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Sample records for anterior cingulate activation

  1. Evidence of Conjoint Activation of the Anterior Insular and Cingulate Cortices during Effortful Tasks.

    PubMed

    Engström, Maria; Karlsson, Thomas; Landtblom, Anne-Marie; Craig, A D Bud

    2014-01-01

    The ability to perform effortful tasks is a topic that has received considerable interest in the research of higher functions of the human brain. Neuroimaging studies show that the anterior insular and the anterior cingulate cortices are involved in a multitude of cognitive tasks that require mental effort. In this study, we investigated brain responses to effort using cognitive tasks with task-difficulty modulations and functional magnetic resonance imaging (fMRI). We hypothesized that effortful performance involves modulation of activation in the anterior insular and the anterior cingulate cortices, and that the modulation correlates with individual performance levels. Healthy participants performed tasks probing verbal working memory capacity using the reading span task, and visual perception speed using the inspection time task. In the fMRI analysis, we focused on identifying effort-related brain activation. The results showed that working memory and inspection time performances were directly related. The bilateral anterior insular and anterior cingulate cortices showed significantly increased activation during each task with common portions that were active across both tasks. We observed increased brain activation in the right anterior insula and the anterior cingulate cortex in participants with low working memory performance. In line with the reported results, we suggest that activation in the anterior insular and cingulate cortices is consistent with the neural efficiency hypothesis (Neubauer).

  2. Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response

    PubMed Central

    Critchley, Hugo D.

    2010-01-01

    There is now a wealth of evidence that anterior insular and anterior cingulate cortices have a close functional relationship, such that they may be considered together as input and output regions of a functional system. This system is typically engaged across cognitive, affective, and behavioural contexts, suggesting that it is of fundamental importance for mental life. Here, we review the literature and reinforce the case that these brain regions are crucial, firstly, for the production of subjective feelings and, secondly, for co-ordinating appropriate responses to internal and external events. This model seeks to integrate higher-order cortical functions with sensory representation and autonomic control: it is argued that feeling states emerge from the raw data of sensory (including interoceptive) inputs and are integrated through representations in conscious awareness. Correspondingly, autonomic nervous system reactivity is particularly important amongst the responses that accompany conscious experiences. Potential clinical implications are also discussed. PMID:20512367

  3. 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.

  4. 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

  5. Pretreatment anterior cingulate activity predicts antidepressant treatment response in major depressive episodes.

    PubMed

    Rentzsch, Johannes; Adli, Mazda; Wiethoff, Katja; Gómez-Carrillo de Castro, Ana; Gallinat, Jürgen

    2014-04-01

    Major depressive disorder leads to substantial individual and socioeconomic costs. Despite the ongoing efforts to improve the treatment for this condition, a trial-and-error approach until an individually effective treatment is established still dominates clinical practice. Searching for clinically useful treatment response predictors is one of the most promising strategies to change this quandary therapeutic situation. This study evaluated the predictive value of a biological and a clinical predictor, as well as a combination of both. Pretreatment EEGs of 31 patients with a major depressive episode were analyzed with neuroelectric brain imaging technique to assess cerebral oscillations related to treatment response. Early improvement of symptoms served as a clinical predictor. Treatment response was assessed after 4 weeks of antidepressant treatment. Responders showed more slow-frequency power in the right anterior cingulate cortex compared to non-responders. Slow-frequency power in this region was found to predict response with good sensitivity (82 %) and specificity (100 %), while early improvement showed lower accuracy (73 % sensitivity and 65 % specificity). Combining both parameters did not further improve predictive accuracy. Pretreatment activity within the anterior cingulate cortex is related to antidepressive treatment response. Our results support the search for biological treatment response predictors using electric brain activity. This technique is advantageous due to its low individual and socioeconomic burden. The benefits of combining both, a clinically and a biologically based predictor, should be further evaluated using larger sample sizes.

  6. 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

  7. Attenuation of negative pain affect produced by unilateral spinal nerve injury in the rat following anterior cingulate cortex activation.

    PubMed

    LaBuda, C J; Fuchs, P N

    2005-01-01

    The affective and the sensory dimensions of pain processing can be differentiated in humans through the use of questionnaires and verbal communication. It is difficult to dissociate these two components of pain processing in rodents, and an understanding of the underlying mechanisms for each component is unclear. The quantification of a novel behavioral response to a repeated noxious cutaneous stimulus together with a measurement of tactile allodynia in nerve-injured rats might be used to differentially explore the sensory and affective components of pain processing in the rat. The present study utilized electrical stimulation of the anterior cingulate cortex, a structure implicated in affective pain processing but not sensory processing, in nerve-injured rats (L5 spinal nerve ligation) and found that the aversive quality of noxious cutaneous hindpaw stimulation was attenuated. There were no effects on sensory processing, because anterior cingulate cortex stimulation did not produce an anti-allodynic effect in L5 spinal nerve ligation animals. Furthermore, anterior cingulate cortex stimulation in animals with bilateral ventrolateral periaqueductal gray area lesions did not affect tactile sensitivity in L5 spinal nerve ligation rats, indicating that an endogenous pain suppression system was not likely activated by anterior cingulate cortex stimulation. However, bilateral ventrolateral periaqueductal gray area lesions in L5 spinal nerve ligation rats blocked the effect produced by anterior cingulate cortex stimulation in the place escape/avoidance paradigm. Specifically, these animals avoided noxious stimulation of the allodynic paw significantly more than anterior cingulate cortex-stimulated, sham or incomplete ventrolateral periaqueductal gray area-lesioned, L5 spinal nerve ligation animals. These findings provide the first quantified report that the activation of the anterior cingulate cortex reduced the aversive quality of repeated noxious tactile stimulation in

  8. 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…

  9. Localizing evoked cortical activity associated with balance reactions: does the anterior cingulate play a role?

    PubMed

    Marlin, Amanda; Mochizuki, George; Staines, William R; McIlroy, William E

    2014-06-15

    The ability to correct balance disturbances is essential for the maintenance of upright stability. Although information about how the central nervous system controls balance reactions in humans remains limited, recent literature highlights a potentially important role for the cerebral cortex. The objective of this study was to determine the neural source of the well-reported balance-evoked N1 response. It was hypothesized that the N1 is associated with an "error-detection" event in response to the induced perturbation and therefore may be associated with activity within the anterior cingulate cortex (ACC). The localized source of the N1 evoked by perturbations to standing balance was compared, within each participant, to the location of an error-related negativity (ERN) known to occur within the ACC while performing a flanker task. In contrast to the main hypotheses, the results revealed that the location of the N1 was not within the ACC. The mean Talairach coordinates for the ERN were (6.47, -4.41, 41.17) mm, corresponding to the cingulate gyrus [Brodmann area (BA) 24], as expected. However, coordinates for the N1 dipole were (5.74, -11.81, 53.73) mm, corresponding to the medial frontal gyrus (BA 6), specifically the supplementary motor area. This may suggest the N1 is linked to the planning and execution of elements of the evoked balance reactions rather than being associated with error or event detection. Alternatively, it is possible that the N1 is associated with variation in the cortical representation due to task-specific differences in the activation of a distributed network of error-related processing. Subsequent work should focus on disentangling these two possible explanations as they relate to the cortical processing linked to reactive balance control.

  10. Alpha Power, Alpha Asymmetry and Anterior Cingulate Cortex Activity in Depressed Males and Females

    PubMed Central

    Jaworska, Natalia; Blier, Pierre; Fusee, Wendy; Knott, Verner

    2012-01-01

    Left fronto-cortical hypoactivity, thought to reflect reduced activity in approach-related systems, and right parietal hypoactivity, associated with emotional under-arousal, have been noted in major depressive disorder (MDD). Altered theta activity in the anterior cingulate cortex (ACC) has also been associated with the disorder. We assessed resting frontal and parietal alpha asymmetry and power in non-medicated MDD (N=53; 29 females) and control (N=43; 23 females) individuals. Theta activity was examined using standardized low-resolution electromagnetic tomography (sLORETA) in the ACC [BA24ab and BA32 comprising the rostral ACC and BA25/subgenual (sg) ACC]. The MDD group, and particularly depressed males, displayed increased overall frontal and parietal alpha power and left midfrontal hypoactivity (alpha2-indexed). They also exhibited increased sgACC theta2 activity. MDD females had increased right parietal activity, suggesting increased emotive arousal. Thus, unmedicated depressed adults were characterized by lower activity in regions implicated in approach/positive affective tendencies as well as diffuse cortical hypoarousal, though sex specific modulations emerged. Altered theta in the sgACC may reflect emotion regulation abnormalities in MDD. PMID:22939462

  11. Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disorder and Prediction of Treatment Response

    PubMed Central

    Nitschke, Jack B.; Sarinopoulos, Issidoros; Oathes, Desmond J.; Johnstone, Tom; Whalen, Paul J.; Davidson, Richard J.; Kalin, Ned H.

    2009-01-01

    Objective The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Method Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Results Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. Conclusions These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder. PMID:19122007

  12. In-Group and Out-Group Membership Mediates Anterior Cingulate Activation to Social Exclusion

    PubMed Central

    Krill, Austen; Platek, Steven M.

    2009-01-01

    Functional magnetic resonance imaging was employed to examine sensitivity to social exclusion in three conditions: same-race, other-race, and self-resembling faces. The anterior cingulate cortex (ACC), specifically the dorsal ACC, has been targeted as a key substrate in the physical and social pain matrix and was hypothesized to regulate activation response to various facial conditions. We show that participants demonstrated greatest ACC activation when being excluded by self-resembling and same-race faces, relative to other-race faces. Additionally, participants expressed greater distress and showed increased ACC activation as a result of exclusion in the same-race condition relative to the other-race condition. A positive correlation between implicit racial bias and activation in the amygdala was also evident. Implicit attitude about other-race faces partly explains levels of concern about exclusion by out-group individuals. These findings suggest that individuals are more distressed and their brain (i.e. neural alarm system) responds with greater activation when being excluded by individuals whom they are more likely to share group membership with. PMID:19597546

  13. 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

    2016-01-01

    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

  14. Decreased ventral anterior cingulate cortex activity is associated with reduced social pain during emotional support.

    PubMed

    Onoda, Keiichi; Okamoto, Yasumasa; Nakashima, Ken'ichiro; Nittono, Hiroshi; Ura, Mitsuhiro; Yamawaki, Shigeto

    2009-01-01

    People feel psychological pain when they are excluded, and this pain is often attenuated when emotional support is received. It is therefore likely that a specific neural mechanism underlies the detection of social exclusion. Similarly, specific neural mechanisms may underlie the beneficial effects of emotional support. Although neuroimaging researchers have recently examined the neural basis of social pain, there is presently no agreement as to which part of the anterior cingulate cortex (ACC) is involved in the perception and modulation of social pain. We hypothesized that activity in those brain regions that are associated with social pain would be correlated with decrements in social pain induced by emotional support. To examine the effects of emotional support on social pain caused by exclusion, we conducted an fMRI study in which participants played a virtual ball-tossing game. Participants were initially included and later excluded from the game. In the latter half of the session from which participants were excluded, participants received emotionally supportive text messages. We found that emotional support led to increased activity in the left lateral/medial prefrontal cortices and some temporal regions. Those individuals who experienced greater attenuation of social pain exhibited lower ventral ACC and higher left lateral prefrontal cortex activation. These results suggest that the ventral ACC underlies social pain, and that emotional support enhances prefrontal cortex activity, which in turn may lead to a weakened affective response. PMID:19562631

  15. 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

    2016-01-01

    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.

  16. Increased anterior cingulate cortex and hippocampus activation in Complex PTSD during encoding of negative words.

    PubMed

    Thomaes, Kathleen; Dorrepaal, Ethy; Draijer, Nel; de Ruiter, Michiel B; Elzinga, Bernet M; Sjoerds, Zsuzsika; van Balkom, Anton J; Smit, Johannes H; Veltman, Dick J

    2013-02-01

    Post-traumatic stress disorder (PTSD) is associated with impaired memory performance coupled with functional changes in brain areas involved in declarative memory and emotion regulation. It is not yet clear how symptom severity and comorbidity affect neurocognitive functioning in PTSD. We performed a functional magnetic resonance imaging (fMRI) study with an emotional declarative memory task in 28 Complex PTSD patients with comorbid depressive and personality disorders, and 21 healthy non-trauma-exposed controls. In Complex PTSD patients--compared to controls--encoding of later remembered negative words vs baseline was associated with increased blood oxygenation level dependent (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend for increased left hippocampus activation. Patients tended to commit more False Alarms to negative words compared to controls, which was associated with enhanced left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses. Severity of child abuse was positively correlated with left ventral ACC activity and severity of depression with (para) hippocampal and ventral ACC activity. Presented results demonstrate functional abnormalities in Complex PTSD in the frontolimbic brain circuit also implicated in fear conditioning models, but generally in the opposite direction, which may be explained by severity of the trauma and severity of comorbid depression in Complex PTSD.

  17. 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

  18. Temporal and spatial dynamics of thalamus-evoked activity in the anterior cingulate cortex.

    PubMed

    Chang, Wei-Chih; Lee, Chia-Ming; Shyu, Bai-Chuang

    2012-10-11

    In the present study, multielectrode array (MEA) recording was used to illustrate the spatial-temporal progression of anterior cingulate cortex (ACC) activity following stimulation of the thalamus in a thalamocingulate pathway-preserved slice. The MEA was placed under the slice that contained the ACC, and 60 channels of extracellular local field potentials evoked by bipolar electrical stimulation within the thalamus were analyzed. Several distinct thalamic-evoked responses were identified. The early negative component (N1; amplitude, -35.7 ± 5.9 μV) emerged in layer VI near the cingulum 8.4 ± 0.5 ms after stimulation. N1 progressed upward to layers V and II/III in a lateral-to-medial direction. Subsequently, a positive component (P; amplitude, 27.0 ± 3.2 μV) appeared 12.0 ± 0.6 ms after stimulation in layer VI. At 26.8 ± 1.1 ms, a second negative component (N2; amplitude, -20.9 ± 2.7 μV) became apparent in layers II/III and V, followed by a more ventrolateral component (N3; amplitude, -18.9 ± 2.9 μV) at 42.8 ± 2.6 ms. These two late components spread downward to layer VI in a medial-to-lateral direction. The trajectory paths of the evoked components were consistently represented with varied medial thalamic stimulation intensities and sites. Both AMPA/kainate and N-methyl-D-aspartate-type glutamate receptors involved in monosynaptic and polysynaptic transmission participated in this thalamocortical pathway. Morphine mainly diminished the two negative synaptic components, and this suppressive effect was reversed by naloxone. The present study confirmed that functional thalamocingulate activity was preserved in the brain-slice preparation. The thalamus-evoked responses were activated and progressed along a deep surface-deep trajectory loop across the ACC layers. Glutamatergic neurotransmitters were crucially involved in information processing. Opioid interneurons may play a modulatory role in regulating the signal flows in the cingulate cortex.

  19. Anterior cingulate activity to monetary loss and basal ganglia activity to monetary gain uniquely contribute to the feedback negativity

    PubMed Central

    Foti, Dan; Weinberg, Anna; Bernat, Edward M.; Proudfit, Greg H.

    2014-01-01

    Objective The feedback negativity (FN) is an event-related potential that differentiates unfavorable versus favorable outcomes. Although thought to reflect error-related activity within the anterior cingulate cortex, recent work indicates the FN may also reflect reward-related activity that has been linked to the basal ganglia. To date, it remains unclear how to reconcile these conflicting perspectives. Methods We decomposed the FN by applying time-frequency analysis to isolate activity unique to monetary losses and gains. The FN was recorded from 84 individuals during a laboratory gambling task. Results Two signals contributed to the FN elicited by unpredictable outcomes: theta activity (4-7 Hz) was increased following monetary loss, and delta activity (< 3 Hz) was increased following monetary gain. Predictable outcomes elicited delta but not theta activity. Source analysis revealed distinct generators, with loss-related theta localized to the anterior cingulate cortex and gain-related delta to a possible source in the striatum. Symptoms of depression, anxiety, and stress reactivity were specifically associated with blunted gain-related delta. Conclusions The FN may be a composite of loss- and gain-related neural activity, reflecting distinct facets of reward processing. Significance Gain-related delta activity may provide unique information about reward dysfunction in major depression and other internalizing psychopathology. PMID:25454338

  20. 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

  1. 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.

  2. Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain.

    PubMed

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

    2015-05-01

    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.

  3. Glutamatergic activation of anterior cingulate cortex mediates the affective component of visceral pain memory in rats.

    PubMed

    Yan, Ni; Cao, Bing; Xu, Jiahe; Hao, Chun; Zhang, Xu; Li, Ying

    2012-01-01

    Studies of both humans and animals suggest that anterior cingulate cortex (ACC) is important for processing pain perception. We identified that perigenul ACC (pACC) sensitization and enhanced visceral pain in a visceral hypersensitive rat in previous studies. Pain contains both sensory and affective dimensions. Teasing apart the mechanisms that control the neural pathways mediating pain affect and sensation in nociceptive behavioral response is a challenge. In this study, using a rodent visceral pain assay that combines the colorectal distension (CRD)-induced visceromotor response (VMR) with the conditioning place avoidance (CPA), we measured a learned behavior that directly reflects the affective component of visceral pain. When CRD was paired with a distinct environment context, the rats spent significantly less time in this compartment on the post-conditioning test days as compared with the pre-conditioning day. Effects were lasted for 14 days. Bilateral pACC lesion significantly reduced CPA scores without reducing acute visceral pain behaviors (CRD-induced VMR). Bilateral administration of non-NMDA receptor antagonist CNQX or NMDA receptor antagonist AP5 into the pACC decreased the CPA scores. AP5 or CNQX at dose of 400 mM produced about 70% inhibition of CRD-CPA in the day 1, 4 and 7, and completely abolished the CPA in the day 14 after conditioning. We concluded that neurons in the pACC are necessary for the "aversiveness" of visceral nociceptor stimulation. pACC activation is critical for the memory processing involved in long-term negative affective state and prediction of aversive stimuli by contextual cue.

  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. Medial profrontal cortex and anterior cingulate cortex in the generation of alpha activity induced by transcendental meditation: a magnetoencephalographic study.

    PubMed

    Yamamoto, Shin; Kitamura, Yoshihiro; Yamada, Norihito; Nakashima, Yoshihiko; Kuroda, Shigetoshi

    2006-02-01

    Previous EEG studies have shown that transcendental meditation (TM) increases frontal and central alpha activity. The present study was aimed at identifying the source of this alpha activity using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously on eight TM practitioners before, during, and after TM. The magnetic field potentials corresponding to TM-induced alpha activities on EEG recordings were extracted, and we attempted to localize the dipole sources using the multiple signal classification (MUSIC) algorithm, equivalent current dipole source analysis, and the multiple spatio-temporal dipole model. Since the dipoles were mapped to both the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), it is suggested that the mPFC and ACC play an important role in brain activity induced by TM.

  6. Short- and long-term changes in anterior cingulate activation during resolution of task-set competition.

    PubMed

    Woodward, Todd S; Ruff, Christian C; Ngan, Elton T C

    2006-01-12

    Alternating between task sets involves detection that the current task set is unfavorable, initiation of a change in set, and application of the new task set while fine-tuning to optimally adjust to the demands of the environment. Functional magnetic resonance imaging (fMRI) studies of cognitive flexibility consistently report activation of the anterior cingulate cortex and/or adjacent pre-supplementary motor regions (ACC/pre-SMA, medial Brodmann's areas 24/32/6), suggesting that these cortical regions are involved in switching task set. In the current study, our objective was to probe whether ACC/pre-SMA activation would decrease for a number of trials following a switch in task set, implying longer-term involvement in fine-tuning adjustments. By measuring activation when switching between word reading and color naming in response to Stroop stimuli, ACC/pre-SMA activation was observed when actively countering the influence of the irrelevant task set, and this activation decreased as a function of the number of trials since a task switch. Basal ganglia and thalamic regions also displayed a decreased response over successive trials after task switches. These findings suggest that the ACC/pre-SMA are not only involved in generating a new course of action, but are also involved (along with subcortical regions) in fine-tuning operations that resolve competition between task sets over subsequent repetitions of the same task. PMID:16376861

  7. Activation of the caudal anterior cingulate cortex due to task-related interference in an auditory Stroop paradigm.

    PubMed

    Haupt, Sven; Axmacher, Nikolai; Cohen, Michael X; Elger, Christian E; Fell, Juergen

    2009-09-01

    Successful information processing requires the focusing of attention on a certain stimulus property and the simultaneous suppression of irrelevant information. The Stroop task is a useful paradigm to study such attentional top-down control in the presence of interference. Here, we investigated the neural correlates of an auditory Stroop task using fMRI. Subjects focused either on tone pitch (relatively high or low; phonetic task) or on the meaning of a spoken word (high/low/good; semantic task), while ignoring the other stimulus feature. We differentiated between task-related (phonetic incongruent vs. semantic incongruent) and sensory-level interference (phonetic incongruent vs. phonetic congruent). Task-related interference activated similar regions as in visual Stroop tasks, including the anterior cingulate cortex (ACC) and the presupplementary motor-area (pre-SMA). More specifically, we observed that the very caudal/posterior part of the ACC was activated and not the dorsal/anterior region. Because identical stimuli but different task demands are compared in this contrast, it reflects conflict at a relatively high processing level. A more conventional contrast between incongruent and congruent phonetic trials was associated with a different cluster in the pre-SMA/ACC which was observed in a large number of previous studies. Finally, functional connectivity analysis revealed that activity within the regions activated in the phonetic incongruent vs. semantic incongruent contrast was more strongly interrelated during semantically vs. phonetically incongruent trials. Taken together, we found (besides activation of regions well-known from visual Stroop tasks) activation of the very caudal and posterior part of the ACC due to task-related interference in an auditory Stroop task. PMID:19180558

  8. Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate.

    PubMed

    Zanchi, Davide; Brody, Arthur L; Montandon, Marie-Louise; Kopel, Rotem; Emmert, Kirsten; Preti, Maria Giulia; Van De Ville, Dimitri; Haller, Sven

    2015-11-01

    Although many smokers try to quit smoking, only about 20-25 percent will achieve abstinence despite 6 months or more of gold-standard treatment. This low success rate suggests long-term changes in the brain related to smoking, which remain poorly understood. We compared ex-smokers to both active smokers and non-smokers using functional magnetic resonance imaging (fMRI) to explore persistent modifications in brain activity and network organization. This prospective and consecutive study includes 18 non-smokers (29.5 ± 6.7 years of age, 11 women), 14 smokers (≥10 cigarettes a day >2 years of smoking, 29.3 ± 6.0 years of age, 10 women) and 14 ex-smokers (>1 year of quitting 30.5 ± 5.7 years of age, 10 women). Participants underwent a block-design fMRI study contrasting smoking cue with control (neutral cue) videos. Data analyses included task-related general linear model, seed-based functional connectivity, voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics (TBSS) of white matter. Smoking cue videos versus control videos activated the right anterior insula in ex-smokers compared with smokers, an effect correlating with cumulative nicotine intake (pack-years). Moreover, ex-smokers had a persistent decrease in functional connectivity between right anterior insula and anterior cingulate cortex (ACC) compared with control participants, but similar to active smokers. Potentially confounding alterations in gray or white matter were excluded in VBM and TBSS analyses. In summary, ex-smokers with long-term nicotine abstinence have persistent and dose-dependent brain network changes notably in the right anterior insula and its connection to the ACC.

  9. 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

  10. 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.

  11. 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

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

    PubMed

    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.

  13. 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.

  14. 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

  15. 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

  16. Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex.

    PubMed

    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.

  17. 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

  18. 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

  19. Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making.

    PubMed

    Khani, Abbas; Kermani, Mojtaba; Hesam, Soghra; Haghparast, Abbas; Argandoña, Enrike G; Rainer, Gregor

    2015-06-01

    Despite the evidence for altered decision making in cannabis abusers, the role of the cannabinoid system in decision-making circuits has not been studied. Here, we examined the effects of cannabinoid modulation during cost-benefit decision making in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), key brain areas involved in decision making. We trained different groups of rats in a delay-based and an effort-based form of cost-benefit T-maze decision-making task. During test days, the rats received local injections of either vehicle or ACEA, a cannabinoid type-1 receptor (CB1R) agonist in the ACC or OFC. We measured spontaneous locomotor activity following the same treatments and characterized CB1Rs localization on different neuronal populations within these regions using immunohistochemistry. We showed that CB1R activation in the ACC impaired decision making such that rats were less willing to invest physical effort to gain high reward. Similarly, CB1R activation in the OFC induced impulsive pattern of choice such that rats preferred small immediate rewards to large delayed rewards. Control tasks ensured that the effects were specific for differential cost-benefit tasks. Furthermore, we characterized widespread colocalizations of CB1Rs on GABAergic axonal ends but few colocalizations on glutamatergic, dopaminergic, and serotonergic neuronal ends. These results provide first direct evidence that the cannabinoid system plays a critical role in regulating cost-benefit decision making in the ACC and OFC and implicate cannabinoid modulation of synaptic ends of predominantly interneurons and to a lesser degree other neuronal populations in these two frontal regions.

  20. 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…

  1. 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

  2. Expectations, gains, and losses in the anterior cingulate cortex

    PubMed Central

    Sallet, Jérôme; Quilodran, René; Rothé, Marie; Vezoli, Julien; Joseph, Jean-Paul; Procyk, Emmanuel

    2007-01-01

    The anterior cingulate cortex (ACC) participates in evaluating actions and outcomes. Little is known on how action/reward values are processed in ACC and if the context in which actions are performed influences this processing. Here we report ACC unit activity of monkeys performing two tasks. The first tested whether the encoding of reward values is context-dependant i.e. dependant on the size of the other rewards available in the current block of trials. The second task tested whether unexpected events signaling a change in reward are represented. We show that the context created by a block design (i.e. the context of possible alternative rewards) influences the encoding of reward values, even if no decision or choice is required. ACC activity encodes the relative and not absolute expected reward values. Moreover, cingulate activity signals and evaluates when reward expectations are violated by unexpected stimuli indicating reward gains or losses. PMID:18189006

  3. 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.

  4. 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

  5. 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.

