Quantifying network behavior in the rat prefrontal cortex: a reproducibility crisis

Decision Making in Recurrent Neuronal Circuits

Resting state vagally mediated heart rate variability (vmHRV) is related to difficulties in emotion regulation (ER). The prefrontal cortex (PFC) provides inhibitory control over the amygdala during ER. Previous studies linked vmHRV with activity in the ventromedial PFC (vmPFC) during implicit ER. To date no study examined the relation between vmHRV and brain activity during explicit ER. vmHRV was measured during a 7 min baseline at T1 2–5 days preceding T2. At T2 n = 24 participants (50% female, Mage = 24.6 years) viewed neutral or emotional pictures of pleasant or unpleasant valence and were instructed to intensify or to reduce their present emotion using two ER strategies (reappraisal and response modulation) or to passively view the picture. Participants rated the valence of their emotional state from pleasant to unpleasant after ER. Whole-brain fMRI data were collected using a 1.5-T-scanner. We observed an association between resting state vmHRV and brain activation in the PFC and the amygdala during ER of unpleasant emotions. Groups based on vmHRV showed significant differences in the modulation of amygdala activity as a function of ER strategy. In participants with high vmHRV amygdala activity was modulated only when using reappraisal and for low vmHRV participants only when using response modulation. Similar, dorsomedial PFC activity in high vmHRV participants was increased when using reappraisal and in low vmHRV participants when using response modulation to regulate unpleasant emotions. These results suggest that individuals with low vmHRV might have difficulties in recruiting prefrontal brain areas necessary for the modulation of amygdala activity during explicit ER.

Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters. Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance. The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters. Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

Distributed Coding of Actual and Hypothetical Outcomes in the Orbital and Dorsolateral Prefrontal Cortex

NMDA Receptors Control Cue-Outcome Selectivity and Plasticity of Orbitofrontal Firing Patterns during Associative Stimulus-Reward Learning

Delay period activity in the dorso-lateral prefrontal cortex (dlPFC) has been linked to the maintenance and control of sensory information in working memory. The stability of working memory related signals found in such delay period activity is believed to support robust memory-guided behavior during sensory perturbations, such as distractors. Here, we directly probed dlPFC’s delay period activity with a diverse set of activity perturbations, and measured their consequences on neural activity and behavior. We applied patterned microstimulation to the dlPFC of monkeys implanted with multi-electrode arrays by electrically stimulating different electrodes in the array while the monkeys performed a memory-guided saccade task. We found that the microstimulation perturbations affected spatial working memory-related signals in individual dlPFC neurons. However, task performance remained largely unaffected. These apparently contradictory observations could be understood by examining different dimensions of the dlPFC population activity. In dimensions where working memory related signals naturally evolved over time, microstimulation impacted neural activity. In contrast, in dimensions containing working memory related signals that were stable over time, microstimulation minimally impacted neural activity. This dissociation explained how working memory-related information could be stably maintained in dlPFC despite the activity changes induced by microstimulation. Thus, working memory processes are robust to a variety of activity perturbations in the dlPFC.

ObjectiveWe aimed to study the neural processing of emotion-denoting words based on a circumplex model of affect, which posits that all emotions can be described as a linear combination of two neurophysiological dimensions, valence and arousal. Based on the circumplex model, we predicted a linear relationship between neural activity and incremental changes in these two affective dimensions.MethodsUsing functional magnetic resonance imaging, we assessed in 10 subjects the correlations of BOLD (blood oxygen level dependent) signal with ratings of valence and arousal during the presentation of emotion-denoting words.ResultsValence ratings correlated positively with neural activity in the left insular cortex and inversely with neural activity in the right dorsolateral prefrontal and precuneus cortices. The absolute value of valence ratings (reflecting the positive and negative extremes of valence) correlated positively with neural activity in the left dorsolateral and medial pre-frontal cortex (PFC), dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal PFC, and inversely with neural activity in the left medial temporal cortex and right amygdala. Arousal ratings and neural activity correlated positively in the left parahippocampus and dorsal anterior cingulate cortex, and inversely in the left dorsolateral PFC and dorsal cerebellum.ConclusionWe found evidence for two neural networks subserving the affective dimensions of valence and arousal. These findings clarify inconsistencies from prior imaging studies of affect by suggesting that two underlying neurophysiological systems, valence and arousal, may subserve the processing of affective stimuli, consistent with the circumplex model of affect.

Chronic antidepressant-like effect of EMD386088, a partial 5-HT6 receptor agonist, in olfactory bulbectomy model may be connected with BDNF and/or CREB signalling pathway.

During adolescence, risk-taking emerges as an important behaviour. One prominent theory proposes that this increased risk-taking results from a dissociation in the maturational timing of the brain regions involved in reward processing and cognitive control. It is hypothesised that the regions involved in reward processing, particularly the limbic system, mature relatively early in adolescence, in tandem with pubertal maturation. In contrast, the cognitive control regions of the brain, found principally within the prefrontal cortex, are proposed to undergo protracted development throughout adolescence. The goal of this functional Magnetic Resonance Imaging (fMRI) study was to explore how developmental changes in brain function when performing a risk-taking task were related to puberty, independently of chronological age. Fifty male participants aged 12–14 years underwent fMRI scanning whilst performing a risk-taking task (the BART task). Indicators of pubertal development were collected, including self-reported pubertal status using Tanner stage diagrams and salivary hormone levels for testosterone, oestradiol and dehydroepiandrosterone (DHEA). Participants were grouped by pubertal status into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n = 23) and late-post puberty (≥Tanner Stage 4 in either pubic hair or gonadal development; n = 26). General linear modelling was used to investigate whether there were differences in neural activity within the reward processing and cognitive control brain networks during the risk-taking task with pubertal development, as measured by Tanner stage puberty groups and hormonal levels. Oestradiol levels were positively correlated with neural activity in the medial prefrontal cortex and orbitofrontal cortex when deciding not to make a risky choice. Testosterone levels and puberty grouping (early-mid vs. late-post) were correlated with prefrontal cortex activation during the processing of outcomes of a risky decision. This study highlights the complexity of the decision-making process, and the extensive network of brain regions involved. It suggests that various aspects of the process of deciding to make a risky decision are related to distinct elements of pubertal development.

