Emotion disrupts neural activity during selective attention in psychopathy

Dimensions of psychopathy are theorized to be associated with distinct cognitive and emotional abnormalities that may represent unique neurobiological risk factors for the disorder. This hypothesis was investigated by examining whether the psychopathic personality dimensions of fearless-dominance and impulsive-antisociality moderated neural activity and behavioral responses associated with selective attention and emotional processing during an emotion-word Stroop task in 49 adults. As predicted, the dimensions evidenced divergent selective-attention deficits and sensitivity to emotional distraction. Fearless-dominance was associated with disrupted attentional control to positive words, and activation in right superior frontal gyrus mediated the relationship between fearless-dominance and errors to positive words. In contrast, impulsive-antisociality evidenced increased behavioral interference to both positive and negative words and correlated positively with recruitment of regions associated with motivational salience (amygdala, orbitofrontal cortex, insula), emotion regulation (temporal cortex, superior frontal gyrus) and attentional control (dorsal anterior cingulate cortex). Individuals high on both dimensions had increased recruitment of regions related to attentional control (temporal cortex, rostral anterior cingulate cortex), response preparation (pre-/post-central gyri) and motivational value (orbitofrontal cortex) in response to negative words. These findings provide evidence that the psychopathy dimensions represent dual sets of risk factors characterized by divergent dysfunction in cognitive and affective processes.     

Looking at the self in front of others: Neural correlates of attentional bias in social anxiety

In social anxiety disorder (SAD), anxiety reactions are triggered by attentional bias to social threats that automatically appear in social situations. The present study aimed to investigate the neural basis and underlying resting-state pathology of attentional bias toward internal and external social threats as a core element of SAD. Twenty-two patients with SAD and 20 control subjects scanned functional magnetic resonance imaging during resting-state and while performing the visual search task. During the task, participants were exposed to internal threat (hearing participants’ own pulse-sounds) and external threat (crowds in facial matrices). Patients showed activations in the lateral orbitofrontal cortex, rostral anterior cingulate cortex and insula in response to internal threat and activations in the posterior cingulate cortex and middle temporal gyrus in response to external threat. In patients, neural activity related to combined internal and external threats in the posterior cingulate cortex was inversely correlated with the functional connectivity strengths with the default mode network during resting-state. These findings suggest that attentional bias may stem from limbic and paralimbic pathology, and the interactive process of internally- and externally-focused attentional bias in SAD is associated with the self-referential function of resting-state.     

Atypical network connectivity for imitation in autism spectrum disorder

Imitation has been considered as one of the precursors for sociocommunicative development. Impairments of imitation in autism spectrum disorder (ASD) could be indicative of dysfunctional underlying neural processes. Neuroimaging studies have found reduced activation in areas associated with imitation, but a functional connectivity MRI network perspective of these regions in autism is unavailable. Functional and effective connectivity was examined in 14 male participants with ASD and 14 matched typically developing (TD) participants. We analyzed intrinsic, low-frequency blood oxygen level dependent (BOLD) fluctuations of three regions in literature found to be associated with imitation (inferior frontal gyrus [IFG], inferior parietal lobule [IPL], superior temporal sulcus [STS]). Direct group comparisons did not show significantly reduced functional connectivity within the imitation network in ASD. Conversely, we observed greater connectivity with frontal regions, particularly superior frontal and anterior cingulate gyri, in the ASD compared to TD group. Structural equation modeling of effective connectivity revealed a significantly reduced effect of IPL on IFG together with an increased influence of a region in dorsal prefrontal cortex (dPFC) on IFG in the ASD group. Our results suggest atypical connectivity of the imitation network with an enhanced role of dPFC, which may relate to behavioral impairments.     

Reduced volume of orbitofrontal cortex in major depression.

BACKGROUND: Functional neuroimaging studies have implicated dysfunction of orbitofrontal cortex in the symptoms of depression, and a recent postmortem study of depressed patients found reduced density of neurons and glia in this area. The purpose of this study was to measure volume of orbitofrontal cortex and other frontal cortical subregions in patients with major depression. METHODS: Magnetic resonance imaging was used to measure volume of the orbitofrontal cortex and other frontal cortical regions in patients with major depression in remission (n = 15) and comparison subjects (n = 20). RESULTS: Patients with depression had a statistically significant 32% smaller medial orbitofrontal (gyrus rectus) cortical volume, without smaller volumes of other frontal regions including anterior cingulate Brodmann's area 24 (subgenual gyrus), anterior cingulate Brodmann's area 32, subcallosal gyrus (Brodmann's area 25), or whole brain volume. The findings were significant after statistically controlling for brain size. CONCLUSIONS: These findings are consistent with smaller orbitofrontal cortical volume in depression.     