  6. 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…

  7. Motivation of extended behaviors by anterior cingulate cortex.

    PubMed

    Holroyd, Clay B; Yeung, Nick

    2012-02-01

    Intense research interest over the past decade has yielded diverse and often discrepant theories about the function of anterior cingulate cortex (ACC). In particular, a dichotomy has emerged between neuropsychological theories suggesting a primary role for ACC in motivating or 'energizing' behavior, and neuroimaging-inspired theories emphasizing its contribution to cognitive control and reinforcement learning. To reconcile these views, we propose that ACC supports the selection and maintenance of 'options' - extended, context-specific sequences of behavior directed toward particular goals - that are learned through a process of hierarchical reinforcement learning. This theory accounts for ACC activity in relation to learning and control while simultaneously explaining the effects of ACC damage as disrupting the motivational context supporting the production of goal-directed action sequences.

  8. 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…

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

    PubMed Central

    García-Cabezas, Miguel Á.; Barbas, Helen

    2016-01-01

    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

  10. 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

  11. 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

  12. Attention for learning signals in anterior cingulate cortex.

    PubMed

    Bryden, Daniel W; Johnson, Emily E; Tobia, Steven C; Kashtelyan, Vadim; Roesch, Matthew R

    2011-12-14

    Learning theory suggests that animals attend to pertinent environmental cues when reward contingencies unexpectedly change so that learning can occur. We have previously shown that activity in basolateral nucleus of amygdala (ABL) responds to unexpected changes in reward value, consistent with unsigned prediction error signals theorized by Pearce and Hall. However, changes in activity were present only at the time of unexpected reward delivery, not during the time when the animal needed to attend to conditioned stimuli that would come to predict the reward. This suggested that a different brain area must be signaling the need for attention necessary for learning. One likely candidate to fulfill this role is the anterior cingulate cortex (ACC). To test this hypothesis, we recorded from single neurons in ACC as rats performed the same behavioral task that we have used to dissociate signed from unsigned prediction errors in dopamine and ABL neurons. In this task, rats chose between two fluid wells that produced varying magnitudes of and delays to reward. Consistent with previous work, we found that ACC detected errors of commission and reward prediction errors. We also found that activity during cue sampling encoded reward size, but not expected delay to reward. Finally, activity in ACC was elevated during trials in which attention was increased following unexpected upshifts and downshifts in value. We conclude that ACC not only signals errors in reward prediction, as previously reported, but also signals the need for enhanced neural resources during learning on trials subsequent to those errors.

  13. Attention for learning signals in anterior cingulate cortex.

    PubMed

    Bryden, Daniel W; Johnson, Emily E; Tobia, Steven C; Kashtelyan, Vadim; Roesch, Matthew R

    2011-12-14

    Learning theory suggests that animals attend to pertinent environmental cues when reward contingencies unexpectedly change so that learning can occur. We have previously shown that activity in basolateral nucleus of amygdala (ABL) responds to unexpected changes in reward value, consistent with unsigned prediction error signals theorized by Pearce and Hall. However, changes in activity were present only at the time of unexpected reward delivery, not during the time when the animal needed to attend to conditioned stimuli that would come to predict the reward. This suggested that a different brain area must be signaling the need for attention necessary for learning. One likely candidate to fulfill this role is the anterior cingulate cortex (ACC). To test this hypothesis, we recorded from single neurons in ACC as rats performed the same behavioral task that we have used to dissociate signed from unsigned prediction errors in dopamine and ABL neurons. In this task, rats chose between two fluid wells that produced varying magnitudes of and delays to reward. Consistent with previous work, we found that ACC detected errors of commission and reward prediction errors. We also found that activity during cue sampling encoded reward size, but not expected delay to reward. Finally, activity in ACC was elevated during trials in which attention was increased following unexpected upshifts and downshifts in value. We conclude that ACC not only signals errors in reward prediction, as previously reported, but also signals the need for enhanced neural resources during learning on trials subsequent to those errors. PMID:22171031

  14. Pleasant human touch is represented in pregenual anterior cingulate cortex.

    PubMed

    Lindgren, Lenita; Westling, Göran; Brulin, Christine; Lehtipalo, Stefan; Andersson, Micael; Nyberg, Lars

    2012-02-15

    Touch massage (TM) is a form of pleasant touch stimulation used as treatment in clinical settings and found to improve well-being and decrease anxiety, stress, and pain. Emotional responses reported during and after TM have been studied, but the underlying mechanisms are still largely unexplored. In this study, we used functional magnetic resonance (fMRI) to test the hypothesis that the combination of human touch (i.e. skin-to-skin contact) with movement is eliciting a specific response in brain areas coding for pleasant sensations. The design included four different touch conditions; human touch with or without movement and rubber glove with or without movement. Force (2.5 N) and velocity (1.5 cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale) and human touch was rated as most pleasant, particularly in combination with movement. The fMRI results revealed that TM stimulation most strongly activated the pregenual anterior cingulate cortex (pgACC). These results are consistent with findings showing pgACC activation during various rewarding pleasant stimulations. This area is also known to be activated by both opioid analgesia and placebo. Together with these prior results, our finding furthers the understanding of the basis for positive TM treatment effects.

  15. 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.

  16. 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

  17. Volitional reduction of anterior cingulate cortex activity produces decreased cue craving in smoking cessation: a preliminary real-time fMRI study.

    PubMed

    Li, Xingbao; Hartwell, Karen J; Borckardt, Jeffery; Prisciandaro, James J; Saladin, Michael E; Morgan, Paul S; Johnson, Kevin A; Lematty, Todd; Brady, Kathleen T; George, Mark S

    2013-07-01

    Numerous research groups are now using analysis of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in 'real time'. In this study, we explored the feasibility of self-regulation of frontal cortical activation using real-time fMRI (rtfMRI) neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a 'reduce craving' paradigm, participants were instructed to 'reduce' their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate 'increase resistance' paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the 'reduce craving' task (P=0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the 'reduce craving' session (P=0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the 'increase resistance' session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue-induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence.

  18. Volitional Reduction of Anterior Cingulate Cortex Activity Produces Decreased Cue Craving in Smoking Cessation: A Preliminary Real-Time fMRI Study

    PubMed Central

    Li, Xingbao; Hartwell, Karen J.; Borckardt, Jeffery; Prisciandaro, James J.; Saladin, Michael E.; Morgan, Paul S.; Johnson, Kevin A.; LeMatty, Todd; Brady, Kathleen T.; George, Mark S.

    2012-01-01

    Numerous research groups are now using analysis of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in “real time”. In this study, we explored the feasibility of self-regulation of frontal cortical activation using real time fMRI (rtfMRI) neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a “reduce craving” paradigm, participants were instructed to “reduce” their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate “increase resistance” paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the “reduce craving” task (p=0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the “reduce craving” session (p=0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the “increase resistance” session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue-induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence. PMID:22458676

  19. 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

  20. 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

  1. 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

  2. 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

  3. Greater anterior cingulate activation and connectivity in response to visual and auditory high-calorie food cues in binge eating: Preliminary findings.

    PubMed

    Geliebter, Allan; Benson, Leora; Pantazatos, Spiro P; Hirsch, Joy; Carnell, Susan

    2016-01-01

    Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups. To examine neural responses to food cues in BE, 10 women with BE and 10 women without BE (non-BE) who were matched for obesity (5 obese and 5 lean in each group) underwent fMRI scanning during presentation of visual (picture) and auditory (spoken word) cues representing high energy density (ED) foods, low-ED foods, and non-foods. We then compared regional brain activation in BE vs. non-BE groups for high-ED vs. low-ED foods. To explore differences in functional connectivity, we also compared psychophysiologic interactions [PPI] with dorsal anterior cingulate cortex [dACC] for BE vs. non-BE groups. Region of interest (ROI) analyses revealed that the BE group showed more activation than the non-BE group in the dACC, with no activation differences in the striatum or orbitofrontal cortex [OFC]. Exploratory PPI analyses revealed a trend towards greater functional connectivity with dACC in the insula, cerebellum, and supramarginal gyrus in the BE vs. non-BE group. Our results suggest that women with BE show hyper-responsivity in the dACC as well as increased coupling with other brain regions when presented with high-ED cues. These differences are independent of body weight, and appear to be associated with the BE phenotype. PMID:26275334

  4. 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

  5. Voluntary modulation of anterior cingulate response to negative feedback.

    PubMed

    Shane, Matthew S; Weywadt, Christina R

    2014-01-01

    Anterior cingulate and medial frontal cortex (dACC/mFC) response to negative feedback represents the actions of a generalized error-monitoring system critical for the management of goal-directed behavior. Magnitude of dACC/mFC response to negative feedback correlates with levels of post-feedback behavioral change, and with proficiency of operant learning processes. With this in mind, it follows that an ability to alter dACC/mFC response to negative feedback may lead to representative changes in operant learning proficiency. To this end, the present study investigated the extent to which healthy individuals would show modulation of their dACC/mFC response when instructed to try to either maximize or minimize their neural response to the presentation of contingent negative feedback. Participants performed multiple runs of a standard time-estimation task, during which they received feedback regarding their ability to accurately estimate a one-second duration. On Watch runs, participants were simply instructed to try to estimate as closely as possible the one second duration. On Increase and Decrease runs, participants performed the same task, but were instructed to "try to increase [decrease] their brain's response every time they received negative feedback". Results indicated that participants showed changes in dACC/mFC response under these differing instructional conditions: dACC/mFC activity following negative feedback was higher in the Increase condition, and dACC activity trended lower in the Decrease condition, compared to the Watch condition. Moreover, dACC activity correlated with post-feedback performance adjustments, and these adjustments were highest in the Increase condition. Potential implications for neuromodulation and facilitated learning are discussed. PMID:25376010

  6. Learned predictions of error likelihood in the anterior cingulate cortex.

    PubMed

    Brown, Joshua W; Braver, Todd S

    2005-02-18

    The anterior cingulate cortex (ACC) and the related medial wall play a critical role in recruiting cognitive control. Although ACC exhibits selective error and conflict responses, it has been unclear how these develop and become context-specific. With use of a modified stop-signal task, we show from integrated computational neural modeling and neuroimaging studies that ACC learns to predict error likelihood in a given context, even for trials in which there is no error or response conflict. These results support a more general error-likelihood theory of ACC function based on reinforcement learning, of which conflict and error detection are special cases.

  7. Attention and sentence processing deficits in Parkinson's disease: the role of anterior cingulate cortex.

    PubMed

    Grossman, M; Crino, P; Reivich, M; Stern, M B; Hurtig, H I

    1992-01-01

    Parkinson's disease (PD) is a complex neurodegenerative condition involving a motor disorder that is related to reduced dopaminergic input to the striatum. Intellectual deficits are also seen in PD, but the pathophysiology of these difficulties is poorly understood. Regional cerebral blood flow (rCBF) was studied in neurologically intact subjects during the performance of attention-demanding, sentence processing tasks using positron emission tomography (PET). The results demonstrated significantly increased rCBF in a distributed set of cerebral regions during the detection of an adjective or a particular agent in a sentence, including anterior cingulate cortex, left inferior and middle frontal cortex, left inferior temporo-occipital cortex, posterolateral temporal cortex, left caudate, and left thalamus. We identified defects in this cerebral network by studying PD patients with two PET techniques. Resting PET studies revealed a significant correlation between regional cerebral glucose metabolism in anterior cingulate cortex and deficits in attending to subtle grammatical aspects of sentences. Studies of PD patients with the PET activation technique revealed little change in anterior cingulate and left frontal CBF during performance of the adjective detection or agent detection tasks. These data suggest that a defect in anterior cingulate cortex contributes to the cognitive impairments observed in PD.

  8. Neurofeedback of the difference in activation of the anterior cingulate cortex and posterior insular cortex: two functionally connected areas in the processing of pain.

    PubMed

    Rance, Mariela; Ruttorf, Michaela; Nees, Frauke; Schad, Lothar R; Flor, Herta

    2014-01-01

    The aim of this study was the analysis of the effect of a learned increase in the dissociation between the rostral anterior cingulate cortex (rACC) and the left posterior insula (pInsL) on pain intensity and unpleasantness and the contribution of each region to the effect, exploring the possibility to influence the perception of pain with neurofeedback methods. We trained ten healthy subjects to increase the difference in the blood oxygenation level-dependent response between the rACC and pInsL to painful electric stimuli. Subjects learned to increase the dissociation with either the rACC (state 1) or the pInsL (state 2) being higher. For feedback we subtracted the signal of one region from the other and provided feedback in four conditions with six trials each yielding two different states: [rACC-pInsL increase (state 1), rACC-pInsL decrease (state 2), pInsL-rACC increase (state 2), pInsL-rACC decrease (state 1)]. Significant changes in the dissociation from trial one to six were seen in all conditions. There were significant changes from trial one to six in the pInsL in three of the four conditions, the rACC showed no significant change. Pain intensity or unpleasantness ratings were unrelated to the dissociation between the regions and the activation in each region. Learning success in the conditions did not significantly correlate and there was no significant correlation between the two respective conditions of one state, i.e., learning to achieve a specific state is not a stable ability. The pInsL seems to be the driving force behind changes in the learned dissociation between the regions. Despite successful differential modulation of activation in areas responsive to the painful stimulus, no corresponding changes in the perception of pain intensity or unpleasantness emerged. Learning to induce different states of dissociation between the areas is not a stable ability since success did not correlate overall or between two conditions of the the same state. PMID

  9. 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

  10. Value, search, persistence and model updating in anterior cingulate cortex.

    PubMed

    Kolling, Nils; Wittmann, Marco K; Behrens, Tim E J; Boorman, Erie D; Mars, Rogier B; Rushworth, Matthew F S

    2016-09-27

    Dorsal anterior cingulate cortex (dACC) carries a wealth of value-related information necessary for regulating behavioral flexibility and persistence. It signals error and reward events informing decisions about switching or staying with current behavior. During decision-making, it encodes the average value of exploring alternative choices (search value), even after controlling for response selection difficulty, and during learning, it encodes the degree to which internal models of the environment and current task must be updated. dACC value signals are derived in part from the history of recent reward integrated simultaneously over multiple time scales, thereby enabling comparison of experience over the recent and extended past. Such ACC signals may instigate attentionally demanding and difficult processes such as behavioral change via interactions with prefrontal cortex. However, the signal in dACC that instigates behavioral change need not itself be a conflict or difficulty signal.

  11. Neural encoding of competitive effort in the anterior cingulate cortex.

    PubMed

    Hillman, Kristin L; Bilkey, David K

    2012-09-01

    In social environments, animals often compete to obtain limited resources. Strategically electing to work against another animal represents a cost-benefit decision. Is the resource worth an investment of competitive effort? The anterior cingulate cortex (ACC) has been implicated in cost-benefit decision-making, but its role in competitive effort has not been examined. We recorded ACC neurons in freely moving rats as they performed a competitive foraging choice task. When at least one of the two choice options demanded competitive effort, the majority of ACC neurons exhibited heightened and differential firing between the goal trajectories. Inter- and intrasession manipulations revealed that differential firing was not attributable to effort or reward in isolation; instead ACC encoding patterns appeared to indicate net utility assessments of available choice options. Our findings suggest that the ACC is important for encoding competitive effort, a cost-benefit domain that has received little neural-level investigation despite its predominance in nature.

  12. Value, search, persistence and model updating in anterior cingulate cortex.

    PubMed

    Kolling, Nils; Wittmann, Marco K; Behrens, Tim E J; Boorman, Erie D; Mars, Rogier B; Rushworth, Matthew F S

    2016-09-27

    Dorsal anterior cingulate cortex (dACC) carries a wealth of value-related information necessary for regulating behavioral flexibility and persistence. It signals error and reward events informing decisions about switching or staying with current behavior. During decision-making, it encodes the average value of exploring alternative choices (search value), even after controlling for response selection difficulty, and during learning, it encodes the degree to which internal models of the environment and current task must be updated. dACC value signals are derived in part from the history of recent reward integrated simultaneously over multiple time scales, thereby enabling comparison of experience over the recent and extended past. Such ACC signals may instigate attentionally demanding and difficult processes such as behavioral change via interactions with prefrontal cortex. However, the signal in dACC that instigates behavioral change need not itself be a conflict or difficulty signal. PMID:27669988

  13. 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

  14. 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

  15. Dorsal anterior cingulate cortex and the value of control.

    PubMed

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

    2016-09-27

    Debates over the function(s) of dorsal anterior cingulate cortex (dACC) have persisted for decades. So too have demonstrations of the region's association with cognitive control. Researchers have struggled to account for this association and, simultaneously, dACC's involvement in phenomena related to evaluation and motivation. We describe a recent integrative theory that achieves this goal. It proposes that dACC serves to specify the currently optimal allocation of control by determining the overall expected value of control (EVC), thereby licensing the associated cognitive effort. The EVC theory accounts for dACC's sensitivity to a wide array of experimental variables, and their relationship to subsequent control adjustments. Finally, we contrast our theory with a recent theory proposing a primary role for dACC in foraging-like decisions. We describe why the EVC theory offers a more comprehensive and coherent account of dACC function, including dACC's particular involvement in decisions regarding foraging or otherwise altering one's behavior.

  16. Dorsal anterior cingulate cortex and the value of control.

    PubMed

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

    2016-09-27

    Debates over the function(s) of dorsal anterior cingulate cortex (dACC) have persisted for decades. So too have demonstrations of the region's association with cognitive control. Researchers have struggled to account for this association and, simultaneously, dACC's involvement in phenomena related to evaluation and motivation. We describe a recent integrative theory that achieves this goal. It proposes that dACC serves to specify the currently optimal allocation of control by determining the overall expected value of control (EVC), thereby licensing the associated cognitive effort. The EVC theory accounts for dACC's sensitivity to a wide array of experimental variables, and their relationship to subsequent control adjustments. Finally, we contrast our theory with a recent theory proposing a primary role for dACC in foraging-like decisions. We describe why the EVC theory offers a more comprehensive and coherent account of dACC function, including dACC's particular involvement in decisions regarding foraging or otherwise altering one's behavior. PMID:27669989

  17. Reduced Somatostatin in Subgenual Anterior Cingulate Cortex in Major Depression

    PubMed Central

    Tripp, Adam; Kota, Rama S.; Lewis, David A.; Sibille, Etienne

    2011-01-01

    Converging evidence suggests a central role for dysfunction of the subgenual anterior cingulate cortex (sgACC) in the pathophysiology of major depressive disorder (MDD). Underlying mechanisms may include altered GABAergic function. Expression of somatostatin (SST), an inhibitory neuropeptide localized to a subset of GABA neurons, has been shown to be lower in the dorsolateral prefrontal cortex of male MDD subjects. Here, to investigate whether alterations in SST may contribute to sgACC dysfunction in MDD, and whether the alterations display sex-specificity, we measured sgACC SST at the mRNA and precursor peptide levels in a large cohort of subjects with MDD. SST mRNA levels were analyzed by quantitative PCR (qPCR) in the postmortem sgACC from male (n=26) and female (n=25) subjects with MDD and sex-matched subjects with no psychiatric diagnosis (n=51). Prepro-SST protein levels were assessed in a subset of subjects (n=42 pairs) by semi-quantitative western blot. The mRNA expression of SST was significantly reduced by 38% in female subjects and by 27% in male subjects with MDD. The characteristic age-related decline in SST expression was observed in control (Pearson R=−0.357, p=0.005) but not MDD (R=−0.104, p=0.234) subjects, as low expression was detected across ages in MDD subjects. Protein expression was similarly reduced by 19% in both MDD groups, and findings were more robust in female (p=0.0056) than in males (p=0.0373) compared to respective controls. In conclusion, low SST represents a robust pathological finding in MDD. Specifically, alterations in SST signaling and/or SST-bearing GABA neurons may represent a critical pathophysiological entity that contributes to sgACC dysfunction and that matches the high female vulnerability to develop MDD. PMID:21232602

  18. 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

  19. Reduced Activation in Lateral Prefrontal Cortex and Anterior Cingulate during Attention and Cognitive Control Functions in Medication-Naive Adolescents with Depression Compared to Controls

    ERIC Educational Resources Information Center

    Halari, Rozmin; Simic, Mima; Pariante, Carmine M.; Papadopoulos, Andrew; Cleare, Anthony; Brammer, Michael; Fombonne, Eric; Rubia, Katya

    2009-01-01

    Background: There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of…

  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. The role of the anterior cingulate cortex in pitch variation during sad affect.

    PubMed

    Barrett, Jennifer; Pike, G Bruce; Paus, Tomás

    2004-01-01

    We examined neural activity, in the frontal lobes, associated with speech production during affective states. Using functional magnetic resonance imaging (fMRI), the blood oxygen level-dependent (BOLD) response to the overt reading of emotionally neutral sentences was measured before and after a happy or sad mood induction. There was no explicit demand to produce affect-congruent speech and a cover story was used to de-emphasize the significance of the speech task in light of our experimental aims. Each fMRI measurement was acquired 6 s after the onset of sentence presentation so that speech could be recorded while the scanner noise was minimal; speech parameters (e.g. pitch variation) were extracted from the sentences and regressed against fMRI data. In the sad group we found the predicted changes in affect and pitch variation. Further, the fMRI data confirmed our hypothesis in that the 'reading effect' (i.e. the BOLD response to reading minus the BOLD response to baseline stimuli) in the supracallosal anterior cingulate cortex covaried negatively with both pitch variation and affect. Our results suggest that the anterior cingulate cortex modulates paralinguistic features of speech during affective states, thus placing this neural structure at the interface between action and emotions. PMID:14725640

  2. 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

  3. 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

  4. Theta-gamma coordination between anterior cingulate and prefrontal cortex indexes correct attention shifts.

    PubMed

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

    2015-07-01

    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.

  5. Differential engagement of anterior cingulate and adjacent medial frontal cortex in adept meditators and non-meditators.

    PubMed

    Hölzel, Britta K; Ott, Ulrich; Hempel, Hannes; Hackl, Andrea; Wolf, Katharina; Stark, Rudolf; Vaitl, Dieter

    2007-06-21

    This study investigated differences in brain activation during meditation between meditators and non-meditators. Fifteen Vipassana meditators (mean practice: 7.9 years, 2h daily) and fifteen non-meditators, matched for sex, age, education, and handedness, participated in a block-design fMRI study that included mindfulness of breathing and mental arithmetic conditions. For the meditation condition (contrasted to arithmetic), meditators showed stronger activations in the rostral anterior cingulate cortex and the dorsal medial prefrontal cortex bilaterally, compared to controls. Greater rostral anterior cingulate cortex activation in meditators may reflect stronger processing of distracting events. The increased activation in the medial prefrontal cortex may reflect that meditators are stronger engaged in emotional processing.

  6. Trace but not delay fear conditioning requires attention and the anterior cingulate cortex.

    PubMed

    Han, C J; O'Tuathaigh, Colm M; van Trigt, Laurent; Quinn, Jennifer J; Fanselow, Michael S; Mongeau, Raymond; Koch, Christof; Anderson, David J

    2003-10-28

    Higher cognitive functions such as attention have been difficult to model in genetically tractable organisms. In humans, attention-distracting stimuli interfere with trace but not delay conditioning, two forms of associative learning. Attention has also been correlated with activation of anterior cingulate cortex (ACC), but its functional significance is unclear. Here we show that a visual distractor interferes selectively with trace but not delay auditory fear conditioning in mice. Trace conditioning is associated with increased neuronal activity in ACC, as assayed by relative levels of c-fos expression, and is selectively impaired by lesions of this structure. The effects of the ACC lesions are unlikely to be caused by indirect impairment of the hippocampus, which is required for mnemonic aspects of trace conditioning. These data suggest that trace conditioning may be useful for studying neural substrates of attention in mice, and implicate the ACC as one such substrate. PMID:14555761

  7. Involvement of the anterior cingulate and frontoinsular cortices in rapid processing of salient facial emotional information

    PubMed Central

    Fan, Jin; Gu, Xiaosi; Liu, Xun; Guise, Kevin G.; Park, Yunsoo; Martin, Laura; de Marchena, Ashley; Tang, Cheuk Y.; Minzenberg, Michael J.; Hof, Patrick R.

    2010-01-01

    The anterior cingulate cortex (ACC) and frontoinsular cortex (FI) have been implicated in processing information across a variety of domains, including those related to attention and emotion. However, their role in rapid information processing, for example, as required for timely processing of salient stimuli, is not well understood. Here, we designed an emotional face priming paradigm and employed functional magnetic resonance imaging to elucidate their role in these mechanisms. Target faces with either neutral or fearful emotion were briefly primed by either neutral or fearful faces, or by blank ovals. Activation in the pregenual ACC and the FI, together with other regions, such as the amygdala, were preferentially activated in response to fearful face priming, suggesting that these regions are involved in the rapid processing of salient facial emotional information. PMID:20937394

  8. Killing two birds with one stone: the potential role of aripiprazole for patients with comorbid major depressive disorder and nicotine dependence via altering brain activity in the anterior cingulate cortex.

    PubMed

    Chu, Che-Sheng; Tzeng, Nian-Sheng; Chang, Hsin-An; Chang, Chuan-Chia; Chen, Tien-Yu

    2014-09-01

    The high comorbidity between major depressive disorder (MDD) and nicotine dependence (ND) is well recognized. Patients with comorbid MDD and ND often have increased suicidal risk and poor outcomes. A dysfunctional dopaminergic brain reward system might be a neurobiological link between MDD and ND. Aripiprazole has been considered as a dopamine stabilizer and was the first atypical antipsychotic agent approved by the US Food and Drug Administration as an adjunctive to the treatment of unipolar MDD. Bupropion is well known as a dual norepinephrine and dopamine reuptake inhibitor, and has been shown to be effective in smoking cessation. One reason bupropion is useful in treating ND is that it enhances the level of dopamine in the brain. Aripiprazole might act as a dopamine agonist similar to the way that bupropion does because of its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. Several recent studies have applied the unique pharmacodynamic characteristics of aripiprazole to treat patients with ND. Based on neuroimaging findings, aripiprazole can reduce substance cravings by altering brain activity, particularly in the brain regions of the anterior cingulate cortex. Therefore, we hypothesize that adjunctive aripiprazole with antidepressant may be an effective treatment for patients with MDD and ND comorbidity. A new drug invention that combines an antidepressant with an adequate dose of aripiprazole thus should be considered. The neurobiological basis for this combination to treat patients with MDD and ND comorbidity deserves further study.

