Changes In Anterior Cingulate Cortex Research Articles

Pathophysiology in cortico-amygdala circuits and excessive aversion processing: the role of oligodendrocytes and myelination.

Stress-related psychiatric illnesses, such as major depressive disorder, anxiety and post-traumatic stress disorder, present with alterations in emotional processing, including excessive processing of negative/aversive stimuli and events. The bidirectional human/primate brain circuit comprising anterior cingulate cortex and amygdala is of fundamental importance in processing emotional stimuli, and in rodents the medial prefrontal cortex-amygdala circuit is to some extent analogous in structure and function. Here, we assess the comparative evidence for: (i) Anterior cingulate/medial prefrontal cortex<->amygdala bidirectional neural circuits as major contributors to aversive stimulus processing; (ii) Structural and functional changes in anterior cingulate cortex<->amygdala circuit associated with excessive aversion processing in stress-related neuropsychiatric disorders, and in medial prefrontal cortex<->amygdala circuit in rodent models of chronic stress-induced increased aversion reactivity; and (iii) Altered status of oligodendrocytes and their oligodendrocyte lineage cells and myelination in anterior cingulate/medial prefrontal cortex<->amygdala circuits in stress-related neuropsychiatric disorders and stress models. The comparative evidence from humans and rodents is that their respective anterior cingulate/medial prefrontal cortex<->amygdala circuits are integral to adaptive aversion processing. However, at the sub-regional level, the anterior cingulate/medial prefrontal cortex structure-function analogy is incomplete, and differences as well as similarities need to be taken into account. Structure-function imaging studies demonstrate that these neural circuits are altered in both human stress-related neuropsychiatric disorders and rodent models of stress-induced increased aversion processing. In both cases, the changes include altered white matter integrity, albeit the current evidence indicates that this is decreased in humans and increased in rodent models. At the cellular-molecular level, in both humans and rodents, the current evidence is that stress disorders do present with changes in oligodendrocyte lineage, oligodendrocytes and/or myelin in these neural circuits, but these changes are often discordant between and even within species. Nonetheless, by integrating the current comparative evidence, this review provides a timely insight into this field and should function to inform future studies-human, monkey and rodent-to ascertain whether or not the oligodendrocyte lineage and myelination are causally involved in the pathophysiology of stress-related neuropsychiatric disorders.

Assessment of Characteristics of Imaging Biomarkers for Quantifying Anterior Cingulate Cortex Changes: A Twin Study of Middle- to Advanced-Aged Populations in East Asia.

Background and Objectives: Our aim was to assess genetic and environmental effects on surface morphological parameters for quantifying anterior cingulate cortex (ACC) changes in middle- to advanced-age East Asians using twin analysis. Materials and Methods: Normal twins over 39 years old comprising 37 monozygotic pairs and 17 dizygotic pairs underwent 3-dimensional (3D) T1-weighted imaging of the brain at 3T. Freesurfer-derived ACC parameters including thickness, standard deviation of thickness (STDthickness), volume, surface area, and sulcal morphological parameters (folding, mean, and Gaussian curvatures) were calculated from 3D T1-weighted volume images. Twin analysis with a model involving phenotype variance components of additive genetic effects (A), common environmental effects (C), and unique environmental effects (E) was performed to assess the magnitude of each genetic and environmental influence on parameters. Results: Most parameters fit best with an AE model. Both thickness (A: left 0.73/right 0.71) and surface area (A: left 0.63/right 0.71) were highly heritable. STDthickness was low to moderately heritable (A: left 0.48/right 0.29). Volume was moderately heritable (A: left 0.37). Folding was low to moderately heritable (A: left 0.44/right 0.28). Mean curvature (A: left 0.37/right 0.65) and Gaussian curvature (A: right 0.79) were moderately to highly heritable. Right volume and left Gaussian curvature fit best with a CE model, indicating a relatively weak contribution of genetic factors to these parameters. Conclusions: When assessing ACC changes in middle- to advanced-age East Asians, one must keep in mind that thickness and surface area appear to be strongly affected by genetic factors, whereas sulcal morphological parameters tend to involve environmental factors.