Increase in prefrontal cortex serotonin 2A receptors following estrogen treatment in postmenopausal women

OBJECTIVE: This study investigated the effect of estrogen on brain serotonin 2A (5-HT(2A)) receptors in postmenopausal women and whether there was any correlation of receptor changes with cognition and mood. METHOD: Ten postmenopausal subjects underwent positron emission tomography measurements of 5-HT(2A) receptor binding with [(18)F]deuteroaltanserin before and after estrogen replacement therapy. RESULTS: 5-HT(2A) receptor binding was significantly increased after estrogen replacement therapy in the right prefrontal cortex (right precentral gyrus [Brodmann's area 9], inferior frontal gyrus [Brodmann's area 47], medial frontal gyrus [Brodmann's area 6, 10] and the anterior cingulate cortex [Brodmann's area 32]). In the inferior frontal gyrus [Brodmann's area 44]), receptor up-regulation was correlated with change in plasma estradiol. Verbal fluency and Trail Making Test performance, but not mood, were significantly improved by estrogen without correlation with receptor changes. CONCLUSIONS: Estrogen increases 5-HT(2A) receptor binding in human prefrontal regions.     

Extraction of situational meaning by integrating multiple meanings in a complex environment: A functional MRI study

Humans extract behaviorally significant meaning from a situation by integrating meanings from multiple components of a complex daily environment. To determine the neural underpinnings of this ability, the authors performed functional magnetic resonance imaging of healthy subjects while the latter viewed naturalistic scenes of two people and an object, including a threatening situation of a person being attacked by an offender with an object. The authors used a two‐factorial design: the object was either aversive or nonaversive, and the offender's action was either directed to the person or elsewhere. This allowed the authors to examine the neural response to object aversiveness and person‐directed intention separately. A task unrelated to threat was also used to address incidental (i.e., subconscious or unintentional) detection. Assuming individual differences in incidental threat detection, the authors used a functional connectivity analysis using principal components analysis of intersubject variability. The left lateral orbitofrontal cortex and medial prefrontal cortex (MPFC) were specifically activated in response to a threatening situation. The threat‐related component of intersubject variability was extracted from these data and showed a significant correlation with personality scores. There was also a correlation between threat‐related intersubject variability and activation for object aversiveness in the left temporal pole and lateral orbitofrontal cortex; person‐directed intention in the left superior frontal gyrus; threatening situations in the left MPFC; and independently for both factors in the right MPFC. Results demonstrate independent processing of object aversiveness and person‐directed intention in the left temporal‐orbitofrontal and superior frontal networks, respectively, and their integration into situational meaning in the MPFC. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Differential roles of inferior frontal and inferior parietal cortex in task switching: Evidence from stimulus‐categorization switching and response‐modality switching

We used fMRI to investigate both common and differential neural mechanisms underlying two distinct types of switching requirements, namely switching between stimulus categorizations (color vs. form) and switching between response modalities (hand vs. foot responses). Both types of switching induced similar behavioral shift costs. However, at the neural level, switching between stimulus categorizations led to left‐hemispheric activations including the inferior frontal gyrus as well as the intraparietal sulcus extending to the superior parietal gyrus and the supramarginal gyrus. In contrast, switching between response modalities was associated mainly with left‐hemispheric activation of the intraparietal sulcus and the supramarginal gyrus. A conjunction analysis indicated common activation of the left intraparietal sulcus and the supramarginal gyrus for both types of switching. Together, these results qualify previous claims about a general role of the left prefrontal cortex in task control by suggesting that the left inferior frontal gyrus is specifically involved in switching between stimulus categorizations, whereas parietal cortex is more generally implicated in the selection of action rules. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Dissociating behavioral disorders in early dementia—An FDG-PET study

