Cognitive modulation of pain-related brain responses depends on behavioral strategy

Interactions of pain and cognition have been studied in humans and animals previously, but the relationship between such behavioral interactions and brain activity is unknown. We aimed to show using functional MRI (fMRI) how a cognitively demanding task (Stroop) modulates pain-related brain activations and conversely, how pain modulates attention-related activity. Reaction time data indicated two types of pain responders: subjects in the A group had a faster Stroop reaction time when pain was concomitant to the attention task, while those in the P group had a slower Stroop performance during painful stimulation. fMRI data obtained during Stroop performance with and without noxious stimulation were subjected to region of interest analyses. We first tested whether brain activity during painful median nerve stimulation was modulated by cognitive load. We next tested whether brain activity during the high conflict cognitive task was modulated by pain. Pain-related activity in three regions, primary (S1), and secondary (S2) somatosensory cortices, and anterior insula, was attenuated by cognitive engagement, but this effect was specific to the A group. Pain-related activations in the caudal and rostral anterior cingulate cortex (ACC) and ventroposterior thalamus were not modulated by cognitive load. None of the areas showing attention-related responses, including bilateral dorsolateral prefrontal and posterior parietal cortices, were modulated by pain. These findings suggest that cortical regions associated with pain can be modulated by cognitive strategies. Furthermore, the distinction of behavioral subgroups may relate to cognitive coping strategies taken by patients with chronic pain.     

Acute tryptophan depletion improves performance and modulates the BOLD response during a Stroop task in healthy females

To gain more insight into the effect of low brain serotonin (5-HT) on brain activation related to conflict, the present study examined the effect of acute tryptophan depletion (ATD) on performance and the blood oxygen level dependent (BOLD) response during a combined cognitive and emotional Stroop task. Fifteen healthy female volunteers were tested during a placebo and tryptophan depletion session in an event-related fMRI design. ATD improved performance during Stroop interference. Two effects of ATD on the BOLD response were found. Firstly, ATD increased the BOLD response in the anterior cingulate cortex (ACC) (BA 32) when incongruent color words were compared with congruent color words in the first Stroop block the participants performed. Secondly, ATD increased the BOLD response in the left precuneus (BA 31) and cuneus (BA 18) during congruent color words. ATD did not affect the BOLD response accompanying emotional stimuli. However, we showed that ATD increased the interference of negative words on color naming. This finding was explained in terms of an emotional processing bias in favor of negative words, which leads to stronger interference of these words. In line with previous studies, the present study showed that a temporary reduction of 5-HT improved Stroop performance and changed the underlying brain activation pattern in healthy female participants. Moreover, we replicated our previous finding that ATD modulated the BOLD response in the dorsomedial prefrontal cortex during tasks that require cognitive control.     

Sex differences in emotion-related cognitive processes in irritable bowel syndrome and healthy control subjects

Greater responsiveness of emotional arousal circuits in relation to delivered visceral pain has been implicated as underlying central pain amplification in irritable bowel syndrome (IBS), with female subjects showing greater responses than male subjects. Functional magnetic resonance imaging was used to measure neural responses to an emotion recognition paradigm, using faces expressing negative emotions (fear and anger). Sex and disease differences in the connectivity of affective and modulatory cortical circuits were studied in 47 IBS (27 premenopausal female subjects) and 67 healthy control subjects (HCs; 38 premenopausal female subjects). Male subjects (IBS + HC) showed greater overall brain responses to stimuli than female subjects in prefrontal cortex, insula, and amygdala. Effective connectivity analyses identified major sex- and disease-related differences in the functioning of brain networks related to prefrontal regions, cingulate, insula, and amygdala. Male subjects had stronger connectivity between anterior cingulate subregions, amygdala, and insula, whereas female subjects had stronger connectivity to and from the prefrontal modulatory regions (medial/dorsolateral cortex). Male IBS subjects demonstrate greater engagement of cortical and affect-related brain circuitry compared to male control subjects and female subjects, when viewing faces depicting emotions previously shown to elicit greater behavioral and brain responses in male subjects.     

Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI

Neuroimagingstudies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have begun to describe the functional neuroanatomy of emotion. Taken separately, specific studies vary in task dimensions and in type(s) of emotion studied and are limited by statistical power and sensitivity. By examining findings across studies, we sought to determine if common or segregated patterns of activations exist across various emotional tasks. We reviewed 55 PET and fMRI activation studies (yielding 761 individual peaks) which investigated emotion in healthy subjects. Peak activation coordinates were transformed into a standard space and plotted onto canonical 3-D brain renderings. We divided the brain into 20 nonoverlapping regions, and characterized each region by its responsiveness across individual emotions (positive, negative, happiness, fear, anger, sadness, disgust), to different induction methods (visual, auditory, recall/imagery), and in emotional tasks with and without cognitive demand. Our review yielded the following summary observations: (1) The medial prefrontal cortex had a general role in emotional processing; (2) fear specifically engaged the amygdala; (3) sadness was associated with activity in the subcallosal cingulate; (4) emotional induction by visual stimuli activated the occipital cortex and the amygdala; (5) induction by emotional recall/imagery recruited the anterior cingulate and insula; (6) emotional tasks with cognitive demand also involved the anterior cingulate and insula. This review provides a critical comparison of findings across individual studies and suggests that separate brain regions are involved in different aspects of emotion.     

Pain modulates cerebral activity during cognitive performance

The present study investigates how pain modulates brain activity during the performance of a semantic cognitive task. Based on previous observations, we hypothesized that a simultaneous painful stimulus will induce an activation increase in brain regions engaged in the cognitive task. High-field BOLD-fMRI experiments were conducted on 12 young healthy subjects, using a 2 x 2 factorial design. Painful stimuli were induced by thermal hot stimulation (46-49 degrees C) on the palmar surface of the hand, using a contact thermode. Cognitive tasks consisted of either word generation (category fluency) or word repetition. Brain activity owing to the semantic tasks in the group was highly consistent with previous neuroimaging studies. When the painful stimulus was added to the cognitive task, activity in brain regions involved in semantic cognition, such as Broca's area, was increased (P < 0.01). Pain also modulated activity in brain areas not directly engaged in cognition. A positive modulation effect was observed in the midcingulate and the dorsomedial prefrontal cortex (P < 0.05). A negative modulation effect was observed in perigenual cingulate cortex, insula, and medial thalamus (P < 0.05).     

Functional Brain Imaging and the Induction of Traumatic Recall: A Cross-Correlational Review Between Neuroimaging And Hypnosis

The behavioral and psychophysiological alterations during recall in patients with trauma disorders often resemble phenomena that are seen in hypnosis. In studies of emotional recall as well as in neuroimaging studies of hypnotic processes similar brain structures are involved: thalamus, hippocampus, amygdala, medial prefrontal cortex, anterior cingulate cortex. This paper focuses on cross-correlations in traumatic recall and hypnotic responses and reviews correlations between the involvement of brain structures in traumatic recall and processes that are involved in hypnotic responsiveness. To further improve uniformity of results of brain imaging specifically for traumatic recall studies, attention is needed for standardization of hypnotic variables, isolation of the emotional process of interest (state), and assessment of trait-related differences.     

Functional brain imaging and the induction of traumatic recall: a cross-correlational review between neuroimaging and hypnosis

The behavioral and psychophysiological alterations during recall in patients with trauma disorders often resemble phenomena that are seen in hypnosis. In studies of emotional recall as well as in neuroimaging studies of hypnotic processes similar brain structures are involved: thalamus, hippocampus, amygdala, medial prefrontal cortex, anterior cingulate cortex. This paper focuses on cross-correlations in traumatic recall and hypnotic responses and reviews correlations between the involvement of brain structures in traumatic recall and processes that are involved in hypnotic responsiveness. To further improve uniformity of results of brain imaging specifically for traumatic recall studies, attention is needed for standardization of hypnotic variables, isolation of the emotional process of interest (state),and assessment of trait-related differences.     

