use reappraisal, particularly during negatively-valenced situations that directly influence the smoker, may aid smoking cessation.

The hidden world within plants: metatranscriptomics unveils the complexity of wood microbiomes.

The importance of plants as complex entities influenced by genomes of the associated microorganisms is now seen as a new source of variability for a more sustainable agriculture, also in the light of ongoing climate change. For this reason, we investigated through metatranscriptomics whether the taxa profile and behaviour of microbial communities associated with the wood of 20-year-old grapevine plants are influenced by the health status of the host. We report for the first time a metatranscriptome from a complex tissue in a real environment, highlighting that this approach is able to define the microbial community better than referenced transcriptomic approaches. In parallel, the use of total RNA enabled the identification of bacterial taxa in healthy samples that, once isolated from the original wood tissue, displayed potential biocontrol activities against a wood-degrading fungal taxon. Furthermore, we revealed an unprecedented high number of new viral entities (~120 new viral species among 180 identified) associated with a single and limited environment and with potential impact on the whole holobiont. Taken together, our results suggest a complex multitrophic interaction in which the viral community also plays a crucial role in raising new ecological questions for the exploitation of microbial-assisted sustainable agriculture.

Abiotic Stress and Belowground Microbiome: The Potential of Omics Approaches.

Nowadays, the worldwide agriculture is experiencing a transition process toward more sustainable production, which requires the reduction of chemical inputs and the preservation of microbiomes' richness and biodiversity. Plants are no longer considered as standalone entities, and the future of agriculture should be grounded on the study of plant-associated microorganisms and all their potentiality. Moreover, due to the climate change scenario and the resulting rising incidence of abiotic stresses, an innovative and environmentally friendly technique in agroecosystem management is required to support plants in facing hostile environments. Plant-associated microorganisms have shown a great attitude as a promising tool to improve agriculture sustainability and to deal with harsh environments. Several studies were carried out in recent years looking for some beneficial plant-associated microbes and, on the basis of them, it is evident that Actinomycetes and arbuscular mycorrhizal fungi (AMF) have shown a considerable number of positive effects on plants' fitness and health. Given the potential of these microorganisms and the effects of climate change, this review will be focused on their ability to support the plant during the interaction with abiotic stresses and on multi-omics techniques which can support researchers in unearthing the hidden world of plant-microbiome interactions. These associated microorganisms can increase plants' endurance of abiotic stresses through several mechanisms, such as growth-promoting traits or priming-mediated stress tolerance. Using a multi-omics approach, it will be possible to deepen these mechanisms and the dynamic of belowground microbiomes, gaining fundamental information to exploit them as staunch allies and innovative weapons against crop abiotic enemies threatening crops in the ongoing global climate change context.

Effects of transcranial electrical stimulation on episodic memory in physiological and pathological ageing.

Memory for personally-relevant past events (episodic memory) is critical for activities of daily living. Decline in this type of declarative long-term memory is a common characteristic of healthy ageing, a process accelerated in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Transcranial electrical stimulation (tES) has been used as a strategy to ameliorate episodic memory. Here, we critically review studies investigating whether tES may improve episodic memory in physiological and pathological ageing. Most of the studies suggest that tES over the prefrontal or temporoparietal cortices can have a positive effect on episodic memory, but the transfer to improvement of execution of daily living activities is still unknown. Further work is needed to better understand the mechanisms underlying the effects of stimulation, combine tES with neuroimaging and optimizing the dosing of stimulation. Future studies should also investigate the optimal timing of stimulation and the combination with medications to induce long-lasting beneficial effects in pathological ageing. More open science efforts should be done to improve rigor and reliability of tES in ageing research.

Double-Stranded RNAs (dsRNAs) as a Sustainable Tool against Gray Mold (Botrytis cinerea) in Grapevine: Effectiveness of Different Application Methods in an Open-Air Environment.

