The Involvement of Antioxidants in Cognitive Decline and Neurodegeneration: Mens Sana in Corpore Sano.

With neurodegenerative disorders being on the rise, a great deal of research from multiple fields is being conducted in order to further knowledge and propose novel therapeutic interventions. Among these investigations, research on the role of antioxidants in contrasting cognitive decline is putting forward interesting and promising results. In this review, we aim to collect evidence that focused on the role of a variety of antioxidants and antioxidant-rich foods in improving or stabilizing cognitive functions, memory, and Alzheimer's disease, the most common neurodegenerative disorder. Specifically, we considered evidence collected on humans, either through longitudinal studies or randomized, placebo-controlled ones, which evaluated cognitive performance, memory abilities, or the progression level of neurodegeneration. Overall, despite a great deal of variety between study protocols, cohorts of participants involved, neuropsychological tests used, and investigated antioxidants, there is a solid trend that suggests that the properties of antioxidants may be helpful in hampering cognitive decline in older people. Thus, the help of future research that will further elucidate the role of antioxidants in neuroprotection will lead to the development of novel interventions that will take into account such findings to provide a more global approach to treating neurodegenerative disorders.

Neuropsychobiology of fear-induced bradycardia in humans: progress and pitfalls.

In the last century, the paradigm of fear conditioning has greatly evolved in a variety of scientific fields. The techniques, protocols, and analysis methods now most used have undergone a progressive development, theoretical and technological, improving the quality of scientific productions. Fear-induced bradycardia is among these techniques and represents the temporary deceleration of heart beats in response to negative outcomes. However, it has often been used as a secondary measure to assess defensive responding to threat, along other more popular techniques. In this review, we aim at paving the road for its employment as an additional tool in fear conditioning experiments in humans. After an overview of the studies carried out throughout the last century, we describe more recent evidence up to the most contemporary research insights. Lastly, we provide some guidelines concerning the best practices to adopt in human fear conditioning studies which aim to investigate fear-induced bradycardia.

'Nip it in the bud': Low-frequency rTMS of the prefrontal cortex disrupts threat memory consolidation in humans.

It is still unclear how the human brain consolidates aversive (e.g., traumatic) memories and whether this process can be disrupted. We hypothesized that the dorsolateral prefrontal cortex (dlPFC) is crucially involved in threat memory consolidation. To test this, we used low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) within the memory stabilization time window to disrupt the expression of threat memory. We combined a differential threat-conditioning paradigm with LF-rTMS targeting the dlPFC in the critical condition, and occipital cortex stimulation, delayed dlPFC stimulation, and sham stimulation as control conditions. In the critical condition, defensive reactions to threat were reduced immediately after brain stimulation, and 1 h and 24 h later. In stark contrast, no decrease was observed in the control conditions, thus showing both the anatomical and temporal specificity of our intervention. We provide causal evidence that selectively targeting the dlPFC within the early consolidation period prevents the persistence and return of conditioned responses. Furthermore, memory disruption lasted longer than the inhibitory window created by our TMS protocol, which suggests that we influenced dlPFC neural activity and hampered the underlying, time-dependent consolidation process. These results provide important insights for future clinical applications aimed at interfering with the consolidation of aversive, threat-related memories.

The role of pre-supplementary motor cortex in action control with emotional stimuli: A repetitive transcranial magnetic stimulation study.

Swiftly halting ongoing motor actions is essential to react to unforeseen and potentially perilous circumstances. However, the neural bases subtending the complex interplay between emotions and motor control have been scarcely investigated. Here, we used an emotional stop signal task (SST) to investigate whether specific neural circuits engaged by action suppression are differently modulated by emotional signals with respect to neutral ones. Participants performed an SST before and after the administration of one session of repetitive transcranial magnetic stimulation (rTMS) over the pre-supplementary motor cortex (pre-SMA), the right inferior frontal gyrus (rIFG), and the left primary motor cortex (lM1). Results show that rTMS over the pre-SMA improved the ability to inhibit prepotent action (i.e., better action control) when emotional stimuli were presented. In contrast, action control in a neutral context was fostered by rTMS over the rIFG. No changes were observed after lM1 stimulation. Intriguingly, individuals with higher impulsivity traits exhibited enhanced motor control when facing neutral stimuli following rIFG stimulation. These results further our understanding of the interplay between emotions and motor functions, shedding light on the selective modulation of neural pathways underpinning these processes.

