Poorer Working Memory Performance Research Articles

Effects of highly purified cannabidiol (CBD) on fMRI of working memory in treatment-resistant epilepsy

ObjectiveWe aimed to determine changes in working memory and functional connectivity via functional magnetic resonance imaging (fMRI)-modified Sternberg task after treatment with highly purified cannabidiol (CBD, Epidiolex®; 100 mg/mL) in patients with treatment-resistant epilepsy (TRE). MethodsTwenty patients with TRE (mean age: 35.8 years; 7 male) performed fMRI Sternberg task before receiving CBD (“PRE”) and after reaching stable dosage of CBD (15–25 mg/kg/day; “ON”). Each patient performed 2 runs of the modified Sternberg task during PRE and ON fMRI. Twenty-three healthy controls (HCs; mean age: 25 years; 11 M) also completed the task. All were presented with a sequence of 2 or 6 letters and instructed to remember them (encoding). After a delay, a single letter was shown, and participants recalled if letter was shown in sequence (retrieval). Paired t-tests were used to analyze accuracy/response times. For each subject, event-related modeling of encoding (2 and 6 letters) and retrieval was performed. Paired t-tests controlling for seizure frequency change and scanner type were performed to assess changes in neural recruitment during encoding and retrieval in key regions of interest. ResultsThere was nonsignificant increase in mean modified Sternberg task accuracy from PRE to ON-CBD (28.6 vs. 32.1%). PRE and ON accuracy was worse than HCs (75.5%, p < 0.001). ON-PRE comparison revealed increased activation in the right inferior frontal gyrus (IFG) during 6-letter encoding. ON-HC comparison revealed increased activation in bilateral IFG and insula during 2-letter encoding. PRE-HC comparison revealed decreased activation in the left middle frontal gyrus during 6-letter encoding. None of these activations were associated with working memory performance. SignificanceTreatment-resistant epilepsy results in poorer working memory performance and lower neural recruitment compared with HCs. Treatment with CBD results in no significant changes in working memory performance and in significant increases in neural activity in regions important for verbal memory and attention compared with HCs during memory encoding.

Cortical iron disrupts functional connectivity networks supporting working memory performance in older adults

Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control for contributions of brain volume. Task performance was positively correlated with strength of task-based functional connectivity (tFC) between brain regions of the frontoparietal working memory network. However, higher cortical iron concentration was associated with lower tFC within this frontoparietal network and with poorer working memory performance after controlling for both cerebral blood flow and brain volume. Our results suggest that high cortical iron concentration disrupts communication within frontoparietal networks supporting working memory and is associated with reduced working memory performance in older adults.

Cerebral Arterial Pulsatility and Global White Matter Microstructure Impact Spatial Working Memory in Older Adults With and Without Cardiovascular Risk Factors.

Aging is associated with an increased prevalence of vascular health conditions that are linked to a disruption in the cerebral vasculature and white matter microstructural organization. In people with cardiovascular risk factors, increased cerebral arterial pulsatility is associated with poorer white matter microstructural organization and cognitive functioning. This study examines the relationship among arterial pulsatility, white matter microstructural organization, and cognitive ability in a healthy adult lifespan sample. One hundred and eighty-nine adults were divided into a younger adult (<50 years, n = 97) and older adult (>50 years, n = 92). The latter were further subdivided into two subgroups with (CV+, n = 25) and without (CV−, n = 67) cardiovascular risk factors. Arterial pulsatility was measured using cardiac-gated phase-contrast flow quantification sequence and three indexes of whole-brain white matter microstructural organization [i.e., fractional anisotropy (FA), radial diffusivity (RaD), mean diffusivity (MD)] were derived from diffusion-weighted imaging (DWI). Cognitive ability was assessed using global cognitive functioning (MoCA) and a measure of working memory [sensitivity (d′) from a 2-back task]. Neither the whole group analysis nor the younger adult group showed an association between measures of arterial pulsatility, global white matter microstructural organization, and cognition. In older adults, higher MD and RaD were associated with increased arterial pulsatility and poorer working memory performance. The indirect pathway from arterial pulsatility to working memory performance via both MD and RaD measures was significant in this group. Interestingly, a comparison of CV+ and CV− subgroups showed that this mediating relationship was only evident in older adults with at least one CV risk factor. These findings are consistent with cardiovascular risk factors as underlying arterial, white matter, and cognitive decline in cognitively normal older adults.

