Responses In Prefrontal Cortex Research Articles

Differing functional mechanisms underlie cognitive control deficits in psychotic spectrum disorders.

Functional underpinnings of cognitive control deficits in unbiased samples (i.e., all comers) of patients with psychotic spectrum disorders (PSD) remain actively debated. While many studies suggest hypofrontality in the lateral prefrontal cortex (PFC) and greater deficits during proactive relative to reactive control, few have examined the full hemodynamic response. Patients with PSD (n = 154) and healthy controls (n = 65) performed the AX continuous performance task (AX-CPT) during rapid (460 ms) functional neuroimaging and underwent full clinical characterization. Behavioural results indicated generalized cognitive deficits (slower and less accurate) across proactive and reactive control conditions in patients with PSD relative to healthy controls. We observed a delayed/prolonged neural response in the left dorsolateral PFC, the sensorimotor cortex and the superior parietal lobe during proactive control for patients with PSD. These proactive hemodynamic abnormalities were better explained by negative rather than by positive symptoms or by traditional diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR), with subsequent simulations unequivocally demonstrating how these abnormalities could be erroneously interpreted as hypoactivation. Conversely, true hypoactivity, unassociated with clinical symptoms or DSM-IV-TR diagnoses, was observed within the ventrolateral PFC during reactive control. In spite of guidance for AX-CPT use in neuroimaging studies, one-third of patients with PSD could not perform the task above chance and were more clinically impaired. Current findings question the utility of the AX-CPT for neuroimaging-based appraisal of cognitive control across the full spectrum of patients with PSD. Previously reported lateral PFC "hypoactivity" during proactive control may be more indicative of a delayed/prolonged neural response, important for rehabilitative purposes. Negative symptoms may better explain certain behavioural and hemodynamic abnormalities in patients with PSD relative to DSM-IV-TR diagnoses.

Altered prefrontal cortex responses in older adults with subjective memory complaints and dementia during dual-task gait: An fNIRS study.

People with cognitive impairments show deficits during physical performances such as gait, in particular during cognitively challenging conditions (i.e. dual-task gait [DTG]). However, it is unclear if people at risk of dementia, such as those with subjective memory complaints (SMC), also display gait and central deficits associated with DTG. In this study, we investigated the effects of single- and dual-task gait (STG and DTG), on left prefrontal cortex (PFC) activation in elderly people with subjective memory complaints (SMC) and Dementia. A total of 58 older adults (aged 65-94years; 26 Healthy; 23 SMC; 9 Dementia) were recruited. Gait spatiotemporal characteristics (i.e. stride velocity and length) were assessed using an instrumented walkway during STG and DTG. Single-channel functional near-infrared spectroscopy over the left PFC was used to measure changes in oxyhaemoglobin (O2 Hb) during gait. Stride velocity and length during STG (all p<.05) and DTG (all p<.000) were significantly impaired in people with Dementia compared to Healthy and SMC individuals. No differences were observed between Healthy and SMC. For STG, a greater increase in O2 Hb (p<.05) was observed in those with Dementia compared to the Healthy and SMC, while no differences were observed between Healthy and SMC. A significant increase and decline in O2 Hb was observed during DTG in the SMC and Dementia groups, respectively, compared to Healthy. Our findings indicate an altered pattern of cerebral haemodynamic response of the left PFC in DTG in people with SMC and Dementia, which may suggest that central changes precede functional impairments in people with SMC.

Prefrontal Cortex Response to Threat: Race by Age Variation in 9-10 Year Old Children.

