Separate Neural Networks for Gains and Losses in Intertemporal Choice

An important and unresolved question is how human brain regions process information and interact with each other in intertemporal choice related to gains and losses. Using psychophysiological interaction and dynamic causal modeling analyses, we investigated the functional interactions between regions involved in the decision-making process while participants performed temporal discounting tasks in both the gains and losses domains. We found two distinct intrinsic valuation systems underlying temporal discounting in the gains and losses domains: gains were specifically evaluated in the medial regions, including the medial prefrontal and orbitofrontal cortices, and losses were evaluated in the lateral dorsolateral prefrontal cortex. In addition, immediate reward or punishment was found to modulate the functional interactions between the dorsolateral prefrontal cortex and distinct regions in both the gains and losses domains: in the gains domain, the mesolimbic regions; in the losses domain, the medial prefrontal cortex, anterior cingulate cortex, and insula. These findings suggest that intertemporal choice of gains and losses might involve distinct valuation systems, and more importantly, separate neural interactions may implement the intertemporal choices of gains and losses. These findings may provide a new biological perspective for understanding the neural mechanisms underlying intertemporal choice of gains and losses.     

Neural correlates of using distancing to regulate emotional responses to social situations

Cognitive reappraisal is a commonly used and highly adaptive strategy for emotion regulation that has been studied in healthy volunteers. Most studies to date have focused on forms of reappraisal that involve reinterpreting the meaning of stimuli and have intermixed social and non-social emotional stimuli. Here we examined the neural correlates of the regulation of negative emotion elicited by social situations using a less studied form of reappraisal known as distancing. Whole brain fMRI data were obtained as participants viewed aversive and neutral social scenes with instructions to either simply look at and respond naturally to the images or to downregulate their emotional responses by distancing. Three key findings were obtained accompanied with the reduced aversive response behaviorally. First, across both instruction types, aversive social images activated the amygdala. Second, across both image types, distancing activated the precuneus and posterior cingulate cortex (PCC), intraparietal sulci (IPS), and middle/superior temporal gyrus (M/STG). Third, when distancing one's self from aversive images, activity increased in dorsal anterior cingulate (dACC), medial prefrontal cortex (mPFC), lateral prefrontal cortex, precuneus and PCC, IPS, and M/STG, meanwhile, and decreased in the amygdala. These findings demonstrate that distancing from aversive social cues modulates amygdala activity via engagement of networks implicated in social perception, perspective-taking, and attentional allocation.     

Self-development: integrating cognitive, socioemotional, and neuroimaging perspectives

This review integrates cognitive, socioemotional, and neuroimaging perspectives on self-development. Neural correlates of key processes implicated in personal and social identity are reported from studies of children, adolescents, and adults, including autobiographical memory, direct and reflected self-appraisals, and social exclusion. While cortical midline structures of medial prefrontal cortex and medial posterior parietal cortex are consistently identified in neuroimaging studies considering personal identity from a primarily cognitive perspective (“who am I?”), additional regions are implicated by studies considering personal and social identity from a more socioemotional perspective (“what do others think about me, where do I fit in?”), especially in child or adolescent samples. The involvement of these additional regions (including tempo–parietal junction and posterior superior temporal sulcus, temporal poles, anterior insula, ventral striatum, anterior cingulate cortex, middle cingulate cortex, and ventrolateral prefrontal cortex) suggests mentalizing, emotion, and emotion regulation are central to self-development. In addition, these regions appear to function atypically during personal and social identity tasks in autism and depression, exhibiting a broad pattern of hypoactivation and hyperactivation, respectively.     