Working memory load-dependent changes in cortical network connectivity estimated by machine learning

Working memory engages multiple distributed brain networks to support goal-directed behavior and higher order cognition. Dysfunction in working memory has been associated with cognitive impairment in neuropsychiatric disorders. It is important to characterize the interactions among cortical networks that are sensitive to working memory load since such interactions can also hint at the impaired dynamics in patients with poor working memory performance. Functional connectivity is a powerful tool used to investigate coordinated activity among local and distant brain regions. Here, we identified connectivity footprints that differentiate task states representing distinct working memory load levels. We employed linear support vector machines to decode working memory load from task-based functional connectivity matrices in 177 healthy adults. Using neighborhood component analysis, we also identified the most important connectivity pairs in classifying high and low working memory loads. We found that between-network coupling among frontoparietal, ventral attention and default mode networks, and within-network connectivity in ventral attention network are the most important factors in classifying low vs. high working memory load. Task-based within-network connectivity profiles at high working memory load in ventral attention and default mode networks were the most predictive of load-related increases in response times. Our findings reveal the large-scale impact of working memory load on the cerebral cortex and highlight the complex dynamics of intrinsic brain networks during active task states.

Nocturnal Hypoxemia Is Associated with Altered Parahippocampal Functional Brain Connectivity in Older Adults at Risk for Dementia.

Obstructive sleep apnea is associated with an increased risk of developing mild cognitive impairment and dementia. Intermittent nocturnal hypoxemia in obstructive sleep apnea is associated with brain changes in key regions that underpin memory. To determine whether older adults with severe nocturnal hypoxemia would exhibit reduced functional connectivity within these regions, with associated deficits in memory. Seventy-two participants 51 years and over underwent polysomnography with continuous blood oxygen saturation recorded via oximetry. The oxygen desaturation index (ODI, 3% dips in oxygen levels per hour) was the primary outcome measure. ODI was split into tertiles, with analyses comparing the lowest and highest tertiles (N = 48). Thirty-five of the 48 participants from these two tertiles had mild cognitive impairment. Participants also underwent resting-state fMRI and comprehensive neuropsychological, medical, and psychiatric assessment. The highest ODI tertile group demonstrated significantly reduced connectivity between the left and right parahippocampal cortex, relative to the lowest ODI tertile group (t(42) = -3.26, p = 0.041, beta = -1.99).The highest ODI tertile group also had poorer working memory performance. In the highest ODI tertile group only, higher left-right parahippocampal functional connectivity was associated with poorer visual memory recall (between-groups z = -2.93, p = 0.0034). Older adults with severe nocturnal hypoxemia demonstrate impaired functional connectivity in medial temporal structures, key regions involved in sleep memory processing and implicated in dementia pathophysiology. Oxygen desaturation and functional connectivity in these individuals each relate to cognitive performance. Research is now required to further elucidate these findings.

Reduced activation of the ventromedial prefrontal cortex during self-referential processing in individuals at ultra-high risk for psychosis.

Defects in self-referential processing and perspective-taking are core characteristics that may underlie psychotic symptoms and impaired social cognition in schizophrenia. Here, we investigated the neural correlates of self-referential processing regardless of the perspective taken and third-person perspective-taking regardless of the target person to judge relevance in individuals at ultra-high risk for psychosis. We also explored relationships between alterations in neural activity and neurocognitive function and basic self ('ipseity') disorder. Twenty-two ultra-high-risk individuals and 28 healthy controls completed a functional magnetic resonance imaging task. While being scanned, participants were asked to take a first-person perspective or to put themselves in their close relative's place thereby adopting a third-person perspective during judgments of the relevance of personality trait adjectives to one's self and a close relative. For self-referential (vs other-referential) processing, ultra-high-risk individuals showed less neural activity in the left ventromedial prefrontal cortex/medial orbitofrontal cortex, which was correlated with poor working memory performance. When taking a third-person perspective (vs first-person perspective), ultra-high-risk individuals showed more activity in the middle occipital gyrus. Taken together, our findings suggest that ultra-high-risk individuals already show aberrant neural activity during self-referential processing which may possibly be related to engagement of working memory resources.

