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Sample records for ipsilateral anterior cingulate

  1. rTMS of the Left Dorsolateral Prefrontal Cortex Modulates Dopamine Release in the Ipsilateral Anterior Cingulate Cortex and Orbitofrontal Cortex

    PubMed Central

    Cho, Sang Soo; Strafella, Antonio P.

    2009-01-01

    Background Brain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson's disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of non-invasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine (DA). Methodology/Principal Findings Healthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [11C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [11C]FLB 457 binding potential (BP) in the ipsilateral subgenual anterior cingulate cortex (ACC) (BA 25/12), pregenual ACC (BA 32) and medial orbitofrontal cortex (BA 11). There were no significant changes in [11C]FLB 457 BP following right DLPFC rTMS. Conclusions/Significance To our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [11C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help to identify the neurobiological effects of TMS for the treatment of different neurological and psychiatric diseases. PMID:19696930

  2. Anterior Cingulate epilepsy: mechanisms and modulation

    PubMed Central

    Chang, Wei-Pang; Shyu, Bai-Chuang

    2014-01-01

    Epilepsy is a common neurological disorder, about 1% population worldwide suffered from this disease. In 1989, the International League Against Epilepsy (ILAE) classified anterior cingulate epilepsy as a form of frontal lobe epilepsy (FLE). FLE is the second most common type of epilepsy. Previous clinical studies showed that FLE account an important cause in refractory epilepsy, therefore to find alternative approach to modulate FLE is very important. Basic research using animal models and brain slice have revealed some insights on the epileptogenesis and modulation of seizure in anterior cingulate cortex (ACC). Interneurons play an important role in the synchronization of cingulate epilepsy. Research has shown that the epileptogenesis of seizure originated from mesial frontal lobe might be caused by a selective increase in nicotine-evoked γ-aminobutyric acid (GABA) inhibition, because the application of the GABAA receptor antagonist picrotoxin inhibited epileptic discharges. Gap junctions are also involved in the regulation of cingulate epilepsy. Previous studies have shown that the application of gap junction blockers could attenuate ACC seizures, while gap junction opener could enhance them in an in vitro preparation. μ-Opioid receptors have been shown to be involved in the epileptic synchronization mechanism in ACC seizures in a brain slice preparation. Application of the μ-opioid agonist DAMGO significantly abolished the ictal discharges in a 4-aminopyridine induced electrographic seizure model in ACC. Basic research has also found that thalamic modulation has an inhibitory effect on ACC seizures. Studies have shown that the medial thalamus may be a target for deep brain stimulation to cure ACC seizures. PMID:24427123

  3. Lesion-negative anterior cingulate epilepsy.

    PubMed

    Lacuey, Nuria; Davila, Javier Chapa; Zonjy, Bilal; Amina, Shahram; Couce, Marta; Turnbull, John; Miller, Jonathan; Lüders, Hans; Lhatoo, Samden D

    2015-06-01

    MRI-negative anterior cingulate epilepsy is a rare entity. Herein, we describe a case of MRI and functional imaging-negative intractable frontal lobe epilepsy in which, initially, secondary bilateral synchrony of surface and intracranial EEG and non-lateralizing semiology rendered identification of the epileptogenic zone difficult. A staged bilateral stereotactic EEG exploration revealed a very focal, putative ictal onset zone in the right anterior cingulate gyrus, as evidenced by interictal and ictal high-frequency oscillations (at 250Hz) and induction of seizures from the same electrode contacts by 50-Hz low-intensity cortical stimulation. This was subsequently confirmed by ILAE class 1 outcome following resection of the ictal onset and irritative zones. Histopathological examination revealed focal cortical dysplasia type 1b (ILAE Commission, 2011) as the cause of epilepsy. The importance of anatomo-electro-clinical correlation is illustrated in this case in which semiological and electrophysiological features pointed to the anatomical localization of a challenging, MRI-negative epilepsy. PMID:26056053

  4. Multiple signals in anterior cingulate cortex

    PubMed Central

    Kolling, N; Behrens, TEJ; Wittmann, MK; Rushworth, MFS

    2016-01-01

    Activity in anterior cingulate cortex (ACC) has been linked both to commitment to a course of action, even when it is associated with costs, and to exploring or searching for alternative courses of action. Here we review evidence that this is due to the presence of multiple signals in ACC reflecting the updating of beliefs and internal models of the environment and encoding aspects of choice value, including the average value of choices afforded by the environment (‘search value’). We contrast this evidence with the influential view that ACC activity is better described as reflecting task difficulty. A consideration of cortical neural network properties explains why ACC may carry such signals and also exhibit sensitivity to task difficulty. PMID:26774693

  5. Reduced Anterior Cingulate Cortex Glutamatergic Concentrations in Childhood Major Depression

    ERIC Educational Resources Information Center

    Mirza, Yousha; Tang, Jennifer; Russell, Aileen; Banerjee, S. Preeya; Bhandari, Rashmi; Ivey, Jennifer; Rose, Michelle; Moore, Gregory J.; Rosenberg, David R.

    2004-01-01

    Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of children with major depressive disorder (MDD). Method: Single-voxel proton magnetic resonance spectroscopic ([.sup.1]H-MRS) examinations of the anterior cingulate cortex were conducted in 13 psychotropic-naive children and adolescents with MDD…

  6. Spindle neurons of the human anterior cingulate cortex

    NASA Technical Reports Server (NTRS)

    Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

  7. Anterior Cingulate Cortex in Schema Assimilation and Expression

    ERIC Educational Resources Information Center

    Wang, Szu-Han; Tse, Dorothy; Morris, Richard G. M.

    2012-01-01

    In humans and in animals, mental schemas can store information within an associative framework that enables rapid and efficient assimilation of new information. Using a hippocampal-dependent paired-associate task, we now report that the anterior cingulate cortex is part of a neocortical network of schema storage with NMDA receptor-mediated…

  8. Anterior Cingulate Cortex γ-Aminobutyric Acid in Depressed Adolescents

    PubMed Central

    Gabbay, Vilma; Mao, Xiangling; Klein, Rachel G.; Ely, Benjamin A.; Babb, James S.; Panzer, Aviva M.; Alonso, Carmen M.; Shungu, Dikoma C.

    2013-01-01

    Context Anhedonia, a core symptom of major depressive disorder (MDD) and highly variable among adolescents with MDD, may involve alterations in the major inhibitory amino acid neurotransmitter system of γ-aminobutyric acid (GABA). Objective To test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD. The associations of GABA alterations with the presence and severity of anhedonia were explored. Design Case-control, cross-sectional study using single-voxel proton magnetic resonance spectroscopy at 3 T. Setting Two clinical research divisions at 2 teaching hospitals. Participants Twenty psychotropic medication-free adolescents with MDD (10 anhedonic, 12 female, aged 12–19 years) with episode duration of 8 weeks or more and 21 control subjects group matched for sex and age. Main Outcome Measures Anterior cingulate cortex GABA levels expressed as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores expressed as a continuous variable. Results Compared with control subjects, adolescents with MDD had significantly decreased ACC GABA/w (t= 3.2; P<.003). When subjects with MDD were categorized based on the presence of anhedonia, only anhedonic patients had decreased GABA/w levels compared with control subjects (t=4.08; P<.001; PTukey<.001). Anterior cingulate cortex GABA/w levels were negatively correlated with anhedonia scores for the whole MDD group (r = −0.50; P = .02), as well as for the entire participant sample including the control subjects (r=−0.54; P<.001). Anterior cingulate cortex white matter was also significantly decreased in adolescents with MDD compared with controls (P=.04). Conclusions These findings suggest that GABA, the major inhibitory neurotransmitter in the brain, may be implicated in adolescent MDD and, more specifically, in those with anhedonia. In addition, use of a continuous rather than categorical scale of anhedonia, as in

  9. The Subgenual Anterior Cingulate Cortex in Mood Disorders

    PubMed Central

    Drevets, Wayne C.; Savitz, Jonathan; Trimble, Michael

    2009-01-01

    INTRODUCTION In the latest edition of our series of neuroanatomical areas of importance for neuropsychiatry, Wayne Drevets, MD, and Jonathan Savitz, PhD, have outlined the clinical importance of the ventral anterior cingulate structures for the regulation of mood. This area was an early target for interventional neurosurgery for depression some half a century ago, and today has become one of the key sites of deep brain stimulation for affective disorders. The anterior cingulate cortex was a part of the initial circuit of Papez thought to be related to the regulation of emotion. However, since then, much experimental work has outlined different cingulate regions with differing anatomical connectivity and functions. Drevets and Savitz draw attention to the subgenual area and describe the local and distant anatomical connectivities that emphasize its relevance for several neuropsychiatric disorders. ABSTRACT The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this “subgenual” ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other

  10. Bilingualism tunes the anterior cingulate cortex for conflict monitoring.

    PubMed

    Abutalebi, Jubin; Della Rosa, Pasquale Anthony; Green, David W; Hernandez, Mireia; Scifo, Paola; Keim, Roland; Cappa, Stefano F; Costa, Albert

    2012-09-01

    Monitoring and controlling 2 language systems is fundamental to language use in bilinguals. Here, we reveal in a combined functional (event-related functional magnetic resonance imaging) and structural neuroimaging (voxel-based morphometry) study that dorsal anterior cingulate cortex (ACC), a structure tightly bound to domain-general executive control functions, is a common locus for language control and resolving nonverbal conflict. We also show an experience-dependent effect in the same region: Bilinguals use this structure more efficiently than monolinguals to monitor nonlinguistic cognitive conflicts. They adapted better to conflicting situations showing less ACC activity while outperforming monolinguals. Importantly, for bilinguals, brain activity in the ACC, as well as behavioral measures, also correlated positively with local gray matter volume. These results suggest that early learning and lifelong practice of 2 languages exert a strong impact upon human neocortical development. The bilingual brain adapts better to resolve cognitive conflicts in domain-general cognitive tasks. PMID:22038906

  11. Increased Rostral Anterior Cingulate Cortex Volume in Chronic Primary Insomnia

    PubMed Central

    Winkelman, John W.; Plante, David T.; Schoerning, Laura; Benson, Kathleen; Buxton, Orfeu M.; O'Connor, Shawn P.; Jensen, J. Eric; Renshaw, Perry F.; Gonenc, Atilla

    2013-01-01

    Background: Recent studies document alterations in cortical and subcortical volumes in patients with chronic primary insomnia (PI) in comparison with normal sleepers. We sought to confirm this observation in two previously studied PI cohorts. Methods: Two separate and independent groups of unmedicated patients who met Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) criteria for PI were compared with two separate, healthy control groups (Study 1: PI = 20, controls = 15; Study 2: PI = 21, controls = 20). Both studies included 2 weeks of sleep diaries supplemented by wrist actigraphy. The 3.0 T MRI-derived rostral anterior cingulate cortex (rACC) volumes were measured with FreeSurfer image analysis suite (version 5.0) and results normalized to total intracranial volume (ICV). Unpaired t-tests (two-tailed) were used to compare rACC volumes between groups. Post hoc correlations of rACC volumes to insomnia severity measures were performed (uncorrected for multiplicity). Results: Both studies demonstrated increases in normalized rACC volume in PI compared with control patients (Study 1: right side P = 0.05, left side P = 0.03; Study 2: right side P = 0.03, left side P = 0.02). In PI patients from Study 1, right rACC volume was correlated with sleep onset latency (SOL) by both diary (r = 0.51, P = 0.02) and actigraphy (r = 0.50, P = 0.03), and with sleep efficiency by actigraphy (r = -0.57, P = 0.01); left rACC volume was correlated with SOL by diary (r = 0.48, P = 0.04), and wake after sleep onset (WASO) (r = 0.49, P = 0.03) and sleep efficiency (r = -0.49, P = 0.03) by actigraphy. In Study 2, right rACC volume was correlated with SOL by diary (r = 0.44, P = 0.05) in PI patients. Conclusions: Rostral ACC volumes are larger in patients with PI compared with control patients. Clinical severity measures in PI correlate with rACC volumes. These data may reflect a compensatory brain response to chronic insomnia and may represent a marker of

  12. Anterior cingulate implants for tinnitus: report of 2 cases.

    PubMed

    De Ridder, Dirk; Joos, Kathleen; Vanneste, Sven

    2016-04-01

    Tinnitus can be distressful, and tinnitus distress has been linked to increased beta oscillatory activity in the dorsal anterior cingulate cortex (dACC). The amount of distress is linked to alpha activity in the medial temporal lobe (amygdala and parahippocampal area), as well as the subgenual (sg)ACC and insula, and the functional connectivity between the parahippocampal area and the sgACC at 10 and 11.5 Hz. The authors describe 2 patients with very severely distressing intractable tinnitus who underwent transcranial magnetic stimulation (TMS) with a double-cone coil targeting the dACC and subsequent implantation of electrodes on the dACC. One of the patients responded to the implant and one did not, even though phenomenologically they both expressed the same tinnitus loudness and distress. The responder has remained dramatically improved for more than 2 years with 6-Hz burst stimulation of the dACC. The 2 patients differed in functional connectivity between the area of the implant and a tinnitus network consisting of the parahippocampal area as well as the sgACC and insula; that is, the responder had increased functional connectivity between these areas, whereas the nonresponder had decreased functional connectivity between these areas. Only the patient with increased functional connectivity linked to the target area of repetitive TMS or implantation might transmit the stimulation current to the entire tinnitus network and thus clinically improve. PMID:26314996

  13. Anterior cingulate cortex and intuitive bias detection during number conservation.

    PubMed

    Simon, Grégory; Lubin, Amélie; Houdé, Olivier; De Neys, Wim

    2015-01-01

    Children's number conservation is often biased by misleading intuitions but the precise nature of these conservation errors is not clear. A key question is whether children detect that their erroneous conservation judgment is unwarranted. The present study reanalyzed available fMRI data to test the implication of the anterior cingulate cortex (ACC) in this detection process. We extracted mean BOLD (Blood Oxygen Level Dependent) signal values in an independently defined ACC region of interest (ROI) during presentation of classic and control number conservation problems. In classic trials, an intuitively cued visuospatial response conflicted with the correct conservation response, whereas this conflict was not present in the control trials. Results showed that ACC activation increased when solving the classic conservation problems. Critically, this increase did not differ between participants who solved the classic problems correctly (i.e., so-called conservers) and incorrectly (i.e., so-called non-conservers). Additional control analyses of inferior and lateral prefrontal ROIs showed that the group of conservers did show stronger activation in the right inferior frontal gyrus and right lateral middle frontal gyrus. In line with recent behavioral findings, these data lend credence to the hypothesis that even non-conserving children detect the biased nature of their judgment. The key difference between conservers and non-conservers seems to lie in a differential recruitment of inferior and lateral prefrontal regions associated with inhibitory control. PMID:25932663

  14. The Dorsal Anterior Cingulate Cortex Modulates Dialectical Self-Thinking

    PubMed Central

    Wang, Fei; Peng, Kaiping; Bai, Yang; Li, Rui; Zhu, Ying; Sun, Pei; Guo, Hua; Yuan, Chun; Rotshtein, Pia; Sui, Jie

    2016-01-01

    Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC) plays a crucial role in conflict monitoring as well as self-related processing. Here, we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking), in which participants had to make a judgment whether a simultaneously presented pair of contradictory or non-contradictory traits properly described them while brain activity was recording using functional magnetic resonance imaging (fMRI). The data showed that activity in the dACC during the processing of self-relevant conflicting information was positively correlated with participants’ dispositional level of naïve dialecticism (measured with the Dialectical Self Scale). Psychophysiological interaction (PPI) analyses further revealed increased functional connectivity between the dACC and the caudate, middle temporal gyrus and hippocampus during the processing of self-relevant conflicting information for dialectical thinkers. These results support the hypothesis that the dACC has a key role in dialectical self-thinking. PMID:26903940

  15. The Dorsal Anterior Cingulate Cortex Modulates Dialectical Self-Thinking.

    PubMed

    Wang, Fei; Peng, Kaiping; Bai, Yang; Li, Rui; Zhu, Ying; Sun, Pei; Guo, Hua; Yuan, Chun; Rotshtein, Pia; Sui, Jie

    2016-01-01

    Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC) plays a crucial role in conflict monitoring as well as self-related processing. Here, we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking), in which participants had to make a judgment whether a simultaneously presented pair of contradictory or non-contradictory traits properly described them while brain activity was recording using functional magnetic resonance imaging (fMRI). The data showed that activity in the dACC during the processing of self-relevant conflicting information was positively correlated with participants' dispositional level of naïve dialecticism (measured with the Dialectical Self Scale). Psychophysiological interaction (PPI) analyses further revealed increased functional connectivity between the dACC and the caudate, middle temporal gyrus and hippocampus during the processing of self-relevant conflicting information for dialectical thinkers. These results support the hypothesis that the dACC has a key role in dialectical self-thinking. PMID:26903940

  16. Kainate-induced network activity in the anterior cingulate cortex.

    PubMed

    Shinozaki, R; Hojo, Y; Mukai, H; Hashizume, M; Murakoshi, T

    2016-06-14

    Anterior cingulate cortex (ACC) plays a pivotal role in higher order processing of cognition, attention and emotion. The network oscillation is considered an essential means for integration of these CNS functions. The oscillation power and coherence among related areas are often dis-regulated in several psychiatric and pathological conditions with a hemispheric asymmetric manner. Here we describe the network-based activity of field potentials recorded from the superficial layer of the mouse ACC in vitro using submerged type recordings. A short activation by kainic acid administration to the preparation induced populational activities ranging over several frequency bands including theta (3-8Hz), alpha (8-12Hz), beta (13-30Hz), low gamma (30-50Hz) and high gamma (50-80Hz). These responses were repeatable and totally abolished by tetrodotoxin, and greatly diminished by inhibitors of ionotropic and metabotropic glutamate receptors, GABAA receptor or gap-junctions. These observations suggest that the kainate-induced network activity can be a useful model of the network oscillation in the ACC circuit. PMID:26993576

  17. Dorsal Anterior Cingulate Cortex: A Bottom-Up View.

    PubMed

    Heilbronner, Sarah R; Hayden, Benjamin Y

    2016-07-01

    The dorsal anterior cingulate cortex (dACC) has attracted great interest from neuroscientists because it is associated with so many important cognitive functions. Despite, or perhaps because of, its rich functional repertoire, we lack a single comprehensive view of its function. Most research has approached this puzzle from the top down, using aggregate measures such as neuroimaging. We provide a view from the bottom up, with a focus on single-unit responses and anatomy. We summarize the strengths and weaknesses of the three major approaches to characterizing the dACC: as a monitor, as a controller, and as an economic structure. We argue that neurons in the dACC are specialized for representing contexts, or task-state variables relevant for behavior, and strategies, or aspects of future plans. We propose that dACC neurons link contexts with strategies by integrating diverse task-relevant information to create a rich representation of task space and exert high-level and abstract control over decision and action. PMID:27090954

  18. Increasing functional connectivity of the anterior cingulate cortex during the course of recovery from Bell's palsy.

    PubMed

    Hu, Sheng; Wu, Yuanyuan; Li, Chuanfu; Park, Kyungmo; Lu, Guangming; Mohamed, Abdalla Z; Wu, Hongli; Xu, Chunsheng; Zhang, Wei; Wang, Linying; Yang, Jun; Qiu, Bensheng

    2015-01-01

    Bell's palsy (BP), a unilateral and idiopathic palsy of the facial nerve, is a common disorder generally followed by a good natural recovery. The aim of this study was to investigate the relationship between the functional connectivity of the anterior cingulate cortex (ACC) and the recovery process of BP. Thirty-seven healthy volunteers and 67 patients were studied by functional MRI (fMRI). The seed regions of bilateral ACC were first extracted from the task-state fMRI data of healthy participants performing the task of mouth opening and closing. The connectivity of bilateral ACC was calculated from resting-state fMRI data of patients in whom only resting-state fMRI data were collected. The correlation between the strength of ACC's connectivity with the duration (time course of disease) was computed by analysis of covariance. It was found that the functional connectivity of the ACC ipsilateral to the lesioned side was enforced as the duration increased. The enforced brain areas included the sensorimotor areas and the ACC contralateral to the palsy. It was suggested that enforced functional connectivity of ACC might be related to cortical reorganization, which is important in the process of BP recovery. PMID:25426823

  19. Early adversity and combat exposure interact to influence anterior cingulate cortex volume in combat veterans☆

    PubMed Central

    Woodward, Steven H.; Kuo, Janice R.; Schaer, Marie; Kaloupek, Danny G.; Eliez, Stephan

    2013-01-01

    Objective Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach. Method Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis. Results As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes. Conclusions In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma. PMID:24179818

  20. Cognitive Functioning after Medial Frontal Lobe Damage Including the Anterior Cingulate Cortex: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J.; Dolan, Raymond J.; Cipolotti, Lisa

    2006-01-01

    Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was…

  1. Cocaine addiction: diffusion tensor imaging study of the inferior frontal and anterior cingulate white matter.

    PubMed

    Romero, Maria J; Asensio, Samuel; Palau, Carmina; Sanchez, Amparo; Romero, Francisco J

    2010-01-30

    Inferior frontal and anterior cingulate white matter integrity in 32 cocaine-dependent subjects was compared with that in 33 age-matched healthy control subjects. Diffusion tensor imaging data were acquired with a 1.5-T magnetic resonance imaging system. Cocaine-dependent subjects presented significantly lower fractional anisotropy values in inferior frontal white matter at the anterior-posterior commissure plane and higher anterior cingulate white matter values than control subjects. White matter integrity was also associated with impulsivity and motivation to change (Readiness to Change Questionnaire). These findings support the hypothesis that cocaine dependence involves a disruption of orbitofrontal connectivity and suggest that the anterior cingulate brain area might play a role in the motivation to change. PMID:19959341

  2. A direct anterior cingulate pathway to the primate primary olfactory cortex may control attention to olfaction.

    PubMed

    García-Cabezas, Miguel Á; Barbas, Helen

    2014-09-01

    Behavioral and functional studies in humans suggest that attention plays a key role in activating the primary olfactory cortex through an unknown circuit mechanism. We report that a novel pathway from the anterior cingulate cortex, an area which has a key role in attention, projects directly to the primary olfactory cortex in rhesus monkeys, innervating mostly the anterior olfactory nucleus. Axons from the anterior cingulate cortex formed synapses mostly with spines of putative excitatory pyramidal neurons and with a small proportion of a neurochemical class of inhibitory neurons that are thought to have disinhibitory effect on excitatory neurons. This novel pathway from the anterior cingulate is poised to exert a powerful excitatory effect on the anterior olfactory nucleus, which is a critical hub for odorant processing via extensive bilateral connections with primary olfactory cortices and the olfactory bulb. Acting on the anterior olfactory nucleus, the anterior cingulate may activate the entire primary olfactory cortex to mediate the process of rapid attention to olfactory stimuli. PMID:23797208

  3. Cognitive control and the anterior cingulate cortex: how conflicting stimuli affect attentional control in the rat

    PubMed Central

    Newman, Lori A.; Creer, David J.; McGaughy, Jill A.

    2014-01-01

    Converging evidence supports the hypothesis that the prefrontal cortex is critical for cognitive control. One prefrontal subregion, the anterior cingulate cortex, is hypothesized to be necessary to resolve response conflicts, disregard salient distractors and alter behavior in response to the generation of an error. These situations all involve goal-oriented monitoring of performance in order to effectively adjust cognitive processes. Several neuropsychological disorders, e.g., schizophrenia, attention deficit hyperactivity and obsessive compulsive disorder, are accompanied by morphological changes in the anterior cingulate cortex. These changes are hypothesized to underlie the impairments on tasks that require cognitive control found in these subjects. A novel conflict monitoring task was used to assess the effects on cognitive control of excitotoxic lesions to anterior cingulate cortex in rats. Prior to surgery all subjects showed improved accuracy on the second of two consecutive, incongruent trials. Lesions to the anterior cingulate cortex abolished this. Lesioned animals had difficulty in adjusting cognitive control on a trial-by-trial basis regardless of whether cognitive changes were increased or decreased. These results support a role for the anterior cingulate cortex in adjustments in cognitive control. PMID:25051488

  4. Cognitive control and the anterior cingulate cortex: how conflicting stimuli affect attentional control in the rat.

    PubMed

    Newman, Lori A; Creer, David J; McGaughy, Jill A

    2015-01-01

    Converging evidence supports the hypothesis that the prefrontal cortex is critical for cognitive control. One prefrontal subregion, the anterior cingulate cortex, is hypothesized to be necessary to resolve response conflicts, disregard salient distractors and alter behavior in response to the generation of an error. These situations all involve goal-oriented monitoring of performance in order to effectively adjust cognitive processes. Several neuropsychological disorders, e.g., schizophrenia, attention deficit hyperactivity and obsessive compulsive disorder, are accompanied by morphological changes in the anterior cingulate cortex. These changes are hypothesized to underlie the impairments on tasks that require cognitive control found in these subjects. A novel conflict monitoring task was used to assess the effects on cognitive control of excitotoxic lesions to anterior cingulate cortex in rats. Prior to surgery all subjects showed improved accuracy on the second of two consecutive, incongruent trials. Lesions to the anterior cingulate cortex abolished this. Lesioned animals had difficulty in adjusting cognitive control on a trial-by-trial basis regardless of whether cognitive changes were increased or decreased. These results support a role for the anterior cingulate cortex in adjustments in cognitive control. PMID:25051488

  5. The anterior insular and anterior cingulate cortices in emotional processing for self-face recognition.

    PubMed

    Morita, Tomoyo; Tanabe, Hiroki C; Sasaki, Akihiro T; Shimada, Koji; Kakigi, Ryusuke; Sadato, Norihiro

    2014-05-01

    Individuals can experience embarrassment when exposed to self-feedback images, depending on the extent of the divergence from the internal representation of the standard self. Our previous work implicated the anterior insular cortex (AI) and the anterior cingulate cortex (ACC) in the processing of embarrassment; however, their exact functional contributions have remained uncertain. Here, we explored the effects of being observed by others while viewing self-face images on the extent of embarrassment, and the activation and connectivity patterns in the AI and ACC. We conducted functional magnetic resonance imaging hyperscanning in pairs of healthy participants using an interaction system that allowed an individual to be observed by a partner in real time. Being observed increased the extent of embarrassment reported when viewing self-face images; a corresponding increase in self-related activity in the right AI suggested that this region played a direct role in the subjective experience. Being observed also increased the functional connectivity between the caudal ACC and prefrontal regions, which are involved in processing the reflective self. The ACC might therefore serve as a hub, integrating information about the reflective self that is used in evaluating perceptual self-face images. PMID:23377900

  6. The anterior insular and anterior cingulate cortices in emotional processing for self-face recognition

    PubMed Central

    Morita, Tomoyo; Tanabe, Hiroki C.; Sasaki, Akihiro T.; Shimada, Koji; Kakigi, Ryusuke

    2014-01-01

    Individuals can experience embarrassment when exposed to self-feedback images, depending on the extent of the divergence from the internal representation of the standard self. Our previous work implicated the anterior insular cortex (AI) and the anterior cingulate cortex (ACC) in the processing of embarrassment; however, their exact functional contributions have remained uncertain. Here, we explored the effects of being observed by others while viewing self-face images on the extent of embarrassment, and the activation and connectivity patterns in the AI and ACC. We conducted functional magnetic resonance imaging hyperscanning in pairs of healthy participants using an interaction system that allowed an individual to be observed by a partner in real time. Being observed increased the extent of embarrassment reported when viewing self-face images; a corresponding increase in self-related activity in the right AI suggested that this region played a direct role in the subjective experience. Being observed also increased the functional connectivity between the caudal ACC and prefrontal regions, which are involved in processing the reflective self. The ACC might therefore serve as a hub, integrating information about the reflective self that is used in evaluating perceptual self-face images. PMID:23377900

  7. Where the brain grows old: decline in anterior cingulate and medial prefrontal function with normal aging.

    PubMed

    Pardo, José V; Lee, Joel T; Sheikh, Sohail A; Surerus-Johnson, Christa; Shah, Hemant; Munch, Kristin R; Carlis, John V; Lewis, Scott M; Kuskowski, Michael A; Dysken, Maurice W

    2007-04-15

    Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer's disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown. PMID:17321756

  8. Ipsilateral hemiparesis and contralateral lower limb paresis caused by anterior cerebral artery territory infarct.

    PubMed

    Xu, Yongfeng; Liu, Lan

    2016-07-01

    Ipsilateral hemiparesis is rare after a supratentorial stroke, and the role of reorganization in the motor areas of unaffected hemisphere is important for the rehabilitation of the stroke patients. In this study, we present a patient who had a subclinical remote infarct in the right pons developed ipsilateral hemiparesis and contralateral lower limb paresis caused by a new infarct in the left anterior cerebral artery territory. Our case suggests that the motor areas of the unaffected hemisphere might be reorganized after stroke, which is important for the rehabilitation of stroke patients. PMID:27356659

  9. Dopamine D1 Receptors in the Anterior Cingulate Cortex Regulate Effort-Based Decision Making

    ERIC Educational Resources Information Center

    Schweimer, Judith; Hauber, Wolfgang

    2006-01-01

    The anterior cingulate cortex (ACC) has been implicated in encoding whether or not an action is worth performing in view of the expected benefit and the cost of performing the action. Dopamine input to the ACC may be critical for this form of effort-based decision making; however, the role of distinct ACC dopamine receptors is yet unknown.…

  10. Anterior Cingulate Volumetric Alterations in Treatment-Naive Adults with ADHD: A Pilot Study

    ERIC Educational Resources Information Center

    Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S., Jr.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.

    2010-01-01

    Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naive adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and…

  11. Reduced Anterior Cingulate Glutamatergic Concentrations in Childhood Ocd and Major Depression Versus Healthy Controls

    ERIC Educational Resources Information Center

    Rosenberg, David R.; Mirza, Yousha; Russell, Aileen; Tang, Jennifer; Smith, Janet M.; Banerjee, Preeya S.; Bhandari, Rashmi; Rose, Michelle; Ivey, Jennifer; Boyd, Courtney; Moore, Gregory J.

    2004-01-01

    Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of pediatric patients with obsessive-compulsive disorder (OCD) without major depressive disorder (MDD) versus pediatric patients with MDD without OCD and healthy controls. Method: Single-voxel proton magnetic resonance spectroscopic examinations…

  12. Response Monitoring, Repetitive Behaviour and Anterior Cingulate Abnormalities in Autism Spectrum Disorders (ASD)

    ERIC Educational Resources Information Center

    Thakkar, Katharine N.; Polli, Frida E.; Joseph, Robert M.; Tuch, David S.; Hadjikhani, Nouchine; Barton, Jason J. S.; Manoach, Dara S.

    2008-01-01

    Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing…

  13. The Role of the Dorsal Anterior Cingulate in Evaluating Behavior for Achieving Gains and Avoiding Losses

    ERIC Educational Resources Information Center

    Magno, Elena; Simoes-Franklin, Cristina; Robertson, Ian H.; Garavan, Hugh

    2009-01-01

    Effective goal-directed behavior relies on a network of regions including anterior cingulate cortex and ventral striatum to learn from negative outcomes in order to improve performance. We employed fMRI to determine if this frontal-striatal system is also involved in instances of behavior that do not presume negative circumstances. Participants…

  14. The effects of stimulation of the anterior cingulate gyrus in cats with freedom of movement

    NASA Technical Reports Server (NTRS)

    Dapres, G.; Cadilhac, J.; Passouant, P.

    1980-01-01

    Stimuli of varying strength, frequency and duration were applied to the anterior cingulate gyrus in unanesthetized cats with freedom of movement. The motor, vegetative and electrical effects of these stimuli, although inconstant, lead to a consideration of the role of this structure in the extrapyramidal control of motricity.

  15. Involvement of the Rat Anterior Cingulate Cortex in Control of Instrumental Responses Guided by Reward Expectancy

    ERIC Educational Resources Information Center

    Schweimer, Judith; Hauber, Wolfgang

    2005-01-01

    The anterior cingulate cortex (ACC) plays a critical role in stimulus-reinforcement learning and reward-guided selection of actions. Here we conducted a series of experiments to further elucidate the role of the ACC in instrumental behavior involving effort-based decision-making and instrumental learning guided by reward-predictive stimuli. In…

  16. Cytoarchitecture and Cortical Connections of the Anterior Cingulate and Adjacent Somatomotor Fields in the Rhesus Monkey

    PubMed Central

    Morecraft, RJ; Stilwell-Morecraft, KS; Cipolloni, PB; Ge, J; McNeal, DW; Pandya, DN

    2012-01-01

    The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining method and the fluorescent retrodgrade tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presense of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity

  17. Preparatory Activity and Connectivity in Dorsal Anterior Cingulate Cortex for Cognitive Control

    PubMed Central

    Schulz, Kurt P.; Bédard, Anne-Claude V.; Czarnecki, Rosa; Fan, Jin

    2011-01-01

    Dorsal anterior cingulate cortex (dACC) is composed of functionally distinct subregions that may contribute to the top-down control of response selection and preparation. Multiple motor areas have been identified in dACC, including an anterior zone implicated in conflict monitoring and a caudal zone involved in movement execution. This study tested the involvement of a third cingulate area, the posterior zone of dACC, in the top-down control of response selection and preparation. Sixteen healthy young adults were scanned with event-related functional magnetic resonance imaging while performing a cued go/no-go task that was designed to minimize response conflicts. The activation and functional connectivity of dACC were tested with standard convolution models and psychophysiological interaction analyses, respectively. Ready cues that informed the direction of the impending response triggered preparatory neural activity in the posterior zone of dACC and strengthened functional connectivity with the anterior and caudal zones of dACC, as well as perigenual anterior cingulate cortex, frontal operculum, dorsolateral prefrontal cortex, sensory association cortices, and extra-pyramidal motor areas. The preparatory cues activated dACC above and beyond the general arousing effects common to cues despite negligible conflict in the go/no-go task. The integration of cognitive, sensorimotor, and incentive signals in dACC places the region in an ideal position to select and prepare appropriate behavioral responses to achieve higher-level goals. PMID:21515388

  18. Exaggerated Activation of Dorsal Anterior Cingulate Cortex During Cognitive Interference: A Monozygotic Twin Study of Posttraumatic Stress Disorder

    PubMed Central

    Shin, Lisa M.; Bush, George; Milad, Mohammed R.; Lasko, Natasha B.; Brohawn, Kathryn Handwerger; Hughes, Katherine C.; Macklin, Michael L.; Gold, Andrea L.; Karpf, Rachel D.; Orr, Scott P.; Rauch, Scott L.; Pitman, Roger K.

    2013-01-01

    Objective Neuroimaging studies have revealed functional abnormalities in the anterior cingulate cortex in posttraumatic stress disorder (PTSD). The goal of the current research was to determine whether hyperresponsivity of the dorsal anterior cingulate in PTSD is an acquired characteristic or familial risk factor. Method Using a case-control twin design, we studied combat-exposed veterans with PTSD (n=12) and their identical combat-unexposed co-twins (n=12), as well as combat-exposed veterans without PTSD (n=14) and their identical combat-unexposed co-twins (n=14). Participants underwent functional magnetic resonance imaging during completion of the Multi-Source Interference Task, which reliably activates the dorsal anterior cingulate. Results Combat veterans with PTSD and their co-twins had significantly greater activation in the dorsal anterior cingulate and tended to have larger response time difference scores, as compared to non-PTSD veterans and their co-twins. Dorsal anterior cingulate activation in the exposed twins was positively correlated with their PTSD symptom severity. Dorsal anterior cingulate activation in the unexposed twins was positively correlated with their combat-exposed co-twins’ PTSD symptom severity, but not with depression or alcohol use severity in the combat-exposed co-twins. Conclusions Hyperresponsivity in the dorsal anterior cingulate appears to be a familial risk factor for the development of PTSD following psychological trauma. PMID:21724666

  19. Neural encoding of opposing strategy values in anterior and posterior cingulate cortex.

    PubMed

    Wan, Xiaohong; Cheng, Kang; Tanaka, Keiji

    2015-05-01

    Humans, and animals, often encounter ambiguous situations that require a decision on whether to take an offense or a defense strategy. Behavioral studies suggest that a strategy decision is frequently made before concrete options are evaluated. It remains enigmatic, however, how a strategy is determined without exploration of options. Here we investigated neural correlates of quick offense-versus-defense strategy decision in a board game, shogi. We found that the rostral anterior cingulate cortex and the posterior cingulate cortex complementally encoded the defense and attack strategy values, respectively. The dorsolateral prefrontal cortex compared the two strategy values. Several brain regions were activated during decision of concrete moves under an instructed strategy, whereas none of them showed correlation with defense or attack strategy values in their activities during strategy decision. These findings suggest that values of alternative strategies represented in different parts of the cingulate cortex have essential roles in intuitive strategy decision-making. PMID:25894290

  20. A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control.

    PubMed

    Tolomeo, Serenella; Christmas, David; Jentzsch, Ines; Johnston, Blair; Sprengelmeyer, Reiner; Matthews, Keith; Douglas Steele, J

    2016-06-01

    Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. It has previously been proposed that this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral anterior cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy control subjects. Using the Ekman 60 faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received anterior cingulotomy were impaired in recognizing negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with this hypothesis, we found that larger volume lesions predicted more impairment in recognizing fear, disgust and anger, and no impairment in recognizing facial expressions of surprise or happiness. However, we found no impairment in recognizing expressions of sadness. Also consistent with the hypothesis, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman's meta-analysis-derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimizing behaviour in the presence of such

  1. Anterior cingulate activity modulates nonlinear decision weight function of uncertain prospects.

    PubMed

    Paulus, Martin P; Frank, Lawrence R

    2006-04-01

    Prospect theory developed by Kahneman and Tversky has been among the most influential psychological models and explains many nonnormative decision-making phenomena, e.g. why people play the lottery or bet on long-shots. A Certainty Equivalent procedure was used during functional magnetic resonance imaging to identify the neural substrates that are important for nonlinear transformation of probabilities to decision weights. Differential activation in the anterior cingulate cortex during high versus low probability prospects correlated (r = 0.84, P < 0.01) with the degree of the nonlinearity of the transformation of probabilities to decision weights, which indicates that risk-seeking behavior for low probability prospects and risk-averse decision-making for mid to high probability prospects may be due to a lack of controlled processing by the anterior cingulate cortex. PMID:16321546

  2. Left anterior cingulate activity predicts intra-individual reaction time variability in healthy adults.

    PubMed

    Johnson, Beth P; Pinar, Ari; Fornito, Alex; Nandam, L Sanjay; Hester, Robert; Bellgrove, Mark A

    2015-06-01

    Within-subject, or intra-individual, variability in reaction time (RT) is increasingly recognised as an important indicator of the efficiency of attentional control, yet there have been few investigations of the neural correlates of trial-to-trial RT variability in healthy adults. We sought to determine the neural correlates of intra-individual RT variability during a go/no-go response inhibition task in 27 healthy, male participants. We found that reduced trial-to-trial RT variability (i.e. greater response stability) was significantly associated with greater activation in the left pregenual anterior cingulate. These results support the role of the left anterior cingulate in the dynamic control of attention and efficient response selection. Greater understanding of intra-individual RT variability and top-down attentional control in healthy adults may help to inform disorders that impact executive/attentional control, such as attention deficit hyperactivity disorder and schizophrenia. PMID:25791710

  3. Pattern recognition analysis of anterior cingulate cortex blood flow to classify depression polarity†

    PubMed Central

    Almeida, J. R. C.; Mourao-Miranda, J.; Aizenstein, H. J.; Versace, A.; Kozel, F. A.; Lu, H.; Marquand, A.; LaBarbara, E. J.; Brammer, M.; Trivedi, M.; Kupfer, D. J.; Phillips, M. L.