Attention to aversive emotion and specific activation of the right insula and right somatosensory cortex

The evaluation of emotional stimuli is based on different levels of information processing, ranging from rather automatic processes to focused attention to the emotional relevance of stimuli. The role of specific brain areas for these processes is a matter of debate. In this event-related fMRI study, we varied the information processing mode of participants exposed to aversive and neutral pictures. Based on four different tasks, participants' attentional focus onto the emotional quality of the stimuli and the own emotional involvement was increased systematically across tasks. Regardless of task, stronger activation to threatening vs. neutral pictures was found in several regions such as the amygdala, anterior insula, anterior cingulate cortex, primary somatosensory cortex and medial prefrontal cortex. However, there was a parametric increase of activation with increasing attention to one's own emotion specifically in the right posterior insula and right primary and secondary somatosensory cortex, i.e. in areas implicated in self-awareness of a person's own body. These findings are in accordance with theories suggesting a crucial role of the perception of bodily states for emotional experiences.     

Disentangling linear and nonlinear brain responses to evoked deep tissue pain

Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional magnetic resonance imaging, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region's functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least 5 different, regionally specific activity profiles in the brain. Linearly increasing (eg, primary somatosensory/motor cortex, insulae) and intensity-independent (eg, secondary somatosensory cortex) activation was noted in traditional pain-processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (eg, posterior cingulate cortex), linearly decreasing (eg, contralateral inferior parietal lobule), and quadratic (U-shaped; eg, medial prefrontal cortex). The latter observation suggests that: (1) different DMN subregions exhibit functional heterogeneity and (2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing.     

Fate of unattended fearful faces in the amygdala is determined by both attentional resources and cognitive modulation

The evidence for amygdala processing of emotional items outside the focus of attention is mixed. We hypothesized that differences in attentional demands may, at least in part, explain prior discrepancies. In the present study, attention was manipulated by parametrically varying the difficulty of a central task, allowing us to compare responses evoked by unattended emotion-laden faces while the attentional load of a central task was varied. Reduced responses to unattended emotional stimuli may also reflect an active suppression of amygdala responses during difficult non-emotional tasks (cognitive modulation). To explicitly assess cognitive modulation, an experimental condition was used in which subjects performed the central task without the presence of irrelevant emotional stimuli. Our findings revealed that amygdala responses were modulated by the focus of attention. Stronger responses were evoked during a sex task (when faces were attended) relative to a bar-orientation task (when faces were unattended). Critically, a valence effect was observed in the right amygdala during low attentional demand conditions, but not during medium or high demand conditions. Moreover, performing a difficult non-emotional task alone was associated with signal decreases in a network of brain regions, including the amygdala. Such robust decreases demonstrate that cognitive modulation comprises a powerful factor in determining amygdala responses. Collectively, our findings reveal that both attentional resources and cognitive modulation govern the fate of unattended fearful faces in the amygdala.     

fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis

Functional magnetic resonance imaging (fMRI) data on motor function have shown adaptive functional changes related to brain injury in multiple sclerosis (MS). We investigated whether patients with MS have altered fMRI activation patterns during attention and memory tasks, and whether functional changes in the brain correlate with the extent of overall tissue damage on conventional MRI. Twenty-two right-handed patients with relapsing-remitting MS (RRMS) and no or only mild deficits at neuropsychological testing and 22 matched healthy subjects were scanned during the Paced Auditory Serial Addition Test (PASAT) and a recall task. fMRI data were analyzed using Statistical Parametric Mapping (SPM99). The relation between fMRI changes during both tasks and T2 lesion load was investigated. During both tasks, patients exhibited significantly greater brain activation than controls and recruited additional brain areas. Task-related functional changes were more significant in patients whose performance matched that of controls than in patients with a lower performance. During the PASAT, brain functional changes involved the right supplementary motor area and cingulate, the bilateral prefrontal, temporal and parietal areas, whereas during the recall task they involved the prefrontal and temporal cortex and basal ganglia bilaterally, and the left thalamus. In patients, activation in specific brain areas during performance of both tasks positively correlated with T2 brain lesions. Patients with RRMS exhibit altered patterns of activation during tasks exploring sustained attention, information processing and memory. During these tasks, fMRI activity is greater in patients with better cognitive function than in those with lower cognitive function. Functional changes in specific brain areas increase with increasing tissue damage suggesting that they may also represent adaptive mechanisms that reflect underlying neural disorganization or disinhibition, possibly associated with MS.     