Altered brain functional connectivity in relation to perception of scrutiny in social anxiety disorder

Although the fear of being scrutinized by others in a social context is a key symptom in social anxiety disorder (SAD), the neural processes underlying the perception of scrutiny have not previously been studied by functional magnetic resonance imaging (fMRI). We used fMRI to map brain activation during a perception-of-scrutiny task in 20 SAD patients and 20 controls. A multi-dimensional analytic approach was used. Scrutiny perception was mediated by activation of the medial frontal cortex, insula-operculum region and cerebellum, and the additional recruitment of visual areas and the thalamus in patients. Between-group comparison demonstrated significantly enhanced brain activation in patients in the primary visual cortex and cerebellum. Functional connectivity mapping demonstrated an abnormal connectivity between regions underlying general arousal and attention. SAD patients showed significantly greater task-induced functional connectivity in the thalamo-cortical and the fronto-striatal circuits. A statistically significant increase in task-induced functional connectivity between the anterior cingulate cortex and scrutiny-perception-related regions was observed in the SAD patients, suggesting the existence of enhanced behavior-inhibitory control. The presented data indicate that scrutiny perception in SAD enhances brain activity in arousal-attention systems, suggesting that fMRI may be a useful tool to explore such a behavioral dimension.     

Overlapping and specific neural correlates for empathizing,affective mentalizing,and cognitive mentalizing: A coordinate‐based meta‐analytic study

While the discussion on the foundations of social understanding mainly revolves around the notions of empathy, affective mentalizing, and cognitive mentalizing, their degree of overlap versus specificity is still unclear. We took a meta‐analytic approach to unveil the neural bases of cognitive mentalizing, affective mentalizing, and empathy, both in healthy individuals and pathological conditions characterized by social deficits such as schizophrenia and autism. We observed partially overlapping networks for cognitive and affective mentalizing in the medial prefrontal, posterior cingulate, and lateral temporal cortex, while empathy mainly engaged fronto‐insular, somatosensory, and anterior cingulate cortex. Adjacent process‐specific regions in the posterior lateral temporal, ventrolateral, and dorsomedial prefrontal cortex might underpin a transition from abstract representations of cognitive mental states detached from sensory facets to emotionally‐charged representations of affective mental states. Altered mentalizing‐related activity involved distinct sectors of the posterior lateral temporal cortex in schizophrenia and autism, while only the latter group displayed abnormal empathy related activity in the amygdala. These data might inform the design of rehabilitative treatments for social cognitive deficits.     

Neurobiology of emotion perception I: The neural basis of normal emotion perception.

There is at present limited understanding of the neurobiological basis of the different processes underlying emotion perception. We have aimed to identify potential neural correlates of three processes suggested by appraisalist theories as important for emotion perception: 1) the identification of the emotional significance of a stimulus; 2) the production of an affective state in response to 1; and 3) the regulation of the affective state. In a critical review, we have examined findings from recent animal, human lesion, and functional neuroimaging studies. Findings from these studies indicate that these processes may be dependent upon the functioning of two neural systems: a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex, predominantly important for processes 1 and 2 and automatic regulation of emotional responses; and a dorsal system, including the hippocampus and dorsal regions of anterior cingulate gyrus and prefrontal cortex, predominantly important for process 3. We suggest that the extent to which a stimulus is identified as emotive and is associated with the production of an affective state may be dependent upon levels of activity within these two neural systems.     

Being with virtual others: Neural correlates of social interaction

To characterize the neural correlates of being personally involved in social interaction as opposed to being a passive observer of social interaction between others we performed an fMRI study in which participants were gazed at by virtual characters (ME) or observed them looking at someone else (OTHER). In dynamic animations virtual characters then showed socially relevant facial expressions as they would appear in greeting and approach situations (SOC) or arbitrary facial movements (ARB). Differential neural activity associated with ME>OTHER was located in anterior medial prefrontal cortex in contrast to the precuneus for OTHER>ME. Perception of socially relevant facial expressions (SOC>ARB) led to differentially increased neural activity in ventral medial prefrontal cortex. Perception of arbitrary facial movements (ARB>SOC) differentially activated the middle temporal gyrus. The results, thus, show that activation of medial prefrontal cortex underlies both the perception of social communication indicated by facial expressions and the feeling of personal involvement indicated by eye gaze. Our data also demonstrate that distinct regions of medial prefrontal cortex contribute differentially to social cognition: whereas the ventral medial prefrontal cortex is recruited during the analysis of social content as accessible in interactionally relevant mimic gestures, differential activation of a more dorsal part of medial prefrontal cortex subserves the detection of self-relevance and may thus establish an intersubjective context in which communicative signals are evaluated.     