    2013-01-01

    Differentiating bipolar from recurrent unipolar depression is a major clinical challenge. In 18 healthy females and 36 females in a depressive episode - 18 with bipolar disorder type I, 18 with recurrent unipolar depression - we applied pattern recognition analysis using subdivisions of anterior cingulate cortex (ACC) blood flow at rest, measured with arterial spin labelling. Subgenual ACC blood flow classified unipolar v. bipolar depression with 81% accuracy (83% sensitivity, 78% specificity). PMID:23969484

  4. Blockade of opioid receptors in anterior cingulate cortex disrupts ethanol-seeking behavior in mice.

    PubMed

    Gremel, Christina M; Young, Emily A; Cunningham, Christopher L

    2011-06-01

    The anterior cingulate cortex (ACC) and opioid receptors have been suggested to play a role in attributing incentive motivational properties to drug-related cues. We examined whether blockade of ACC opioid receptors would reduce cue-induced ethanol-seeking behavior in mice. We show that intra-ACC opioid receptor blockade disrupted expression of an ethanol-induced conditioned place preference, suggesting that endogenous opioid modulation in the ACC may be critical for maintaining the cue's conditioned rewarding effects. PMID:21219940

  5. The effects of neurofeedback training in the cognitive division of the anterior cingulate gyrus.

    PubMed

    Cannon, Rex; Lubar, Joel; Congedo, Marco; Thornton, Keri; Towler, Kerry; Hutchens, Teresa

    2007-03-01

    This study examines the efficacy of neurofeedback training in the cognitive division of the anterior cingulate gyrus and describes its relationship with cortical regions known to be involved in executive functions. This study was conducted with eight non-clinical students, four male and four female, with a mean age of twenty-two. Learning occurred in the ACcd at significant levels over sessions and in the anterior regions that receive projections from the AC. There appears to be a multidimensional executive circuit that increases in the same frequency in apparent synchrony with the AC and it may be possible to train this sub-cortical region using LNFB. PMID:17365119

  6. Distinct neuronal organizations of the caudal cingulate motor area and supplementary motor area in monkeys for ipsilateral and contralateral hand movements

    PubMed Central

    Nakayama, Yoshihisa; Yokoyama, Osamu

    2015-01-01

    The caudal cingulate motor area (CMAc) and the supplementary motor area (SMA) play important roles in movement execution. The present study aimed to characterize the functional organization of these regions during movement by investigating laterality representations in the CMAc and SMA of monkeys via an examination of neuronal activity during a button press movement with either the right or left hand. Three types of movement-related neuronal activity were observed: 1) with only the contralateral hand, 2) with only the ipsilateral hand, and 3) with either hand. Neurons in the CMAc represented contralateral and ipsilateral hand movements to the same degree, whereas neuronal representations in the SMA were biased toward contralateral hand movement. Furthermore, recording neuronal activities using a linear-array multicontact electrode with 24 contacts spaced 150 μm apart allowed us to analyze the spatial distribution of neurons exhibiting particular hand preferences at the submillimeter scale. The CMAc and SMA displayed distinct microarchitectural organizations. The contralateral, ipsilateral, and bilateral CMAc neurons were distributed homogeneously, whereas SMA neurons exhibiting identical hand preferences tended to cluster. These findings indicate that the CMAc, which is functionally organized in a less structured manner than the SMA is, controls contralateral and ipsilateral hand movements in a counterbalanced fashion, whereas the SMA, which is more structured, preferentially controls contralateral hand movements. PMID:25717163

  7. Distinct neuronal organizations of the caudal cingulate motor area and supplementary motor area in monkeys for ipsilateral and contralateral hand movements.

    PubMed

    Nakayama, Yoshihisa; Yokoyama, Osamu; Hoshi, Eiji

    2015-04-01

    The caudal cingulate motor area (CMAc) and the supplementary motor area (SMA) play important roles in movement execution. The present study aimed to characterize the functional organization of these regions during movement by investigating laterality representations in the CMAc and SMA of monkeys via an examination of neuronal activity during a button press movement with either the right or left hand. Three types of movement-related neuronal activity were observed: 1) with only the contralateral hand, 2) with only the ipsilateral hand, and 3) with either hand. Neurons in the CMAc represented contralateral and ipsilateral hand movements to the same degree, whereas neuronal representations in the SMA were biased toward contralateral hand movement. Furthermore, recording neuronal activities using a linear-array multicontact electrode with 24 contacts spaced 150 μm apart allowed us to analyze the spatial distribution of neurons exhibiting particular hand preferences at the submillimeter scale. The CMAc and SMA displayed distinct microarchitectural organizations. The contralateral, ipsilateral, and bilateral CMAc neurons were distributed homogeneously, whereas SMA neurons exhibiting identical hand preferences tended to cluster. These findings indicate that the CMAc, which is functionally organized in a less structured manner than the SMA is, controls contralateral and ipsilateral hand movements in a counterbalanced fashion, whereas the SMA, which is more structured, preferentially controls contralateral hand movements. PMID:25717163

  8. EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex.

    PubMed

    Lim, Jonathan W C; Donahoo, Amber-Lee S; Bunt, Jens; Edwards, Timothy J; Fenlon, Laura R; Liu, Ying; Zhou, Jing; Moldrich, Randal X; Piper, Michael; Gobius, Ilan; Bailey, Timothy L; Wray, Naomi R; Kessaris, Nicoletta; Poo, Mu-Ming; Rubenstein, John L R; Richards, Linda J

    2015-11-01

    Transcription factors act during cortical development as master regulatory genes that specify cortical arealization and cellular identities. Although numerous transcription factors have been identified as being crucial for cortical development, little is known about their downstream targets and how they mediate the emergence of specific neuronal connections via selective axon guidance. The EMX transcription factors are essential for early patterning of the cerebral cortex, but whether EMX1 mediates interhemispheric connectivity by controlling corpus callosum formation remains unclear. Here, we demonstrate that in mice on the C57Bl/6 background EMX1 plays an essential role in the midline crossing of an axonal subpopulation of the corpus callosum derived from the anterior cingulate cortex. In the absence of EMX1, cingulate axons display reduced expression of the axon guidance receptor NRP1 and form aberrant axonal bundles within the rostral corpus callosum. EMX1 also functions as a transcriptional activator of Nrp1 expression in vitro, and overexpression of this protein in Emx1 knockout mice rescues the midline-crossing phenotype. These findings reveal a novel role for the EMX1 transcription factor in establishing cortical connectivity by regulating the interhemispheric wiring of a subpopulation of neurons within the mouse anterior cingulate cortex. PMID:26534986

  9. Prefrontal Thinning Affects Functional Connectivity and Regional Homogeneity of the Anterior Cingulate Cortex in Depression

    PubMed Central

    Späti, Jakub; Hänggi, Jürgen; Doerig, Nadja; Ernst, Jutta; Sambataro, Fabio; Brakowski, Janis; Jäncke, Lutz; grosse Holtforth, Martin; Seifritz, Erich; Spinelli, Simona

    2015-01-01

    Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment. PMID:25598428

  10. Increased task demand during spatial memory testing recruits the anterior cingulate cortex.

    PubMed

    Carr, Joshua K; Fournier, Neil M; Lehmann, Hugo

    2016-09-01

    We examined whether increasing retrieval difficulty in a spatial memory task would promote the recruitment of the anterior cingulate cortex (ACC) similar to what is typically observed during remote memory retrieval. Rats were trained on the hidden platform version of the Morris Water Task and tested three or 30 d later. Retrieval difficulty was manipulated by removing several prominent extra-pool cues from the testing room. Immediate early gene expression (c-Fos) in the ACC was greater following the cue removal and comparable to remote memory retrieval (30-d retention interval) levels, supporting the view of increased ACC contribution during high cognitive-demand memory processes. PMID:27531834

  11. Superior vena caval syndrome and ipsilateral pleural effusion: A rare presentation of anterior mediastinal thymoma.

    PubMed

    Das, Anirban; Pandit, Sudipta; Choudhury, Sabyasachi; Das, Sibes K; Basuthakur, Sumitra

    2014-10-01

    Incidence of thymic malignancies is very low. Thymoma, a tumor of thymus gland, is of epithelial origin and is most common anterior mediastinal tumor. In most cases, thymomas are localized and locally advanced thymomas may rarely present with superior vena caval obstruction (SVCO) and malignant pleural deposits. Microscopically, capsular invasion is noted in case of locally advanced thymomas, which behave like a malignant neoplasm. Complete surgical removal of the tumor along with intact capsule is the treatment modality of choice in case of localized tumors. Neoadjuvant radiotherapy (RT) and chemotherapy followed by surgical resection of residual tumor is useful in case of locally advanced tumors. RT is especially useful in case of SVCO to relieve the distressing respiratory symptoms. Here, we report a rare case of locally advanced thymoma, complicated by SVCO and ipsilateral pleural effusion in a 53-year-old male patient. PMID:25378848

  12. Temporal filtering of reward signals in the dorsal anterior cingulate cortex during a mixed-strategy game.

    PubMed

    Seo, Hyojung; Lee, Daeyeol

    2007-08-01

    The process of decision making in humans and other animals is adaptive and can be tuned through experience so as to optimize the outcomes of their choices in a dynamic environment. Previous studies have demonstrated that the anterior cingulate cortex plays an important role in updating the animal's behavioral strategies when the action outcome contingencies change. Moreover, neurons in the anterior cingulate cortex often encode the signals related to expected or actual reward. We investigated whether reward-related activity in the anterior cingulate cortex is affected by the animal's previous reward history. This was tested in rhesus monkeys trained to make binary choices in a computer-simulated competitive zero-sum game. The animal's choice behavior was relatively close to the optimal strategy but also revealed small systematic biases that are consistent with the use of a reinforcement learning algorithm. In addition, the activity of neurons in the dorsal anterior cingulate cortex that was related to the reward received by the animal in a given trial often was modulated by the rewards in the previous trials. Some of these neurons encoded the rate of rewards in previous trials, whereas others displayed activity modulations more closely related to the reward prediction errors. In contrast, signals related to the animal's choices were represented only weakly in this cortical area. These results suggest that neurons in the dorsal anterior cingulate cortex might be involved in the subjective evaluation of choice outcomes based on the animal's reward history. PMID:17670983

  13. Interareal Spike-Train Correlations of Anterior Cingulate and Dorsal Prefrontal Cortex during Attention Shifts.

    PubMed

    Oemisch, Mariann; Westendorff, Stephanie; Everling, Stefan; Womelsdorf, Thilo

    2015-09-23

    The anterior cingulate cortex (ACC) and prefrontal cortex (PFC) are believed to coactivate during goal-directed behavior to identify, select, and monitor relevant sensory information. Here, we tested whether coactivation of neurons across macaque ACC and PFC would be evident at the level of pairwise neuronal correlations during stimulus selection in a spatial attention task. We found that firing correlations emerged shortly after an attention cue, were evident for 50-200 ms time windows, were strongest for neuron pairs in area 24 (ACC) and areas 8 and 9 (dorsal PFC), and were independent of overall firing rate modulations. For a subset of cell pairs from ACC and dorsal PFC, the observed functional spike-train connectivity carried information about the direction of the attention shift. Reliable firing correlations were evident across area boundaries for neurons with broad spike waveforms (putative excitatory neurons) as well as for pairs of putative excitatory neurons and neurons with narrow spike waveforms (putative interneurons). These findings reveal that stimulus selection is accompanied by slow time scale firing correlations across those ACC/PFC subfields implicated to control and monitor attention. This functional coupling was informative about which stimulus was selected and thus indexed possibly the exchange of task-relevant information. We speculate that interareal, transient firing correlations reflect the transient coordination of larger, reciprocally interacting brain networks at a characteristic 50-200 ms time scale. Significance statement: Our manuscript identifies interareal spike-train correlations between primate anterior cingulate and dorsal prefrontal cortex during a period where attentional stimulus selection is likely controlled by these very same circuits. Interareal correlations emerged during the covert attention shift to one of two peripheral stimuli, proceeded on a slow 50-200 ms time scale, and occurred between putative pyramidal and

  14. Motivation and affective judgments differentially recruit neurons in the primate dorsolateral prefrontal and anterior cingulate cortex.

    PubMed

    Amemori, Ken-ichi; Amemori, Satoko; Graybiel, Ann M

    2015-02-01

    The judgment of whether to accept or to reject an offer is determined by positive and negative affect related to the offer, but affect also induces motivational responses. Rewarding and aversive cues influence the firing rates of many neurons in primate prefrontal and cingulate neocortical regions, but it still is unclear whether neurons in these regions are related to affective judgment or to motivation. To address this issue, we recorded simultaneously the neuronal spike activities of single units in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex (ACC) of macaque monkeys as they performed approach-avoidance (Ap-Av) and approach-approach (Ap-Ap) decision-making tasks that can behaviorally dissociate affective judgment and motivation. Notably, neurons having activity correlated with motivational condition could be distinguished from neurons having activity related to affective judgment, especially in the Ap-Av task. Although many neurons in both regions exhibited similar, selective patterns of task-related activity, we found a larger proportion of neurons activated in low motivational conditions in the dlPFC than in the ACC, and the onset of this activity was significantly earlier in the dlPFC than in the ACC. Furthermore, the temporal onsets of affective judgment represented by neuronal activities were significantly slower in the low motivational conditions than in the other conditions. These findings suggest that motivation and affective judgment both recruit dlPFC and ACC neurons but with differential degrees of involvement and timing. PMID:25653353

  15. Surface-based morphometry of the anterior cingulate cortex in first episode schizophrenia.

    PubMed

    Fornito, Alex; Yücel, Murat; Wood, Stephen J; Adamson, Chris; Velakoulis, Dennis; Saling, Michael M; McGorry, Patrick D; Pantelis, Christos

    2008-04-01

    The anterior cingulate cortex (ACC) appears to be critically involved in the pathophysiology of schizophrenia, but past attempts at characterizing pathological changes in the region using magnetic resonance imaging have been restricted by a limited appreciation of its functional and anatomical diversity and a reliance on relatively coarse metrics (e.g., volume) to index anatomical change. In this study, we applied a novel, surface-based protocol to T1-weighted scans acquired from 40 first episode schizophrenia patients and 40 healthy controls individually matched for age, sex, and morphology of the paracingulate sulcus, a major anatomical variation that has been shown to affect morphometric estimates in the region. The surface-based approach enabled calculation of regional grey matter volume, surface area and curvature, cortical thickness, and depth of the cingulate sulcus, with sub-millimeter precision. Relative to controls, schizophrenia patients displayed a bilateral reduction in thickness of paralimbic regions of the ACC, along with a concomitant increase in surface area of both the limbic and paralimbic ACC. No differences were identified for regional grey matter volume, surface curvature, or CS depth. These findings illustrate the advantages of moving beyond traditional volume-based approaches when investigating cortical morphometry, and indicate that the early stages of schizophrenia are associated with a specific pattern of ACC abnormalities that cannot be attributed to variations in sulcal and gyral morphology. PMID:17525988

  16. Postsynaptic potentiation of corticospinal projecting neurons in the anterior cingulate cortex after nerve injury

    PubMed Central

    2014-01-01

    Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain. PMID:24890933

  17. Motivation and Affective Judgments Differentially Recruit Neurons in the Primate Dorsolateral Prefrontal and Anterior Cingulate Cortex

    PubMed Central

    Amemori, Ken-ichi; Amemori, Satoko

    2015-01-01

    The judgment of whether to accept or to reject an offer is determined by positive and negative affect related to the offer, but affect also induces motivational responses. Rewarding and aversive cues influence the firing rates of many neurons in primate prefrontal and cingulate neocortical regions, but it still is unclear whether neurons in these regions are related to affective judgment or to motivation. To address this issue, we recorded simultaneously the neuronal spike activities of single units in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex (ACC) of macaque monkeys as they performed approach–avoidance (Ap–Av) and approach–approach (Ap–Ap) decision-making tasks that can behaviorally dissociate affective judgment and motivation. Notably, neurons having activity correlated with motivational condition could be distinguished from neurons having activity related to affective judgment, especially in the Ap–Av task. Although many neurons in both regions exhibited similar, selective patterns of task-related activity, we found a larger proportion of neurons activated in low motivational conditions in the dlPFC than in the ACC, and the onset of this activity was significantly earlier in the dlPFC than in the ACC. Furthermore, the temporal onsets of affective judgment represented by neuronal activities were significantly slower in the low motivational conditions than in the other conditions. These findings suggest that motivation and affective judgment both recruit dlPFC and ACC neurons but with differential degrees of involvement and timing. PMID:25653353

  18. Pain Inhibition by Optogenetic Activation of Specific Anterior Cingulate Cortical Neurons

    PubMed Central

    Gu, Ling; Uhelski, Megan L.; Anand, Sanjay; Romero-Ortega, Mario; Kim, Young-tae; Fuchs, Perry N.; Mohanty, Samarendra K.

    2015-01-01

    Cumulative evidence from both humans and animals suggests that the anterior cingulate cortex (ACC) is important for pain-related perception, and thus a likely target for pain relief therapy. However, use of existing electrode based ACC stimulation has not significantly reduced pain, at least in part due to the lack of specificity and likely co-activation of both excitatory and inhibitory neurons. Herein, we report a dramatic reduction of pain behavior in transgenic mice by optogenetic stimulation of the inhibitory neural circuitry of the ACC expressing channelrhodopsin-2. Electrophysiological measurements confirmed that stimulation of ACC inhibitory neurons is associated with decreased neural activity in the ACC. Further, a distinct optogenetic stimulation intensity and frequency-dependent inhibition of spiking activity in the ACC was observed. Moreover, we confirmed specific electrophysiological responses from different neuronal units in the thalamus, in response to particular types of painful stimuli (i,e., formalin injection, pinch), which we found to be modulated by optogenetic control of the ACC inhibitory neurons. These results underscore the inhibition of the ACC as a clinical alternative in inhibiting chronic pain, and leads to a better understanding of the pain processing circuitry of the cingulate cortex. PMID:25714399

  19. The Anterior Cingulate Gyrus and Social Cognition: Tracking the Motivation of Others.

    PubMed

    Apps, Matthew A J; Rushworth, Matthew F S; Chang, Steve W C

    2016-05-18

    The anterior cingulate cortex (ACC) is implicated in a broad range of behaviors and cognitive processes, but it has been unclear what contribution, if any, the ACC makes to social behavior. We argue that anatomical and functional evidence suggests that a specific sub-region of ACC-in the gyrus (ACCg)-plays a crucial role in processing social information. We propose that the computational properties of the ACCg support a contribution to social cognition by estimating how motivated other individuals are and dynamically updating those estimates when further evidence suggests they have been erroneous. Notably this model, based on vicarious motivation and error processing, provides a unified account of neurophysiological and neuroimaging evidence that the ACCg is sensitive to costs, benefits, and errors during social interactions. Furthermore, it makes specific, testable predictions about a key mechanism that may underpin variability in socio-cognitive abilities in health and disease. PMID:27196973

  20. The expected value of control: an integrative theory of anterior cingulate cortex function.

    PubMed

    Shenhav, Amitai; Botvinick, Matthew M; Cohen, Jonathan D

    2013-07-24

    The dorsal anterior cingulate cortex (dACC) has a near-ubiquitous presence in the neuroscience of cognitive control. It has been implicated in a diversity of functions, from reward processing and performance monitoring to the execution of control and action selection. Here, we propose that this diversity can be understood in terms of a single underlying function: allocation of control based on an evaluation of the expected value of control (EVC). We present a normative model of EVC that integrates three critical factors: the expected payoff from a controlled process, the amount of control that must be invested to achieve that payoff, and the cost in terms of cognitive effort. We propose that dACC integrates this information, using it to determine whether, where and how much control to allocate. We then consider how the EVC model can explain the diverse array of findings concerning dACC function. PMID:23889930

  1. Synapses with inhibitory neurons differentiate anterior cingulate from dorsolateral prefrontal pathways associated with cognitive control

    PubMed Central

    Medalla, M.; Barbas, H.

    2009-01-01

    Summary The primate dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) focus attention on relevant signals and suppress noise in cognitive tasks. However, their synaptic interactions and unique roles in cognitive control are unknown. We report that two distinct pathways to DLPFC area 9, one from the neighboring area 46 and the other from the functionally distinct ACC, similarly innervate excitatory neurons associated with selecting relevant stimuli. However, ACC has more prevalent and larger synapses with inhibitory neurons and preferentially innervates calbindin inhibitory neurons, which reduce noise by inhibiting excitatory neurons. In contrast, area 46 mostly innervates calretinin inhibitory neurons, which disinhibit excitatory neurons. These synaptic specializations suggest that ACC has a greater impact in reducing noise in dorsolateral areas during challenging cognitive tasks involving conflict, error, or reversing decisions, mechanisms that are disrupted in schizophrenia. These observations highlight the unique roles of the DLPFC and ACC in cognitive control. PMID:19249280

  2. The expected value of control: An integrative theory of anterior cingulate cortex function

    PubMed Central

    Shenhav, Amitai; Botvinick, Matthew M.; Cohen, Jonathan D.

    2013-01-01

    Summary The dorsal anterior cingulate cortex (dACC) has a near-ubiquitous presence in the neuroscience of cognitive control. It has been implicated in a diversity of functions, from reward processing and performance monitoring to the execution of control and action selection. Here, we propose that this diversity can be understood in terms of a single underlying function: allocation of control based on an evaluation of the expected value of control (EVC). We present a normative model of EVC that integrates three critical factors: the expected payoff from a controlled process, the amount of control that must be invested to achieve that payoff, and the cost in terms of cognitive effort. We propose that dACC integrates this information, using it to determine whether, where and how much control to allocate. We then consider how the EVC model can explain the diverse array of findings concerning dACC function. PMID:23889930

  3. Observational learning computations in neurons of the human anterior cingulate cortex.

    PubMed

    Hill, Michael R; Boorman, Erie D; Fried, Itzhak

    2016-01-01

    When learning from direct experience, neurons in the primate brain have been shown to encode a teaching signal used by algorithms in artificial intelligence: the reward prediction error (PE)-the difference between how rewarding an event is, and how rewarding it was expected to be. However, in humans and other species learning often takes place by observing other individuals. Here, we show that, when humans observe other players in a card game, neurons in their rostral anterior cingulate cortex (rACC) encode both the expected value of an observed choice, and the PE after the outcome was revealed. Notably, during the same task neurons recorded in the amygdala (AMY) and the rostromedial prefrontal cortex (rmPFC) do not exhibit this type of encoding. Our results suggest that humans learn by observing others, at least in part through the encoding of observational PEs in single neurons in the rACC. PMID:27598687

  4. Behavioral variability through stochastic choice and its gating by anterior cingulate cortex.

    PubMed

    Tervo, Dougal G R; Proskurin, Mikhail; Manakov, Maxim; Kabra, Mayank; Vollmer, Alison; Branson, Kristin; Karpova, Alla Y

    2014-09-25

    Behavioral choices that ignore prior experience promote exploration and unpredictability but are seemingly at odds with the brain's tendency to use experience to optimize behavioral choice. Indeed, when faced with virtual competitors, primates resort to strategic counter prediction rather than to stochastic choice. Here, we show that rats also use history- and model-based strategies when faced with similar competitors but can switch to a "stochastic" mode when challenged with a competitor that they cannot defeat by counter prediction. In this mode, outcomes associated with an animal's actions are ignored, and normal engagement of anterior cingulate cortex (ACC) is suppressed. Using circuit perturbations in transgenic rats, we demonstrate that switching between strategic and stochastic behavioral modes is controlled by locus coeruleus input into ACC. Our findings suggest that, under conditions of uncertainty about environmental rules, changes in noradrenergic input alter ACC output and prevent erroneous beliefs from guiding decisions, thus enabling behavioral variation. PAPERCLIP: PMID:25259917

  5. Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain.

    PubMed

    Bliss, Tim V P; Collingridge, Graham L; Kaang, Bong-Kiun; Zhuo, Min

    2016-08-01

    The anterior cingulate cortex (ACC) is activated in both acute and chronic pain. In this Review, we discuss increasing evidence from rodent studies that ACC activation contributes to chronic pain states and describe several forms of synaptic plasticity that may underlie this effect. In particular, one form of long-term potentiation (LTP) in the ACC, which is triggered by the activation of NMDA receptors and expressed by an increase in AMPA-receptor function, sustains the affective component of the pain state. Another form of LTP in the ACC, which is triggered by the activation of kainate receptors and expressed by an increase in glutamate release, may contribute to pain-related anxiety. PMID:27307118

  6. Empathic responsiveness in amygdala and anterior cingulate cortex in youths with psychopathic traits

    PubMed Central

    Marsh, Abigail A.; Finger, Elizabeth C.; Fowler, Katherine A.; Adalio, Christopher J.; Jurkowitz, Ilana T.N.; Schechter, Julia C.; Pine, Daniel S.; Decety, Jean; Blair, R. J. R.

    2013-01-01

    Background Psychopathic traits are associated with increases in antisocial behaviors such as aggression and are characterized by reduced empathy for others’ distress. This suggests that psychopathic traits may also impair empathic pain sensitivity. However, whether psychopathic traits affect responses to the pain of others versus the self has not been previously assessed. Method We used whole-brain functional magnetic resonance imaging (fMRI) scanning to measure neural activation in 14 adolescents with Oppositional Defiant Disorder or Conduct Disorder and psychopathic traits, as well as 21 healthy controls matched on age, sex, and intelligence. Activation in structures associated with empathic pain perception was assessed as adolescents viewed photographs of pain-inducing injuries. Adolescents imagined either that the body in each photograph was their own or that it belonged to another person. Behavioral and neuroimaging data were analyzed using random-effects analysis of variance. Results Youths with psychopathic traits showed reduced activity within regions associated with empathic pain as the depicted pain increased. These regions included rostral anterior cingulate cortex, ventral striatum (putamen), and amygdala. Reductions in amygdala activity particularly occurred when the injury was perceived as occurring to another. Empathic pain responses within both amygdala and rostral anterior cingulate cortex were negatively correlated with the severity of psychopathic traits as indexed by PCL:YV scores. Conclusions Youths with psychopathic traits show less responsiveness in regions implicated in the affective response to another’s pain as the perceived intensity of this pain increases. Moreover, this reduced responsiveness appears to predict symptom severity. PMID:23488588

  7. Learning to cope with stress modulates anterior cingulate cortex stargazin expression in monkeys and mice.

    PubMed

    Lee, Alex G; Capanzana, Roxanne; Brockhurst, Jacqueline; Cheng, Michelle Y; Buckmaster, Christine L; Absher, Devin; Schatzberg, Alan F; Lyons, David M

    2016-05-01

    Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping with gains in subsequent emotion regulation. Here we investigate the effects of learning to cope with stress on anterior cingulate cortex gene expression in monkeys and mice. Anterior cingulate cortex is involved in learning, memory, cognitive control, and emotion regulation. Monkeys and mice were randomized to either stress coping or no-stress treatment conditions. Profiles of gene expression were acquired with HumanHT-12v4.0 Expression BeadChip arrays adapted for monkeys. Three genes identified in monkeys by arrays were then assessed in mice by quantitative real-time polymerase chain reaction. Expression of a key gene (PEMT) involved in acetylcholine biosynthesis was increased in monkeys by coping but this result was not verified in mice. Another gene (SPRY2) that encodes a negative regulator of neurotrophic factor signaling was decreased in monkeys by coping but this result was only partly verified in mice. The CACNG2 gene that encodes stargazin (also called TARP gamma-2) was increased by coping in monkeys as well as mice randomized to coping with or without subsequent behavioral tests of emotionality. As evidence of coping effects distinct from repeated stress exposures per se, increased stargazin expression induced by coping correlated with diminished emotionality in mice. Stargazin modulates glutamate receptor signaling and plays a role in synaptic plasticity. Molecular mechanisms of synaptic plasticity that mediate learning and memory in the context of coping with stress may provide novel targets for new treatments of disorders in human mental health. PMID:27003116

  8. Post-Learning Infusion of Anisomycin into the Anterior Cingulate Cortex Impairs Instrumental Acquisition through an Effect on Reinforcer Valuation

    ERIC Educational Resources Information Center

    Jonkman, Sietse; Everitt, Barry J.

    2009-01-01

    The integrity of the rodent anterior cingulate cortex (ACC) is essential for various aspects of instrumental behavior, but it is not clear if the ACC is important for the acquisition of a simple instrumental response. Here, it was demonstrated that post-session infusions of anisomycin into the rat ACC completely prevented the acquisition of…

  9. Involvement of the Anterior Cingulate Cortex in Formation, Consolidation, and Reconsolidation of Recent and Remote Contextual Fear Memory

    ERIC Educational Resources Information Center

    Einarsson, Einar O.; Nader, Karim

    2012-01-01

    It has been suggested that memories become more stable and less susceptible to the disruption of reconsolidation over weeks after learning. Here, we test this by targeting the anterior cingulate cortex (ACC) and test its involvement in the formation, consolidation, and reconsolidation of recent and remote contextual fear memory. We found that…

  10. Reduced Error-Related Activation in Two Anterior Cingulate Circuits Is Related to Impaired Performance in Schizophrenia

    ERIC Educational Resources Information Center

    Polli, Frida E.; Barton, Jason J. S.; Thakkar, Katharine N.; Greve, Douglas N.; Goff, Donald C.; Rauch, Scott L.; Manoach, Dara S.

    2008-01-01

    To perform well on any challenging task, it is necessary to evaluate your performance so that you can learn from errors. Recent theoretical and experimental work suggests that the neural sequellae of error commission in a dorsal anterior cingulate circuit index a type of contingency- or reinforcement-based learning, while activation in a rostral…

  11. Anterior Cingulate Cortex and Cognitive Control: Neuropsychological and Electrophysiological Findings in Two Patients with Lesions to Dorsomedial Prefrontal Cortex

    ERIC Educational Resources Information Center

    Lovstad, M.; Funderud, I.; Meling, T.; Kramer, U. M.; Voytek, B.; Due-Tonnessen, P.; Endestad, T.; Lindgren, M.; Knight, R. T.; Solbakk, A. K.

    2012-01-01

    Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial…

  12. An Herbal Nasal Drop Enhanced Frontal and Anterior Cingulate Cortex Activity

    PubMed Central

    Chan, Agnes S.; Cheung, Mei-chun; Sze, Sophia L.; Leung, Winnie W.; Shi, Dejian

    2011-01-01

    The present study examined the neuro-electrophysiological activity of the brain associated with the application of a herbal remedy developed by a Shaolin monk based upon the Chan healing principle of clearing the orifices (i.e., the nasal cavities). A repeated-measures design was used. Fourteen normal adults were administered herbal remedy and saline solution intranasally on separate sessions. Two intervals of eyes-closed resting EEG data were obtained individually before and after each administration. Results showed that only the herbal remedy but not the saline solution induced elevation in cordance, an index correlated with cerebral perfusion, in the anterior brain region. In addition, the activity of the anterior cingulate cortex (ACC), as examined by the LORETA analysis, was also increased after the application of the herbal remedy but not saline solution. The present study provided some preliminary evidence suggesting that the herbal nasal drop enhanced the activity of the frontal lobe and ACC. Implications for the potential clinical application of the herbal remedy to treat patients with frontal lobe disorders were discussed. PMID:19996154

  13. Resting-state functional connectivity in anterior cingulate cortex in normal aging

    PubMed Central

    Cao, Weifang; Luo, Cheng; Zhu, Bin; Zhang, Dan; Dong, Li; Gong, Jinnan; Gong, Diankun; He, Hui; Tu, Shipeng; Yin, Wenjie; Li, Jianfu; Chen, Huafu; Yao, Dezhong

    2014-01-01

    Growing evidence suggests that normal aging is associated with cognitive decline and well-maintained emotional well-being. The anterior cingulate cortex (ACC) is an important brain region involved in emotional and cognitive processing. We investigated resting-state functional connectivity (FC) of two ACC subregions in 30 healthy older adults vs. 33 healthy younger adults, by parcellating into rostral (rACC) and dorsal (dACC) ACC based on clustering of FC profiles. Compared with younger adults, older adults demonstrated greater connection between rACC and anterior insula, suggesting that older adults recruit more proximal dACC brain regions connected with insula to maintain a salient response. Older adults also demonstrated increased FC between rACC and superior temporal gyrus and inferior frontal gyrus, decreased integration between rACC and default mode, and decreased dACC-hippocampal and dACC-thalamic connectivity. These altered FCs reflected rACC and dACC reorganization, and might be related to well emotion regulation and cognitive decline in older adults. Our findings provide further insight into potential functional substrates of emotional and cognitive alterations in the aging brain. PMID:25400578

  14. A meta-analysis of the anterior cingulate contribution to social pain

    PubMed Central

    Lemogne, Cedric; Hinfray, Sophie; Huguet, Pascal; Grynszpan, Ouriel; Tartour, Eric; George, Nathalie; Fossati, Philippe

    2015-01-01

    Many functional magnetic resonance imaging studies have explored the neural correlates of social pain that results from social threat, exclusion, rejection, loss or negative evaluation. Although activations have consistently been reported within the anterior cingulate cortex (ACC), it remains unclear which ACC subdivision is particularly involved. To provide a quantitative estimation of the specific involvement of ACC subdivisions in social pain, we conducted a voxel-based meta-analysis. The literature search identified 46 articles that included 940 subjects, the majority of which used the cyberball task. Significant likelihoods of activation were found in both the ventral and dorsal ACC for both social pain elicitation and self-reported distress during social pain. Self-reported distress involved more specifically the subgenual and pregenual ACC than social pain-related contrasts. The cyberball task involved the anterior midcingulate cortex to a lesser extent than other experimental tasks. During social pain, children exhibited subgenual activations to a greater extent than adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball studies was related to the length of exclusion phases. The present meta-analysis contributes to a better understanding of the role of ACC subdivisions in social pain, and it could be of particular importance for guiding future studies of social pain and its neural underpinnings. PMID:25140048

  15. A meta-analysis of the anterior cingulate contribution to social pain.

    PubMed

    Rotge, Jean-Yves; Lemogne, Cedric; Hinfray, Sophie; Huguet, Pascal; Grynszpan, Ouriel; Tartour, Eric; George, Nathalie; Fossati, Philippe

    2015-01-01

    Many functional magnetic resonance imaging studies have explored the neural correlates of social pain that results from social threat, exclusion, rejection, loss or negative evaluation. Although activations have consistently been reported within the anterior cingulate cortex (ACC), it remains unclear which ACC subdivision is particularly involved. To provide a quantitative estimation of the specific involvement of ACC subdivisions in social pain, we conducted a voxel-based meta-analysis. The literature search identified 46 articles that included 940 subjects, the majority of which used the cyberball task. Significant likelihoods of activation were found in both the ventral and dorsal ACC for both social pain elicitation and self-reported distress during social pain. Self-reported distress involved more specifically the subgenual and pregenual ACC than social pain-related contrasts. The cyberball task involved the anterior midcingulate cortex to a lesser extent than other experimental tasks. During social pain, children exhibited subgenual activations to a greater extent than adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball studies was related to the length of exclusion phases. The present meta-analysis contributes to a better understanding of the role of ACC subdivisions in social pain, and it could be of particular importance for guiding future studies of social pain and its neural underpinnings. PMID:25140048