Contribution of chronic pain and neuroticism to abnormal forebrain gray matter in patients with temporomandibular disorder

Cortical plasticity is thought to occur following continuous barrage of nociceptive afferent signals to the brain. Hence, chronic pain is presumed to induce anatomical and physiological changes in the brain over time. Inherent factors, some pre-dating the onset of chronic pain, may also contribute to brain abnormalities present in patients. In this study we used structural MRI to examine whether patients with chronic temporomandibular (TMD) pain have abnormalities in gray matter (GM) within brain areas implicated in pain, modulation and sensorimotor function. We found that patients with TMD have cortical thickening in the primary somatosensory cortex (S1), frontal polar and the ventrolateral prefrontal cortex (PFC). These findings provide a structural basis for previous findings of TMD pain and cognitive sluggishness in TMD. We then examined the contribution of TMD characteristics to GM abnormalities. We found that 1) GM in the sensory thalamus positively correlated to TMD duration, 2) cortical thickness in the primary motor (M1) and the anterior mid-cingulate cortices (aMCC) were negatively correlated to pain intensity, and 3) pain unpleasantness was negatively correlated to cortical thickness in the orbitofrontal cortex (OFC). These findings suggest that an individual's TMD pain history contributes to GM in the brain. Lastly, we examined the contribution of a potential pre-existing vulnerability due to neuroticism. In the TMD patients, we found that there was an abnormal positive correlation between neuroticism and OFC thickness, in contrast to the negative correlation found in the healthy controls. Therefore, neuroticism may contribute to TMD pathophysiology. In sum, our data suggest that GM in the brain of patients with chronic TMD pain can be shaped by both personality and pain characteristics.     

The responsive amygdala: Treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.     

Sex differences in functional brain activation during noxious visceral stimulation in rats

Studies in healthy human subjects and patients with irritable bowel syndrome suggest sex differences in cerebral nociceptive processing. Here we examine sex differences in functional brain activation in the rat during colorectal distention (CRD), a preclinical model of acute visceral pain. [¹⁴C]-iodoantipyrine was injected intravenously in awake, non-restrained female rats during 60- or 0-mmHg CRD while electromyographic abdominal activity (EMG) and pain behavior were recorded. Regional cerebral blood flow-related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of three-dimensionally reconstructed brains. Sex differences were addressed by comparing the current data with our previously published data collected from male rats. While sex differences in EMG and pain scores were modest, significant differences were noted in functional brain activation. Females showed widespread changes in limbic (amygdala, hypothalamus) and paralimbic structures (ventral striatum, nucleus accumbens, raphe), while males demonstrated broad cortical changes. Sex differences were apparent in the homeostatic afferent network (parabrachial nucleus, thalamus, insular and dorsal anterior cingulate cortices), in an emotional–arousal network (amygdala, locus coeruleus complex), and in cortical areas modulating these networks (prefrontal cortex). Greater activation of the ventromedial prefrontal cortex and broader limbic/paralimbic changes in females suggest greater engagement of affective mechanisms during visceral pain. Greater cortical activation in males is consistent with the concept of greater cortical inhibitory effects on limbic structures in males, which may relate to differences in attentional and cognitive attribution to visceral stimuli. These findings show remarkable similarities to reported sex differences in brain responses to visceral stimuli in humans.     