Baclofen ameliorates spatial working memory impairments induced by chronic cerebral hypoperfusion via up-regulation of HCN2 expression in the PFC in rats

BackgroundPrevious epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanisms in the brain may have masked pesticide-related associations in studies that relied purely on neuropsychological measures. MethodsWe conducted a functional neuroimaging study in 48 farmworkers from Zarcero County, Costa Rica, in 2016. We measured concentrations of 13 insecticide, fungicide, or herbicide metabolites or parent compounds in urine samples collected during two study visits (approximately 3–5 weeks apart). We assessed cortical brain activation in the prefrontal cortex during tasks of working memory, attention, and cognitive flexibility using functional near-infrared spectroscopy (fNIRS). We estimated associations of pesticide exposure with cortical brain activation using multivariable linear regression models adjusted for age and education level. ResultsWe found that higher concentrations of insecticide metabolites were associated with reduced activation in the prefrontal cortex during a working memory task. For example, 3,5,6-trichloro-2-pyridinol (TCPy; a metabolite of the organophosphate chlorpyrifos) was associated with reduced activation in the left dorsolateral prefrontal cortex (β = −2.3; 95% CI: −3.9, −0.7 per two-fold increase in TCPy). Similarly, 3-phenoxybenzoic acid (3-PBA; a metabolite of pyrethroid insecticides) was associated with bilateral reduced activation in the dorsolateral prefrontal cortices (β = −3.1; 95% CI: −5.0, −1.2 and −2.3; 95% CI: −4.5, −0.2 per two-fold increase in 3-PBA for left and right cortices, respectively). These associations were similar, though weaker, for the attention and cognitive flexibility tasks. We observed null associations of fungicide and herbicide biomarker concentrations with cortical brain activation during the three tasks that were administered. ConclusionOur findings suggest that organophosphate and pyrethroid insecticides may impact cortical brain activation in the prefrontal cortex – neural dynamics that could potentially underlie previously reported associations with cognitive and behavioral function. Furthermore, our study demonstrates the feasibility and utility of fNIRS in epidemiological field studies.

Neuropsychological tests that require shifting an attentional set, such as the Wisconsin Card Sorting Test, are sensitive to frontal lobe damage. Although little information is available for humans, an animal experiment suggested that different regions of the prefrontal cortex may contribute to set shifting behavior at different levels of processing. Behavioral studies also suggest that set shifting trials are more time consuming than non-set shifting trials (i.e. switch cost) and that this may be underpinned by differences at the neural level. We determined whether there were differential neural responses associated with two different levels of shifting behavior, that of reversal of stimulus-response associations within a perceptual dimension or that of shifting an attentional set between different perceptual dimensions. Neural activity in the antero-dorsal prefrontal cortex increased only in attentional set shifting, in which switch costs were significant. Activity in the postero-ventral prefrontal cortex increased not only in set shifting but also in reversing stimulus-response associations, in which switch costs were absent. We conclude that these distinct regions in the human prefrontal cortex provide different levels of attention control in response selection. Thus, the antero-dorsal prefrontal cortex may be critical for higher order control of attention, i.e. attentional set shifting, whereas the postero-ventral area may be related to a lower level of shift, i.e. reorganizing stimulus-response associations.

Homovanillic acid in caudate and pre-frontal cortex following neuroleptics

Negative socio-emotional resonance in schizophrenia: a functional magnetic resonance imaging hypothesis

Reports an error in "Intraindividual variability in neural activity in the prefrontal cortex during active walking in older adults" by Roee Holtzer, Daliah Ross and Meltem Izzetoglu (Psychology and Aging, 2020[Dec], Vol 35[8], 1201-1214). In the article, the following acknowledgment of Dr. Jennifer Yuan was missing from the author note: "The authors would like to acknowledge and thank Dr. Jennifer Yuan for her previous doctoral work that relates to the subject matter of this article." The online version of this article has been corrected. (The following abstract of the original article appeared in record 2020-85077-001.) Intraindividual variability in gait and cognitive performance is distinct from central-tendency measures and associated with clinical outcomes in aging. Knowledge concerning intraindividual variability in neural activity, however, has been relatively scarce, and no research to date has reported on such variability during active walking. The current study addressed this major gap in knowledge. Participants were community-residing older adults (n = 394; mean age = 76.29 ± 6.65 years; %female = 55). Functional near-infrared spectroscopy (fNIRS) was used to measure oxygenated hemoglobin (HbO2) in the prefrontal cortex under three experimental conditions: single-task-walk, single-task-alpha (cognitive task), and dual-task-walk, which required the participants to perform the two single tasks simultaneously. Intraindividual variability in neural activity was operationalized using the standard deviation of fNIRS-derived HbO2 observations assessed during a 30-s interval in each experimental condition. The increase in intraindividual variability in neural activity in the dual-task-walk condition compared to both single-task conditions was associated with the presence of cognitive impairments and being a male. Furthermore, measures of intraindividual variability in neural activity and gait performance were positively correlated only under the dual-task-walk condition. Intraindividual variability in the neural activity of gait may be a novel marker for age-related impairments in mobility and cognitive function. (PsycInfo Database Record (c) 2021 APA, all rights reserved).