Considerable research has suggested that race and age are two major determinants of brain development, including but not limited to development of the prefrontal cortex (PFC). Minorities' Diminished Returns (MDRs), however, suggests that race (as a proxy of racism) may interact with various determinants of human and brain development. Minimal knowledge, however, exists on whether age and race also interact on shaping PFC response to threat among American children. Using data from a task-based functional brain imaging study and considering race as a sociological rather than a biological construct, we investigated combined effects of race and age on prefrontal cortical (PFC) response to threat. We explored racial heterogeneities in the association between age and PFC response to threat by comparing Black and White children. This study used the task-based functional Magnetic Resonance Imaging (fMRI) data from the Adolescents Brain Cognitive Development (ABCD) study, a national, landmark, multi-center brain imaging investigation of 9-10 years old children in the US. The primary outcomes were mean beta weights of n-back runs measuring PFC response to threating versus neutral face contrast in the following regions of interest (ROIs): left hemisphere-lateral orbito-frontal, left hemisphere -superior-frontal, right hemisphere -caudal middle frontal, and right hemisphere -superior frontal cortex. The independent variable was age. Covariates were sex, ethnicity, family socioeconomic status, and neighborhood socioeconomic status. Race was the focal moderator. To analyze the data, we used linear regression models without and with interactions and SES as covariates. We included 5,066 9-10 years old children. Age and race did not show direct effects on PFC response to threatening relative to neutral faces. While ethnicity, sex, and socioeconomic status were controlled, age and race showed a systematic interaction on PFC response to threatening relative to neutral faces. For American children, race and age do not have direct effects but multiplicative effects on PFC response to threat. The results may be reflective of social inequalities in how Black and White children are socialized and developed. The results are important given the role of the PFC in regulating the limbic system response to threat. Coordinated work of the limbic system and PFC is a core element of children's behavioral and emotional development. Future research is needed on how social stratification and racism shape emotion processing and regulation of American children in response to threat.

The association of prefrontal cortex response during a natural reward cue-reactivity paradigm, anhedonia, and demoralization in persons maintained on methadone

Persons with opioid use disorder (OUD) often experience anhedonia and demoralization, yet there is relatively little research on the pathophysiology of anhedonia and demoralization in OUD treatment and recovery. In the current study, persons maintained on methadone (N = 29) underwent a natural reward-cue paradigm during functional near-infrared spectroscopy (fNIRS) imaging. Natural reward cues included highly palatable food, positive social interactions (e.g., a happy family at the dinner table), and emotional intimacy (e.g. couples embracing or kissing, but no erotic images). Participants also self-reported symptoms of anhedonia on the Snaith-Hamilton Pleasure Scale (SHPS) and demoralization on the Demoralization Scale II (DS-II). Participants who reported clinically-significant anhedonia on the SHPS displayed decreased neural activity in the right prefrontal cortex (PFC) in response to natural reward cues (F(1,25) = 3.612, p = 0.027, ηp2 = 0.302). In linear regression models of positive social cues, decreased neural activity in the right VMPFC was associated with increased SHPS total score (F(1,27) = 7.131, R2 = 0.209, p = .013), and decreased neural activity in an area encompassing the right lateral VMPFC and DLPFC was associated with increased DS-II total score (F(1,27) = 10.641, R2 = 0.283, p = 0.003). This study provides initial evidence that the prefrontal cortex is involved in the pathophysiology of anhedonia and demoralization in persons in recovery from OUD. Anhedonia and demoralization are important treatment outcomes that should be queried along with a constellation of physical and mental health outcomes, to assess areas of needed improvement in methadone maintenance and other OUD treatment modalities.

Dysfunction of the Prefrontal Cortex in Betel-Quid-Dependent Chewers.

Betel quid is the fourth most popular psychoactive agent worldwide. Imaging studies have found altered brain structure in prefrontal cortex (PFC) in betel-quid dependent (BQD) chewers. However, the brain function in PFC associated with BQ use still remains unclear. The present study aimed to examine brain functional activity in PFC in individuals with BQD. This study recruited 48 participants with BQD and 22 normal controls (NCs). Both BQ-specific cue reactivity and Go/NoGo tasks were administered with functional magnetic resonance imaging (fMRI). Behavioral results showed a deficit in the choice reaction time task in BQD group. The fMRI results of the cue reactivity task suggested that, individuals with BQD exhibited responses in right ventromedial PFC, left posterior cingulate cortex (PCC), left lateral parietal lobe (LPL), left middle temporal gyrus and left visual cortex, when seeing BQ images compared with control images. In the Go/NoGo task, relative to NCs group, individuals with BQD showed higher activity in right dorsolateral PFC, right PCC and bilateral LPL between NoGo and Go trials. Across these two tasks, we consistently found disrupted function in PFC in individuals with BQD, which might lead to impaired craving and response inhibition in BQ addiction. Results of current study might shed light on the neural mechanisms involved in BQ use, which could be used as potential guidelines for diagnosis and treatment of BQ dependence.