阿尔茨海默病情绪记忆相关脑灰质体积改变

目的 探讨阿尔茨海默病（AD）患者情绪记忆改变与灰质容积变化的相关性。方法 对25例AD患者（AD组）及25名正常对照（NC组）进行情绪记忆行为学检测,获取行为学成绩。采用MRI 3D结构相用VBM8和SPM8软件处理,得到相对灰质体积改变的脑区,做为ROI,采用REST软件提值,并与行为学成绩行相关性分析。结果 AD组受试对负性与中性图片反应正确率差异无统计学意义（P=0.56）。与NC组比较,AD组灰质体积缩小的脑区包括双侧颞下回、颞中回、海马、海马旁回、杏仁核、梭状回、楔前叶、后扣带回、左侧脑岛、右侧舌回、左侧额叶眶内侧回、左侧内侧前额叶、右侧额下回岛盖部、左侧中央前回及右侧丘脑（FWE校正,P<0.025）;其中双侧杏仁核、双侧后扣带回、左侧海马、左侧脑岛、左侧颞下回、左侧颞中回、左侧额叶眶内侧回、右侧额下回岛盖部、左侧内侧前额叶的相对灰质体积与情绪图片记忆反应正确率呈正相关（P均<0.05）。结论 AD患者负性图片情绪增强效应损害,可能与杏仁核和海马等情绪记忆系统脑区萎缩有关。     

The effect of appraisal level on processing of emotional prosody in meaningless speech

In visual perception of emotional stimuli, low- and high-level appraisal processes have been found to engage different neural structures. Beyond emotional facial expression, emotional prosody is an important auditory cue for social interaction. Neuroimaging studies have proposed a network for emotional prosody processing that involves a right temporal input region and explicit evaluation in bilateral prefrontal areas. However, the comparison of different appraisal levels has so far relied upon using linguistic instructions during low-level processing, which might confound effects of processing level and linguistic task. In order to circumvent this problem, we examined processing of emotional prosody in meaningless speech during gender labelling (implicit, low-level appraisal) and emotion labelling (explicit, high-level appraisal). While bilateral amygdala, left superior temporal sulcus and right parietal areas showed stronger blood oxygen level-dependent (BOLD) responses during implicit processing, areas with stronger BOLD responses during explicit processing included the left inferior frontal gyrus, bilateral parietal, anterior cingulate and supplemental motor cortex. Emotional versus neutral prosody evoked BOLD responses in right superior temporal gyrus, bilateral anterior cingulate, left inferior frontal gyrus, insula and bilateral putamen. Basal ganglia and right anterior cingulate responses to emotional versus neutral prosody were particularly pronounced during explicit processing. These results are in line with an amygdala-prefrontal-cingulate network controlling different appraisal levels, and suggest a specific role of the left inferior frontal gyrus in explicit evaluation of emotional prosody. In addition to brain areas commonly related to prosody processing, our results suggest specific functions of anterior cingulate and basal ganglia in detecting emotional prosody, particularly when explicit identification is necessary.     

Neural Correlates of Three Neurocognitive Intervention Strategies: A Preliminary Step Towards Personalized Treatment for Psychological Disorders

Brain-based behavioral interventions targeting specific neurocognitive mechanisms show initial promise in the treatment of emotional disorders, but personalization of such approaches will be facilitated if brain targets are empirically established. As a preliminary step, we conducted a proof-of-concept study to test whether particular emotion regulatory neural circuitry can be differentially targeted by specific neurocognitive tasks, and whether these tasks effectively inhibit amygdala activity. Eleven healthy individuals underwent an idiographic sadness and guilt induction. Brain response was measured via fMRI during 4 subsequent emotion regulation conditions: fixation, cognitive reappraisal (selected to target the ventrolateral prefrontal cortex), working memory practice (selected to target the dorsolateral prefrontal cortex), and visual distraction (Tetris; selected to target occipital cortex). In whole-brain comparisons to fixation, hypotheses were upheld. Reappraisal uniquely activated left venrolateral prefrontal cortex, working memory practice uniquely activated left dorsolateral prefrontal cortex, and Tetris uniquely activated bilateral occipitoparietal cortex, activations that were largely robust at the single-subject level. All tasks inhibited amygdala activity relative to fixation. Data support examining whether repeated exposure to these tasks in psychiatric patients affects neural abnormalities implicated in emotional disorders. Ideally, psychiatric treatment will be accelerated by matching specific treatments to patients with specific neural profiles.     

Hypervigilance and attentional fixedness in chronic musculoskeletal pain: consistency of findings across modified stroop and dot-probe tasks.