The neurophysiological bases of emotion: An fMRI study of the affective circumplex using emotion-denoting words

Objective: We aimed to study the neural processing of emotion‐denoting words based on a circumplex model of affect, which posits that all emotions can be described as a linear combination of two neurophysiological dimensions, valence and arousal. Based on the circumplex model, we predicted a linear relationship between neural activity and incremental changes in these two affective dimensions. Methods: Using functional magnetic resonance imaging, we assessed in 10 subjects the correlations of BOLD (blood oxygen level dependent) signal with ratings of valence and arousal during the presentation of emotion‐denoting words. Results: Valence ratings correlated positively with neural activity in the left insular cortex and inversely with neural activity in the right dorsolateral prefrontal and precuneus cortices. The absolute value of valence ratings (reflecting the positive and negative extremes of valence) correlated positively with neural activity in the left dorsolateral and medial prefrontal cortex (PFC), dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal PFC, and inversely with neural activity in the left medial temporal cortex and right amygdala. Arousal ratings and neural activity correlated positively in the left parahippocampus and dorsal anterior cingulate cortex, and inversely in the left dorsolateral PFC and dorsal cerebellum. Conclusion: We found evidence for two neural networks subserving the affective dimensions of valence and arousal. These findings clarify inconsistencies from prior imaging studies of affect by suggesting that two underlying neurophysiological systems, valence and arousal, may subserve the processing of affective stimuli, consistent with the circumplex model of affect. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

The neuroscience of group membership

The present study aimed to uncover the neural activity associated with specific in-group and out-group word related stimuli, to examine the neuroanatomical basis of group membership concept representation, and investigate to what extent neural processes represent 'in-group' differently from 'out-group'. Participants' brain activity was measured with functional MRI while they had to categorize social, in-group and out-group words and non-social, living and non-living words. The results showed that a network of brain regions previously identified as the 'social brain', including the cortical midline structures, tempo-parietal junction and the anterior temporal gyrus showed enhanced activation for social words versus non-social words. Crucially, the processing of in-group words compared to the out-group words activated a specific network including the ventral medial prefrontal and anterior and dorsal cingulate cortex. These regions correspond to a neural network previously identified as the 'personal self'. Our results suggest that the 'social' and 'personal self' are closely related and that we derive our self image from the groups we belong to.     

A response‐locking protocol to boost sensitivity for fMRI‐based neurochronometry

The timeline of brain‐wide neural activity relative to a behavioral event is crucial when decoding the neural implementation of a cognitive process. Yet, fMRI assesses neural processes indirectly via delayed and regionally variable hemodynamics. This method‐inherent temporal distortion impacts the interpretation of behavior‐linked neural timing. Here we describe a novel behavioral protocol that aims at disentangling the BOLD dynamics of the pre‐ and post‐response periods in response time tasks. We tested this response‐locking protocol in a perceptual decision‐making (random dot) task. Increasing perceptual difficulty produced expected activity increases over a broad network involving the lateral/medial prefrontal cortex and the anterior insula. However, response‐locking revealed a previously unreported functional dissociation within this network. preSMA and anterior premotor cortex (prePMV) showed post‐response activity modulations while anterior insula and anterior cingulate cortex did not. Furthermore, post‐response BOLD activity at preSMA showed a modulation in timing but not amplitude while this pattern was reversed at prePMV. These timeline dissociations with response‐locking thus revealed three functionally distinct sub‐networks in what was seemingly one shared distributed network modulated by perceptual difficulty. These findings suggest that our novel response‐locked protocol could boost the timing‐related sensitivity of fMRI.     