Grapevine is one of the most important and globally widespread fruit species, with a high impact on the economy of many countries but with an intense environmental effect. Therefore, new environmentally friendly defense strategies against fungal pathogens are needed for more sustainable agriculture. A novel emerging approach is spray-induced gene silencing (SIGS), which concerns the exogenous application of double-stranded RNA (dsRNA) inducing enhanced plant resistance against fungal pathogens. Here, we tested the ability of SIGS to prevent and counteract infection of Botrytis cinerea, one of the most economically impacting pathogens of grapevine. In particular, we tested three independent approaches for dsRNA delivery into plants: i) high pressure spraying of leaves; ii) petiole adsorption of dsRNAs; iii) postharvest spraying of bunches. We demonstrated that independently from the method of application, SIGS can reduce virulence of the fungus. Moreover, we also observed three different levels of efficacy depending on the method of application. Thus, the present data provide crucial information on the possibility to exploit SIGS as an alternative sustainable and ecofriendly strategy for grapevine pre- and postharvest protection.

Transcranial direct current stimulation facilitates response inhibition through dynamic modulation of the fronto-basal ganglia network.

BACKGROUND: Response inhibition refers to the ability to stop an on-going action quickly when it is no longer appropriate. Previous studies showed that transcranial direct current stimulation (tDCS) applied with the anode over the right inferior frontal cortex (rIFC), a critical node of the fronto-basal ganglia inhibitory network, improved response inhibition. However, the tDCS effects on brain activity and network connectivity underlying this behavioral improvement are not known. OBJECTIVE: This study aimed to address the effects of tDCS applied with the anode over the rIFC on brain activity and network functional connectivity underlying the behavioral change in response inhibition. METHODS: Thirty participants performed a stop-signal task in a typical laboratory setting as a baseline during the first study visit (i.e., Session 1). In the second visit (at least 24 h after Session 1), all participants underwent resting-state functional magnetic resonance imaging (rsfMRI) scans before and after 1.5 mA tDCS (Anodal or Sham). Immediately following the post-tDCS rsfMRI, participants performed the same stop-signal task as in Session 1 during an event-related fMRI (efMRI) scan in a 3T scanner. Changes in task performance, i.e., the stop-signal response time (SSRT), a measure of response inhibition efficiency, was determined relative to the participants' own baseline performance in Session 1. RESULTS: Consistent with previous findings, Anodal tDCS facilitated the SSRT. efMRI results showed that Anodal tDCS strengthened the functional connectivity between right pre-supplementary motor area (rPreSMA) and subthalamic nuclei during Stop responses. rsfMRI revealed changes in intrinsic connectivity between rIFC and caudate, and between rIFC, rPreSMA, right inferior parietal cortex (rIPC), and right dorsolateral prefrontal cortex (rDLPFC) after Anodal tDCS. In addition, corresponding to the regions of rsfMRI connectivity change, the efMRI BOLD signal in the rDLPFC and rIPC during Go responses accounted for 74% of the variance in SSRT after anodal tDCS, indicating an effect of tDCS on the Go-Stop process. CONCLUSION: These results indicate that tDCS with the anode over the rIFC facilitates response inhibition by modulating neural activity and functional connectivity in the fronto-basal ganglia as well as rDLPFC and rIPC as an integral part of the response inhibition network.

Effects of Transcranial Direct Current Stimulation on Episodic Memory in Amnestic Mild Cognitive Impairment: A Pilot Study.

OBJECTIVES: Episodic memory is impaired in amnestic mild cognitive impairment (aMCI), which is posited as a potential prodromal form of Alzheimer's disease. Reactivated existing memories become sensitive to modification during reconsolidation. There is evidence that the lateral prefrontal cortex (PFC) plays causal role in episodic memory reconsolidation. Transcranial direct current stimulation (tDCS) applied to the PFC after a contextual reminder enhanced episodic memory performance up to 1 month, conceivably through reconsolidation, in older adults with subjective memory complaints, a condition that may represent a "pre-mild cognitive impairment" stage. The aim of this pilot study was to test the effect of PFC-tDCS (anode over left lateral PFC, cathode over right supraorbital area) after a contextual reminder on episodic memory in older adults with aMCI. METHOD: Older adults with aMCI learned a list of words. Twenty-four hours later, tDCS (Active or Sham) was applied after a contextual reminder. Memory retrieval (free recall and recognition) was tested 48 hrs and 1 month after the learning session. RESULTS: Active tDCS enhanced recognition memory relative to Sham stimulation. DISCUSSION: Modulating reconsolidation with PFC-tDCS might be a novel intervention to enhance episodic memories in aMCI.