  16. Encoding of Vicarious Reward Prediction in Anterior Cingulate Cortex and Relationship with Trait Empathy

    PubMed Central

    Apps, Matthew A.J.; Roiser, Jonathan P.; Viding, Essi

    2015-01-01

    Empathy—the capacity to understand and resonate with the experiences of others—can depend on the ability to predict when others are likely to receive rewards. However, although a plethora of research has examined the neural basis of predictions about the likelihood of receiving rewards ourselves, very little is known about the mechanisms that underpin variability in vicarious reward prediction. Human neuroimaging and nonhuman primate studies suggest that a subregion of the anterior cingulate cortex in the gyrus (ACCg) is engaged when others receive rewards. Does the ACCg show specialization for processing predictions about others' rewards and not one's own and does this specialization vary with empathic abilities? We examined hemodynamic responses in the human brain time-locked to cues that were predictive of a high or low probability of a reward either for the subject themselves or another person. We found that the ACCg robustly signaled the likelihood of a reward being delivered to another. In addition, ACCg response significantly covaried with trait emotion contagion, a necessary foundation for empathizing with other individuals. In individuals high in emotion contagion, the ACCg was specialized for processing others' rewards exclusively, but for those low in emotion contagion, this region also responded to information about the subject's own rewards. Our results are the first to show that the ACCg signals probabilistic predictions about rewards for other people and that the substantial individual variability in the degree to which the ACCg is specialized for processing others' rewards is related to trait empathy. SIGNIFICANCE STATEMENT Successfully cooperating, competing, or empathizing with others can depend on our ability to predict when others are going to get something rewarding. Although many studies have examined how the brain processes rewards we will get ourselves, very little is known about vicarious reward processing. Here, we show that a

  17. The Role of the Subgenual Anterior Cingulate Cortex and Amygdala in Environmental Sensitivity to Infant Crying

    PubMed Central

    Mutschler, Isabella; Ball, Tonio; Kirmse, Ursula; Wieckhorst, Birgit; Pluess, Michael; Klarhöfer, Markus; Meyer, Andrea H.; Wilhelm, Frank H.; Seifritz, Erich

    2016-01-01

    Newborns and infants communicate their needs and physiological states through crying and emotional facial expressions. Little is known about individual differences in responding to infant crying. Several theories suggest that people vary in their environmental sensitivity with some responding generally more and some generally less to environmental stimuli. Such differences in environmental sensitivity have been associated with personality traits, including neuroticism. This study investigated whether neuroticism impacts neuronal, physiological, and emotional responses to infant crying by investigating blood-oxygenation-level dependent (BOLD) responses using functional magnetic resonance imaging (fMRI) in a large sample of healthy women (N = 102) with simultaneous skin conductance recordings. Participants were repeatedly exposed to a video clip that showed crying infants and emotional responses (valence, arousal, and irritation) were assessed after every video clip presentation. Increased BOLD signal during the perception of crying infants was found in brain regions that are associated with emotional responding, the amygdala and anterior insula. Significant BOLD signal decrements (i.e., habituation) were found in the fusiform gyrus, middle temporal gyrus, superior temporal gyrus, Broca’s homologue on the right hemisphere, (laterobasal) amygdala, and hippocampus. Individuals with high neuroticism showed stronger activation in the amygdala and subgenual anterior cingulate cortex (sgACC) when exposed to infant crying compared to individuals with low neuroticism. In contrast to our prediction we found no evidence that neuroticism impacts fMRI-based measures of habituation. Individuals with high neuroticism showed elevated skin conductance responses, experienced more irritation, and perceived infant crying as more unpleasant. The results support the hypothesis that individuals high in neuroticism are more emotionally responsive, experience more negative emotions, and

  18. The Role of the Subgenual Anterior Cingulate Cortex and Amygdala in Environmental Sensitivity to Infant Crying.

    PubMed

    Mutschler, Isabella; Ball, Tonio; Kirmse, Ursula; Wieckhorst, Birgit; Pluess, Michael; Klarhöfer, Markus; Meyer, Andrea H; Wilhelm, Frank H; Seifritz, Erich

    2016-01-01

    Newborns and infants communicate their needs and physiological states through crying and emotional facial expressions. Little is known about individual differences in responding to infant crying. Several theories suggest that people vary in their environmental sensitivity with some responding generally more and some generally less to environmental stimuli. Such differences in environmental sensitivity have been associated with personality traits, including neuroticism. This study investigated whether neuroticism impacts neuronal, physiological, and emotional responses to infant crying by investigating blood-oxygenation-level dependent (BOLD) responses using functional magnetic resonance imaging (fMRI) in a large sample of healthy women (N = 102) with simultaneous skin conductance recordings. Participants were repeatedly exposed to a video clip that showed crying infants and emotional responses (valence, arousal, and irritation) were assessed after every video clip presentation. Increased BOLD signal during the perception of crying infants was found in brain regions that are associated with emotional responding, the amygdala and anterior insula. Significant BOLD signal decrements (i.e., habituation) were found in the fusiform gyrus, middle temporal gyrus, superior temporal gyrus, Broca's homologue on the right hemisphere, (laterobasal) amygdala, and hippocampus. Individuals with high neuroticism showed stronger activation in the amygdala and subgenual anterior cingulate cortex (sgACC) when exposed to infant crying compared to individuals with low neuroticism. In contrast to our prediction we found no evidence that neuroticism impacts fMRI-based measures of habituation. Individuals with high neuroticism showed elevated skin conductance responses, experienced more irritation, and perceived infant crying as more unpleasant. The results support the hypothesis that individuals high in neuroticism are more emotionally responsive, experience more negative emotions, and may

  19. Attention for speaking: domain-general control from the anterior cingulate cortex in spoken word production

    PubMed Central

    Piai, Vitória; Roelofs, Ardi; Acheson, Daniel J.; Takashima, Atsuko

    2013-01-01

    Accumulating evidence suggests that some degree of attentional control is required to regulate and monitor processes underlying speaking. Although progress has been made in delineating the neural substrates of the core language processes involved in speaking, substrates associated with regulatory and monitoring processes have remained relatively underspecified. We report the results of an fMRI study examining the neural substrates related to performance in three attention-demanding tasks varying in the amount of linguistic processing: vocal picture naming while ignoring distractors (picture-word interference, PWI); vocal color naming while ignoring distractors (Stroop); and manual object discrimination while ignoring spatial position (Simon task). All three tasks had congruent and incongruent stimuli, while PWI and Stroop also had neutral stimuli. Analyses focusing on common activation across tasks identified a portion of the dorsal anterior cingulate cortex (ACC) that was active in incongruent trials for all three tasks, suggesting that this region subserves a domain-general attentional control function. In the language tasks, this area showed increased activity for incongruent relative to congruent stimuli, consistent with the involvement of domain-general mechanisms of attentional control in word production. The two language tasks also showed activity in anterior-superior temporal gyrus (STG). Activity increased for neutral PWI stimuli (picture and word did not share the same semantic category) relative to incongruent (categorically related) and congruent stimuli. This finding is consistent with the involvement of language-specific areas in word production, possibly related to retrieval of lexical-semantic information from memory. The current results thus suggest that in addition to engaging language-specific areas for core linguistic processes, speaking also engages the ACC, a region that is likely implementing domain-general attentional control. PMID:24368899

  20. Impaired rapid error monitoring but intact error signaling following rostral anterior cingulate cortex lesions in humans

    PubMed Central

    Maier, Martin E.; Di Gregorio, Francesco; Muricchio, Teresa; Di Pellegrino, Giuseppe

    2015-01-01

    Detecting one’s own errors and appropriately correcting behavior are crucial for efficient goal-directed performance. A correlate of rapid evaluation of behavioral outcomes is the error-related negativity (Ne/ERN) which emerges at the time of the erroneous response over frontal brain areas. However, whether the error monitoring system’s ability to distinguish between errors and correct responses at this early time point is a necessary precondition for the subsequent emergence of error awareness remains unclear. The present study investigated this question using error-related brain activity and vocal error signaling responses in seven human patients with lesions in the rostral anterior cingulate cortex (rACC) and adjoining ventromedial prefrontal cortex, while they performed a flanker task. The difference between errors and correct responses was severely attenuated in these patients indicating impaired rapid error monitong, but they showed no impairment in error signaling. However, impaired rapid error monitoring coincided with a failure to increase response accuracy on trials following errors. These results demonstrate that the error monitoring system’s ability to distinguish between errors and correct responses at the time of the response is crucial for adaptive post-error adjustments, but not a necessary precondition for error awareness. PMID:26136674

  1. Longitudinal stability of the folding pattern of the anterior cingulate cortex during development.

    PubMed

    Cachia, A; Borst, G; Tissier, C; Fisher, C; Plaze, M; Gay, O; Rivière, D; Gogtay, N; Giedd, J; Mangin, J-F; Houdé, O; Raznahan, A

    2016-06-01

    Prenatal processes are likely critical for the differences in cognitive ability and disease risk that unfold in postnatal life. Prenatally established cortical folding patterns are increasingly studied as an adult proxy for earlier development events - under the as yet untested assumption that an individual's folding pattern is developmentally fixed. Here, we provide the first empirical test of this stability assumption using 263 longitudinally-acquired structural MRI brain scans from 75 typically developing individuals spanning ages 7 to 32 years. We focus on the anterior cingulate cortex (ACC) - an intensely studied cortical region that presents two qualitatively distinct and reliably classifiable sulcal patterns with links to postnatal behavior. We show - without exception-that individual ACC sulcal patterns are fixed from childhood to adulthood, at the same time that quantitative anatomical ACC metrics are undergoing profound developmental change. Our findings buttress use of folding typology as a postnatally-stable marker for linking variations in early brain development to later neurocognitive outcomes in ex utero life. PMID:26974743

  2. Dopaminergic Modulation of Excitatory Transmission in the Anterior Cingulate Cortex of Adult Mice.

    PubMed

    Darvish-Ghane, Soroush; Yamanaka, Manabu; Zhuo, Min

    2016-01-01

    Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 μM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 μM). Furthermore, selective postsynaptic application of GDP-β-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 μM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of potentiation and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 μM) and sulpiride (100 μM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA. PMID:27317578

  3. Astrocytic activation in the anterior cingulate cortex is critical for sleep disorder under neuropathic pain.

    PubMed

    Yamashita, Akira; Hamada, Asami; Suhara, Yuki; Kawabe, Rui; Yanase, Makoto; Kuzumaki, Naoko; Narita, Michiko; Matsui, Ryosuke; Okano, Hideyuki; Narita, Minoru

    2014-06-01

    Insomnia, depression, and anxiety disorder are common problems for people with neuropathic pain. In this study, mild noxious heat stimuli increased the duration and number of spontaneous pain-like behaviors in sciatic nerve-ligated mice. We used functional magnetic resonance imaging to visualize the increased blood oxygenation level-dependent signal intensity in the anterior cingulate cortex (ACC) of mice with sciatic nerve ligation under mild noxious stimuli. Such stimuli significantly increased the release of glutamate in the ACC of nerve-ligated mice. In addition, sciatic nerve ligation and mild noxious stimuli changed the morphology of astrocytes in the ACC. Treatment of cortical astrocytes with glutamate caused astrocytic activation, as detected by a stellate morphology. Furthermore, glutamate induced the translocation of GAT-3 to astrocyte cell membranes using primary cultured glial cells from the mouse cortex. Moreover, the GABA level at the synaptic cleft in the ACC of nerve-ligated mice was significantly decreased exposure to mild noxious stimuli. Finally, we investigated whether astrocytic activation in the ACC could directly mediate sleep disorder. With the optogenetic tool channel rhodopsin-2 (ChR2), we demonstrated that selective photostimulation of these astrocytes in vivo triggered sleep disturbance. Taken together, these results suggest that neuropathic pain-like stimuli activated astrocytes in the ACC and decreased the extracellular concentration of GABA via an increase in the release of glutamate. Furthermore, these findings provide novel evidence that astrocytic activation in the ACC can mimic sleep disturbance in mice. PMID:24488840

  4. Folding of the anterior cingulate cortex partially explains inhibitory control during childhood: a longitudinal study.

    PubMed

    Borst, G; Cachia, A; Vidal, J; Simon, G; Fischer, C; Pineau, A; Poirel, N; Mangin, J-F; Houdé, O

    2014-07-01

    Difficulties in cognitive control including inhibitory control (IC) are related to the pathophysiology of several psychiatric conditions. In healthy subjects, IC efficiency in childhood is a strong predictor of academic and professional successes later in life. The dorsal anterior cingulate cortex (ACC) is one of the core structures responsible for IC. Although quantitative structural characteristics of the ACC contribute to IC efficiency, the qualitative structural brain characteristics contributing to IC development are less-understood. Using anatomical magnetic resonance imaging, we investigated whether the ACC sulcal pattern at age 5, a stable qualitative characteristic of the brain determined in utero, explains IC at age 9. 18 children performed Stroop tasks at age 5 and age 9. Children with asymmetrical ACC sulcal patterns (n=7) had better IC efficiency at age 5 and age 9 than children with symmetrical ACC sulcal patterns (n=11). The ACC sulcal patterns appear to affect specifically IC efficiency given that the ACC sulcal patterns had no effect on verbal working memory. Our study provides the first evidence that the ACC sulcal pattern - a qualitative structural characteristic of the brain not affected by maturation and learning after birth - partially explains IC efficiency during childhood. PMID:24642370

  5. Postnatal development of the electrophysiological properties of somatostatin interneurons in the anterior cingulate cortex of mice.

    PubMed

    Pan, Geng; Yang, Jian-Ming; Hu, Xing-Yue; Li, Xiao-Ming

    2016-01-01

    Somatostatin (SST)-positive interneurons in the anterior cingulate cortex (ACC) play important roles in neuronal diseases, memory and cognitive functions. However, their development in the ACC remains unclear. Using postnatal day 3 (P3) to P45 GIN mice, we found that most of the intrinsic membrane properties of SST interneurons in the ACC were developmentally mature after the second postnatal week and that the development of these neurons differed from that of parvalbumin (PV) interneurons in the prefrontal cortex. In addition, electrical coupling between SST interneurons appeared primarily between P12-14. The coupling probability plateaued at approximately P21-30, with a non-age-dependent development of coupling strength. The development of excitatory chemical afferents to SST interneurons occurred earlier than the development of inhibitory chemical afferents. Furthermore, eye closure attenuated the development of electrical coupling probability at P21-30 but had no effect on coupling strength. Eye closure also delayed the development of inhibitory chemical afferent frequency but had no effect on the excitatory chemical afferent amplitude, frequency or rise time. Our data suggest that SST interneurons in the ACC exhibit inherent developmental characteristics distinct from other interneuron subtypes, such as PV interneurons, and that some of these characteristics are subject to environmental regulation. PMID:27319800

  6. Perceptual load modulates anterior cingulate cortex response to threat distractors in generalized social anxiety disorder.

    PubMed

    Wheaton, Michael G; Fitzgerald, Daniel A; Phan, K Luan; Klumpp, Heide

    2014-09-01

    Generalized social anxiety disorder (gSAD) is associated with impoverished anterior cingulate cortex (ACC) engagement during attentional control. Attentional Control Theory proposes such deficiencies may be offset when demands on resources are increased to execute goals. To test the hypothesis attentional demands affect ACC response 23 patients with gSAD and 24 matched controls performed an fMRI task involving a target letter in a string of identical targets (low load) or a target letter in a mixed letter string (high load) superimposed on fearful, angry, and neutral face distractors. Regardless of load condition, groups were similar in accuracy and reaction time. Under low load gSAD patients showed deficient rostral ACC recruitment to fearful (vs. neutral) distractors. For high load, increased activation to fearful (vs. neutral) distractors was observed in gSAD suggesting a compensatory function. Results remained after controlling for group differences in depression level. Findings indicate perceptual demand modulates ACC in gSAD. PMID:24978315

  7. Loss of dopamine D2 receptors increases parvalbumin-positive interneurons in the anterior cingulate cortex.

    PubMed

    Graham, Devon L; Durai, Heather H; Garden, Jamie D; Cohen, Evan L; Echevarria, Franklin D; Stanwood, Gregg D

    2015-02-18

    Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders. PMID:25393953

  8. Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex

    PubMed Central

    2015-01-01

    Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders. PMID:25393953

  9. Effects of dopamine D1 modulation of the anterior cingulate cortex in a fear conditioning procedure

    PubMed Central

    Pezze, M.A.; Marshall, H.J.; Domonkos, A.; Cassaday, H.J.

    2016-01-01

    The anterior cingulate cortex (AC) component of the medial prefrontal cortex (mPFC) has been implicated in attention and working memory as measured by trace conditioning. Since dopamine (DA) is a key modulator of mPFC function, the present study evaluated the role of DA receptor agents in rat AC, using trace fear conditioning. A conditioned stimulus (CS, noise) was followed by an unconditioned stimulus (US, shock) with or without a 10 s trace interval interposed between these events in a between-subjects design. Conditioned suppression of drinking was assessed in response to presentation of the CS or an experimental background stimulus (flashing lights, previously presented for the duration of the conditioning session). The selective D1 agonist SKF81297 (0.05 μg/side) or D1 antagonist SCH23390 (0.5 μg/side) was administered by intra-cerebral microinfusion directly into AC. It was predicted that either of these manipulations should be sufficient to impair trace (but not delay) conditioning. Counter to expectation, there was no effect of DA D1 modulation on trace conditioning as measured by suppression to the noise CS. However, rats infused with SKF81297 acquired stronger conditioned suppression to the experimental background stimulus than those infused with SCH23390 or saline. Thus, the DA D1 agonist SKF81297 increased conditioned suppression to the contextual background light stimulus but was otherwise without effect on fear conditioning. PMID:26343307

  10. Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset

    PubMed Central

    Jackson, Stacey A. W.; Horst, Nicole K.; Pears, Andrew; Robbins, Trevor W.; Roberts, Angela C.

    2016-01-01

    Two learning mechanisms contribute to decision-making: goal-directed actions and the “habit” system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior. PMID:27130662

  11. Light therapy and serotonin transporter binding in the anterior cingulate and prefrontal cortex

    PubMed Central

    Harrison, S. J.; Tyrer, A. E.; Levitan, R. D.; Xu, X.; Houle, S.; Wilson, A. A.; Nobrega, J. N.; Rusjan, P. M.; Meyer, J. H.

    2016-01-01

    Objective To investigate the effects of light therapy on serotonin transporter binding (5-HTT BPND), an index of 5-HTT levels, in the anterior cingulate and prefrontal cortices (ACC and PFC) of healthy individuals during the fall and winter. Twenty-five per cent of healthy individuals experience seasonal mood changes that affect functioning. 5-HTT BPND has been found to be higher across multiple brain regions in the fall and winter relative to spring and summer, and elevated 5-HTT BPND may lead to extracellular serotonin loss and low mood. We hypothesized that, during the fall and winter, light therapy would reduce 5-HTT BPND in the ACC and PFC, which sample brain regions involved in mood regulation. Method In a single-blind, placebo-controlled, counterbalanced, crossover design, [11C]DASB positron emission tomography was used measure 5-HTT BPND following light therapy and placebo conditions during fall and winter. Results In winter, light therapy significantly decreased 5-HTT BPND by 12% in the ACC relative to placebo (F1,9 = 18.04, P = 0.002). In the fall, no significant change in 5-HTT BPND was found in any region across conditions. Conclusion These results identify, for the first time, a central biomarker associated with the intervention of light therapy in humans which may be applied to further develop this treatment for prevention of seasonal depression. PMID:25891484

  12. Anatomical abnormalities of the anterior cingulate and paracingulate cortex in patients with bipolar I disorder.

    PubMed

    Fornito, Alex; Malhi, Gin S; Lagopoulos, Jim; Ivanovski, Belinda; Wood, Stephen J; Saling, Michael M; Pantelis, Christos; Yücel, Murat

    2008-02-28

    Abnormalities of the anterior cingulate cortex (ACC) are thought to be involved in the pathophysiology of bipolar disorder, but structural Magnetic Resonance Imaging (MRI) studies have reported variable findings. Reasons for this include a failure to consider variability in regional cortical folding patterns and a reliance on relatively coarse measures (e.g., volume) to index anatomical change. We sought to overcome these limitations by combining a novel protocol for parcellating the ACC and adjacent paracingulate cortex (PaC) that accounts for inter-individual variations in sulcal and gyral morphology with a cortical surface-based approach that allowed calculation of regional grey matter volume, surface area and cortical thickness in 24 patients with bipolar I disorder and 24 matched controls. No changes in grey matter volume or surface area were identified in any region, but patients did show significant reductions in cortical thickness in the left rostral PaC and right dorsal PaC that were not attributable to group differences in cortical folding patterns. These findings suggest that bipolar disorder is associated with more pronounced changes in the PaC, and that reliance on volumetric measures alone may obscure more subtle differences. PMID:18207705

  13. Effects of anterior cingulate fissurization on cognitive control during stroop interference.

    PubMed

    Huster, Rene J; Wolters, Carsten; Wollbrink, Andreas; Schweiger, Elisabeth; Wittling, Werner; Pantev, Christo; Junghofer, Markus

    2009-04-01

    The midcingulate cortex, as part of the more anteriorly located cingulate regions, is thought to play a major role in cognitive processes like conflict monitoring or response selection. Regarding midcingulate fissurization, the occurrence of a second or paracingulate sulcus is more common in the left than in the right hemisphere and has been shown to be associated with an advantageous performance on tests of executive functions. However, the cognitive mechanisms underlying such behavioral differences are completely unknown. The current study addressed this issue by comparing subjects with a low and a high degree of left hemispheric midcingulate fissurization while collecting behavioral as well as electrophysiological correlates of Stroop interference. A high degree of fissurization was associated with decreased behavioral Stroop interference accompanied by a stronger and prolonged frontal negative potential to incongruent trials starting around 320 ms. This increased frontal negativity is assumed to reflect an enhanced activity of a conflict monitoring system located in the midcingulate cortex. In contrast and starting around 400 ms, subjects with low fissurization revealed an increased positivity over parieto-occipital regions suggesting a compensatory need for enhanced effortful cognitive control in this group. These results contribute to the understanding of the neuronal implementation of individual differences regarding attentional mechanisms. PMID:18570202

  14. Mild Blast Events Alter Anxiety, Memory, and Neural Activity Patterns in the Anterior Cingulate Cortex

    PubMed Central

    Xie, Kun; Kuang, Hui; Tsien, Joe Z.

    2013-01-01

    There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. PMID:23741416

  15. Reinforcement learning signals in the anterior cingulate cortex code for others' false beliefs.

    PubMed

    Apps, M A J; Green, R; Ramnani, N

    2013-01-01

    The ability to recognise that another's belief is false is a hallmark of our capacity to understand others' mental states. It has been suggested that the computational and neural mechanisms that underpin learning about others' mental states may be similar to those that underpin first-person Reinforcement Learning (RL). In RL, unexpected decision-making outcomes constitute prediction errors (PE), which are coded for by neurons in the Anterior Cingulate Cortex (ACC). Does the ACC signal the PEs (false beliefs) of others about the outcomes of their decisions? We scanned subjects using fMRI while they monitored a third-person's decisions and similar responses made by a computer. The outcomes of the trials were manipulated, such that the actual outcome was unexpectedly different from the predicted outcome on 1/3 of trials. We examined activity time-locked to privileged information which indicated the actual outcomes only to subjects. Activity in the gyral ACC was found when the outcomes of the third-person's decisions were unexpectedly positive. Activity in the sulcal ACC was found when the third-person's or computer's outcomes were unexpectedly positive. We suggest that a property of the ACC is that it codes PEs, with a portion of the gyral ACC specialised for processing the PEs of others. PMID:22982355

  16. Theta–gamma coordination between anterior cingulate and prefrontal cortex indexes correct attention shifts

    PubMed Central

    Voloh, Benjamin; Valiante, Taufik A.; Everling, Stefan; Womelsdorf, Thilo

    2015-01-01

    Anterior cingulate and lateral prefrontal cortex (ACC/PFC) are believed to coordinate activity to flexibly prioritize the processing of goal-relevant over irrelevant information. This between-area coordination may be realized by common low-frequency excitability changes synchronizing segregated high-frequency activations. We tested this coordination hypothesis by recording in macaque ACC/PFC during the covert utilization of attention cues. We found robust increases of 5–10 Hz (theta) to 35–55 Hz (gamma) phase–amplitude correlation between ACC and PFC during successful attention shifts but not before errors. Cortical sites providing theta phases (i) showed a prominent cue-induced phase reset, (ii) were more likely in ACC than PFC, and (iii) hosted neurons with burst firing events that synchronized to distant gamma activity. These findings suggest that interareal theta–gamma correlations could follow mechanistically from a cue-triggered reactivation of rule memory that synchronizes theta across ACC/PFC. PMID:26100868

  17. Individual Differences in Anterior Cingulate Activation Associated with Attentional Bias Predict Cocaine Use After Treatment

    PubMed Central

    Marhe, Reshmi; Luijten, Maartje; van de Wetering, Ben J M; Smits, Marion; Franken, Ingmar H A

    2013-01-01

    Drug-dependent patients often relapse into drug use after treatment. Behavioral studies show that enhanced attentional bias to drug cues is a precursor of relapse. The present functional magnetic resonance imaging (fMRI) study examined whether brain regions involved in attentional bias are predictive of cocaine use after treatment. Attentional bias-related brain activity was measured—with a cocaine Stroop task—in cocaine-dependent patients during their first week in detoxification treatment and was used to predict cocaine use at 3-month follow-up. The predictive value of attentional bias-related brain activity in a priori defined regions of interest, in addition to other measures such as self-reports of substance severity, craving, and behavioral attentional bias were examined. The results show that craving in the week before treatment and individual variability in attentional bias-related activity in the dorsal anterior cingulate cortex (dACC) were significant predictors of days of cocaine use at 3-month follow-up and accounted for 45% in explained variance. Brain activity in the dACC uniquely contributed 22% of explained variance to the prediction model. These findings suggest that hyperactive attentional bias-related brain activity in the dACC might be a biomarker of relapse vulnerability as early as in the first week of detoxification treatment. Ultimately, this may help to develop individually tailored treatment interventions to reduce relapse risk. PMID:23303067

  18. Structural and functional associations of the rostral anterior cingulate cortex with subjective happiness.

    PubMed

    Matsunaga, Masahiro; Kawamichi, Hiroaki; Koike, Takahiko; Yoshihara, Kazufumi; Yoshida, Yumiko; Takahashi, Haruka K; Nakagawa, Eri; Sadato, Norihiro

    2016-07-01

    Happiness is one of the most fundamental human goals, which has led researchers to examine the source of individual happiness. Happiness has usually been discussed regarding two aspects (a temporary positive emotion and a trait-like long-term sense of being happy) that are interrelated; for example, individuals with a high level of trait-like subjective happiness tend to rate events as more pleasant. In this study, we hypothesized that the interaction between the two aspects of happiness could be explained by the interaction between structure and function in certain brain regions. Thus, we first assessed the association between gray matter density (GMD) of healthy participants and trait-like subjective happiness using voxel-based morphometry (VBM). Further, to assess the association between the GMD and brain function, we conducted functional magnetic resonance imaging (MRI) using the task of positive emotion induction (imagination of several emotional life events). VBM indicated that the subjective happiness was positively correlated with the GMD of the rostral anterior cingulate cortex (rACC). Functional MRI demonstrated that experimentally induced temporal happy feelings were positively correlated with subjective happiness level and rACC activity. The rACC response to positive events was also positively correlated with its GMD. These results provide convergent structural and functional evidence that the rACC is related to happiness and suggest that the interaction between structure and function in the rACC may explain the trait-state interaction in happiness. PMID:27085503

  19. Role of right pregenual anterior cingulate cortex in self-conscious emotional reactivity

    PubMed Central

    Sollberger, Marc; Seeley, William W.; Rankin, Katherine P.; Ascher, Elizabeth A.; Rosen, Howard J.; Miller, Bruce L.; Levenson, Robert W.

    2013-01-01

    Self-conscious emotions such as embarrassment arise when one’s actions fail to meet salient social expectations and are accompanied by marked physiological and behavioral activation. We investigated the neural correlates of self-conscious emotional reactivity in 27 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease that disrupts self-conscious emotion and targets brain regions critical for emotional functioning early in the disease course, and in 33 healthy older controls. Subjects participated in an embarrassing karaoke task in which they watched a video clip of themselves singing. They also watched a sad film clip; these data were used to control for non-self-conscious emotional reactivity in response to audiovisual stimuli. Using Freesurfer to quantify regional brain volumes from structural magnetic resonance imaging, right pregenual anterior cingulate cortex (pACC) gray matter volume was the only brain region that was a significant predictor of self-conscious emotion. Smaller pACC volume was associated with attenuated physiological and behavioral self-conscious emotional reactivity, and this relationship was not specific to diagnosis. We argue that these results reflect the significant role that right pACC plays in the visceromotor responding that accompanies self-conscious emotion and that neurodegeneration in this region may underlie the self-conscious emotional decline seen in bvFTD. PMID:22345371

  20. Association between trait emotional awareness and dorsal anterior cingulate activity during emotion is arousal-dependent.

    PubMed

    McRae, Kateri; Reiman, Eric M; Fort, Carolyn L; Chen, Kewei; Lane, Richard D

    2008-06-01

    The dorsal anterior cingulate cortex (dACC) is commonly thought to subserve primarily cognitive functions, but has been strongly implicated in the allocation of attention to emotional information. In a previous positron emission tomography (PET) study, we observed that women with higher emotional awareness as measured by the Levels of Emotional Awareness Scale (LEAS) showed greater changes in regional cerebral blood flow (rCBF) in dACC induced by emotional films and recall. In the current study, we tested whether these effects were due to the processing of any non-neutral stimulus, or were specific to conditions of high emotional arousal. Our results extend the previous finding by demonstrating a positive correlation between emotional awareness and dACC activity only in the context of viewing highly arousing pictures. No such relationship was observed when comparing pleasant or unpleasant pictures to neutral or to each other. We also observed that the relationship between LEAS and dACC activity was present in both sexes but stronger in women than men. These results reinforce the concept that greater trait awareness of one's own emotional experiences is associated with greater engagement of the dACC during emotional arousal, which we suggest may reflect greater attentional processing of emotional information. PMID:18406175

  1. Helping behavior induced by empathic concern attenuates anterior cingulate activation in response to others' distress.

    PubMed

    Kawamichi, Hiroaki; Yoshihara, Kazufumi; Sugawara, Sho K; Matsunaga, Masahiro; Makita, Kai; Hamano, Yuki H; Tanabe, Hiroki C; Sadato, Norihiro

    2016-04-01

    Helping behavior is motivated by empathic concern for others in distress. Although empathic concern is pervasive in daily life, its neural mechanisms remain unclear. Empathic concern involves the suppression of the emotional response to others' distress, which occurs when individuals distance themselves emotionally from the distressed individual. We hypothesized that helping behavior induced by empathic concern, accompanied by perspective-taking, would attenuate the neural activation representing aversive feelings. We also predicted reward system activation due to the positive feeling resulting from helping behavior. Participant underwent functional magnetic resonance imaging while playing a virtual ball-toss game. In some blocks ("concern condition"), one player ("isolated player") did not receive ball-tosses from other players. In this condition, participants increased ball-tosses to the isolated player (helping behavior). Participants then evaluated the improved enjoyment of the isolated player resulting from their helping behavior. Anterior cingulate activation during the concern condition was attenuated by the evaluation of the effect of helping behavior. The right temporoparietal junction, which is involved in perspective-taking and the dorsal striatum, part of the reward system, were also activated during the concern condition. These results suggest that humans can attenuate affective arousal by anticipating the positive outcome of empathic concern through perspective-taking. PMID:26032190

  2. Functional Connectivity of the Caudal Anterior Cingulate Cortex Is Decreased in Autism

    PubMed Central

    Zhou, Yuanyue; Shi, Lijuan; Cui, Xilong; Wang, Suhong; Luo, Xuerong

    2016-01-01

    The anterior cingulate cortex (ACC) is frequently reported to have functionally distinct sub-regions that play key roles in different intrinsic networks. However, the contribution of the ACC, which is connected to several cortical areas and the limbic system, to autism is not clearly understood, although it may be involved in dysfunctions across several distinct but related functional domains. By comparing resting-state fMRI data from persons with autism and healthy controls, we sought to identify the abnormalities in the functional connectivity (FC) of ACC sub-regions in autism. The analyses found autism-related reductions in FC between the left caudal ACC and the right rolandic operculum, insula, postcentral gyrus, superior temporal gyrus, and the middle temporal gyrus. The FC (z-scores) between the left caudal ACC and the right insula was negatively correlated with the Stereotyped Behaviors and Restricted Interests scores of the autism group. These findings suggest that the caudal ACC is recruited selectively in the pathomechanism of autism. PMID:26985666

  3. Predicting aversive events and terminating fear in the mouse anterior cingulate cortex during trace fear conditioning.

    PubMed

    Steenland, Hendrik W; Li, Xiang-Yao; Zhuo, Min

    2012-01-18

    A variety of studies have implicated the anterior cingulate cortex (ACC) in fear, including permanent storage of fear memory. Recent pharmacological and genetic studies indicate that early synaptic plasticity in the ACC may also contribute to certain forms of fear memory at early time points. However, no study has directly examined the possible changes in neuronal activity of ACC neurons in freely behaving mice during early learning. In the present study, we examined the neural responses of the ACC during trace fear conditioning. We found that ACC putative pyramidal and nonpyramidal neurons were involved in the termination of fear behavior ("un-freezing"), and the spike activity of these neurons was reduced during freezing. Some of the neurons were also found to acquire un-freezing locked activity and change their tuning. The results implicate the ACC neurons in fear learning and controlling the abolition of fear behavior. We also show that the ACC is important for making cue-related fear memory associations in the trace fear paradigm as measured with tone-evoked potentials and single-unit activity. Collectively, our findings indicate that the ACC is involved in predicting future aversive events and terminating fear during trace fear. PMID:22262906

  4. Mild blast events alter anxiety, memory, and neural activity patterns in the anterior cingulate cortex.

    PubMed

    Xie, Kun; Kuang, Hui; Tsien, Joe Z

    2013-01-01

    There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. PMID:23741416

  5. Visual and noxious electrical stimulus-evoked membrane-potential responses in anterior cingulate cortical neurons.

    PubMed

    Ma, Li-Qing; Ning, Li; Wang, Zhiru; Wang, Ying-Wei

    2016-01-01

    Anterior cingulate cortex (ACC) is known to participate in numerous brain functions, such as memory storage, emotion, attention, as well as perception of acute and chronic pain. ACC-dependent brain functions often rely on ACC processing of various forms of environmental information. To understand the neural basis of ACC functions, previous studies have investigated ACC responses to environmental stimulation, particularly complex sensory stimuli as well as award and aversive stimuli, but this issue remains to be further clarified. Here, by performing whole-cell recording in vivo in anaesthetized adult rats, we examined membrane-potential (MP) responses of layer II/III ACC neurons that were evoked by a brief flash of visual stimulation and pain-related electrical stimulation delivered to hind paws. We found that ~54 and ~81 % ACC neurons exhibited excitatory MP responses, subthreshold or suprathreshold, to the visual stimulus and the electrical stimulus, respectively, with no cell showing inhibitory MP responses. We further found that the visually evoked ACC response could be greatly diminished by local lidocaine infusion in the visual thalamus, and only their temporal patterns but not amplitudes could be changed by large-scale visual cortical lesions. Our in vivo whole-cell recording data characterized in ACC neurons a visually evoked response, which was largely dependent on the visual thalamus but not visual cortex, as well as a noxious electrical stimulus-evoked response. These findings may provide potential mechanisms that are used for ACC functions on the basis of sensory information processing. PMID:27585569

  6. The beneficial effects of meditation: contribution of the anterior cingulate and locus coeruleus

    PubMed Central

    Craigmyle, Nancy A.

    2013-01-01

    During functional magnetic resonance imaging studies of meditation the cortical salience detecting and executive networks become active during “awareness of mind wandering,” “shifting,” and “sustained attention.” The anterior cingulate (AC) is activated during “awareness of mind wandering.” The AC modulates both the peripheral sympathetic nervous system (SNS) and the central locus coeruleus (LC) norepinephrine systems, which form the principal neuromodulatory system, regulating in multiple ways both neuronal and non-neuronal cells to maximize adaptation in changing environments. The LC is the primary source of central norepinephrine (C-NE) and nearly the exclusive source of cortical norepinephrine. Normally activated by novel or salient stimuli, the AC initially inhibits the SNS reflexively, lowering peripheral norepinephrine and activates the LC, increasing C-NE. Moderate levels of C-NE enhance working memory through alpha 2 adrenergic receptors, while higher levels of C-NE, acting on alpha 1 and beta receptors, enhance other executive network functions such as the stopping of ongoing behavior, attentional set-shifting, and sustained attention. The actions of the AC on both the central and peripheral noradrenergic systems are implicated in the beneficial effects of meditation. This paper will explore some of the known functions and interrelationships of the AC, SNS, and LC with respect to their possible relevance to meditation. PMID:24137145

  7. Predictive decision making driven by multiple time-linked reward representations in the anterior cingulate cortex

    PubMed Central

    Wittmann, Marco K.; Kolling, Nils; Akaishi, Rei; Chau, Bolton K. H.; Brown, Joshua W.; Nelissen, Natalie; Rushworth, Matthew F. S.

    2016-01-01

    In many natural environments the value of a choice gradually gets better or worse as circumstances change. Discerning such trends makes predicting future choice values possible. We show that humans track such trends by comparing estimates of recent and past reward rates, which they are able to hold simultaneously in the dorsal anterior cingulate cortex (dACC). Comparison of recent and past reward rates with positive and negative decision weights is reflected by opposing dACC signals indexing these quantities. The relative strengths of time-linked reward representations in dACC predict whether subjects persist in their current behaviour or switch to an alternative. Computationally, trend-guided choice can be modelled by using a reinforcement-learning mechanism that computes a longer-term estimate (or expectation) of prediction errors. Using such a model, we find a relative predominance of expected prediction errors in dACC, instantaneous prediction errors in the ventral striatum and choice signals in the ventromedial prefrontal cortex. PMID:27477632

  8. Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear.