Neural Correlates of Theory of Mind Are Preserved in Young Women With Anorexia Nervosa.

People with anorexia nervosa (AN) commonly exhibit social difficulties, which may be related to problems with understanding the perspectives of others, commonly known as Theory of Mind (ToM) processing. However, there is a dearth of literature investigating the neural basis of these differences in ToM and at what age they emerge. This study aimed to test for differences in the neural correlates of ToM processes in young women with AN, and young women weight-restored (WR) from AN, as compared to healthy control participants (HC). Based on previous findings in AN, we hypothesized that young women with current or prior AN, as compared to HCs, would exhibit a reduced neural response in the medial prefrontal cortex (mPFC), the inferior frontal gyrus, and the temporo-parietal junction (TPJ) whilst completing a ToM task. We recruited 73 young women with AN, 45 WR young women, and 70 young women without a history of AN to take part in the current study. Whilst undergoing a functional magnetic resonance imaging (fMRI) scan, participants completed the Frith-Happé task, which is a commonly used measure of ToM with demonstrated reliability and validity in adult populations. In this task, participants viewed the movements of triangles, which depicted either action movements, simple interactions, or complex social interactions. Viewing trials with more complex social interactions in the Frith-Happé task was associated with increased brain activation in regions including the right TPJ, the bilateral mPFC, the cerebellum, and the dorsolateral prefrontal cortex. There were no group differences in neural activation in response to the ToM contrast. Overall, these results suggest that the neural basis of spontaneous mentalizing is preserved in most young women with AN.

Potential role of primed microglia during obesity on the mesocorticolimbic circuit in autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disease which involves functional and structural defects in selective central nervous system (CNS) regions that harm function and individual ability to process and respond to external stimuli. Individuals with ASD spend less time engaging in social interaction compared to non-affected subjects. Studies employing structural and functional magnetic resonance imaging reported morphological and functional abnormalities in the connectivity of the mesocorticolimbic reward pathway between the nucleus accumbens and the ventral tegmental area (VTA) in response to social stimuli, as well as diminished medial prefrontal cortex in response to visual cues, whereas stronger reward system responses for the non-social realm (e.g., video games) than social rewards (e.g., approval), associated with caudate nucleus responsiveness in ASD children. Defects in the mesocorticolimbic reward pathway have been modulated in transgenic murine models using D2 dopamine receptor heterozygous (D2+/-) or dopamine transporter knockout mice, which exhibit sociability deficits and repetitive behaviors observed in ASD phenotypes. Notably, the mesocorticolimbic reward pathway is modulated by systemic and central inflammation, such as primed microglia, which occurs during obesity or maternal overnutrition. Therefore, we propose that a positive energy balance during obesity/maternal overnutrition coordinates a systemic and central inflammatory crosstalk that modulates the dopaminergic neurotransmission in selective brain areas of the mesocorticolimbic reward pathway. Here, we will describe how obesity/maternal overnutrition may prime microglia, causing abnormalities in dopamine neurotransmission of the mesocorticolimbic reward pathway, postulating a possible immune role in the development of ASD.

Negative Learning Bias in Depression Revisited: Enhanced Neural Response to Surprising Reward Across Psychiatric Disorders