  9. Short-term meditation induces white matter changes in the anterior cingulate.

    PubMed

    Tang, Yi-Yuan; Lu, Qilin; Geng, Xiujuan; Stein, Elliot A; Yang, Yihong; Posner, Michael I

    2010-08-31

    The anterior cingulate cortex (ACC) is part of a network implicated in the development of self-regulation and whose connectivity changes dramatically in development. In previous studies we showed that 3 h of mental training, based on traditional Chinese medicine (integrative body-mind training, IBMT), increases ACC activity and improves self-regulation. However, it is not known whether changes in white matter connectivity can result from small amounts of mental training. We here report that 11 h of IBMT increases fractional anisotropy (FA), an index indicating the integrity and efficiency of white matter in the corona radiata, an important white-matter tract connecting the ACC to other structures. Thus IBMT could provide a means for improving self-regulation and perhaps reducing or preventing various mental disorders.

  10. 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

  11. Errors without Conflict: Implications for Performance Monitoring Theories of Anterior Cingulate Cortex

    ERIC Educational Resources Information Center

    van Veen, V.; Holroyd, C.B.; Cohen, J.D.; Stenger, V.A.; Carter, C.S.

    2004-01-01

    Recent theories of the neural basis of performance monitoring have emphasized a central role for the anterior cingulate cortex (ACC). Replicating an earlier event-related potential (ERP) study, which showed an error feedback negativity that was modeled as having an ACC generator, we used event-related fMRI to investigate whether the ACC would…

  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 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.

  14. Increased Task Demand during Spatial Memory Testing Recruits the Anterior Cingulate Cortex

    ERIC Educational Resources Information Center

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

    2016-01-01

    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…

  15. 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…

  16. 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…

  17. 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.…

  18. 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…

  19. 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…

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Cross-modal sensory processing in the anterior cingulate and medial prefrontal cortices.

    PubMed

    Laurienti, Paul J; Wallace, Mark T; Maldjian, Joseph A; Susi, Christina M; Stein, Barry E; Burdette, Jonathan H

    2003-08-01

    One of the principal functions of the nervous system is to synthesize information from multiple sensory channels into a coherent behavioral and perceptual gestalt. A critical feature of this multisensory synthesis is the sorting and coupling of information derived from the same event. One of the singular features of stimuli conveying such information is their contextual or semantic congruence. Illustrating this fact, subjects are typically faster and more accurate when performing tasks that include congruent compared to incongruent cross-modal stimuli. Using functional magnetic resonance imaging, we demonstrate that activity in select brain areas is sensitive to the contextual congruence among cross-modal cues and to task difficulty. The anterior cingulate gyrus and adjacent medial prefrontal cortices showed significantly greater activity when visual and auditory stimuli were contextually congruent (i.e., matching) than when they were nonmatching. Although activity in these regions was also dependent on task difficulty, showing decreased activity with decreasing task difficulty, the activity changes associated with stimulus congruence predominated. PMID:12874776

  6. Cross-modal sensory processing in the anterior cingulate and medial prefrontal cortices.

    PubMed

    Laurienti, Paul J; Wallace, Mark T; Maldjian, Joseph A; Susi, Christina M; Stein, Barry E; Burdette, Jonathan H

    2003-08-01

    One of the principal functions of the nervous system is to synthesize information from multiple sensory channels into a coherent behavioral and perceptual gestalt. A critical feature of this multisensory synthesis is the sorting and coupling of information derived from the same event. One of the singular features of stimuli conveying such information is their contextual or semantic congruence. Illustrating this fact, subjects are typically faster and more accurate when performing tasks that include congruent compared to incongruent cross-modal stimuli. Using functional magnetic resonance imaging, we demonstrate that activity in select brain areas is sensitive to the contextual congruence among cross-modal cues and to task difficulty. The anterior cingulate gyrus and adjacent medial prefrontal cortices showed significantly greater activity when visual and auditory stimuli were contextually congruent (i.e., matching) than when they were nonmatching. Although activity in these regions was also dependent on task difficulty, showing decreased activity with decreasing task difficulty, the activity changes associated with stimulus congruence predominated.

  7. 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

  8. 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

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

    PubMed

    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.

  10. 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

  11. Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse.

    PubMed

    Koike, Hiroyuki; Demars, Michael P; Short, Jennifer A; Nabel, Elisa M; Akbarian, Schahram; Baxter, Mark G; Morishita, Hirofumi

    2016-03-01

    Attention is disrupted commonly in psychiatric disorders, yet mechanistic insight remains limited. Deficits in this function are associated with dorsal anterior cingulate cortex (dACC) excitotoxic lesions and pharmacological disinhibition; however, a causal relationship has not been established at the cellular level. Moreover, this association has not yet been examined in a genetically tractable species such as mice. Here, we reveal that dACC neurons causally contribute to attention processing by combining a chemogenetic approach that reversibly suppresses neural activity with a translational, touchscreen-based attention task in mice. We virally expressed inhibitory hM4Di DREADD (designer receptor exclusively activated by a designer drug) in dACC neurons, and examined the effects of this inhibitory action with the attention-based five-choice serial reaction time task. DREADD inactivation of the dACC neurons during the task significantly increased omission and correct response latencies, indicating that the neuronal activities of dACC contribute to attention and processing speed. Selective inactivation of excitatory neurons in the dACC not only increased omission, but also decreased accuracy. The effect of inactivating dACC neurons was selective to attention as response control, motivation, and locomotion remain normal. This finding suggests that dACC excitatory neurons play a principal role in modulating attention to task-relevant stimuli. This study establishes a foundation to chemogenetically dissect specific cell-type and circuit mechanisms underlying attentional behaviors in a genetically tractable species.

  12. 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

  13. Subgenual anterior cingulate responses to peer rejection: A marker of adolescents’ risk for depression

    PubMed Central

    MASTEN, CARRIE L.; EISENBERGER, NAOMI I.; BOROFSKY, LARISSA A.; MCNEALY, KRISTIN; PFEIFER, JENNIFER H.; DAPRETTO, MIRELLA

    2011-01-01

    Extensive developmental research has linked peer rejection during adolescence with a host of psychopathological outcomes, including depression. Moreover, recent neuroimaging research has suggested that increased activity in the subgenual region of the anterior cingulate cortex (subACC), which has been consistently linked with depression, is related to heightened sensitivity to peer rejection among adolescents. The goal of the current study was to directly test the hypothesis that adolescents’ subACC responses are predictive of their risk for future depression, by examining the relationship between subACC activity during peer rejection and increases in depressive symptoms during the following year. During a functional magnetic resonance imaging scan, 20 13-year-olds were ostensibly excluded by peers during an online social interaction. Participants’ depressive symptoms were assessed via parental reports at the time of the scan and 1 year later. Region of interest and whole-brain analyses indicated that greater subACC activity during exclusion was associated with increases in parent-reported depressive symptoms during the following year. These findings suggest that subACC responsivity to social exclusion may serve as a neural marker of adolescents’ risk for future depression and have implications for understanding the relationship between sensitivity to peer rejection and the increased risk of depression that occurs during adolescence. PMID:21262054

  14. 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…

  15. Hierarchical Error Representation: A Computational Model of Anterior Cingulate and Dorsolateral Prefrontal Cortex.

    PubMed

    Alexander, William H; Brown, Joshua W

    2015-11-01

    Anterior cingulate and dorsolateral prefrontal cortex (ACC and dlPFC, respectively) are core components of the cognitive control network. Activation of these regions is routinely observed in tasks that involve monitoring the external environment and maintaining information in order to generate appropriate responses. Despite the ubiquity of studies reporting coactivation of these two regions, a consensus on how they interact to support cognitive control has yet to emerge. In this letter, we present a new hypothesis and computational model of ACC and dlPFC. The error representation hypothesis states that multidimensional error signals generated by ACC in response to surprising outcomes are used to train representations of expected error in dlPFC, which are then associated with relevant task stimuli. Error representations maintained in dlPFC are in turn used to modulate predictive activity in ACC in order to generate better estimates of the likely outcomes of actions. We formalize the error representation hypothesis in a new computational model based on our previous model of ACC. The hierarchical error representation (HER) model of ACC/dlPFC suggests a mechanism by which hierarchically organized layers within ACC and dlPFC interact in order to solve sophisticated cognitive tasks. In a series of simulations, we demonstrate the ability of the HER model to autonomously learn to perform structured tasks in a manner comparable to human performance, and we show that the HER model outperforms current deep learning networks by an order of magnitude. PMID:26378874

  16. The association of interoceptive awareness and alexithymia with neurotransmitter concentrations in insula and anterior cingulate.

    PubMed

    Ernst, Jutta; Böker, Heinz; Hättenschwiler, Joe; Schüpbach, Daniel; Northoff, Georg; Seifritz, Erich; Grimm, Simone

    2014-06-01

    Alexithymia and increased interoceptive awareness have been associated with affective disorders as well as with altered insula and anterior cingulate cortex (ACC) function. Brain imaging studies have demonstrated an association between neurotransmitter function and affective disorders as well as personality traits. Here, we first examined the relationship between alexithymic facets as assessed with the Toronto Alexithymia Scale (TAS-20) and interoceptive awareness (assessed with the Body Perception Questionnaire) in 18 healthy subjects. Second, we investigated their association with glutamate and gamma-aminobutyric acid (GABA) concentrations in the left insula and the ACC using 3-Tesla proton magnetic resonance spectroscopy. Behaviorally, we found a close association between alexithymia and interoceptive awareness. Furthermore, glutamate levels in the left insula were positively associated with both alexithymia and awareness of autonomic nervous system reactivity, while GABA concentrations in ACC were selectively associated with alexithymia. Although preliminary, our results suggest that increased glutamate-mediated excitatory transmission-related to enhanced insula activity-reflects increased interoceptive awareness in alexithymia. Suppression of the unspecific emotional arousal evoked by increased awareness of bodily responses in alexithymics might thus be reflected in decreased neuronal activity mediated by increased GABA concentration in ACC. PMID:23596189

  17. Biphasic effects of the anterior cingulate cortex stimulation on glabrous skin blood flow in rats.

    PubMed

    He, Ji-Wei; Herath, Pushpani M; Peng, Yuan Bo

    2010-10-14

    A growing body of evidence indicates that the anterior cingulate cortex (ACC) is associated with sensory, cognition and emotion processing. We have shown that electrical stimulation of rat ACC depressed the spinal cord dorsal horn neuron activity in response to noxious stimuli, possibly through a release of GABA. GABA may elicit dorsal root reflexes (DRRs) to induce peripheral vasodilatation. On the other hand, the ACC may also regulate autonomic flow via the lateral hypothalamus (LH). The goal of this work was to investigate the role of ACC in regulating autonomic activity. A laser Doppler imager was used to continuously monitor rat glabrous skin blood perfusion in both hind paws, while a simultaneous heart rate (HR) and DRRs were recorded to assess contributions of sympathetic flow and sensory afferent to the ACC-induced vascular change. Twenty-three rats were divided into three groups: a unilateral electrolytic LH lesion group (n = 6), a sham lesion group (n = 9), and a control group (neither lesion nor stimulation, n = 8). ACC stimulation induced a biphasic systemic vascular response, with an initial transient cutaneous vasoconstriction followed by a prolonged vasodilatation. Unilateral LH lesion did not alter this biphasic response. A short-term tachycardia occurred in response to the ACC stimulation, but did not correlate with the prolonged vasodilatation. No significant change in DRRs was found (in 35 fibers). ACC stimulation induced a biphasic vascular response in the skin. Data are consistent with sympathetic contribution. However, other mechanisms should also be involved.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. Mirth and laughter elicited by electrical stimulation of the human anterior cingulate cortex.

    PubMed

    Caruana, Fausto; Avanzini, Pietro; Gozzo, Francesca; Francione, Stefano; Cardinale, Francesco; Rizzolatti, Giacomo

    2015-10-01

    Laughter is a complex motor behavior that, typically, expresses mirth. Despite its fundamental role in social life, knowledge about the neural basis of laughter is very limited and mostly based on a few electrical stimulation (ES) studies carried out in epileptic patients. In these studies laughter was elicited from temporal areas where it was accompanied by mirth and from frontal areas plus an anterior cingulate case where laughter without mirth was observed. On the basis of these findings, it has been proposed a dichotomy between temporal lobe areas processing the emotional content of laughter and anterior cingulate cortex (ACC) and motor areas responsible of laughter production. The present study is aimed to understand the role of ACC in laughter. We report the effects of stimulation of 10 rostral, pregenual ACC (pACC) patients in which the ES elicited laughter. In half of the patients ES elicited a clear burst of laughter with mirth, while in the other half mirth was not evident. This large dataset allow us to offer a more reliable picture of the functional contribute of this region in laughter, and to precisely localize it in the cingulate cortex. We conclude that the pACC is involved in both the motor and the affective components of emotions, and challenge the validity of a sharp dichotomy between motor and emotional centers for laughing. Finally, we suggest a possible anatomical network for the production of positive emotional expressions.

  6. Dissociable effects of surprise and model update in parietal and anterior cingulate cortex.

    PubMed

    O'Reilly, Jill X; Schüffelgen, Urs; Cuell, Steven F; Behrens, Timothy E J; Mars, Rogier B; Rushworth, Matthew F S

    2013-09-17

    Brains use predictive models to facilitate the processing of expected stimuli or planned actions. Under a predictive model, surprising (low probability) stimuli or actions necessitate the immediate reallocation of processing resources, but they can also signal the need to update the underlying predictive model to reflect changes in the environment. Surprise and updating are often correlated in experimental paradigms but are, in fact, distinct constructs that can be formally defined as the Shannon information (IS) and Kullback-Leibler divergence (DKL) associated with an observation. In a saccadic planning task, we observed that distinct behaviors and brain regions are associated with surprise/IS and updating/DKL. Although surprise/IS was associated with behavioral reprogramming as indexed by slower reaction times, as well as with activity in the posterior parietal cortex [human lateral intraparietal area (LIP)], the anterior cingulate cortex (ACC) was specifically activated during updating of the predictive model (DKL). A second saccade-sensitive region in the inferior posterior parietal cortex (human 7a), which has connections to both LIP and ACC, was activated by surprise and modulated by updating. Pupillometry revealed a further dissociation between surprise and updating with an early positive effect of surprise and late negative effect of updating on pupil area. These results give a computational account of the roles of the ACC and two parietal saccade regions, LIP and 7a, by which their involvement in diverse tasks can be understood mechanistically. The dissociation of functional roles between regions within the reorienting/reprogramming network may also inform models of neurological phenomena, such as extinction and Balint syndrome, and neglect.

  7. 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

  8. Anterior cingulate cortex and the Stroop task: neuropsychological evidence for topographic specificity.

    PubMed

    Swick, Diane; Jovanovic, Jelena

    2002-01-01

    Neuroimaging studies have implicated the anterior cingulate cortex (ACC) in many aspects of attention and cognition. Major theories of ACC function have proposed a role in conflict monitoring, executive control, response selection, and general arousal. Although the ACC is often treated as a unitary structure, extensive evidence suggests it exhibits anatomical and functional specificity. ACC activity during the Stroop color word interference task has been of particular interest. The purpose of the present study was to determine whether two different ACC subregions are necessary for intact color naming performance in the Stroop task. One experiment utilized blocked trial and mixed trial designs to emulate neuroimaging studies and to compare interference and facilitation effects, respectively. A third variant manipulated the probabilities of congruent and incongruent trials to alter levels of interference and cognitive control, or engagement of strategic processes, on a block by block basis. Two patients with focal lesions in either right mid-caudal (patient D.L.) or left rostral to mid-dorsal ACC (patient R.N.) exhibited distinctive performance profiles in these three versions of the Stroop task, providing further support for topographic specificity of function within the human ACC. Contrary to predictions from some neuroimaging experiments, damage to right mid-caudal ACC was associated with normal levels of interference and accurate performance on incongruent trials. Instead, D.L. showed reduced levels of facilitation relative to controls. Further, interference was not modulated by the probability manipulation in D.L., suggesting equivalently high levels of cognitive control in both conditions. Conversely, damage to left mid-dorsal ACC resulted in consistently lower accuracy on incongruent trials, indicating deficits in maintaining task set and inhibiting the automatic response. These results can help to constrain interpretations of ACC activations in functional

  9. Insula and anterior cingulate GABA levels in post-traumatic stress disorder: Preliminary findings using magnetic resonance spectroscopy

    PubMed Central

    Rosso, Isabelle M.; Weiner, Melissa R.; Crowley, Davidan J; Silveri, Marisa M.; Rauch, Scott L.; Jensen, J. Eric

    2013-01-01

    Background Increased reactivity of the insular cortex and decreased activity of the dorsal anterior cingulate (ACC) are seen in functional imaging studies of post-traumatic stress disorder (PTSD), and may partly explain the persistent fear- and anxiety-proneness that characterize the disorder. A possible neurochemical correlate is altered function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). We report results from what we believe is the first study applying proton magnetic resonance spectroscopy (1H-MRS) to measure brain GABA in PTSD. Methods Thirteen adults with DSM-IV PTSD and 13 matched healthy control subjects underwent single voxel 1H-MRS at 4 Tesla. GABA was measured in the right anterior insula and dorsal anterior cingulate, using MEGAPRESS spectral editing. Subjects were interviewed with the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale, and also completed the State and Trait Anxiety Inventory. Results Insula GABA was significantly lower in PTSD subjects than in controls, and dorsal ACC GABA did not differ significantly between the groups. Insula GABA was not significantly associated with severity of PTSD symptoms. However, lower insula GABA was associated with significantly higher state and trait anxiety in the subject sample as a whole. Conclusions PTSD is associated with reduced GABA in the right anterior insula. This preliminary evidence of the 1H-MRS GABA metabolite as a possible biomarker of PTSD encourages replication in larger samples and examination of relations with symptom dimensions. Future studies also should examine whether insula GABA is a marker of anxiety proneness, cutting across clinical diagnostic categories. PMID:23861191

  10. 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

  11. Writing errors in ALS related to loss of neuronal integrity in the anterior cingulate gyrus.

    PubMed

    Yabe, Ichiro; Tsuji-Akimoto, Sachiko; Shiga, Tohru; Hamada, Shinsuke; Hirata, Kenji; Otsuki, Mika; Kuge, Yuji; Tamaki, Nagara; Sasaki, Hidenao

    2012-04-15

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of motor neuron and various cognitive deficits including writing errors. (11)C-flumazenil (FMZ), the positron emission tomography (PET) GABA(A) receptor ligand, is a marker of cortical dysfunction. The objective of this study was to investigate the relationship between cognitive deficits and loss of neuronal integrity in ALS patients using (11)C-FMZ PET. Ten patients with ALS underwent both neuropsychological tests and (11)C-FMZ-PET. The binding potential (BP) of FMZ was calculated from (11)C-FMZ PET images. There were no significant correlations between the BP and most test scores except for the writing error index (WEI), which was measured by the modified Western Aphasia Battery - VB (WAB-IVB) test. The severity of writing error was associated with loss of neuronal integrity in the bilateral anterior cingulate gyrus with mild right predominance (n=9; x=4 mm, y=36 mm, z=4 mm, Z=5.1). The results showed that writing errors in our patients with ALS were related to dysfunction in the anterior cingulate gyrus.

  12. Proton MR Spectroscopy: Higher Right Anterior Cingulate N-Acetylaspartate/Choline Ratio in Asperger Syndrome Compared with Healthy Controls

    PubMed Central

    Oner, O.; Devrimci-Ozguven, H.; Oktem, F.; Yagmurlu, B.; Baskak, B.; Munir, K.M.

    2011-01-01

    BACKGROUND AND PURPOSE One former study reported higher prefrontal N-acetylaspartate (NAA) levels in patients with Asperger syndrome (AS). The objective of the current study was to test the hypothesis that patients with AS would have higher dorsolateral prefrontal and anterior cingulate cortex NAA/creatine (Cr) and that NAA/Cr would be correlated with symptom severity. MATERIALS AND METHODS NAA/choline (Cho), NAA/Cr, and Cho/Cr values revealed by 1H-MR spectroscopy in 14 right-handed male patients with AS (6 medicated with risperidone), 17–38 years of age, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were compared with those of 21 right-handed male controls frequency-matched by age and intelligence quotient scores. RESULTS Patients with AS had significantly higher anterior cingulate NAA/Cho levels (z = –2.18, P = .028); there was a statistical trend for higher anterior cingulate NAA/Cr (z = –1.81, P = .069) that was significant when only the unmedicated patients with AS were taken into account (z = –1.95, P = .050). There were no significant differences in dorsolateral prefrontal MR spectroscopy values. CONCLUSIONS Our findings show that individuals with AS had higher NAA/Cho levels in the right anterior cingulate compared with healthy controls and that higher anterior cingulate NAA/Cho levels were correlated with higher Yale-Brown Obsessive Compulsive Scale total scores. PMID:17846198

  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. 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

  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. 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.

  17. 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

  18. 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.

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

    PubMed Central

    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

  20. 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

  1. 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

  2. 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…

  3. 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…

  4. 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…

  5. 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

  6. FMRI activations of amygdala, cingulate cortex, and auditory cortex by infant laughing and crying.

    PubMed

    Sander, Kerstin; Frome, Yvonne; Scheich, Henning

    2007-10-01

    One of the functions of emotional vocalizations is the regulation of social relationships like those between adults and children. Listening to infant vocalizations is known to engage amygdala as well as anterior and posterior cingulate cortices. But, the functional relationships between these structures still need further clarification. Here, nonparental women and men listened to laughing and crying of preverbal infants and to vocalization-derived control stimuli, while performing a pure tone detection task during low-noise functional magnetic resonance imaging. Infant vocalizations elicited stronger activation in amygdala and anterior cingulate cortex (ACC) of women, whereas the alienated control stimuli elicited stronger activation in men. Independent of listeners' gender, auditory cortex (AC) and posterior cingulate cortex (PCC) were more strongly activated by the control stimuli than by infant laughing or crying. The gender-dependent correlates of neural activity in amygdala and ACC may reflect neural predispositions in women for responses to preverbal infant vocalizations, whereas the gender-independent similarity of activation patterns in PCC and AC may reflect more sensory-based and cognitive levels of neural processing. In comparison to our previous work on adult laughing and crying, the infant vocalizations elicited manifold higher amygdala activation.

  7. 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

  8. 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

  9. Association of Anterior Cingulate Glutathione with Sleep Apnea in Older Adults At-Risk for Dementia

    PubMed Central

    Duffy, Shantel L.; Lagopoulos, Jim; Terpening, Zoe; Lewis, Simon J.G.; Grunstein, Ron; Mowszowski, Loren; Cross, Nathan; Hermens, Daniel F.; Hickie, Ian B.; Naismith, Sharon L.

    2016-01-01

    Study Objectives: Sleep disordered breathing (SDB) is common in older adults and is strongly associated with cognitive decline, with increasing evidence suggesting that it may represent a risk factor for dementia. Given that SDB is characterized by intermittent episodes of hypoxemia during sleep, it is possible that cognitive impairment may relate to cerebral oxidative stress. This study aimed to examine the relationship between nocturnal markers of hypoxemia and proton magnetic resonance spectroscopy (1H-MRS) markers of oxidative stress within the anterior cingulate cortex (ACC) of the brain. Methods: Twenty-four older adults (mean age = 67.9 y) at-risk for dementia were recruited from our Healthy Brain Ageing Research Clinic. At-risk was defined as participants seeking help for assessment and/or intervention for cognitive decline, including those with subjective and/or objective cognitive complaints. This could occur in the context of prior depression or risk factors (e.g., vascular) for dementia. All participants underwent psychiatric, medical and neuropsychological assessment followed by overnight polysomnography. In addition, participants underwent 1H-MRS to derive levels of ACC metabolite glutathione (GSH) reported as a ratio to creatine (GSH/Cr). Results: Increased levels of GSH/Cr were associated with lower oxygen desaturation (r = −0.54, P = 0.007) and more severe apnea-hypopnea index scores during rapid eye movement sleep (r = 0.42, P = 0.050). In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition: r = −0.49, P = 0.015; set shifting: r = −0.43, P = 0.037). Conclusions: Markers of nocturnal hypoxemia and SDB are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia. Further work focused on utilizing this biomarker for the early identification and treatment of this

  10. An unusual population of pyramidal neurons in the anterior cingulate cortex of hominids contains the calcium-binding protein calretinin.

    PubMed

    Hof, P R; Nimchinsky, E A; Perl, D P; Erwin, J M

    2001-07-20

    In the context of an on-going comparative analysis of primate neocortex evolution, we describe the occurrence and distribution of a previously unrecognized group of pyramidal neurons, restricted to the superficial part of layer V in the anterior cingulate cortex of hominids and characterized by immunoreactivity to the calcium-binding protein, calretinin. These neurons were rare in orangutans, more numerous in gorillas and common chimpanzees, while humans had the highest numbers. These calretinin-containing pyramidal cells were not observed in the cingulate cortex of any other primate or mammalian species. This finding, together with other recent observations on the hominoid cingulate cortex, is interesting when considering primate neocortical evolution, as it indicates possible adaptive and anatomical modifications in a cortical region critical for the integration of many aspects of autonomic function, vocalization, and cognitive processes.

  11. 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

  12. 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

  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 Central

    Delevich, Kristen; Tucciarone, Jason; Huang, Z. Josh

    2015-01-01

    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. Reduced anterior cingulate gray matter volume in treatment-naïve clinically depressed adolescents☆

    PubMed Central

    Pannekoek, Justine Nienke; van der Werff, Steven J.A.; van den Bulk, Bianca G.; van Lang, Natasja D.J.; Rombouts, Serge A.R.B.; van Buchem, Mark A.; Vermeiren, Robert R.J.M.; van der Wee, Nic J.A.

    2014-01-01

    Adolescent depression is associated with increased risk for suicidality, social and educational impairment, smoking, substance use, obesity, and depression in adulthood. It is of relevance to further our insight in the neurobiological mechanisms underlying this disorder in the developing brain, as this may be essential to optimize treatment and prevention of adolescent depression and its negative clinical trajectories. The equivocal findings of the limited number of studies on neural abnormalities in depressed youth stress the need for further neurobiological investigation of adolescent depression. We therefore performed a voxel-based morphometry study of the hippocampus, amygdala, superior temporal gyrus, and anterior cingulate cortex (ACC) in 26 treatment-naïve, clinically depressed adolescents and 26 pair-wise matched healthy controls. Additionally, an exploratory whole-brain analysis was performed. Clinically depressed adolescents showed a volume reduction of the bilateral dorsal ACC compared to healthy controls. However, no association was found between gray matter volume of the ACC and clinical severity scores for depression or anxiety. Our finding of a smaller ACC in clinically depressed adolescents is consistent with literature on depressed adults. Future research is needed to investigate if gray matter abnormalities precede or follow clinical depression in adolescents. PMID:24501702

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

    PubMed

    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.