    PubMed

    Pissiota, Anna; Frans, Orjan; Michelgård, Asa; Appel, Lieuwe; Långström, Bengt; Flaten, Magne Arve; Fredrikson, Mats

    2003-09-01

    The human startle response is modulated by emotional experiences, with startle potentiation associated with negative affect. We used positron emission tomography with 15O-water to study neural networks associated with startle modulation by phobic fear in a group of subjects with specific snake or spider phobia, but not both, during exposure to pictures of their feared and non-feared objects, paired and unpaired with acoustic startle stimuli. Measurement of eye electromyographic activity confirmed startle potentiation during the phobic as compared with the non-phobic condition. Employing a factorial design, we evaluated brain correlates of startle modulation as the interaction between startle and affect, using the double subtraction contrast (phobic startle vs. phobic alone) vs. (non-phobic startle vs. non-phobic alone). As a result of startle potentiation, a significant increase in regional cerebral blood flow was found in the left amygdaloid-hippocampal region, and medially in the affective division of the anterior cingulate cortex (ACC). These results provide evidence from functional brain imaging for a modulatory role of the amygdaloid complex on startle reactions in humans. They also point to the involvement of the affective ACC in the processing of startle stimuli during emotionally aversive experiences. The co-activation of these areas may reflect increased attention to fear-relevant stimuli. Thus, we suggest that the amygdaloid area and the ACC form part of a neural system dedicated to attention and orientation to danger, and that this network modulates startle during negative affect. PMID:12956731

  9. Successful choice behavior is associated with distinct and coherent network states in anterior cingulate cortex

    PubMed Central

    Lapish, Christopher C.; Durstewitz, Daniel; Chandler, L. Judson; Seamans, Jeremy K.

    2008-01-01

    Successful decision making requires an ability to monitor contexts, actions, and outcomes. The anterior cingulate cortex (ACC) is thought to be critical for these functions, monitoring and guiding decisions especially in challenging situations involving conflict and errors. A number of different single-unit correlates have been observed in the ACC that reflect the diverse cognitive components involved. Yet how ACC neurons function as an integrated network is poorly understood. Here we show, using advanced population analysis of multiple single-unit recordings from the rat ACC during performance of an ecologically valid decision-making task, that ensembles of neurons move through different coherent and dissociable states as the cognitive requirements of the task change. This organization into distinct network patterns with respect to both firing-rate changes and correlations among units broke down during trials with numerous behavioral errors, especially at choice points of the task. These results point to an underlying functional organization into cell assemblies in the ACC that may monitor choices, outcomes, and task contexts, thus tracking the animal's progression through “task space.” PMID:18708525

  10. Increased G Protein-Coupled Receptor Kinase (GRK) Expression in the Anterior Cingulate Cortex in Schizophrenia

    PubMed Central

    Funk, Adam J.; Haroutunian, Vahram; Meador-Woodruff, James H.; McCullumsmith, Robert E.

    2014-01-01

    Background Current pharmacological treatments for schizophrenia target G protein-coupled receptors (GPCRs), including dopamine receptors. Ligand bound GPCRs are regulated by a family of G protein-coupled receptor kinases (GRKs), members of which uncouple the receptor from heterotrimeric G proteins, desensitize the receptor, and induce receptor internalization via the arrestin family of scaffolding and signaling molecules. GRKs initiate the activation of downstream signaling pathways, can regulate receptors and signaling molecules independent of GPCR phosphorylation, and modulate epigenetic regulators like histone deacetylases (HDACs). We hypothesize that expression of GRK proteins are altered in schizophrenia, consistent with previous findings of alterations up and downstream from this family of molecules that facilitate intracellular signaling processes. Methods In this study we measured protein expression via Western blot analysis for GRKs 2, 3, 5, and 6 in the anterior cingulate cortex of patients with schizophrenia (N = 36) and a comparison group (N = 33). To control for antipsychotic treatment we measured these same targets in haloperidol treated vs. untreated rats (N = 10 for both). Results We found increased levels of GRK5 in schizophrenia. No changes were detected in GRK protein expression in rats treated with haloperidol decanoate for 9 months. Conclusion These data suggest that increased GRK5 expression may contribute the the pathophysiology of schizophrenia via abnormal regulation of the cytoskeleton, endocytosis, signaling, GPCRs, and histone modification. PMID:25153362

  11. Localization of function in anterior cingulate cortex: from psychosurgery to functional neuroimaging.

    PubMed

    Gasquoine, Philip Gerard

    2013-03-01

    Early localizationists linked anterior cingulate cortex (ACC: Brodmann's area 24 and adjacent regions) with emotional behavior, paving the way for bilateral cingulotomy psychosurgery in severe, treatment resistant, cases of obsessive-compulsive disorder, chronic pain, depression, and substance abuse. Neuropsychological follow-up of such cases demonstrated executive function impairment. Abnormal neuroimaged activity in ACC has been found in many psychiatric conditions, including obsessive-compulsive disorder, chronic pain, substance abuse, and schizophrenia. With healthy participants, increased neuroimaged activity in ACC has been linked with challenging executive function tasks, homeostatically incongruous physical states, and the encoding of the pleasant/averseness of stimuli. There is disagreement on the cortical substrate subsumed by the term ACC, the existence of functionally distinct ACC subregions (e.g., dorsal: cognitive vs. ventral: emotion), and the interpretation of functional neuroimaging studies. Synthesis of neuropsychological and functional neuroimaging studies suggests ACC contributes to behavior by modifying responses especially in reaction to challenging cognitive and physical states that require additional effortful cognitive control. This is accomplished by monitoring the emotional salience of stimuli, exerting control over the autonomic nervous system, and modulating cognitive activity. PMID:23313645

  12. Impaired reward processing by anterior cingulate cortex in children with attention deficit hyperactivity disorder.

    PubMed

    Umemoto, Akina; Lukie, Carmen N; Kerns, Kimberly A; Müller, Ulrich; Holroyd, Clay B

    2014-06-01

    Decades of research have examined the neurocognitive mechanisms of cognitive control, but the motivational factors underlying task selection and performance remain to be elucidated. We recently proposed that anterior cingulate cortex (ACC) utilizes reward prediction error signals carried by the midbrain dopamine system to learn the value of tasks according to the principles of hierarchical reinforcement learning. According to this position, disruption of the ACC-dopamine interface can disrupt the selection and execution of extended, task-related behaviors. To investigate this issue, we recorded the event-related brain potential (ERP) from children with attention deficit hyperactivity disorder (ADHD), which is strongly associated with ACC-dopamine dysfunction, and from typically developing children while they navigated a simple "virtual T-maze" to find rewards. Depending on the condition, the feedback stimuli on each trial indicated that the children earned or failed to earn either money or points. We found that the reward positivity, an ERP component proposed to index the impact of dopamine-related reward signals on ACC, was significantly larger with money feedback than with points feedback for the children with ADHD, but not for the typically developing children. These results suggest that disruption of the ACC-dopamine interface may underlie the impairments in motivational control observed in childhood ADHD. PMID:24874420

  13. Dopaminergic Modulation of Excitatory Transmission in the Anterior Cingulate Cortex of Adult Mice

    PubMed Central

    Darvish-Ghane, Soroush; Yamanaka, Manabu

    2016-01-01

    Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 μM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 μM). Furthermore, selective postsynaptic application of GDP-β-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 μM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of potentiation and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 μM) and sulpiride (100 μM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA. PMID:27317578

  14. The mediodorsal thalamus drives feedforward inhibition in the anterior cingulate cortex via parvalbumin interneurons.

    PubMed

    Delevich, Kristen; Tucciarone, Jason; Huang, Z Josh; Li, Bo

    2015-04-01

    Although the medial prefrontal cortex (mPFC) is classically defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD), the nature of information transfer between MD and mPFC is poorly understood. In sensory thalamocortical pathways, thalamic recruitment of feedforward inhibition mediated by fast-spiking, putative parvalbumin-expressing (PV) interneurons is a key feature that enables cortical neurons to represent sensory stimuli with high temporal fidelity. Whether a similar circuit mechanism is in place for the projection from the MD (a higher-order thalamic nucleus that does not receive direct input from the periphery) to the mPFC is unknown. Here we show in mice that inputs from the MD drive disynaptic feedforward inhibition in the dorsal anterior cingulate cortex (dACC) subregion of the mPFC. In particular, we demonstrate that axons arising from MD neurons directly synapse onto and excite PV interneurons that in turn mediate feedforward inhibition of pyramidal neurons in layer 3 of the dACC. This feedforward inhibition in the dACC limits the time window during which pyramidal neurons integrate excitatory synaptic inputs and fire action potentials, but in a manner that allows for greater flexibility than in sensory cortex. These findings provide a foundation for understanding the role of MD-PFC circuit function in cognition. PMID:25855185

  15. Ramping ensemble activity in dorsal anterior cingulate neurons during persistent commitment to a decision.

    PubMed

    Blanchard, Tommy C; Strait, Caleb E; Hayden, Benjamin Y

    2015-10-01

    We frequently need to commit to a choice to achieve our goals; however, the neural processes that keep us motivated in pursuit of delayed goals remain obscure. We examined ensemble responses of neurons in macaque dorsal anterior cingulate cortex (dACC), an area previously implicated in self-control and persistence, in a task that requires commitment to a choice to obtain a reward. After reward receipt, dACC neurons signaled reward amount with characteristic ensemble firing rate patterns; during the delay in anticipation of the reward, ensemble activity smoothly and gradually came to resemble the postreward pattern. On the subset of risky trials, in which a reward was anticipated with 50% certainty, ramping ensemble activity evolved to the pattern associated with the anticipated reward (and not with the anticipated loss) and then, on loss trials, took on an inverted form anticorrelated with the form associated with a win. These findings enrich our knowledge of reward processing in dACC and may have broader implications for our understanding of persistence and self-control. PMID:26334016

  16. Spatiotemporal Spike Coding of Behavioral Adaptation in the Dorsal Anterior Cingulate Cortex.

    PubMed

    Logiaco, Laureline; Quilodran, René; Procyk, Emmanuel; Arleo, Angelo

    2015-08-01

    The frontal cortex controls behavioral adaptation in environments governed by complex rules. Many studies have established the relevance of firing rate modulation after informative events signaling whether and how to update the behavioral policy. However, whether the spatiotemporal features of these neuronal activities contribute to encoding imminent behavioral updates remains unclear. We investigated this issue in the dorsal anterior cingulate cortex (dACC) of monkeys while they adapted their behavior based on their memory of feedback from past choices. We analyzed spike trains of both single units and pairs of simultaneously recorded neurons using an algorithm that emulates different biologically plausible decoding circuits. This method permits the assessment of the performance of both spike-count and spike-timing sensitive decoders. In response to the feedback, single neurons emitted stereotypical spike trains whose temporal structure identified informative events with higher accuracy than mere spike count. The optimal decoding time scale was in the range of 70-200 ms, which is significantly shorter than the memory time scale required by the behavioral task. Importantly, the temporal spiking patterns of single units were predictive of the monkeys' behavioral response time. Furthermore, some features of these spiking patterns often varied between jointly recorded neurons. All together, our results suggest that dACC drives behavioral adaptation through complex spatiotemporal spike coding. They also indicate that downstream networks, which decode dACC feedback signals, are unlikely to act as mere neural integrators. PMID:26266537

  17. Predictive decision making driven by multiple time-linked reward representations in the anterior cingulate cortex.

    PubMed

    Wittmann, Marco K; Kolling, Nils; Akaishi, Rei; Chau, Bolton K H; Brown, Joshua W; Nelissen, Natalie; Rushworth, Matthew F S

    2016-01-01

    In many natural environments the value of a choice gradually gets better or worse as circumstances change. Discerning such trends makes predicting future choice values possible. We show that humans track such trends by comparing estimates of recent and past reward rates, which they are able to hold simultaneously in the dorsal anterior cingulate cortex (dACC). Comparison of recent and past reward rates with positive and negative decision weights is reflected by opposing dACC signals indexing these quantities. The relative strengths of time-linked reward representations in dACC predict whether subjects persist in their current behaviour or switch to an alternative. Computationally, trend-guided choice can be modelled by using a reinforcement-learning mechanism that computes a longer-term estimate (or expectation) of prediction errors. Using such a model, we find a relative predominance of expected prediction errors in dACC, instantaneous prediction errors in the ventral striatum and choice signals in the ventromedial prefrontal cortex. PMID:27477632

  18. Dorsal Anterior Cingulate Thickness Is Related to Alexithymia in Childhood Trauma-Related PTSD.

    PubMed

    Demers, Lauren A; Olson, Elizabeth A; Crowley, David J; Rauch, Scott L; Rosso, Isabelle M

    2015-01-01

    Alexithymia, or "no words for feelings", is highly prevalent in samples with childhood maltreatment and posttraumatic stress disorder (PTSD). The dorsal anterior cingulate cortex (dACC) has been identified as a key region involved in alexithymia, early life trauma, and PTSD. Functional alterations in the dACC also have been associated with alexithymia in PTSD. This study examined whether dACC morphology is a neural correlate of alexithymia in child maltreatment-related PTSD. Sixteen adults with PTSD and a history of childhood sexual abuse, physical abuse, or exposure to domestic violence, and 24 healthy controls (HC) completed the Toronto Alexithymia Scale 20 (TAS-20) and underwent magnetic resonance imaging. Cortical thickness of the dACC was measured using FreeSurfer, and values were correlated with TAS-20 scores, controlling for sex and age, in both groups. Average TAS-20 score was significantly higher in the PTSD than the HC group. TAS-20 scores were significantly positively associated with dACC thickness only in the PTSD group. This association was strongest in the left hemisphere and for TAS-20 subscales that assess difficulty identifying and describing feelings. We found that increasing dACC gray matter thickness is a neural correlate of greater alexithymia in the context of PTSD with childhood maltreatment. While findings are correlational, they motivate further inquiry into the relationships between childhood adversity, emotional awareness and expression, and dACC morphologic development in trauma-related psychopathology. PMID:26439117

  19. Potentiation of synaptic transmission in Rat anterior cingulate cortex by chronic itch.

    PubMed

    Zhang, Ting-Ting; Shen, Feng-Yan; Ma, Li-Qing; Wen, Wen; Wang, Bin; Peng, Yuan-Zhi; Wang, Zhi-Ru; Zhao, Xuan

    2016-01-01

    Itch and pain share similar mechanisms. It has been well documented that the anterior cingulate cortex (ACC) is important for pain-related perception. ACC has also been approved to be a potential pruritus-associated brain region. However, the mechanism of sensitization in pruriceptive neurons in the ACC is not clear. In current study, a chronic itch model was established by diphenylcyclopropenone (DCP) application. We found that both the frequency and amplitude of miniature excitatory postsynaptic currents in the ACC were enhanced after the formation of chronic itch. The paired-pulse ratio in ACC neurons recorded from the DCP group were smaller than those recorded in control group at the 50-ms interval. We also observe a significant increase in the AMPA/NMDA ratio in the DCP group. Moreover, an increased inward rectification of AMPARs in ACC pyramidal neurons was observed in the DCP group. Interestingly, the calculated ratio of silent synapses was significantly reduced in the DCP group compared with controls. Taken together, we conclude that a potentiation of synaptic transmission in the ACC can be induced by chronic itch, and unsilencing silent synapses, which probably involved recruitment of AMPARS, contributed to the potentiation of postsynaptic transmission. PMID:27472923

  20. Perigenual anterior cingulate event-related potential precedes stop signal errors

    PubMed Central

    Chang, Andrew; Chen, Chien-Chung; Li, Hsin-Hung; Li, Chiang-Shan R.

    2015-01-01

    Momentary lapses in attention disrupt goal-directed behavior. Attentional lapse has been associated with increased “default-mode” network (DMN) activity. In our previous fMRI study of a stop signal task (SST), greater activation of the perigenual anterior cingulate cortex (pgACC) – an important node of the DMN – predicts stop signal errors. In event-related potential (ERP) studies, the amplitude of an error-preceding positivity (EPP) also predicts response error. However, it is not clear whether the EPP originates from DMN regions. Here, we combined high-density array EEG and an SST to examine response-locked ERPs of error preceding trials in twenty young adult participants. The results showed an EPP in go trials that preceded stop error than stop success trials. Importantly, source modeling identified the origin of the EPP in the pgACC. By employing a bootstrapping procedure, we further confirmed that pgACC rather than the dorsal ACC as the source provides a better fit to the EPP. Together, these results suggest that attentional lapse in association with EPP in the pgACC anticipates failure in response inhibition. PMID:25700955

  1. Anatomical Abnormalities of the Anterior Cingulate Cortex in Schizophrenia: Bridging the Gap Between Neuroimaging and Neuropathology

    PubMed Central

    Fornito, Alex; Yücel, Murat; Dean, Brian; Wood, Stephen J.; Pantelis, Christos

    2009-01-01

    The anterior cingulate cortex (ACC) is a functionally heterogeneous region involved in diverse cognitive and emotional processes that support goal-directed behaviour. Structural magnetic resonance imaging (MRI) and neuropathological findings over the past two decades have converged to suggest abnormalities in the region may represent a neurobiological basis for many of the clinical manifestations of schizophrenia. However, while each approach offers complimentary information that can provide clues regarding underlying patholophysiological processes, the findings from these 2 fields are seldom integrated. In this article, we review structural neuroimaging and neuropathological studies of the ACC, focusing on the unique information they provide. The available imaging data suggest grey matter reductions in the ACC precede psychosis onset in some categories of high-risk individuals, show sub-regional specificity, and may progress with illness duration. The available post-mortem findings indicate these imaging-related changes are accompanied by reductions in neuronal, synaptic, and dendritic density, as well as increased afferent input, suggesting the grey matter differences observed with MRI arise from alterations in both neuronal and non-neuronal tissue compartments. We discuss the potential mechanisms that might facilitate integration of these findings and consider strategies for future research. PMID:18436528

  2. Electrophysiological Correlates of a Versatile Executive Control System in the Monkey Anterior Cingulate Cortex.

    PubMed

    Michelet, Thomas; Bioulac, Bernard; Langbour, Nicolas; Goillandeau, Michel; Guehl, Dominique; Burbaud, Pierre

    2016-04-01

    When a subject faces conflicting situations, decision-making becomes uncertain. The human dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in the monitoring of such situations, and its neural activity is thought to be involved in behavioral adjustment. However, this hypothesis is mainly based on neuroimaging results and is challenged by animal studies that failed to report any neuronal correlates of conflict monitoring. This discrepancy is thought be due either to methodological or more fundamental cross-species differences. In this study, we eliminated methodological biases and recorded single-neuron activity in monkeys performing a Stroop-like task. We found specific changes in dACC activity during incongruent trials but only in a small subpopulation of cells. Critically, these changes were not related to reaction time and were absent before any incorrect action was taken. A larger fraction of neurons exhibited sustained activity during the whole decision period, whereas another subpopulation of neurons was modulated by reaction time, with a gradual increase in their firing rate that peaked at movement onset. Most of the neurons found in these subpopulations exhibited activity after the delivery of an external negative feedback stimulus that indicated an error had been made. These findings, which are consistent with an executive control role, reconcile various theories of prefrontal cortex function and support the homology between human and monkey cognitive architectures. PMID:25631057

  3. Postnatal development of the electrophysiological properties of somatostatin interneurons in the anterior cingulate cortex of mice

    PubMed Central

    Pan, Geng; Yang, Jian-Ming; Hu, Xing-Yue; Li, Xiao-Ming

    2016-01-01

    Somatostatin (SST)-positive interneurons in the anterior cingulate cortex (ACC) play important roles in neuronal diseases, memory and cognitive functions. However, their development in the ACC remains unclear. Using postnatal day 3 (P3) to P45 GIN mice, we found that most of the intrinsic membrane properties of SST interneurons in the ACC were developmentally mature after the second postnatal week and that the development of these neurons differed from that of parvalbumin (PV) interneurons in the prefrontal cortex. In addition, electrical coupling between SST interneurons appeared primarily between P12–14. The coupling probability plateaued at approximately P21–30, with a non-age-dependent development of coupling strength. The development of excitatory chemical afferents to SST interneurons occurred earlier than the development of inhibitory chemical afferents. Furthermore, eye closure attenuated the development of electrical coupling probability at P21–30 but had no effect on coupling strength. Eye closure also delayed the development of inhibitory chemical afferent frequency but had no effect on the excitatory chemical afferent amplitude, frequency or rise time. Our data suggest that SST interneurons in the ACC exhibit inherent developmental characteristics distinct from other interneuron subtypes, such as PV interneurons, and that some of these characteristics are subject to environmental regulation. PMID:27319800

  4. Spatiotemporal Spike Coding of Behavioral Adaptation in the Dorsal Anterior Cingulate Cortex

    PubMed Central

    Logiaco, Laureline; Quilodran, René; Procyk, Emmanuel; Arleo, Angelo

    2015-01-01

    The frontal cortex controls behavioral adaptation in environments governed by complex rules. Many studies have established the relevance of firing rate modulation after informative events signaling whether and how to update the behavioral policy. However, whether the spatiotemporal features of these neuronal activities contribute to encoding imminent behavioral updates remains unclear. We investigated this issue in the dorsal anterior cingulate cortex (dACC) of monkeys while they adapted their behavior based on their memory of feedback from past choices. We analyzed spike trains of both single units and pairs of simultaneously recorded neurons using an algorithm that emulates different biologically plausible decoding circuits. This method permits the assessment of the performance of both spike-count and spike-timing sensitive decoders. In response to the feedback, single neurons emitted stereotypical spike trains whose temporal structure identified informative events with higher accuracy than mere spike count. The optimal decoding time scale was in the range of 70–200 ms, which is significantly shorter than the memory time scale required by the behavioral task. Importantly, the temporal spiking patterns of single units were predictive of the monkeys’ behavioral response time. Furthermore, some features of these spiking patterns often varied between jointly recorded neurons. All together, our results suggest that dACC drives behavioral adaptation through complex spatiotemporal spike coding. They also indicate that downstream networks, which decode dACC feedback signals, are unlikely to act as mere neural integrators. PMID:26266537

  5. Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset.

    PubMed

    Jackson, Stacey A W; Horst, Nicole K; Pears, Andrew; Robbins, Trevor W; Roberts, Angela C

    2016-07-01

    Two learning mechanisms contribute to decision-making: goal-directed actions and the "habit" system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior. PMID:27130662

  6. Hyperlexia and ambient echolalia in a case of cerebral infarction of the left anterior cingulate cortex and corpus callosum.

    PubMed

    Suzuki, Tadashi; Itoh, Shouichi; Hayashi, Mototaka; Kouno, Masako; Takeda, Katsuhiko

    2009-10-01

    We report the case of a 69-year-old woman with cerebral infarction in the left anterior cingulate cortex and corpus callosum. She showed hyperlexia, which was a distinctive reading phenomenon, as well as ambient echolalia. Clinical features also included complex disorders such as visual groping, compulsive manipulation of tools, and callosal disconnection syndrome. She read words written on the cover of a book and repeated words emanating from unrelated conversations around her or from hospital announcements. The combination of these two features due to a focal lesion has never been reported previously. The supplementary motor area may control the execution of established subroutines according to external and internal inputs. Hyperlexia as well as the compulsive manipulation of tools could be interpreted as faulty inhibition of preexisting essentially intact motor subroutines by damage to the anterior cingulate cortex reciprocally interconnected with the supplementary motor area. PMID:19585352

  7. Dopamine and serotonin imbalances in the left anterior cingulate and pyriform cortices following the repeated intermittent administration of cocaine.

    PubMed

    Heidbreder, C A; Oertle, T; Feldon, J

    1999-03-01

    Studies on the neurobiology of cocaine abuse suggest that cocaine directly modifies the activity of dopamine neurons projecting from the dopamine-synthesizing cells of the ventral tegmental area to the nucleus accumbens. The repeated use of cocaine produces persistent adaptations within the mesocorticolimbic system and the resulting changes in monoamine neurotransmission may lead to behavioral sensitization. The present series of experiments sought to determine the effects of the repeated, intermittent challenge that took place two days after discontinuation of the pretreatment regimen; (ii) the ex vivo levels of biogenic monoamines, choline and acetylcholine in the nucleus accumbens, the dorsolateral caudate nucleus, as well as the anterior cingulate, frontal motor, frontal somatosensory and pyriform cortices; and (iii) the degree of neurochemical relationship between the left and right hemispheres. The repeated administration of cocaine produced sensitized behavioral responses to a subsequent challenge. Neurochemical correlates of repeated cocaine administration were observed at the cortical level and included a significant decrease in serotonin levels in the left anterior cingulate and pyriform cortices and an increase in dopamine metabolism in the left pyriform cortex. Furthermore, a shift in the interhemispheric coupling coefficient matrix for dopamine neurotransmission was observed in both the pyriform cortex and nucleus accumbens of cocaine-sensitized animals suggesting that, in these structures, the two hemispheres are operating independently. These results demonstrate that cocaine produces alterations in specific dopaminergic and serotonergic pathways that arise from the mesencephalon and project towards both the anterior cingulate and pyriform cortices. PMID:10199606

  8. Dorsal anterior cingulate cortex modulates supplementary motor area in coordinated unimanual motor behavior

    PubMed Central

    Asemi, Avisa; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A.; Bressler, Steven L.

    2015-01-01

    Motor control is integral to all types of human behavior, and the dorsal Anterior Cingulate Cortex (dACC) is thought to play an important role in the brain network underlying motor control. Yet the role of the dACC in motor control is under-characterized. Here we aimed to characterize the dACC’s role in adolescent brain network interactions during a simple motor control task involving visually coordinated unimanual finger movements. Network interactions were assessed using both undirected and directed functional connectivity analysis of functional Magnetic Resonance Imaging (fMRI) Blood-Oxygen-Level-Dependent (BOLD) signals, comparing the task with a rest condition. The relation between the dACC and Supplementary Motor Area (SMA) was compared to that between the dACC and Primary Motor Cortex (M1). The directed signal from dACC to SMA was significantly elevated during motor control in the task. By contrast, the directed signal from SMA to dACC, both directed signals between dACC and M1, and the undirected functional connections of dACC with SMA and M1, all did not differ between task and rest. Undirected coupling of dACC with both SMA and dACC, and only the dACC-to-SMA directed signal, were significantly greater for a proactive than a reactive task condition, suggesting that dACC plays a role in motor control by maintaining stimulus timing expectancy. Overall, these results suggest that the dACC selectively modulates the SMA during visually coordinated unimanual behavior in adolescence. The role of the dACC as an important brain area for the mediation of task-related motor control may be in place in adolescence, continuing into adulthood. The task and analytic approach described here should be extended to the study of healthy adults to examine network profiles of the dACC during basic motor behavior. PMID:26089783

  9. Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic.

    PubMed

    Ruland, Tillmann; Domschke, Katharina; Schütte, Valerie; Zavorotnyy, Maxim; Kugel, Harald; Notzon, Swantje; Vennewald, Nadja; Ohrmann, Patricia; Arolt, Volker; Pfleiderer, Bettina; Zwanzger, Peter

    2015-10-01

    An excitatory-inhibitory neurotransmitter dysbalance has been suggested in pathogenesis of panic disorder. The neuropeptide S (NPS) system has been implicated in modulating GABA and glutamate neurotransmission in animal models and to genetically drive altered fear circuit function and an increased risk of panic disorder in humans. Probing a multi-level imaging genetic risk model of panic, in the present magnetic resonance spectroscopy (MRS) study brain glutamate+glutamine (Glx) levels in the bilateral anterior cingulate cortex (ACC) during a pharmacological cholecystokinin tetrapeptide (CCK-4) panic challenge were assessed depending on the functional neuropeptide S receptor gene (NPSR1) rs324981 A/T variant in a final sample of 35 healthy male subjects. The subjective panic response (Panic Symptom Scale; PSS) as well as cortisol and ACTH levels were ascertained throughout the experiment. CCK-4 injection was followed by a strong panic response. A significant time×genotype interaction was detected (p=.008), with significantly lower ACC Glx/Cr levels in T allele carriers as compared to AA homozygotes 5min after injection (p=.003). CCK-4 induced significant HPA axis stimulation, but no effect of genotype was discerned. The present pilot data suggests NPSR1 gene variation to modulate Glx levels in the ACC during acute states of stress and anxiety, with blunted, i.e. possibly maladaptive ACC glutamatergic reactivity in T risk allele carriers. Our results underline the notion of a genetically driven rapid and dynamic response mechanism in the neural regulation of human anxiety and further strengthen the emerging role of the NPS system in anxiety. PMID:26235955

  10. Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization.

    PubMed

    Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M

    2015-10-01

    Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. PMID:26165137

  11. Anterior cingulate cortex hypoactivations to an emotionally salient task in cocaine addiction

    PubMed Central

    Goldstein, Rita Z.; Alia-Klein, Nelly; Tomasi, Dardo; Carrillo, Jean Honorio; Maloney, Thomas; Woicik, Patricia A.; Wang, Ruiliang; Telang, Frank; Volkow, Nora D.

    2009-01-01

    Anterior cingulate cortex (ACC) hypoactivations during cognitive processing characterize drug addicted individuals as compared with healthy controls. However, impaired behavioral performance or task disengagement may be crucial factors. We hypothesized that ACC hypoactivations would be documented in groups matched for performance on an emotionally salient task. Seventeen individuals with current cocaine use disorders (CUD) and 17 demographically matched healthy controls underwent functional magnetic resonance imaging during performance of a rewarded drug cue-reactivity task previously shown to engage the ACC. Despite lack of group differences in objective or subjective task-related performance, CUD showed more ACC hypoactivations throughout this emotionally salient task. Nevertheless, intensity of emotional salience contributed to results: (i) CUD with the largest rostroventral ACC [Brodmann Area (BA) 10, 11, implicated in default brain function] hypoactivations to the most salient task condition (drug words during the highest available monetary reward), had the least task-induced cocaine craving; (ii) CUD with the largest caudal-dorsal ACC (BA 32) hypoactivations especially to the least salient task condition (neutral words with no reward) had the most frequent current cocaine use; and (iii) responses to the most salient task condition in both these ACC major subdivisions were positively intercorrelated in the controls only. In conclusion, ACC hypoactivations in drug users cannot be attributed to task difficulty or disengagement. Nevertheless, emotional salience modulates ACC responses in proportion to drug use severity. Interventions to strengthen ACC reactivity or interconnectivity may be beneficial in enhancing top-down monitoring and emotion regulation as a strategy to reduce impulsive and compulsive behavior in addiction. PMID:19478067

  12. Specific Contributions of Ventromedial, Anterior Cingulate, and Lateral Prefrontal Cortex for Attentional Selection and Stimulus Valuation

    PubMed Central

    Kaping, Daniel; Vinck, Martin; Hutchison, R. Matthew; Everling, Stefan; Womelsdorf, Thilo

    2011-01-01

    Attentional control ensures that neuronal processes prioritize the most relevant stimulus in a given environment. Controlling which stimulus is attended thus originates from neurons encoding the relevance of stimuli, i.e. their expected value, in hand with neurons encoding contextual information about stimulus locations, features, and rules that guide the conditional allocation of attention. Here, we examined how these distinct processes are encoded and integrated in macaque prefrontal cortex (PFC) by mapping their functional topographies at the time of attentional stimulus selection. We find confined clusters of neurons in ventromedial PFC (vmPFC) that predominantly convey stimulus valuation information during attention shifts. These valuation signals were topographically largely separated from neurons predicting the stimulus location to which attention covertly shifted, and which were evident across the complete medial-to-lateral extent of the PFC, encompassing anterior cingulate cortex (ACC), and lateral PFC (LPFC). LPFC responses showed particularly early-onset selectivity and primarily facilitated attention shifts to contralateral targets. Spatial selectivity within ACC was delayed and heterogeneous, with similar proportions of facilitated and suppressed responses during contralateral attention shifts. The integration of spatial and valuation signals about attentional target stimuli was observed in a confined cluster of neurons at the intersection of vmPFC, ACC, and LPFC. These results suggest that valuation processes reflecting stimulus-specific outcome predictions are recruited during covert attentional control. Value predictions and the spatial identification of attentional targets were conveyed by largely separate neuronal populations, but were integrated locally at the intersection of three major prefrontal areas, which may constitute a functional hub within the larger attentional control network. PMID:22215982

  13. Comparing the actions of lanicemine and ketamine in depression: key role of the anterior cingulate.

    PubMed

    Downey, Darragh; Dutta, Arpan; McKie, Shane; Dawson, Gerard R; Dourish, Colin T; Craig, Kevin; Smith, Mark A; McCarthy, Dennis J; Harmer, Catherine J; Goodwin, Guy M; Williams, Steve; Deakin, J F William

    2016-06-01

    Intravenous infusion of lanicemine (formerly AZD6765), a low trapping non-selective N-methyl-D-aspartate (NMDA) receptor antagonist, induces antidepressant effects with a similar time course to ketamine. We investigated whether a single dose lanicemine infusion would reproduce the previously reported decrease in subgenual anterior cingulate cortex (sgACC) activity evoked by ketamine, a potential mechanism of antidepressant efficacy. Sixty un-medicated adults meeting the criteria for major depressive disorder were randomly assigned to receive constant intravenous infusions of ketamine, lanicemine or saline during a 60min pharmacological magnetic resonance imaging (phMRI) scan. Both ketamine and lanicemine gradually increased the blood oxygen level dependent signal in sgACC and rostral ACC as the primary outcome measure. No decreases in signal were seen in any region. Interviewer-rated psychotic and dissociative symptoms were minimal following administration of lanicemine. There was no significant antidepressant effect of either infusion compared to saline. The previously reported deactivation of sgACC after ketamine probably reflects the rapid and pronounced subjective effects evoked by the bolus-infusion method used in the previous study. Activation of the ACC was observed following two different NMDA compounds in both Manchester and Oxford using different 3T MRI scanners, and this effect predicted improvement in mood 1 and 7 days post-infusion. These findings suggest that the initial site of antidepressant action for NMDA antagonists may be the ACC (NCT01046630. A Phase I, Multi-centre, Double-blind, Placebo-controlled Parallel Group Study to Assess the pharmacoMRI Effects of AZD6765 in Male and Female Subjects Fulfilling the Criteria for Major Depressive Disorder; http://clinicaltrials.gov/show/NCT01046630). PMID:27133029

  14. Neurotoxicity and reactive astrogliosis in the anterior cingulate cortex in acute ciguatera poisoning.

    PubMed

    Zhang, Xu; Cao, Bing; Wang, Jun; Liu, Jin; Tung, Vivian Oi Vian; Lam, Paul Kwan Sing; Chan, Leo Lai; Li, Ying

    2013-06-01

    Ciguatoxins (CTXs) cause long-term disturbance of cerebral functions. The primary mechanism of neurotoxicity is related to their interaction with voltage-gated sodium channels. However, until now, the neurological targets for CTXs in the brain of intact animals have not been described. In our study, 1 day following oral exposure to 0.26 ng/g of Pacific ciguatoxin 1 (P-CTX-1), we performed in vivo electrophysiological recordings in the rat anterior cingulate cortex (ACC) and identified the increase in spontaneous firings and enhanced responses to visceral noxious stimulation. Local field recordings characterized the P-CTX-1-induced synaptic potentiation and blockage of the induction of electrical stimulation-induced long-term potentiation in the medial thalamus (MT)-ACC pathway. Furthermore, intracerebroventricular administration of P-CTX-1 at doses of 1.0, 5.0, and 10 nM produced a dose-dependent increase in ACC neuronal firings and MT-ACC synaptic transmission. Further studies showed upregulated Na(+) channel expression in astrocytes under pathological conditions. We hypothesized that the astrocytes might have been activated in the ciguatera poisoning in vivo. Increases in glial fibrillary acid protein expression were detected in reactive astrocytes in the rat ACC. The activation of astroglia was further indicated by activation of the gap junction protein connexin 43 and upregulation of excitatory amino acid transporter 2 expression suggesting that glutamate was normally rapidly cleared from the synaptic cleft during acute ciguatera poisoning. However, neurotoxicity and reactive astrogliosis were not detected in the ACC after 7 days of P-CTX-1 exposure. The present results are the first characterization of P-CTX-1-invoked brain cortex neuronal excitotoxicity in vivo and supported the theme that neuron and astroglia signals might play roles in acute ciguatera poisoning. PMID:23494292

  15. Insula–Dorsal Anterior Cingulate Cortex Coupling is Associated with Enhanced Brain Reactivity to Smoking Cues

    PubMed Central

    Janes, Amy C; Farmer, Stacey; Peechatka, Alyssa L; Frederick, Blaise de B; Lukas, Scott E

    2015-01-01

    The insula plays a critical role in maintaining nicotine dependence and reactivity to smoking cues. More broadly, the insula and the dorsal anterior cingulate cortex (dACC) are key nodes of the salience network (SN), which integrates internal and extrapersonal information to guide behavior. Thus, insula–dACC interactions may be integral in processing salient information such as smoking cues that facilitate continued nicotine use. We evaluated functional magnetic resonance imaging (fMRI) data from nicotine-dependent participants during rest, and again when they viewed smoking-related images. Greater insula–dACC coupling at rest was significantly correlated with enhanced smoking cue-reactivity in brain areas associated with attention and motor preparation, including the visual cortex, right ventral lateral prefrontal cortex, and the dorsal striatum. In an independent cohort, we found that insula–dACC connectivity was stable over 1-h delay and was not influenced by changes in subjective craving or expired carbon monoxide, suggesting that connectivity strength between these regions may be a trait associated with heightened cue-reactivity. Finally, we also showed that insula reactivity to smoking cues correlates with a rise in cue-reactivity throughout the entire SN, indicating that the insula's role in smoking cue-reactivity is not functionally independent, and may actually represent the engagement of the entire SN. Collectively, these data provide a more network-level understanding of the insula's role in nicotine dependence and shows a relationship between inherent brain organization and smoking cue-reactivity. PMID:25567427

  16. Frontal and rostral anterior cingulate (rACC) theta EEG in depression: implications for treatment outcome?

    PubMed

    Arns, Martijn; Etkin, Amit; Hegerl, Ulrich; Williams, Leanne M; DeBattista, Charles; Palmer, Donna M; Fitzgerald, Paul B; Harris, Anthony; deBeuss, Roger; Gordon, Evian

    2015-08-01

    In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingulate (rACC), as estimated by source localization of scalp-recorded electroencenphalogram (EEG), has been associated with response to antidepressant treatments, whereas elevated frontal theta has been linked to non-response. This study used source localization to attempt to integrate these apparently opposite results and test, whether antidepressant response is associated with elevated rACC theta and non-response with elevated frontal theta and whether theta activity is a differential predictor of response to different types of commonly used antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, international, randomized, prospective practical trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed and source localization (eLORETA) was employed to extract theta from the rACC and frontal cortex. Patients with MDD had elevated theta in both frontal cortex and rACC, with small effect sizes. High frontal and rACC theta were associated with treatment non-response, but not with non-remission, and this effect was most pronounced in a subgroup with previous treatment failures. Low theta in frontal cortex and rACC are found in responders to antidepressant treatments with a small effect size. Future studies should investigate in more detail the role of previous treatment (failure) in the association between theta and treatment outcome. PMID:25936227

  17. Endogenous Opioid Activity in the Anterior Cingulate Cortex Is Required for Relief of Pain

    PubMed Central

    Navratilova, Edita; Xie, Jennifer Yanhua; Meske, Diana; Qu, Chaoling; Morimura, Kozo; Okun, Alec; Arakawa, Naohisa; Ossipov, Michael; Fields, Howard L.

