Deficiency in contextual and enhanced responding in cued fear learning may contribute to the development of posttraumatic stress disorder (PTSD). We examined the responses to aversive Pavlovian conditioning with an unpredictable spatial context as conditioned stimulus compared to a predictable context. We hypothesized that the PTSD group would demonstrate less hippocampal and ventromedial prefrontal cortex (vmPFC) activation during acquisition and extinction of unpredictable contexts and an over-reactive amygdala response in the predictable contexts compared to controls.

A novel combined differential cue-context conditioning paradigm was applied using virtual reality with spatial contexts that required configural and cue processing. We assessed 20 patients with PTSD, 21 healthy trauma-exposed (TC) and 22 non-trauma-exposed (HC) participants using functional magnetic resonance imaging, skin conductance responses, and self-report measures.

During fear acquisition, patients with PTSD compared to TC showed lower activity in the hippocampi in the unpredictable and higher activity in the amygdalae in the predictable context. During fear extinction, TC compared to patients and HC showed higher brain activity in the vmPFC in the predictable context. There were no significant differences in self-report or skin conductance responses.

Our results suggest that patients with PTSD differ in brain activation from controls in regions such as the hippocampus, the amygdala, and the vmPFC in the processing of unpredictable and predictable contexts. Deficient encoding of more complex configurations might lead to a preponderance of cue-based predictions in PTSD. Exposure-based treatments need to focus on improving predictability of contextual processing and reducing enhanced cue reactivity.

The world’s population has been exposed to traumatic events and high levels of stress due to the ongoing COVID-19 outbreak. Stress is known currently as a universal experience, but the concept was first defined in 1936 by Hans Selye. It has been shown that stress is associated with impairments in neuroplasticity (e.g. neuronal atrophy and synaptic loss in the hippocampus, prefrontal cortex) and has a crucial role in almost all mental disorders.

In this paper we aim to highlight the recent theoretical and experimental advances in neuroscience regarding stress induced neuroplasticity.

We analyzed scientific literature written in English and published between 2019-2021. We used the electronic portal PubMed-NCBI.

In the last few years, molecular and cellular studies on animal models of stress related and stress-induced psychopathologies revealed alterations in gene expression, micro ARNs expression, as well as in intracellular signaling pathways that mediate the stress induced adaptations. These findings have led to new theories regarding depression and anxiety in the molecular neurobiology field. It has been shown that stress reduces BDNF expression inducing neuronal atrophy in various brain areas. Contrastingly, other studies have demonstrated that chronic antidepressant treatment increases BDNF expression. Furthermore, a crucial role has been assigned to miRNAs in the development of chronic stress-induced depression-like behavior and neuroplasticity.

We hope that this paper will increase interest in the field of stress induced cellular and molecular changes. More research needs to be pursued in order to achieve a deeper understanding of the pathophysiology of stress-induced mental disorders.

No significant relationships.

A better understanding of the genetic, molecular and cellular mechanisms of brain-derived neurotrophic factor (BDNF) and its association with neuroplasticity could play a pivotal role in finding future therapeutic targets for novel drugs in major depressive disorder (MDD). Because there are conflicting results regarding the exact role of BDNF polymorphisms in MDD still, we set out to systematically review the current evidence regarding BDNF-related mutations in MDD.

We conducted a keyword-guided search of the PubMed and Embase databases, using ‘BDNF’ or ‘brain-derived neurotrophic factor’ and ‘major depressive disorder’ and ’single-nucleotide polymorphism’. We included all publications in line with our exclusion and inclusion criteria that focused on BDNF-related mutations in the context of MDD.

Our search yielded 427 records in total. After screening and application of our eligibility criteria, 71 studies were included in final analysis. According to present overall scientific data, there is a possibly major pathophysiological role for BDNF neurotrophic systems to play in MDD. However, on the one hand, the synthesis of evidence makes clear that likely no overall association of BDNF-related mutations with MDD exists. On the other hand, it can be appreciated that solidifying evidence emerged on specific significant sub-conditions and stratifications based on various demographic, clinico-phenotypical and neuromorphological variables.

Further research should elucidate specific BDNF-MDD associations based on demographic, clinico-phenotypical and neuromorphological variables. Furthermore, biomarker approaches, specifically combinatory ones, involving BDNF should be further investigated.

The present study examined the differential effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on neuropsychological functioning in children with traumatic brain injury (TBI) relative to orthopedic injury (OI).

Participants were drawn from a prospective, longitudinal study of children who sustained a TBI (n = 69) or OI (n = 72) between 3 and 7 years of age. Children completed a battery of neuropsychological measures targeting attention, memory, and executive functions at four timepoints spanning the immediate post-acute period to 18 months post-injury. Children also completed a comparable age-appropriate battery of measures approximately 7 years post-injury. Parents rated children’s dysexecutive behaviors at all timepoints.