  17. 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

  18. Right anterior cingulate: a neuroanatomical correlate of aggression and defiance in boys.

    PubMed

    Boes, Aaron D; Tranel, Daniel; Anderson, Steven W; Nopoulos, Peg

    2008-06-01

    Variation in emotional processes may contribute to aggressive and defiant behavior. This study assessed these problem behaviors in a large sample of children and adolescents in relation to the volume of two cortical regions with prominent roles in emotion processing, the anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC). One hundred seventeen participants (61 boys, 56 girls), ages 7-17, were recruited from the community. Aggressive and defiant behavior was measured using the parent- and teacher-reported Pediatric Behavior Scale and volumetric measures were generated using structural MRI. Regression analyses indicated a significant sex X ACC volume interaction in predicting aggressive and defiant behavior, without significant results for the vmPFC. Follow-up analyses showed that aggressive and defiant behavior is associated with decreased right ACC volume in boys and a nonsignificant reduction in left ACC volume in girls. These results are consistent with the notion that the right ACC acts as a neuroanatomical correlate of aggression and defiance in boys. The authors discuss this finding in light of its implications for understanding the neural correlates of antisocial behavior. PMID:18513137

  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. 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

  1. Anterior cingulate engagement in a foraging context reflects choice difficulty, not foraging value.

    PubMed

    Shenhav, Amitai; Straccia, Mark A; Cohen, Jonathan D; Botvinick, Matthew M

    2014-09-01

    Previous theories predict that human dorsal anterior cingulate (dACC) should respond to decision difficulty. An alternative theory has been recently advanced that proposes that dACC evolved to represent the value of 'non-default', foraging behavior, calling into question its role in choice difficulty. However, this new theory does not take into account that choosing whether or not to pursue foraging-like behavior can also be more difficult than simply resorting to a default. The results of two neuroimaging experiments show that dACC is only associated with foraging value when foraging value is confounded with choice difficulty; when the two are dissociated, dACC engagement is only explained by choice difficulty, and not the value of foraging. In addition to refuting this new theory, our studies help to formalize a fundamental connection between choice difficulty and foraging-like decisions, while also prescribing a solution for a common pitfall in studies of reward-based decision making.

  2. Anterior Cingulate Engagement in a Foraging Context Reflects Choice Difficulty, Not Foraging Value

    PubMed Central

    Shenhav, Amitai; Straccia, Mark A.; Cohen, Jonathan D.; Botvinick, Matthew M.

    2014-01-01

    Previous theories predict that human dorsal anterior cingulate (dACC) should respond to decision difficulty. An alternative theory has been recently advanced which proposes that dACC evolved to represent the value of “non-default,” foraging behavior, calling into question its role in choice difficulty. However, this new theory does not take into account that choosing whether or not to pursue foraging-like behavior can also be more difficult than simply resorting to a “default.” The results of two neuroimaging experiments show that dACC is only associated with foraging value when foraging value is confounded with choice difficulty; when the two are dissociated, dACC engagement is only explained by choice difficulty, and not the value of foraging. In addition to refuting this new theory, our studies help to formalize a fundamental connection between choice difficulty and foraging-like decisions, while also prescribing a solution for a common pitfall in studies of reward-based decision making. PMID:25064851

  3. 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

  4. 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

  5. Performance Monitoring Local Field Potentials in the Medial Frontal Cortex of Primates: Anterior Cingulate Cortex

    PubMed Central

    Emeric, Erik E.; Brown, Joshua W.; Leslie, Melanie; Pouget, Pierre; Stuphorn, Veit; Schall, Jeffrey D.

    2009-01-01

    We describe intracranial local field potentials (LFP) recorded in the anterior cingulate cortex (ACC) of macaque monkeys performing a saccade countermanding task. The most prominent feature at ∼70% of sites was greater negative polarity after errors than after rewarded correct trials. This negative polarity was also evoked in unrewarded correct trials. The LFP evoked by the visual target was much less polarized, and the weak presaccadic modulation was insufficient to control the initiation of saccades. When saccades were cancelled, LFP modulation decreased slightly with the magnitude of response conflict that corresponds to the coactivation of gaze-shifting and -holding neurons estimated from the probability of canceling. However, response time adjustments on subsequent trials were not correlated with LFP polarity on individual trials. The results provide clear evidence that error- and feedback-related, but not conflict-related, signals are carried by the LFP in the macaque ACC. Finding performance monitoring field potentials in the ACC of macaque monkeys establishes a bridge between event-related potential and functional brain-imaging studies in humans and neurophysiology studies in non-human primates. PMID:18077665

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. The anterior cingulate cortex may enhance inhibition of lateral prefrontal cortex via m2 cholinergic receptors at dual synaptic sites.

    PubMed

    Medalla, Maria; Barbas, Helen

    2012-10-31

    The anterior cingulate cortex (ACC) and dorsolateral prefrontal cortices (DLPFC) share robust excitatory connections. However, during rapid eye movement (REM) sleep, when cortical activity is dominated by acetylcholine, the ACC is activated but DLPFC is suppressed. Using pathway tracing and electron microscopy in nonhuman primates (Macaca mulatta), we tested the hypothesis that the opposite states may reflect specific modulation by acetylcholine through strategic synaptic localization of muscarinic m2 receptors, which inhibit neurotransmitter release presynaptically, but are thought to be excitatory postsynaptically. In the ACC pathway to DLPFC (area 32 to area 9), m2 receptors predominated in ACC axon terminals and in more than half of the targeted dendrites of presumed inhibitory neurons, suggesting inhibitory cholinergic influence. In contrast, in a pathway linking the DLPFC area 46 to DLPFC area 9, postsynaptic m2 receptors predominated in targeted spines of presumed excitatory neurons, consistent with their mutual activation in working memory. These novel findings suggest that presynaptic and postsynaptic specificity of m2 cholinergic receptors may help explain the differential engagement of ACC and DLPFC areas in REM sleep for memory consolidation and synergism in awake states for cognitive control.

  14. Dorsal anterior cingulate cortex integrates reinforcement history to guide voluntary behavior.

    PubMed

    Holroyd, Clay B; Coles, Michael G H

    2008-05-01

    Two competing types of theory have been proposed about the function of dorsal anterior cingulate cortex (dACC): evaluative theories hold that dACC monitors ongoing behavior to detect errors or conflict, whereas response selection theories hold that dACC is directly involved in the decision making process. In particular, one response selection theory proposes that dACC utilizes reward prediction error signals carried by the midbrain dopamine system to decide which of several competing motor control systems should be given control over the motor system (Holroyd and Coles, 2002). The theory further proposes that the impact of these dopamine signals on dACC determines the amplitude of a component of the event-related brain potential called the error-related negativity (ERN). In the present study, we applied this theory to a decision making problem that requires participants to select between two response options in which an erroneous choice is not clearly defined. Rather, the reward received for a particular response evolves in relation to the individual's previous behavior. We adapted a computational model associated with the theory to simulate human performance and the ERN in the task, and tested the predictions of the model against empirical ERP data. Our results indicate that ERN amplitude reflects the subjective value attributed by each participant to their response options as derived from their recent reward history. This finding is consistent with the position that dACC integrates the recent history of reinforcements to guide voluntary choice behavior, as opposed to evaluating behaviors per se.

  15. 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

  16. Sex differences in GABAergic gene expression occur in the anterior cingulate cortex in schizophrenia.

    PubMed

    Bristow, Greg C; Bostrom, John A; Haroutunian, Vahram; Sodhi, Monsheel S

    2015-09-01

    GABAergic dysfunction has been strongly implicated in the pathophysiology of schizophrenia. In this study, we analyzed the expression levels of several GABAergic genes in the anterior cingulate cortex (ACC) of postmortem subjects with schizophrenia (n=21) and a comparison group of individuals without a history of psychiatric illness (n=18). Our analyses revealed a significant sex by diagnosis effect, along with significant differences in GABAergic gene expression based on medication status. Analyses revealed that in male groups, the expression of GABAergic genes was generally lower in schizophrenia cases compared to the controls, with significantly lower expression levels of GABA-Aα5, GABA-Aβ1, and GABA-Aε. In females, the expression of GABAergic genes was higher in the schizophrenia cases, with significantly higher expression of the GABA-Aβ1 and GAD67 genes. Analysis of the effect of medication in the schizophrenia subjects revealed significantly higher expression of GABA-Aα1-3, GABA-Aβ2, GABA-Aγ2, and GAD67 in the medicated group compared to the unmedicated group. These data show that sex differences in the expression of GABAergic genes occur in the ACC in schizophrenia. Therefore, our data support previous findings of GABAergic dysfunction in schizophrenia and emphasize the importance of considering sex in analyses of the pathophysiology of schizophrenia. Sex differences in the GABAergic regulation of ACC function may contribute to the differences observed in the symptoms of male and female patients with schizophrenia. In addition, our findings indicate that antipsychotic medications may alter GABAergic signaling in the ACC, supporting the potential of GABAergic targets for the development of novel antipsychotic medication.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  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.

  4. 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

  5. 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

  6. Is endogenous D-serine in the rostral anterior cingulate cortex necessary for pain-related negative affect?

    PubMed

    Ren, Wen-Hua; Guo, Ji-Dong; Cao, Hong; Wang, Hua; Wang, Pei-Fen; Sha, Hong; Ji, Ru-Rong; Zhao, Zhi-Qi; Zhang, Yu-Qiu

    2006-03-01

    Functional activation of NMDA receptors requires co-activation of glutamate- and glycine-binding sites. D-serine is considered to be an endogenous ligand for the glycine site of NMDA receptors. Using a combination of a rat formalin-induced conditioned place avoidance (F-CPA) behavioral model and whole-cell patch-clamp recording in rostral anterior cingulate cortex (rACC) slices, we examined the effects of d-amino acid oxidase (DAAO), an endogenous D-serine-degrading enzyme, and 7-chlorokynurenate (7Cl-KYNA), an antagonist of the glycine site of NMDA receptors, on pain-related aversion. Degradation of endogenous D-serine with DAAO, or selective blockade of the glycine site of NMDA receptors by 7Cl-KYNA, effectively inhibited NMDA-evoked currents in rACC slices. Intra-rACC injection of DAAO (0.1 U) and 7Cl-KYNA (2 and 0.2 mM, 0.6 microL per side) 20 min before F-CPA conditioning greatly attenuated F-CPA scores, but did not affect formalin-induced acute nociceptive behaviors and electric foot shock-induced conditioned place avoidance. This study reveals for the first time that endogenous D-serine plays a critical role in pain-related aversion by activating the glycine site of NMDA receptors in the rACC. Furthermore, these results extend our hypothesis that activation of NMDA receptors in the rACC is necessary for the acquisition of specific pain-related negative emotion. Thus a new and promising strategy for the prevention of chronic pain-induced emotional disturbance might be raised.

  7. 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

  8. 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.

  9. Cognitive control functions of anterior cingulate cortex in macaque monkeys performing a Wisconsin Card Sorting Test analog.

    PubMed

    Kuwabara, Masaru; Mansouri, Farshad A; Buckley, Mark J; Tanaka, Keiji

    2014-05-28

    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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Dissociable neural responses related to pain intensity, stimulus intensity, and stimulus awareness within the anterior cingulate cortex: a parametric single-trial laser functional magnetic resonance imaging study.

    PubMed

    Büchel, Christian; Bornhovd, Karin; Quante, Markus; Glauche, Volkmar; Bromm, Burkhard; Weiller, Cornelius

    2002-02-01

    Neuroimaging studies have demonstrated activations in the anterior cingulate cortex (ACC) related to the affective component of pain, but not to stimulus intensity. However, it is possible that the low spatial resolution of positron emission tomography, as used in the majority of these studies, obscured areas coding stimulus intensity. We revisited this issue, using a parametric single-trial functional magnetic resonance imaging design, and investigated pain, stimulus intensity, and stimulus awareness (i.e., pain unrelated) responses within the ACC in nine healthy volunteers. Four different stimulus intensities ranging from warm to painful (300-600 mJ) were applied with a thulium yttrium-aluminum granite infrared laser in a randomized order and rated by the subjects on a five point scale (P0-P4). Pain-related regions in the ventral posterior ACC showed a response that did not distinguish between innocuous trials (P0 and P1) but showed a positive linear relationship with the blood oxygenation level-dependent contrast signal for painful trials (P2-P4). Regions in the dorsal anterior ACC along the cingulate sulcus differentiated between P0 (not perceived) and P1 but exhibited no additional signal increase with P2; these regions are related to stimulus awareness and probably to cognitive processing. Most importantly, we identified a region in the dorsal posterior ACC showing a response that discriminated between nonpainful trials (P0 and P1); therefore, this region was simply related to basic sensory processing and not to pain intensity. Stimulus-related activations were all located adjacent to the cingulate motor area, highlighting the strategic link of stimulus processing and response generation in the posterior ACC.

  15. 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.

  16. Self-harm in schizophrenia is associated with dorsolateral prefrontal and posterior cingulate activity.

    PubMed

    Lee, Kwang-Hyuk; Pluck, Graham; Lekka, Nicoletta; Horton, Andrew; Wilkinson, Iain D; Woodruff, Peter W R

    2015-08-01

    Self-harm, such as self-cutting, self-poisoning or jumping from height, regardless of intentions, is common among people with schizophrenia. We wished to investigate brain activations relating to self-harm, in order to test whether these activations could differentiate between schizophrenia patients with self-harm and those without. We used event-related functional MRI with a go/no-go response inhibition paradigm. Fourteen schizophrenia patients with a history of self-harm were compared with 14 schizophrenia patients without a history of self-harm and 17 healthy control participants. In addition, we used standard clinical measures and neuropsychological tests to assess risk factors associated with self-harm. The right dorsolateral prefrontal cortex (DLPFC) and the left posterior cingulate cortex differentiated all three groups; brain activation in these regions being greatest in the control group, and the self-harm patient group being greater than in the non-self-harm patient group. In the self-harm patient group, right DLPFC activity was positively correlated with severity of suicidal thinking. In addition, both patient groups showed less activation in the right orbitofrontal cortex, left ventral anterior cingulate cortex and right thalamus. This is the first study to report right DLPFC activation in association with self-harm and suicidal thinking in patients with schizophrenia. This area could be a target for future neuromodulation studies to treat suicidal thinking and self-harm behaviors in patients with schizophrenia.

  17. 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

  18. 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

  19. 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

  20. Dissociated roles of the anterior cingulate cortex in reward and conflict processing as revealed by the feedback error-related negativity and N200.

    PubMed

    Baker, Travis E; Holroyd, Clay B

    2011-04-01

    The reinforcement learning theory of the error-related negativity (ERN) holds that the impact of reward signals carried by the midbrain dopamine system modulates activity of the anterior cingulate cortex (ACC), alternatively disinhibiting and inhibiting the ACC following unpredicted error and reward events, respectively. According to a recent formulation of the theory, activity that is intrinsic to the ACC produces a component of the event-related brain potential (ERP) called the N200, and following unpredicted rewards, the N200 is suppressed by extrinsically applied positive dopamine reward signals, resulting in an ERP component called the feedback-ERN (fERN). Here we demonstrate that, despite extensive spatial and temporal overlap between the two ERP components, the functional processes indexed by the N200 (conflict) and the fERN (reward) are dissociable. These results point toward avenues for future investigation.

  1. Dissociated roles of the anterior cingulate cortex in reward and conflict processing as revealed by the feedback error-related negativity and N200.

    PubMed

    Baker, Travis E; Holroyd, Clay B

    2011-04-01

    The reinforcement learning theory of the error-related negativity (ERN) holds that the impact of reward signals carried by the midbrain dopamine system modulates activity of the anterior cingulate cortex (ACC), alternatively disinhibiting and inhibiting the ACC following unpredicted error and reward events, respectively. According to a recent formulation of the theory, activity that is intrinsic to the ACC produces a component of the event-related brain potential (ERP) called the N200, and following unpredicted rewards, the N200 is suppressed by extrinsically applied positive dopamine reward signals, resulting in an ERP component called the feedback-ERN (fERN). Here we demonstrate that, despite extensive spatial and temporal overlap between the two ERP components, the functional processes indexed by the N200 (conflict) and the fERN (reward) are dissociable. These results point toward avenues for future investigation. PMID:21295109

  2. 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

  3. Effect of Acupuncture on Functional Connectivity of Anterior Cingulate Cortex for Bell's Palsy Patients with Different Clinical Duration.

    PubMed

    Wu, Hongli; Kan, Hongxing; Li, Chuanfu; Park, Kyungmo; Zhu, Yifang; Mohamed, Abdalla Z; Xu, Chunsheng; Wu, Yuanyuan; Zhang, Wei; Yang, Jun

    2015-01-01

    Acupuncture is widely used in the treatment of Bell's palsy (BP) in many countries, but its underlying physiological mechanism remained controversial. In order to explore the potential mechanism, changes of functional connectivity (FC) of anterior cingulate gyrus (ACC) were investigated. We collected 20 healthy (control group) participants and 28 BP patients with different clinical duration accepted resting state functional MRI (rfMRI) scans before and after acupuncture, respectively. The FC of ACC before and after acupuncture was compared with paired t-test and the detailed results are presented in the paper. Our results showed that effects of the acupuncture on FC were closely related to clinical duration in patients with BP, which suggested that brain response to acupuncture was closely connected with the status of brain functional connectivity and implied that acupuncture plays a homeostatic role in the BP treatment. PMID:26161125

  4. Age-related changes in anterior cingulate cortex glutamate in schizophrenia: A (1)H MRS Study at 7 Tesla.

    PubMed

    Brandt, Allison S; Unschuld, Paul G; Pradhan, Subechhya; Lim, Issel Anne L; Churchill, Gregory; Harris, Ashley D; Hua, Jun; Barker, Peter B; Ross, Christopher A; van Zijl, Peter C M; Edden, Richard A E; Margolis, Russell L

    2016-04-01

    The extent of age-related changes in glutamate and other neurometabolites in the anterior cingulate cortex (ACC) in individuals with schizophrenia remain unclear. Magnetic resonance spectroscopy (MRS) at 7 T, which yields precise measurements of various metabolites and can distinguish glutamate from glutamine, was used to determine levels of ACC glutamate and other metabolites in 24 individuals with schizophrenia and 24 matched controls. Multiple regression analysis revealed that ACC glutamate decreased with age in patients but not controls. No changes were detected in levels of glutamine, N-acetylaspartate, N-acetylaspartylglutamic acid, myo-inositol, GABA, glutathione, total creatine, and total choline. These results suggest that age may be an important modifier of ACC glutamate in schizophrenia. PMID:26925800

  5. 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

  6. Decision making in the Balloon Analogue Risk Task (BART): anterior cingulate cortex signals loss aversion but not the infrequency of risky choices.

    PubMed

    Fukunaga, Rena; Brown, Joshua W; Bogg, Tim

    2012-09-01

    The inferior frontal gyrus/anterior insula (IFG/AI) and anterior cingulate cortex (ACC) are key regions involved in risk appraisal during decision making, but accounts of how these regions contribute to decision making under risk remain contested. To help clarify the roles of these and other related regions, we used a modified version of the Balloon Analogue Risk Task (Lejuez et al., Journal of Experimental Psychology: Applied, 8, 75-84, 2002) to distinguish between decision-making and feedback-related processes when participants decided to pursue a gain as the probability of loss increased parametrically. Specifically, we set out to test whether the ACC and IFG/AI regions correspond to loss aversion at the time of decision making in a way that is not confounded with either reward-seeking or infrequency effects. When participants chose to discontinue inflating the balloon (win option), we observed greater ACC and mainly bilateral IFG/AI activity at the time of decision as the probability of explosion increased, consistent with increased loss aversion but inconsistent with an infrequency effect. In contrast, we found robust vmPFC activity when participants chose to continue inflating the balloon (risky option), consistent with reward seeking. However, in the cingulate and in mainly bilateral IFG regions, blood-oxygenation-level-dependent activation decreased when participants chose to inflate the balloon as the probability of explosion increased, findings that are consistent with a reduced loss aversion signal. Our results highlight the existence of distinct reward-seeking and loss-averse signals during decision making, as well as the importance of distinguishing between decision and feedback signals. PMID:22707378

  7. The microRNA network is altered in anterior cingulate cortex of patients with unipolar and bipolar depression.

    PubMed

    Azevedo, Joshua A; Carter, Bradley S; Meng, Fan; Turner, David L; Dai, Manhong; Schatzberg, Alan F; Barchas, Jack D; Jones, Edward G; Bunney, William E; Myers, Richard M; Akil, Huda; Watson, Stanley J; Thompson, Robert C

    2016-11-01

    MicroRNAs (miRNAs) are small, non-coding RNAs acting as post-transcriptional regulators of gene expression. Though implicated in multiple CNS disorders, miRNAs have not been examined in any psychiatric disease state in anterior cingulate cortex (AnCg), a brain region centrally involved in regulating mood. We performed qPCR analyses of 29 miRNAs previously implicated in psychiatric illness (major depressive disorder (MDD), bipolar disorder (BP) and/or schizophrenia (SZ)) in AnCg of patients with MDD and BP versus controls. miR-132, miR-133a and miR-212 were initially identified as differentially expressed in BP, miR-184 in MDD and miR-34a in both MDD and BP (although none survived multiple correction testing and must be considered preliminary). In silico target prediction algorithms identified putative targets of differentially expressed miRNAs. Nuclear Co-Activator 1 (NCOA1), Nuclear Co-Repressor 2 (NCOR2) and Phosphodiesterase 4B (PDE4B) were selected based upon predicted targeting by miR-34a (with NCOR2 and PDE4B both targeted by miR-184) and published relevance to psychiatric illness. Luciferase assays identified PDE4B as a target of miR-34a and miR-184, while NCOA1 and NCOR2 were targeted by miR-34a and 184, respectively. qPCR analyses were performed to determine whether changes in miRNA levels correlated with mRNA levels of validated targets. NCOA1 showed an inverse correlation with miR-34a in BP, while NCOR2 demonstrated a positive correlation. In sum, this is the first study to demonstrate miRNA changes in AnCg in psychiatric illness and validate miR-34a as differentially expressed in CNS in MDD. These findings support a mechanistic role for miRNAs in the regulation of stress-responsive genes disrupted in psychiatric illness. PMID:27468165

  8. 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

  9. 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

  10. 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…

  11. Task-dependent posterior cingulate activation in mild cognitive impairment

    PubMed Central

    Ries, Michele L.; Schmitz, Taylor W.; Kawahara-Baccus, Tisha N.; Torgerson, Britta M.; Trivedi, Mehul A.; Johnson, Sterling C.

    2009-01-01

    Neuroimaging research has demonstrated that the posterior cingulate cortex (PCC) is functionally compromised in individuals diagnosed with amnestic Mild Cognitive Impairment (MCI), a major risk factor for the development of Alzheimer’s disease (AD). In functional magnetic resonance imaging (fMRI) studies with healthy participants, this same region is active during self-appraisal (requiring retrieval of semantic knowledge about the self) as well as episodic recognition of recently-learned information. Administering both types of tasks to people with MCI may reveal important information regarding the role of the PCC in recollection. This study investigated fMRI activation in the PCC in individuals with MCI and age, gender, and education-matched controls across two tasks. The first task was a visual episodic recognition task in which participants indicated whether pictures had or had not been presented during a study session. The second task was an autobiographical self-appraisal task in which subjects rated themselves on a set of trait adjectives. Results of a conjunction analysis revealed the PCC as the sole region commonly active during both tasks in the healthy older adults. Furthermore, additional analysis revealed an interaction in the PCC indicating a task-dependent response in the MCI group. MCI participants showed PCC activation during self-appraisal, but not during episodic retrieval. These results suggest in MCI that the PCC shows functional degradation during episodic retrieval of visual information learned in the laboratory. In contrast, the PCC’s role in retrieval and evaluation of highly-elaborated information regarding the self is more well-preserved. PMID:16102979

  12. 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.

  13. 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

  14. Development of anterior cingulate functional connectivity from late childhood to early adulthood.

    PubMed

    Kelly, A M Clare; Di Martino, Adriana; Uddin, Lucina Q; Shehzad, Zarrar; Gee, Dylan G; Reiss, Philip T; Margulies, Daniel S; Castellanos, F Xavier; Milham, Michael P

    2009-03-01

    Human cerebral development is remarkably protracted. Although microstructural processes of neuronal maturation remain accessible only to morphometric post-mortem studies, neuroimaging tools permit the examination of macrostructural aspects of brain development. The analysis of resting-state functional connectivity (FC) offers novel possibilities for the investigation of cerebral development. Using seed-based FC methods, we examined the development of 5 functionally distinct cingulate-based intrinsic connectivity networks (ICNs) in children (n = 14, 10.6 +/- 1.5 years), adolescents (n = 12, 15.4 +/- 1.2) and young adults (n=14, 22.4 +/- 1.2). Children demonstrated a more diffuse pattern of correlation with voxels proximal to the seed region of interest (ROI) ("local FC"), whereas adults exhibited more focal patterns of FC, as well as a greater number of significantly correlated voxels at long distances from the seed ROI. Adolescents exhibited intermediate patterns of FC. Consistent with evidence for different maturational time courses, ICNs associated with social and emotional functions exhibited the greatest developmental effects. Our findings demonstrate the utility of FC for the study of developing functional organization. Moreover, given that ICNs are thought to have an anatomical basis in neuronal connectivity, measures of FC may provide a quantitative index of brain maturation in healthy subjects and those with neurodevelopmental disorders.

  15. 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

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

    PubMed

    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

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

    PubMed

    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.

  18. 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

  19. 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

  20. Executive function and error detection: The effect of motivation on cingulate and ventral striatum activity.

    PubMed

    Simões-Franklin, Cristina; Hester, Robert; Shpaner, Marina; Foxe, John J; Garavan, Hugh

    2010-03-01

    Reacting appropriately to errors during task performance is fundamental to successful negotiation of our environment. This is especially true when errors will result in a significant penalty for the person performing a given task, be they financial or otherwise. Error responses and monitoring states were manipulated in a GO/NOGO task by introducing a financial punishment for errors. This study employed a mixed block design alternating between punishment and no punishment (neutral) conditions, enabling an assessment of tonic changes associated with cognitive control as well as trial-specific effects. Behavioural results revealed slower responses and fewer commission errors in the punishment condition. The dorsal anterior cingulate cortex (ACC) had equal trial-specific activity for errors in the neutral and punishment conditions but had greater tonic activity throughout the punishment condition. A region of interest analysis revealed different activation patterns between the dorsal and the rostral parts of the ACC with the rostral ACC having only trial-specific activity for errors in the punishment condition, an activity profile similar to one observed in the nucleus accumbens. This study suggests that there is a motivational influence on cognitive processes in the ACC and nucleus accumbens and hints at a dissociation between tonic proactive activity and phasic reactive error-related activity.