    2015-01-01

    Pain is aversive, and its relief elicits reward mediated by dopaminergic signaling in the nucleus accumbens (NAc), a part of the mesolimbic reward motivation pathway. How the reward pathway is engaged by pain-relieving treatments is not known. Endogenous opioid signaling in the anterior cingulate cortex (ACC), an area encoding pain aversiveness, contributes to pain modulation. We examined whether endogenous ACC opioid neurotransmission is required for relief of pain and subsequent downstream activation of NAc dopamine signaling. Conditioned place preference (CPP) and in vivo microdialysis were used to assess negative reinforcement and NAc dopaminergic transmission. In rats with postsurgical or neuropathic pain, blockade of opioid signaling in the rostral ACC (rACC) inhibited CPP and NAc dopamine release resulting from non-opioid pain-relieving treatments, including peripheral nerve block or spinal clonidine, an α2-adrenergic agonist. Conversely, pharmacological activation of rACC opioid receptors of injured, but not pain-free, animals was sufficient to stimulate dopamine release in the NAc and produce CPP. In neuropathic, but not sham-operated, rats, systemic doses of morphine that did not affect withdrawal thresholds elicited CPP and NAc dopamine release, effects that were prevented by blockade of ACC opioid receptors. The data provide a neural explanation for the preferential effects of opioids on pain affect and demonstrate that engagement of NAc dopaminergic transmission by non-opioid pain-relieving treatments depends on upstream ACC opioid circuits. Endogenous opioid signaling in the ACC appears to be both necessary and sufficient for relief of pain aversiveness. PMID:25948274

  18. Reproducibility of Neurochemical Profile Quantification in Pregenual Cingulate, Anterior Midcingulate, and Bilateral Posterior Insular Subdivisions Measured at 3 Tesla

    PubMed Central

    de Matos, Nuno M. P.; Meier, Lukas; Wyss, Michael; Meier, Dieter; Gutzeit, Andreas; Ettlin, Dominik A.; Brügger, Mike

    2016-01-01

    The current report assessed measurement reproducibility of proton magnetic resonance spectroscopy at 3 Tesla in the left and right posterior insular, pregenual anterior cingulate, and anterior midcingulate cortices. Ten healthy male volunteers aged 21–30 years were tested at four different days, of which nine were included in the data analysis. Intra- and inter-subject variability of myo-inositol, creatine, glutamate, total-choline, total-N-acetylaspartate, and combined glutamine–glutamate were calculated considering the influence of movement parameters, age, daytime of measurements, and tissue composition. Overall mean intra-/inter-subject variability for all neurochemicals combined revealed small mean coefficients of variation across the four regions: 5.3/9.05% in anterior midcingulate, 6.6/8.84% in pregenual anterior cingulate, 7.3/10.00% in left posterior and 8.2/10.55% in right posterior insula. Head movement, tissue composition and day time revealed no significant explanatory variance contribution suggesting a negligible influence on the data. A strong correlation between Cramer–Rao Lower Bounds (a measure of fitting errors) and the mean intra-subject coefficients of variation (r = 0.799, p < 0.001) outlined the importance of low fitting errors in order to obtain robust and finally meaningful measurements. The present findings confirm proton magnetic resonance spectroscopy as a reliable tool to measure brain neurochemistry in small subregions of the human brain. PMID:27445745

  19. Reproducibility of Neurochemical Profile Quantification in Pregenual Cingulate, Anterior Midcingulate, and Bilateral Posterior Insular Subdivisions Measured at 3 Tesla.

    PubMed

    de Matos, Nuno M P; Meier, Lukas; Wyss, Michael; Meier, Dieter; Gutzeit, Andreas; Ettlin, Dominik A; Brügger, Mike

    2016-01-01

    The current report assessed measurement reproducibility of proton magnetic resonance spectroscopy at 3 Tesla in the left and right posterior insular, pregenual anterior cingulate, and anterior midcingulate cortices. Ten healthy male volunteers aged 21-30 years were tested at four different days, of which nine were included in the data analysis. Intra- and inter-subject variability of myo-inositol, creatine, glutamate, total-choline, total-N-acetylaspartate, and combined glutamine-glutamate were calculated considering the influence of movement parameters, age, daytime of measurements, and tissue composition. Overall mean intra-/inter-subject variability for all neurochemicals combined revealed small mean coefficients of variation across the four regions: 5.3/9.05% in anterior midcingulate, 6.6/8.84% in pregenual anterior cingulate, 7.3/10.00% in left posterior and 8.2/10.55% in right posterior insula. Head movement, tissue composition and day time revealed no significant explanatory variance contribution suggesting a negligible influence on the data. A strong correlation between Cramer-Rao Lower Bounds (a measure of fitting errors) and the mean intra-subject coefficients of variation (r = 0.799, p < 0.001) outlined the importance of low fitting errors in order to obtain robust and finally meaningful measurements. The present findings confirm proton magnetic resonance spectroscopy as a reliable tool to measure brain neurochemistry in small subregions of the human brain. PMID:27445745

  20. Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD)

    PubMed Central

    Thakkar, Katharine N.; Polli, Frida E.; Joseph, Robert M.; Tuch, David S.; Hadjikhani, Nouchine; Barton, Jason J.S.

    2008-01-01

    Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing factors to autistic disorders. We investigated whether ACC structure and function during response monitoring were associated with repetitive behaviour in ASD. We compared ACC activation to correct and erroneous antisaccades using rapid presentation event-related functional MRI in 14 control and ten ASD participants. Because response monitoring is the product of coordinated activity in ACC networks, we also examined the microstructural integrity of the white matter (WM) underlying this brain region using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) in 12 control and 12 adult ASD participants. ACC activation and FA were examined in relation to Autism Diagnostic Interview-Revised ratings of restricted and repetitive behaviour. Relative to controls, ASD participants: (i) made more antisaccade errors and responded more quickly on correct trials; (ii) showed reduced discrimination between error and correct responses in rostral ACC (rACC), which was primarily due to (iii) abnormally increased activation on correct trials and (iv) showed reduced FA in WM underlying ACC. Finally, in ASD (v) increased activation on correct trials and reduced FA in rACC WM were related to higher ratings of repetitive behaviour. These findings demonstrate functional and structural abnormalities of the ACC in ASD that may contribute to repetitive behaviour. rACC activity following errors is thought to reflect affective appraisal of the error. Thus, the hyperactive rACC response to correct trials can be interpreted as a misleading affective signal that something is awry, which may trigger repetitive attempts at correction

  1. Prefrontal and anterior cingulate cortex abnormalities in Tourette Syndrome: evidence from voxel-based morphometry and magnetization transfer imaging

    PubMed Central

    Müller-Vahl, Kirsten R; Kaufmann, Jörn; Grosskreutz, Julian; Dengler, Reinhard; Emrich, Hinderk M; Peschel, Thomas

    2009-01-01

    Background Pathophysiological evidence suggests an involvement of fronto-striatal circuits in Tourette syndrome (TS). To identify TS related abnormalities in gray and white matter we used optimized voxel-based morphometry (VBM) and magnetization transfer imaging (MTI) which are more sensitive to tissue alterations than conventional MRI and provide a quantitative measure of macrostructural integrity. Methods Volumetric high-resolution anatomical T1-weighted MRI and MTI were acquired in 19 adult, unmedicated male TS patients without co-morbidities and 20 age- and sex-matched controls on a 1.5 Tesla neuro-optimized GE scanner. Images were pre-processed and analyzed using an optimized version of VBM in SPM2. Results Using VBM, TS patients showed significant decreases in gray matter volumes in prefrontal areas, the anterior cingulate gyrus, sensorimotor areas, left caudate nucleus and left postcentral gyrus. Decreases in white matter volumes were detected in the right inferior frontal gyrus, the left superior frontal gyrus and the anterior corpus callosum. Increases were found in the left middle frontal gyrus and left sensorimotor areas. In MTI, white matter reductions were seen in the right medial frontal gyrus, the inferior frontal gyrus bilaterally and the right cingulate gyrus. Tic severity was negatively correlated with orbitofrontal structures, the right cingulate gyrus and parts of the parietal-temporal-occipital association cortex bilaterally. Conclusion Our MRI in vivo neuropathological findings using two sensitive and unbiased techniques support the hypothesis that alterations in frontostriatal circuitries underlie TS pathology. We suggest that anomalous frontal lobe association and projection fiber bundles cause disinhibition of the cingulate gyrus and abnormal basal ganglia function. PMID:19435502

  2. Anterior cingulate cortex mediates the relationship between O3PUFAs and executive functions in APOE e4 carriers

    PubMed Central

    Zamroziewicz, Marta K.; Paul, Erick J.; Rubin, Rachael D.; Barbey, Aron K.

    2015-01-01

    Introduction: Although diet has a substantial influence on the aging brain, the relationship between biomarkers of diet and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between omega-3 polyunsaturated fatty acids (O3PUFAs) and executive functions in at-risk (APOE e4 carriers), cognitively intact older adults. We hypothesized that higher levels of O3PUFAs are associated with better performance in a particular component of the executive functions, namely cognitive flexibility, and that this relationship is mediated by gray matter volume of a specific region thought to be important for cognitive flexibility, the anterior cingulate cortex. Methods: We examined 40 cognitively intact adults between the ages of 65 and 75 with the APOE e4 polymorphism to investigate the relationship between biomarkers of O3PUFAs, tests of cognitive flexibility (measured by the Delis-Kaplan Executive Function System Trail Making Test), and gray matter volume within regions of the prefrontal cortex (PFC). Results: A mediation analysis revealed that gray matter volume within the left rostral anterior cingulate cortex partially mediates the relationship between O3PUFA biomarkers and cognitive flexibility. Conclusion: These results suggest that the anterior cingulate cortex acts as a mediator of the relationship between O3PUFAs and cognitive flexibility in cognitively intact adults thought to be at risk for cognitive decline. Through their link to executive functions and neuronal measures of PFC volume, O3PUFAs show potential as a nutritional therapy to prevent dysfunction in the aging brain. PMID:26052283

  3. Anterior Cingulate Cortico-Hippocampal Dysconnectivity in Unaffected Relatives of Schizophrenia Patients: A Stochastic Dynamic Causal Modeling Study.

    PubMed

    Xi, Yi-Bin; Li, Chen; Cui, Long-Biao; Liu, Jian; Guo, Fan; Li, Liang; Liu, Ting-Ting; Liu, Kang; Chen, Gang; Xi, Min; Wang, Hua-Ning; Yin, Hong

    2016-01-01

    Familial risk plays a significant role in the etiology of schizophrenia (SZ). Many studies using neuroimaging have demonstrated structural and functional alterations in relatives of SZ patients, with significant results found in diverse brain regions involving the anterior cingulate cortex (ACC), caudate, dorsolateral prefrontal cortex (DLPFC), and hippocampus. This study investigated whether unaffected relatives of first episode SZ differ from healthy controls (HCs) in effective connectivity measures among these regions. Forty-six unaffected first-degree relatives of first episode SZ patients-according to the DSM-IV-were studied. Fifty HCs were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI). We used stochastic dynamic causal modeling (sDCM) to estimate the directed connections between the left ACC, right ACC, left caudate, right caudate, left DLPFC, left hippocampus, and right hippocampus. We used Bayesian parameter averaging (BPA) to characterize the differences. The BPA results showed hyperconnectivity from the left ACC to right hippocampus and hypoconnectivity from the right ACC to right hippocampus in SZ relatives compared to HCs. The pattern of anterior cingulate cortico-hippocampal connectivity in SZ relatives may be a familial feature of SZ risk, appearing to reflect familial susceptibility for SZ. PMID:27512370

  4. Anterior Cingulate Cortico-Hippocampal Dysconnectivity in Unaffected Relatives of Schizophrenia Patients: A Stochastic Dynamic Causal Modeling Study

    PubMed Central

    Xi, Yi-Bin; Li, Chen; Cui, Long-Biao; Liu, Jian; Guo, Fan; Li, Liang; Liu, Ting-Ting; Liu, Kang; Chen, Gang; Xi, Min; Wang, Hua-Ning; Yin, Hong

    2016-01-01

    Familial risk plays a significant role in the etiology of schizophrenia (SZ). Many studies using neuroimaging have demonstrated structural and functional alterations in relatives of SZ patients, with significant results found in diverse brain regions involving the anterior cingulate cortex (ACC), caudate, dorsolateral prefrontal cortex (DLPFC), and hippocampus. This study investigated whether unaffected relatives of first episode SZ differ from healthy controls (HCs) in effective connectivity measures among these regions. Forty-six unaffected first-degree relatives of first episode SZ patients—according to the DSM-IV—were studied. Fifty HCs were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI). We used stochastic dynamic causal modeling (sDCM) to estimate the directed connections between the left ACC, right ACC, left caudate, right caudate, left DLPFC, left hippocampus, and right hippocampus. We used Bayesian parameter averaging (BPA) to characterize the differences. The BPA results showed hyperconnectivity from the left ACC to right hippocampus and hypoconnectivity from the right ACC to right hippocampus in SZ relatives compared to HCs. The pattern of anterior cingulate cortico-hippocampal connectivity in SZ relatives may be a familial feature of SZ risk, appearing to reflect familial susceptibility for SZ. PMID:27512370

  5. Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study

    PubMed Central

    Pastorello, Bruno F.; Leite, Cláudia da Costa; Henning, Anke; Moreno, Ricardo A.; Garcia Otaduy, Maria Concepción

    2016-01-01

    Objective: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Methods: Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm3) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Results: Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. Conclusion: This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis. PMID:27207914

  6. Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala.

    PubMed

    Feinstein, Justin S; Khalsa, Sahib S; Salomons, Tim V; Prkachin, Kenneth M; Frey-Law, Laura A; Lee, Jennifer E; Tranel, Daniel; Rudrauf, David

    2016-04-01

    Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience. PMID:25577137

  7. Astrocyte and glutamate markers in the superficial, deep, and white matter layers of the anterior cingulate gyrus in schizophrenia.

    PubMed

    Katsel, Pavel; Byne, William; Roussos, Panos; Tan, Weilun; Siever, Larry; Haroutunian, Vahram

    2011-05-01

    Most studies of the neurobiology of schizophrenia have focused on neurotransmitter systems, their receptors, and downstream effectors. Recent evidence suggests that it is no longer tenable to consider neurons and their functions independently of the glia that interact with them. Although astrocytes have been viewed as harbingers of neuronal injury and CNS stress, their principal functions include maintenance of glutamate homeostasis and recycling, mediation of saltatory conduction, and even direct neurotransmission. Results of studies of astrocytes in schizophrenia have been variable, in part because of the assessment of single and not necessarily universal markers and/or assessment of non-discrete brain regions. We used laser capture microdissection to study three distinct partitions of the anterior cingulate gyrus (layers I-III, IV-VI, and the underlying white matter) in the brains of 18 well-characterized persons with schizophrenia and 21 unaffected comparison controls. We studied the mRNA expression of nine specific markers known to be localized to astrocytes. The expression of astrocyte markers was not altered in the superficial layers or the underlying white matter of the cingulate cortex of persons with schizophrenia. However, the expression of some astrocyte markers (diodinase type II, aquaporin-4, S100β, glutaminase, excitatory amino-acid transporter 2, and thrombospondin), but not of others (aldehyde dehydrogenase 1 family member L1, glial fibrillary acidic protein, and vimentin) was significantly reduced in the deep layers of the anterior cingulate gyrus. These findings suggest that a subset of astrocytes localized to specific cortical layers is adversely affected in schizophrenia and raise the possibility of glutamatergic dyshomeostasis in selected neuronal populations. PMID:21270770

  8. Anatomical and functional overlap within the insula and anterior cingulate cortex during interoception and phobic symptom provocation.

    PubMed

    Caseras, Xavier; Murphy, Kevin; Mataix-Cols, David; López-Solà, Marina; Soriano-Mas, Carles; Ortriz, Hector; Pujol, Jesus; Torrubia, Rafael

    2013-05-01

    The anterior insula and the dorsal anterior cingulate cortex (ACC) are regarded as key brain structures associated with the integration of perceived phobic characteristics of external stimuli and the perception of ones own body responses that leads to emotional feelings. To test to what extent the activity in these two brain structures anatomically and functionally overlap during phobic reactions and interoception, we submitted the same group of phobic participants (n = 29; either spider or blood-injection-injury (BII) phobics) and controls (n = 17) to both type of experimental paradigms. Results showed that there was a clear anatomical overlap in the Blood Oxygen Level-Dependent (BOLD) responses within the anterior insula and ACC elicited during phobic symptom provocation and during interoceptive awareness. The activity within these two brain structures also showed to be correlated in the spider phobia group, but not in the BII phobic participants. Our results seem to support the idea that the activity within these two brain areas would be associated with the integration of perceived stimuli characteristics and bodily responses that lead to what we label as "fear." However, that seems not to be the case in BII phobia, where more research is needed in order to clarify to what extent that could be associated with the idiosyncratic physiological response that these patients present in front of phobic stimuli (i.e., drop in heart rate and blood pressure). PMID:22162203

  9. Combat veterans with comorbid PTSD and mild TBI exhibit a greater inhibitory processing ERP from the dorsal anterior cingulate cortex.

    PubMed

    Shu, I-Wei; Onton, Julie A; O'Connell, Ryan M; Simmons, Alan N; Matthews, Scott C

    2014-10-30

    Posttraumatic stress disorder (PTSD) is common among combat personnel with mild traumatic brain injury (mTBI). While patients with either PTSD or mTBI share abnormal activation of multiple frontal brain areas, anterior cingulate cortex (ACC) activity during inhibitory processing may be particularly affected by PTSD. To further test this hypothesis, we recorded electroencephalography from 32 combat veterans with mTBI-17 of whom were also comorbid for PTSD (mTBI+PTSD) and 15 without PTSD (mTBI-only). Subjects performed the Stop Task, a validated inhibitory control task requiring inhibition of initiated motor responses. We observed a larger inhibitory processing eventrelated potential (ERP) in veterans with mTBI+PTSD, including greater N200 negativity. Furthermore, greater N200 negativity correlated with greater PTSD severity. This correlation was most dependent on contributions from the dorsal ACC. Support vector machine analysis demonstrated that N200 and P300 amplitudes objectively classified veterans into mTBI-only or mTBI+PTSD groups with 79.4% accuracy. Our results support a model where, in combat veterans with mTBI, larger ERPs from cingulate areas are associated with greater PTSD severity and likely related to difficulty controlling ongoing brain processes, including trauma-related thoughts and feelings. PMID:25150386

  10. Memory consolidation of fear conditioning: bi-stable amygdala connectivity with dorsal anterior cingulate and medial prefrontal cortex.

    PubMed

    Feng, Pan; Feng, Tingyong; Chen, Zhencai; Lei, Xu

    2014-11-01

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of memory consolidation of fear conditioning is not well understood. To address this question, we measured brain activity and the changes in functional connectivity following fear acquisition using resting-state functional magnetic resonance imaging. The amygdala-dorsal anterior cingulate cortex (dACC) and hippocampus-insula functional connectivity were enhanced, whereas the amygdala-medial prefrontal cortex (mPFC) functional coupling was decreased during fear memory consolidation. Furthermore, the amygdala-mPFC functional connectivity was negatively correlated with the subjective fear ratings. These findings suggest the amygdala functional connectivity with dACC and mPFC may play an important role in memory consolidation of fear conditioning. The change of amygdala-mPFC functional connectivity could predict the subjective fear. Accordingly, this study provides a new perspective for understanding fear memory consolidation. PMID:24194579

  11. Provisional hypotheses for the molecular genetics of cognitive development: Imaging genetic pathways in the anterior cingulate cortex

    PubMed Central

    Fossella, John; Fan, Jin; Liu, Xun; Guise, Kevin; Brocki, Karin; Hof, Patrick R.; Kittappa, Raja; McKay, Ronald; Posner, Michael

    2008-01-01

    Brain imaging genetic research involves a multitude of methods and spans many traditional levels of analysis. Given the vast permutations among several million common genetic variants with thousands of brain tissue voxels and a wide array of cognitive tasks that activate specific brain systems, we are prompted to develop specific hypotheses that synthesize converging evidence and state clear predictions about the anatomical sources, magnitude and direction (increases vs. decreases) of allele- and task-specific brain activity associations. To begin to develop a framework for shaping our imaging genetic hypotheses, we focus on previous results and the wider imaging genetic literature. Particular emphasis is placed on converging evidence that links system-level and biochemical studies with models of synaptic function. In shaping our own imaging genetic hypotheses on the development of Attention Networks, we review relevant literature on core models of synaptic physiology and development in the anterior cingulate cortex. PMID:18261834

  12. Roles of the Lateral Habenula and Anterior Cingulate Cortex in Negative Outcome Monitoring and Behavioral Adjustment in Nonhuman Primates.

    PubMed

    Kawai, Takashi; Yamada, Hiroshi; Sato, Nobuya; Takada, Masahiko; Matsumoto, Masayuki

    2015-11-18

    Animals monitor the outcome of their choice and adjust subsequent choice behavior using the outcome information. Together with the anterior cingulate cortex (ACC), the lateral habenula (LHb) has recently attracted attention for its crucial role in monitoring negative outcome. To investigate their contributions to subsequent behavioral adjustment, we recorded single-unit activity from the LHb and ACC in monkeys performing a reversal learning task. The monkey was required to shift a previous choice to the alternative if the choice had been repeatedly unrewarded in past trials. We found that ACC neurons stored outcome information from several past trials, whereas LHb neurons detected the ongoing negative outcome with shorter latencies. ACC neurons, but not LHb neurons, signaled a behavioral shift in the next trial. Our findings suggest that, although both the LHb and the ACC represent signals associated with negative outcome, these structures contribute to subsequent behavioral adjustment in different ways. PMID:26481035

  13. Memory consolidation of fear conditioning: Bi-stable amygdala connectivity with dorsal anterior cingulate and medial prefrontal cortex

    PubMed Central

    Feng, Pan; Chen, Zhencai; Lei, Xu

    2014-01-01

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of memory consolidation of fear conditioning is not well understood. To address this question, we measured brain activity and the changes in functional connectivity following fear acquisition using resting-state functional magnetic resonance imaging. The amygdala–dorsal anterior cingulate cortex (dACC) and hippocampus–insula functional connectivity were enhanced, whereas the amygdala–medial prefrontal cortex (mPFC) functional coupling was decreased during fear memory consolidation. Furthermore, the amygdala–mPFC functional connectivity was negatively correlated with the subjective fear ratings. These findings suggest the amygdala functional connectivity with dACC and mPFC may play an important role in memory consolidation of fear conditioning. The change of amygdala-mPFC functional connectivity could predict the subjective fear. Accordingly, this study provides a new perspective for understanding fear memory consolidation. PMID:24194579

  14. Neuronal activity in primate dorsal anterior cingulate cortex signals task conflict and predicts adjustments in pupil-linked arousal

    PubMed Central

    Ebitz, R. Becket; Platt, Michael L.

    2014-01-01

    Summary Whether driving a car, shopping for food, or paying attention in a classroom of boisterous teenagers, it’s often hard to maintain focus on goals in the face of distraction. Brain imaging studies in humans implicate the dorsal anterior cingulate cortex (dACC) in regulating the conflict between goals and distractors. Here we show for the first time that single dACC neurons signal conflict between task goals and distractors in the rhesus macaque, particularly for biologically-relevant social stimuli. For some neurons, task conflict signals predicted subsequent changes in pupil size—a peripheral index of arousal linked to noradrenergic tone—associated with reduced distractor interference. dACC neurons also responded to errors and these signals predicted adjustments in pupil size. These findings provide the first neurophysiological endorsement of the hypothesis that dACC regulates conflict, in part, via modulation of pupil-linked processes such as arousal. PMID:25654259

  15. Stereological assessment of the dorsal anterior cingulate cortex in schizophrenia: absence of changes in neuronal and glial densities

    PubMed Central

    Höistad, Malin; Heinsen, Helmut; Wicinski, Bridget; Schmitz, Christoph; Hof, Patrick R.

    2012-01-01

    Aims The prefrontal and anterior cingulate cortices are implicated in schizophrenia, and many studies have assessed volume, cortical thickness, and neuronal densities or numbers in these regions. Available data however are rather conflicting and no clear cortical alteration pattern has been established. Changes in oligodendrocytes and white matter have been observed in schizophrenia, introducing a hypothesis about a myelin deficit as a key event in disease development. Methods We investigated the dorsal anterior cingulate cortex (dACC) in 13 males with schizophrenia and 13 age- and gender-matched controls. We assessed stereologically the dACC volume, neuronal and glial densities, total neuron and glial numbers, and glia/neuron (GNI) ratios in both layers II-III and V-VI. Results We observed no differences in neuronal or glial densities. No changes were observed in dACC cortical volume, total neuron numbers, and total glial numbers in schizophrenia. This contrasts with previous findings and suggests that the dACC may not undergo as severe changes in schizophrenia as is generally believed. However, we observed higher glial densities in layers V-VI than in layers II-III in both controls and patients with schizophrenia, pointing to possible layer-specific effects on oligodendrocyte distribution during development. Conclusions Using rigorous stereological methods, we demonstrate a seemingly normal cortical organization in an important neocortical area for schizophrenia, emphasizing the importance of such morphometric approaches in quantitative neuropathology. We discuss the significance of subregion- and layer-specific alterations in the development of schizophrenia, and the discrepancies between post-mortem histopathological studies and in vivo brain imaging findings in patients. PMID:22860626

  16. Reversible Akinetic Mutism after Aneurysmal Subarachnoid Haemorrhage in the Territory of the Anterior Cerebral Artery without Permanent Ischaemic Damage to Anterior Cingulate Gyri

    PubMed Central

    Sibille, François-Xavier; Duprez, Thierry; van Pesch, Vincent; Giglioli, Simone

    2016-01-01

    We report on two cases of transient akinetic mutism after massive subarachnoid haemorrhage due to the rupture of an intracranial aneurysm of the anterior cerebral artery (ACA). In the two cases, vasospasm could not be demonstrated by imaging studies throughout the clinical course. Both patients shared common radiological features: a hydrocephalus due to haemorrhagic contamination of the ventricular system and a mass effect of a subpial hematoma on the borders of the corpus callosum. Patients were also investigated using auditory event-related evoked potentials at acute stage. In contrast to previous observations of akinetic mutism, P300 wave could not be recorded. Both patients had good recovery and we hypothesized that this unexpectedly favourable outcome was due to the absence of permanent structural damage to the ACA territory, with only transient dysfunction due to a reversible mass effect on cingulate gyri. PMID:27418987

  17. Inactivation of the Anterior Cingulate Cortex Impairs Extinction of Rabbit Jaw Movement Conditioning and Prevents Extinction-Related Inhibition of Hippocampal Activity

    ERIC Educational Resources Information Center

    Griffin, Amy L.; Berry, Stephen D.

    2004-01-01

    Although past research has highlighted the involvement of limbic structures such as the anterior cingulate cortex (ACC) and hippocampus in learning, few have addressed the nature of their interaction. The current study of rabbit jaw movement conditioning used a combination of reversible lesions and electrophysiology to examine the involvement of…

  18. Abnormalities in the Anterior Cingulate Cortex Associated with Attentional and Inhibitory Control Deficits: A Neurophysiological Study on Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Chan, Agnes S.; Han, Yvonne M. Y.; Leung, Winnie Wing-man; Leung, Connie; Wong, Virginia C. N.; Cheung, Mei-chun

    2011-01-01

    Previous studies showed that the anterior cingulate cortex (ACC) is activated when individuals engage in attention and inhibitory control tasks. The present study examined whether ACC activity is associated with behavioral performance of the two tasks. Twenty normal and 20 children with autism spectrum disorders (ASDs) were subjected to…

  19. Reduced Activation in Right Lateral Prefrontal Cortex and Anterior Cingulate Gyrus in Medication-Naive Adolescents with Attention Deficit Hyperactivity Disorder during Time Discrimination

    ERIC Educational Resources Information Center

    Smith, Anna B.; Taylor, Eric; Brammer, Michael; Halari, Rozmin; Rubia, Katya

    2008-01-01

    Background: Patients with attention deficit hyperactivity disorder (ADHD) under-perform when discriminating between durations differing by several hundred milliseconds. This function involves right prefrontal and anterior cingulate (AC) brain regions, which are structurally and functionally compromised in this patient group during executive tasks.…

  20. Glutamine and Glutamate Levels in Children and Adolescents with Bipolar Disorder: A 4.0-T Proton Magnetic Resonance Spectroscopy Study of the Anterior Cingulate Cortex

    ERIC Educational Resources Information Center

    Moore, Constance M.; Frazier, Jean A.; Glod, Carol A.; Breeze, Janis L.; Dieterich, Megan; Finn, Chelsea T.; deB. Frederick, Blaise; Renshaw, Perry F.

    2007-01-01

    Objective: The purpose of this study was to use proton magnetic resonance spectroscopy, at 4.0 T, to explore the glutamine and glutamate levels in the anterior cingulate cortex of children and adolescents with bipolar disorder (BPD; medicated and unmedicated) and healthy comparison subjects (HCSs). We hypothesized that unmedicated children with…

  1. Macro and micro structures in the dorsal anterior cingulate cortex contribute to individual differences in self-monitoring.

    PubMed

    Yang, Junyi; Tian, Xue; Wei, Dongtao; Liu, Huijuan; Zhang, Qinglin; Wang, Kangcheng; Chen, Qunlin; Qiu, Jiang

    2016-06-01

    Individual differences in self-monitoring, which are the capability to adjust behavior to adapt to social situations, influence a wide range of social behaviors. However, understanding of focal differences in brain structures related to individual self-monitoring is minimal, particularly when micro and macro structures are considered simultaneously. The present study investigates the relationship between self-monitoring and brain structure in a relatively large sample of young adults. Voxel-based morphometry (VBM) revealed a significant positive correlation between self-monitoring and gray matter volume in the dorsal cingulate anterior cortex (dACC), dorsal lateral prefrontal cortex (DLPFC), and bilateral ventral striatum (VS). Further analysis revealed a significant negative correlation between self-monitoring and white matter (WM) integrity, as indexed by fractional anisotropy (FA) in the anterior cingulum (ACG) bundle. Moreover, there was a significant positive correlation between self-monitoring and mean radius diffusion (RD). These results shed light on the structural neural basis of variation in self-monitoring. PMID:25958159

  2. Disrupted causal connectivity anchored on the anterior cingulate cortex in first-episode medication-naive major depressive disorder.

    PubMed

    Feng, Zhan; Xu, Shunliang; Huang, Manli; Shi, Yushu; Xiong, Bing; Yang, Hong

    2016-01-01

    In recent years, major depressive disorder (MDD) has been demonstrated to be associated with abnormalities in neural networks, particularly the prefrontal-limbic network (PLN). However, there are few current studies that have examined information flow in the PLN. In this study, Granger causality analysis (GCA), based on signed regression coefficient, was used to explore changes in causal connectivity in resting-state PLNs of MDD patients. A total of 23 first-episode medication-naïve MDD patients and 20 normal control participants were subjected to resting-state functional magnetic resonance imaging (RS-fMRI) scans. Increased causal effects of the right insular cortex, right putamen and right caudate on the rostral anterior cingulate cortex (rACC) and reduced causal effects of bilateral dorsolateral prefrontal cortex (DLPFC) and left orbitofrontal cortex (OFC) on the rACC were found in MDD patients compared to normal controls. The extensive reduction in the causal effect of the prefrontal cortex (PFC) demonstrates impaired top-down cognitive control in MDD patients. Changes in the causal relationship between the right insula and rACC suggest problems in coordination of the default mode network by the right anterior insular cortex (rAI). These findings provide valuable insight into MDD-related neural network disorders reported in previous RS-fMRI studies and may potentially guide clinical treatment of MDD in the future. PMID:26234517

  3. Structural connectivity of the anterior cingulate in children with unilateral cerebral palsy due to white matter lesions

    PubMed Central

    Scheck, Simon M.; Pannek, Kerstin; Raffelt, David A.; Fiori, Simona; Boyd, Roslyn N.; Rose, Stephen E.

    2015-01-01

    In this work we investigate the structural connectivity of the anterior cingulate cortex (ACC) and its link with impaired executive function in children with unilateral cerebral palsy (UCP) due to periventricular white matter lesions. Fifty two children with UCP and 17 children with typical development participated in the study, and underwent diffusion and structural MRI. Five brain regions were identified for their high connectivity with the ACC using diffusion MRI fibre tractography: the superior frontal gyrus, medial orbitofrontal cortex, rostral middle frontal gyrus, precuneus and isthmus cingulate. Structural connectivity was assessed in pathways connecting these regions to the ACC using three diffusion MRI derived measures: fractional anisotropy (FA), mean diffusivity (MD) and apparent fibre density (AFD), and compared between participant groups. Furthermore we investigated correlations of these measures with executive function as assessed by the Flanker task. The ACC–precuneus tract had significantly different MD (p < 0.0001) and AFD (p = 0.0072) between groups, with post-hoc analysis showing significantly increased MD in the right hemisphere of children with left hemiparesis compared with controls. The ACC–superior frontal gyrus tract had significantly different FA (p = 0.0049) and MD (p = 0.0031) between groups. AFD in this tract (contralateral to side of hemiparesis; right hemisphere in controls) showed a significant relationship with Flanker task performance (p = 0.0045, β = −0.5856), suggesting that reduced connectivity correlates with executive dysfunction. Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function. PMID:26640762

  4. No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex

    PubMed Central

    2014-01-01

    One major interest in the study of transient receptor potential vanilloid type 1 (TRPV1) in sensory system is that it may serve as a drug target for treating chronic pain. While the roles of TRPV1 in peripheral nociception and sensitization have been well documented, less is known about its contribution to pain-related cortical plasticity. Here, we used 64 multi-electrode array recording to examine the potential role of TRPV1 in two major forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), in the anterior cingulate cortex (ACC). We found that pharmacological blockade of TRPV1 with either [(E)-3-(4-t-Butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide] (AMG9810, 10 μM) or N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791, 20 μM) failed to affect LTP induced by strong theta burst stimulation in the ACC of adult mice. Similarly, neither AMG9810 nor SB366791 blocked the cingulate LTD induced by low-frequency stimulation. Analysis of the results from different layers of the ACC obtained the same conclusions. Spatial distribution of LTP or LTD-showing channels among the ACC network was also unaltered by the TRPV1 antagonists. Since cortical LTP and LTD in the ACC play critical roles in chronic pain triggered by inflammation or nerve injury, our findings suggest that TRPV1 may not be a viable target for treating chronic pain, especially at the cortical level. PMID:24708859

  5. Muscarinic receptor binding increases in anterior thalamus and cingulate cortex during discriminative avoidance learning

    SciTech Connect

    Vogt, B.A.; Gabriel, M.; Vogt, L.J.; Poremba, A.; Jensen, E.L.; Kubota, Y.; Kang, E. )

    1991-06-01

    Training-induced neuronal activity develops in the mammalian limbic system during discriminative avoidance conditioning. This study explores behaviorally relevant changes in muscarinic ACh receptor binding in 52 rabbits that were trained to one of five stages of conditioned response acquisition. Sixteen naive and 10 animals yoked to criterion performance served as control cases. Upon reaching a particular stage of training, the brains were removed and autoradiographically assayed for 3H-oxotremorine-M binding with 50 nM pirenzepine (OxO-M/PZ) or for 3H-pirenzepine binding in nine limbic thalamic nuclei and cingulate cortex. Specific OxO-M/PZ binding increased in the parvocellular division of the anterodorsal nucleus early in training when the animals were first exposed to pairing of the conditional and unconditional stimuli. Elevated binding in this nucleus was maintained throughout subsequent training. In the parvocellular division of the anteroventral nucleus (AVp), OxO-M/PZ binding progressively increased throughout training, reached a peak at the criterion stage of performance, and returned to control values during extinction sessions. Peak OxO-M/PZ binding in AVp was significantly elevated over that for cases yoked to criterion performance. In the magnocellular division of the anteroventral nucleus (AVm), OxO-M/PZ binding was elevated only during criterion performance of the task, and it was unaltered in any other limbic thalamic nuclei. Specific OxO-M/PZ binding was also elevated in most layers in rostral area 29c when subjects first performed a significant behavioral discrimination. Training-induced alterations in OxO-M/PZ binding in AVp and layer Ia of area 29c were similar and highly correlated.

  6. Scopolamine into the anterior cingulate cortex diminishes nociception in a neuropathic pain model in the rat: an interruption of 'nociception-related memory acquisition'?