Genetic differences associated with dopamine and serotonin release mediate fear-induced bradycardia in the human brain.

Fear-induced bradycardia, a transient heartbeat deceleration following exposure to threat, is a physiological index observable in humans, especially in fear conditioning experiments. While gaining interest in recent years, it is still currently underemployed in neuroscientific research compared to more popular physiological indices. Besides its use in research, it could also constitute a valuable resource in a clinical psychiatry setting, as many disorders are also characterized by altered heart rate responses. However, differences in fear-induced bradycardia may also be subtended by genetic interindividual differences, thus suggesting precaution when recommending its use in the clinical setting. Here, we discussed the first endeavors that aimed at clarifying the genetic underpinnings of heart rate variations, which suggest that individual genetic differences have a role in defining the characteristics of heart rate responses. Given this, translating heart rate measurements in the clinical setting must be implemented with caution. Future endeavors in this field will aim at identifying these differences even further, thus allowing for more precise clinical interventions.

Stopping in (e)motion: Reactive action inhibition when facing valence-independent emotional stimuli.

Emotions are able to impact our ability to control our behaviors. However, it is not clear whether emotions play a detrimental or an advantageous effect on action control and whether the valence of the emotional stimuli differently affects such motor abilities. One way to measure reactive inhibitory control is the stop-signal task (SST), which estimates the ability to cancel outright a response to the presentation of a stop signal by means of the stop signal reaction times (SSRT). Impaired as well as facilitated action control has been found when faced with emotional stimuli such as stop signals in SSTs and mixed results were observed for positive versus negative stimuli. Here, we aimed to investigate these unresolved issues more deeply. Action control capabilities were tested in 60 participants by means of a SST, in which the stop signals were represented by a fearful and a happy body posture together with their neutral counterpart. Results showed that both positive and negative body postures enhanced the ability to suppress an ongoing action compared to neutral body postures. These results demonstrate that emotional valence-independent emotional stimuli facilitate action control and suggest that emotional stimuli may trigger increased sensory representation and/or attentional processing that may have promote stop-signal processing and hence improved inhibitory performance.

The Influence of Vicarious Fear-Learning in "Infecting" Reactive Action Inhibition.

Since the dawn of cognitive neuroscience, emotions have been recognized to impact on several executive processes, such as action inhibition. However, the complex interplay between emotional stimuli and action control is not yet fully understood. One way to measure inhibitory control is the stop-signal task (SST), which estimates the ability to cancel outright an action to the presentation of a stop signal by means of the stop-signal reaction times (SSRTs). Impaired as well as facilitated action control has been found when faced with intrinsic emotional stimuli as stop signals in SSTs. Here, we aimed at investigating more deeply the power of negative stimuli to influence our action control, testing the hypothesis that a previously neutral stimulus [i.e., the image of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], which has been conditioned through vicarious fear learning, has the same impact on reactive action inhibition performance as an intrinsically negative stimulus (i.e., a fearful face or body). Action control capabilities were tested in 90 participants by means of a SST, in which the stop signals were represented by different negative stimuli. Results showed that the SARS-CoV-2 image enhanced the ability to suppress an ongoing action similarly to observing fearful facial expressions or fearful body postures. Interestingly, we found that this effect was predicted by impulsivity traits: for example, the less self-control the participants had, the less they showed emotional facilitation for inhibitory performance. These results demonstrated that vicarious fear learning has a critical impact on cognitive abilities, making a neutral image as threatening as phylogenetically innate negative stimuli and able to impact on our behavioral control.