Oren Contreras-Rodríguez

Task-Induced Deactivation from Rest Extends beyond the Default Mode Brain Network

Activity decreases, or deactivations, of midline and parietal cortical brain regions are routinely observed in human functional neuroimaging studies that compare periods of task-based cognitive performance with passive states, such as rest. It is now widely held that such task-induced deactivations index a highly organized ‘default-mode network’ (DMN): a large-scale brain system whose discovery has had broad implications in the study of human brain function and behavior. In this work, we show that common task-induced deactivations from rest also occur outside of the DMN as a function of increased task demand. Fifty healthy adult subjects performed two distinct functional magnetic resonance imaging tasks that were designed to reliably map deactivations from a resting baseline. As primary findings, increases in task demand consistently modulated the regional anatomy of DMN deactivation. At high levels of task demand, robust deactivation was observed in non-DMN regions, most notably, the posterior insular cortex. Deactivation of this region was directly implicated in a performance-based analysis of experienced task difficulty. Together, these findings suggest that task-induced deactivations from rest are not limited to the DMN and extend to brain regions typically associated with integrative sensory and interoceptive processes.

The contribution of sensory system functional connectivity reduction to clinical pain in fibromyalgia

Summary Clinical pain in fibromyalgia is associated with functional changes at different brain levels in a pattern suggesting a general weakening of sensory integration. ABSTRACT Fibromyalgia typically presents with spontaneous body pain with no apparent cause and is considered pathophysiologically to be a functional disorder of somatosensory processing. We have investigated potential associations between the degree of self‐reported clinical pain and resting‐state brain functional connectivity at different levels of putative somatosensory integration. Resting‐state functional magnetic resonance imaging was obtained in 40 women with fibromyalgia and 36 control subjects. A combination of functional connectivity‐based measurements were used to assess (1) the basic pain signal modulation system at the level of the periaqueductal gray (PAG); (2) the sensory cortex with an emphasis on the parietal operculum/secondary somatosensory cortex (SII); and (3) the connectivity of these regions with the self‐referential “default mode” network. Compared with control subjects, a reduction of functional connectivity was identified across the 3 levels of neural processing, each showing a significant and complementary correlation with the degree of clinical pain. Specifically, self‐reported pain in fibromyalgia patients correlated with (1) reduced connectivity between PAG and anterior insula; (2) reduced connectivity between SII and primary somatosensory, visual, and auditory cortices; and (3) increased connectivity between SII and the default mode network. The results confirm previous research demonstrating abnormal functional connectivity in fibromyalgia and show that alterations at different levels of sensory processing may contribute to account for clinical pain. Importantly, reduced functional connectivity extended beyond the somatosensory domain and implicated visual and auditory sensory modalities. Overall, this study suggests that a general weakening of sensory integration underlies clinical pain in fibromyalgia.

Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

BACKGROUND Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy. METHODS High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping. RESULTS Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy. CONCLUSIONS Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with psychopathy.

Effects of Duloxetine Treatment on Brain Response to Painful Stimulation in Major Depressive Disorder

Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology.

Amygdala activation and symptom dimensions in obsessive-compulsive disorder

BACKGROUND Despite knowledge of amygdala involvement in fear and anxiety, its contribution to the pathophysiology of obsessive-compulsive disorder (OCD) remains controversial. In the context of neuroimaging studies, it seems likely that the heterogeneity of the disorder might have contributed to a lack of consistent findings. AIMS To assess the influence of OCD symptom dimensions on amygdala responses to a well-validated emotional face-matching paradigm. METHOD Cross-sectional functional magnetic resonance imaging (fMRI) study of 67 patients with OCD and 67 age-, gender- and education-level matched healthy controls. RESULTS The severity of aggression/checking and sexual/religious symptom dimensions were significantly associated with heightened amygdala activation in those with OCD when responding to fearful faces, whereas no such correlations were seen for other symptom dimensions. CONCLUSIONS Amygdala functional alterations in OCD appear to be specifically modulated by symptom dimensions whose origins may be more closely linked to putative amygdala-centric processes, such as abnormal fear processing.