    PubMed

    Ortega-Legaspi, J Manuel; López-Avila, Alberto; Coffeen, Ulises; del Angel, Rosendo; Pellicer, Francisco

    2003-01-01

    The cingulate cortex plays a key role in the affective component related to pain perception. This structure receives cholinergic projections and also plays a role in memory processing. Therefore, we propose that the cholinergic system in the anterior cingulate cortex is involved in the nociceptive memory process. We used scopolamine (10 microg in 0.25 mircrol/saline) microinjected into the anterior cingulate cortex, either before thermonociception followed by a sciatic denervation, between thermonociception and denervation or after both procedures (n=10 each). The vehicle group (saline solution 0.9%, n=14) was microinjected before thermonociception. Chronic nociception was measured by the autotomy score, which onset and incidence were also determined. Group scopolamine-thermonociception-denervation (STD) presented the lowest autotomy score as compared to vehicle and group thermonociception-denervation-scopolamine (TDS) (vehicle vs. STD, p=0.002, STD vs. TDS, p=0.001). Group thermonociception-scopolamine-denervation (TSD) showed a diminished autotomy score when compared to TDS (p=0.053). STD group showed a delay in the onset of AB as compared to the rest of the groups. Group TSD presented a significative delay (p=0.048) in AB onset when compared to group TDS. There were no differences in the incidence between groups. The results show that nociception-related memory processed in the anterior cingulate cortex is susceptible of being modified by the cholinergic transmission blockade. When scopolamine is microinjected prior to the nociceptive stimuli, nociception-related memory acquisition is prevented. The evidence obtained in this study shows the role of the anterior cingulate cortex in the acquisition of nociception-related memory. PMID:12935794

  7. Cortical thinning of the right anterior cingulate cortex in spider phobia: a magnetic resonance imaging and spectroscopy study.

    PubMed

    Linares, I M P; Jackowski, A P; Trzesniak, C M F; Arrais, K C; Chagas, M H N; Sato, J R; Santos, A C; Hallak, J E C; Zuardi, A W; Nardi, A E; Coimbra, N C; Crippa, J A S

    2014-08-12

    There a lack of consistent neuroimaging data on specific phobia (SP) and a need to assess volumetric and metabolic differences in structures implicated in this condition. The aim of this study is investigate possible metabolic (via (1)H MRS) and cortical thickness abnormalities in spider-phobic patients compared to healthy volunteers. Participants were recruited via public advertisement and underwent clinical evaluations and MRI scans. The study started in 2010 and the investigators involved were not blind in respect to patient groupings. The study was conducted at the Ribeirão Preto Medical School University Hospital of the University of São Paulo, Brazil. Patients with spider phobia (n=19) were matched to 17 healthy volunteers with respect to age, education and socio-economic status. The spider SP group fulfilled the diagnostic criteria for spider phobia according to the Structured Clinical Interview for DSM-IV. None of the participants had a history of neurological, psychiatric or other relevant organic diseases, use of prescribed psychotropic medication or substance abuse. All imaging and spectroscopy data were collected with a 3 T MRI scanner equipped with 25 mT gradient coils in 30-minute scans. The Freesurfer image analysis package and LC Model software were used to analyze data. The hypothesis being tested was formulated before the data collection (neural correlates of SP would include the amygdala, insula, anterior cingulate gyrus and others). The results indicated the absence of metabolic alterations, but thinning of the right anterior cingulate cortex (ACC) in the SP group when compared to the healthy control group (mean cortical thickness±SD: SP=2.11±0.45 mm; HC=2.16±0.42 mm; t (34)=3.19, p=0.001 [-35.45, 71.00, -23.82]). In spectroscopy, the ratios between N-acetylaspartate and creatine and choline levels were measured. No significant effect or correlation was found between MRS metabolites and scores in the Spider Phobia Questionnaire and Beck

  8. Comparison of anterior cingulate vs. insular cortex as targets for real-time fMRI regulation during pain stimulation

    PubMed Central

    Emmert, Kirsten; Breimhorst, Markus; Bauermann, Thomas; Birklein, Frank; Van De Ville, Dimitri; Haller, Sven

    2014-01-01

    Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network, notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group) for AIC and ACC feedback. First, a functional localizer using block-design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC. Second, subjects were asked to down-regulate the BOLD activation in four neurofeedback runs during identical pain stimulation. Data analysis included task-related and functional connectivity analysis. At the behavioral level, pain ratings significantly decreased during feedback vs. localizer runs, but there was no difference between AIC and ACC groups. Concerning neuroimaging, ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down-regulation (17/28) in both task-related and functional connectivity analysis. The functional connectivity toward the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex. Consequently, the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the caudate nucleus, although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally, the caudate, an important area involved in pain perception and suppression, could be a good rt-fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain

  9. The von Economo neurons in fronto-insular and anterior cingulate cortex

    PubMed Central

    Allman, John M.; Tetreault, Nicole A.; Hakeem, Atiya Y.; Manaye, Kebreten F.; Semendeferi, Katerina; Erwin, Joseph M.; Park, Soyoung; Goubert, Virginie; Hof, Patrick R.

    2011-01-01

    The von Economo neurons (VENs) are large bipolar neurons located in fronto-insular cortex (FI) and anterior limbic area (LA) in great apes and humans but not in other primates. Our stereological counts of VENs in FI and LA show them to be more numerous in humans than in apes. In humans, small numbers of VENs appear the 36th week post conception, with numbers increasing during the first eight months after birth. There are significantly more VENs in the right hemisphere in postnatal brains; this may be related to asymmetries in the autonomic nervous system. VENs are also present in elephants and whales and may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI and LA to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of fronto-temporal dementia implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging. PMID:21534993

  10. The von Economo neurons in the frontoinsular and anterior cingulate cortex.

    PubMed

    Allman, John M; Tetreault, Nicole A; Hakeem, Atiya Y; Manaye, Kebreten F; Semendeferi, Katerina; Erwin, Joseph M; Park, Soyoung; Goubert, Virginie; Hof, Patrick R

    2011-04-01

    The von Economo neurons (VENs) are large bipolar neurons located in the frontoinsular cortex (FI) and limbic anterior (LA) area in great apes and humans but not in other primates. Our stereological counts of VENs in FI and LA show them to be more numerous in humans than in apes. In humans, small numbers of VENs appear the 36th week postconception, with numbers increasing during the first 8 months after birth. There are significantly more VENs in the right hemisphere in postnatal brains; this may be related to asymmetries in the autonomic nervous system. VENs are also present in elephants and whales and may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI and LA to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of frontotemporal dementia (FTD) implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging. PMID:21534993

  11. Combined rTMS treatment targeting the Anterior Cingulate and the Temporal Cortex for the Treatment of Chronic Tinnitus.

    PubMed

    Kreuzer, Peter M; Lehner, Astrid; Schlee, Winfried; Vielsmeier, Veronika; Schecklmann, Martin; Poeppl, Timm B; Landgrebe, Michael; Rupprecht, Rainer; Langguth, Berthold

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a tinnitus treatment option. Promising results have been obtained by consecutive stimulation of lateral frontal and auditory brain regions. We investigated a combined stimulation paradigm targeting the anterior cingulate cortex (ACC) with double cone coil rTMS, followed by stimulation of the temporo-parietal junction area with a figure-of-eight coil. The study was conducted as a randomized, double-blind pilot trial in 40 patients suffering from chronic tinnitus. We compared mediofrontal stimulation with double-cone-coil, (2000 stimuli, 10 Hz) followed by left temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz) to left dorsolateral-prefrontal-cortex stimulation with figure-of-eight-coil (2000 stimuli, 10 Hz) followed by temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz). The stimulation was feasible with comparable dropout rates in both study arms; no severe adverse events were registered. Responder rates did not differ in both study arms. There was a significant main effect of time for the change in the TQ score, but no significant time x group interaction. This pilot study demonstrated the feasibility of combined mediofrontal/temporoparietal-rTMS-stimulation with double cone coil in tinnitus patients but failed to show better outcome compared to an actively rTMS treated control group. PMID:26667790

  12. Decision-making deficits associated with disrupted synchronization between basolateral amygdala and anterior cingulate cortex in rats after tooth loss.

    PubMed

    Xu, Xiaoxiang; Cao, Bing; Wang, Jun; Yu, Tianran; Li, Ying

    2015-07-01

    Human studies have shown that multiple teeth loss was significantly associated with cognitive impairment, dementia and Alzheimer's disease. However, the causal relationship between tooth loss and cognitive deficits has not been clarified. Rodents demonstrate human-like cognitive faculties. In this study by performing rat gambling task (RGT), we reported that prolonged tooth loss condition by extracting all left molars in the rats led to an increase in the proportion of poor decision-makers, and decrease in the proportion of good decision-makers compared with controls. No influence was detected on the general activity and motivation after tooth loss. Recent experiments have shown that decision-making performances in the RGT rely on the functional integrity of the amygdala and anterior cingulate cortex (ACC). The theta band brain oscillation has been acknowledged for extensive cognitive functions. Here, we performed multiple-electrode array recordings of local field potential (LFP) in anesthetized rats. The results exhibited an increase in accumulative power of the theta frequency of LFP in the basolateral amygdala (BLA) and decrease of theta power in the ACC in tooth loss rats. Furthermore, cross-correlation analysis displayed that tooth loss suppressed the synchronization of theta frequency of LFP between the BLA and ACC, indicating reduced neuronal communications between these two regions. In conclusion, we demonstrate for the first time that tooth loss leads to higher-order cognitive deficits accompanied by the alteration of theta frequency of LFP in brain circuitries and disruption of neural network integrity. PMID:25684327

  13. Not so bad: avoidance and aversive discounting modulate threat appraisal in anterior cingulate and medial prefrontal cortex

    PubMed Central

    Schlund, Michael W.; Brewer, Adam T.; Richman, David M.; Magee, Sandy K.; Dymond, Simon

    2015-01-01

    The dorsal anterior cingulate (adACC) and dorsal medial prefrontal cortex (dmPFC) play a central role in the discrimination and appraisal of threatening stimuli. Yet, little is known about what specific features of threatening situations recruit these regions and how avoidance may modulate appraisal and activation through prevention of aversive events. In this investigation, 30 healthy adults underwent functional neuroimaging while completing an avoidance task in which responses to an Avoidable CS+ threat prevented delivery of an aversive stimulus, but not to an Unavoidable CS+ threat. Extinction testing was also completed where CSs were presented without aversive stimulus delivery and an opportunity to avoid. The Avoidable CS+ relative to the Unavoidable CS+ was associated with reductions in ratings of negative valence, fear, and US expectancy and activation. Greater regional activation was consistently observed to the Unavoidable CS+ during avoidance, which declined during extinction. Individuals exhibiting greater aversive discounting—that is, those more avoidant of immediate monetary loss compared to a larger delayed loss—also displayed greater activation to the Unavoidable CS+, highlighting aversive discounting as a significant individual difference variable. These are the first results linking adACC/dmPFC reactivity to avoidance-based reductions of aversive events and modulation of activation by individual differences in aversive discounting. PMID:26113813

  14. Modulation of Beta-Band Activity in the Subgenual Anterior Cingulate Cortex during Emotional Empathy in Treatment-Resistant Depression.

    PubMed

    Merkl, Angela; Neumann, Wolf-Julian; Huebl, Julius; Aust, Sabine; Horn, Andreas; Krauss, Joachim K; Dziobek, Isabel; Kuhn, Jens; Schneider, Gerd-Helge; Bajbouj, Malek; Kühn, Andrea A

    2016-06-01

    Deep brain stimulation (DBS) is a promising approach in treatment-resistant depression (TRD). TRD is associated with problems in interpersonal relationships, which might be linked to impaired empathy. Here, we investigate the influence of DBS in the subgenual anterior cingulate cortex (sgACC) on empathy in patients with TRD and explore the pattern of oscillatory sgACC activity during performance of the multifaceted empathy test. We recorded local field potential activity directly from sgACC via DBS electrodes in patients. Based on previous behavioral findings, we expected disrupted empathy networks. Patients showed increased empathic involvement ratings toward negative stimuli as compared with healthy subjects that were significantly reduced after 6 months of DBS. Stimulus-related oscillatory activity pattern revealed a broad desynchronization in the beta (14-35 Hz) band that was significantly larger during patients' reported emotional empathy for negative stimuli than when patients reported to have no empathy. Beta desynchronization for empathic involvement correlated with self-reported severity of depression. Our results indicate a "negativity bias" in patients that can be reduced by DBS. Moreover, direct recordings show activation of the sgACC area during emotional processing and propose that changes in beta-band oscillatory activity in the sgACC might index empathic involvement of negative emotion in TRD. PMID:25994959

  15. Brain-derived neurotrophic factor in the anterior cingulate cortex is involved in the formation of fear memory.

    PubMed

    Li, Qing-Qing; Li, Bao-Ming

    2015-10-25

    Brain-derived neurotrophic factor (BDNF), a small dimeric secretory protein, plays a vital role in activity-dependent synaptic plasticity, learning and memory. It has been shown that BDNF in the hippocampus and amygdala participates in the formation of fear memory. However, little is known about the functional role of BDNF in the anterior cingulate cortex (ACC). To address this question, we examined the mRNA and protein levels of BDNF in the ACC of rats at various time points after fear conditioning, using quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). The results showed that BDNF exhibited a temporally specific increase in both mRNA and protein levels after CS (tone) and US (foot shock) was paired. Such increase did not occur after the animals were exposed to CS or US alone. When BDNF antibody was locally infused into the ACC prior to CS-US pairing, both contextual and auditory fear memories were severely impaired. Taken together, these results suggest that BDNF in the ACC is required for the formation of fear memory. PMID:26490062

  16. Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism

    PubMed Central

    2013-01-01

    Background Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. The anterior cingulate cortex (ACC) has been implicated in autism as well as in glutamatergic neurotransmission. We hypothesized that alterations in the glutamate-glutamine cycle in the ACC might play a role in the pathophysiology of autism. Methods We performed Western blot analyses for the protein expression levels of enzymes in the glutamate-glutamine cycle, including glutamine synthetase, kidney-type glutaminase, liver-type glutaminase, and glutamate dehydrogenases 1 and 2, in the ACC of postmortem brain of individuals with autism (n = 7) and control subjects (n = 13). Results We found that the protein levels of kidney-type glutaminase, but not those of the other enzymes measured, in the ACC were significantly lower in subjects with autism than in controls. Conclusion The results suggest that reduced expression of kidney-type glutaminase may account for putative alterations in glutamatergic neurotransmission in the ACC in autism. PMID:23531457

  17. Contribution of anterior cingulate cortex and descending pain inhibitory system to analgesic effect of lemon odor in mice

    PubMed Central

    2014-01-01

    Background Affections are thought to regulate pain perception through the descending pain inhibitory system in the central nervous system. In this study, we examined in mice the affective change by inhalation of the lemon oil, which is well used for aromatherapy, and the effect of lemon odor on pain sensation. We also examined the anterior cingulate cortex (ACC) and descending pain inhibitory system to such regulation of pain. Results In the elevated plus maze, the time spent in the open arms was increased by inhalation of lemon oil. The pain behavior induced by injection of formalin into the hind paw was decreased. By inhalation of lemon oil, the number of c-Fos expression by formalin injection was significantly increased in the ACC, periaqueductal grey (PAG), nucleu raphe magnus (NRM) and locus ceruleus, and decreased in the spinal dorsal horn (SDH). The destruction of the ACC with ibotenic acid led to prevent the decrease of formalin-evoked nocifensive behavior in mice exposed to lemon oil. In these mice, the change of formalin-induced c-Fos expression in the ACC, lateral PAG, NRM and SDH by lemon odor was also prevented. Antagonize of dopamine D1 receptor in the ACC prevented to the analgesic effect of lemon oil. Conclusions These results suggest that the analgesic effect of lemon oil is induced by dopamine-related activation of ACC and the descending pain inhibitory system. PMID:24555533

  18. Network Profiles of the Dorsal Anterior Cingulate and Dorsal Prefrontal Cortex in Schizophrenia During Hippocampal-Based Associative Memory.

    PubMed

    Woodcock, Eric A; Wadehra, Sunali; Diwadkar, Vaibhav A

    2016-01-01

    Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n = 12) and healthy control (HC) subjects (n = 10) participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC) and the dorsal anterior cingulate cortex (dACC) as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance (ANOVA) with seed (dPFC vs. dACC), group (patients vs. controls), and memory process (encoding and retrieval) as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness' characterization as a disconnection syndrome. PMID:27092063

  19. Initiation of Joint Attention is Associated with Morphometric Variation in the Anterior Cingulate Cortex of Chimpanzees (Pan troglodytes)

    PubMed Central

    Hopkins, William D.; Taglialatela, Jared P.

    2012-01-01

    In developing human children, joint attention is an important preverbal skill fundamental to the development of language. Poor joint attention skills have been described as a behavioral risk factor for some neurodevelopmental disorders, such as autism spectrum disorder. It has been hypothesized that the anterior cingulate cortex (ACC) plays an important role in the development of joint attention in human children. Here, we tested whether the morphometry and lateralization of the ACC differed between chimpanzees that were classified as either consistently or inconsistently engaging in joint attention with a human experimenter. Results showed that chimpanzees that performed poorly on the joint attention task had larger grey matter volumes in the ACC compared to apes that performed well on the task. In addition, both population-level asymmetries and sex differences in the volume of GM were found within the ACC. Specifically, females had relatively larger GM volumes in two of the three subregions of the ACC compared to males, and significant leftward asymmetries were found for two of the subregions whereas a rightward biases was observed in the third. Based on these findings, we suggest that the ACC plays in important role in mediating joint attention, not just in humans, but also chimpanzees. We further suggest that the differences found between groups may reflect inherent differences in the amount of white matter within the ACC, thereby suggesting reduced connectivity between the ACC and other cortical regions in chimpanzees with poor joint attention skills. PMID:23300067

  20. Network Profiles of the Dorsal Anterior Cingulate and Dorsal Prefrontal Cortex in Schizophrenia During Hippocampal-Based Associative Memory

    PubMed Central

    Woodcock, Eric A.; Wadehra, Sunali; Diwadkar, Vaibhav A.

    2016-01-01

    Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n = 12) and healthy control (HC) subjects (n = 10) participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC) and the dorsal anterior cingulate cortex (dACC) as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance (ANOVA) with seed (dPFC vs. dACC), group (patients vs. controls), and memory process (encoding and retrieval) as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness’ characterization as a disconnection syndrome. PMID:27092063

  1. Schizophrenia symptom and functional correlates of anterior cingulate cortex activation to emotion stimuli: An fMRI investigation.

    PubMed

    Nelson, Brady D; Bjorkquist, Olivia A; Olsen, Emily K; Herbener, Ellen S

    2015-12-30

    Schizophrenia is a chronic mental illness characterized by distinct positive and negative symptoms and functional impairment. The anterior cingulate cortex (ACC) is a region of the brain's limbic system that is hypoactive during emotion processing in schizophrenia. Recent evidence suggests the hypoactive ACC in schizophrenia is due to negative (and not positive) symptoms. However, this finding has not been replicated and the functional significance of this relationship remains unclear. The present study examined the association between positive and negative symptoms, ACC activation to emotional images, and functional outcome in schizophrenia. Specifically, 16 schizophrenia/schizoaffective disorder (SZ/SZAF) and 15 control (CON) participants underwent an fMRI scan while completing an emotional picture-rating task. SZ/SZAF participants also completed clinician-rated measures of positive and negative symptoms and functional abilities. SZ/SZAF participants with high negative symptoms had reduced ACC activation to pleasant images relative to those with low negative symptoms and CON, who did not differ. Furthermore, amongst all SZ/SZAF participants poorer social functioning was associated with decreased ACC activation to pleasant images. Finally, ACC activation partially mediated the relationship between negative symptoms and social dysfunction. These results provide evidence of the functional significance of the relationship between negative symptoms and ACC dysfunction in schizophrenia. PMID:26596521

  2. Combined rTMS treatment targeting the Anterior Cingulate and the Temporal Cortex for the Treatment of Chronic Tinnitus

    PubMed Central

    Kreuzer, Peter M.; Lehner, Astrid; Schlee, Winfried; Vielsmeier, Veronika; Schecklmann, Martin; Poeppl, Timm B.; Landgrebe, Michael; Rupprecht, Rainer; Langguth, Berthold

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a tinnitus treatment option. Promising results have been obtained by consecutive stimulation of lateral frontal and auditory brain regions. We investigated a combined stimulation paradigm targeting the anterior cingulate cortex (ACC) with double cone coil rTMS, followed by stimulation of the temporo-parietal junction area with a figure-of-eight coil. The study was conducted as a randomized, double-blind pilot trial in 40 patients suffering from chronic tinnitus. We compared mediofrontal stimulation with double-cone-coil, (2000 stimuli, 10 Hz) followed by left temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz) to left dorsolateral-prefrontal-cortex stimulation with figure-of-eight-coil (2000 stimuli, 10 Hz) followed by temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz). The stimulation was feasible with comparable dropout rates in both study arms; no severe adverse events were registered. Responder rates did not differ in both study arms. There was a significant main effect of time for the change in the TQ score, but no significant time x group interaction. This pilot study demonstrated the feasibility of combined mediofrontal/temporoparietal-rTMS-stimulation with double cone coil in tinnitus patients but failed to show better outcome compared to an actively rTMS treated control group. PMID:26667790

  3. Abrupt changes in the patterns and complexity of anterior cingulate cortex activity when food is introduced into an environment

    PubMed Central

    Caracheo, Barak F.; Emberly, Eldon; Hadizadeh, Shirin; Hyman, James M.; Seamans, Jeremy K.

    2013-01-01

    Foraging typically involves two distinct phases, an exploration phase where an organism explores its local environment in search of needed resources and an exploitation phase where a discovered resource is consumed. The behavior and cognitive requirements of exploration and exploitation are quite different and yet organisms can quickly and efficiently switch between them many times during a foraging bout. The present study investigated neural activity state dynamics in the anterior cingulate sub-region of the rat medial prefrontal cortex (mPFC) when a reliable food source was introduced into an environment. Distinct and largely independent states were detected using a Hidden Markov Model (HMM) when food was present or absent in the environment. Measures of neural entropy or complexity decreased when rats went from exploring the environment to exploiting a reliable food source. Exploration in the absence of food was associated with many weak activity states, while bouts of food consumption were characterized by fewer stronger states. Widespread activity state changes in the mPFC may help to inform foraging decisions and focus behavior on what is currently most prominent or valuable in the environment. PMID:23745102

  4. Exposure to blue wavelength light modulates anterior cingulate cortex activation in response to 'uncertain' versus 'certain' anticipation of positive stimuli.

    PubMed

    Alkozei, Anna; Smith, Ryan; Killgore, William D S

    2016-03-11

    Blue wavelength light has been used as an effective treatment for some types of mood disorders and circadian rhythm related sleep problems. We hypothesized that acute exposure to blue wavelength light would directly affect the functioning of neurocircuity implicated in emotion regulation (i.e., ventromedial prefrontal cortex, amygdala, insula, and anterior cingulate cortex [ACC]) during 'certain' and 'uncertain' anticipation of negative and positive stimuli. Thirty-five healthy adults were randomized to receive a thirty-minute exposure to either blue (active) or amber (placebo) light, immediately followed by an emotional anticipation task during functional magnetic resonance imaging (fMRI). In contrast to placebo, participants in the blue light group showed significantly reduced activation within the rostral ACC during 'uncertain' anticipation (i.e., uncertainty regarding whether a positive or negative stimulus would be shown) in comparison to 'certain' anticipation of a positive stimulus. These findings may be explicable in terms of interactions between blue light exposure and the influence of specific neuromodulators on ACC-mediated decision-making mechanisms. PMID:26806862

  5. Social and emotional functions in three patients with medial frontal lobe damage including the anterior cingulate cortex

    PubMed Central

    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Dolan, Ray; Shallice, Tim; Cipolotti, Lisa

    2009-01-01

    Introduction The aim of this study was to explore social and emotional functions in patients with medial frontal damage including the anterior cingulate cortex (ACC). Methods Three patients with medial frontal lobe lesions primarily involving the ACC performed tasks on motivational decision making, emotional facial expression recognition, and social cognition, including theory of mind (ToM). Their performance on these tasks was compared with age and education matched healthy controls. Results Patient performance on the motivational decision making and social situations tasks did not differ from controls. Selective emotional facial expression recognition impairment for fear was evident in one patient with a unilateral right ACC lesion (patient 3). ToM impairment was present in only one patient with a bilateral ACC lesion (patient 2). In contrast, the two patients with unilateral right ACC lesions had intact ToM (patients 1 and 3). Conclusions These findings suggest that medial frontal lobe lesions primarily involving the ACC do not appear to critically disrupt motivational decision making or social situation processing. The ACC plays a role in processing particular types of emotion (fear). Bilateral ACC damage impairs ToM processing, but unilateral damage to the right ACC is not sufficient to disrupt ToM. PMID:17354076

  6. Higher Media Multi-Tasking Activity Is Associated with Smaller Gray-Matter Density in the Anterior Cingulate Cortex

    PubMed Central

    Loh, Kep Kee; Kanai, Ryota

    2014-01-01

    Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences. PMID:25250778

  7. Medial prefrontal cortex-dorsal anterior cingulate cortex connectivity during behavior selection without an objective correct answer.

    PubMed

    Nakao, Takashi; Osumi, Takahiro; Ohira, Hideki; Kasuya, Yukinori; Shinoda, Jun; Yamada, Jitsuhiro; Northoff, Georg

    2010-10-01

    Life choices (e.g., occupational choice) often include situations with two or more possible correct answers, thereby putting us in a situation of conflict. Recent reports have described that the evaluation of conflict might be crucially mediated by neural activity in the dorsal anterior cingulate cortex (dACC), although the reduction of conflict might rather be associated with neural activity in the medial prefrontal cortex (MPFC). What remains unclear is whether these regions mutually interact, thereby raising the question of their functional connectivity during conflict situations. Using psychophysiological interaction (PPI) analyses of functional magnetic resonance imaging (fMRI) data, this study shows that the dACC co-varied significantly higher with the MPFC during an occupational choice task with two possible correct answers when compared to the control task: a word-length task with one possible correct answer. These results suggest that the MPFC has a functional relation with dACC, especially in conflict situations where there is no objective correct answer. Taken together, this lends support to the assumption that the MPFC might be crucial in biasing the decision, thereby reducing conflict. PMID:20655361

  8. Inhibition of mammalian target of rapamycin activation in the rostral anterior cingulate cortex attenuates pain-related aversion in rats.

    PubMed

    Lu, Bo; Jiang, Jingyan; Sun, Jianliang; Xiao, Chun; Meng, Bo; Zheng, Jinwei; Li, Xiaoyu; Wang, Ruichun; Wu, Guorong; Chen, Junping

    2016-09-01

    Pain is a complex experience that comprises both sensory and affective dimensions. Mammalian target of rapamycin (mTOR) plays an important role in the modulation of neuronal plasticity associated with the pathogenesis of pain sensation. However, the role of mTOR in pain affect is unclear. Using a formalin-induced conditioned place avoidance (F-CPA) test, the current study investigated the effects of the mTOR specific inhibitor rapamycin on noxious stimulation induced aversion in the rostral anterior cingulate cortex (rACC). Intraplantar injection of 5% formalin was associated with significant activation of mTOR, as well as p70 ribosomal S6 protein (p70S6K), its downstream effector, in the rACC. The inhibition of mTOR activation with rapamycin disrupted pain-related aversion; however, this inhibition did not affect formalin-induced spontaneous nociceptive behaviors in rats. These findings demonstrated for the first time that mTOR and its downstream pathway in the rACC contribute to the induction of pain-related negative emotion. PMID:27163752

  9. Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices

    PubMed Central

    Khalsa, Sahib S.; Damasio, Antonio; Tranel, Daniel; Landini, Gregory; Williford, Kenneth

    2012-01-01

    It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). Such a proposal predicts that damage to these regions should disrupt or even abolish SA. We tested this prediction in a rare neurological patient with extensive bilateral brain damage encompassing the insula, ACC, mPFC, and the medial temporal lobes. In spite of severe amnesia, which partially affected his “autobiographical self”, the patient's SA remained fundamentally intact. His Core SA, including basic self-recognition and sense of self-agency, was preserved. His Extended SA and Introspective SA were also largely intact, as he has a stable self-concept and intact higher-order metacognitive abilities. The results suggest that the insular cortex, ACC and mPFC are not required for most aspects of SA. Our findings are compatible with the hypothesis that SA is likely to emerge from more distributed interactions among brain networks including those in the brainstem, thalamus, and posteromedial cortices. PMID:22927899

  10. Neurochemical abnormalities in anterior cingulate cortex on betel quid dependence: a 2D 1H MRS investigation

    PubMed Central

    Liu, Tao; Li, Jianjun; Huang, Shixiong; Zhao, Zhongyan; Yang, Guoshuai; Pan, Mengjie; Li, Changqing; Chen, Feng; Pan, Suyue

    2015-01-01

    The effects of betel quid dependence (BQD) on biochemical changes remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered neurochemicals in Magnetic Resonance Spectroscopy Imaging (MRSI) and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an 2D 1H-MRS study to observe brain biochemical alterations in the anterior cingulated cortex (ACC) associated with the severity of BQD and duration of BQD. In the bilateral ACC, our study found NAA/Cr were lower in BQD individuals compared to the healthy controls, Cho/Cr and Glx/Cr were higher in individuals with BQD compared to the healthy group, but increase was noted for mI/Cr in BQD individuals only in the left ACC. NAA/Cr ratios of the right ACC negatively correlated with BQDS and duration, NAA/Cr ratios of the left ACC negatively correlated with duration, Glx/Cr ratios of the right ACC positively correlated with BQDS. The findings of the study support previous analyses of a role for ACC area in the mediation of BQ addiction and mechanistically explain past observations of reduced ACC grey matter in BQD patients. These data jointly point to state related abnormalities of BQ effect and provide a novel strategy of therapeutic intervention designed to normalize Glu transmission and function during treating BQ addiction. PMID:26885276

  11. Binge alcohol consumption in emerging adults: anterior cingulate cortical ‘thinness’ is associated with alcohol use patterns

    PubMed Central

    Mashhoon, Yasmin; Czerkawski, Charles; Crowley, David J.; Cohen-Gilbert, Julia E.; Sneider, Jennifer T.; Silveri, Marisa M.

    2014-01-01

    Background The brain undergoes dynamic and requisite changes into the early twenties that are associated with improved cognitive efficiency, particularly in prefrontal regions that are still undergoing neuromaturation. As alcohol consumption is typically initiated and progresses to binge drinking during this time, the objective of the present study was to investigate the impact of binge alcohol consumption on frontal lobe cortical thickness in emerging adults. Methods Twenty-three binge drinking (BD; 11 females, mean age 21.5 ± 1.4) and thirty-one light drinking (LD; 15 females, mean age 21.9 ± 1.6) emerging adults underwent high-resolution magnetic resonance imaging at 3 Tesla. Cortical surface reconstruction and thickness estimation were performed using Freesurfer for three a priori brain regions of interest: bilateral anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and parieto-occipital sulcus (POS). Cortical thickness measurements were then compared between BD and LD groups. Results Cortical thickness was significantly lower in BD than LD in the right middle ACC (mid-ACC; p≤0.05) and in the left dorsal PCC (dPCC; p≤0.01). No significant differences in cortical thickness were observed in the POS. Cortical thickness in the mid-ACC correlated negatively with higher quantity and frequency of drinks consumed (p<0.01), and positively with the number of days elapsed since most recent use (p<0.05). Furthermore, less cortical thickness in the mid-ACC in the BD group alone correlated with reported patterns of high quantity and frequency of alcohol consumption (p≤0.05). Conclusions Findings suggest that past and recent patterns of intermittent heavy alcohol consumption are associated with less frontal cortical thickness (i.e. ‘thinness’) of the right mid-ACC and left dPCC in emerging adults, but not the POS. While cortical thinness could have predated binge drinking, this pattern of maladaptive consumption may have acute neurotoxic effects

  12. Relationship of Alexithymia Ratings to Dopamine D2-type Receptors in Anterior Cingulate and Insula of Healthy Control Subjects but Not Methamphetamine-Dependent Individuals

    PubMed Central

    Okita, Kyoji; Ghahremani, Dara G.; Payer, Doris E.; Robertson, Chelsea L.; Mandelkern, Mark A.

    2016-01-01

    Background: Individuals with substance-use disorders exhibit emotional problems, including deficits in emotion recognition and processing, and this class of disorders also has been linked to deficits in dopaminergic markers in the brain. Because associations between these phenomena have not been explored, we compared a group of recently abstinent methamphetamine-dependent individuals (n=23) with a healthy-control group (n=17) on dopamine D2-type receptor availability, measured using positron emission tomography with [18F]fallypride. Methods: The anterior cingulate and anterior insular cortices were selected as the brain regions of interest, because they receive dopaminergic innervation and are thought to be involved in emotion awareness and processing. The Toronto Alexithymia Scale, which includes items that assess difficulty in identifying and describing feelings as well as externally oriented thinking, was administered, and the scores were tested for association with D2-type receptor availability. Results: Relative to controls, methamphetamine-dependent individuals showed higher alexithymia scores, reporting difficulty in identifying feelings. The groups did not differ in D2-type receptor availability in the anterior cingulate or anterior insular cortices, but a significant interaction between group and D2-type receptor availability in both regions, on self-report score, reflected significant positive correlations in the control group (higher receptor availability linked to higher alexithymia) but nonsignificant, negative correlations (lower receptor availability linked to higher alexithymia) in methamphetamine-dependent subjects. Conclusions: The results suggest that neurotransmission through D2-type receptors in the anterior cingulate and anterior insular cortices influences capacity of emotion processing in healthy people but that this association is absent in individuals with methamphetamine dependence. PMID:26657175

  13. Glutamine and Glutamate Levels in Children and Adolescents With Bipolar Disorder: A 4.0-T Proton Magnetic Resonance Spectroscopy Study of the Anterior Cingulate Cortex

    PubMed Central

    MOORE, CONSTANCE M.; FRAZIER, JEAN A.; GLOD, CAROL A.; BREEZE, JANIS L.; DIETERICH, MEGAN; FINN, CHELSEA T.; FREDERICK, BLAISE DEB.; RENSHAW, PERRY F.

    2014-01-01

    Objective The purpose of this study was to use proton magnetic resonance spectroscopy, at 4.0 T, to explore the glutamine and glutamate levels in the anterior cingulate cortex of children and adolescents with bipolar disorder (BPD; medicated and unmedicated) and healthy comparison subjects (HCSs). We hypothesized that unmedicated children with BPD would have reduced glutamine and glutamate levels compared with HCSs and medicated children with BPD. Method Spectra were acquired from the anterior cingulate cortex in 22 children and adolescents with DSM-IV-TR BPD, type 1 (13 female: age 12.6 ± 4.4 years: 7 of the subjects with BPD were unmedicated at the time of the scan) and 10 HCSs (7 female: age 12.3 ± 2.5 years). Results Unmedicated subjects with BPD had significantly lower glutamine levels than HCSs or medicated subjects with BPD. There were no differences in glutamate levels between the three groups. Conclusions These results are consistent with there being an abnormality in anterior cingulate cortex glia in untreated children and adolescents with BPD. The results of this pilot study may be important in helping us better understand the pathophysiology of child and adolescent BPD. In addition, this observation may help to develop better and more targeted treatments, in particular those affecting the metabolism of glutamine, perhaps by regulation of glutamine synthetase activity. PMID:17420688

  14. Low serotonin1B receptor binding potential in the anterior cingulate cortex in drug-free patients with recurrent major depressive disorder.

