The cingulate cortex and limbic systems for emotion, action, and memory.
ABSTRACT: Evidence is provided for a new conceptualization of the connectivity and functions of the cingulate cortex in emotion, action, and memory. The anterior cingulate cortex receives information from the orbitofrontal cortex about reward and non-reward outcomes. The posterior cingulate cortex receives spatial and action-related information from parietal cortical areas. It is argued that these inputs allow the cingulate cortex to perform action-outcome learning, with outputs from the midcingulate motor area to premotor areas. In addition, because the anterior cingulate cortex connects rewards to actions, it is involved in emotion; and because the posterior cingulate cortex has outputs to the hippocampal system, it is involved in memory. These apparently multiple different functions of the cingulate cortex are related to the place of this proisocortical limbic region in brain connectivity.
Project description:Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures.Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose.Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the "nonjudging" subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later.These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.
Project description:We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.
Project description:Humans tend to reduce inequitable distributions. Previous neuroimaging studies have shown that inequitable decisions are related to brain regions that associated with negative emotion and signaling conflict. In the highly complex human social environment, our opinions and behaviors can be affected by social information. In current study, we used a modified dictator game to investigate the effect of social influence on making an equitable decision. We found that the choices of participants in present task was influenced by the choices of peers. However, participants' decisions were influenced by equitable rather than inequitable group choices. fMRI results showed that brain regions that related to norm violation and social conflict were related to the inequitable social influence. The neural responses in the dorsomedial prefrontal cortex, rostral cingulate zone, and insula predicted subsequent conforming behavior in individuals. Additionally, psychophysiological interaction analysis revealed that the interconnectivity between the dorsal striatum and insula was elevated in advantageous inequity influence versus no-social influence conditions. We found decreased functional connectivity between the medial prefrontal cortex and insula, supplementary motor area, posterior cingulate gyrus and dorsal anterior cingulate cortex in the disadvantageous inequity influence versus no-social influence conditions. This suggests that a disadvantageous inequity influence may decrease the functional connectivity among brain regions that are related to reward processes. Thus, the neural mechanisms underlying social influence in an equitable decision may be similar to those implicated in social norms and reward processing.
Project description:Unipolar and bipolar depressive episodes have a similar clinical presentation that suggests common dysfunction of the brain's reward system. Here, we evaluated the relationship of both dimensional depression severity and diagnostic category to reward system function in both bipolar and unipolar depression. In total, 89 adults were included, including 27 with bipolar depression, 25 with unipolar depression, and 37 healthy comparison subjects. Subjects completed both a monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across disorders, depression severity was significantly associated with reduced activation for wins compared with losses in bilateral ventral striatum, anterior cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting-state connectivity within this reward network was also diminished in proportion to depression severity, most notably connectivity strength in the left ventral striatum. In addition, there were categorical differences between patient groups: resting-state connectivity at multiple reward network nodes was higher in bipolar than in unipolar depression. Reduced reward system task activation and resting-state connectivity therefore appear to be a brain phenotype that is dimensionally related to depression severity in both bipolar and unipolar depression. In contrast, categorical differences in reward system resting connectivity between unipolar and bipolar depression may reflect differential risk of mania. Reward system dysfunction thus represents a common brain mechanism with relevance that spans categories of psychiatric diagnosis.
Project description:This study examined neural features of emotional responses to errors. We specifically examined whether directed emotion regulation of negative emotion associated with error modulates action-monitoring functions of anterior cingulate cortex, including conflict monitoring, error processing, and error prevention. Seventeen healthy adults performed a continuous performance task during assessment by fMRI. In each block, participants were asked either to increase or decrease their negative emotional responses or to react naturally after error commission. Emotion regulation instructions were associated with modulation of rostral and dorsal anterior activity and of their effective connectivity following errors and conflict. Cingulate activity and connectivity predicted subsequent errors. These data may suggest that responses to errors are affected by emotion and that aspects of emotion and cognition are inextricably linked, even during a nominally cognitive task.
Project description:Altered resting-state (RS) brain activity, as a measure of functional connectivity (FC), is commonly observed in chronic pain. Identifying a reliable signature pattern of altered RS activity for chronic pain could provide strong mechanistic insights and serve as a highly beneficial neuroimaging-based diagnostic tool. We collected and analyzed RS functional magnetic resonance imaging data from female patients with urologic chronic pelvic pain syndrome (N = 45) and matched healthy participants (N = 45) as part of an NIDDK-funded multicenter project (www.mappnetwork.org). Using dual regression and seed-based analyses, we observed significantly decreased FC of the default mode network to 2 regions in the posterior medial cortex (PMC): the posterior cingulate cortex (PCC) and the left precuneus (threshold-free cluster enhancement, family-wise error corrected P < 0.05). Further investigation revealed that patients demonstrated increased FC between the PCC and several brain regions implicated in pain, sensory, motor, and emotion regulation processes (eg, insular cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus, putamen, amygdala, hippocampus). The left precuneus demonstrated decreased FC to several regions of pain processing, reward, and higher executive functioning within the prefrontal (orbitofrontal, anterior cingulate, ventromedial prefrontal) and parietal cortices (angular gyrus, superior and inferior parietal lobules). The altered PMC connectivity was associated with several phenotype measures, including pain and urologic symptom intensity, depression, anxiety, quality of relationships, and self-esteem levels in patients. Collectively, these findings indicate that in patients with urologic chronic pelvic pain syndrome, regions of the PMC are detached from the default mode network, whereas neurological processes of self-referential thought and introspection may be joined to pain and emotion regulatory processes.