Behavioral impairments occur frequently in dementia. Studies with magnetic resonance imaging, measuring atrophy, have systematically investigated their neural correlates. Such a systematic approach has not yet been applied to imaging with [¹⁸F] fluorodeoxyglucose positron emission tomography (FDG-PET), although regional hypometabolism may precede and exceed atrophy in dementia. The present study related all behavioral disorders as assessed with the Neuropsychiatric Inventory to reductions in brain glucose utilization as measured by FDG-PET with Statistical Parametric Mapping (SPM5). It included 54 subjects mainly with early Alzheimer's disease, frontotemporal lobar degeneration, and subjective cognitive impairment. Apathy, disinhibition and eating disorders – most frequent in frontotemporal lobar degeneration – correlated significantly with regional brain hypometabolism. Whereas a single regressor analysis and conjunction analysis revealed largely overlapping frontomedian regions that were associated with all three behavioral domains, a disjunction analysis identified three specific neural networks for each behavioral disorder, independent of dementia severity. Apathy was related to the ventral tegmental area, a component of the motivational dopaminergic network; disinhibition to both anterior temporal lobes including the anterior hippocampi and left amygdala, caudate head, orbitofrontal cortex and insulae; and eating disorders to the right lateral (orbito) frontal cortex/insula. Our study contributes to the understanding of behavioral deficits in early dementia and suggests specific diagnostic and therapeutic approaches.     

Pubertal testosterone influences threat-related amygdala–orbitofrontal cortex coupling

Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala–orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala–OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed.     

Face perception is mediated by a distributed cortical network

The neural system associated with face perception in the human brain was investigated using functional magnetic resonance imaging (fMRI). In contrast to many studies that focused on discreet face-responsive regions, the objective of the current study was to demonstrate that regardless of stimulus format, emotional valence, or task demands, face perception evokes activation in a distributed cortical network. Subjects viewed various stimuli (line drawings of unfamiliar faces and photographs of unfamiliar, famous, and emotional faces) and their phase scrambled versions. A network of face-responsive regions was identified that included the inferior occipital gyrus, fusiform gyrus, superior temporal sulcus, hippocampus, amygdala, inferior frontal gyrus, and orbitofrontal cortex. Although bilateral activation was found in all regions, the response in the right hemisphere was stronger. This hemispheric asymmetry was manifested by larger and more significant clusters of activation and larger number of subjects who showed the effect. A region of interest analysis revealed that while all face stimuli evoked activation within all regions, viewing famous and emotional faces resulted in larger spatial extents of activation and higher amplitudes of the fMRI signal. These results indicate that a mere percept of a face is sufficient to localize activation within the distributed cortical network that mediates the visual analysis of facial identity and expression.     

Neural evidence for reduced apprehensiveness of familiarized stimuli in a mere exposure paradigm

Mere familiarization with a stimulus increases liking for it or similar stimuli ("mere exposure" effects) as well as perceptual fluency, indexed by the speed and accuracy of categorizing it or similar stimuli ("priming" effects). Candidate mechanisms proposed to explain mere exposure effects include both increased positive affect associated with greater perceptual fluency, and reduced negative affect associated with diminished apprehensiveness of novel stimuli. Although these two mechanisms are not mutually exclusive, it is difficult for behavioral measures to disentangle them, since increased liking or other indices of greater positive affect toward exposed stimuli could result from increases in positive feelings or decreases in negative feelings or both. The present study sought to clarify this issue by building on research showing a dissociation at the neural level in which the lateral orbitofrontal cortex (LOFC) is activated more by negatively valenced than by neutral or positively valenced stimuli, with the reverse effect for medial orbitofrontal cortex (MOFC). Supporting the reduced apprehensiveness hypothesis, we found lower LOFC activation to familiarized faces and objects (repetition suppression). We did not find evidence to support the positive affect hypothesis in increased activation to familiarized stimuli in MOFC or in other parts of the reward circuit that respond more to positively valenced stimuli (repetition enhancement), although enhancement effects were shown in some regions.     

Neuroimaging of valence decisions in children and adults

To date, the neural underpinnings of affective components in language processing in children remain largely unknown. To fill this gap, the present study examined behavioural and neural correlates of children and adults performing the same auditory valence decision task with an event-related fMRI paradigm. Based on previous findings in adults, activations in anterior and posterior cingulate cortex, orbitofrontal cortex and left inferior frontal gyrus were expected for both positive and negative valence categories. Recent behavioural findings on valence decisions showed similar ratings and reaction time patterns in children and adults. This finding was successfully replicated in the present study. On a neural level, our analysis of affective language processing showed activations in regions associated with both semantic (superior and middle temporal and frontal) and affective (anterior and posterior cingulate, orbitofrontal and inferior frontal, insula and amygdala) processing. Neural activations in children and adults were systematically different in explicit affective word processing. In particular, adults showed a more distributed semantic network activation while children recruited additional subcortical structures.     

