The critical role of the orbitofrontal cortex for regret in an economic decision-making task.

Regret affects decision-making behavior, which is mediated by a cognitive process known as counterfactual thinking in economic science. Several studies indicate that orbitofrontal cortex (OFC) plays a crucial role in decision-making behavior. However, the neural correlates of regret trait and the function of the OFC in decision-making remain unclear. In this study, we employed a typical monetary decision-making task, a modified 'Wheel of Fortune gamble' paradigm, to investigate decision-making behavior and its neural mechanism. We combined voxel-based morphometry (VBM) and task-evoked functional magnetic resonance imaging (fMRI) analyses to explore the neural substrates of regret trait. VBM analyses revealed that individual Regret Scale Score was negatively associated with the gray-matter volume (GMV) in the frontal and temporal areas, including the bilateral OFC. These results indicate that individuals with high regret trait have smaller GMV in these areas. Moreover, we found stronger task-evoked activation of the left OFC in high regret trait individuals during the decision-maker's choice (choose conditions) phase, whereas we did not find this relationship in computer-selected's (follow conditions) choice phase. Using generalized psychophysiological interactions (PPI) analysis, we further found that the functional connectivity of the left OFC to right inferior frontal gyrus and left cerebellum was stronger in the complete feedback choose condition (under regret theoretical framework) than partial feedback choose condition (under disappointment theoretical framework). These findings verify the critical role of the OFC in the decision-making, more importantly, provide novel insights into the morphological and functional substrates of individual regret trait.

Histological assessment of optogenetic tools to study fronto-visual and fronto-parietal cortical networks in the rhesus macaque.

Optogenetics offers unprecedented possibilities to investigate cortical networks. Yet, the number of successful optogenetic applications in non-human primates is still low, and the consequences of opsin expression in the primate brain are not well documented. We assessed histologically if we can target cerebrocortical networks with three common optogenetic constructs (AAV2/5-CaMKIIα-eNpHR3.0-mCherry, -ChR2-eYFP, -C1V1-mCherry). The frontal eye field or the dorsal premotor area of rhesus macaques were virally injected, and the resulting transduction spread, expression specificity, and opsin trafficking into axons projecting to parietal and visual areas were examined. After variable periods (2-24 months), expression was robust for all constructs at the injection sites. The CaMKIIα promoter driven-expression was predominant, but not exclusive, in excitatory neurons. In the case of eNpHR3.0-mCherry and ChR2-eYFP, opsins were present in axonal projections to target areas, in which sparse, retrogradely transduced neurons could also be found. Finally, the intracellular distribution of opsins differed: ChR2-eYFP had almost exclusive membrane localization, while eNpHR3.0-mCherry and C1V1-mCherry showed additional intracellular accumulations, which might affect neuronal survival in the long-term. Results indicate that all three constructs can be used for local neuronal modulation, but axonal stimulation and long-term use require additional considerations of construct selection and verification.

A genetic perspective on the relationship between eudaimonic -and hedonic well-being.

Whether hedonism or eudaimonia are two distinguishable forms of well-being is a topic of ongoing debate. To shed light on the relation between the two, large-scale available molecular genetic data were leveraged to gain more insight into the genetic architecture of the overlap between hedonic and eudaimonic well-being. Hence, we conducted the first genome-wide association studies (GWAS) of eudaimonic well-being (N = ~108 K) and linked it to a GWAS of hedonic well-being (N = ~222 K). We identified the first two genome-wide significant independent loci for eudaimonic well-being and six independent loci for hedonic well-being. Joint analyses revealed a moderate phenotypic correlation (r = 0.53) and a high genetic correlation (rg = 0.78) between eudaimonic and hedonic well-being. This indicates that the genetic etiology of hedonic and eudaimonic well-being is substantially shared, with divergent (environmental) factors contributing to their phenotypic divergence. Loci regulating expression showed significant enrichment in the brain cortex, brain cerebellum, frontal cortex, as well as the cerebellar hemisphere for eudaimonic well-being. No significant enrichment for hedonic well-being is observed, although brain tissues were top ranked. Genetic correlations patterns with a range of positive and negative related phenotypes were largely similar for hedonic -and eudaimonic well-being. Our results reveal a large overlap between the genes that influence hedonism and the genes that influence eudaimonia.