Altered frontal white matter microstructure is associated with working memory impairments in adolescents with congenital heart disease: A diffusion tensor imaging study.

Children and adolescents with congenital heart disease (CHD) are at risk for mild to moderate cognitive impairments. In particular, impaired working memory performance has been found in CHD patients of all ages. Working memory is an important domain of higher order cognitive function and is crucial for everyday activities, with emerging importance in adolescence. However, the underlying neural correlate of working memory impairments in CHD is not yet fully understood. Diffusion tensor imaging and tract based spatial statistics analyses were conducted in 47 adolescent survivors of childhood cardiopulmonary bypass surgery (24 females) and in 44 healthy controls (24 females) between 11 and 16 years of age (mean age=13.9, SD=1.6). Fractional anisotropy (FA) of white matter diffusion was compared between groups and was correlated with working memory performance, derived from the Wechsler Intelligence Scale for Children-IV. CHD patients had significantly poorer working memory compared to controls (p=0.001). Widespread bilateral reduction in FA was observed in CHD patients compared to healthy controls (threshold-free cluster enhancement (TFCE) corrected p < 0.05). This reduction in FA was present both in cyanotic and acyanotic CHD patients compared to healthy controls (both p < 0.001). The FA reduction in the frontal lobe, mainly in the forceps minor, was associated with poorer working memory performance in both patients with CHD and healthy controls (TFCE corrected p < 0.05). The current findings underline that in CHD patients, irrespective of disease severity, disrupted or delayed maturation of white matter may persist into adolescence and is associated with working memory impairments, particularly if present in the frontal lobe. Adolescence, which is a crucial period for prefrontal brain maturation, may offer a window of opportunity for intervention in order to support the maturation of frontal brain regions and therefore improve higher order cognitive function in patients with CHD.

Obesity is associated with poor working memory in women, not men: Findings from a nationally representative dataset of U.S. adults

A growing body of research has linked obesity to lower working memory performance. However, sex differences are often found in associations between obesity and cognition, and little work has examined potential sex differences in the association between obesity and working memory. To address this issue, the present research uses data from Wave IV of The National Longitudinal Study of Adolescent to Adult Health (N = 4,769, mean age = 29) to examine whether sex moderated the association between excess weight and working memory. As expected, we found that obesity was associated with poorer working memory, but—importantly—this association was exclusively seen in women, not men. These results held when treating BMI as a continuous or categorical variable (e.g., normal weight, obese), as well as with and without controlling for covariates. The present results therefore indicate that the association between obesity and poorer working memory performance may be sex-dependent. These results suggest that interventions targeted at reducing obesity should be tailored to an individual’s sex, as adherence to these interventions often requires working memory.

Hierarchical recruitment of competition alleviates working memory overload in a frontoparietal model.

The storage limitations of visual working memory have been the subject of intense research interest for several decades, but few studies have systematically investigated the dependence of these limitations on memory load that exceeds our retention abilities. Under this real-world scenario, performance typically declines beyond a critical load among low-performing subjects, a phenomenon known as working memory overload. We used a frontoparietal cortical model to test the hypothesis that high-performing subjects select a manageable number of items for storage, thereby avoiding overload. The model accounts for behavioral and electrophysiological data from high-performing subjects in a parameter regime where competitive encoding in its prefrontal network selects items for storage, interareal projections sustain their representations after stimulus offset, and weak dynamics in its parietal network limit their mutual interference. Violation of these principles accounts for these data among low-performing subjects, implying that poor visual working memory performance reflects poor control over frontoparietal circuitry, making testable predictions for experiments.