BackgroundPrior work has proposed that major depressive disorder (MDD) is associated with a specific cognitive bias: patients with depression seem to learn more from punishment than from reward. This learning bias has been associated with blunting of reward-related neural responses in the striatum. A key question is whether negative learning bias is also present in patients with MDD and comorbid disorders and whether this bias is specific to depression or shared across disorders. MethodsWe employed a transdiagnostic approach assessing a heterogeneous group of (nonpsychotic) psychiatric patients from the MIND-Set (Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders) cohort with and without MDD but also with anxiety, attention-deficit/hyperactivity disorder, and/or autism (n = 66) and healthy control subjects (n = 24). To investigate reward and punishment learning, we employed a deterministic reversal learning task with functional magnetic resonance imaging. ResultsIn contrast to previous studies, patients with MDD did not exhibit impaired reward learning or reduced reward-related neural activity anywhere in the brain. Interestingly, we observed consistently increased neural responses in the bilateral lateral prefrontal cortex of patients when they received a surprising reward. This increase was not specific to MDD, but generalized to anxiety, attention-deficit/hyperactivity disorder, and autism. Critically, increased prefrontal activity to surprising reward scaled with transdiagnostic symptom severity, particularly that associated with concentration and attention, as well as the number of diagnoses; patients with more comorbidities showed a stronger prefrontal response to surprising reward. ConclusionsPrefrontal enhancement may reflect compensatory working memory recruitment, possibly to counteract the inability to swiftly update reward expectations. This neural mechanism may provide a candidate transdiagnostic index of psychiatric severity.

Naltrexone modulates contextual processing in depression.

Context, the information surrounding an experience, can significantly alter the meaning and the affective responses to events. Yet the biological mechanisms through which context modulate experiences are not entirely understood. Here, we hypothesized that the µ-opioid system-extensively implicated in placebo effects, a clinical phenomenon thought to rely on contextual processing-modulates the effects of contextual information on emotional attributions in patients with depression. To test this hypothesis, 20 unmedicated patients with depression completed a randomized, double-blind, placebo-controlled, crossover study of one dose of 50 mg of naltrexone, or placebo immediately before completing two sessions of the Contextual Framing fMRI task. This task captures effects of valenced contextual cues (pleasant vs. unpleasant) on emotional attribution (the rating of subtle emotional faces: fearful, neutral, or happy). Behaviorally, we found that emotional attribution was significantly moderated by the interaction between contextual cues and subtle emotional faces, such that participants' ratings of valenced faces (fearful and happy), compared to neutral, were more negative during unpleasant, compared to pleasant context cues. At a neural level, context-induced blood-oxygen-level-dependent responses in the ventromedial prefrontal cortex, the dorsal anterior cingulate, the dorsolateral prefrontal cortex, and the lateral orbitofrontal cortex, significantly moderated the effects of context on emotional attribution, and were blunted by naltrexone. Furthermore, the effects of naltrexone on emotional attribution were partially abolished in more severely depressed patients. Our results provide insights into the molecular alterations underlying context representation in patients with depression, providing pivotal early data for future treatment studies.

Chrna5 is Essential for a Rapid and Protected Response to Optogenetic Release of Endogenous Acetylcholine in Prefrontal Cortex.

Optimal attention performance requires cholinergic modulation of corticothalamic neurons in the prefrontal cortex. These pyramidal cells express specialized nicotinic acetylcholine receptors containing the α5 subunit encoded by Chrna5 Disruption of this gene impairs attention, but the advantage α5 confers on endogenous cholinergic signaling is unknown. To ascertain this underlying mechanism, we used optogenetics to stimulate cholinergic afferents in prefrontal cortex brain slices from compound-transgenic wild-type and Chrna5 knock-out mice of both sexes. These electrophysiological experiments identify that Chrna5 is critical for the rapid onset of the postsynaptic cholinergic response. Loss of α5 slows cholinergic excitation and delays its peak, and these effects are observed in two different optogenetic mouse lines. Disruption of Chrna5 does not otherwise perturb the magnitude of the response, which remains strongly mediated by nicotinic receptors and tightly controlled by autoinhibition via muscarinic M2 receptors. However, when conditions are altered to promote sustained cholinergic receptor stimulation, it becomes evident that α5 also works to protect nicotinic responses against desensitization. Rescuing Chrna5 disruption thus presents the double challenge of improving the onset of nicotinic signaling without triggering desensitization. Here, we identify that an agonist for the unorthodox α-α nicotinic binding site can allosterically enhance the cholinergic pathway considered vital for attention. Treatment with NS9283 restores the rapid onset of the postsynaptic cholinergic response without triggering desensitization. Together, this work demonstrates the advantages of speed and resilience that Chrna5 confers on endogenous cholinergic signaling, defining a critical window of interest for cue detection and attentional processing.SIGNIFICANCE STATEMENT The α5 nicotinic receptor subunit (Chrna5) is important for attention, but its advantage in detecting endogenous cholinergic signals is unknown. Here, we show that α5 subunits permit rapid cholinergic responses in prefrontal cortex and protect these responses from desensitization. Our findings clarify why Chrna5 is required for optimal attentional performance under demanding conditions. To treat the deficit arising from Chrna5 disruption without triggering desensitization, we enhanced nicotinic receptor affinity using NS9283 stimulation at the unorthodox α-α nicotinic binding site. This approach successfully restored the rapid-onset kinetics of endogenous cholinergic neurotransmission. In summary, we reveal a previously unknown role of Chrna5 as well as an effective approach to compensate for genetic disruption and permit fast cholinergic excitation of prefrontal attention circuits.