Family poverty affects the rate of human infant brain growth.

Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

Utility of intraindividual reaction time variability to predict white matter hyperintensities: a potential assessment tool for clinical contexts?

Intraindividual variability (IIV) refers to reaction time (RT) variation across the trials of a given cognitive task. Little research has contrasted different measures of IIV or assessed how many RT trials are required to provide a robust measure of the construct. We, therefore, investigated three measures of IIV (raw SD, coefficient of variation, and intraindividual SD statistically removing time-on-task effects) in relation to frontal white matter hyperintensities (obtained through structural MRI) in 415 cognitively normal community-dwelling adults aged 44 to 48 years. Results indicated the three IIV measures did not differ greatly in predictions of white matter hyperintensities, although it is possible that time-on-task effects were influential. As few as 20 trials taking approximately 52 s to administer provided a reliable prediction of frontal white matter hyperintensities. We conclude that future work should evaluate the comparative utility of different IIV measures in relation to persons exhibiting clear neuropathology.

Quantitative effect of the neonatal fontanel on synthetic near infrared spectroscopy measurements.

Near infrared spectroscopy (NIRS) is a functional imaging technique allowing measurement of local cerebral oxygenation. This modality is particularly adapted to critically ill neonates, as it can be used at the bedside and is a suitable and noninvasive tool for carrying out longitudinal studies. However, NIRS is sensitive to the imaged medium and consequently to the optical properties of biological tissues in which photons propagate. In this study, the effect of the neonatal fontanel was investigated by predicting photon propagation using a probabilistic Monte Carlo approach. Two anatomical newborn head models were created from computed tomography and magnetic resonance images: (1) a realistic model including the fontanel tissue and (2) a model in which the fontanel was replaced by skull tissue. Quantitative change in absorption due to simulated activation was compared for the two models for specific regions of activation and optical arrays simulated in the temporal area. A correction factor was computed to quantify the effect of the fontanel and defined by the ratio between the true and recovered change. The results show that recovered changes in absorption were more precise when determined with the anatomical model including the fontanel. The results suggest that the fontanel should be taken into account in quantification of NIRS responses to avoid misinterpretation in experiments involving temporal areas, such as language or auditory studies.

Neural correlates of socioeconomic status in the developing human brain.

Socioeconomic disparities in childhood are associated with remarkable differences in cognitive and socio-emotional development during a time when dramatic changes are occurring in the brain. Yet, the neurobiological pathways through which socioeconomic status (SES) shapes development remain poorly understood. Behavioral evidence suggests that language, memory, social-emotional processing, and cognitive control exhibit relatively large differences across SES. Here we investigated whether volumetric differences could be observed across SES in several neural regions that support these skills. In a sample of 60 socioeconomically diverse children, highly significant SES differences in regional brain volume were observed in the hippocampus and the amygdala. In addition, SES × age interactions were observed in the left superior temporal gyrus and left inferior frontal gyrus, suggesting increasing SES differences with age in these regions. These results were not explained by differences in gender, race or IQ. Likely mechanisms include differences in the home linguistic environment and exposure to stress, which may serve as targets for intervention at a time of high neural plasticity.

Relationships between cognitive function and frontal grey matter volumes and thickness in middle aged and early old-aged adults: the PATH Through Life Study.