Altered Functional Magnetic Resonance Imaging Responses to Nonpainful Sensory Stimulation in Fibromyalgia Patients

Fibromyalgia (FM) is a disorder characterized by chronic pain and enhanced responses to acute noxious events. However, the sensory systems affected in FM may extend beyond pain itself, as FM patients show reduced tolerance to non‐nociceptive sensory stimulation. Characterizing the neural substrates of multisensory hypersensitivity in FM may thus provide important clues about the underlying pathophysiology of the disorder. The aim of this study was to characterize brain responses to non‐nociceptive sensory stimulation in FM patients and their relationship to subjective sensory sensitivity and clinical pain severity.

Functional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects

Cocaine addiction is characterized by persistent decision‐making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine‐dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting‐state activation. Ten cocaine‐dependent subjects and 14 non‐drug‐using controls participated in the study. Cocaine‐dependent subjects were carefully selected to discard potentially confounding co‐morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting‐state. During the moral dilemmas task, cocaine‐dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting‐state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine‐dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making.

Structural covariance of the neostriatum with regional gray matter volumes

The caudate and putamen nuclei have been traditionally divided into dorsal and ventral territories based on their segregated patterns of functional and anatomical connectivity with distributed cortical regions. Activity-dependent structural plasticity may potentially lead to the development of regional volume correlations, or structural covariance, between the different components of each cortico-striatal circuit. Here, we studied the whole-brain structural covariance patterns of four neostriatal regions belonging to distinct cortico-striatal circuits. We also assessed the potential modulating influence of laterality, age and gender. T1-weighted three-dimensional magnetic resonance images were obtained from ninety healthy participants (50 females). Following data pre-processing, the mean signal value per hemisphere was calculated for the ‘seed’ regions of interest, located in the dorsal and ventral caudate and the dorsal–caudal and ventral–rostral putamen. Statistical parametric mapping was used to estimate whole-brain voxel-wise structural covariance patterns for each striatal region, controlling for the shared anatomical variance between regions in order to obtain maximally specific structural covariance patterns. As predicted, segregated covariance patterns were observed. Age was found to be a relevant modulator of the covariance patterns of the right caudate regions, while laterality effects were observed for the dorsal–caudal putamen. Gender effects were only observed via an interaction with age. The different patterns of structural covariance are discussed in detail, as well as their similarities with the functional and anatomical connectivity patterns reported for the same striatal regions in other studies. Finally, the potential mechanisms underpinning the phenomenon of volume correlations between distant cortico-striatal structures are also discussed.

Ventral and Dorsal Striatum Networks in Obesity: Link to Food Craving and Weight Gain.

BACKGROUND The food addiction model proposes that obesity overlaps with addiction in terms of neurobiological alterations in the striatum and related clinical manifestations (i.e., craving and persistence of unhealthy habits). Therefore, we aimed to examine the functional connectivity of the striatum in excess-weight versus normal-weight subjects and to determine the extent of the association between striatum connectivity and individual differences in food craving and changes in body mass index (BMI). METHODS Forty-two excess-weight participants (BMI > 25) and 39 normal-weight participants enrolled in the study. Functional connectivity in the ventral and dorsal striatum was indicated by seed-based analyses on resting-state data. Food craving was indicated with subjective ratings of visual cues of high-calorie food. Changes in BMI between baseline and 12 weeks follow-up were assessed in 28 excess-weight participants. Measures of connectivity in the ventral striatum and dorsal striatum were compared between groups and correlated with craving and BMI change. RESULTS Participants with excess weight displayed increased functional connectivity between the ventral striatum and the medial prefrontal and parietal cortices and between the dorsal striatum and the somatosensory cortex. Dorsal striatum connectivity correlated with food craving and predicted BMI gains. CONCLUSIONS Obesity is linked to alterations in the functional connectivity of dorsal striatal networks relevant to food craving and weight gain. These neural alterations are associated with habit learning and thus compatible with the food addiction model of obesity.

Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity.

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine‐targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting‐state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co‐morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed‐based analyses to characterize the connectivity of regions displaying between‐group differences. We examined the relationships between seed‐based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large‐scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed‐based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision‐making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus–outcome learning. Orbitofrontal–subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large‐scale ventral corticostriatal–amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.