Poor working memory performance in healthy elderly adults with electroencephalographic risk of cognitive decline affects syntactic processing

ObjectiveTo examine the effects of working memory (WM) load and gender agreement on sentence processing as a function of the electroencephalographic risk (i.e., abnormally high values of theta absolute power) of cognitive decline in older adults. MethodsEvent-related potentials (ERPs) were collected from Spanish speakers (22 older adults belonged to the Risk group, mean age = 67.7 years; 22 older adults belonged to the Control group, mean age = 65.2 years) while reading sentences to detect grammatical errors. Sentences varied with regard to (1) the gender agreement of the noun and adjective, where gender of the adjective either agreed or disagreed with the noun, and (2) WM load (i.e., the number of words between the noun and adjective in the sentence). ResultsThe Risk group showed a lower percentage of correct answers and longer reaction times than the Control group. The Risk group also showed a different pattern of ERP components, which was characterized by smaller amplitude and longer latency of the P600a component under high WM load conditions. ConclusionThe findings suggest that the Risk group shows difficulties integrating information associated with the previous sentence context. SignificanceThe electroencephalographic risk factor of cognitive decline might be not only a predictor of but also an indicator of current decline.

Altered working memory-related brain responses and white matter microstructure in extremely preterm-born children at school age

Preterm birth poses a risk for neurocognitive and behavioral development. Preterm children, who have not been diagnosed with neurological or cognitive deficits, enter normal schools and are expected to succeed as their term-born peers. Here we tested the hypotheses that despite an uneventful development after preterm birth, these children might exhibit subtle abnormalities in brain function and white-matter microstructure at school-age. We recruited 7.5-year-old children born extremely prematurely (<28 weeks’ gestation), and age- and gender-matched term-born controls (≥37 weeks’ gestation). We applied fMRI during working-memory (WM) tasks, and investigated white-matter microstructure with diffusion tensor imaging. Compared with controls, preterm-born children performed WM tasks less accurately, had reduced activation in several right prefrontal areas, and weaker deactivation of right temporal lobe areas. The weaker prefrontal activation correlated with poorer WM performance. Preterm-born children had higher fractional anisotropy (FA) and lower diffusivity than controls in several white-matter areas, and in the posterior cerebellum, the higher FA associated with poorer visuospatial test scores. In controls, higher FA and lower diffusivity correlated with faster WM performance. Together these findings demonstrate weaker WM-related brain activations and altered white matter microstructure in children born extremely preterm, who had normal global cognitive ability.

The role of goal cueing in kindergarteners’ working memory

Goal neglect has been shown to contribute to kindergarteners’ poor executive control. Hence, presenting goal cues during a task improves children’s performance in inhibition and switching tasks. The current study aimed at extending these findings to working memory (WM) by examining the extent to which kindergarteners’ poor WM performance can result from neglecting the goal to recall memoranda at the end of the retention interval. This question was addressed by introducing goal cues, either visual (Experiments 1 and 2a) or auditory–verbal (Experiment 2b), during the retention interval in a Brown–Peterson task. Results showed no evidence of recall improvement for any cue. However, kindergarteners rehearsed more often in the presence of a visual goal cue, whereas recall was impaired with the presentation of an auditory–verbal goal cue. This suggests that introducing a goal cue in the retention interval of a WM task triggers the use of rehearsal in kindergarteners, albeit without any benefit in WM performance. This contrasts sharply with findings on other executive control tasks. Reasons why goal cues failed to improve kindergarteners’ WM performance are discussed.

Reversing working memory decline in the elderly.

Noninvasive delivery of alternating electrical currents to temporal and prefrontal brain regions improves working memory and reverses age-related changes in brain dynamics in the elderly, report Reinhart and Nguyen in this issue of Nature Neuroscience. They also report a similar effect in young adults with poor working memory performance.