Aging alters neural activity at event boundaries in the hippocampus and Posterior Medial network

Recent research has highlighted a role for the hippocampus and a Posterior Medial cortical network in signaling event boundaries. However, little is known about whether or how these neural processes change over the course of healthy aging. Here, 546 cognitively normal participants 18–88 years old viewed a short movie while brain activity was measured using fMRI. The hippocampus and regions of the Posterior Medial network show increased activity at event boundaries, but these boundary-evoked responses decrease with age. Boundary-evoked activity in the posterior hippocampus predicts performance on a separate test of memory for stories, suggesting that hippocampal activity during event segmentation may be a broad indicator of individual differences in episodic memory ability. In contrast, boundary-evoked responses in the medial prefrontal cortex and middle temporal gyrus increase across the age range. These findings suggest that aging may alter neural processes for segmenting and remembering continuous real-world experiences.

Dorsolateral prefrontal cortex response to negative tweets relates to executive functioning.

Cognitive performance can become impaired when a stimulus evokes an emotional response. Social media often elicits emotional reactions, but, despite social media's ubiquity, cognitive and neural consequences of exposure to negative online content are relatively unknown. Fifty-seven human adults (18-29years; 38 female) who identified with at least one historically-marginalized group performed a novel 'Tweet Task'. While undergoing functional magnetic resonance imaging, participants completed a spatial reasoning task before and after reading a set of actual tweets. Participants were randomly assigned to read negative, discriminatory tweets from President Trump (Negative Condition) or neutral tweets (Neutral Condition). Participants in the Negative Condition reported worsening affect and demonstrated performance interference post-tweet compared to those in the Neutral Condition. Affect post-tweet was associated with parametric reductions in left dorsolateral prefrontal cortex, which predicted variance in performance beyond elicited negative affect. Performance effects were demonstrated on an unrelated spatial reasoning task suggesting that engaging with negative, emotionally-arousing content on social media can have deleterious effects on executive functioning in non-social domains.

Me first: Neural representations of fairness during three-party interactions

One hallmark of human morality is a deep sense of fairness. People are motivated by both self-interest and a concern for the welfare of others. However, it remains unclear whether these motivations rely on similar neural computations, and the extent to which such computations influence social decision-making when self-fairness and other-fairness motivations compete. In this study, two groups of participants engaged in the role of responder in a three-party Ultimatum Game while being scanned with functional MRI (N = 32) or while undergoing high-density electroencephalography (N = 40). In both studies, participants accepted more OtherFair offers when they themselves received fair offers. Though SelfFairness was reliably decoded from scalp voltages by 170 ms, and from hemodynamic responses in right insula and dorsolateral prefrontal cortex, there was no overlap between neural representations of fairness for self and for other. Distinct neural computations and mechanisms seem to be involved when making decisions about fairness in three-party contexts, which are anchored in an egocentric, self-serving bias.

Play, but not observing play, engages rat medial prefrontal cortex.