Longitudinal mixed models revealed a significant allele status × injury group interaction with a medium effect size for verbal fluency. Cross-sectional models at 7 years post-injury revealed non-significant but medium effect sizes for the allele status x injury group interaction for fluid reasoning and immediate and delayed verbal memory. Post hoc stratified analyses revealed a consistent pattern of poorer neuropsychological functioning in Met carriers relative to Val/Val homozygotes in the TBI group, with small effect sizes; the opposite trend or no appreciable effect was observed in the OI group.

The results suggest a differential effect of the BDNF Val66Met polymorphism on verbal fluency, and possibly fluid reasoning and immediate and delayed verbal memory, in children with early TBI relative to OI. The Met allele—associated with reduced activity-dependent secretion of BDNF—may confer risk for poorer neuropsychological functioning in children with TBI.

To identify novel associations between modifiable physical and health variables, Alzheimer’s disease (AD) biomarkers, and cognitive function in a cohort of older adults with Mild Cognitive Impairment (MCI).

Metrics of cardiometabolic risk, stress, inflammation, neurotrophic/growth factors, AD, and cognition were assessed in 154 MCI participants (Mean age = 74.1 years) from the Alzheimer’s Disease Neuroimaging Initiative. Partial Least Squares analysis was employed to examine associations among these physiological variables and cognition.

Latent variable 1 revealed a unique combination of AD biomarkers, neurotrophic/growth factors, education, and stress that were significantly associated with specific domains of cognitive function, including episodic memory, executive function, processing speed, and language, representing 45.2% of the cross-block covariance in the data. Age, body mass index, and metrics tapping basic attention or premorbid IQ were not significant.

Our data-driven analysis highlights the significant relationships between metrics associated with AD pathology, neuroprotection, and neuroplasticity, primarily with tasks tapping episodic memory, executive function, processing speed, and verbal fluency rather than more basic tasks that do not require mental manipulation (basic attention and vocabulary). These data also indicate that biological metrics are more strongly associated with episodic memory, executive function, and processing speed than chronological age in older adults with MCI.

Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Previous research has led to the designation of 3,4-methylenedioxymethamphetamine (MDMA) as a Breakthrough Therapy for treatment of post-traumatic stress disorder (PTSD) when administered as an adjunct to psychotherapy.

Here we report the findings of the first randomized, double-blind, Phase 3 trial assessing the efficacy and safety of 3 sessions with a flexible dose of MDMA or placebo administered under direct observation to participants with severe PTSD (n = 100) as an adjunct to inner-directed psychotherapy.

Change in PTSD symptoms (CAPS-5) and functional impairment (SDS) were assessed by a central, blinded Independent Rater Pool at baseline and following each treatment session. Adverse events (AEs), concomitant medications, suicidal ideation and behavior were tracked throughout the study. Vital signs were measured during experimental sessions. The primary endpoint was 18 weeks post-randomization.

Change in CAPS-5 and SDS, placebo-subtracted Cohen’s d effect size, and a responder analysis will be presented. There were three serious AEs of suicidal ideation or behavior reported. MDMA was well tolerated, with some treatment emergent AEs occurring at greater frequency for the MDMA group during and after experimental sessions.

If MDMA-assisted psychotherapy significantly attenuates PTSD symptomatology and associated functional impairment, these results will form the basis for marketing authorization applications worldwide, including among participants with dissociative subtype of PTSD, depression, history of alcohol and substance use disorders, and adverse childhood experiences.

No significant relationships.

Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation.

To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD).

Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG.

There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling.

This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)

Previous research on art therapy (AT) in cognitive aging has been lacking. AT can potentially engender significant cognitive gains, due to its rigorous cognitive involvement, making it useful to tackle age-related cognitive decline. Along with these cognitive gains, associated neuroplastic changes are hypothesized to arise from AT as well. The current intervention examined the effects of an AT intervention on cognitive outcomes and cortical thickness (CT) among participants with mild cognitive impairment.

Participants were assigned to AT (n = 22) and an active control group (n = 27). In both, weekly 45-min sessions were carried out across 3 months. Cognitive assessments and structural magnetic resonance imaging scans were carried out at baseline and 3-month follow-up. Whole brain analyses on CT were carried out. Cognitive outcomes were analyzed using hierarchical linear models.

Significant gains in immediate memory and working memory span were observed in the AT group, relative to the control group. Significantly increased CT in the AT group, relative to controls, was observed in a right middle frontal gyrus (MFG) cluster. Furthermore, CT changes in this cluster were significantly and positively correlated with changes in immediate memory.

These findings highlighted the role of MFG neuroplasticity in enhancing certain cognitive functions in AT. AT is a neuroplastic intervention capable of engendering significant cognitive gains and associated cortical changes in the context of age-related cognitive decline, even when executed as a low-intensity intervention across 3 months. Given the preliminary nature of these findings, future larger sampled studies are needed.