Volition and “free will”

Philosophers have debated the “free will” for centuries, yet it is only in recent years that voluntary actions have become an object of investigation for cognitive neuroscience. This review begins by attempting a definition of volition (i.e., the mental state associated specifically with voluntary actions) that could be relevant for cognitive neuroscience. We then review the neuropsychology of volition. Alterations in voluntary behaviour in neurological and psychiatric patients first suggested the possibility that specific cognitive processes of volition have specific bases in the brain. These findings counter traditional dogmas that human volition is somehow ineffable, and instead suggest that voluntary actions depend on specific brain circuitry that is accessible to scientific investigation.The second part of the review focuses on the experimental psychology of volition. A number of studies have combined a systematic manipulation of experimental conditions, and recording of brain processes associated with voluntary action. We argue that this combination is most likely to identify the brain processes specifically associated with volition, and we therefore review these studies systematically. For example, several studies link the Readiness Potential of the EEG to preparatory conscious preplanning of actions. Further, a meta-analysis of neuroimaging studies (PET/ fMRI) reveals a distinctive pattern of activations for choosing one among many possible actions - a key element of volition. The medial frontal cortex appears to make a key contribution to both these biomarkers of volition.

Brain Imaging Biomarkers for Chronic Pain

The prevalence of chronic pain has reached epidemic levels. In addition to personal suffering chronic pain is associated with psychiatric and medical co-morbidities, notably substance misuse, and a huge a societal cost amounting to hundreds of billions of dollars annually in medical cost, lost wages, and productivity. Chronic pain does not have a cure or quantitative diagnostic or prognostic tools. In this manuscript we provide evidence that this situation is about to change. We first start by summarizing our current understanding of the role of the brain in the pathogenesis of chronic pain. We particularly focus on the concept of learning in the emergence of chronic pain, and the implication of the limbic brain circuitry and dopaminergic signaling, which underly emotional learning and decision making, in this process. Next, we summarize data from our labs and from other groups on the latest brain imaging findings in different chronic pain conditions focusing on results with significant potential for translation into clinical applications. The gaps in the study of chronic pain and brain imaging are highlighted in throughout the overview. Finally, we conclude by discussing the costs and benefits of using brain biomarkers of chronic pain and compare to other potential markers.

Patterns of Arc mRNA expression in the rat brain following dual recall of fear- and reward-based socially acquired information

The ability to learn new information and behaviors is a vital component of survival in most animal species. This learning can occur via direct experience or through observation of another individual (i.e., social learning). While research focused on understanding the neural mechanisms of direct learning is prevalent, less work has aimed at understanding the brain circuitry mediating the acquisition and recall of socially acquired information. We aimed to further elucidate the mechanisms underlying recall of socially acquired information by having rats sequentially recall a socially transmitted food preference (STFP) and a fear association via fear conditioning by-proxy (FCbP). Brain tissue was processed for mRNA expression of the immediate early gene (IEG) Arc, which reliably expresses in the cell nucleus following transcription before migrating to the cytoplasm over the next 25 minutes. Given this timeframe, we were able to identify whether Arc transcription was triggered by STFP recall, FCbP recall, or following recall of both memories. Surprisingly - and contrary to past research examining expression of other IEGs following STFP or FCbP recall separately - we found no differences in any of the Arc expression measures across a number of prefrontal regions and the vCA3 of the hippocampus between controls, demonstrators, and observers, though we did detect an overall effect of sex in a number of regions. We theorize that these results may indicate that relatively little Arc-dependent neural restructuring is taking place in the prefrontal cortices following recall of a recently socially acquired information or directly acquired fear associations in these areas.

Help or flight: Neural defensive circuits promote helping under threat in humans

Helping of conspecifics under threat has been observed across species. In humans, the dominant view proposes that empathy is the key proximal mechanism driving helping motivation in a threatening context, but little is known about how one s own defensive responses to the threat may guide helping decisions. In this pre-registered study, we manipulated threat imminence to activate the entire defensive brain circuitry, and assess the impact of different defensive responses on risky helping behaviour. Forty-nine participants underwent fMRI scanning while making trial-by-trial decisions about whether or not to help a co-participant avoid aversive shocks at the risk of receiving a shock themselves. Helping decisions were prompted under imminent and distal threat, based on the spatiotemporal distance to the administration of the shock to the co-participant. We found that greater engagement of reactive fear circuits (insula, ACC, PAG) during the threat presentation led to helping decisions, whereas engagement of cognitive fear circuits (hippocampus and vmPFC) preceded decisions not to help. Relying on representational similarity analysis, we identified how the defensive circuitry uniquely represented the threat to oneself, and the distress of the co-participant during the task. Importantly, we found that the strength with which the amygdala represented the threat to oneself, and not the other s distress, predicted decisions to help. Our results demonstrate that defensive neural circuits coordinating fast escape from immediate danger may also facilitate decisions to help others, potentially by engaging neurocognitive systems implicated in caregiving across mammals. Taken together, our findings provide novel insights into the proximal basis of altruistic responding, suggesting that defensive responses may play a more important role in helping than previously understood.