    PubMed

    Tiger, Mikael; Farde, Lars; Rück, Christian; Varrone, Andrea; Forsberg, Anton; Lindefors, Nils; Halldin, Christer; Lundberg, Johan

    2016-07-30

    The pathophysiology of major depressive disorder (MDD) is not fully understood and the diagnosis is largely based on history and clinical examination. So far, several lines of preclinical data and a single imaging study implicate a role for the serotonin1B (5-HT1B) receptor subtype. We sought to study 5-HT1B receptor binding in brain regions of reported relevance in patients with MDD. Subjects were examined at the Karolinska Institutet PET centre using positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369. Ten drug-free patients with recurrent MDD and ten control subjects matched for age and sex were examined. The main outcome measure was [(11)C]AZ10419369 binding in brain regions of reported relevance in the pathophysiology of MDD. The [(11)C]AZ10419369 binding potential was significantly lower in the MDD group compared with the healthy control group in the anterior cingulate cortex (20% between-group difference), the subgenual prefrontal cortex (17% between-group difference), and in the hippocampus (32% between-group difference). The low anterior cingulate [(11)C]AZ10419369 binding potential in patients with recurrent MDD positions 5-HT1B receptor binding in this region as a putative biomarker for MDD and corroborate a role of the anterior cingulate cortex and associated areas in the pathophysiology of recurrent MDD. PMID:27269199

  15. Anterior cingulate hyperactivations during negative emotion processing among men with schizophrenia and a history of violent behavior

    PubMed Central

    Tikàsz, Andràs; Potvin, Stéphane; Lungu, Ovidiu; Joyal, Christian C; Hodgins, Sheilagh; Mendrek, Adrianna; Dumais, Alexandre

    2016-01-01

    Background Evidence suggests a 2.1–4.6 times increase in the risk of violent behavior in schizophrenia compared to the general population. Current theories propose that the processing of negative emotions is defective in violent individuals and that dysfunctions within the neural circuits involved in emotion processing are implicated in violence. Although schizophrenia patients show enhanced sensitivity to negative stimuli, there are only few functional neuroimaging studies that have examined emotion processing among men with schizophrenia and a history of violence. Objective The present study aimed to identify the brain regions with greater neurofunctional alterations, as detected by functional magnetic resonance imaging during an emotion processing task, of men with schizophrenia who had engaged in violent behavior compared with those who had not. Methods Sixty men were studied; 20 with schizophrenia and a history of violence, 19 with schizophrenia and no violence, and 21 healthy men were scanned while viewing positive, negative, and neutral images. Results Negative images elicited hyperactivations in the anterior cingulate cortex (ACC), left and right lingual gyrus, and the left precentral gyrus in violent men with schizophrenia, compared to nonviolent men with schizophrenia and healthy men. Neutral images elicited hyperactivations in the right and left middle occipital gyrus, left lingual gyrus, and the left fusiform gyrus in violent men with schizophrenia, compared to the other two groups. Discussion Violent men with schizophrenia displayed specific increases in ACC in response to negative images. Given the role of the ACC in information integration, these results indicate a specific dysfunction in the processing of negative emotions that may trigger violent behavior in men with schizophrenia. PMID:27366072

  16. Meditation reduces pain-related neural activity in the anterior cingulate cortex, insula, secondary somatosensory cortex, and thalamus

    PubMed Central

    Nakata, Hiroki; Sakamoto, Kiwako; Kakigi, Ryusuke

    2014-01-01

    Recent studies have shown that meditation inhibits or relieves pain perception. To clarify the underlying mechanisms for this phenomenon, neuroimaging methods, such as functional magnetic resonance imaging, and neurophysiological methods, such as magnetoencephalography and electroencephalography, have been used. However, it has been difficult to interpret the results, because there is some paradoxical evidence. For example, some studies reported increased neural responses to pain stimulation during meditation in the anterior cingulate cortex (ACC) and insula, whereas others showed a decrease in these regions. There have been inconsistent findings to date. Moreover, in general, since the activities of the ACC and insula are correlated with pain perception, the increase in neural activities during meditation would be related to the enhancement of pain perception rather than its reduction. These contradictions might directly contribute to the ‘mystery of meditation.’ In this review, we presented previous findings for brain regions during meditation and the anatomical changes that occurred in the brain with long-term meditation training. We then discussed the findings of previous studies that examined pain-related neural activity during meditation. We also described the brain mechanisms responsible for pain relief during meditation, and possible reasons for paradoxical evidence among previous studies. By thoroughly overviewing previous findings, we hypothesized that meditation reduces pain-related neural activity in the ACC, insula, secondary somatosensory cortex, and thalamus. We suggest that the characteristics of the modulation of this activity may depend on the kind of meditation and/or number of years of experience of meditation, which were associated with paradoxical findings among previous studies that investigated pain-related neural activities during meditation. PMID:25566158

  17. Orbitofrontal and anterior cingulate cortex neurons selectively process cocaine-associated environmental cues in the rhesus monkey.

    PubMed

    Baeg, Eun Ha; Jackson, Mark E; Jedema, Hank P; Bradberry, Charles W

    2009-09-16

    Encounters with stimuli associated with drug use are believed to contribute to relapse. To probe the neurobiology of environmentally triggered drug use, we have conducted single-unit recordings in rhesus monkeys during presentation of two distinct types of drug paired cues that differentially support drug-seeking. The animals were highly conditioned to these cues via exposure during self-administration procedures conducted over a 4 year period. The cues studied were a discriminative cue that signaled response-contingent availability of cocaine, and a discrete cue that was temporally paired with the cocaine infusion (0.1 or 0.5 mg/kg). Two cortical regions consistently activated by cocaine-associated cues in human imaging studies are the orbitofrontal (OFC) and anterior cingulate cortex (ACC), though little is known about cortical neuronal activity responses to drug cues. We simultaneously recorded single-unit activity in OFC and ACC as well as in dorsal striatum in rhesus monkeys during cocaine self-administration. Dorsal striatal neurons were less engaged by drug cues than cortical regions. Between OFC and ACC, distinct functionality was apparent in neuronal responses. OFC neurons preferentially responded to the discriminative cue, consistent with a role in cue-induced drug-seeking. In contrast, the ACC did not respond more to the discriminative cue than to the discrete cue. Also distinct from the OFC, ACC showed sustained firing throughout the 18 s duration of the discrete cue. This pattern of sustained activation in ACC is consistent with a role in reward expectation and/or in mediating behavioral effects of discrete cues paired with drug infusions. PMID:19759309

  18. Systems reconsolidation reveals a selective role for the anterior cingulate cortex in generalized contextual fear memory expression.

    PubMed

    Einarsson, Einar Ö; Pors, Jennifer; Nader, Karim

    2015-01-01

    After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory. PMID:25091528

  19. Women's Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex.

    PubMed

    Nakagawa, Jun; Takahashi, Muneyoshi; Okada, Rieko; Matsushima, Eisuke; Matsuda, Tetsuya

    2015-01-01

    Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman's perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1) the giver and (2) the type of the gift (the gift's social meaning). In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift's social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI) study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1) the female participant's attitude toward the male acquaintance (liked vs. uninteresting) and (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods--preference for the member is a powerful modulator of social reward processing. PMID:26301954

  20. Anterior cingulate and frontal lobe white matter spectroscopy in early childhood of former very LBW premature infants.

    PubMed

    Phillips, John P; Ruhl, David; Montague, Erica; Gasparovic, Charles; Caprihan, Arvind; Ohls, Robin K; Schrader, Ronald; Lowe, Jean R

    2011-03-01

    Neurometabolic sequelae of children born at very LBW (VLBW) are not well characterized in early childhood. Proton magnetic resonance spectroscopy (1H-MRS) and developmental assessments were acquired from children age 18-22 mo (16 VLBW/7 term) and 3-4 y (12 VLBW/8 term) from the anterior cingulate and left frontal periventricular white matter. Metabolites obtained included combined N-acetylaspartylglutamate and N-acetylaspartate (NAA), total choline-containing compounds (Cho), combined glutamate and glutamine (Glx), combined creatine and phosphocreatine (Cr), myoinositol (mI), and the following ratios: NAA/Cr, Cho/Cr, Glx/Cr, mI/Cr, and NAA/Cho. Significant differences were present only in white matter: at 18-22 mo, NAA was decreased in VLBW children (p < 0.04), and at 3-4 y, VLBW children showed lower Cr (p < 0.01), lower NAA/Cho (p < 0.005), higher Glx/Cr (p < 0.02), and higher Cho/Cr (p < 0.005). On developmental testing, VLBW children scored lower on language expression (p < 0.05) and on the A-not-B test of early executive function (p < 0.01) at 18-22 mo and had lower verbal intelligence quotient (IQ) (p < 0.005), performance IQ (p < 0.04), and several measures of early executive function including the bear-dragon test (p < 0.004), gift delay (p < 0.07), and summary categorization score (p < 0.03) at 3-4 y. VLBW children may have neurometabolic and developmental abnormalities that persist at least through early childhood. PMID:21135758

  1. Women’s Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex

    PubMed Central

    Nakagawa, Jun; Takahashi, Muneyoshi; Okada, Rieko; Matsushima, Eisuke; Matsuda, Tetsuya

    2015-01-01

    Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman’s perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1) the giver and (2) the type of the gift (the gift’s social meaning). In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift’s social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI) study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1) the female participant’s attitude toward the male acquaintance (liked vs. uninteresting) and (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods—preference for the member is a powerful modulator of social reward processing. PMID:26301954

  2. Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice

    PubMed Central

    2015-01-01

    Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined glial fibrillary acidic protein (GFAP; an astrocyte marker) immunoreactivity and gene expression of GFAP, glutamate transporters and receptor subunits by real time PCR in the anterior cingulate cortex (ACC) at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. The ACC, an area in the brain involved in pain perception and modulation, was chosen because changes in this area might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold and GFAP immunoreactivity increased in the ACC of paclitaxel-treated mice. The 6 glutamate transporters (GLAST, GLT-1 EAAC1, EAAT4, VGLUT-1 and VGLUT-2) quantified were not significantly altered by paclitaxel treatment. Of the 12 ionotropic glutamate receptor subunits transcripts analysed 6 (GLuA1, GLuA3, GLuK2, GLuK3, GLuK5 and GLuN1) were significantly up-regulated, whereas GLuA2, GLuK1, GLuK4, GLuN2A and GLuN2B were not significantly altered and GLuA4 was lowly expressed. Amongst the 8 metabotropic receptor subunits analysed only mGLuR8 was significantly elevated. In conclusion, during PINP there is astrocyte activation, with no change in glutamate transporter expression and differential up-regulation of glutamate receptor subunits in the ACC. Thus, targeting astrocyte activation and the glutamatergic system might be another therapeutic avenue for management of PINP. PMID:26528412

  3. Cognitive and neural strategies during control of the anterior cingulate cortex by fMRI neurofeedback in patients with schizophrenia.

    PubMed

    Cordes, Julia S; Mathiak, Krystyna A; Dyck, Miriam; Alawi, Eliza M; Gaber, Tilman J; Zepf, Florian D; Klasen, Martin; Zvyagintsev, Mikhail; Gur, Ruben C; Mathiak, Klaus

    2015-01-01

    Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF) seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC), a central hub for cognitive processing, is one of the brain regions known to be dysfunctional in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI) in patients with schizophrenia to enable them to control their ACC activity. Training was performed over 3 days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI). Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. In a stepwise regression analysis, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, patients with schizophrenia can learn to regulate localized brain activity. However, cognitive strategies and neural network location differ from healthy controls. These data emphasize that for therapeutic interventions in patients with schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social NF based on fMRI may be one method to accomplish precise learning targets. PMID:26161073

  4. [Comparison of membrane electrical properties of somatic nociceptive and non-nociceptive neurons of the anterior cingulate gyrus in cats].

    PubMed

    Zhang, Yong; Yao, Yang; Yang, Yu; Wu, Min-Fan

    2015-04-25

    Using intracellular potential recording technique in vivo, a series of hyperpolarizing and depolarizing currents at different intensities with a 50-ms duration were injected to somatic nociceptive neurons (SNNs) and somatic non-nociceptive neurons (SNNNs) in the anterior cingulate gyrus (ACG) of cats. The membrane electrical responses of the neurons were recorded, and the membrane electrical parameters of the neurons were calculated for comparative study on membrane electrical properties of SNNs and SNNNs of the ACG. A total of 188 ACG neurons from 57 cats were recorded. Among the 188 neurons, 172 (91.5%) and 16 (8.5%) were SNNs and SNNNs, respectively. The I-V curves of SNNs and SNNNs in the ACG were "S" shapes. When the absolute value of injected current intensity was less than or equal to 1 nA (≤ 1 nA), the I and V of I-V curves of both SNNs and SNNNs were linearly correlated (rSNNs = 0.99, rSNNNs = 0.99). When the absolute value of injected current intensity was more than 1 nA, both SNNs and SNNNs showed a certain inward or outward rectification behavior. Compared with SNNNs, SNNs had stronger rectification and lower adaptability (P < 0.01). With the increase of injected current intensity, the changes of frequency of discharges of SNNs were higher than those of SNNNs. In addition, the membrane resistance (Rm), the membrane capacity (Cm) and the time constant (τ) of SNNs were larger than those of SNNNs (P < 0.05 or P < 0.01). The differences in the membrane electrical properties between SNNs and SNNNs in the ACG suggested the disparity in neuronal cell size and cell membrane structure between them. The results of this study provided the experimental basis for deeply elucidating the mechanisms of somatic nociceptive sensation and characteristics on the membrane electrical aspects of ACG neurons. PMID:25896048

  5. Anterior cingulate cortex surface area relates to behavioral inhibition in adolescents with and without heavy prenatal alcohol exposure.

    PubMed

    Migliorini, Robyn; Moore, Eileen M; Glass, Leila; Infante, M Alejandra; Tapert, Susan F; Jones, Kenneth Lyons; Mattson, Sarah N; Riley, Edward P

    2015-10-01

    Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure correlates of this deficit have not been determined with sufficient detail. We examined the hypothesis that the structure of the anterior cingulate cortex (ACC) relates to inhibition performance in youth with histories of heavy prenatal alcohol exposure (AE, n = 32) and non-exposed controls (CON, n = 21). Adolescents (12-17 years) underwent structural magnetic resonance imaging yielding measures of gray matter volume, surface area, and thickness across four ACC subregions. A subset of subjects were administered the NEPSY-II Inhibition subtest. MANCOVA was utilized to test for group differences in ACC and inhibition performance and multiple linear regression was used to probe ACC-inhibition relationships. ACC surface area was significantly smaller in AE, though this effect was primarily driven by reduced right caudal ACC (rcACC). AE also performed significantly worse on inhibition speed but not on inhibition accuracy. Regression analyses with the rcACC revealed a significant group × ACC interaction. A smaller rcACC surface area was associated with slower inhibition completion time for AE but was not significantly associated with inhibition in CON. After accounting for processing speed, smaller rcACC surface area was associated with worse (i.e., slower) inhibition regardless of group. Examining processing speed independently, a decrease in rcACC surface area was associated with faster processing speed for CON but not significantly associated with processing speed in AE. Results support the theory that caudal ACC may monitor reaction time in addition to inhibition and highlight the possibility of delayed ACC neurodevelopment in prenatal alcohol exposure. PMID:26025509

  6. Greater externalizing personality traits predict less error-related insula and anterior cingulate cortex activity in acutely abstinent cigarette smokers

    PubMed Central

    Carroll, Allison J.; Sutherland, Matthew T.; Salmeron, Betty Jo; Ross, Thomas J.; Stein, Elliot A.

    2014-01-01

    Attenuated activity in performance-monitoring brain regions following erroneous actions may contribute to the repetition of maladaptive behaviors such as continued drug use. Externalizing is a broad personality construct characterized by deficient impulse control, vulnerability to addiction, and reduced neurobiological indices of error processing. The insula and dorsal anterior cingulate cortex (dACC) are regions critically linked with error processing as well as the perpetuation of cigarette smoking. As such, we examined the interrelations between externalizing tendencies, erroneous task performance, and error-related insula and dACC activity in overnight-deprived smokers (n=24) and nonsmokers (n=20). Participants completed a self-report measure assessing externalizing tendencies (Externalizing Spectrum Inventory) and a speeded Flanker task during fMRI scanning. We observed that higher externalizing tendencies correlated with the occurrence of more performance errors among smokers but not nonsmokers. Suggesting a neurobiological contribution to such sub-optimal performance among smokers, higher externalizing also predicted less recruitment of the right insula and dACC following error commission. Critically, this error-related activity fully mediated the relationship between externalizing traits and error rates. That is, higher externalizing scores predicted less error-related right insula and dACC activity and, in turn, less error-related activity predicted more errors. Relating such regional activity with a clinically-relevant construct, less error-related right insula and dACC responses correlated with higher tobacco craving during abstinence. Given that inadequate error-related neuronal responses may contribute to continued drug use despite negative consequences, these results suggest that externalizing tendencies and/or compromised error processing among subsets of smokers may be relevant factors for smoking cessation success. PMID:24354662

  7. The dorsal prefrontal and dorsal anterior cingulate cortices exert complementary network signatures during encoding and retrieval in associative memory.

    PubMed

    Woodcock, Eric A; White, Richard; Diwadkar, Vaibhav A

    2015-09-01

    Cognitive control includes processes that facilitate execution of effortful cognitive tasks, including associative memory. Regions implicated in cognitive control during associative memory include the dorsal prefrontal (dPFC) and dorsal anterior cingulate cortex (dACC). Here we investigated the relative degrees of network-related interactions originating in the dPFC and dACC during oscillating phases of associative memory: encoding and cued retrieval. Volunteers completed an established object-location associative memory paradigm during fMRI. Psychophysiological interactions modeled modulatory network interactions from the dPFC and dACC during memory encoding and retrieval. Results were evaluated in second level analyses of variance with seed region and memory process as factors. Each seed exerted differentiable modulatory effects during encoding and retrieval. The dACC exhibited greater modulation (than the dPFC) on the fusiform and parahippocampal gyrus during encoding, while the dPFC exhibited greater modulation (than the dACC) on the fusiform, hippocampus, dPFC and basal ganglia. During retrieval, the dPFC exhibited greater modulation (than the dACC) on the parahippocampal gyrus, hippocampus, superior parietal lobule, and dPFC. The most notable finding was a seed by process interaction indicating that the dACC and the dPFC exerted complementary modulatory control on the hippocampus during each of the associative memory processes. These results provide evidence for differentiable, yet complementary, control-related modulation by the dACC and dPFC, while establishing the primacy of dPFC in exerting network control during both associative memory phases. Our approach and findings are relevant for understanding basic processes in human memory and psychiatric disorders that impact associative memory-related networks. PMID:25960314

  8. Cortical thinning in the anterior cingulate cortex predicts multiple sclerosis patients' fluency performance in a lateralised manner

    PubMed Central

    Geisseler, Olivia; Pflugshaupt, Tobias; Bezzola, Ladina; Reuter, Katja; Weller, David; Schuknecht, Bernhard; Brugger, Peter; Linnebank, Michael

    2015-01-01

    Cognitive impairment is as an important feature of Multiple Sclerosis (MS), and might be even more relevant to patients than mobility restrictions. Compared to the multitude of studies investigating memory deficits or basic cognitive slowing, executive dysfunction is a rarely studied cognitive domain in MS, and its neural correlates remain largely unexplored. Even rarer are topological studies on specific cognitive functions in MS. Here we used several structural MRI parameters – including cortical thinning and T2 lesion load – to investigate neural correlates of executive dysfunction, both on a global and a regional level by means of voxel- and vertex-wise analyses. Forty-eight patients with relapsing-remitting MS and 48 healthy controls participated in the study. Five executive functions were assessed, i.e. verbal and figural fluency, working memory, interference control and set shifting. Patients scored lower than controls in verbal and figural fluency only, and displayed widespread cortical thinning. On a global level, cortical thickness independently predicted verbal fluency performance, when controlling for lesion volume and central brain atrophy estimates. On a regional level, cortical thinning in the anterior cingulate region correlated with deficits in verbal and figural fluency and did so in a lateralised manner: Left-sided thinning was related to reduced verbal – but not figural – fluency, whereas the opposite pattern was observed for right-sided thinning. We conclude that executive dysfunction in MS patients can specifically affect verbal and figural fluency. The observed lateralised clinico-anatomical correlation has previously been described in brain-damaged patients with large focal lesions only, for example after stroke. Based on focal grey matter atrophy, we here show for the first time comparable lateralised findings in a white matter disease with widespread pathology. PMID:26759784

  9. Cognitive Control Functions of Anterior Cingulate Cortex in Macaque Monkeys Performing a Wisconsin Card Sorting Test Analog

    PubMed Central

    Kuwabara, Masaru; Mansouri, Farshad A.; Buckley, Mark J.

    2014-01-01

    Monkeys were trained to select one of three targets by matching in color or matching in shape to a sample. Because the matching rule frequently changed and there were no cues for the currently relevant rule, monkeys had to maintain the relevant rule in working memory to select the correct target. We found that monkeys' error commission was not limited to the period after the rule change and occasionally occurred even after several consecutive correct trials, indicating that the task was cognitively demanding. In trials immediately after such error trials, monkeys' speed of selecting targets was slower. Additionally, in trials following consecutive correct trials, the monkeys' target selections for erroneous responses were slower than those for correct responses. We further found evidence for the involvement of the cortex in the anterior cingulate sulcus (ACCs) in these error-related behavioral modulations. First, ACCs cell activity differed between after-error and after-correct trials. In another group of ACCs cells, the activity differed depending on whether the monkeys were making a correct or erroneous decision in target selection. Second, bilateral ACCs lesions significantly abolished the response slowing both in after-error trials and in error trials. The error likelihood in after-error trials could be inferred by the error feedback in the previous trial, whereas the likelihood of erroneous responses after consecutive correct trials could be monitored only internally. These results suggest that ACCs represent both context-dependent and internally detected error likelihoods and promote modes of response selections in situations that involve these two types of error likelihood. PMID:24872558

  10. Effects of serotonin depletion on punishment processing in the orbitofrontal and anterior cingulate cortices of healthy women.

    PubMed

    Helmbold, K; Zvyagintsev, M; Dahmen, B; Bubenzer-Busch, S; Gaber, T J; Crockett, M J; Klasen, M; Sánchez, C L; Eisert, A; Konrad, K; Habel, U; Herpertz-Dahlmann, B; Zepf, F D

    2015-06-01

    Diminished synthesis of the neurotransmitter serotonin (5-HT) has been linked to disrupted impulse control in aversive contexts. However, the neural correlates underlying a serotonergic modulation of female impulsivity remain unclear. The present study investigated punishment-induced inhibition in healthy young women. Eighteen healthy female subjects (aged 20-31) participated in a double-blinded, counterbalanced, placebo-controlled, within subjects, repeated measures study. They were assessed on two randomly assigned occasions that were controlled for menstrual cycle phase. In a randomized order, one day, acute tryptophan depletion (ATD) was used to reduce 5-HT synthesis in the brain. On the other day, participants received a tryptophan-balanced amino acid load (BAL) as a control condition. Three hours after administration of ATD/BAL, neural activity was recorded during a modified Go/No-Go task implementing reward or punishment processes using functional magnetic resonance imaging (fMRI). Neural activation during No-Go trials in punishment conditions after BAL versus ATD administration correlated positively with the magnitude of central 5-HT depletion in the ventral and subgenual anterior cingulate cortices (ACC). Furthermore, neural activation in the medial orbitofrontal cortex (mOFC) and the dorsal ACC correlated positively with trait impulsivity. The results indicate reduced neural sensitivity to punishment after short-term depletion of 5-HT in brain areas related to emotion regulation (subgenual ACC) increasing with depletion magnitude and in brain areas related to appraisal and expression of emotions (mOFC and dorsal ACC), increasing with trait impulsivity. This suggests a serotonergic modulation of neural circuits related to emotion regulation, impulsive behavior, and punishment processing in females. PMID:25869157

  11. Comparison of anterior cingulate and primary somatosensory neuronal responses to noxious laser-heat stimuli in conscious, behaving rats.

    PubMed

    Kuo, Chung-Chih; Yen, Chen-Tung

    2005-09-01

    In this study, we investigated single-unit responses of the primary sensorimotor cortex (SmI) and anterior cingulate cortex (ACC) to noxious stimulation of the tail of the rat. The influences of morphine on these nociceptive responses were also compared. Multiple single-unit activities were recorded from two eight-channel microwire arrays chronically implanted in the tail region of the SmI and ACC, respectively. CO2 laser-heat irradiation of the middle part of the tail at an intensity slightly higher than that causing a maximal tail flick response was used as a specific noxious stimulus. Examined individually, ACC neurons were less responsive than SmI neurons to laser-heat stimulus, in that only 51% of the ACC units (n = 125) responded compared with 88% of the SmI units (n = 74). Among these responsive ACC units, many had a very long latency and long-lasting excitatory type of response that was seldom found in the SmI. When ensemble activities were examined, laser heat evoked both short- (60 approximately 150 ms) and long-latency (151 approximately 600 ms) responses in the SmI and ACC. Latencies of both responses were longer in the ACC. Furthermore, a single dose of 2.5-10 mg/kg morphine intraperitoneally suppressed only the long latency response in the SmI, but significantly attenuated both responses in the ACC. These effects of morphine were completely blocked by prior treatment with the opiate receptor blocker, naloxone. These results provide further evidence suggesting that the SmI and ACC may play different roles in processing noxious information. PMID:16105955

  12. Cognitive and neural strategies during control of the anterior cingulate cortex by fMRI neurofeedback in patients with schizophrenia

    PubMed Central

    Cordes, Julia S.; Mathiak, Krystyna A.; Dyck, Miriam; Alawi, Eliza M.; Gaber, Tilman J.; Zepf, Florian D.; Klasen, Martin; Zvyagintsev, Mikhail; Gur, Ruben C.; Mathiak, Klaus

    2015-01-01

    Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF) seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC), a central hub for cognitive processing, is one of the brain regions known to be dysfunctional in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI) in patients with schizophrenia to enable them to control their ACC activity. Training was performed over 3 days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI). Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. In a stepwise regression analysis, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, patients with schizophrenia can learn to regulate localized brain activity. However, cognitive strategies and neural network location differ from healthy controls. These data emphasize that for therapeutic interventions in patients with schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social NF based on fMRI may be one method to accomplish precise learning targets. PMID:26161073

  13. Dorsal Anterior Cingulate Cortex Responses to Repeated Social Evaluative Feedback in Young Women with and without a History of Depression

    PubMed Central

    Dedovic, Katarina; Slavich, George M.; Muscatell, Keely A.; Irwin, Michael R.; Eisenberger, Naomi I.

    2016-01-01

    The dorsal anterior cingulate cortex (dACC) is recruited when a person is socially rejected or negatively evaluated. However, it remains to be fully understood how this region responds to repeated exposure to personally-relevant social evaluation, in both healthy populations and those vulnerable to Major Depressive Disorder (MDD), as well as how responding in these regions is associated with subsequent clinical functioning. To address this gap in the literature, we recruited 17 young women with past history of MDD (previously depressed) and 31 healthy controls and exposed them to a social evaluative session in a neuroimaging environment. In two bouts, participants received an equal amount of positive, negative, and neutral feedback from a confederate. All participants reported increases in feelings of social evaluation in response to the evaluative task. However, compared to healthy controls, previously depressed participants tended to show greater increases in depressed mood following the task. At the neural level, in response to negative (vs. positive) feedback, no main effect of group or evaluation periods was observed. However, a significant interaction between group and evaluation periods was found. Specifically, over the two bouts of evaluation, activity in the dACC decreased among healthy participants while it increased among previously depressed individuals. Interestingly and unexpectedly, in the previously depressed group specifically, this increased activity in dACC over time was associated with lower levels of depressive symptoms at baseline and at 6-months following the evaluation session (controlling for baseline levels). Thus, the subset of previously depressed participants who showed increases in the recruitment of the dACC over time in response to the negative evaluation seemed to fair better emotionally. These findings suggest that examining how the dACC responds to repeated bouts of negative evaluation reveals a new dimension to the role of the d

  14. Not all effort is equal: the role of the anterior cingulate cortex in different forms of effort-reward decisions

    PubMed Central

    Holec, Victoria; Pirot, Heather L.; Euston, David R.

    2014-01-01

    The rat anterior cingulate cortex (ACC) mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., “courage”). As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm (HRA) but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the HRA. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain tasks. PMID:24478659

  15. Anterior cingulate cortex and insula response during indirect and direct processing of emotional faces in generalized social anxiety disorder

    PubMed Central

    2013-01-01

    Background Generalized social anxiety disorder (gSAD) is associated with a heightened neural sensitivity to signals that convey threat, as evidenced by exaggerated amygdala and/or insula activation when processing face stimuli that express negative emotions. Less clear in the brain pathophysiology of gSAD are cortical top down control mechanisms that moderate reactivity in these subcortical emotion processing regions. This study evaluated amygdala, insula, and anterior cingulate cortex (ACC) activity in gSAD with a novel “Emotional Faces Shifting Attention Task” (EFSAT), an adaptation of perceptual assessment tasks well-known to elicit amygdala response. In healthy volunteers, the task has been shown to engage the amygdala when attention is directed to emotional faces and the ACC when attention is directed to shapes, away from emotional faces. Methods During functional MRI, 29 participants with gSAD and 27 healthy controls viewed images comprising a trio of faces (angry, fear, or happy) alongside a trio of geometric shapes (circles, rectangles, or triangles) within the same field of view. Participants were instructed to match faces or match shapes, effectively directing attention towards or away from emotional information, respectively. Results Participants with gSAD exhibited greater insula, but not amygdala, activation compared to controls when attending to emotional faces. In contrast, when attention was directed away from faces, controls exhibited ACC recruitment, which was not evident in gSAD. Across participants, greater ACC activation was associated with less insula activation. Conclusions Evidence that individuals with gSAD exhibited exaggerated insula reactivity when attending to emotional faces in EFSAT is consistent with other studies suggesting that the neural basis of gSAD may involve insula hyper-reactivity. Furthermore, greater ACC response in controls than gSAD when sustained goal-directed attention is required to shift attention away from

  16. Does low self-esteem enhance social pain? The relationship between trait self-esteem and anterior cingulate cortex activation induced by ostracism.

    PubMed

    Onoda, Keiichi; Okamoto, Yasumasa; Nakashima, Ken'ichiro; Nittono, Hiroshi; Yoshimura, Shinpei; Yamawaki, Sigeto; Yamaguchi, Shuhei; Ura, Mitsuhiro

    2010-12-01

    According to sociometer theory, self-esteem serves as a barometer of the extent to which individuals are socially included or excluded by others. We hypothesized that trait self-esteem would be related to social pain responsiveness, and we used functional magnetic resonance imaging to experimentally investigate this potential relationship. Participants (n = 26) performed a cyberball task, a computerized game of catch during which the participants were excluded from the game. Participants then rated the degree of social pain experienced during both inclusion in and exclusion from the game. Individuals with lower trait self-esteem reported increased social pain relative to individuals with higher trait self-esteem, and such individuals also demonstrated a greater degree of dorsal anterior cingulate cortex activation. A psychophysiological interaction analysis revealed a positive connectivity between the dorsal anterior cingulate and prefrontal cortices for the lower trait self-esteem group, and a corresponding negative connectivity for the higher trait self-esteem group. Heightened dorsal anterior cortex activity and a corresponding connection with the prefrontal cortex might be one possible explanation for the greater levels of social pain observed experienced by individuals with low trait self-esteem. PMID:20144945

  17. Does low self-esteem enhance social pain? The relationship between trait self-esteem and anterior cingulate cortex activation induced by ostracism

    PubMed Central

    Okamoto, Yasumasa; Nakashima, Ken’ichiro; Nittono, Hiroshi; Yoshimura, Shinpei; Yamawaki, Sigeto; Yamaguchi, Shuhei; Ura, Mitsuhiro

    2010-01-01

    According to sociometer theory, self-esteem serves as a barometer of the extent to which individuals are socially included or excluded by others. We hypothesized that trait self-esteem would be related to social pain responsiveness, and we used functional magnetic resonance imaging to experimentally investigate this potential relationship. Participants (n = 26) performed a cyberball task, a computerized game of catch during which the participants were excluded from the game. Participants then rated the degree of social pain experienced during both inclusion in and exclusion from the game. Individuals with lower trait self-esteem reported increased social pain relative to individuals with higher trait self-esteem, and such individuals also demonstrated a greater degree of dorsal anterior cingulate cortex activation. A psychophysiological interaction analysis revealed a positive connectivity between the dorsal anterior cingulate and prefrontal cortices for the lower trait self-esteem group, and a corresponding negative connectivity for the higher trait self-esteem group. Heightened dorsal anterior cortex activity and a corresponding connection with the prefrontal cortex might be one possible explanation for the greater levels of social pain observed experienced by individuals with low trait self-esteem. PMID:20144945

  18. Elevated Glutamatergic Compounds in Pregenual Anterior Cingulate in Pediatric Autism Spectrum Disorder Demonstrated by 1H MRS and 1H MRSI

    PubMed Central

    Bejjani, Anthony; O'Neill, Joseph; Kim, John A.; Frew, Andrew J.; Yee, Victor W.; Ly, Ronald; Kitchen, Christina; Salamon, Noriko; McCracken, James T.; Toga, Arthur W.; Alger, Jeffry R.; Levitt, Jennifer G.

    2012-01-01

    Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy (1H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging (1H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD. PMID:22848344

  19. Assessing the Molecular Genetics of the Development of Executive Attention in Children: Focus on Genetic Pathways Related to the Anterior Cingulate Cortex and Dopamine

    PubMed Central

    Brocki, Karin; Clerkin, Suzanne M.; Guise, Kevin G.; Fan, Jin; Fossella, John A.

    2009-01-01

    It is well-known that children show gradual and protracted improvement in an array of behaviors involved in the conscious control of thought and emotion. Non-invasive neuroimaging in developing populations has revealed many neural correlates of behavior, particularly in the developing cingulate cortex and fronto-striatal circuits. These brain regions, themselves, undergo protracted molecular and cellular change in the first two decades of human development and, as such, are ideal regions of interest for cognitive- and imaging-genetic studies that seek to link processes at the biochemical and synaptic levels to brain activity and behavior. We review our research to-date that employs both adult and child-friendly versions of the Attention Network Task (ANT) in an effort to begin to describe the role of specific genes in the assembly of a functional attention system. Presently, we constrain our predictions for genetic association studies by focusing on the role of the anterior cingulate cortex (ACC) and of dopamine in the development of executive attention. PMID:19344637

  20. Anterior cingulate cortex-related connectivity in first-episode schizophrenia: a spectral dynamic causal modeling study with functional magnetic resonance imaging

    PubMed Central

    Cui, Long-Biao; Liu, Jian; Wang, Liu-Xian; Li, Chen; Xi, Yi-Bin; Guo, Fan; Wang, Hua-Ning; Zhang, Lin-Chuan; Liu, Wen-Ming; He, Hong; Tian, Ping; Yin, Hong; Lu, Hongbing

    2015-01-01

    Understanding the neural basis of schizophrenia (SZ) is important for shedding light on the neurobiological mechanisms underlying this mental disorder. Structural and functional alterations in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, and medial prefrontal cortex (MPFC) have been implicated in the neurobiology of SZ. However, the effective connectivity among them in SZ remains unclear. The current study investigated how neuronal pathways involving these regions were affected in first-episode SZ using functional magnetic resonance imaging (fMRI). Forty-nine patients with a first-episode of psychosis and diagnosis of SZ—according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision—were studied. Fifty healthy controls (HCs) were included for comparison. All subjects underwent resting state fMRI. We used spectral dynamic causal modeling (DCM) to estimate directed connections among the bilateral ACC, DLPFC, hippocampus, and MPFC. We characterized the differences using Bayesian parameter averaging (BPA) in addition to classical inference (t-test). In addition to common effective connectivity in these two groups, HCs displayed widespread significant connections predominantly involved in ACC not detected in SZ patients, but SZ showed few connections. Based on BPA results, SZ patients exhibited anterior cingulate cortico-prefrontal-hippocampal hyperconnectivity, as well as ACC-related and hippocampal-dorsolateral prefrontal-medial prefrontal hypoconnectivity. In summary, spectral DCM revealed the pattern of effective connectivity involving ACC in patients with first-episode SZ. This study provides a potential link between SZ and dysfunction of ACC, creating an ideal situation to associate mechanisms behind SZ with aberrant connectivity among these cognition and emotion-related regions. PMID:26578933

  1. Functional magnetic resonance spectroscopy of glutamate in schizophrenia and major depressive disorder: anterior cingulate activity during a color-word Stroop task

    PubMed Central

    Taylor, Reggie; Neufeld, Richard W J; Schaefer, Betsy; Densmore, Maria; Rajakumar, Nagalingam; Osuch, Elizabeth A; Williamson, Peter C; Théberge, Jean

    2015-01-01

    Background: Glutamate abnormalities have been suggested to be associated with symptoms of schizophrenia. Using functional magnetic resonance spectroscopy (1H-fMRS), it is possible to monitor glutamate dynamically in the activated brain areas, which has yet to be reported in schizophrenia. It was hypothesized that subjects with schizophrenia would have weaker glutamatergic responses in the anterior cingulate to a color-word Stroop Task. AIMS: The aim of this study was to gain insight into the health of GLU neurotransmission and the GLU-GLN cycle in SZ using a 1H-fMRS protocol. Methods: Spectra were acquired from the anterior cingulate of 16 participants with schizophrenia, 16 healthy controls and 16 participants with major depressive disorder (MDD) while performing the Stroop task in a 7T magnetic resonance imaging scanner. 1H-fMRS spectra were acquired for 20 min in which there were three 4-min blocks of cross fixation interleaved with two 4-min blocks of the Stroop paradigm. Results: A repeated-measures analysis of variance revealed a main effect of time for glutamate concentrations of all groups (P<0.001). The healthy control group increased glutamate concentrations in the first run of the Stroop task (P=0.006) followed by a decrease in the recovery period (P=0.007). Neither the schizophrenia (P=0.107) nor MDD (P=0.081) groups had significant glutamate changes in the first run of the task, while the schizophrenia group had a significant increase in glutamine (P=0.005). The MDD group decreased glutamate concentrations in the second run of the task (P=0.003), as did all the groups combined (P=0.003). Conclusions: 1H-fMRS data were successfully acquired from psychiatric subjects with schizophrenia and mood disorder using a cognitive paradigm for the first time. Future study designs should further elucidate the glutamatergic response to functional activation in schizophrenia. PMID:27336037

  2. Resting-state functional connectivity between the dorsal anterior cingulate cortex and thalamus is associated with risky decision-making in nicotine addicts

    PubMed Central

    Wei, Zhengde; Yang, Nannan; Liu, Ying; Yang, Lizhuang; Wang, Ying; Han, Long; Zha, Rujing; Huang, Ruiqi; Zhang, Peng; Zhou, Yifeng; Zhang, Xiaochu

    2016-01-01

    Nicotine addiction is associated with risky behaviors and abnormalities in local brain areas related to risky decision-making such as the dorsal anterior cingulate cortex (dACC), anterior insula (AI), and thalamus. Although these brain abnormalities are anatomically separated, they may in fact belong to one neural network. However, it is unclear whether circuit-level abnormalities lead to risky decision-making in smokers. In the current study, we used task-based functional magnetic resonance imaging (fMRI) and examined resting-state functional connectivity (RSFC) to study how connectivity between the dACC, insula, and thalamus influence risky decision-making in nicotine addicts. We found that an increase in risky decision-making was associated with stronger nicotine dependence and stronger RSFC of the dACC-rAI (right AI), the dACC-thalamus, the dACC-lAI (left AI), and the rAI-lAI, but that risky decision-making was not associated with risk level-related activation. Furthermore, the severity of nicotine dependence positively correlated with RSFC of the dACC-thalamus but was not associated with risk level-related activation. Importantly, the dACC-thalamus coupling fully mediated the effect of nicotine-dependent severity on risky decision-making. These results suggest that circuit-level connectivity may be a critical neural link between risky decision-making and severity of nicotine dependence in smokers. PMID:26879047

  3. Resting-state functional connectivity between the dorsal anterior cingulate cortex and thalamus is associated with risky decision-making in nicotine addicts.