The effect of meditation on brain structure: cortical thickness mapping and diffusion tensor imaging

A convergent line of neuroscientific evidence suggests that meditation alters the functional and structural plasticity of distributed neural processes underlying attention and emotion. The purpose of this study was to examine the brain structural differences between a well-matched sample of long-term meditators and controls. We employed whole-brain cortical thickness analysis based on magnetic resonance imaging, and diffusion tensor imaging to quantify white matter integrity in the brains of 46 experienced meditators compared with 46 matched meditation-naïve volunteers. Meditators, compared with controls, showed significantly greater cortical thickness in the anterior regions of the brain, located in frontal and temporal areas, including the medial prefrontal cortex, superior frontal cortex, temporal pole and the middle and interior temporal cortices. Significantly thinner cortical thickness was found in the posterior regions of the brain, located in the parietal and occipital areas, including the postcentral cortex, inferior parietal cortex, middle occipital cortex and posterior cingulate cortex. Moreover, in the region adjacent to the medial prefrontal cortex, both higher fractional anisotropy values and greater cortical thickness were observed. Our findings suggest that long-term meditators have structural differences in both gray and white matter.     

Gender differences in the functional neuroanatomy of emotional episodic autobiographical memory

Autobiographical memory is based on interactions between episodic memory contents, associated emotions, and a sense of self-continuity along the time axis of one's life. The functional neuroanatomy subserving autobiographical memory is known to include prefrontal, medial and lateral temporal, as well as retrosplenial brain areas; however, whether gender differences exist in neural correlates of autobiographical memory remains to be clarified. We reanalyzed data from a previous functional magnetic resonance imaging (fMRI) experiment to investigate gender-related differences in the neural bases of autobiographical memories with differential remoteness and emotional valence. On the behavioral level, there were no significant gender differences in memory performance or emotional intensity of memories. Activations common to males and females during autobiographical memory retrieval were observed in a bilateral network of brain areas comprising medial and lateral temporal regions, including hippocampal and parahippocampal structures, posterior cingulate, as well as prefrontal cortex. In males (relative to females), all types of autobiographical memories investigated were associated with differential activation of the left parahippocampal gyrus. By contrast, right dorsolateral prefrontal cortex was activated differentially by females. In addition, the right insula was activated differentially in females during remote and negative memory retrieval. The data show gender-related differential neural activations within the network subserving autobiographical memory in both genders. We suggest that the differential activations may reflect gender-specific cognitive strategies during access to autobiographical memories that do not necessarily affect the behavioral level of memory performance and emotionality.     

Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey

The origin and termination of axonal connections between the orbital and medial prefrontal cortex (OMPFC) and the temporal, insular, and opercular cortex have been analyzed with anterograde and retrograde axonal tracers, injected in the OMPFC or temporal cortex. The results show that there are two distinct, complementary, and reciprocal neural systems, related to the previously defined "orbital" and "medial" prefrontal networks. The orbital prefrontal network, which includes areas in the central and lateral part of the orbital cortex, is connected with vision-related areas in the inferior temporal cortex (especially area TEav) and the fundus and ventral bank of the superior temporal sulcus (STSf/v), and with somatic sensory-related areas in the frontal operculum (OPf) and dysgranular insular area (Id). No connections were found between the orbital network and auditory areas. The orbital network is also connected with taste and olfactory cortical areas and the perirhinal cortex and appears to be involved in assessment of sensory objects, especially food. The medial prefrontal network includes areas on the medial surface of the frontal lobe, medial orbital areas, and two caudolateral orbital areas. It is connected with the rostral superior temporal gyrus (STGr) and the dorsal bank of the superior temporal sulcus (STSd). This region is rostral to the auditory parabelt areas, and there are only relatively light connections between the auditory areas and the medial network. This system, which is also connected with the entorhinal, parahippocampal, and cingulate/retrosplenial cortex, may be involved in emotion and other self-referential processes.     