Glia-Driven Brain Circuit Refinement Is Altered by Early-Life Adversity: Behavioral Outcomes

Early-life adversity (ELA), often clinically referred to as “adverse childhood experiences (ACE),” is the exposure to stress-inducing events in childhood that can result in poor health outcomes. ELA negatively affects neurodevelopment in children and adolescents resulting in several behavioral deficits and increasing the risk of developing a myriad of neuropsychiatric disorders later in life. The neurobiological mechanisms by which ELA alters neurodevelopment in childhood have been the focus of numerous reviews. However, a comprehensive review of the mechanisms affecting adolescent neurodevelopment (i.e., synaptic pruning and myelination) is lacking. Synaptic pruning and myelination are glia-driven processes that are imperative for brain circuit refinement during the transition from adolescence to adulthood. Failure to optimize brain circuitry between key brain structures involved in learning and memory, such as the hippocampus and prefrontal cortex, leads to the emergence of maladaptive behaviors including increased anxiety or reduced executive function. As such, we review preclinical and clinical literature to explore the immediate and lasting effects of ELA on brain circuit development and refinement. Finally, we describe a number of therapeutic interventions best-suited to support adolescent neurodevelopment in children with a history of ELA.

How Is the Norepinephrine System Involved in the Antiepileptic Effects of Vagus Nerve Stimulation?

Vagus Nerve Stimulation (VNS) is an adjunctive treatment for patients suffering from inoperable drug-resistant epilepsy. Although a complete understanding of the mediators involved in the antiepileptic effects of VNS and their complex interactions is lacking, VNS is known to trigger the release of neurotransmitters that have seizure-suppressing effects. In particular, norepinephrine (NE) is a neurotransmitter that has been associated with the clinical effects of VNS by preventing seizure development and by inducing long-term plastic changes that could restore a normal function of the brain circuitry. However, the biological requisites to become responder to VNS are still unknown. In this review, we report evidence of the critical involvement of NE in the antiepileptic effects of VNS in rodents and humans. Moreover, we emphasize the hypothesis that the functional integrity of the noradrenergic system could be a determining factor to obtain clinical benefits from the therapy. Finally, encouraging avenues of research involving NE in VNS treatment are discussed. These could lead to the personalization of the stimulation parameters to maximize the antiepileptic effects and potentially improve the response rate to the therapy.

COVID-19 Induced New-onset Psychosis: A Case Report from Oman

Neurobehavioral impairment associated with COVID-19 infection has been recently documented in the literature. COVID-19 infection has also been associated with an increased risk for developing psychiatric symptoms, including rare reports on psychosis. We report a case of a 46-year-old male with no significant medical, family, and psychiatric history admitted to the hospital with COVID-19-related psychosis. Possible contributory factors for his condition are discussed, including the relationship between infections and the brain circuitry, inadvertent iatrogenic effects of pharmaceuticals used to manage COVID-19, as well as diathesis-stress associated with the tribulation of the prevailing pandemic.

Migraine in Multiple Sclerosis Patients Affects Functional Connectivity of the Brain Circuitry Involved in Pain Processing

Migraine is particularly common in patients with multiple sclerosis (MS) and has been linked to the dysfunction of the brain circuitry modulating the peripheral nociceptive stimuli. Using MRI, we explored whether changes in the resting state-functional connectivity (RS-FC) may characterize the occurrence of migraine in patients with MS. The RS-FC characteristics in concerned brain regions were explored in 20 MS patients with migraine (MS+M) during the interictal phase, and compared with 19 MS patients without migraine (MS-M), which served as a control group. Functional differences were correlated to the frequency and severity of previous migraine attacks, and with the resulting impact on daily activities. In MS+M, the loss of periaqueductal gray matter (PAG) positive connectivity with the default mode network and the left posterior cranial pons was associated with an increase of migraine attacks frequency. In contrast, the loss of PAG negative connectivity with sensorimotor and visual network was linked to migraine symptom severity and related daily activities impact. Finally, a PAG negative connection was established with the prefrontal executive control network. Migraine in MS+M patients and its impact on daily activities, underlies RS-FC rearrangements between brain regions involved in pain perception and modulation.