Effects of transcranial direct current stimulation over the posterior parietal cortex on episodic memory reconsolidation.

Consolidated memories may return to labile/unstable states after their reactivation, thus requiring a restabilization process that is known as reconsolidation. During this time-limited reconsolidation window, reactivated existing memories can be strengthened, weakened or updated with new information. Previous studies have shown that non-invasive stimulation of the lateral prefrontal cortex after memory reactivation strengthened existing verbal episodic memories through reconsolidation, an effect documented by enhanced delayed memory recall (24 h post-reactivation). However, it remains unknown whether the left posterior parietal cortex (PPC), a region involved during reactivation of existing episodic memories, contributes to reconsolidation. To address this question, in this double-blind experiment healthy participants (n = 27) received transcranial direct current stimulation (tDCS) with the anode over the left PPC after reactivation of previously learned verbal episodic memories. Memory recall was tested 24 h later. To rule out unspecific effects of memory reactivation or tDCS alone, we included two control groups: one that receives tDCS with the anode over the left PPC without reactivation (n = 27) and another one that receives tDCS with the anode over a control site (primary visual cortex) after reactivation (n = 27). We hypothesized that tDCS with the anode over the left PPC after memory reactivation would enhance delayed recall through reconsolidation relative to the two control groups. No significant between groups differences in the mean number of words recalled on day 3 occurred, suggesting no beneficial effect of tDCS over the left PPC. Alternative explanations were discussed, including efficacy of tDCS, different stimulation parameters, electrode montage, and stimulation site within the PPC.

Transcranial direct current stimulation applied after encoding facilitates episodic memory consolidation in older adults.

Episodic memory shows the largest degree of age-related memory decline. There is evidence that consolidation, the process that stabilizes memories after encoding, is reduced in older adults. Previous studies have shown that transcranial direct current stimulation (tDCS) applied during intentional encoding or immediately after a contextual reminder enhanced delayed episodic memory performance, suggesting a potential interaction between tDCS and consolidation or reconsolidation processes. The present randomized, double-blind, sham-controlled study addressed the question whether tDCS applied immediately after verbal encoding enhances episodic memory recall through consolidation in healthy older adults. Twenty-eight participants received tDCS (Active or Sham) over the prefrontal cortex (anode over the left dorsolateral prefrontal cortex and cathode over the contralateral supraorbital region), a brain region contributing to episodic memory function. Verbal recall was tested two days and one month later. The results showed that recall performance at one month was enhanced in the Active tDCS group relative to the Sham group. These findings suggest that tDCS applied off-line immediately after encoding over the prefrontal cortex interacts with the processes promoting consolidation of episodic memories in healthy older adults. Targeting consolidation by means of tDCS might be a novel strategy for reducing episodic memory decline.

Transcutaneous spinal direct current stimulation improves locomotor learning in healthy humans.