Relationship between changes in metabolic syndrome constituent components over 12 months of treatment and cognitive performance in first-episode schizophrenia

Few studies have investigated the longitudinal effects of treatment-emergent metabolic syndrome changes on cognitive performance in first-episode psychosis. The aim of the present study was to determine the associations between changes in metabolic syndrome constituent component over 12months of treatment and end-point cognitive performance in schizophrenia spectrum disorders. This single site-cohort study included 72 minimally treated or antipsychotic-naïve first-episode patients. Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Our primary objective of interest was the relationship between metabolic syndrome constituent component changes over 12months of treatment and end-point cognitive performance. Secondary objectives included investigating whether this relationship was affected by age, sex, antipsychotic dose, treatment duration and substance use. Weight gain predicted better overall cognition (p = 0.02) at end-point, adjusting for age, sex, substance use, baseline cognitive score and BMI, modal antipsychotic dose and treatment duration. Weight loss (p = 0.04) and substance use (p = 0.01) were both associated with poorer working memory performance at end-point. Low baseline BMI showed differential effects on end-point working memory performance in substance users (unfavorable) compared to non-users (favorable) (p < 0.05). In conclusion, weight gain over the course of antipsychotic treatment is associated with better overall cognitive performance and the working memory domain in first-episode schizophrenia spectrum disorder patients. In contrast, low baseline BMI may represent an unfavorable marker in substance users, who demonstrated weight loss compared to non-users.

Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese.

Alzheimer's disease is the most common neurodegenerative disease, and has a high level of genetic heritability and population heterogeneity. In this study, we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer's disease, followed by independent validation, imaging analysis and function characterization. We identified an exome-wide significant rare missense variant rs3792646 (p.K420Q) in the C7 gene in the discovery stage (P = 1.09 × 10−6, odds ratio = 7.853) and confirmed the association in different cohorts and a combined sample (1615 cases and 2832 controls, Pcombined = 2.99 × 10−7, odds ratio = 1.930). The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood, thus resulting in an earlier age of disease onset. Overexpression of the mutant p.K420Q disturbed cell viability, immune activation and β-amyloid processing. Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons. These findings suggested that C7 is a novel risk gene for Alzheimer's disease in Han Chinese.

Urinary tetrahydrocannabinol is associated with poorer working memory performance and alterations in associated brain activity.

Worldwide, cannabis is one of the most widely used psychoactive substances and cannabis use has been implicated in poorer performance in several cognitive domains, including working memory (WM). However, the neural mechanisms underlying these WM decrements are not well understood and the current study investigated the association of cannabis involvement with WM performance and associated neural activation in the Human Connectome Project (N = 1038). Multiple indicators of cannabis involvement were examined in relation to behavioral performance and brain activity in a visual N-back task using functional magnetic resonance imaging. A positive urine drug screen for tetrahydocannabinol (THC+ status), the principal psychoactive constituent in cannabis, was associated with worse WM performance and differential brain response in areas previously linked to WM performance. Furthermore, decreases in blood-activation-level-dependent (BOLD) signal in WM task-positive brain regions and increases in task-negative regions mediated the relationship between THC+ status and WM performance. In contrast, WM performance and BOLD response during the N-back task were not associated with total lifetime cannabis use, age of first use, or other indicators of involvement, suggesting that the effects of cannabis on WM were short-term residual effects, rather than long-term persistent effects. These findings elucidate differential influences of cannabis involvement on neurocognition and have significant potential implications for occupational performance in diverse settings.

Dimensions of childhood adversity have distinct associations with neural systems underlying executive functioning.

Childhood adversity is associated with increased risk for psychopathology. Neurodevelopmental pathways underlying this risk remain poorly understood. A recent conceptual model posits that childhood adversity can be deconstructed into at least two underlying dimensions, deprivation and threat, that are associated with distinct neurocognitive consequences. This model argues that deprivation (i.e., a lack of cognitive stimulation and learning opportunities) is associated with poor executive function (EF), whereas threat is not. We examine this hypothesis in two studies measuring EF at multiple levels: performance on EF tasks, neural recruitment during EF, and problems with EF in daily life. In Study 1, deprivation (low parental education and child neglect) was associated with greater parent-reported problems with EF in adolescents (N = 169; 13-17 years) after adjustment for levels of threat (community violence and abuse), which were unrelated to EF. In Study 2, low parental education was associated with poor working memory (WM) performance and inefficient neural recruitment in the parietal and prefrontal cortex during high WM load among adolescents (N = 51, 13-20 years) after adjusting for abuse, which was unrelated to WM task performance and neural recruitment during WM. These findings constitute strong preliminary evidence for a novel model of the neurodevelopmental consequences of childhood adversity.