Altered brain creatine cycle metabolites in bipolar I disorder with childhood abuse: A 1H magnetic resonance spectroscopy study

BackgroundChildhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy (1H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD. ObjectiveTo investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects. MethodsFifty-nine BD I euthymic patients and fifty-nine HC subjects were assessed using the Childhood Trauma Questionnaire (CTQ) and underwent a 3-Tesla 1H-MRS scan. Severity of childhood abuse (physical, sexual and emotional) and its association with levels of brain metabolites was analyzed within each group. ResultsBD patients had higher total scores on the CTQ and higher severity rates of sexual and physical abuse compared to HC subjects. Greater severity of physical and sexual abuse was associated with increased ACC PCr level and lower Cr/PCr ratio in the BD group only. ConclusionSexual and physical abuse in BD patients, but not in HC subjects, appeared to be associated with creatine metabolism in the ACC, which can influence neuronal mitochondrial energy production. Further studies should investigate whether this is the mechanism underlying the association between CA and worse clinical outcomes in BD.

Abnormal metabolite concentrations and amygdala volume in patients with recent-onset posttraumatic stress disorder

BackgroundPrevious psychoradiological studies of posttraumatic stress disorder (PTSD) were mainly of patients at a chronic stage, focusing on brain regions outside the amygdala. The goals of this study were to investigate the early biochemical and structural changes of anterior cingulate cortex (ACC) and amygdala in patients with PTSD and to explore their relationships. MethodsSeventy-eight drug-naïve PTSD subjects and 71 non-PTSD age- and sex-matched control subjects were enrolled, all of whom had suffered the same earthquake about one year before. Single-voxel proton magnetic resonance spectroscopy (1H-MRS) was performed and absolute metabolite concentrations in ACC and bilateral amygdalae were estimated with LCModel. Bilateral amygdalae were manually outlined and their volumes were calculated and corrected for the total intracranial volume. ResultsThe PTSD group showed significantly increased N-acetylaspartate (NAA) concentration in the ACC, increased creatine (Cr) concentration in the left amygdala, and increased myo-inositol (mI) concentration in the right amygdala, compared to non-PTSD controls. The NAA concentration in ACC was negatively correlated with the time since trauma. The PTSD group showed significantly decreased volumes of bilateral amygdalae compared to non-PTSD controls, but amygdala volumes were not correlated with metabolite concentrations. LimitationsLongitudinal studies are needed to explore the metabolic and structural changes of PTSD at different stages. The volume of ACC was not measured. ConclusionsThis concurrent increase in some metabolite concentrations and decrease of amygdala volumes may represent a pattern of biochemical and morphological changes in recent-onset PTSD which is different from that reported in chronic PTSD.

Open label smoking cessation with varenicline is associated with decreased glutamate levels and functional changes in anterior cingulate cortex: preliminary findings.

Rationale: Varenicline, the most effective single agent for smoking cessation, is a partial agonist at α4β2 nicotinic acetylcholine receptors. Increasing evidence implicates glutamate in the pathophysiology of addiction and one of the benefits of treatment for smoking cessation is the ability to regain cognitive control.Objective: To evaluate the effects of 12-week varenicline administration on glutamate levels in the dorsal anterior cingulate cortex (dACC) and functional changes within the cognitive control network.Methods: We used single-voxel proton magnetic resonance spectroscopy (1H-MRS) in the dACC and functional MRI (fMRI) during performance of a Stroop color-naming task before and after smoking cessation with varenicline in 11 healthy smokers (open label design). Using the dACC as a seed region, we evaluated functional connectivity changes using a psychophysiological interaction (PPI) analysis.Results: We observed a significant decrease in dACC glutamate + glutamine (Glx)/Cr levels as well as significant blood oxygen level-dependent signal (BOLD) decreases in the rostral ACC/medial orbitofrontal cortex and precuneus/posterior cingulate cortex. These BOLD changes are suggestive of alterations in default mode network (DMN) function and are further supported by the results of the PPI analysis that revealed changes in connectivity between the dACC and regions of the DMN. Baseline measures of nicotine dependence and craving positively correlated with baseline Glx/Cr levels.Conclusions: These results suggest possible mechanisms of action for varenicline such as reduction in Glx levels in dACC and shifts in BOLD connectivity between large scale brain networks. They also suggest a role for ACC Glx in the modulation of behavior. Due to the preliminary nature of this study (lack of control group and small sample size), future studies are needed to replicate these findings.

Meditation states and traits: EEG, ERP, and neuroimaging studies.