  1. 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

  2. Vagus Nerve Stimulation Alters Phase Synchrony of the Anterior Cingulate Cortex and Facilitates Decision Making in Rats

    PubMed Central

    Cao, Bing; Wang, Jun; Shahed, Mahadi; Jelfs, Beth; Chan, Rosa H. M.; Li, Ying

    2016-01-01

    Vagus nerve stimulation (VNS) can enhance memory and cognitive functions in both rats and humans. Studies have shown that VNS influenced decision-making in epileptic patients. However, the sites of action involved in the cognitive-enhancement are poorly understood. By employing a conscious rat model equipped with vagus nerve cuff electrode, we assess the role of chronic VNS on decision-making in rat gambling task (RGT). Simultaneous multichannel-recordings offer an ideal setup to test the hypothesis that VNS may induce alterations of in both spike-field-coherence and synchronization of theta oscillations across brain areas in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). Daily VNS, administered immediately following training sessions of RGT, caused an increase in ‘good decision-maker’ rats. Neural spikes in the ACC became synchronized with the ongoing theta oscillations of local field potential (LFP) in BLA following VNS. Moreover, cross-correlation analysis revealed synchronization between the ACC and BLA. Our results provide specific evidence that VNS facilitates decision-making and unveils several important roles for VNS in regulating LFP and spike phases, as well as enhancing spike-phase coherence between key brain areas involved in cognitive performance. These data may serve to provide fundamental notions regarding neurophysiological biomarkers for therapeutic VNS in cognitive impairment. PMID:27731403

  3. Anterior cingulate cortex instigates adaptive switches in choice by integrating immediate and delayed components of value in ventromedial prefrontal cortex.

    PubMed

    Economides, Marcos; Guitart-Masip, Marc; Kurth-Nelson, Zeb; Dolan, Raymond J

    2014-02-26

    Actions can lead to an immediate reward or punishment and a complex set of delayed outcomes. Adaptive choice necessitates the brain track and integrate both of these potential consequences. Here, we designed a sequential task whereby the decision to exploit or forego an available offer was contingent on comparing immediate value and a state-dependent future cost of expending a limited resource. Crucially, the dynamics of the task demanded frequent switches in policy based on an online computation of changing delayed consequences. We found that human subjects choose on the basis of a near-optimal integration of immediate reward and delayed consequences, with the latter computed in a prefrontal network. Within this network, anterior cingulate cortex (ACC) was dynamically coupled to ventromedial prefrontal cortex (vmPFC) when adaptive switches in choice were required. Our results suggest a choice architecture whereby interactions between ACC and vmPFC underpin an integration of immediate and delayed components of value to support flexible policy switching that accommodates the potential delayed consequences of an action.

  4. 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

  5. Resting state functional connectivity of the anterior cingulate cortex in veterans with and without post-traumatic stress disorder.

    PubMed

    Kennis, Mitzy; Rademaker, Arthur R; van Rooij, Sanne J H; Kahn, René S; Geuze, Elbert

    2015-01-01

    Post-traumatic stress disorder (PTSD) is an anxiety disorder that is associated with structural and functional alterations in several brain areas, including the anterior cingulate cortex (ACC). Here, we examine resting state functional connectivity of ACC subdivisions in PTSD, using a seed-based approach. Resting state magnetic resonance images were obtained from male veterans with (n = 31) and without (n = 25) PTSD, and healthy male civilian controls (n = 25). Veterans with and without PTSD (combat controls) had reduced functional connectivity compared to healthy controls between the caudal ACC and the precentral gyrus, and between the perigenual ACC and the superior medial gyrus and middle temporal gyrus. Combat controls had increased connectivity between the rostral ACC and precentral/middle frontal gyrus compared to PTSD patients and healthy civilian controls. The resting state functional connectivity differences in the perigenual ACC network reported here indicate that veterans differ from healthy controls, potentially due to military training, deployment, and/or trauma exposure. In addition, specific alterations in the combat controls may potentially be related to resilience. These results underline the importance of distinguishing trauma-exposed (combat) controls from healthy civilian controls when studying PTSD.

  6. Contributions of the anterior cingulate cortex and amygdala to pain- and fear-conditioned place avoidance in rats.

    PubMed

    Gao, Yong-Jing; Ren, Wen-Hua; Zhang, Yu-Qiu; Zhao, Zhi-Qi

    2004-07-01

    The pain experience includes a sensory-discriminative and an affective-emotional component. The sensory component of pain has been extensively studied, while data about the negative affective component of pain are quite limited. The anterior cingulate cortex (ACC), and amygdala are thought to be key neural substrates underlying emotional responses. Using formalin-induced conditioned place avoidance (F-CPA) and electric foot-shock conditioned place avoidance (S-CPA) models, the present study observed the effects of bilateral excitotoxic (quinolinic acid 200 nmol/microl) lesions of the ACC and amygdala on pain and fear induced negative emotion, as well as on sensory component of pain. In the place-conditioning paradigm, both intraplantar (i.pl.) injection of formalin and electric foot-shock produced conditioned place avoidance. Excitotoxin-induced lesion of either the ACC or amygdala significantly reduced the magnitude of F-CPA. However, the decrease in the magnitude of S-CPA occurred only in the amygdala, but not ACC lesioned animals. Neither ACC nor amygdala lesion significantly changed formalin-induced acute nociceptive behaviors. These results suggest that the amygdala is involved in both pain- and fear-related negative emotion, and the ACC might play a critical role in the expression of pain-related negative emotion.

  7. 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

  8. Upregulation of the rostral anterior cingulate cortex can alter the perception of emotions: fMRI-based neurofeedback at 3 and 7 T.

    PubMed

    Gröne, M; Dyck, M; Koush, Y; Bergert, S; Mathiak, K A; Alawi, E M; Elliott, M; Mathiak, K

    2015-03-01

    Recent advances in real-time functional magnetic resonance imaging (rt-fMRI) techniques enable online feedback about momentary brain activity from a localized region of interest. The anterior cingulate cortex (ACC) as a central hub for cognitive and emotional networks and its modulation has been suggested to elicit mood changes. In the presented real-time fMRI neurofeedback experiment at a 3 and a 7 T scanner we enabled participants to regulate ACC activity within one training session. The session consisted of three training runs of 8.5 min where subjects received online feedback about their current ACC activity. Before and after each run we presented emotional prosody. Subjects rated these stimuli according to their emotional valence and arousal, which served as an implicit mood measure. We found increases in ACC activation at 3 T (n = 15) and at 7 T (n = 9) with a higher activation success for the 3 T group. FMRI signal control of the rostral ACC depended on signal quality and predicted a valence bias in the rating of emotional prosody. Real-time fMRI neurofeedback of the ACC is feasible at different magnetic field strengths and can modulate localized ACC activity and emotion perception. It promises non-invasive therapeutic approaches for different psychiatric disorders characterized by impaired self-regulation.

  9. Reward value enhances post-decision error-related activity in the cingulate cortex.

    PubMed

    Taylor, Jessica E; Ogawa, Akitoshi; Sakagami, Masamichi

    2016-06-01

    By saying "Anyone who has never made a mistake has never tried anything new", Albert Einstein himself allegedly implied that the making and processing of errors are essential for behavioral adaption to a new or changing environment. These essential error-related cognitive and neural processes are likely influenced by reward value. However, previous studies have not dissociated accuracy and value and so the distinct effect of reward on error processing in the brain remained unknown. Therefore, we set out to investigate this at various points in decision-making. We used functional magnetic resonance imaging to scan participants while they completed a random dot motion discrimination task where reward and non-reward were associated with stimuli via classical conditioning. Pre-error activity was found in the medial frontal cortex prior to response but this was not related to reward value. At response time, error-related activity was found to be significantly greater in reward than non-reward trials in the midcingulate cortex. Finally at outcome time, error-related activity was found in the anterior cingulate cortex in non-reward trials. These results show that reward value enhances post-decision but not pre-decision error-related activities and these results therefore have implications for theories of error correction and confidence.

  10. Reward value enhances post-decision error-related activity in the cingulate cortex.

    PubMed

    Taylor, Jessica E; Ogawa, Akitoshi; Sakagami, Masamichi

    2016-06-01

    By saying "Anyone who has never made a mistake has never tried anything new", Albert Einstein himself allegedly implied that the making and processing of errors are essential for behavioral adaption to a new or changing environment. These essential error-related cognitive and neural processes are likely influenced by reward value. However, previous studies have not dissociated accuracy and value and so the distinct effect of reward on error processing in the brain remained unknown. Therefore, we set out to investigate this at various points in decision-making. We used functional magnetic resonance imaging to scan participants while they completed a random dot motion discrimination task where reward and non-reward were associated with stimuli via classical conditioning. Pre-error activity was found in the medial frontal cortex prior to response but this was not related to reward value. At response time, error-related activity was found to be significantly greater in reward than non-reward trials in the midcingulate cortex. Finally at outcome time, error-related activity was found in the anterior cingulate cortex in non-reward trials. These results show that reward value enhances post-decision but not pre-decision error-related activities and these results therefore have implications for theories of error correction and confidence. PMID:26739226

  11. 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

  12. 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

  13. Self-Referential Processing of Negative Stimuli within the Ventral Anterior Cingulate Gyrus and Right Amygdala

    ERIC Educational Resources Information Center

    Yoshimura, Shinpei; Ueda, Kazutaka; Suzuki, Shin-ichi; Onoda, Keiichi; Okamoto, Yasumasa; Yamawaki, Shigeto

    2009-01-01

    Neural activity associated with self-referential processing of emotional stimuli was investigated using whole brain functional magnetic resonance imaging (fMRI). Fifteen healthy subjects underwent fMRI scanning while making judgments about positive and negative trait words in four conditions (self-reference, other-reference, semantic processing,…

  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. 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.

  16. 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

  17. 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

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

    PubMed

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

    2016-01-01

    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.

  19. 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

  20. 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

  1. Lesion of the rostral anterior cingulate cortex eliminates the aversiveness of spontaneous neuropathic pain following partial or complete axotomy.

    PubMed

    Qu, Chaoling; King, Tamara; Okun, Alec; Lai, Josephine; Fields, Howard L; Porreca, Frank

    2011-07-01

    Neuropathic pain is often "spontaneous" or "stimulus-independent." Such pain may result from spontaneous discharge in primary afferent nociceptors in injured peripheral nerves. However, whether axotomized primary afferent nociceptors give rise to pain is unclear. The rostral anterior cingulate cortex (rACC) mediates the negative affective component of inflammatory pain. Whether the rACC integrates the aversive component of chronic spontaneous pain arising from nerve injury is not known. Here, we used the principle of negative reinforcement to show that axotomy produces an aversive state reflecting spontaneous pain driven from injured nerves. Additionally, we investigated whether the rACC contributes to the aversiveness of nerve injury-induced spontaneous pain. Partial or complete hind paw denervation was produced by sciatic or sciatic/saphenous axotomy, respectively. Conditioned place preference resulting from presumed pain relief was observed following spinal clonidine in animals with sciatic axotomy but not in sham-operated controls. Similarly, lidocaine administration into the rostral ventromedial medulla (RVM) produced place preference selectively in animals with sciatic/saphenous axotomy. In rats with spinal nerve ligation (SNL) injury, lesion of the rACC blocked the reward elicited by RVM lidocaine but did not alter acute stimulus-evoked hypersensitivity. Lesion of the rACC did not block cocaine-induced reward, indicating that rACC blockade did not impair memory encoding or retrieval but did impair spontaneous aversiveness. These data indicate that spontaneous pain arising from injured nerve fibers produces a tonic aversive state that is mediated by the rACC. Identification of the circuits mediating aversiveness of chronic pain should facilitate the development of improved therapies.

  2. 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

  3. Genetic Modulation of GABA Levels in the Anterior Cingulate Cortex by GAD1 and COMT

    PubMed Central

    Marenco, Stefano; Savostyanova, Antonina A; van der Veen, Jan Willem; Geramita, Matthew; Stern, Alexa; Barnett, Alan S; Kolachana, Bhaskar; Radulescu, Eugenia; Zhang, Fengyu; Callicott, Joseph H; Straub, Richard E; Shen, Jun; Weinberger, Daniel R

    2010-01-01

    γ-Aminobutyric acid (GABA)-ergic transmission is critical for normal cortical function and is likely abnormal in a variety of neuropsychiatric disorders. We tested the in vivo effects of variations in two genes implicated in GABA function on GABA concentrations in prefrontal cortex of living subjects: glutamic acid decarboxylase 1 (GAD1), which encodes GAD67, and catechol-o-methyltransferase (COMT), which regulates synaptic dopamine in the cortex. We studied six single nucleotide polymorphisms (SNPs) in GAD1 previously associated with risk for schizophrenia or cognitive dysfunction and the val158met polymorphism in COMT in 116 healthy volunteers using proton magnetic resonance spectroscopy. Two of the GAD1 SNPs (rs1978340 (p=0.005) and rs769390 (p=0.004)) showed effects on GABA levels as did COMT val158met (p=0.04). We then tested three SNPs in GAD1 (rs1978340, rs11542313, and rs769390) for interaction with COMT val158met based on previous clinical results. In this model, rs11542313 and COMT val158met showed significant main effects (p=0.001 and 0.003, respectively) and a trend toward a significant interaction (p=0.05). Interestingly, GAD1 risk alleles for schizophrenia were associated with higher GABA/Cre, and Val-Val homozygotes had high GABA/Cre levels when on a GAD1 risk genotype background (N=6). These results support the importance of genetic variation in GAD1 and COMT in regulating prefrontal cortical GABA function. The directionality of the effects, however, is inconsistent with earlier evidence of decreased GABA activity in schizophrenia. PMID:20357758

  4. Impact of family history of alcoholism on glutamine/glutamate ratio in anterior cingulate cortex in substance-naïve adolescents.

    PubMed

    Cohen-Gilbert, Julia E; Sneider, Jennifer T; Crowley, David J; Rosso, Isabelle M; Jensen, J Eric; Silveri, Marisa M

    2015-12-01

    Neuroimaging studies of individuals with family histories of alcoholism provide evidence suggesting neurobiological risk factors for alcoholism. Youth family history positive (FH+) for alcoholism exhibit increased impulsivity compared to family history negative (FH-) peers in conjunction with altered functional activation in prefrontal cortex, including anterior cingulate cortex (ACC). This study examined glutamate (Glu) and glutamine (Gln), amino acids vital to protein synthesis, cellular metabolism and neurotransmission, acquired from ACC and parieto-occipital cortex (POC) using magnetic resonance spectroscopy (MRS) at 4T. Participants were 28 adolescents (13 male, 12-14 yrs) and 31 emerging adults (16 male, 18-25 yrs), stratified into FH- and FH+ groups. Significantly higher ACC Gln/Glu was observed in emerging adults versus adolescents in FH- but not FH+ groups. In FH- adolescents, higher impulsivity was significantly associated with higher ACC Gln/Glu. In FH+ emerging adults, higher impulsivity was negatively associated with ACC Gln/Glu. No differences or associations were observed for POC. These findings provide preliminary evidence that family history of alcoholism is associated with a neurochemical profile that may influence normative age differences in glutamatergic metabolites and their association with impulse control, which together could confer greater genetic risk of addiction later in life.

  5. 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

  6. The origin of projections from the posterior cingulate and retrosplenial cortices to the anterior, medial dorsal and laterodorsal thalamic nuclei of macaque monkeys

    PubMed Central

    Aggleton, John P; Saunders, Richard C; Wright, Nicholas F; Vann, Seralynne D

    2014-01-01

    Interactions between the posterior cingulate cortex (areas 23 and 31) and the retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal medial thalamic nuclei are thought to support various aspects of cognition, including memory and spatial processing. To detail these interactions better, the present study used retrograde tracers to reveal the origins of the corticothalamic projections in two closely related monkey species (Macaca mulatta, Macaca fascicularis). The medial dorsal thalamic nucleus received only light cortical inputs, which predominantly arose from area 23. Efferents to the anterior medial thalamic nucleus also arose principally from area 23, but these projections proved more numerous than those to the medial dorsal nucleus and also involved additional inputs from areas 29 and 30. The anterior ventral and laterodorsal thalamic nuclei had similar sources of inputs from the posterior cingulate and retrosplenial cortices. For both nuclei, the densest projections arose from areas 29 and 30, with numbers of thalamic inputs often decreasing when going dorsal from area 23a to 23c and to area 31. In all cases, the corticothalamic projections almost always arose from the deepest cortical layer. The different profiles of inputs to the anterior medial and anterior ventral thalamic nuclei reinforce other anatomical and electrophysiological findings suggesting that these adjacent thalamic nuclei serve different, but complementary, functions supporting memory. While the lack of retrosplenial connections singled out the medial dorsal nucleus, the very similar connection patterns shown by the anterior ventral and laterodorsal nuclei point to common roles in cognition. PMID:24134130

  7. Age-Related Changes in the Functional Network Underlying Specific and General Autobiographical Memory Retrieval: A Pivotal Role for the Anterior Cingulate Cortex

    PubMed Central

    Martinelli, Pénélope; Sperduti, Marco; Devauchelle, Anne-Dominique; Kalenzaga, Sandrine; Gallarda, Thierry; Lion, Stéphanie; Delhommeau, Marion; Anssens, Adèle; Amado, Isabelle; Meder, Jean François; Krebs, Marie-Odile; Oppenheim, Catherine; Piolino, Pascale

    2013-01-01

    Age-related changes in autobiographical memory (AM) recall are characterized by a decline in episodic details, while semantic aspects are spared. This deleterious effect is supposed to be mediated by an inefficient recruitment of executive processes during AM retrieval. To date, contrasting evidence has been reported on the neural underpinning of this decline, and none of the previous studies has directly compared the episodic and semantic aspects of AM in elderly. We asked 20 young and 17 older participants to recall specific and general autobiographical events (i.e., episodic and semantic AM) elicited by personalized cues while recording their brain activity by means of fMRI. At the behavioral level, we confirmed that the richness of episodic AM retrieval is specifically impoverished in aging and that this decline is related to the reduction of executive functions. At the neural level, in both age groups, we showed the recruitment of a large network during episodic AM retrieval encompassing prefrontal, cortical midline and posterior regions, and medial temporal structures, including the hippocampus. This network was very similar, but less extended, during semantic AM retrieval. Nevertheless, a greater activity was evidenced in the dorsal anterior cingulate cortex (dACC) during episodic, compared to semantic AM retrieval in young participants, and a reversed pattern in the elderly. Moreover, activity in dACC during episodic AM retrieval was correlated with inhibition and richness of memories in both groups. Our findings shed light on the direct link between episodic AM retrieval, executive control, and their decline in aging, proposing a possible neuronal signature. They also suggest that increased activity in dACC during semantic AM retrieval in the elderly could be seen as a compensatory mechanism underpinning successful AM performance observed in aging. These results are discussed in the framework of recently proposed models of neural reorganization in aging

  8. Effect of Dopamine Transporter Gene (SLC6A3) Variation on Dorsal Anterior Cingulate Function in Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Brown, Ariel B.; Biederman, Joseph; Valera, Eve M.; Doyle, Alysa E.; Bush, George; Spencer, Thomas; Monuteaux, Michael C.; Mick, Eric; Whitfield-Gabrieli, Susan; Makris, Nikos; LaViolette, Peter S.; Oscar-Berman, Marlene; Faraone, Stephen V.; Seidman, Larry J.

    2010-01-01

    Objective - Although Attention-Deficit/Hyperactivity Disorder (ADHD) is associated both with brain alterations in attention and executive function (EF) circuitry and with genetic variations within the dopamine system (including the dopamine transporter gene [SLC6A3]), few studies have directly investigated how genetic variations are linked to brain alterations. We sought to examine how a polymorphism in the 3’ untranslated region (UTR) of SLC6A3, associated with ADHD in meta-analysis, might contribute to variation in dorsal anterior cingulate cortex (dACC) function in subjects with ADHD. Method - We collected fMRI scans of 42 individuals with ADHD, all of European descent and over the age of 17, while they performed the Multi-Source Interference Task (MSIT), a cognitive task shown to activate dACC. SLC6A3 3’ UTR variable number tandem repeat (VNTR) polymorphisms were genotyped and brain activity was compared for groups based on allele status. Results - ADHD individuals homozygous for the 10R allele showed significant hypoactivation in the left dACC compared to 9R-carriers. Exploratory analysis also showed trends toward hypoactivation in the 10R homozygotes in left cerebellar vermis and right lateral prefrontal cortex. Further breakdown of genotype groups showed similar activation in individuals heterozygous and homozygous for the 9R allele. Conclusions - Alterations in activation of attention and EF networks found previously to be involved in ADHD are likely influenced by SLC6A3 genotype. This genotype may contribute to heterogeneity of brain alterations found within ADHD samples. PMID:19676101

  9. Inflammation Causes Mood Changes Through Alterations in Subgenual Cingulate Activity and Mesolimbic Connectivity

    PubMed Central

    Harrison, Neil A.; Brydon, Lena; Walker, Cicely; Gray, Marcus A.; Steptoe, Andrew; Critchley, Hugo D.

    2009-01-01

    Background Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-α induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines. Objectives To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing. Methods In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Mood questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed an implicit emotional face perception task during functional magnetic resonance imaging. Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression. Results Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours. Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex (sACC) (a region implicated in the etiology of depression) during emotional face processing. Furthermore, inflammation-associated mood change reduced connectivity of sACC to amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6. Conclusions Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli. Peripheral cytokines modulate this mood-dependent sACC connectivity, suggesting a common

  10. Women with Multiple Chemical Sensitivity Have Increased Harm Avoidance and Reduced 5-HT1A Receptor Binding Potential in the Anterior Cingulate and Amygdala

    PubMed Central

    Åhs, Fredrik; Savic, Ivanka

    2013-01-01

    Multiple chemical sensitivity (MCS) is a common condition, characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the underlying mechanisms are unknown. Contrary to the expectations it was recently found that persons with MCS activate the odor-processing brain regions less than controls, while their activation of the anterior cingulate cortex (ACC) is increased. The present follow-up study was designed to test the hypotheses that MCS subjects have increased harm avoidance and deviations in the serotonin system, which could render them intolerant to environmental odors. Twelve MCS and 11 control subjects, age 22–44, all working or studying females, were included in a PET study where 5-HT1A receptor binding potential (BP) was assessed after bolus injection of [11C]WAY100635. Psychological profiles were assessed by the Temperament and Character Inventory and the Swedish universities Scales of Personality. All MCS and 12 control subjects were also tested for emotional startle modulation in an acoustic startle test. MCS subjects exhibited significantly increased harm avoidance, and anxiety compared to controls. They also had a reduced 5-HT1A receptor BP in amygdala (p = 0.029), ACC (p = 0.005) (planned comparisons, significance level 0.05), and insular cortex (p = 0.003; significance level p<0.005 with Bonferroni correction), and showed an inverse correlation between degree of anxiety and the BP in the amygdala (planned comparison). No group by emotional category difference was found in the startle test. Increased harm avoidance and the observed changes in the 5-HT1A receptor BP in the regions processing harm avoidance provides a plausible pathophysiological ground for the symptoms described in MCS, and yields valuable information for our general understanding of idiopathic environmental intolerances. PMID:23349968

  11. 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

  12. Connectivity from the ventral anterior cingulate to the amygdala is modulated by appetitive motivation in response to facial signals of aggression

    PubMed Central

    Passamonti, Luca; Rowe, James B.; Ewbank, Michael; Hampshire, Adam; Keane, Jill; Calder, Andrew J.

    2008-01-01

    For some people facial expressions of aggression are intimidating, for others they are perceived as provocative, evoking an aggressive response. Identifying the key neurobiological factors that underlie this variation is fundamental to our understanding of aggressive behaviour. The amygdala and the ventral anterior cingulate cortex (ACC) have been implicated in aggression. Using functional magnetic resonance imaging (fMRI), we studied how the interaction between these regions is influenced by the drive to obtain reward (reward–drive or appetitive motivation), a personality trait consistently associated with aggression. Two distinct techniques showed that the connectivity between the ventral ACC and the amygdala was strongly correlated with personality, with high reward–drive participants displaying reduced negative connectivity. Furthermore, the direction of this effect was restricted from ventral ACC to the amygdala but not vice versa. The personality-mediated variation in the pathway from the ventral anterior cingulate cortex to the amygdala provides an account of why signals of aggression are interpreted as provocative by some individuals more than others. PMID:18722533

  13. Intra- and Interhemispheric Propagation of Electrophysiological Synchronous Activity and Its Modulation by Serotonin in the Cingulate Cortex of Juvenile Mice.

    PubMed

    Rovira, Víctor; Geijo-Barrientos, Emilio

    2016-01-01

    Disinhibition of the cortex (e.g., by GABA -receptor blockade) generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14-20 days), the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7) than in retrosplenial cortex slices (RSC: 21.99 ± 2.75 ms, n = 5; p<0.05), which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s). We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere), and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges.

  14. Intra- and Interhemispheric Propagation of Electrophysiological Synchronous Activity and Its Modulation by Serotonin in the Cingulate Cortex of Juvenile Mice

    PubMed Central

    Rovira, Víctor; Geijo-Barrientos, Emilio

    2016-01-01

    Disinhibition of the cortex (e.g., by GABA -receptor blockade) generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14–20 days), the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7) than in retrosplenial cortex slices (RSC: 21.99 ± 2.75 ms, n = 5; p<0.05), which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s). We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere), and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges. PMID:26930051

  15. Intra- and Interhemispheric Propagation of Electrophysiological Synchronous Activity and Its Modulation by Serotonin in the Cingulate Cortex of Juvenile Mice.

    PubMed

    Rovira, Víctor; Geijo-Barrientos, Emilio

    2016-01-01

    Disinhibition of the cortex (e.g., by GABA -receptor blockade) generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14-20 days), the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7) than in retrosplenial cortex slices (RSC: 21.99 ± 2.75 ms, n = 5; p<0.05), which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s). We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere), and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges. PMID:26930051

  16. Alterations in brain connectivity in three sub-regions of the anterior cingulate cortex in heroin-dependent individuals: Evidence from resting state fMRI.