Social exclusion weakens storage capacity and attentional filtering ability in visual working memory.

Social exclusion has been found to impair visual working memory (WM), while the underlying neural processes are currently unclear. Using two experiments, we tested whether the poor WM performance caused by exclusion was due to reduced storage capacity, impaired attentional filtering ability or both. The Cyberball game was used to manipulate social exclusion. Seventy-four female participants performed WM tasks while event-related potentials were recorded. In Experiment 1, participants were made to remember the orientations of red rectangles while ignoring salient green rectangles. Results showed that exclusion impaired the ability to filter out irrelevant items from WM, as reflected by the similar contralateral delay activity (CDA) amplitudes for one-target-one-distractor condition and two-targets condition, as well as the similar CDA amplitudes for two-targets-two-distractors condition and four-targets condition in excluded individuals. In Experiment 2, participants were asked to remember 1–5 colored squares. Results showed that exclusion reduced storage capacity, as the CDA amplitudes reached asymptote at loads of two items for exclusion group and at loads of three items for inclusion group. Together, these two experiments provided complementary evidence that WM deficits caused by social exclusion were due to reduced storage capacity and impaired attentional filtering ability.

Are Early Physical Activity and Sedentary Behaviors Related to Working Memory at 7 and 14 Years of Age?

To evaluate the role of extracurricular physical activity and sedentary behavior at preschool and primary school age on working memory at primary school age and adolescence, respectively. This prospective study was based on a birth cohort across 4 Spanish regions. In the 3 younger subcohorts (n = 1093), parents reported lifestyle habits of child at age 4 years of age on a questionnaire, and children performed a computerized working memory task at 7 years of age. In the older subcohort (n = 307), the questionnaire was completed at 6 years of age and working memory was tested at 14 years of age. Adjusted regression models were developed to investigate the associations between lifestyle habits and working memory. Low extracurricular physical activity levels at 4 years of age were associated with a nonsignificant 0.95% (95% CI -2.81 to 0.92) reduction of correct responses in the working memory task at age 7 years of age. Low extracurricular physical activity levels at 6 years of age were associated with a 4.22% (95% CI -8.05 to -0.39) reduction of correct responses at age 14 years. Television watching was not associated with working memory. Other sedentary behaviors at 6 year of age were associated with a 5.07% (95% CI -9.68 to -0.46) reduction of correct responses in boys at 14 years of age. Low extracurricular physical activity levels at preschool and primary school ages were associated with poorer working memory performance at primary school age and adolescence, respectively. High sedentary behavior levels at primary school age were related negatively to working memory in adolescent boys.

Cognitive Characterization of Schizophrenia Risk Variants Involved in Synaptic Transmission: Evidence of CACNA1C's Role in Working Memory.

With >100 common variants associated with schizophrenia risk, establishing their biological significance is a priority. We sought to establish cognitive effects of risk variants at loci implicated in synaptic transmission by (1) identifying GWAS schizophrenia variants whose associated gene function is related to synaptic transmission, and (2) testing for association between these and measures of neurocognitive function. We selected variants, reported in the largest GWAS to date, associated with genes involved in synaptic transmission. Associations between genotype and cognitive test score were analyzed in a discovery sample (988 Irish participants, including 798 with psychosis), and replication samples (528 UK patients with schizophrenia/schizoaffective disorder; 921 German participants including 362 patients with schizophrenia). Three loci showed significant associations with neuropsychological performance in the discovery samples. This included an association between the rs2007044 (risk allele G) within CACNA1C and poorer working memory performance (increased errors B (95% CI)=0.635-4.535, p=0.012), an effect driven mainly by the psychosis groups. In an fMRI analysis of working memory performance (n=84 healthy participants, a subset of the discovery sample), we further found evidence that the same CACNA1C allele was associated with decreased functional connectivity between the right dorsolateral prefrontal cortex and right superior occipital gyrus/cuneus and anterior cingulate cortex. In conclusion, these data provide evidence to suggest that the CACNA1C risk variant rs2007044 is associated with poorer memory function that may result from risk carriers' difficulty with top-down initiated responses caused by dysconnectivity between the right DLPFC and several cortical regions.