Results from modified Stroop and dot-probe tasks have provided mixed evidence regarding attentional biases for sensory and affect pain stimuli in chronic pain patients. No studies have compared the same groups of chronic pain and healthy control participants on both tasks. We tested 36 patients with chronic musculoskeletal pain and 29 healthy control subjects on the modified Stroop and dot-probe tasks. Stimuli comprised affect pain, sensory pain, physical catastrophe, and neutral words. There was no evidence to suggest differential processing of threat cues by patients and control subjects on the modified Stroop task. All participants did, however, show differential processing of affect pain words. This was evident on both masked and unmasked presentation formats. There were no significant interactions between clinical status and threat word type observed for any of the indices of selective attention derived from the dot-probe task, but all participants had difficulty disengaging attention from affective pain and health catastrophe words. Findings were not influenced by individual differences in mood, anxiety, or fear of pain. Correlational analyses of the standard (unmasked) Stroop interference index and dot-probe indices of selective attention revealed a consistent lack of significant association, suggesting that the 2 tasks might be measuring different phenomena. Taken together, these findings provide evidence that chronic pain patients and healthy control participants do not differ in the way they attend to threatening linguistic stimuli. PERSPECTIVE: Some patients with chronic pain might have trouble paying attention to anything other than the affective components of pain and associated catastrophic health consequences. Interventions that specifically target this attentional fixedness might facilitate shifting attention to other targets and thereby reduce pain-specific anxiety and fear.     

Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers

Studies have revealed abnormalities in resting-state functional connectivity in those with major depressive disorder specifically in areas such as the dorsal anterior cingulate, thalamus, amygdala, the pallidostriatum and subgenual cingulate. However, the effect of antidepressant medications on human brain function is less clear and the effect of these drugs on resting-state functional connectivity is unknown. Forty volunteers matched for age and gender with no previous psychiatric history received either citalopram (SSRI; selective serotonergic reuptake inhibitor), reboxetine (SNRI; selective noradrenergic reuptake inhibitor) or placebo for 7 days in a double-blind design. Using resting-state functional magnetic resonance imaging and seed based connectivity analysis we selected the right nucleus accumbens, the right amygdala, the subgenual cingulate and the dorsal medial prefrontal cortex as seed regions. Mood and subjective experience were also measured before and after drug administration using self-report scales. Despite no differences in mood across the three groups, we found reduced connectivity between the amygdala and the ventral medial prefrontal cortex in the citalopram group and the amygdala and the orbitofrontal cortex for the reboxetine group. We also found reduced striatal-orbitofrontal cortex connectivity in the reboxetine group. These data suggest that antidepressant medications can decrease resting-state functional connectivity independent of mood change and in areas known to mediate reward and emotional processing in the brain. We conclude that hypothesis-driven seed based analysis of resting-state fMRI supports the proposition that antidepressant medications might work by normalising the elevated resting-state functional connectivity seen in depressed patients.     

Sex differences in brain activity during aversive visceral stimulation and its expectation in patients with chronic abdominal pain: a network analysis

Differences in brain responses to aversive visceral stimuli may underlie previously reported sex differences in symptoms as well as perceptual and emotional responses to such stimuli in patients with irritable bowel syndrome (IBS). The goal of the current study was to identify brain networks activated by expected and delivered aversive visceral stimuli in male and female patients with chronic abdominal pain, and to test for sex differences in the effective connectivity of the circuitry comprising these networks. Network analysis was applied to assess the brain response of 46 IBS patients (22 men and 24 women) recorded using [15O] water positron emission tomography during rest/baseline and expected and delivered aversive rectal distension. Functional connectivity results from partial least squares analyses provided support for the hypothesized involvement of 3 networks corresponding to: 1) visceral afferent information processing (thalamus, insula and dorsal anterior cingulate cortex, orbital frontal cortex), 2) emotional-arousal (amygdala, rostral and subgenual cingulate regions, and locus coeruleus complex) and 3) cortical modulation (frontal and parietal cortices). Effective connectivity results obtained via structural equation modeling indicated that sex-related differences in brain response are largely due to alterations in the effective connectivity of emotional-arousal circuitry rather than visceral afferent processing circuits. Sex differences in the cortico-limbic circuitry involved in emotional-arousal, pain facilitation and autonomic responses may underlie the observed differences in symptoms, and in perceptual and emotional responses to aversive visceral stimuli.