Gender differences in psychological processes have been of great interest in a variety of fields. While the majority of research in this area has focused on specific differences in relation to test performance, this study sought to determine the underlying neurofunctional differences observed during working memory, a pivotal cognitive process shown to be predictive of academic achievement and intelligence. Using the BrainMap database, we performed a meta-analysis and applied activation likelihood estimation to our search set. Our results demonstrate consistent working memory networks across genders, but also provide evidence for gender-specific networks whereby females consistently activate more limbic (e.g., amygdala and hippocampus) and prefrontal structures (e.g., right inferior frontal gyrus), and males activate a distributed network inclusive of more parietal regions. These data provide a framework for future investigation using functional or effective connectivity methods to elucidate the underpinnings of gender differences in neural network recruitment during working memory tasks.

Mild cognitive impairment (MCI) and early Alzheimer’s disease (AD) are characterized by blood–brain barrier (BBB) breakdown leading to abnormal BBB permeability ahead of brain atrophy or dementia. Previous findings in AD mouse models have reported the beneficial effect of extra-virgin olive oil (EVOO) against AD, which improved BBB and memory functions and reduced brain amyloid-β (Aβ) and related pathology. This work aimed to translate these preclinical findings to humans in individuals with MCI. We examined the effect of daily consumption of refined olive oil (ROO) and EVOO for 6 months in MCI subjects on BBB permeability (assessed by contrast-enhanced MRI), and brain function (assessed using functional-MRI) as the primary outcomes. Cognitive function and AD blood biomarkers were also assessed as the secondary outcomes. Twenty-six participants with MCI were randomized with 25 participants completed the study. EVOO significantly improved clinical dementia rating (CDR) and behavioral scores. EVOO also reduced BBB permeability and enhanced functional connectivity. While ROO consumption did not alter BBB permeability or brain connectivity, it improved CDR scores and increased functional brain activation to a memory task in cortical regions involved in perception and cognition. Moreover, EVOO and ROO significantly reduced blood Aβ42/Aβ40 and p-tau/t-tau ratios, suggesting that both altered the processing and clearance of Aβ. In conclusion, EVOO and ROO improved CDR and behavioral scores; only EVOO enhanced brain connectivity and reduced BBB permeability, suggesting EVOO biophenols contributed to such an effect. This proof-of-concept study justifies further clinical trials to assess olive oil’s protective effects against AD and its potential role in preventing MCI conversion to AD and related dementias.

Bioactive plant-based compounds have shown promise as protective agents across multiple domains including improvements in neurological and psychological measures. Methodological challenges have limited our understanding of the neurophysiological changes associated with polyphenol-rich supplements such as whole coffee cherry extract (WCCE). In the current study, we (1) compared 100 mg of WCCE to a placebo using an acute, randomized, double-blind, within-subject, cross-over design, and we (2) conducted a phytochemical analysis of WCCE. The primary objective of the study was to determine the neurophysiological and behavioral changes that resulted from the acute administration of WCCE. We hypothesized that WCCE would increase brain-derived neurotrophic factor (BDNF) and glutamate levels while also increasing neurofunctional measures in cognitive brain regions. Furthermore, we expected there to be increased behavioral performance associated with WCCE, as measured by reaction time and accuracy. Participants underwent four neuroimaging scans (pre- and post-WCCE and placebo) to assess neurofunctional/metabolic outcomes using functional magnetic resonance imaging and magnetic resonance spectroscopy. The results suggest that polyphenol-rich WCCE is associated with decreased reaction time and may protect against cognitive errors on tasks of working memory and response inhibition. Behavioral findings were concomitant with neurofunctional changes in structures involved in decision-making and attention. Specifically, we found increased functional connectivity between the anterior cingulate and regions involved in sensory and decision-making networks. Additionally, we observed increased BDNF and an increased glutamate/gamma-aminobutyric acid (GABA) ratio following WCCE administration. These results suggest that WCCE is associated with acute neurophysiological changes supportive of faster reaction times and increased, sustained attention.

Substantial effort has been directed toward understanding complex associations between cannabis and pain, yet we have many, and sometimes conflicting, theories regarding cannabinoid analgesia. Although acute effects of cannabis on pain have received considerable attention, long-term effects remain understudied. Two studies were conducted. First, during the laboratory study, we measured pain ratings and pain tolerance in response to pressure-based mechanical pain among recreational cannabis users (n = 33) and cannabis non-users (n = 31). Linear mixed-effects models demonstrated that: (i) pain ratings (0-100 VAS) were not different between groups (B = 1.57 (95% CI: -10.84, 13.99), p = 0.801), (ii) pain tolerance (0-240 mmHg) was associated with anxiety (B = -5.33 (95% CI: -8.29, -2.33) p < 0.001), and (iii) users had lower tolerance after controlling for anxiety (B = -24.62 (95% CI: -49.32, 0.43), p = 0.046). Second, during the internet study, we retested these associations using more ecologically relevant endpoints in a separate sample. Participants completed the Graded Chronic Pain Scale, and pain-related daily interference was compared between users (n = 185) and non-users (n = 586). Linear models showed that interference (0-10 points) was associated with anxiety (B = 0.07 (95% CI: 0.06, 0.09), p < 0.001) and users reported greater interference after controlling for anxiety (B = 0.27 (95% CI: 0.09, 0.46), p = 0.003). Together, these outcomes suggest that regular cannabis use is associated with differences in pain processing, although additional studies are needed to provide enhanced mechanistic understanding.