Altered executive control network resting-state connectivity in social anxiety disorder

Objectives: Research into the neural basis of social anxiety disorder (SAD) suggests alterations in prefrontal networks, which may in turn disrupt regulation of the limbic system. Better understanding of the disturbed interface between these networks may improve current pathogenic models of this disorder. Methods: Applying group independent component analysis (ICA) to recordings of fMRI resting-state, connectivity in the executive control network was studied in 18 patients with SAD and 15 age- and sex-matched healthy controls. Results: Results revealed a dissociation within the left executive control network, with SAD patients showing decreased connectivity of the orbitofrontal gyrus and increased connectivity of the middle frontal gyrus compared to healthy controls. In a subsequent seed-based functional connectivity analysis, patients with SAD displayed increased connectivity between the left orbitofrontal gyrus and the left amygdala. Conclusions: Findings suggest that hypo-connectivity in the executive control network and hyper-connectivity between the orbitofrontal cortex and the amygdala may reflect a disturbance in the balance between top-down and bottom-up control processes, potentially contributing to the development of SAD.     

Dissociating behavioral disorders in early dementia-An FDG-PET study

Behavioral impairments occur frequently in dementia. Studies with magnetic resonance imaging, measuring atrophy, have systematically investigated their neural correlates. Such a systematic approach has not yet been applied to imaging with [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET), although regional hypometabolism may precede and exceed atrophy in dementia. The present study related all behavioral disorders as assessed with the Neuropsychiatric Inventory to reductions in brain glucose utilization as measured by FDG-PET with Statistical Parametric Mapping (SPM5). It included 54 subjects mainly with early Alzheimer's disease, frontotemporal lobar degeneration, and subjective cognitive impairment. Apathy, disinhibition and eating disorders - most frequent in frontotemporal lobar degeneration - correlated significantly with regional brain hypometabolism. Whereas a single regressor analysis and conjunction analysis revealed largely overlapping frontomedian regions that were associated with all three behavioral domains, a disjunction analysis identified three specific neural networks for each behavioral disorder, independent of dementia severity. Apathy was related to the ventral tegmental area, a component of the motivational dopaminergic network; disinhibition to both anterior temporal lobes including the anterior hippocampi and left amygdala, caudate head, orbitofrontal cortex and insulae; and eating disorders to the right lateral (orbito) frontal cortex/insula. Our study contributes to the understanding of behavioral deficits in early dementia and suggests specific diagnostic and therapeutic approaches.     

Consequences, action, and intention as factors in moral judgments: an FMRI investigation

The traditional philosophical doctrines of Consequentialism, Doing and Allowing, and Double Effect prescribe that moral judgments and decisions should be based on consequences, action (as opposed to inaction), and intention. This study uses functional magnetic resonance imaging to investigate how these three factors affect brain processes associated with moral judgments. We find the following: (1) Moral scenarios involving only a choice between consequences with different amounts of harm elicit activity in similar areas of the brain as analogous non-moral scenarios; (2) Compared to analogous non-moral scenarios, moral scenarios in which action and inaction result in the same amount of harm elicit more activity in areas associated with cognition (such as the dorsolateral prefrontal cortex) and less activity in areas associated with emotion (such as the orbitofrontal cortex and temporal pole); (3) Compared to analogous non-moral scenarios, conflicts between goals of minimizing harm and of refraining from harmful action elicit more activity in areas associated with emotion (orbitofrontal cortex and temporal pole) and less activity in areas associated with cognition (including the angular gyrus and superior frontal gyrus); (4) Compared to moral scenarios involving only unintentional harm, moral scenarios involving intentional harm elicit more activity in areas associated with emotion (orbitofrontal cortex and temporal pole) and less activity in areas associated with cognition (including the angular gyrus and superior frontal gyrus). These findings suggest that different kinds of moral judgment are preferentially supported by distinguishable brain systems.     