    PubMed

    Zhang, Y; Gong, J; Xie, C; Ye, E M; Jin, X; Song, H; Yang, Z; Shao, Y

    2015-01-22

    Previous studies that utilized task-based approaches have demonstrated that the chronic use of heroin is associated with altered activity of the anterior cingulate cortex (ACC). However, few studies have focused on examining the variation in resting-state functional connectivity in heroin-dependent individuals, which might help further understanding the mechanisms underlying heroin addiction. Due to the structural and functional heterogeneity of the ACC, we systematically mapped the resting-state functional connectivity patterns of three sub-regions of the ACC in heroin-dependent individuals, wondered whether the partition of three sub-regions of the ACC is feasible in heroin-dependent individuals, and identified how heroin affected the correlated activities among three sub-regions of the ACC using resting-state functional magnetic resonance imaging (fMRI). In the present study, fMRI data were acquired from 21 heroin-dependent individuals (Her group) and 15 non-addicted controls (CN group). Compared to controls, there were reduced functional connectivities in the dorsal ACC (dACC) and rostral ACC (rACC) networks with different areas of the dorsal striatum (the caudate and the putamen) in the Her group. Meanwhile, there exhibited an inverted alteration of pattern for orbital frontal cortex (OFC) and superior frontal gyrus (SFG) in the functional connectivity network with the dACC and subcallosal ACC (sACC), and a different alteration of the cerebellum and the amygdala in the functional connectivity network with the rACC and the sACC. In addition, we also found reduced connectivities between dACC and rACC, as well as reduced connectivities between sACC and dACC. Our findings of variations of functional connectivities in three sub-regions of ACC in Her group implied that these sub-regions of the ACC together with other key brain areas (such as dorsal striatum, OFC, SFG, cerebellum, amygdale, etc.) might potentially play independent and/or overlapping roles in heroin

  17. Differential emotional experience induces elevated spine densities on basal dendrites of pyramidal neurons in the anterior cingulate cortex of Octodon degus.

    PubMed

    Helmeke, C; Poeggel, G; Braun, K

    2001-01-01

    It appears likely that, in analogy to the synaptic development of sensory and motor cortices, which critically depends on sensory or motor stimulation (Rosenzweig and Bennett, 1996), the synaptic development of limbic cortical regions are modulated by early postnatal cognitive and emotional experiences. The very first postnatal experience, which takes place in a confined and stable familial environment, is the interaction of the newborn individual with the parents and siblings (Gray, 1958). The aim of this quantitative morphological study was to analyze the impact of different degrees of juvenile emotional experience on the synaptic development in a limbic cortical area, the dorsal anterior cingulate cortex, a region which is involved in the perception and regulation of emotions. We study the precocious trumpet-tailed rat (Octodon degus) as the animal model, because, like human babies, this species is born with functional visual and acoustic systems and the pups are therefore capable of detecting even subtle environmental changes immediately after birth (Reynolds and Wright, 1979; Poeggel and Braun, 1996; Braun et al., 2000; Ovtscharoff and Braun, 2001). The results demonstrate that already a subtle disturbance of the familial environment such as handling induced significantly elevated spine densities on the basal dendrites of layer III cortical pyramidal neurons. More severe disturbances of the emotional environment, such as periodic parental deprivation with or without subsequent chronic social isolation, resulted in an elevation of spine densities of similar magnitude as seen after handling and in addition, altered spine densities confined to specific dendritic segments were observed in these groups. These observations unveil the remarkable sensitivity of the dorsal anterior cingulate cortex towards environmental influences and behavioral experiences during phases of postnatal development. The behavioral consequences of these experience-induced synaptic changes

  18. Lifetime use of cannabis from longitudinal assessments, cannabinoid receptor (CNR1) variation, and reduced volume of the right anterior cingulate.

    PubMed

    Hill, Shirley Y; Sharma, Vinod; Jones, Bobby L

    2016-09-30

    Lifetime measures of cannabis use and co-occurring exposures were obtained from a longitudinal cohort followed an average of 13 years at the time they received a structural MRI scan. MRI scans were analyzed for 88 participants (mean age=25.9 years), 34 of whom were regular users of cannabis. Whole brain voxel based morphometry analyses (SPM8) were conducted using 50 voxel clusters at p=0.005. Controlling for age, familial risk, and gender, we found reduced volume in Regular Users compared to Non-Users, in the lingual gyrus, anterior cingulum (right and left), and the rolandic operculum (right). The right anterior cingulum reached family-wise error statistical significance at p=0.001, controlling for personal lifetime use of alcohol and cigarettes and any prenatal exposures. CNR1 haplotypes were formed from four CNR1 SNPs (rs806368, rs1049353, rs2023239, and rs6454674) and tested with level of cannabis exposure to assess their interactive effects on the lingual gyrus, cingulum (right and left) and rolandic operculum, regions showing cannabis exposure effects in the SPM8 analyses. These analyses used mixed model analyses (SPSS) to control for multiple potentially confounding variables. Level of cannabis exposure was associated with decreased volume of the right anterior cingulum and showed interaction effects with haplotype variation.

  19. Lifetime use of cannabis from longitudinal assessments, cannabinoid receptor (CNR1) variation, and reduced volume of the right anterior cingulate.

    PubMed

    Hill, Shirley Y; Sharma, Vinod; Jones, Bobby L

    2016-09-30

    Lifetime measures of cannabis use and co-occurring exposures were obtained from a longitudinal cohort followed an average of 13 years at the time they received a structural MRI scan. MRI scans were analyzed for 88 participants (mean age=25.9 years), 34 of whom were regular users of cannabis. Whole brain voxel based morphometry analyses (SPM8) were conducted using 50 voxel clusters at p=0.005. Controlling for age, familial risk, and gender, we found reduced volume in Regular Users compared to Non-Users, in the lingual gyrus, anterior cingulum (right and left), and the rolandic operculum (right). The right anterior cingulum reached family-wise error statistical significance at p=0.001, controlling for personal lifetime use of alcohol and cigarettes and any prenatal exposures. CNR1 haplotypes were formed from four CNR1 SNPs (rs806368, rs1049353, rs2023239, and rs6454674) and tested with level of cannabis exposure to assess their interactive effects on the lingual gyrus, cingulum (right and left) and rolandic operculum, regions showing cannabis exposure effects in the SPM8 analyses. These analyses used mixed model analyses (SPSS) to control for multiple potentially confounding variables. Level of cannabis exposure was associated with decreased volume of the right anterior cingulum and showed interaction effects with haplotype variation. PMID:27500453

  20. 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

  1. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

    SciTech Connect

    Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, d.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-09-21

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  2. Localization of brain activity by temporal anti-correlation with the posterior cingulate cortex.

    PubMed

    Wang, Shijie; Zhang, Zhiqiang; Lu, Guangming; Luo, Limin

    2007-01-01

    The default mode network of brain function hypothesis has recently attracted more attention in the neuro-science community. In this study, we addressed a new data-driven method that based on temporal anti-correlation with the posterior cingulate cortex, one node of the default mode network, to localize the brain activation related to task and spontaneous epileptic discharges. The experimental results of real fMRI data analysis show not only the task-related activation region can be robustly recognized without any prior information on the functional activation paradigm, but also the epileptogenic zone in some patients with frequent interictal epileptiform discharges can be localized reliably using resting-state fMRI without EEG. PMID:18003186

  3. 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

  4. Anterior cingulate cortex gray matter volume mediates an association between 2D:4D ratio and trait aggression in women but not men.

    PubMed

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

    2015-06-01

    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.

  5. Refinement of dendritic and synaptic networks in the rodent anterior cingulate and orbitofrontal cortex: critical impact of early and late social experience.

    PubMed

    Bock, Jörg; Murmu, Reena Prity; Ferdman, Neta; Leshem, Micah; Braun, Katharina

    2008-04-01

    The process of weaning programs the neurobehavioral development and therefore provides a critical formative period for adult behavior. However, the neural substrates underlying these behavioral changes are largely unknown. To test the hypothesis that during childhood neuronal networks in the prefrontal cortex are reorganized in response to the timing and extent of social interactions, we analyzed the length, ramification, and spine density of apical and basal dendrites of layer II/III pyramidal neurons in four groups of male rats. (1) Early weaning at postnatal day (PND) 21 + postweaning social rearing (EWS), (2) late weaning at PND 30 + postweaning social rearing (LWS), (3) early weaning + postweaning social isolation (EWI), (4) late weaning + postweaning social isolation (LWI). Compared with late weaned animals, the early weaned animals displayed elevated spine densities on apical and basal dendrites only in the anterior cingulate (ACd), but not in the orbitofrontal cortex (OFC), irrespective of the postweaning housing conditions. For dendritic length and complexity an interaction between the factors weaning and postweaning rearing conditions was observed. In the ACd the EWI animals had longer and more complex apical dendrites compared with all other groups, whereas in the OFC the EWI animals displayed a significant reduction of apical dendritic length and complexity compared with the EWS group. Taken together, our findings show that the timing as well as the amount of social contact with family members significantly affects the refinement of prefrontal cortical synaptic networks, which are essential for emotional and cognitive behavior. PMID:18278801

  6. Dissociable contributions of anterior cingulate cortex and basolateral amygdala on a rodent cost/benefit decision-making task of cognitive effort.

    PubMed

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

    2014-06-01

    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.

  7. Dissociable contributions of anterior cingulate cortex and basolateral amygdala on a rodent cost/benefit decision-making task of cognitive effort.

    PubMed

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

    2014-06-01

    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

  8. 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

  9. Caudal Cingulate Infarction Manifesting Astasia

    PubMed Central

    Satow, Takeshi; Komuro, Taro; Kobayashi, Akira

    2014-01-01

    Introduction Astasia is a rare presenting symptom of stroke, usually known as ‘thalamic astasia’, induced by a lesion in the ventrolateral thalamus. We report a case of caudal cingulate infarction manifesting astasia. Case Presentation A 58-year-old male presented with inability to sit, stand and walk (astasia). No apparent motor weakness was noticed in the extremities. MRI revealed cerebral infarction in the caudal cingulate gyrus, which was located between the vertical commissure anterior (VCA) line and vertical commissure posterior (VPC) line. His symptoms persisted for 1 year to a lesser degree. Conclusion Lesions in the caudal cingulate gyrus can present with astasia. The responsible lesion is located in the cingulate gyrus between the VCA and VPC line, which might correspond to the caudal cingulate zone in humans. We should keep in mind that astasia can be a presenting symptom of stroke. PMID:24575027

  10. Cytoarchitecture and neurocytology of rabbit cingulate cortex.

    PubMed

    Vogt, Brent A

    2016-09-01

    The rabbit cingulate cortex is highly differentiated in contrast to rodents and numerous recent advances suggest the rabbit area map needs revision. Immunohistochemistry was used to assess cytoarchitecture with neuron-specific nuclear binding protein (NeuN) and neurocytology with intermediate neurofilament proteins, parvalbumin and glutamic acid decarboxylase. Key findings include: (1) Anterior cingulate cortex (ACC) area 32 has dorsal and ventral divisions. (2) Area 33 is part of ACC. (3) Midcingulate cortex (MCC) has anterior and posterior divisions and this was verified with extensive quantitative analysis and a horizontal series of sections. (4) NeuN, also known as Fox-3, is not limited to somata and formed nodules, granular clusters and striations in the apical dendrites of pyramidal neurons. (5) Area 30 forms a complex of anterior and posterior parts with further medial and lateral divisions. (6) Area 29b has two divisions and occupies substantially more volume than in rat. (7) Area 29a begins with a subsplenial component and extends relatively further caudal than in rat. As similar areal designations are often used among species, direct comparisons were made of rabbit areas with those in rat and monkey. The dichotomy of MCC is of particular interest to studies of pain as anterior MCC is most frequently activated in human acute pain studies and the rabbit can be used to study this subregion. Finally, the area 30 complex is not primarily dysgranular as in rat and is more differentiated than in any other mammal including human. The large and highly differentiated rabbit cingulate cortex provides a unique model for assessing cingulate cortex, pain processing and RNA splicing functions. PMID:26462665

  11. Hypnotic induction decreases anterior default mode activity.

    PubMed

    McGeown, William J; Mazzoni, Giuliana; Venneri, Annalena; Kirsch, Irving

    2009-12-01

    The 'default mode' network refers to cortical areas that are active in the absence of goal-directed activity. In previous studies, decreased activity in the 'default mode' has always been associated with increased activation in task-relevant areas. We show that the induction of hypnosis can reduce anterior default mode activity during rest without increasing activity in other cortical regions. We assessed brain activation patterns of high and low suggestible people while resting in the fMRI scanner and while engaged in visual tasks, in and out of hypnosis. High suggestible participants in hypnosis showed decreased brain activity in the anterior parts of the default mode circuit. In low suggestible people, hypnotic induction produced no detectable changes in these regions, but instead deactivated areas involved in alertness. The findings indicate that hypnotic induction creates a distinctive and unique pattern of brain activation in highly suggestible subjects. PMID:19782614

  12. Choosing the lesser of two evils, the better of two goods: specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate in object choice.

    PubMed

    Blair, Karina; Marsh, Abigail A; Morton, John; Vythilingam, Meena; Jones, Matthew; Mondillo, Krystal; Pine, Daniel C; Drevets, Wayne C; Blair, James R

    2006-11-01

    The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning.

  13. The antinociceptive effect of stimulating the retrosplenial cortex in the rat tail-flick test but not in the formalin test involves the rostral anterior cingulate cortex.

    PubMed

    Reis, Gláucia Melo; Fais, Rafael Sobrano; Prado, Wiliam A

    2015-04-01

    The stimulation of the retrosplenial cortex (RSC) is antinociceptive in the rat tail-flick and formalin tests. The rat RSC is caudal to and send projections to the ipsilateral anterior cingulate cortex (ACC), which is also involved in pain processing. This study demonstrated that pre-treating the rostral (rACC), but not the caudal ACC with CoCl2 (1mM), or the rACC ablation increased the duration of the antinociceptive effect evoked by a 15-s period of electrical stimulation (AC, 60Hz, 20μA) of the RSC in the rat tail-flick. Injecting the GABA-A antagonist bicuculline (50ng/0.25μL), but not the GABA-B antagonist phaclofen (300ng/0.25μL) into the rACC also increased the duration of the stimulation-induced antinociception from the RSC. In contrast, the effects of rACC stimulation persisted after the injection of CoCl2 (1mM) into the RSC. The injection of CoCl2 into the rACC did not change the nociceptive behavior of rats during phase 1 of the formalin response but reduced licking response duration during phase 2. This effect was similar in sham or stimulated animals at the RSC. We conclude that the antinociceptive effect of stimulating the RSC in the rat tail-flick test is modulated by the rACC involving GABA-A receptors in this cortex. In contrast, the antinociceptive effect of stimulating the RSC in the formalin test does not involve the rACC.

  14. Relationship of γ-aminobutyric acid and glutamate+glutamine concentrations in the perigenual anterior cingulate cortex with performance of Cambridge Gambling Task.

    PubMed

    Fujihara, Kazuyuki; Narita, Kosuke; Suzuki, Yusuke; Takei, Yuichi; Suda, Masashi; Tagawa, Minami; Ujita, Koichi; Sakai, Yuki; Narumoto, Jin; Near, Jamie; Fukuda, Masato

    2015-04-01

    The anterior cingulate cortex (ACC), consisting of the perigenual ACC (pgACC) and mid-ACC (i.e., affective and cognitive areas, respectively), plays a significant role in the performance of gambling tasks, which are used to measure decision-making behavior under conditions of risk. Although recent neuroimaging studies have suggested that the γ-aminobutyric acid (GABA) concentration in the pgACC is associated with decision-making behavior, knowledge regarding the relationship of GABA concentrations in subdivisions of the ACC with gambling task performance is still limited. The aim of our magnetic resonance spectroscopy study is to investigate in 20 healthy males the relationship of concentrations of GABA and glutamate+glutamine (Glx) in the pgACC, mid-ACC, and occipital cortex (OC) with multiple indexes of decision-making behavior under conditions of risk, using the Cambridge Gambling Task (CGT). The GABA/creatine (Cr) ratio in the pgACC negatively correlated with delay aversion score, which corresponds to the impulsivity index. The Glx/Cr ratio in the pgACC negatively correlated with risk adjustment score, which is reported to reflect the ability to change the amount of the bet depending on the probability of winning or losing. The scores of CGT did not significantly correlate with the GABA/Cr or Glx/Cr ratio in the mid-ACC or OC. Results of this study suggest that in the pgACC, but not in the mid-ACC or OC, GABA and Glx concentrations play a distinct role in regulating impulsiveness and risk probability during decision-making behavior under conditions of risk, respectively.

  15. 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

  16. Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia.

    PubMed

    Kristiansen, L V; Beneyto, M; Haroutunian, V; Meador-Woodruff, J H

    2006-08-01

    Abnormal expression of the N-methyl-D-Aspartate (NMDA) receptor and its interacting molecules of the postsynaptic density (PSD) are thought to be involved in the pathophysiology of schizophrenia. Frontal regions of neocortex including dorsolateral prefrontal (DLPFC) and anterior cingulate cortex (ACC) are essential for cognitive and behavioral functions that are affected in schizophrenia. In this study, we have measured protein expression of two alternatively spliced isoforms of the NR1 subunit (NR1C2 and NR1C2') as well as expression of the NR2A-D subunits of the NMDA receptor in DLPFC and ACC in post-mortem samples from elderly schizophrenic patients and a comparison group. We found significantly increased expression of NR1C2' but not of NR1C2 in ACC, suggesting altered NMDA receptor cell membrane expression in this cortical area. We did not find significant changes in the expression of either of the NR1 isoforms in DLPFC. We did not detect changes of any of the NR2 subunits studied in either cortical area. In addition, we studied expression of the NMDA-interacting PSD molecules NF-L, SAP102, PSD-95 and PSD-93 in ACC and DLPFC at both transcriptional and translational levels. We found significant changes in the expression of NF-L in DLPFC, and PSD-95 and PSD-93 in ACC; increased transcript expression was associated with decreased protein expression, suggesting abnormal translation and/or accelerated protein degradation of these molecules in schizophrenia. Our findings suggest abnormal regional processing of the NMDA receptor and its associated PSD molecules, possibly involving transcription, translation, trafficking and protein stability in cortical areas in schizophrenia.

  17. 5-Hydroxytryptamine (serotonin)2A receptors in rat anterior cingulate cortex mediate the discriminative stimulus properties of d-lysergic acid diethylamide.

    PubMed

    Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine; Smith, Randy L

    2007-02-01

    d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.

  18. Reduced cytochrome oxidase activity in the retrosplenial cortex after lesions to the anterior thalamic nuclei.

    PubMed

    Mendez-Lopez, Magdalena; Arias, Jorge L; Bontempi, Bruno; Wolff, Mathieu

    2013-08-01

    The anterior thalamic nuclei (ATN) make a critical contribution to hippocampal system functions. Growing experimental work shows that the effects of ATN lesions often resemble those of hippocampal lesions and both markedly reduce the expression of immediate-early gene markers in the retrosplenial cortex, which still appears normal by standard histological means. This study shows that moderate ATN damage was sufficient to produce severe spatial memory impairment as measured in a radial-arm maze. Furthermore, ATN rats exhibited reduced cytochrome oxidase activity in the most superficial cortical layers of the granular retrosplenial cortex, and, to a lesser extent, in the anterior cingulate cortex. By contrast, no change in cytochrome oxidase activity was observed in other limbic cortical regions or in the hippocampal formation. Altogether our results indicate that endogenous long-term brain metabolic capacity within the granular retrosplenial cortex is compromised by even limited ATN damage.

  19. Errors Recruit both Cognitive and Emotional Monitoring Systems: Simultaneous Intracranial Recordings in the Dorsal Anterior Cingulate Gyrus and Amygdala Combined with fMRI

    ERIC Educational Resources Information Center

    Pourtois, Gilles; Vocat, Roland; N'Diaye, Karim; Spinelli, Laurent; Seeck, Margitta; Vuilleumier, Patrik

    2010-01-01

    We studied error monitoring in a human patient with unique implantation of depth electrodes in both the left dorsal cingulate gyrus and medial temporal lobe prior to surgery. The patient performed a speeded go/nogo task and made a substantial number of commission errors (false alarms). As predicted, intracranial Local Field Potentials (iLFPs) in…

  20. Stimulus-Outcome Learnability Differentially Activates Anterior Cingulate and Hippocampus at Feedback Processing

    ERIC Educational Resources Information Center

    Rodriguez, Paul F.

    2009-01-01

    Memory systems are known to be influenced by feedback and error processing, but it is not well known what aspects of outcome contingencies are related to different memory systems. Here we use the Rescorla-Wagner model to estimate prediction errors in an fMRI study of stimulus-outcome association learning. The conditional probabilities of outcomes…

  1. Anterior Cingulate Cortex Activation Is Related to Learning Potential on the WCST in Schizophrenia Patients

    ERIC Educational Resources Information Center

    Pedersen, Anya; Wilmsmeier, Andreas; Wiedl, Karl H.; Bauer, Jochen; Kueppers, Kerstin; Koelkebeck, Katja; Kohl, Waldemar; Kugel, Harald; Arolt, Volker; Ohrmann, Patricia

    2012-01-01

    The remediation of executive function in patients with schizophrenia is important in rehabilitation because these skills affect the patient's capacity to function in the community. There is evidence that instructional techniques can improve deficits in the Wisconsin Card Sorting Test (WCST) in some schizophrenia patients. We used a standard…

  2. Increased anterior insula activity in anxious individuals is linked to diminished perceived control

    PubMed Central

    Alvarez, R P; Kirlic, N; Misaki, M; Bodurka, J; Rhudy, J L; Paulus, M P; Drevets, W C

    2015-01-01

    Individuals with high-trait anxiety frequently report decreased perceived control. However, it is unclear how these processes are instantiated at a neural level. Prior research suggests that individuals prone to anxiety may have exaggerated activity in the anterior insula and altered activity in the cingulate cortex during anticipation of aversive events. Thus, we hypothesized that anxiety proneness influences anterior insula activation during anticipation of unpredictable threat through decreased perceived control. Forty physically healthy adults underwent neuroimaging while they explored computer-simulated contexts associated either with or without the threat of an unpredictable shock. Skin conductance, anxiety ratings and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging were used to assess responses to threat versus no threat. Perceived control was measured using the Anxiety Control Questionnaire-Revised. Mediation analysis examined how anxiety proneness influenced BOLD activity. Anticipation of unpredictable threat resulted in increased skin conductance responses, anxiety ratings and enhanced activation in bilateral insula, anterior midcingulate cortex (aMCC) and bed nucleus of the stria terminalis. Individuals with greater anxiety proneness and less perceived control showed greater activity in dorsal anterior insula (dAI). Perceived control mediated the relationship between anxiety proneness and dAI activity. Increased dAI activity was associated with increased activity in aMCC, which correlated with increased exploratory behavior. Results provide evidence that exaggerated insula activation during the threat of unpredictable shock is directly related to low perceived control in anxiety-prone individuals. Perceived control thus may constitute an important treatment target to modulate insula activity during anxious anticipation in anxiety-disordered individuals. PMID:26125154

  3. Dimensions of depressive symptoms and cingulate volumes in older adults

    PubMed Central

    McLaren, M E; Szymkowicz, S M; O'Shea, A; Woods, A J; Anton, S D; Dotson, V M

    2016-01-01

    Clinical depression and subthreshold depressive symptoms in older adults have been linked to structural changes in the cingulate gyrus. The cingulate comprises functionally distinct subregions that may have distinct associations with different types, or symptom dimensions, of depression. This study examined the relationship between symptom dimensions of depression and gray matter volumes in the anterior cingulate, posterior cingulate and isthmus of the cingulate in a nonclinical sample. The study included 41 community-dwelling older adults between the ages of 55 and 81. Participants received a structural magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale. Subscale scores for depressed mood, somatic symptoms and lack of positive affect were calculated, and Freesurfer was used to extract cingulate gray matter volumes. Regression analyses were conducted to examine the relationship between depressive symptoms and volumes of cingulate subregions while controlling for sex, age and estimated total intracranial volume. Higher scores on the depressed mood subscale were associated with larger volumes in the left posterior cingulate and smaller volumes in the isthmus cingulate. Higher scores on the somatic symptoms subscale were significantly related to smaller volumes in the posterior cingulate. A trend was observed for a positive relationship between higher scores on the lack of positive affect subscale and larger volumes in the anterior cingulate cortex. These results are consistent with previous findings of altered cingulate volumes with increased depressive symptomatology and suggest specific symptom dimensions of depression may differ in their relationship with subregions of the cingulate. PMID:27093070

  4. Social Anxiety Modulates Risk Sensitivity through Activity in the Anterior Insula

    PubMed Central

    Tang, Grace S.; van den Bos, Wouter; Andrade, Eduardo B.; McClure, Samuel M.

    2012-01-01

    Decision neuroscience offers the potential for decomposing differences in behavior across individuals into components of valuation intimately tied to brain function. One application of this approach lies in novel conceptualizations of behavioral attributes that are aberrant in psychiatric disorders. We investigated the relationship between social anxiety and behavior in a novel socially determined risk task. Behaviorally, higher scores on a social phobia inventory (SPIN) among healthy participants were associated with an increase in risky responses. Furthermore, activity in a region of the dorsal anterior insula (dAI) scaled in proportion to SPIN score in risky versus non-risky choices. This region of the insula was functionally connected to areas in the intraparietal sulcus and anterior cingulate cortex that were related to decision-making across all participants. Overall, social anxiety was associated with decreased risk aversion in our task, consistent with previous results investigating risk taking in many everyday behaviors. Moreover, this difference was linked to the anterior insula, a region commonly implicated in risk attitudes and socio-emotional processes. PMID:22319462

  5. Strong Manual Acupuncture Stimulation of “Huantiao” (GB 30) Reduces Pain-Induced Anxiety and p-ERK in the Anterior Cingulate Cortex in a Rat Model of Neuropathic Pain

    PubMed Central

    Shao, Xiao-mei; Shen, Zui; Sun, Jing; Fang, Fang; Fang, Jun-fan; Wu, Yuan-yuan; Fang, Jian-qiao

    2015-01-01

    Persistent neuropathic pain is associated with anxiety. The phosphorylation of extracellular signal-regulated kinase (p-ERK) in the anterior cingulate cortex (ACC) plays an important role in pain-induced anxiety. Acupuncture is widely used for pain and anxiety. However, little is known about which acupuncture technique is optimal on pain-induced anxiety and the relationship between acupuncture effect and p-ERK. The rat model was induced by L5 spinal nerve ligation (SNL). Male adult SD rats were randomly divided into control, SNL, strong manual acupuncture (sMA), mild manual acupuncture (mMA), and electroacupuncture (EA) group. Bilateral “Huantiao” (GB 30) were stimulated by sMA, mMA, and EA, respectively. The pain withdrawal thresholds (PWTs) and anxiety behavior were measured, and p-ERK protein expression and immunoreactivity cells in ACC were detected. PWTs increased significantly in both sMA and EA groups. Meanwhile, anxiety-like behavior was improved significantly in the sMA and mMA groups. Furthermore, the overexpression of p-ERK induced by SNL was downregulated by strong and mild manual acupuncture. Therefore, strong manual acupuncture on bilateral “Huantiao” (GB 30) could be a proper therapy relieving both pain and pain-induced anxiety. The effect of different acupuncture techniques on pain-induced anxiety may arise from the regulation of p-ERK in ACC. PMID:26770252

  6. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment.