Neuroelectric and imaging studies of meditation are reviewed. Electroencephalographic measures indicate an overall slowing subsequent to meditation, with theta and alpha activation related to proficiency of practice. Sensory evoked potential assessment of concentrative meditation yields amplitude and latency changes for some components and practices. Cognitive event-related potential evaluation of meditation implies that practice changes attentional allocation. Neuroimaging studies indicate increased regional cerebral blood flow measures during meditation. Taken together, meditation appears to reflect changes in anterior cingulate cortex and dorsolateral prefrontal areas. Neurophysiological meditative state and trait effects are variable but are beginning to demonstrate consistent outcomes for research and clinical applications. Psychological and clinical effects of meditation are summarized, integrated, and discussed with respect to neuroimaging data.

A review of EEG, ERP, and neuroimaging studies of creativity and insight.

Creativity is a cornerstone of what makes us human, yet the neural mechanisms underlying creative thinking are poorly understood. A recent surge of interest into the neural underpinnings of creative behavior has produced a banquet of data that is tantalizing but, considered as a whole, deeply self-contradictory. We review the emerging literature and take stock of several long-standing theories and widely held beliefs about creativity. A total of 72 experiments, reported in 63 articles, make up the core of the review. They broadly fall into 3 categories: divergent thinking, artistic creativity, and insight. Electroencephalographic studies of divergent thinking yield highly variegated results. Neuroimaging studies of this paradigm also indicate no reliable changes above and beyond diffuse prefrontal activation. These findings call into question the usefulness of the divergent thinking construct in the search for the neural basis of creativity. A similarly inconclusive picture emerges for studies of artistic performance, except that this paradigm also often yields activation of motor and temporoparietal regions. Neuroelectric and imaging studies of insight are more consistent, reflecting changes in anterior cingulate cortex and prefrontal areas. Taken together, creative thinking does not appear to critically depend on any single mental process or brain region, and it is not especially associated with right brains, defocused attention, low arousal, or alpha synchronization, as sometimes hypothesized. To make creativity tractable in the brain, it must be further subdivided into different types that can be meaningfully associated with specific neurocognitive processes.

Meditation states and traits: EEG, ERP, and neuroimaging studies.

Neuroelectric and imaging studies of meditation are reviewed. Electroencephalographic measures indicate an overall slowing subsequent to meditation, with theta and alpha activation related to proficiency of practice. Sensory evoked potential assessment of concentrative meditation yields amplitude and latency changes for some components and practices. Cognitive event-related potential evaluation of meditation implies that practice changes attentional allocation. Neuroimaging studies indicate increased regional cerebral blood flow measures during meditation. Taken together, meditation appears to reflect changes in anterior cingulate cortex and dorsolateral prefrontal areas. Neurophysiological meditative state and trait effects are variable but are beginning to demonstrate consistent outcomes for research and clinical applications. Psychological and clinical effects of meditation are summarized, integrated, and discussed with respect to neuroimaging data.

Prenatal Exposure to Cocaine Impairs Neuronal Coding of Attention and Discriminative Learninga.

Cingulate cortex and related areas of the thalamus are critically involved in the mediation of discriminative avoidance learning, wherein rabbits step in response to an acoustic conditional stimulus (CS+) to avoid foot shock and they learn to ignore a different acoustic stimulus (CS-) not followed by shock. Studies of multi-unit neuronal activity recorded simultaneously in many cingulothalamic areas have documented massive learning-related neuronal firing changes during the course of behavioral acquisition. Stimulated by findings (this volume) of neurobiological changes in anterior cingulate cortex in rabbits exposed in utero to cocaine, we investigated behavioral learning and correlated neuronal activity in several cingulothalamic areas in cocaine-exposed rabbits. In an initial study, training-induced enhancement of cingulate cortical neuronal firing in response to the CS+ and CS- was abolished in rabbits exposed to cocaine in utero. Yet discriminative neuronal activity (greater firing in response to the CS+ than to the CS-) did develop during training, and behavioral learning was normal in the cocaine-exposed rabbits. In a second study, we reduced the salience of the CS+ and CS- by employing 200 msec CSs rather than standard 500 msec CSs. Early training-stage development of anterior cingulate cortical discriminative neuronal activity was abolished, the elicited neuronal discharge profiles were altered, and behavioral learning was impaired in rabbits exposed to cocaine, relative to saline-exposed controls. The specificity of these changes to low-salience CSs suggested that prenatal cocaine results in disturbed associative attentional processes of anterior cingulate cortex in adult rabbits. Consideration of the neuronal response profile alterations together with other reported neurobiological changes suggested that the cocaine-related attentional deficit is due to impaired dopaminergic afferent activation of GABA neurons in anterior cingulate cortex.