RAB2A Polymorphism impacts prefrontal morphology,functional connectivity,and working memory

Calbindin‐containing γ‐aminobutyric acid (GABA)ergic interneurons in the prefrontal cortex (PFC) have been found to play an important role in working memory (WM) and their malfunctions have been linked to psychiatric disorders. A recent genome‐wide association and expression‐SNP study indicated that the RAB2A gene was associated with the density of prefrontal calbindin‐positive neurons, suggesting this gene may have a broader influence on prefrontal structure and function. Using multimodal MRI and behavioral tasks, the current study investigated the effect of RAB2A on prefrontal morphology, resting‐state functional connectivity, and WM performance in a large sample of healthy Han Chinese subjects. Results showed that the RAB2A AGCAAA haplotype was associated with improved WM accuracy, increased cortical thickness in the left inferior frontal gyrus, and decreased functional connectivity between the left inferior frontal gyrus and the left dorsolateral PFC. Our findings provide consistent evidence supporting the effect of RAB2A on the structure and function of the PFC and related cognitive functions. These results should provide new insights into the neural mechanisms underlying the GABAergic genes' role in WM as well as its dysfunction. Hum Brain Mapp 36:4372–4382, 2015. © 2015 Wiley Periodicals, Inc.     

Medial cortex activity, self-reflection and depression

Using functional magnetic resonance imaging, we investigated neural activity associated with self-reflection in depressed [current major depressive episode (MDE)] and healthy control participants, focusing on medial cortex areas previously shown to be associated with self-reflection. Both the MDE and healthy control groups showed greater activity in anterior medial cortex (medial frontal gyrus, anterior cingulate gyrus) when cued to think about hopes and aspirations compared with duties and obligations, and greater activity in posterior medial cortex (precuneus, posterior cingulate) when cued to think about duties and obligations (Experiment 1). However, the MDE group showed less activity than controls in the same area of medial frontal cortex when self-referential cues were more ambiguous with respect to valence (Experiment 2), and less deactivation in a non-self-referential condition in both experiments. Furthermore, individual differences in rumination were positively correlated with activity in both anterior and posterior medial cortex during non-self-referential conditions. These results provide converging evidence for a dissociation of anterior and posterior medial cortex depending on the focus of self-relevant thought. They also provide neural evidence consistent with behavioral findings that depression is associated with disruption of positively valenced thoughts in response to ambiguous cues, and difficulty disengaging from self-reflection when it is appropriate to do so.     

Relation of obesity to neural activation in response to food commercials

Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors.     

Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization

To test a prediction of our previous computational model of cortico‐hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI‐adapted category‐learning task that has two phases, an initial phase in which associations are learned through trial‐and‐error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning‐related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands. Hum Brain Mapp 35:3122–3131, 2014. © 2013 Wiley Periodicals, Inc .     

The impact of dystrobrevin‐binding protein 1 (DTNBP1) on neural correlates of episodic memory encoding and retrieval

Episodic memory impairment is a frequently reported symptom in schizophrenia. It has been shown to be associated with reduced neural activity of the hippocampus and prefrontal cortex. Given the high heritability of schizophrenia the question arises if alterations in brain activity are modulated by susceptibility genes and might be detectable in healthy risk allele carriers. The present study investigated the effect of the single nucleotide polymorphism (SNP) rs1018381 (P1578) of the dystrobrevin‐binding protein 1 (DTNBP1) on brain activity in 84 healthy subjects assessed by functional magnetic resonance imaging (fMRI) while they performed an episodic memory task comprising encoding and retrieval of faces. During encoding, the group of risk allele carriers (n = 29) showed enhanced neural activity in the left middle frontal gyrus (BA 11) and bilaterally in the cuneus (BA 17, 7) when compared with the nonrisk carrier group (n = 55). During retrieval, the risk group (compared to the non risk group) showed increased right hemispheric neural activity comprising the medial frontal gyrus (BA 9), inferior frontal gyrus (BA 9), and inferior parietal lobule (BA 40). Since there were no behavioral performance differences, increased neural activity of the risk group might be interpreted as a correlate of higher effort or differing cognitive strategies in order to compensate for a genetically determined slight cognitive deficit. Interestingly, the laterality of increased prefrontal activity is in accordance with the well known hemispheric encoding/retrieval asymmetry (HERA) model of episodic memory. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.