Rats have elaborate cognitive capacities for playing Hide & Seek. Playing Hide & Seek strongly engages medial prefrontal cortex and the activity of prefrontal cortex neurons reflects the structure of the game. We wondered if prefrontal neurons would also show a mirroring of play-related neural activity. Specifically, we asked how does the activity in the rat medial prefrontal cortex differ when the animal plays itself versus when it observes others playing. Consistent with our previous work, when the animal plays itself we observed medial prefrontal cortex activity that was sharply locked to game events. Observing play, however, did not lead to a comparable activation of rat medial prefrontal cortex. Firing rates during observing play were lower than during real play. The modulation of responses in medial prefrontal cortex by game events was strong during playing Hide & Seek, but weak during observing Hide & Seek. We conclude the rat prefrontal cortex does not mirror play events under our experimental conditions.

Prefrontal cortex hypoactivity distinguishes severe from mild-to-moderate social anxiety as revealed by a palm-sized near-infrared spectroscopy system.

The purpose of this study was to compare prefrontal cortex (PFC) activity among subjects with differing social anxiety (SA) severity levels to identify a possible biomarker for severe SA. Further, SA is generally under-diagnosed, so we examined if such measurements could be acquired conveniently, non-invasively, and at low cost using a portable near-infrared spectroscopy (NIRS) system. We classified 96 participants into three groups based on Liebowitz Social Anxiety Scale (LSAS) total score: Low SA (LSA, n = 40), Moderate SA (MSA, n = 39), and High SA (HSA, n = 17). We compared the prefrontal hemodynamic responses among LSAS severity groups during a verbal fluency task using a palm-sized NIRS system. The HSA group exhibited a significantly lower hemodynamic response in the left PFC compared to LSA and MSA groups, whereas there was no significant difference between LSA and MSA groups. There was also no significant difference in the right PFC hemodynamic response among groups. Differences in the severity of SA symptoms may be related to the left PFC function. Low PFC activity during specific cognitive tasks may provide a biomarker for distinguishing severe from mild/moderate SA symptoms to guide subsequent therapeutic decisions.

Where Sounds Occur Matters: Context Effects Influence Processing of Salient Vocalisations.

The social context in which a salient human vocalisation is heard shapes the affective information it conveys. However, few studies have investigated how visual contextual cues lead to differential processing of such vocalisations. The prefrontal cortex (PFC) is implicated in processing of contextual information and evaluation of saliency of vocalisations. Using functional Near-Infrared Spectroscopy (fNIRS), we investigated PFC responses of young adults (N = 18) to emotive infant and adult vocalisations while they passively viewed the scenes of two categories of environmental contexts: a domestic environment (DE) and an outdoors environment (OE). Compared to a home setting (DE) which is associated with a fixed mental representation (e.g., expect seeing a living room in a typical house), the outdoor setting (OE) is more variable and less predictable, thus might demand greater processing effort. From our previous study in Azhari et al. (2018) that employed the same experimental paradigm, the OE context was found to elicit greater physiological arousal compared to the DE context. Similarly, we hypothesised that greater PFC activation will be observed when salient vocalisations are paired with the OE compared to the DE condition. Our finding supported this hypothesis: the left rostrolateral PFC, an area of the brain that facilitates relational integration, exhibited greater activation in the OE than DE condition which suggests that greater cognitive resources are required to process outdoor situational information together with salient vocalisations. The result from this study bears relevance in deepening our understanding of how contextual information differentially modulates the processing of salient vocalisations.

The neural basis of hot and cold cognition in depressed patients, unaffected relatives, and low-risk healthy controls: An fMRI investigation

BackgroundModern cognitive neuropsychological models of depression posit that negatively biased emotional (“hot”) processing confers risk for depression, while preserved executive function (“cold”) cognition promotes resilience. MethodsWe compared neural responses during hot and cold cognitive tasks in 99 individuals: those at familial risk for depression (N = 30 unaffected first-degree relatives of depressed individuals) and those currently experiencing a major depressive episode (N = 39 unmedicated depressed patients) with low-risk healthy controls (N = 30). Primary analyses assessed neural activation on two functional magnetic resonance imaging tasks previously associated with depression: dorsolateral prefrontal cortex (DLPFC) responsivity during the n-back working memory task; and amygdala and subgenual anterior cingulate cortex (sgACC) responsivity during incidental emotional face processing. ResultsDepressed patients exhibited significantly attenuated working memory-related DLPFC activation, compared to low-risk controls and unaffected relatives; unaffected relatives did not differ from low-risk controls. We did not observe a complementary pattern during emotion processing. However, we found preliminary support that greater DLPFC activation was associated with lower amygdala response during emotion processing. LimitationsThese findings require confirmation in a longitudinal study to observe each individual's risk of developing depression; without this, we cannot identify the true risk level of the first-degree relative or low-risk control group. ConclusionsThese findings have implications for understanding the neural mechanisms of risk and resilience in depression: they are consistent with the suggestion that preserved executive function might confer resilience to developing depression in first-degree relatives of depressed patients.