Project description:Obesity has been associated with brain alterations characterised by poorer interaction between a hypersensitive reward system and a comparatively weaker prefrontal-cognitive control system. These alterations may occur as early as in adolescence, but this notion remains unclear, as no studies so far have examined global functional connectivity in adolescents with excess weight.We investigated functional connectivity in a sample of 60 adolescents with excess weight and 55 normal weight controls. We first identified parts of the brain displaying between-group global connectivity differences and then characterised the extent of the differences in functional network integrity and their association with reward sensitivity.Adolescent obesity was linked to neuroadaptations in functional connectivity within brain hubs linked to interoception (insula), emotional memory (middle temporal gyrus) and cognitive control (dorsolateral prefrontal cortex) (pFWE < 0.05). The connectivity between the insula and the anterior cingulate cortex was reduced in comparison to controls, as was the connectivity between the middle temporal gyrus and the posterior cingulate cortex and cuneus/precuneus (pFWE < 0.05). Conversely, the middle temporal gyrus displayed increased connectivity with the orbitofrontal cortex (pFWE < 0.05). Critically, these networks were correlated with sensitivity to reward (p < 0.05).These findings suggest that adolescent obesity is linked to disrupted functional connectivity in brain networks relevant to maintaining balance between reward, emotional memories and cognitive control. Our findings may contribute to reconceptualization of obesity as a multi-layered brain disorder leading to compromised motivation and control, and provide a biological account to target prevention strategies for adolescent obesity.
Project description:Emotion regulation deficits figure prominently in generalized anxiety disorder (GAD) and in other anxiety and mood disorders. Research examining emotion regulation and top-down modulation has implicated reduced coupling of the amygdala with prefrontal cortex and anterior cingulate cortex, suggesting altered frontolimbic white matter connectivity in GAD.To investigate structural connectivity between ventral prefrontal cortex or anterior cingulate cortex areas and the amygdala in GAD and to assess associations with functional connectivity between those areas.Participants underwent diffusion-tensor imaging and functional magnetic resonance imaging.University magnetic resonance imaging facility.Forty-nine patients with GAD and 39 healthy volunteer control subjects, including a matched subset of 21 patients having GAD without comorbid Axis I diagnoses and 21 healthy volunteers matched for age, sex, and education.The mean fractional anisotropy values in the left and right uncinate fasciculus, as measured by tract-based analysis for diffusion-tensor imaging data.Lower mean fractional anisotropy values in the bilateral uncinate fasciculus indicated reduced frontolimbic structural connectivity in patients with GAD. This reduction in uncinate fasciculus integrity was most pronounced for patients without comorbidity and was not observed in other white matter tracts. Across all participants, higher fractional anisotropy values were associated with more negative functional coupling between the pregenual anterior cingulate cortex and the amygdala during the anticipation of aversion.Reduced structural connectivity of a major frontolimbic pathway suggests a neural basis for emotion regulation deficits in GAD. The functional significance of these structural differences is underscored by decreased functional connectivity between the anterior cingulate cortex and the amygdala in individuals with reduced structural integrity of the uncinate fasciculus.
Project description:Pediatric obsessive-compulsive disorder is characterized by abnormalities of frontal-striatal-thalamic circuitry that appear near illness onset and persist over its course. Distinct frontal-striatal-thalamic loops through cortical centers for cognitive control (anterior cingulate cortex) and emotion processing (ventral medial frontal cortex) follow unique maturational trajectories, and altered connectivity within distinct loops may be differentially associated with OCD at specific stages of development.Altered development of striatal and thalamic connectivity to medial frontal cortex was tested in 60 OCD patients compared with 61 healthy control subjects at child, adolescent, and adult stages of development, using resting-state functional connectivity MRI.OCD in the youngest patients was associated with reduced connectivity of dorsal striatum and medial dorsal thalamus to rostral and dorsal anterior cingulate cortex, respectively. Increased connectivity of dorsal striatum to ventral medial frontal cortex was observed in patients at all developmental stages. In child patients, reduced connectivity between dorsal striatum and rostral anterior cingulate cortex correlated with OCD severity.Frontal-striatal-thalamic loops involved in cognitive control are hypoconnected in young patients near illness onset, whereas loops implicated in emotion processing are hyperconnected throughout the illness.