A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia

Functional neuroimaging studies suggest that a lateral network in the brain is associated with the sensory aspects of pain perception while a medial network is associated with affective aspects. The highest concentration of opioid receptors is in the medial network. There is significant evidence that endogenous opioids are central to the experience of pain and analgesia. We applied an integrative multimodal imaging approach during acupuncture. We found functional magnetic resonance imaging signal changes in the orbitofrontal cortex, insula, and pons and [11C]diprenorphine positron emission tomography signal changes in the orbitofrontal cortex, medial prefrontal cortex, insula, thalamus, and anterior cingulate cortex. These findings include brain regions within both the lateral and medial pain networks.     

Ventromedial prefrontal activity correlates with depressed mood in adolescent children

In adults, the medial prefrontal cortex and anterior cingulate gyrus are preferentially activated during emotion-related processes, including normal sadness and pathological depression. It is not clear, however, whether similar regional activity is also characteristic of depressed mood during adolescence. We correlated whole brain activity during a fear face perception task with scores on the Beck Depression Inventory in 16 adolescents undergoing functional magnetic resonance imaging. After controlling for age, depressed mood scores correlated with increased activity within the ventromedial prefrontal cortex and rostral anterior cingulate gyrus, consistent with findings previously reported for sadness and depression in adults, suggesting that the neural substrates of depressed mood are established early in life and remain relatively consistent across development into adulthood.     

Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates

The prefrontal cortex has been implicated in a variety of cognitive and executive processes, including working memory, decision-making, inhibitory response control, attentional set-shifting and the temporal integration of voluntary behaviour. This article reviews current progress in our understanding of the rodent prefrontal cortex, especially evidence for functional divergence of the anatomically distinct sub-regions of the rat prefrontal cortex. Recent findings suggest clear distinctions between the dorsal (precentral and anterior cingulate) and ventral (prelimbic, infralimbic and medial orbital) sub-divisions of the medial prefrontal cortex, and between the orbitofrontal cortex (ventral orbital, ventrolateral orbital, dorsal and ventral agranular cortices) and the adjacent medial wall of the prefrontal cortex. The dorso-medial prefrontal cortex is implicated in memory for motor responses, including response selection, and the temporal processing of information. Ventral regions of the medial prefrontal cortex are implicated in interrelated 'supervisory' attentional functions, including attention to stimulus features and task contingencies (or action-outcome rules), attentional set-shifting, and behavioural flexibility. The orbitofrontal cortex is implicated in lower-order discriminations, including reversal of stimulus-reward associations (reversal learning), and choice involving delayed reinforcement. It is anticipated that a greater understanding of the prefrontal cortex will come from using tasks that load specific cognitive and executive processes, in parallel with discovering new ways of manipulating the different sub-regions and neuromodulatory systems of the prefrontal cortex.     

Brain network dynamics during error commission

Previous studies suggest that the anterior cingulate and other prefrontal brain regions might form a functionally-integrated error detection network in the human brain. This study examined whole brain functional connectivity to both correct and incorrect button presses using independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data collected from 25 adolescent and 25 adult healthy participants (ages 11-37) performing a visual Go/No-Go task. Correct responses engaged a network comprising left lateral prefrontal cortex, left postcentral gyrus/inferior parietal lobule, striatum, and left cerebellum. In contrast, a similar network was uniquely engaged during errors, but this network was not integrated with activity in regions believed to be engaged for higher-order cognitive control over behavior. A medial/dorsolateral prefrontal-parietal neural network responded to all No-Go stimuli, but with significantly greater activity to errors. ICA analyses also identified a third error-related circuit comprised of anterior temporal lobe, limbic, and pregenual cingulate cortices, possibly representing an affective response to errors. There were developmental differences in error-processing activity within many of these neural circuits, typically reflecting greater hemodynamic activation in adults. These findings characterize the spatial structure of neural networks underlying error commission and identify neurobiological differences between adolescents and adults.     