The study examined the relationship of lateral frontal cortical volume and thickness with cognitive function in two samples of healthy middle aged (MA, 44-48 years old) and early old-age (OA, 64-68 years old) adults. T1-weighted magnetic resonance imaging scans were acquired in 400 MA and 397 OA adults from respective random community samples. Cortical volumes and thickness were measured with a surface-based segmentation procedure (http://surfer.nmr.mgh.harvard.edu). Volumes of lateral frontal grey matter were found to be significantly lower for OA than MA. Structure-function relationships were investigated using path analyses. In OA, smaller lateral frontal volumes were associated with better episodic memory (EM) (p<0.012, B=-0.117), and Symbol-Digit Modalities Test (SDM) (p<0.031, B=-0.118) performance. Smaller frontal cortical thickness was also associated with better EM (p<0.01) and SDM (p<0.01) performance in OA. However, in MA greater cortical thickness was associated with better EM and (p<0.01) and reaction time (RT) (p<0.01). OA cohort showed significant positive correlations between Total Brain Volume and SDM, Digit-Backwards span and RT. Possible explanations and implications of the relationships in the context of cognitive aging in healthy adults, and limitations of cross-sectional research are discussed.

Variability in frontotemporal brain structure: the importance of recruitment of African Americans in neuroscience research.

BACKGROUND: Variation in brain structure is both genetically and environmentally influenced. The question about potential differences in brain anatomy across populations of differing race and ethnicity remains a controversial issue. There are few studies specifically examining racial or ethnic differences and also few studies that test for race-related differences in context of other neuropsychiatric research, possibly due to the underrepresentation of ethnic minorities in clinical research. It is within this context that we conducted a secondary data analysis examining volumetric MRI data from healthy participants and compared the volumes of the amygdala, hippocampus, lateral ventricles, caudate nucleus, orbitofrontal cortex (OFC) and total cerebral volume between Caucasian and African-American participants. We discuss the importance of this finding in context of neuroimaging methodology, but also the need for improved recruitment of African Americans in clinical research and its broader implications for a better understanding of the neural basis of neuropsychiatric disorders. METHODOLOGY/PRINCIPAL FINDINGS: This was a case control study in the setting of an academic medical center outpatient service. Participants consisted of 44 Caucasians and 33 ethnic minorities. The following volumetric data were obtained: amygdala, hippocampus, lateral ventricles, caudate nucleus, orbitofrontal cortex (OFC) and total cerebrum. Each participant completed a 1.5 T magnetic resonance imaging (MRI). Our primary finding in analyses of brain subregions was that when compared to Caucasians, African Americans exhibited larger left OFC volumes (F (1,68) = 7.50, p = 0.008). CONCLUSIONS: The biological implications of our findings are unclear as we do not know what factors may be contributing to these observed differences. However, this study raises several questions that have important implications for the future of neuropsychiatric research.

Von Economo neurons in the elephant brain.

Von Economo neurons (VENs), previously found in humans, all of the great ape species, and four cetacean species, are also present in African and Indian elephants. The VENs in the elephant are primarily found in similar locations to those in the other species. They are most abundant in the frontoinsular cortex (area FI) and are also present at lower density in the anterior cingulate cortex. Additionally, they are found in a dorsolateral prefrontal area and less abundantly in the region of the frontal pole. The VEN morphology appears to have arisen independently in hominids, cetaceans, and elephants, and may reflect a specialization for the rapid transmission of crucial social information in very large brains.

Calculating the cost of acting in frontal cortex.

To make informed and successful decisions, it is vital to be able to evaluate whether the expected benefits of a course of action make it worth tolerating the costs incurred to obtain them. The frontal lobe has been implicated in several aspects of goal-directed action selection, social interaction, and optimal choice behavior. However, its exact contribution has remained elusive. Here, we discuss a series of studies in rats and primates examining the effect of discrete lesions on different aspects of cost-benefit decision making. Rats with excitotoxic lesions of the anterior cingulate cortex became less willing to invest effort for reward but showed no change when having to tolerate delays. Orbitofrontal cortex-lesioned rats, by contrast, became more impulsive, yet were just as prepared as normal animals to expend energy to obtain reward. The sulcal region of primate anterior cingulate cortex was also shown to be essential for dynamically integrating over time the recent history of choices and outcomes. Selecting a particular course of action may also come at the expense of gathering important information about other individuals. Evaluating social information when deciding whether to respond was demonstrated to be a function of the anterior cingulate gyrus. Taken together, this indicates that there may be dissociable pathways in the frontal lobe for managing different types of response cost and for gathering social information.