BACKGROUND: Ambulation is an essential aspect of daily living and is often impaired after brain and spinal cord injuries. Despite the implementation of standard neurorehabilitative care, locomotor recovery is often incomplete. OBJECTIVE: In this randomized, sham-controlled, double-blind, parallel design study, we aimed to determine if anodal transcutaneous spinal direct current stimulation (anodal tsDCS) could improve training effects on locomotion compared to sham (sham tsDCS) in healthy subjects. METHODS: 43 participants underwent a single backwards locomotion training (BLT) session on a reverse treadmill with concurrent anodal (n = 22) or sham (n = 21) tsDCS. The primary outcome measure was speed gain measured 24 h post-training. We hypothesized that anodal tsDCS + BLT would improve training effects on backward locomotor speed compared to sham tsDCS + BLT. A subset of participants (n = 31) returned for two additional training days of either anodal (n = 16) or sham (n = 15) tsDCS and underwent (n = 29) H-reflex testing immediately before, immediately after, and 30 min post-training over three consecutive days. RESULTS: A single session of anodal tsDCS + BLT elicited greater speed gain at 24 h relative to sham tsDCS + BLT (p = 0.008, two-sample t-test, adjusted for one interim analysis after the initial 12 subjects). Anodal tsDCS + BLT resulted in higher retention of the acquired skill at day 30 relative to sham tsDCS + BLT (p = 0.002) in the absence of significant group differences in online or offline learning over the three training days (p = 0.467 and p = 0.131). BLT resulted in transient down-regulation of H-reflex amplitude (Hmax/Mmax) in both test groups (p < 0.0001). However, the concurrent application of anodal-tsDCS with BLT elicited a longer lasting effect than sham-tsDCS + BLT (p = 0.050). CONCLUSION: tsDCS improved locomotor skill acquisition and retention in healthy subjects and prolonged the physiological exercise-mediated downregulation of excitability of the alpha motoneuron pool. These results suggest that this strategy is worth exploring in neurorehabilitation of locomotor function.

A Preliminary Comparison of Motor Learning Across Different Non-invasive Brain Stimulation Paradigms Shows No Consistent Modulations.

Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1) on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task) and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI). We compared anodal transcranial direct current stimulation (tDCS), paired associative stimulation (PAS25), and intermittent theta burst stimulation (iTBS), along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants (n = 28) were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online), 1 day after training (consolidation), and 1 week after training (retention). We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning.

Strengthening of Existing Episodic Memories Through Non-invasive Stimulation of Prefrontal Cortex in Older Adults with Subjective Memory Complaints.

Episodic memory is critical to daily life functioning. This type of declarative memory declines with age and is the earliest cognitive function to be compromised in Alzheimer's disease (AD). Subjective memory complaints are commonly reported by older adults and have been considered a risk factor for developing AD. The possibilities for prevention of memory disorders in older adults have increased substantially in recent years. Previous studies have shown that anodal transcranial Direct Current Stimulation (tDCS) applied over the left lateral prefrontal cortex (PFC) after a contextual reminder strengthened existing verbal episodic memories, conceivably through reconsolidation, in elderly people. In this study, we hypothesized that anodal tDCS applied over the left lateral PFC after a contextual reminder would improve delayed memory retrieval relative to placebo (sham) stimulation in elderly individuals with SMC. Twenty-two subjects learned a list of words. Twenty-four hour later, tDCS (anodal or placebo) was applied over the left lateral PFC after a contextual reminder. Memory retrieval was tested 48h and 30 days later. These findings showed that anodal tDCS over the left lateral PFC strengthened existing episodic memories, a behavioral effect documented by improved recognition up to 30 days, relative to placebo stimulation. This study suggests that tDCS after a contextual reminder can induce long-lasting beneficial effects by facilitating the consolidation processes and opens up the possibility to design specific non-invasive interventions aimed at preventing memory decline in this at-risk population.

Lasting deficit in inhibitory control with mild traumatic brain injury.

Being able to focus on a complex task and inhibit unwanted actions or interfering information (i.e., inhibitory control) are essential human cognitive abilities. However, it remains unknown the extent to which mild traumatic brain injury (mTBI) may impact these critical functions. In this study, seventeen patients and age-matched healthy controls (HC) performed a variant of the Stroop task and attention-demanding 4-choice response tasks (4CRT) with identical stimuli but two contexts: one required only routine responses and the other with occasional response conflicts. The results showed that mTBI patients performed equally well as the HC when the 4CRT required only routine responses. However, when the task conditions included occasional response conflicts, mTBI patients with even a single concussion showed a significant slow-down in all responses and higher error rates relative to the HC. Results from event-related functional magnetic resonance imaging (efMRI) revealed altered neural activity in the mTBI patients in the cerebellum-thalamo-cortical and the fronto-basal-ganglia networks regulating inhibitory control. These results suggest that even without apparent difficulties in performing complex attention-demanding but routine tasks, patients with mTBI may experience long-lasting deficits in regulating inhibitory control when situations call for rapid conflict resolutions.