The neural basis of mood-congruent processing biases in depression

BACKGROUND: Mood-congruent processing biases are among the most robust research findings in neuropsychological studies of depression. Depressed patients show preferential processing of negatively toned stimuli across a range of cognitive tasks. The present study aimed to determine whether these behavioral abnormalities are associated with specific neural substrates. METHODS: Ten depressed patients and 11 healthy control subjects underwent scanning during performance of an emotional go/no-go task using functional magnetic resonance imaging. The task allowed comparison among neural response to happy, sad, and neutral words, in the context of these words as targets (ie, stimuli to which subjects were required to make a motor response) or distractors (ie, stimuli to which the motor response was withheld). RESULTS: Depressed patients showed attenuated neural responses to emotional relative to neutral targets in ventral cingulate and posterior orbitofrontal cortices. However, patients showed elevated responses specific to sad targets in rostral anterior cingulate extending to anterior medial prefrontal cortex. Unlike controls, patients showed differential neural response to emotional, particularly sad, distractors in the lateral orbitofrontal cortex. CONCLUSIONS: These findings suggest a distinct neural substrate for mood-congruent processing biases in performance. The medial and orbital prefrontal regions may play a key role in mediating the interaction between mood and cognition in affective disorder.     

Differentiating between self and others: an ALE meta-analysis of fMRI studies of self-recognition and theory of mind

The perception of self and others is a key aspect of social cognition. In order to investigate the neurobiological basis of this distinction we reviewed two classes of task that study self-awareness and awareness of others (theory of mind, ToM). A reliable task to measure self-awareness is the recognition of one’s own face in contrast to the recognition of others’ faces. False-belief tasks are widely used to identify neural correlates of ToM as a measure of awareness of others. We performed an activation likelihood estimation meta-analysis, using the fMRI literature on self-face recognition and false-belief tasks. The brain areas involved in performing false-belief tasks were the medial prefrontal cortex (MPFC), bilateral temporo-parietal junction, precuneus, and the bilateral middle temporal gyrus. Distinct self-face recognition regions were the right superior temporal gyrus, the right parahippocampal gyrus, the right inferior frontal gyrus/anterior cingulate cortex, and the left inferior parietal lobe. Overlapping brain areas were the superior temporal gyrus, and the more ventral parts of the MPFC. We confirmed that self-recognition in contrast to recognition of others’ faces, and awareness of others involves a network that consists of separate, distinct neural pathways, but also includes overlapping regions of higher order prefrontal cortex where these processes may be combined. Insights derived from the neurobiology of disorders such as autism and schizophrenia are consistent with this notion.     

Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity

Neuroimaging studies of painful stimuli in humans have identified a network of brain regions that is more extensive than identified previously in electrophysiological and anatomical studies of nociceptive pathways. This extensive network has been described as a pain matrix of brain regions that mediate the many interrelated aspects of conscious processing of nociceptive input such as perception, evaluation, affective response, and emotional memory. We used functional magnetic resonance imaging in healthy human subjects to distinguish brain regions required for pain sensory encoding from those required for cognitive evaluation of pain intensity. The results suggest that conscious cognitive evaluation of pain intensity in the absence of any sensory stimulation activates a network that includes bilateral anterior insular cortex/frontal operculum, dorsal lateral prefrontal cortex, bilateral medial prefrontal cortex/anterior cingulate cortex, right superior parietal cortex, inferior parietal lobule, orbital prefrontal cortex, and left occipital cortex. Increased activity common to both encoding and evaluation was observed in bilateral anterior insula/frontal operculum and medial prefrontal cortex/anterior cingulate cortex. We hypothesize that these two regions play a crucial role in bridging the encoding of pain sensation and the cognitive processing of sensory input.