Assessment of cerebrocortical regions associated with sexual arousal in premenopausal and menopausal women by using BOLD-based functional MRI.

PURPOSE: The aim of this study was to compare the cerebral regions associated with sexual arousal between premenopausal and menopausal women by using functional magnetic resonance imaging (f MRI). MATERIALS AND METHODS: Ten premenopausal and 10 menopausal women underwent fMRI on a 1.5T MR scanner using the blood oxygen level dependent technique. To identify the activated brain regions associated with sexual response, brain activation was assessed during 1 minute of a nonerotic film, followed by 4 minutes of an erotic film. RESULTS: The overall activation ratios of the premenopausal women were greater than those of the menopausal women by approximately 8% on average. The limbic, temporal association areas, and parietal lobe showed greater enhancement of signal intensities in premenopausal women. However, signal enhancement in the genu of the corpus callosum and superior frontal gyrus was dominant in menopausal women. CONCLUSIONS: The activated brain center associated with visually evoked sexual arousal showed qualitative and quantitative differences between premenopausal and menopausal women.

In vivo assessment of human visual system connectivity with transcranial electrical stimulation during functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) was used to investigate local and distant cerebral activation induced by transcranial electrical stimulation in order to noninvasively map functional connectivity in the human visual system. Stimulation with lateromedially directed currents and the anode 4.5 cm dorsally to the inion over the right visual cortex induced phosphenes extending into the contralateral lower quadrant of the visual field. fMRI showed a focal hemodynamic response underneath the anode in extrastriate cortex and distant coactivation in subcortical (lateral geniculate nucleus), cortical visual (striate and extrastriate), and visuomotor areas (frontal and supplementary eye fields). This pattern of activation resembles a network of presumably interconnected visual and visuomotor areas. Analysis of activation sites supplies new information about cerebral correlates of phosphenes and shows that the cortical region underneath the cranial stimulation site is not necessarily the origin of behavioral and/or perceptual effects of transcranial stimulation. We conclude that combining transcranial electrical stimulation of neural tissue with simultaneous fMRI offers the possibility to study noninvasively cerebral connectivity in the human brain.

Quantitative assessment of possible age-related change in synaptic numbers in the human frontal cortex.

To investigate possible age-associated changes in human synaptic connectivity, superior-middle frontal cortex (Brodmann area 9) was evaluated with ultrastructural techniques. Short post mortem autopsy tissue was obtained from 37 cognitive normal individuals ranging in age from 20 to 89 years. A minimum of five subjects represented each decade of life. Synaptic volume density (Nv) was quantified in lamina III and V of the superior-middle frontal cortex employing the physical disector. The stereological assessment demonstrated maintenance of Nv in both lamina III and V of the frontal cortex. The lack of synaptic decline in the frontal cortex in neurologically normal individuals older than 65 years lends support to the idea that many stereotypic views of age-related changes in the CNS do not apply to all brain regions. It also suggests that synaptic loss observed in pathological conditions such as Alzheimer's disease, may be the result of the disease process and not a consequence of normal aging.

Neuroanatomical correlates of the assessment of facial attractiveness.

Frontal cortical damage can lead to changes in affective aspects of personality. However, the difficulty of dissociating such abnormalities from cognitive disorders has overshadowed most previous findings. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) while normal subjects were assessing facial attractiveness. Two left frontal regions showed a significant increase in rCBF while assessing facial attractiveness. The increased rCBF in the left anterior frontal cortex correlated with the overall percentage of assessments of a face as unattractive, while that in the left fronto-temporal junction correlated with the percentage of assessments of a face as attractive. These findings provide direct evidence that the left frontal regions are engaged in the assessment of facial attractiveness.