    PubMed

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-03-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with 'psychoticism', a trait associated with a lack of empathic concern and antisocial tendencies, and with 'need for cognition', a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others.

  7. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment

    PubMed Central

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-01-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with ‘psychoticism’, a trait associated with a lack of empathic concern and antisocial tendencies, and with ‘need for cognition’, a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others. PMID:23280149

  8. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment.

    PubMed

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-03-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with 'psychoticism', a trait associated with a lack of empathic concern and antisocial tendencies, and with 'need for cognition', a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others. PMID:23280149

  9. Negative BOLD response and serotonin concentration within rostral subgenual portion of the anterior cingulate cortex for long-allele carriers during perceptual processing of emotional tasks

    NASA Astrophysics Data System (ADS)

    Hadi, Shamil M.; Siadat, Mohamad R.; Babajani-Feremi, Abbas

    2012-03-01

    We investigated the effect of synaptic serotonin concentration on hemodynamic responses. The stimuli paradigm involved the presentation of fearful and threatening facial expressions to a set of 24 subjects who were either5HTTLPR long- or short-allele carriers (12 of each type in each group). The BOLD signals of the rACC from subjects of each group were averaged to increase the signal-to-noise ratio. We used a Bayesian approach to estimate the parameters of the underlying hemodynamic model. Our results, during this perceptual processing of emotional task, showed a negative BOLD signal in the rACC in the subjects with long-alleles. In contrast, the subjects with short-alleles showed positive BOLD signals in the rACC. These results suggest that high synaptic serotonin concentration in the rACC inhibits neuronal activity in a fashion similar to GABA, and a consequent negative BOLD signal ensues.

  10. Distributions of transmitter receptors in the macaque cingulate cortex.

    PubMed

    Bozkurt, Ahmet; Zilles, Karl; Schleicher, Axel; Kamper, Lars; Arigita, Ernesto Sanz; Uylings, Harry B M; Kötter, Rolf

    2005-03-01

    The primate cingulate cortex is structurally and functionally complex. Although no studies have investigated the regional densities of multiple neurotransmitter receptor systems, such information would be useful for assessing its functions and disease vulnerabilities. We quantified nine different receptors in five transmitter systems by in vitro autoradiographic mapping of the cingulate cortex of macaque monkeys with the aim to link cytoarchitectonic regions and functional specialization. Receptor mapping substantiated the subdivision of the cingulate cortex into anterior versus posterior regions. In anterior cingulate cortex (ACC) AMPA glutamatergic receptors and GABA(A) inhibitory receptors were present in significantly higher concentrations than the modulatory alpha-adrenergic and muscarinic receptors. These differences were absent in the posterior cingulate cortex (PCC). By contrast, NMDA receptor densities were significantly higher than AMPA receptor densities in PCC, but not in ACC. The midcingulate area 24' shared more features with ACC than PCC. This area was characterized by the highest ratios of NMDA receptors to alpha-adrenergic, muscarinic and 5-HT2 receptors among all cingulate regions. Compared to rostrocaudal divisions, the differences between dorsoventral subdivisions a-c were small in all regions of cingulate cortex, and only muscarinic and alpha-adrenergic receptor densities followed the degree of cytoarchitectonic differentiation. We conclude that multiple receptor mapping reveals a highly differentiated classification of cingulate cortex with a characteristic predominance of fast ionotropic excitatory and inhibitory receptors in ACC, but a strong and varied complement of NMDA and metabotropic receptors in PCC.

  11. Cingulate and thalamic metabolites in obsessive-compulsive disorder.

    PubMed

    O'Neill, Joseph; Lai, Tsz M; Sheen, Courtney; Salgari, Giulia C; Ly, Ronald; Armstrong, Casey; Chang, Susanna; Levitt, Jennifer G; Salamon, Noriko; Alger, Jeffry R; Feusner, Jamie D

    2016-08-30

    Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity. PMID:27317876

  12. siRNA-mediated downregulation of GluN2B in the rostral anterior cingulate cortex attenuates mechanical allodynia and thermal hyperalgesia in a rat model of pain associated with bone cancer

    PubMed Central

    XU, YONGGUANG; WANG, GONGMING; ZOU, XULI; YANG, ZAIQI; WANG, QIN; FENG, HAO; ZHANG, MENGYUAN

    2016-01-01

    It has previously been suggested that the upregulation of GluN2B-containing N-methyl D-aspartate receptors (GluN2B) within the rostral anterior cingulate cortex (rACC) may contribute to the development of chronic pain. The present study used a rat model of bone cancer pain in order to investigate whether lentiviral-mediated delivery of small interfering RNAs targeting GluN2B (LV-GluN2B) could attenuate pain associated with bone cancer, by selectively decreasing GluN2B expression within the rACC. Sprague Dawley rats were inoculated with osteosarcoma cells into the intramedullary space of the right tibia in order to induce persistent bone cancer-associated pain. Intra-rACC administration of the lentiviral siRNA was performed in the tumor bearing rats; and reverse transcription-quantitative polymerase chain reaction and western blotting were performed in order to detect the expression levels of GluN2B. Pain behavior changes were evaluated via paw withdrawal threshold and latency determinations. Marked and region-selective decreases in the mRNA and protein expression levels of GluN2B were detected in the rACC following the intra-rACC administration of LV-GluN2B. Furthermore, the rats also exhibited pain behavior changes corresponding to the decreased levels of GluN2B. By post-operative day 14, inoculation of osteosarcoma cells had significantly enhanced mechanical allodynia and thermal hyperalgesia in the rats, which were subsequently attenuated by the intra-rACC administration of LV-GluN2B. Notably, the paw withdrawal threshold and latency of the tumor-bearing rats had recovered to normal levels, by day 14 post-administration. The results of the present study suggest that GluN2B within the rACC may be a potential target for RNA interference therapy for the treatment of pain associated with bone cancer. Furthermore, the lentiviral vector delivery strategy may be a promising novel approach for the treatment of bone cancer pain. PMID:26889244

  13. Monetary reward suppresses anterior insula activity during social pain.

    PubMed

    Cristofori, Irene; Harquel, Sylvain; Isnard, Jean; Mauguière, François; Sirigu, Angela

    2015-12-01

    Social pain after exclusion by others activates brain regions also involved in physical pain. Here we evaluated whether monetary reward could compensate for the negative feeling of social pain in the brain. To address this question we used the unique technique of intracranial electroencephalography in subjects with drug resistant epilepsy. Specifically, we recorded theta activity from intracranial electrodes implanted in the insular cortex while subjects experienced conditions of social inclusion and exclusion associated with monetary gain and loss. Our study confirmed that theta rhythm in the insular cortex is the neural signature of social exclusion. We found that while monetary gain suppresses the effect of social pain in the anterior insula, there is no such effect in the posterior insula. These results imply that the anterior insula can use secondary reward signals to compensate for the negative feeling of social pain. Hence, here we propose that the anterior insula plays a pivotal role in integrating contingencies to update social pain feelings. Finally, the possibility to modulate the theta rhythm through the reward system might open new avenues of research for treating pathologies related to social exclusion. PMID:25964499

  14. Monetary reward suppresses anterior insula activity during social pain.

    PubMed

    Cristofori, Irene; Harquel, Sylvain; Isnard, Jean; Mauguière, François; Sirigu, Angela

    2015-12-01

    Social pain after exclusion by others activates brain regions also involved in physical pain. Here we evaluated whether monetary reward could compensate for the negative feeling of social pain in the brain. To address this question we used the unique technique of intracranial electroencephalography in subjects with drug resistant epilepsy. Specifically, we recorded theta activity from intracranial electrodes implanted in the insular cortex while subjects experienced conditions of social inclusion and exclusion associated with monetary gain and loss. Our study confirmed that theta rhythm in the insular cortex is the neural signature of social exclusion. We found that while monetary gain suppresses the effect of social pain in the anterior insula, there is no such effect in the posterior insula. These results imply that the anterior insula can use secondary reward signals to compensate for the negative feeling of social pain. Hence, here we propose that the anterior insula plays a pivotal role in integrating contingencies to update social pain feelings. Finally, the possibility to modulate the theta rhythm through the reward system might open new avenues of research for treating pathologies related to social exclusion.

  15. The Integration of Negative Affect, Pain, and Cognitive Control in the Cingulate Cortex

    PubMed Central

    Shackman, Alexander J.; Salomons, Tim V.; Slagter, Heleen A.; Fox, Andrew S.; Winter, Jameel J.; Davidson, Richard J.

    2011-01-01

    Preface It has been argued that emotion, pain, and cognitive control are functionally segregated in distinct subdivisions of the cingulate cortex. But recent observations encourage a fundamentally different view. Imaging studies indicate that negative affect, pain, and cognitive control activate an overlapping region of dorsal cingulate, the anterior midcingulate cortex (aMCC). Anatomical studies reveal that aMCC constitutes a hub where information about reinforcers can be linked to motor centers responsible for expressing affect and executing goal-directed behavior. Computational modeling and other kinds of evidence suggest that this intimacy reflects control processes that are common to all three domains. These observations compel a reconsideration of dorsal cingulate’s contribution to negative affect and pain. PMID:21331082

  16. Neural overlap between resting state and self-relevant activity in human subcallosal cingulate cortex--single unit recording in an intracranial study.

    PubMed

    Lipsman, Nir; Nakao, Takashi; Kanayama, Noriaki; Krauss, Joachim K; Anderson, Adam; Giacobbe, Peter; Hamani, Clement; Hutchison, William D; Dostrovsky, Jonathan O; Womelsdorf, Thilo; Lozano, Andres M; Northoff, Georg

    2014-11-01

    High activity of the default mode network (DMN) has been proposed to be central in processing self-relevant events. Thus far, this hypothesis of DMN function has not been tested directly using neurophysiological techniques. To test for the link between frontal midline DMN activity and self-relevant processing we measured neuronal activity (single-neurons' firing rates) in human subcallosal cingulate cortex (SCC) in the course of Deep Brain Stimulation surgery. We find that firing rates in SCC did not change during the presentation of specifically self-relevant stimuli when compared to the preceding pre-stimulus resting state level. In contrast, we observed significant changes in firing rates during other names in SCC. Such rest-self overlap seems to be specific for SCC since increase in firing rates in response to self-relevant stimuli were observed in another region, the subthalamic nucleus, in a group of Parkinson patients receiving deep brain stimulation surgery. These results suggest specific relationship between resting state and self-related activity, rest-self overlap, in specifically SCC as core region of the default-mode network.

  17. Altered SPECT 123I-iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa

    PubMed Central

    Nagamitsu, Shinichiro; Sakurai, Rieko; Matsuoka, Michiko; Chiba, Hiromi; Ozono, Shuichi; Tanigawa, Hitoshi; Yamashita, Yushiro; Kaida, Hayato; Ishibashi, Masatoshi; Kakuma, Tatsuki; Croarkin, Paul E.; Matsuishi, Toyojiro

    2016-01-01

    Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using 123I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). “Depression–Dejection” and “Confusion” POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered

  18. Purkinje Cell Activity in the Cerebellar Anterior Lobe after Rabbit Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Green, John T.; Steinmetz, Joseph E.

    2005-01-01

    The cerebellar anterior lobe may play a critical role in the execution and proper timing of learned responses. The current study was designed to monitor Purkinje cell activity in the rabbit cerebellar anterior lobe after eyeblink conditioning, and to assess whether Purkinje cells in recording locations may project to the interpositus nucleus.…

  19. The will to persevere induced by electrical stimulation of the human cingulate gyrus.

    PubMed

    Parvizi, Josef; Rangarajan, Vinitha; Shirer, William R; Desai, Nikita; Greicius, Michael D

    2013-12-18

    Anterior cingulate cortex (ACC) is known to be involved in functions such as emotion, pain, and cognitive control. While studies in humans and nonhuman mammals have advanced our understanding of ACC function, the subjective correlates of ACC activity have remained largely unexplored. In the current study, we show that electrical charge delivery in the anterior midcingulate cortex (aMCC) elicits autonomic changes and the expectation of an imminent challenge coupled with a determined attitude to overcome it. Seed-based, resting-state connectivity analysis revealed that the site of stimulation in both patients was at the core of a large-scale distributed network linking aMCC to the frontoinsular and frontopolar as well as some subcortical regions. This report provides compelling, first-person accounts of electrical stimulation of this brain network and suggests its possible involvement in psychopathological conditions that are characterized by a reduced capacity to endure psychological or physical distress. PMID:24316296

  20. Plasma corticosterone responses to lesions and stimulations of the limbic thalami nuclei, medial mammillary nucleus and cingulate cortex.

    PubMed

    Suárez, M; Perassi, N I

    1988-06-01

    The influence of extrahypothalamic limbic structures on adrenocortical activity was investigated in female adult rats. Bilateral lesions on the anteromedial thalami nucleus (AMTN), anteroventral thalami nucleus (AVTN) or the posterior cingulate cortex (PCC) all elicited a significant decrease on plasma corticosterone, while their electrochemical stimulation produced a significant increase with respect to animals with sham lesions or sham stimulation. In contrast, after lesions of the dorsomedial thalami nucleus (DMTN), medial mammillary nucleus (pars lateralis) (MMN) or retrosplenial cortex (RC), values of plasma corticosterone were significantly higher than those found in controls, whereas following their stimulation plasma corticosterone levels were lower than in controls. Bilateral lesions or stimulations of anterior cingulate cortex had no significant effect upon corticosterone secretion. These findings may be interpreted as indicative of the existence of excitatory (AMTN, AVTN, and PCC) and inhibitory (DMTN, MMN and RC) central nervous structures for the control of corticoadrenal secretion besides those already known.

  1. Hedonic Hotspots Regulate Cingulate-driven Adaptation to Cognitive Demands.

    PubMed

    van Steenbergen, Henk; Band, Guido P H; Hommel, Bernhard; Rombouts, Serge A R B; Nieuwenhuis, Sander

    2015-07-01

    Positive hedonic states are known to attenuate the impact of demanding events on our body and brain, supporting adaptive behavior in response to changes in the environment. We used functional magnetic resonance imaging to examine the neural mechanism of this hedonic regulation. The effect of hedonic state (as induced by funny vs. neutral cartoons) on flexible behavioral and neural adaptation to cognitive demands was assessed in a flanker task in female volunteers. Behavioral results showed that humor reduced the compensatory adjustments to cognitive demands, as observed in sequential adaptations. This modulation was also reflected in midcingulate cortex (MCC; also known as the dorsal anterior cingulate cortex, ACC) activation. Furthermore, hedonic context increased activation in ventral striatum (VS) and ventral pallidum (VP). These hedonic hotspots attenuated the medial prefrontal cortex response to the cognitive demands in the ACC (also known as the rostral ACC). Activity in the ACC proved predictive of subsequent behavioral adaptation. Moreover, psychophysiological interaction analyses revealed that the MCC and the ACC were functionally connected with VS and VP, respectively. These observations reveal how MCC-VS and VP-ACC interactions are involved in the detection and hedonic modulation of behavioral adaptations to cognitive demands, which supports behavioral flexibility.

  2. Subconjunctival Sirolimus for the Treatment of Chronic Active Anterior Uveitis: Results of a Pilot Trial

    PubMed Central

    Sen, H. Nida; Larson, Theresa A.; Meleth, Annal D.; Smith, Wendy M.; Nussenblatt, Robert B.

    2012-01-01

    Purpose To evaluate the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis Design Prospective, non-randomized, open-label clinical trial. Methods This single-center pilot trial enrolled 5 patients with chronic active anterior uveitis. The study drug was administered as single subconjunctival injection of 30μL (1,320μg) sirolimus in the study eye at the baseline visit. Study visits were performed at baseline, 2 weeks, 4 weeks and monthly until 4 months, and included a complete ophthalmic exam, review of systems, adverse event assessment at each visit, physical exam and ancillary ophthalmic testing at some visits. The primary outcome measure was a 2-step reduction in the anterior chamber inflammation within 4 weeks of injection of the study drug. Results There were 3 females and 2 males; 4 patients had idiopathic anterior uveitis and one had psoriatic arthritis-associated anterior uveitis. Three of the five patients met the primary outcome criteria by showing at least a 2-step decrease in inflammation within 4 weeks, 2 patients showed a 1-step decrease in inflammation within the same time frame. No recurrence was encountered during a 4 month follow-up. There were no serious adverse events. Conclusions Subconjunctival sirolimus appears to be well tolerated in this pilot trial and shows promise as a treatment for active inflammation in patients with chronic anterior uveitis. Larger studies are needed to assess its usefulness in uveitis. PMID:22465364

  3. [Effects of activator and activator + anterior high-pull headgear on the growth direction of Class 2 cases].

    PubMed

    Uner, O; Akkaya, S; Buyruk, F

    1989-04-01

    In this study which the effects of activator and activator + anterior high-pull headgear on the growth direction of skeletal class 2 cases for a period of approximately 9 months; 33 cases having a mean age of 10.59 years; ANB angles 4.5 degrees and over were studied. Activator treatment has been applied to the 11 of the 22 treatment cases, the others have had the activator + anterior high-pull headgear treatment. The control group, 11 patients, has only been observed in terms of the growth and development without having any treatment. At the end of the study; it was found that the decrease in ANB angle and the increase in SL dimension in the treatment groups; the increase in anterior lower face height in the activator group and the increase in the ratio of posterior to anterior face height were statistically significant.

  4. Improvement of cognitive flexibility and cingulate blood flow correlates after atypical antipsychotic treatment in drug-naive patients with first-episode schizophrenia.

    PubMed

    Pardo, Bernardo M; Garolera, Maite; Ariza, Mar; Pareto, Deborah; Salamero, Manel; Valles, Vicenç; Delgado, Luis; Alberni, Joan

    2011-12-30

    The aim of this study was to examine the changes in cognitive flexibility and associated cerebral blood flow in the anterior cingulate lobe of drug-naive patients with first-episode schizophrenia who were treated with atypical antipsychotics for 6 weeks. Single photon emission computed tomography (SPECT) images were obtained from 8 healthy subjects both at rest and while performing the flexibility subtest of the TAP (Test for Attentional Performance). SPECT images were obtained in parallel from 8 first-episode drug-naive schizophrenic patients while they were performing the same task both before and after 6 weeks of neuroleptic treatment. In the control group, an increase in the perfusion indices of the dorsal section of the anterior cingulate gyrus was observed in the activation condition. Task performance was altered and the level of perfusion of the brain region related to the task execution was significantly decreased in the patients at baseline. After treatment, there was a significant improvement in both task performance and the level of perfusion of the dorsal section of the anterior cingulate. We conclude that treatment with second-generation neuroleptics improves cognitive flexibility, and there was a relationship between such improvements and normalization of perfusion indices of the involved brain areas.

  5. Ketamine modulates subgenual cingulate connectivity with the memory-related neural circuit-a mechanism of relevance to resistant depression?

    PubMed

    Wong, Jing J; O'Daly, Owen; Mehta, Mitul A; Young, Allan H; Stone, James M

    2016-01-01

    Background. Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions. Methods. Thirteen right-handed healthy male subjects underwent a 15 min resting state fMRI with an infusion of intravenous ketamine (target blood level = 150 ng/ml) starting at 5 min. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results. Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC activity became negatively correlated with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion. Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.

  6. Ketamine modulates subgenual cingulate connectivity with the memory-related neural circuit-a mechanism of relevance to resistant depression?

    PubMed

    Wong, Jing J; O'Daly, Owen; Mehta, Mitul A; Young, Allan H; Stone, James M

    2016-01-01

    Background. Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions. Methods. Thirteen right-handed healthy male subjects underwent a 15 min resting state fMRI with an infusion of intravenous ketamine (target blood level = 150 ng/ml) starting at 5 min. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results. Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC activity became negatively correlated with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion. Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis. PMID:26925332

  7. Anterior Medial Prefrontal Cortex Exhibits Activation during Task Preparation but Deactivation during Task Execution

    PubMed Central

    Koshino, Hideya; Minamoto, Takehiro; Ikeda, Takashi; Osaka, Mariko; Otsuka, Yuki; Osaka, Naoyuki

    2011-01-01

    Background The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. Methodology/Principal Findings Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. Conclusions/Significance The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing. PMID:21829668

  8. Cingulate GABA levels inversely correlate with the intensity of ongoing chronic knee osteoarthritis pain

    PubMed Central

    Reckziegel, Diane; Raschke, Felix; Cottam, William J

    2016-01-01

    Background This study aims to investigate the role of the mid-anterior cingulate cortex γ-aminobutyric acid levels in chronic nociceptive pain. The molecular mechanisms of pain chronification are not well understood. In fibromyalgia, low mid-anterior cingulate cortex γ-aminobutyric acid was associated with high pain suggesting a role of prefrontal disinhibition. We hypothesize that mid-anterior cingulate cortex GABAergic disinhibition may underpin chronic pain independent of the pain etiology and comorbid negative affect. Proton magnetic resonance spectra were acquired at 3T from the mid-anterior cingulate cortex in 20 patients with chronic painful knee osteoarthritis, and 19 healthy pain-free individuals using a point resolved spectroscopy sequence optimized for detection of γ-aminobutyric acid. Participants underwent questionnaires for negative affect (depression and anxiety) and psychophysical pain phenotyping. Results No differences in mid-anterior cingulate cortex γ-aminobutyric acid or other metabolite levels were detected between groups. Ratings of perceived intensity of ongoing osteoarthritis pain were inversely correlated with γ-aminobutyric acid (r = −0.758, p < 0.001), but no correlations were seen for negative affect or pain thresholds. The pain γ-aminobutyric acid interrelation remained strong when controlling for depression (r = −0.820, p < 0.001). Combined levels of glutamine and glutamate were unrelated to psychometric or to pain thresholds. Conclusion Our study supports mid-anterior cingulate cortex γ-aminobutyric acid as a potential marker of pain severity in chronic nociceptive pain states independent of negative affect. The findings suggest that GABAergic disinhibition of the salience network may underlie sensitization to averse stimuli as a mechanism contributing to pain chronification. PMID:27206661

  9. Distribution and Properties of Visceral Nociceptive Neurons in Rabbit Cingulate Cortex

    PubMed Central

    Sikes, Robert W.; Vogt, Leslie J.; Vogt, Brent A.

    2008-01-01

    Human imaging localizes most visceral nociceptive responses to anterior cingulate cortex (ACC), however, imaging in conscious subjects cannot completely control anticipatory and reflexive activity or resolve neuron activity. This study overcame these shortcomings by recording individual neuron responses in 12 anesthetized and paralyzed rabbits to define the visceronociceptive response pattern by region and layer. Balloon distension was applied to the colon at innocuous (15 mmHg) or noxious (60 mmHg) intensities, and innocuous and noxious mechanical, thermal and electrical stimuli were applied to the skin. Simultaneous recording from multiple regions assured differences were not due to anesthesia and neuron responses were resolved by spike sorting using principal components analysis. Of the total 346 neurons, 48% were nociceptive; responding to noxious levels of visceral or cutaneous stimulation, or both. Visceronociceptive neurons were most frequent in ACC (39%) and midcingulate cortex (MCC, 36%) and infrequent in retrosplenial cortex (RSC, 12%). In contrast, cutaneous nociceptive units were higher in MCC (MCC, 43%; ACC, 32%; RSC, 23%). Visceral-specific neurons were proportionately more frequent in ACC (37%), while cutaneous-specific units predominated in RSC (62.5%). Visceral nociceptive response durations were longer than those for cutaneous responses. Postmortem analysis of electrode tracks confirmed regional designations, and laminar analysis found inhibitory responses mainly in superficial layers and excitatory in deep layers. Thus, cingulate visceral nociception extends beyond ACC, this is the first report of nociceptive activity in RSC including nociceptive cutaneous responses, and these regional differences require a new model of cingulate nociceptive processing. PMID:18022321

  10. Investigating age-related changes in anterior and posterior neural activity throughout the information processing stream.

    PubMed

    Alperin, Brittany R; Tusch, Erich S; Mott, Katherine K; Holcomb, Phillip J; Daffner, Kirk R

    2015-10-01

    Event-related potential (ERP) and other functional imaging studies often demonstrate age-related increases in anterior neural activity and decreases in posterior activity while subjects carry out task demands. It remains unclear whether this "anterior shift" is limited to late cognitive operations like those indexed by the P3 component, or is evident during other stages of information processing. The temporal resolution of ERPs provided an opportunity to address this issue. Temporospatial principal component analysis (PCA) was used to identify underlying components that may be obscured by overlapping ERP waveforms. ERPs were measured during a visual oddball task in 26 young, 26 middle-aged, and 29 old subjects who were well-matched for IQ, executive function, education, and task performance. PCA identified six anterior factors peaking between ∼140 ms and 810 ms, and four posterior factors peaking between ∼300 ms and 810 ms. There was an age-related increase in the amplitude of anterior factors between ∼200 and 500 ms, and an age-associated decrease in amplitude of posterior factors after ∼500 ms. The increase in anterior processing began as early as middle-age, was sustained throughout old age, and appeared to be linear in nature. These results suggest that age-associated increases in anterior activity occur after early sensory processing has taken place, and are most prominent during a period in which attention is being marshaled to evaluate a stimulus. In contrast, age-related decreases in posterior activity manifest during operations involved in stimulus categorization, post-decision monitoring, and preparation for an upcoming event. PMID:26295684

  11. Muscle activation characteristics in cross-country skiers with a history of anterior compartment pain.

    PubMed

    Federolf, Peter; Bakker, Emily

    2012-11-01

    A large proportion of elite cross-country skiers suffer from chronic anterior compartment syndrome (CACS). This study used surface electromyograms (EMGs) to investigate whether differences existed in the activation characteristics of the tibialis anterior muscle between elite cross-country skiers with a history of anterior compartment pain (symptomatic group) and a pain-free control group. Based on self-reported pain symptoms, twelve young, national-level cross-country ski athletes were assigned to a symptomatic group (N = 5), a control group (N = 4), or analyzed individually if their diagnosis was not certain (N = 3). During skating, EMGs were recorded on five lower leg muscles. The relative increase in EMG power per step when increasing the effort level of skating was larger in the symptomatic group than in the control group for tibialis anterior (143 +/- 12% vs. 125 +/- 23%; Cohen's d = 1.17), peroneus longus (123 +/- 24% vs. 107 +/- 6%; d = 0.91), and gastrocnemius lateralis (167 +/- 51% vs. 117 +/- 12%; d = 1.64). The symptomatic group showed more power in the lower frequency bands of the tibialis anterior's EMG spectra (p < 0.001), whereas no group differences were found in other muscles (all p > 0.2). Within the step cycle, these differences appeared in the swing phase and in the gliding phase during single leg support. The observed differences in the EMG spectra may serve as an early identification of athletes who are at risk of developing CACS.