Systemic inflammation is associated with differential neural reactivity and connectivity to affective images.

Systemic inflammation is increasingly appreciated as a predictor of health and well-being. Further, inflammation has been shown to influence and be influenced by affective experiences. Although prior work has substantiated associations between inflammatory and affective processes, fewer studies have investigated the neurobiological correlates that underlie links between systemic, low-grade inflammation and affective reactivity. Thus, the current study examined whether markers of systemic inflammation (i.e. interleukin-6, C-reactive protein) are associated with differential patterns of neural activation and connectivity in corticolimbic regions in response to affective images. We investigated this question in a sample of 66 adults (44 women, M age = 54.98 years, range = 35–76) from the Midlife in the United States study. Higher levels of inflammation were associated with lower activity in limbic regions (i.e. amygdala, hippocampus, anterior insula, temporal pole) when viewing positive (vs neutral) images. Higher levels of inflammation were also associated with greater connectivity between the hippocampus and the medial prefrontal cortex in response to positive images. Inflammatory markers were not associated with significant differences in activation or connectivity to negative images. These findings highlight the utility of health neuroscience approaches in demonstrating that physiological processes such as inflammation are related to how our brains respond to affective information.

Variability in Aberrant Prefrontal Cortex Response in Relation to Cognitive Impairment and Cognitive Improvement - How can This be Reconciled?

Variability in Aberrant Prefrontal Cortex Response in Relation to Cognitive Impairment and Cognitive Improvement - How can This be Reconciled?

Effects of Transcranial Direct Current Stimulation on Baseline and Slope of Prefrontal Cortex Hemodynamics During a Spatial Working Memory Task.

Background: Transcranial direct current stimulation (tDCS) has been shown to be an inexpensive, safe, and effective way of augmenting a variety of cognitive abilities. Relatively recent advances in neuroimaging technology have provided the ability to measure brain activity concurrently during active brain stimulation rather than after stimulation. The effects on brain activity elicited by tDCS during active tDCS reported by initial studies have been somewhat conflicted and seemingly dependent on whether a behavioral improvement was observed.Objective: The current study set out to address questions regarding behavioral change, within and between-participant designs as well as differentiating the effects on hemodynamic amplitude and baseline during active tDCS stimulation.Methods: We tested the effects of transcranial direct current stimulation (tDCS) on anterior hemodynamics in prefrontal cortex during performance on a spatial memory task. Prefrontal cortex activity was measured with functional near infrared spectroscopy (fNIRS), a wearable and portable neuroimaging technique that utilizes near infrared light to measure cortical oxygenated and deoxygenated hemoglobin changes non-invasively. There were two groups, one group (n = 10) received only sham stimulation and the other group (n = 11) received sham followed by anodal stimulation to right ventral lateral prefrontal cortex.Results: Analyses revealed an increase in spatial memory performance following tDCS stimulation. This augmented performance was accompanied by changes to oxygenation (HbO–HbR) at the onset of the hemodynamic response in bilateral dorsolateral prefrontal cortex and left ventral medial prefrontal cortex. In these regions we also observed that stimulation improved neural processing efficiency, by reducing oxygenation and increasing performance from block to block. During and following tDCS stimulation, it was also observed that in bilateral dorsolateral prefrontal cortex the relationship between performance and oxygenation inverted, from a negative relationship to a positive relationship.Conclusion: The results suggest that tDCS is predominately a mechanism for changing neurons propensity for activity as opposed to their strength of activity. tDCS not only alters the efficiency of task relevant processing, but also the nature in which hemodynamic resources are used during augmented task performance.