    PubMed

    Wei, Zhengde; Yang, Nannan; Liu, Ying; Yang, Lizhuang; Wang, Ying; Han, Long; Zha, Rujing; Huang, Ruiqi; Zhang, Peng; Zhou, Yifeng; Zhang, Xiaochu

    2016-01-01

    Nicotine addiction is associated with risky behaviors and abnormalities in local brain areas related to risky decision-making such as the dorsal anterior cingulate cortex (dACC), anterior insula (AI), and thalamus. Although these brain abnormalities are anatomically separated, they may in fact belong to one neural network. However, it is unclear whether circuit-level abnormalities lead to risky decision-making in smokers. In the current study, we used task-based functional magnetic resonance imaging (fMRI) and examined resting-state functional connectivity (RSFC) to study how connectivity between the dACC, insula, and thalamus influence risky decision-making in nicotine addicts. We found that an increase in risky decision-making was associated with stronger nicotine dependence and stronger RSFC of the dACC-rAI (right AI), the dACC-thalamus, the dACC-lAI (left AI), and the rAI-lAI, but that risky decision-making was not associated with risk level-related activation. Furthermore, the severity of nicotine dependence positively correlated with RSFC of the dACC-thalamus but was not associated with risk level-related activation. Importantly, the dACC-thalamus coupling fully mediated the effect of nicotine-dependent severity on risky decision-making. These results suggest that circuit-level connectivity may be a critical neural link between risky decision-making and severity of nicotine dependence in smokers. PMID:26879047

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

    PubMed Central

    Wheelock, Muriah D.; Reid, Meredith A.; To, Harrison; White, David M.; Cropsey, Karen L.; Lahti, Adrienne C.

    2014-01-01

    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. PMID:25071576

  5. Amygdala and Dorsal Anterior Cingulate Connectivity during an Emotional Working Memory Task in Borderline Personality Disorder Patients with Interpersonal Trauma History

    PubMed Central

    Krause-Utz, Annegret; Elzinga, Bernet M.; Oei, Nicole Y. L.; Paret, Christian; Niedtfeld, Inga; Spinhoven, Philip; Bohus, Martin; Schmahl, Christian

    2014-01-01

    Working memory is critically involved in ignoring emotional distraction while maintaining goal-directed behavior. Antagonistic interactions between brain regions implicated in emotion processing, e.g., amygdala, and brain regions involved in cognitive control, e.g., dorsolateral and dorsomedial prefrontal cortex (dlPFC, dmPFC), may play an important role in coping with emotional distraction. We previously reported prolonged reaction times associated with amygdala hyperreactivity during emotional distraction in interpersonally traumatized borderline personality disorder (BPD) patients compared to healthy controls (HC): Participants performed a working memory task, while neutral versus negative distractors (interpersonal scenes from the International Affective Picture System) were presented. Here, we re-analyzed data from this study using psychophysiological interaction analysis. The bilateral amygdala and bilateral dorsal anterior cingulate cortex (dACC) were defined as seed regions of interest. Whole-brain regression analyses with reaction times and self-reported increase of dissociation were performed. During emotional distraction, reduced amygdala connectivity with clusters in the left dorsolateral and ventrolateral PFC was observed in the whole group. Compared to HC, BPD patients showed a stronger coupling of both seeds with a cluster in the right dmPFC and stronger positive amygdala connectivity with bilateral (para)hippocampus. Patients further demonstrated stronger positive dACC connectivity with left posterior cingulate, insula, and frontoparietal regions during emotional distraction. Reaction times positively predicted amygdala connectivity with right dmPFC and (para)hippocampus, while dissociation positively predicted amygdala connectivity with right ACC during emotional distraction in patients. Our findings suggest increased attention to task-irrelevant (emotional) social information during a working memory task in interpersonally traumatized patients

  6. Amygdala and Dorsal Anterior Cingulate Connectivity during an Emotional Working Memory Task in Borderline Personality Disorder Patients with Interpersonal Trauma History.

    PubMed

    Krause-Utz, Annegret; Elzinga, Bernet M; Oei, Nicole Y L; Paret, Christian; Niedtfeld, Inga; Spinhoven, Philip; Bohus, Martin; Schmahl, Christian

    2014-01-01

    Working memory is critically involved in ignoring emotional distraction while maintaining goal-directed behavior. Antagonistic interactions between brain regions implicated in emotion processing, e.g., amygdala, and brain regions involved in cognitive control, e.g., dorsolateral and dorsomedial prefrontal cortex (dlPFC, dmPFC), may play an important role in coping with emotional distraction. We previously reported prolonged reaction times associated with amygdala hyperreactivity during emotional distraction in interpersonally traumatized borderline personality disorder (BPD) patients compared to healthy controls (HC): Participants performed a working memory task, while neutral versus negative distractors (interpersonal scenes from the International Affective Picture System) were presented. Here, we re-analyzed data from this study using psychophysiological interaction analysis. The bilateral amygdala and bilateral dorsal anterior cingulate cortex (dACC) were defined as seed regions of interest. Whole-brain regression analyses with reaction times and self-reported increase of dissociation were performed. During emotional distraction, reduced amygdala connectivity with clusters in the left dorsolateral and ventrolateral PFC was observed in the whole group. Compared to HC, BPD patients showed a stronger coupling of both seeds with a cluster in the right dmPFC and stronger positive amygdala connectivity with bilateral (para)hippocampus. Patients further demonstrated stronger positive dACC connectivity with left posterior cingulate, insula, and frontoparietal regions during emotional distraction. Reaction times positively predicted amygdala connectivity with right dmPFC and (para)hippocampus, while dissociation positively predicted amygdala connectivity with right ACC during emotional distraction in patients. Our findings suggest increased attention to task-irrelevant (emotional) social information during a working memory task in interpersonally traumatized patients

  7. Analysis of coherent activity between retrosplenial cortex, hippocampus, thalamus, and anterior cingulate cortex during retrieval of recent and remote context fear memory.

    PubMed

    Corcoran, Kevin A; Frick, Brendan J; Radulovic, Jelena; Kay, Leslie M

    2016-01-01

    Memory for contextual fear conditioning relies upon the retrosplenial cortex (RSC) regardless of how long ago conditioning occurred, whereas areas connected to the RSC, such as the dorsal hippocampus (DH) and anterior cingulate cortex (ACC) appear to play time-limited roles. To better understand whether these brain regions functionally interact during memory processing and how the passage of time affects these interactions, we simultaneously recorded local field potentials (LFPs) from these three regions as well as anterior dorsal thalamus (ADT), which provides one of the strongest inputs to RSC, and measured coherence of oscillatory activity within the theta (4-12Hz) and gamma (30-80Hz) frequency bands. We identified changes of theta coherence related to encoding, retrieval, and extinction of context fear, whereas changes in gamma coherence were restricted to fear extinction. Specifically, exposure to a novel context and retrieval of recently acquired fear conditioning memory were associated with increased theta coherence between RSC and all three other structures. In contrast, RSC-DH and RSC-ADT theta coherence were decreased in mice that successfully retrieved, relative to mice that failed to retrieve, remote memory. Greater RSC-ADT theta and gamma coherence were observed during recent, compared to remote, extinction of freezing responses. Thus, the degree of coherence between RSC and connected brain areas may predict and contribute to context memory retrieval and retrieval-related phenomena such as fear extinction. Importantly, although theta coherence in this circuit increases during memory encoding and retrieval of recent memory, failure to decrease RSC-DH theta coherence might be linked to retrieval deficit in the long term, and possibly contribute to aberrant memory processing characteristic of neuropsychiatric disorders. PMID:26691782

  8. Altered resting state functional connectivity of anterior cingulate cortex in drug naïve adolescents at the earliest stages of anorexia nervosa.

    PubMed

    Gaudio, Santino; Piervincenzi, Claudia; Beomonte Zobel, Bruno; Romana Montecchi, Francesca; Riva, Giuseppe; Carducci, Filippo; Quattrocchi, Carlo Cosimo

    2015-01-01

    Previous Resting-State Functional Connectivity (RSFC) studies have shown several functional alterations in adults with or recovered from long Anorexia Nervosa (AN). The aim of this paper was to investigate whole brain RSFC in adolescents with AN in the earliest stages, less than 6 months, of the disorder. Sixteen drug-naïve outpatient female adolescents with AN-restrictive type (AN-r) (mean age: 15,8; SD 1,7) were compared to 16 age-matched healthy female (mean age: 16,3; SD 1,4). Relevant resting state networks (RSNs) were identified using independent component analysis (ICA) from functional magnetic resonance imaging data; a dual regression technique was used to detect between-group differences in the RSNs. Between-group differences of the functional connectivity maps were found in the executive control network (ECN). Particularly, decreased temporal correlation was observed in AN-r patients relative to healthy controls between the ECN functional connectivity maps and the anterior cingulate cortex (p < 0.05 corrected). Our results in AN adolescents may represent an early trait-related biomarker of the disease. Considering that the above mentioned network and its area are mainly involved in cognitive control and emotional processing, our findings could explain the impaired cognitive flexibility in relation to body image and appetite in AN patients. PMID:26043139

  9. A Longitudinal (6-week) 3T (1)H-MRS Study on the Effects of Lithium Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression.

    PubMed

    Machado-Vieira, Rodrigo; Gattaz, Wagner F; Zanetti, Marcus V; De Sousa, Rafael T; Carvalho, Andre F; Soeiro-de-Souza, Marcio G; Leite, Claudia C; Otaduy, Maria C

    2015-12-01

    The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no longitudinal study has specifically evaluated lithium׳s effects on ACC metabolites using (1)H-MRS, as well as its association with clinical improvement in bipolar depression. This (1)H-MRS (TE=35ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NAA), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate+glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (mI/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium׳s therapeutic effects in BD. PMID:26428274

  10. Asymmetry of the Endogenous Opioid System in the Human Anterior Cingulate: a Putative Molecular Basis for Lateralization of Emotions and Pain

    PubMed Central

    Watanabe, Hiroyuki; Fitting, Sylvia; Hussain, Muhammad Z.; Kononenko, Olga; Iatsyshyna, Anna; Yoshitake, Takashi; Kehr, Jan; Alkass, Kanar; Druid, Henrik; Wadensten, Henrik; Andren, Per E.; Nylander, Ingrid; Wedell, Douglas H.; Krishtal, Oleg; Hauser, Kurt F.; Nyberg, Fred; Karpyak, Victor M.; Yakovleva, Tatjana; Bakalkin, Georgy

    2015-01-01

    Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the μ-, δ-, and κ-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 “classical” neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential δ-/μ- and κ-/μ-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this κ-opioid agonist to δ-/μ-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left–right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain. PMID:23960211

  11. Dysfunctional Activation and Brain Network Profiles in Youth with Obsessive-Compulsive Disorder: A Focus on the Dorsal Anterior Cingulate during Working Memory.

    PubMed

    Diwadkar, Vaibhav A; Burgess, Ashley; Hong, Ella; Rix, Carrie; Arnold, Paul D; Hanna, Gregory L; Rosenberg, David R

    2015-01-01

    Brain network dysfunction is emerging as a central biomarker of interest in psychiatry, in large part, because psychiatric conditions are increasingly seen as disconnection syndromes. Understanding dysfunctional brain network profiles in task-active states provides important information on network engagement in an experimental context. This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes. Here we investigated brain network profiles in youth with obsessive-compulsive disorder (OCD), contrasting them with a group of age-comparable controls. Network interactions were assessed during simple working memory: in particular, we focused on the modulation by the dorsal anterior cingulate cortex (dACC) of cortical, striatal, and thalamic regions. The focus on the dACC was motivated by its hypothesized role in the pathophysiology of OCD. However, its task-active network signatures have not been investigated before. Network interactions were modeled using psychophysiological interaction, a simple directional model of seed to target brain interactions. Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand. The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype. PMID:25852529

  12. The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: Integration of resting EEG, fMRI, and volumetric techniques

    PubMed Central

    Wacker, Jan; Dillon, Daniel G.; Pizzagalli, Diego A.

    2009-01-01

    Anhedonia, the reduced propensity to experience pleasure, is a promising endophenotype and vulnerability factor for several psychiatric disorders, including depression and schizophrenia. In the present study, we used resting electroencephalograms, functional magnetic resonance imaging, and volumetric analyses to probe putative associations between anhedonia and individual differences in key nodes of the brain’s reward system in a non-clinical sample. We found that anhedonia, but not other symptoms of depression or anxiety, was correlated with reduced nucleus accumbens (NAcc) responses to rewards (gains in a monetary incentive delay task), reduced NAcc volume, and increased resting delta current density (i.e., decreased resting activity) in the rostral anterior cingulate cortex (rACC), an area previously implicated in positive subjective experience. In addition, NAcc reward responses were inversely associated with rACC resting delta activity, supporting the hypothesis that delta might be lawfully related to activity within the brain’s reward circuit. Taken together, these results help elucidate the neural basis of anhedonia and strengthen the argument for anhedonia as an endophenotype for depression. PMID:19457367

  13. Dissociable Contributions of Anterior Cingulate Cortex and Basolateral Amygdala on a Rodent Cost/Benefit Decision-Making Task of Cognitive Effort

    PubMed Central

    Hosking, Jay G; Cocker, Paul J; Winstanley, Catharine A

    2014-01-01

    Personal success often requires the choice to expend greater effort for larger rewards, and deficits in such effortful decision making accompany a number of illnesses including depression, schizophrenia, and attention-deficit/hyperactivity disorder. Animal models have implicated brain regions such as the basolateral amygdala (BLA) and anterior cingulate cortex (ACC) in physical effort-based choice, but disentangling the unique contributions of these two regions has proven difficult, and effort demands in industrialized society are predominantly cognitive in nature. Here we utilize the rodent cognitive effort task (rCET), a modification of the five-choice serial reaction-time task, wherein animals can choose to expend greater visuospatial attention to obtain larger sucrose rewards. Temporary inactivation (via baclofen–muscimol) of BLA and ACC showed dissociable effects: BLA inactivation caused hard-working rats to ‘slack off' and ‘slacker' rats to work harder, whereas ACC inactivation caused all animals to reduce willingness to expend mental effort. Furthermore, BLA inactivation increased the time needed to make choices, whereas ACC inactivation increased motor impulsivity. These data illuminate unique contributions of BLA and ACC to effort-based decision making, and imply overlapping yet distinct circuitry for cognitive vs physical effort. Our understanding of effortful decision making may therefore require expanding our models beyond purely physical costs. PMID:24496320

  14. Resting-state synchrony between anterior cingulate cortex and precuneus relates to body shape concern in anorexia nervosa and bulimia nervosa.

    PubMed

    Lee, Seojung; Ran Kim, Kyung; Ku, Jeonghun; Lee, Jung-Hyun; Namkoong, Kee; Jung, Young-Chul

    2014-01-30

    Cortical areas supporting cognitive control and salience demonstrate different neural responses to visual food cues in patients with eating disorders. This top-down cognitive control, which interacts with bottom-up appetitive responses, is tightly integrated not only in task conditions but also in the resting-state. The dorsal anterior cingulate cortex (dACC) is a key node of a large-scale network that is involved in self-referential processing and cognitive control. We investigated resting-state functional connectivity of the dACC and hypothesized that altered connectivity would be demonstrated in cortical midline structures involved in self-referential processing and cognitive control. Seed-based resting-state functional connectivity was analyzed in women with anorexia nervosa (N=18), women with bulimia nervosa (N=20) and age matched healthy controls (N=20). Between group comparisons revealed that the anorexia nervosa group exhibited stronger synchronous activity between the dACC and retrosplenial cortex, whereas the bulimia nervosa group showed stronger synchronous activity between the dACC and medial orbitofrontal cortex. Both groups demonstrated stronger synchronous activity between the dACC and precuneus, which correlated with higher scores of the Body Shape Questionnaire. The dACC-precuneus resting-state synchrony might be associated with the disorder-specific rumination on eating, weight and body shape in patients with eating disorders. PMID:24300085

  15. Altered resting state functional connectivity of anterior cingulate cortex in drug naïve adolescents at the earliest stages of anorexia nervosa

    PubMed Central

    Gaudio, Santino; Piervincenzi, Claudia; Beomonte Zobel, Bruno; Romana Montecchi, Francesca; Riva, Giuseppe; Carducci, Filippo; Cosimo Quattrocchi, Carlo

    2015-01-01

    Previous Resting-State Functional Connectivity (RSFC) studies have shown several functional alterations in adults with or recovered from long Anorexia Nervosa (AN). The aim of this paper was to investigate whole brain RSFC in adolescents with AN in the earliest stages, less than 6 months, of the disorder. Sixteen drug-naïve outpatient female adolescents with AN-restrictive type (AN-r) (mean age: 15,8; SD 1,7) were compared to 16 age-matched healthy female (mean age: 16,3; SD 1,4). Relevant resting state networks (RSNs) were identified using independent component analysis (ICA) from functional magnetic resonance imaging data; a dual regression technique was used to detect between-group differences in the RSNs. Between-group differences of the functional connectivity maps were found in the executive control network (ECN). Particularly, decreased temporal correlation was observed in AN-r patients relative to healthy controls between the ECN functional connectivity maps and the anterior cingulate cortex (p < 0.05 corrected). Our results in AN adolescents may represent an early trait-related biomarker of the disease. Considering that the above mentioned network and its area are mainly involved in cognitive control and emotional processing, our findings could explain the impaired cognitive flexibility in relation to body image and appetite in AN patients. PMID:26043139

  16. Neurotransmitter changes during interference task in anterior cingulate cortex: evidence from fMRI-guided functional MRS at 3 T.

    PubMed

    Kühn, Simone; Schubert, Florian; Mekle, Ralf; Wenger, Elisabeth; Ittermann, Bernd; Lindenberger, Ulman; Gallinat, Jürgen

    2016-06-01

    Neural activity as indirectly observed in blood oxygenation level-dependent (BOLD) response is thought to reflect changes in neurotransmitter flux. In this study, we used fMRI-guided functional magnetic resonance spectroscopy (MRS) to measure metabolite/BOLD associations during a cognitive task at 3 T. GABA and glutamate concentration in anterior cingulate cortex (ACC) were determined by means of MRS using the SPECIAL pulse sequence before, during and after the performance of a manual Stroop task. MRS voxel positions were centred around individuals' BOLD activity during Stroop performance. Levels of GABA and glutamate showed inverted U-shape patterns across measurement time points (before, during, and after task), glutamine increased linearly and total creatine did not change. The GABA increase during task performance was associated with ACC BOLD signal changes in both congruent and incongruent Stroop conditions. Using an fMRI-guided MRS approach, an association between induced inhibitory neurotransmitter increase and BOLD changes was observed. The proposed procedure might allow the in vivo investigation of normal and dysfunctional associations between neurotransmitters and BOLD signal crucial for cerebral functioning. PMID:25976598

  17. Anterior Cingulate Cortex Gray Matter Volume Mediates an Association between 2D:4D Ratio and Trait Aggression in Women but not Men

    PubMed Central

    Gorka, Adam X.; Norman, Rachel E.; Radtke, Spenser R.; Carré, Justin M.; Hariri, Ahmad R.

    2015-01-01

    Previous research demonstrates that prenatal testosterone exposure increases aggression, possibly through its effects on the structure and function of neural circuits supporting threat detection and emotion regulation. Here we examined associations between regional gray matter volume, trait aggression, and the ratio of the second and fourth digit of the hand (2D:4D ratio) as a putative index of prenatal testosterone exposure in 464 healthy young adult volunteers. Our analyses revealed a significant positive correlation between 2D:4D ratio and gray matter volume of the dorsal anterior cingulate cortex (dACC), a brain region supporting, emotion regulation, conflict monitoring, and behavioral inhibition. Subsequent analyses demonstrated that reduced (i.e., masculinized) gray matter volume in the dACC mediated the relationship between 2D:4D ratio and aggression in women, but not men. Expanding on this gender-specific mediation, additional analyses demonstrated that the shared variance between 2D:4D ratio, dACC gray matter volume, and aggression in women reflected the tendency to engage in cognitive reappraisal of emotionally provocative stimuli. Our results provide novel evidence that 2D:4D ratio is associated with masculinization of dACC gray matter volume, and that this neural phenotype mediates, in part, the expression of trait aggression in women. PMID:25827959

  18. Dysfunctional Activation and Brain Network Profiles in Youth with Obsessive-Compulsive Disorder: A Focus on the Dorsal Anterior Cingulate during Working Memory

    PubMed Central

    Diwadkar, Vaibhav A.; Burgess, Ashley; Hong, Ella; Rix, Carrie; Arnold, Paul D.; Hanna, Gregory L.; Rosenberg, David R.

    2015-01-01

    Brain network dysfunction is emerging as a central biomarker of interest in psychiatry, in large part, because psychiatric conditions are increasingly seen as disconnection syndromes. Understanding dysfunctional brain network profiles in task-active states provides important information on network engagement in an experimental context. This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes. Here we investigated brain network profiles in youth with obsessive-compulsive disorder (OCD), contrasting them with a group of age-comparable controls. Network interactions were assessed during simple working memory: in particular, we focused on the modulation by the dorsal anterior cingulate cortex (dACC) of cortical, striatal, and thalamic regions. The focus on the dACC was motivated by its hypothesized role in the pathophysiology of OCD. However, its task-active network signatures have not been investigated before. Network interactions were modeled using psychophysiological interaction, a simple directional model of seed to target brain interactions. Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand. The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype. PMID:25852529

  19. (1)H-MRS asymmetry changes in the anterior and posterior cingulate gyrus in patients with mild cognitive impairment and mild Alzheimer's disease.

    PubMed

    Guo, Zhongwei; Liu, Xiaozheng; Hou, Hongtao; Wei, Fuquan; Chen, Xingli; Shen, Yuedi; Chen, Wei

    2016-08-01

    Alzheimer's disease (AD) is the most common cause of dementia worldwide. Amnestic mild cognitive impairment (aMCI) is often the prodromal stage to AD. Most patients with aMCI harbor the pathologic changes of AD and demonstrate transition to AD at a rate of 10%-15% per year. Patients with AD and aMCI experience progressive brain metabolite changes. Accumulating evidence indicates that the asymmetry changes of left and right brain happen in the early stage of AD. However, the features of asymmetry changes in both anterior cingulate gyrus (ACG) and posterior cingulate gyrus (PCG) are still unclear. Here, we examine the left-right asymmetry changes of metabolites in ACG and PCG. Fifteen cases of mild AD patients meeting criteria for probable AD of NINDS-ADRDA, thirteen cases of aMCI according to the Mayo Clinic Alzheimer's Disease Research Center criteria, and sixteen cases of age-matched normal controls (NC) received Proton magnetic resonance spectroscopy ((1)H-MRS) for measurement of NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr ratios in the PCG and ACG bilaterally. We analyzed (1)H-MRS data by paired t-test to validate the left-right asymmetry of (1)H-MRS data in the PCG and ACG. In AD, there was a significant difference in mI/Cr between the left and right ACG (P<0.001) and the left and right PCG (P=0.007). In aMCI, there was a significant difference in mI/Cr between the left and right ACG (P<0.001). In NC, there were no differences in the ratio value of metabolites NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr between the left and right ACG and PCG. Thus, the left-right asymmetry of mI/Cr in the ACG and PCG may be an important biological indicator of mild AD. PMID:27423359

  20. Astrocytes are involved in long-term facilitation of neuronal excitation in the anterior cingulate cortex of mice with inflammatory pain.

    PubMed

    Ikeda, Hiroshi; Mochizuki, Keiichi; Murase, Kazuyuki

    2013-12-01

    Neuronal plasticity in the pain-processing pathway is thought to be a mechanism underlying pain hypersensitivity and negative emotions occurring during a pain state. Recent evidence suggests that the activation of astrocytes in the anterior cingulate cortex (ACC) contributes to the development of negative emotions during pain hypersensitivity after peripheral inflammation. However, it is unknown whether these activated astrocytes contribute to neuronal plasticity in the ACC. In this study, by using optical imaging with voltage- and Ca(2+)-sensitive dyes, we examined the long-term facilitation of neuronal excitation induced by high-frequency conditioning stimulation (HFS) in ACC slices of control mice and mice with peripheral inflammation induced by the injection of complete Freund adjuvant (CFA) to the hind paw. Immunoreactivity of glial fibrillary acidic protein in laminae II-III of the ACC in the CFA-injected mice was higher than in the control mice. Neuronal excitation in ACC slices from the CFA-injected mice was gradually increased by HFS, and the magnitude of this long-term facilitation was greater than in the control mice. The long-term facilitation in the CFA-injected mice was inhibited by the astroglial toxin, the N-methyl-d-aspartate (NMDA) receptor antagonist and NMDA receptor glycine binding site antagonist. The increase of intracellular Ca(2+) concentration in astrocytes during HFS was higher in the CFA-injected mice than in the control mice and was inhibited by l-α-aminoadipate (l-α-AA). These results suggest that the activation of astrocytes in the ACC plays a crucial role in the development of negative emotions and LTP during pain hypersensitivity after peripheral inflammation. PMID:23988365

  1. Contrasting changes in extracellular dopamine and glutamate along the rostrocaudal axis of the anterior cingulate cortex of the rat following an acute d-amphetamine or dopamine challenge

    PubMed Central

    Ash, Elizabeth S.; Heal, David J.; Clare Stanford, S.

    2014-01-01

    There is evidence for functional specificity of subregions along the rostrocaudal axis of the anterior cingulate cortex (ACC). The subregion-specific distribution of dopaminergic afferents and glutamatergic efferents along the ACC make these obvious candidates for coding such regional responses. We investigated this possibility using microdialysis in freely-moving rats to compare changes in extracellular dopamine and glutamate in the rostral (‘rACC': Cg1 and Cg3 (prelimbic area)) and caudal (‘cACC’: Cg1 and Cg2) ACC induced by systemic or local administration of d-amphetamine. Systemic administration of d-amphetamine (3 mg/kg, i.p.) caused a transient increase in extracellular dopamine in the rACC, but an apparent increase in the cACC of the same animals was less clearly defined. Local infusion of d-amphetamine increased dopamine efflux in the rACC, only. Glutamate efflux in the rACC was increased by local infusion of dopamine (5–50 μM), which had negligible effect in the cACC, but only systemic administration of d-amphetamine increased glutamate efflux and only in the cACC. The asymmetry in the neurochemical responses within the rACC and cACC, to the same experimental challenges, could help explain why different subregions are recruited in the response to specific environmental and somatosensory stimuli and should be taken into account when studying the regulation of neurotransmission in the ACC. This article is part of the Special Issue entitled ‘CNS Stimulants’. PMID:24747182

  2. 4-Methylcatechol prevents derangements of brain-derived neurotrophic factor and TrkB-related signaling in anterior cingulate cortex in chronic pain with depression-like behavior.

    PubMed

    Ishikawa, Kozo; Yasuda, Seiko; Fukuhara, Kayoko; Iwanaga, Yasutake; Ida, Yuika; Ishikawa, Junko; Yamagata, Hirotaka; Ono, Midori; Kakeda, Takahiro; Ishikawa, Toshizo

    2014-03-01

    Chronic pain with mood disorder, resulting from a peripheral nerve injury, is a serious clinical problem affecting the quality of life. A lack of brain-derived neurotrophic factor (BDNF) and abnormal intercellular signaling in the brain can mediate this symptom. BDNF is induced in cultured neurons by 4-methylcatechol (4-MC), but little is known about its role in pain-emotion. Thus, we characterized the actions of 4-MC on TrkB receptor-related pERK and BDNF mRNA in discreet brain regions related to pain-emotion after chronic pain in rat. Rats implanted with a stainless steel cannula into the lateral ventricular were subjected to chronic constriction injury (CCI). Pain was assessed by changes in paw withdrawal latency (PWL) to heat stimuli after CCI. Immobility time during the forced swimming testing was measured for depression-like behavior. Analgesic and antidepression modulations with 4-MC were examined by an anti-BDNF antibody (K252a, a TrkB receptor inhibitor). The animals were perfused and fixed (4% paraformaldehyde) for immunohistochemistry analysis (c-FOS/pERK). BDNF mRNA expression (anterior cingulate cortex) was determined using reverse transcription-PCR. Rats showed a sustained decrease in PWL, associated with a prolonged immobility time after CCI. 4-MC reduced decreases in PWL and increased immobility time. 4-MC reduced increases in pERK immunoreactivity and decreases in BDNF mRNA expression in regions related to pain and the limbic system. Anti-BDNF blocked effects induced by 4-MC. We suggest that a lack of BDNF associated with activated extracellular signal-regulated kinase in the pain-emotion network may be involved in depression-like behavior during chronic pain. 4-MC ameliorates pain-emotion symptoms by inducing BDNF and normalizing pERK activities. PMID:24518228

  3. Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder

    PubMed Central

    Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine

    2016-01-01

    Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724

  4. A dual but asymmetric role of the dorsal anterior cingulate cortex in response inhibition and switching from a non-salient to salient action.

    PubMed

    Manza, Peter; Hu, Sien; Chao, Herta H; Zhang, Sheng; Leung, Hoi-Chung; Li, Chiang-Shan R

    2016-07-01

    Response inhibition and salience detection are among the most studied psychological constructs of cognitive control. Despite a growing body of work, how inhibition and salience processing interact and engage regional brain activations remains unclear. Here, we examined this issue in a stop signal task (SST), where a prepotent response needs to be inhibited to allow an alternative, less dominant response. Sixteen adult individuals performed two versions of the SST each with 25% (SST25) and 75% (SST75) of stop trials. We posited that greater regional activations to the infrequent trial type in each condition (i.e., to stop as compared to go trials in SST25 and to go as compared to stop trials in SST75) support salience detection. Further, successful inhibition in stop trials requires attention to the stop signal to trigger motor inhibition, and the stop signal reaction time (SSRT) has been used to index the efficiency of motor response inhibition. Therefore, greater regional activations to stop as compared to go success trials in association with the stop signal reaction time (SSRT) serve to expedite response inhibition. In support of an interactive role, the dorsal anterior cingulate cortex (dACC) increases activation to salience detection in both SST25 and SST75, but only mediates response inhibition in SST75. Thus, infrequency response in the dACC supports motor inhibition only when stopping has become a routine. In contrast, although the evidence is less robust, the pre-supplementary motor area (pre-SMA) increases activity to the infrequent stimulus and supports inhibition in both SST25 and SST75. These findings clarify a unique role of the dACC and add to the literature that distinguishes dACC and pre-SMA functions in cognitive control. PMID:27126003

  5. Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: a voxel-based morphometric analysis

    PubMed Central

    Webb, C. A.; Weber, M.; Mundy, E. A.; Killgore, W. D. S.

    2014-01-01

    Background Studies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research. Method To examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants. Results The severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression. Conclusions Reduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations. PMID:25066703

  6. The formation of recent and remote memory is associated with time-dependent formation of dendritic spines in the hippocampus and anterior cingulate cortex.

    PubMed

    Restivo, Leonardo; Vetere, Gisella; Bontempi, Bruno; Ammassari-Teule, Martine

    2009-06-24

    Although hippocampal-cortical interactions are crucial for the formation of enduring declarative memories, synaptic events that govern long-term memory storage remain mostly unclear. We present evidence that neuronal structural changes, i.e., dendritic spine growth, develop sequentially in the hippocampus and anterior cingulate cortex (aCC) during the formation of recent and remote contextual fear memory. We found that mice placed in a conditioning chamber for one 7 min conditioning session and exposed to five footshocks (duration, 2 s; intensity, 0.7 mA; interstimulus interval, 60 s) delivered through the grid floor exhibited robust fear response when returned to the experimental context 24 h or 36 d after the conditioning. We then observed that their fear response at the recent, but not the remote, time point was associated with an increase in spine density on hippocampal neurons, whereas an inverse temporal pattern of spine density changes occurred on aCC neurons. At each time point, hippocampal or aCC structural alterations were achieved even in the absence of recent or remote memory tests, thus suggesting that they were not driven by retrieval processes. Furthermore, ibotenic lesions of the hippocampus impaired remote memory and prevented dendritic spine growth on aCC neurons when they were performed immediately after the conditioning, whereas they were ineffective when performed 24 d later. These findings reveal that gradual structural changes modifying connectivity in hippocampal-cortical networks underlie the formation and expression of remote memory, and that the hippocampus plays a crucial but time-limited role in driving structural plasticity in the cortex. PMID:19553460

  7. Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder.

    PubMed

    Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine

    2016-01-01

    Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724

  8. Activation of mGluR1 contributes to neuronal hyperexcitability in the rat anterior cingulate cortex via inhibition of HCN channels.

    PubMed

    Gao, Shi-Hao; Wen, Hui-Zhong; Shen, Lin-Lin; Zhao, Yan-Dong; Ruan, Huai-Zhen

    2016-06-01

    Neuronal hyperexcitability in the anterior cingulate cortex (ACC) is considered as one of the most important pathological changes responsible for the chronification of neuropathic pain. However, the underlying mechanisms remain elusive. In the present study, we investigated the possible mechanisms using a rat model of chronic constriction injury (CCI) to the sciatic nerve. We found a substantial decrease in hyperpolarization-activated/cyclic nucleotide-gated (HCN) currents in layer 5 pyramidal neurons (L5 PNs) in ACC slices, which dramatically increased the excitability of these neurons. This effect could be mimicked in sham slices by activating group 1 metabotropic glutamate receptors, and be blocked in CCI slices by inhibiting metabotropic glutamate receptor subtype 1 (mGluR1). Next, the inhibition of HCN currents was reversed by a protein kinase C (PKC) inhibitor, followed by a reduced neuronal hyperexcitability. Furthermore, HCN channel subtype 1 (HCN1) level was significantly reduced after CCI, whereas mGluR1 level increased. These changes were mainly observed in L5 of the ACC, where HCN1 and mGluR1 were highly colocalized. For behavioral tests, intra-ACC microinjection of mGluR1-shRNA suppressed the CCI-induced behavioral hypersensitivity, particularly thermal hyperalgesia, but not aversive behavior, and this effect was attenuated by the pre-blockade of HCN channels. Taken together, the neuronal hyperexcitability of ACC L5 PNs likely results from an upregulation of mGluR1 and a downstream pathway involving PKC activation and a downregulation of HCN1 in the early phase of neuropathic pain. These alterations may at least in part contribute to the development of behavioral hypersensitivity in CCI rats. PMID:26829470

  9. Interhemispheric Asymmetries and Theta Activity in the Rostral Anterior Cingulate Cortex as EEG Signature of HIV-Related Depression: Gender Matters.

    PubMed

    Kremer, Heidemarie; Lutz, Franz P C; McIntosh, Roger C; Dévieux, Jessy G; Ironson, Gail

    2016-04-01

    Resting EEGs of 40 people living with HIV (PLWH) on long-term antiretroviral treatment were examined for z-scored deviations from a healthy control (normative database) to examine the main and interaction effects of depression and gender. Regions of interest were frontal (alpha) and central (all bands) for interhemispheric asymmetries in quantitative EEGs and theta in the rostral anterior cingulate cortex (rACC) in low-resolution electromagnetic tomography (LORETA). Z-scored normed deviations of depressed PLWH, compared with nondepressed, showed right-dominant interhemispheric asymmetries in all regions. However, after adjusting for multiple testing, significance remained only central for theta, alpha, and beta. Reversed (left-dominant) frontal alpha asymmetry is a potential EEG marker of depression in the HIV negative population that was not reversed in depressive PLWH; however, corresponding with extant literature, gender had an effect on the size of frontal alpha asymmetry. The LORETA analysis revealed a trending interactional effect of depression and gender on theta activity in the rACC in Brodmann area 32. We found that compared to men, women had greater right-dominant frontal alpha-asymmetry and elevated theta activity in voxels of the rACC, which may indicate less likelihood of depression and a higher likelihood of response to antidepressants. In conclusion, subtle EEG deviations, such as right-dominant central theta, alpha, and beta asymmetries and theta activity in the rACC may mark HIV-related depressive symptoms and may predict the likelihood of response to antidepressants but gender effects need to be taken into account. Although this study introduced the use of LORETA to examine the neurophysiological correlates of negative affect in PLWH, further research is needed to assess the utility of this tool in diagnostics and treatment monitoring of depression in PLWH. PMID:25568149

  10. A network-level analysis of cognitive flexibility reveals a differential influence of the anterior cingulate cortex in bilinguals versus monolinguals.

    PubMed

    Becker, Theresa M; Prat, Chantel S; Stocco, Andrea

    2016-05-01

    Mounting evidence suggests that bilingual development may change the brain in a way that gives rise to differences in non-linguistic cognitive functioning; however, only a limited number of studies have investigated the mechanism by which bilingualism shapes the brain. The current study used a network-level analysis to investigate differences in the mechanisms by which bilinguals and monolinguals flexibly adapt their neural networks in the face of novel task demands. Three competing hypotheses concerning differences in network-level adaptation were examined using Dynamic Causal Modeling of data from 15 bilinguals and 14 monolinguals who performed a Rapid Instructed Task Learning paradigm. The results demonstrated that the best-fitting model for the data from both groups specified that novel task execution is accomplished through a modulation of the influence of the anterior cingulate cortex (ACC) on the dorsolateral prefrontal cortex (DLPFC) and on the striatum. Further examination of the best-fitting model revealed that ACC activity increased DLPFC and striatal activity in bilinguals but decreased activity in these regions in monolinguals. Interestingly, an increased positive connection between the ACC and striatum was associated with decreased accuracy across groups. Taken together, the results suggest that regardless of language experience, the ACC plays a critical role in cognitive flexibility, but the exact influence of the ACC on other primary control regions seems to be dependent on language experience. When paired with the behavioral results, these results suggest that bilinguals and monolinguals may employ different neurocognitive mechanisms for conflict monitoring to flexibly adapt to novel situations. PMID:26796713