  12. Tibial translation and muscle activation during rehabilitation exercises 5 weeks after anterior cruciate ligament reconstruction.

    PubMed

    Tagesson, S; Oberg, B; Kvist, J

    2010-02-01

    The aim of this study was to compare different rehabilitation exercises with respect to dynamic anterior tibial translation and muscle activation 5 weeks after an anterior cruciate ligament (ACL) reconstruction. Another aim was to compare the ACL-reconstructed knee with the ACL-injured and the uninjured knees for differences in anterior tibial translation and muscle activation during the exercises. Sagittal tibial translation and muscle activation were measured during the Lachman test (static translation) and during seven rehabilitation exercises (dynamic translation) in 19 patients. Results obtained 5 weeks after ACL reconstruction were compared with those obtained before the ACL reconstruction (ACL-deficient and uninjured knee). After ACL reconstruction the seated knee extension produced more anterior tibial translation than the straight leg raise and standing on one leg. The ACL reconstruction reduced the static and the dynamic tibial translation and the tibial translations measured in ACL-reconstructed knees were similar to those measured in uninjured knees. After ACL reconstruction, the patients used a joint stiffening strategy that used more hamstring activation and reduced the dynamic tibial translation. Although all exercises tested are suitable for rehabilitation after ACL reconstruction, to protect the graft from excessive strain, the straight leg raise and squat on one leg are preferable for quadriceps training in the early phase of rehabilitation.

  13. Feelings of warmth correlate with neural activity in right anterior insular cortex.

    PubMed

    Olausson, H; Charron, J; Marchand, S; Villemure, C; Strigo, I A; Bushnell, M C

    2005-11-25

    The neural coding of perception can differ from that for the physical attributes of a stimulus. Recent studies suggest that activity in right anterior insular cortex may underlie thermal perception, particularly that of cold. We now examine whether this region is also important for the perception of warmth. We applied cutaneous warm stimuli on the left leg (warmth) in normal subjects (n = 7) during functional magnetic resonance imaging (fMRI). After each stimulus, subjects rated their subjective intensity of the stimulus using a visual analogue scale (VAS), and correlations were determined between the fMRI signal and the VAS ratings. We found that intensity ratings of warmth correlated with the fMRI signal in the right (contralateral to stimulation) anterior insular cortex. These results, in conjunction with previous reports, suggest that the right anterior insular cortex is important for different types of thermal perception.

  14. Physiological time structure of the tibialis anterior motor activity during sleep in mice, rats and humans.

    PubMed

    Silvani, Alessandro; Lo Martire, Viviana; Salvadè, Agnese; Bastianini, Stefano; Ferri, Raffaele; Berteotti, Chiara; Baracchi, Francesca; Pace, Marta; Bassetti, Claudio L; Zoccoli, Giovanna; Manconi, Mauro

    2015-12-01

    The validation of rodent models for restless legs syndrome (Willis-Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild-type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non-rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter-rater sensitivity of 92-95% and false-positive rates of 13-19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non-rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals <10 s mainly occurred in series of two-three events, their occurrence rate in humans being lower than in mice and similar to that in rats. In conclusion, this study proposes reliable rules for scoring tibialis anterior electromyogram events during non-rapid eye movement sleep in mice and rats, demonstrating that their physiological time structure is similar to that of healthy young human subjects. These results strengthen the basis for translational rodent models of periodic limb movements during sleep and restless legs syndrome/Willis-Ekbom disease.

  15. Neural circuitry involved in quitting after repeated failures: role of the cingulate and temporal parietal junction

    PubMed Central

    Zhao, Weihua; Kendrick, Keith M; Chen, Fei; Li, Hong; Feng, Tingyong

    2016-01-01

    The more times people fail the more likely they are to give up, however little is known about the neural mechanisms underlying this impact of repeated failure on decision making. Here we have used a visual shape discrimination task with computer-controlled feedback combined with functional magnetic resonance imaging (fMRI) to investigate the neural circuits involved. The behavioral task confirmed that the more times subjects experienced failure the more likely they were to give up, with three successive failures being the key threshold and the majority of subjects reaching the point where they decided to quit and try a new stimulus set after three or four failures. The fMRI analysis revealed activity changes in frontal, parietal, temporal, limbic and striatal regions, especially anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and temporal parietal junction (TPJ) associated with the number of previous failures experienced. Furthermore, their parameter estimates were predictive of subjects’ quitting rate. Thus, subjects reach the point where they decide to quit after three/four failures and this is associated with differential changes in brain regions involved in error monitoring and reward which regulate both failure detection and changes in decision-making strategy. PMID:27097529

  16. Head formation: OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm.

    PubMed

    Ip, Chi Kin; Fossat, Nicolas; Jones, Vanessa; Lamonerie, Thomas; Tam, Patrick P L

    2014-10-01

    The Otx2 gene encodes a paired-type homeobox transcription factor that is essential for the induction and the patterning of the anterior structures in the mouse embryo. Otx2 knockout embryos fail to form a head. Whereas previous studies have shown that Otx2 is required in the anterior visceral endoderm and the anterior neuroectoderm for head formation, its role in the anterior mesendoderm (AME) has not been assessed specifically. Here, we show that tissue-specific ablation of Otx2 in the AME phenocopies the truncation of the embryonic head of the Otx2 null mutant. Expression of Dkk1 and Lhx1, two genes that are also essential for head formation, is disrupted in the AME of the conditional Otx2-deficient embryos. Consistent with the fact that Dkk1 is a direct target of OTX2, we showed that OTX2 can interact with the H1 regulatory region of Dkk1 to activate its expression. Cross-species comparative analysis, RT-qPCR, ChIP-qPCR and luciferase assays have revealed two conserved regions in the Lhx1 locus to which OTX2 can bind to activate Lhx1 expression. Abnormal development of the embryonic head in Otx2;Lhx1 and Otx2;Dkk1 compound mutant embryos highlights the functional intersection of Otx2, Dkk1 and Lhx1 in the AME for head formation.

  17. Impaired anterior insular activation during risky decision making in young adults with internet gaming disorder.

    PubMed

    Lee, Deokjong; Lee, Junghan; Yoon, Kang Joon; Kee, Namkoong; Jung, Young-Chul

    2016-05-25

    Internet gaming disorder is defined as excessive and compulsive use of the internet to engage in games that leads to clinically significant psychosocial impairment. We tested the hypothesis that individuals with internet gaming disorder would be less sensitive to high-risk situations and show aberrant brain activation related to risk prediction processing. Young adults with internet gaming disorder underwent functional MRI while performing a risky decision-making task. The healthy control group showed stronger activations within the dorsal attention network and the anterior insular cortex, which were not found in the internet gaming disorder group. Our findings imply that young adults with internet gaming disorder show impaired anterior insular activation during risky decision making, which might make them vulnerable when they need to adapt new behavioral strategies in high-risk situations. PMID:27092470

  18. [Intracerebral and subarachnoid hemorrhages after administration of recombinant tissue plasminogen activator in a patient with acute ischemicstroke due to anterior cerebral artery dissection: a case report].

    PubMed

    Ueyama, Ken; Koyama, Seigo; Nakamura, Ryoichi

    2011-06-01

    A 45-year-old man was admitted to our hospital for treatment of right hemiparesis. At admission, he was alert and well oriented. His verbal comprehension seemed good, but his speech was not fluent. He could not stand or walk owing to the right hemiparesis, which was severe in the lower extremity. Computed tomographic (CT) scans on admission showed no abnormality. Diffusion weighted magnetic resonance imaging performed after the CT showed a high-intensity lesion in the left cingulate gyrus. Magnetic resonance angiography (MRA) revealed occlusion and irregularity of the left A2 portion of the anterior cerebral artery (ACA). At 1 h 50 min after the onset of the hemiparesis, recombinant tissue plasminogen activator (rt-PA; 0.6 mg/kg) was administered intravenously. At 1 h after the administration of rt-PA, he became drowsy and his right hemiparesis deteriorated. CT scans performed again showed a hematoma in the left frontal lobe and subarachnoid hemorrhage in the anterior interhemispheric fissure. He was treated conservatively. MRA performed on the 18th day after admission showed recanalization of the left ACA and abnormal dilatation of the left A2 segment. The abnormal dilatation was also depicted by 3D-CT angiography (3D-CTA) performed on the 26th day after admission and even on the 33rd and 77th days. As seen in our case, the definite diagnosis of dissection confined to the ACA frequently needs serial angiographies; therefore, its diagnosis immediately after the onset is often difficult. Thrombolytic therapy by intravenous administration of rt-PA for cerebral infarction caused by dissection of the ACA may recanalize the occluded site and facilitate the progression of the dissection, resulting in intracerebral and/or subarachnoid hemorrhages. In patients with cerebral infarction due to ACA dissection, strict control of blood pressure and careful observation are necessary after thrombolytic therapy by rt-PA.

  19. Knowing good from bad: differential activation of human cortical areas by positive and negative outcomes.

    PubMed

    Nieuwenhuis, Sander; Slagter, Heleen A; von Geusau, Niels J Alting; Heslenfeld, Dirk J; Holroyd, Clay B

    2005-06-01

    Previous research has identified a component of the event-related brain potential (ERP), the feedback-related negativity, that is elicited by feedback stimuli associated with unfavourable outcomes. In the present research we used event-related functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) recordings to test the common hypothesis that this component is generated in the caudal anterior cingulate cortex. The EEG results indicated that our paradigm, a time estimation task with trial-to-trial performance feedback, elicited a large feedback-related negativity (FRN). Nevertheless, the fMRI results did not reveal any area in the caudal anterior cingulate cortex that was differentially activated by positive and negative performance feedback, casting doubt on the notion that the FRN is generated in this brain region. In contrast, we found a number of brain areas outside the posterior medial frontal cortex that were activated more strongly by positive feedback than by negative feedback. These included areas in the rostral anterior cingulate cortex, posterior cingulate cortex, right superior frontal gyrus, and striatum. An anatomically constrained source model assuming equivalent dipole generators in the rostral anterior cingulate, posterior cingulate, and right superior frontal gyrus produced a simulated scalp distribution that corresponded closely to the observed scalp distribution of the FRN. These results support a new hypothesis regarding the neural generators of the FRN, and have important implications for the use of this component as an electrophysiological index of performance monitoring and reward processing. PMID:15978024

  20. Anterior Cruciate Ligament Injury: Compensation during Gait using Hamstring Muscle Activity

    PubMed Central

    Catalfamo, Paola Formento; Aguiar, Gerardo; Curi, Jorge; Braidot, Ariel

    2010-01-01

    Previous research has shown that an increase in hamstring activation may compensate for anterior tibial transalation (ATT) in patients with anterior cruciate ligament deficient knee (ACLd); however, the effects of this compensation still remain unclear. The goals of this study were to quantify the activation of the hamstring muscles needed to compensate the ATT in ACLd knee during the complete gait cycle and to evaluate the effect of this compensation on quadriceps activation and joint contact forces. A two dimensional model of the knee was used, which included the tibiofemoral and patellofemoral joints, knee ligaments, the medial capsule and two muscles units. Simulations were conducted to determine the ATT in healthy and ACLd knee and the hamstring activation needed to correct the abnormal ATT to normal levels (100% compensation) and to 50% compensation. Then, the quadriceps activation and the joint contact forces were calculated. Results showed that 100% compensation would require hamstring and quadriceps activations larger than their maximum isometric force, and would generate an increment in the peak contact force at the tibiofemoral (115%) and patellofemoral (48%) joint with respect to the healthy knee. On the other hand, 50% compensation would require less force generated by the muscles (less than 0.85 of maximum isometric force) and smaller contact forces (peak tibiofemoral contact force increased 23% and peak patellofemoral contact force decreased 7.5% with respect to the healthy knee). Total compensation of ATT by means of increased hamstring activity is possible; however, partial compensation represents a less deleterious strategy. PMID:20721326

  1. Default-Mode Network Activity Identified by Group Independent Component Analysis

    NASA Astrophysics Data System (ADS)

    Liu, Conghui; Zhuang, Jie; Peng, Danling; Yu, Guoliang; Yang, Yanhui

    Default-mode network activity refers to some regional increase in blood oxygenation level-dependent (BOLD) signal during baseline than cognitive tasks. Recent functional imaging studies have found co-activation in a distributed network of cortical regions, including ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PPC) that characterize the default mode of human brain. In this study, general linear model and group independent component analysis (ICA) were utilized to analyze the fMRI data obtained from two language tasks. Both methods yielded similar, but not identical results and detected a resting deactivation network at some midline regions including anterior and posterior cingulate cortex and precuneus. Particularly, the group ICA method segregated functional elements into two separate maps and identified ventral cingulate component and fronto-parietal component. These results suggest that these two components might be linked to different mental function during "resting" baseline.

  2. Structural brain correlates of unconstrained motor activity in people with schizophrenia.

    PubMed

    Farrow, Tom F D; Hunter, Michael D; Wilkinson, Iain D; Green, Russell D J; Spence, Sean A

    2005-11-01

    Avolition affects quality of life in chronic schizophrenia. We investigated the relationship between unconstrained motor activity and the volume of key executive brain regions in 16 male patients with schizophrenia. Wristworn actigraphy monitors were used to record motor activity over a 20 h period. Structural magnetic resonance imaging brain scans were parcellated and individual volumes for anterior cingulate cortex and dorsolateral prefrontal cortex extracted. Patients'total activity was positively correlated with volume of left anterior cingulate cortex. These data suggest that the volume of specific executive structures may affect (quantifiable) motor behaviours, having further implications for models of the 'will' and avolition.

  3. Neural Signatures of Value Comparison in Human Cingulate Cortex during Decisions Requiring an Effort-Reward Trade-off

    PubMed Central

    Kennerley, Steven W.; Friston, Karl; Bestmann, Sven

    2016-01-01

    Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome-based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. SIGNIFICANCE STATEMENT The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is

  4. Left anterior temporal cortex actively engages in speech perception: A direct cortical stimulation study.

    PubMed

    Matsumoto, Riki; Imamura, Hisaji; Inouchi, Morito; Nakagawa, Tomokazu; Yokoyama, Yohei; Matsuhashi, Masao; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2011-04-01

    Recent neuroimaging studies proposed the importance of the anterior auditory pathway for speech comprehension. Its clinical significance is implicated by semantic dementia or pure word deafness. Neurodegenerative or cerebrovascular nature, however, precluded precise localization of the cortex responsible for speech perception. Electrical cortical stimulation could delineate such localization by producing transient, functional impairment. We investigated engagement of the left anterior temporal cortex in speech perception by means of direct electrical cortical stimulation. Subjects were two partial epilepsy patients, who underwent direct cortical stimulation as a part of invasive presurgical evaluations. Stimulus sites were coregistered to presurgical 3D-MRI, and then to MNI standard space for anatomical localization. Separate from the posterior temporal language area, electrical cortical stimulation revealed a well-restricted language area in the anterior part of the superior temporal sulcus and gyrus (aSTS/STG) in both patients. Auditory sentence comprehension was impaired upon electrical stimulation of aSTS/STG. In one patient, additional investigation revealed that the functional impairment was restricted to auditory sentence comprehension with preserved visual sentence comprehension and perception of music and environmental sounds. Both patients reported that they could hear the voice but not understand the sentence well (e.g., heard as a series of meaningless utterance). The standard coordinates of this restricted area at left aSTS/STG well corresponded with the coordinates of speech perception reported in neuroimaging activation studies in healthy subjects. The present combined anatomo-functional case study, for the first time, demonstrated that aSTS/STG in the language dominant hemisphere actively engages in speech perception.

  5. Fiction feelings in Harry Potter: haemodynamic response in the mid-cingulate cortex correlates with immersive reading experience.

    PubMed

    Hsu, Chun-Ting; Conrad, Markus; Jacobs, Arthur M

    2014-12-01

    Immersion in reading, described as a feeling of 'getting lost in a book', is a ubiquitous phenomenon widely appreciated by readers. However, it has been largely ignored in cognitive neuroscience. According to the fiction feeling hypothesis, narratives with emotional contents invite readers more to be empathic with the protagonists and thus engage the affective empathy network of the brain, the anterior insula and mid-cingulate cortex, than do stories with neutral contents. To test the hypothesis, we presented participants with text passages from the Harry Potter series in a functional MRI experiment and collected post-hoc immersion ratings, comparing the neural correlates of passage mean immersion ratings when reading fear-inducing versus neutral contents. Results for the conjunction contrast of baseline brain activity of reading irrespective of emotional content against baseline were in line with previous studies on text comprehension. In line with the fiction feeling hypothesis, immersion ratings were significantly higher for fear-inducing than for neutral passages, and activity in the mid-cingulate cortex correlated more strongly with immersion ratings of fear-inducing than of neutral passages. Descriptions of protagonists' pain or personal distress featured in the fear-inducing passages apparently caused increasing involvement of the core structure of pain and affective empathy the more readers immersed in the text. The predominant locus of effects in the mid-cingulate cortex seems to reflect that the immersive experience was particularly facilitated by the motor component of affective empathy for our stimuli from the Harry Potter series featuring particularly vivid descriptions of the behavioural aspects of emotion.

  6. Fiction feelings in Harry Potter: haemodynamic response in the mid-cingulate cortex correlates with immersive reading experience.

    PubMed

    Hsu, Chun-Ting; Conrad, Markus; Jacobs, Arthur M

    2014-12-01

    Immersion in reading, described as a feeling of 'getting lost in a book', is a ubiquitous phenomenon widely appreciated by readers. However, it has been largely ignored in cognitive neuroscience. According to the fiction feeling hypothesis, narratives with emotional contents invite readers more to be empathic with the protagonists and thus engage the affective empathy network of the brain, the anterior insula and mid-cingulate cortex, than do stories with neutral contents. To test the hypothesis, we presented participants with text passages from the Harry Potter series in a functional MRI experiment and collected post-hoc immersion ratings, comparing the neural correlates of passage mean immersion ratings when reading fear-inducing versus neutral contents. Results for the conjunction contrast of baseline brain activity of reading irrespective of emotional content against baseline were in line with previous studies on text comprehension. In line with the fiction feeling hypothesis, immersion ratings were significantly higher for fear-inducing than for neutral passages, and activity in the mid-cingulate cortex correlated more strongly with immersion ratings of fear-inducing than of neutral passages. Descriptions of protagonists' pain or personal distress featured in the fear-inducing passages apparently caused increasing involvement of the core structure of pain and affective empathy the more readers immersed in the text. The predominant locus of effects in the mid-cingulate cortex seems to reflect that the immersive experience was particularly facilitated by the motor component of affective empathy for our stimuli from the Harry Potter series featuring particularly vivid descriptions of the behavioural aspects of emotion. PMID:25304498

  7. An electromyographic analysis of the knee during functional activities. II. The anterior cruciate ligament-deficient and -reconstructed profiles.

    PubMed

    Ciccotti, M G; Kerlan, R K; Perry, J; Pink, M

    1994-01-01

    This study compared the electromyographic activity of normal (N = 22), rehabilitated anterior cruciate ligament-deficient (N = 8), and -reconstructed knees (N = 10) while subjects performed activities. Each subject had evaluation of 8 muscles during 7 functional activities. Sixty-seven percent of the differences in the quadriceps muscle reflected increased activity in the vastus lateralis muscle of the rehabilitated group; 75% of the differences in the hamstrings muscles noted increased biceps femoris muscle activity in the rehabilitated group; 56% of the differences in the lower leg musculature showed increased tibialis anterior muscle activity in the rehabilitated group. Eighty-six percent of the statistically different intervals involved rehabilitated subjects demonstrating increased activity over reconstructed or normal subjects or both. The presence of a quadriceps-hamstrings muscles coordinated response was identified consistently in all 3 groups in each activity. This study supports surgical reconstruction for the anterior cruciate ligament-deficient knee. It also demonstrates the importance of the vastus lateralis, biceps femoris, and tibialis anterior musculature in the rehabilitation of the anterior cruciate ligament-deficient patient. The presence of a quadriceps-hamstrings muscles coordinated response indicates that mechanoreceptors mediating this reflex arc exist in structures other than the cruciate ligament.

  8. Right anterior superior temporal activation predicts auditory sentence comprehension following aphasic stroke.

    PubMed

    Crinion, Jenny; Price, Cathy J

    2005-12-01

    Previous studies have suggested that recovery of speech comprehension after left hemisphere infarction may depend on a mechanism in the right hemisphere. However, the role that distinct right hemisphere regions play in speech comprehension following left hemisphere stroke has not been established. Here, we used functional magnetic resonance imaging (fMRI) to investigate narrative speech activation in 18 neurologically normal subjects and 17 patients with left hemisphere stroke and a history of aphasia. Activation for listening to meaningful stories relative to meaningless reversed speech was identified in the normal subjects and in each patient. Second level analyses were then used to investigate how story activation changed with the patients' auditory sentence comprehension skills and surprise story recognition memory tests post-scanning. Irrespective of lesion site, performance on tests of auditory sentence comprehension was positively correlated with activation in the right lateral superior temporal region, anterior to primary auditory cortex. In addition, when the stroke spared the left temporal cortex, good performance on tests of auditory sentence comprehension was also correlated with the left posterior superior temporal cortex (Wernicke's area). In distinct contrast to this, good story recognition memory predicted left inferior frontal and right cerebellar activation. The implication of this double dissociation in the effects of auditory sentence comprehension and story recognition memory is that left frontal and left temporal activations are dissociable. Our findings strongly support the role of the right temporal lobe in processing narrative speech and, in particular, auditory sentence comprehension following left hemisphere aphasic stroke. In addition, they highlight the importance of the right anterior superior temporal cortex where the response was dissociated from that in the left posterior temporal lobe.

  9. Active Stiffness and Strength in People With Unilateral Anterior Shoulder Instability: A Bilateral Comparison

    PubMed Central

    Olds, Margie; McNair, Peter; Nordez, Antoine; Cornu, Christophe

    2011-01-01

    Context: Active muscle stiffness might protect the unstable shoulder from recurrent dislocation. Objective: To compare strength and active stiffness in participants with unilateral anterior shoulder instability and to examine the relationship between active stiffness and functional ability. Design: Cross-sectional study. Setting: University research laboratory. Patients or Other Participants: Participants included 16 males (age range, 16–40 years; height = 179.4 ± 6.1 cm; mass = 79.1 ± 6.8 kg) with 2 or more episodes of unilateral traumatic anterior shoulder instability. Main Outcome Measure(s): Active stiffness and maximal voluntary strength were measured bilaterally in participants. In addition, quality of life, function, and perceived instability were measured using the Western Ontario Stability Index, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, and Single Alpha Numeric Evaluation, respectively. Results: We found less horizontal adduction strength (t15 = −4.092, P = .001) and less stiffness at 30% (t14 = −3.796, P = .002) and 50% (t12 = −2.341, P = .04) maximal voluntary strength in the unstable than stable shoulder. Active stiffness was not correlated with quality of life, function, or perceived instability (r range, 0.0–0.25; P > .05). Conclusions: The observed reduction in stiffness in the unstable shoulder warrants inclusion of exercises in the rehabilitation program to protect the joint from perturbations that might lead to dislocation. The lack of association between active stiffness and quality of life, function, or perceived instability might indicate that stiffness plays a less direct role in shoulder stability. PMID:22488190

  10. Monoamine activity in anterior hypothalamus of guinea pig pups separated from their mothers.

    PubMed

    Harvey, A T; Moore, H; Lucot, J B; Hennessy, M B

    1994-02-01

    Brief isolation in a novel environment increased the ratios of 3-methoxy-4-hydroxyphenylethylene glycol to norepinephrine (MHPG:NE) and dihydroxyphenylacetic acid to dopamine (DOPAC:DA) in the anterior hypothalamus of guinea pig pups. Ratios were significantly elevated after 90 min of isolation and for MHPG:NE, after 30 min of isolation; changes were due to increases in MHPG and DOPAC. Home cage isolation produced no change in any measure of catecholamine activity. No changes in levels of serotonin or its metabolite were observed. In 1 experiment, resting levels of NE and DOPAC:DA were predictive of the rate of separation-induced vocalization. Maternal separation in the context of novelty increases hypothalamic NE and DA activity; however, both isolation and novelty are required because neither maternal separation in the home cage nor exposure to a novel cage together with the mother had any discernible effect. PMID:7514878

  11. Muscle activity amplitudes and co-contraction during stair ambulation following anterior cruciate ligament reconstruction.

    PubMed

    Hall, Michelle; Stevermer, Catherine A; Gillette, Jason C

    2015-04-01

    The purpose of this study was to compare muscle activity amplitudes and co-contraction in those with anterior cruciate ligament (ACL) reconstruction to healthy controls during stair negotiation. Eighteen participants with unilateral ACL reconstruction and 17 healthy controls performed stair ascent and descent while surface electromyography was recorded from knee and hip musculature. During stair ascent, the ACL group displayed higher gluteus maximus activity (1-50% stance, p = 0.02), higher vastus lateralis:biceps femoris co-contraction (51-100% stance, p = 0.01), and higher vastus lateralis:vastus medialis co-contraction (51-100% stance, p = 0.05). During stair descent, the ACL group demonstrated higher gluteus maximus activity (1-50% stance, p = 0.01; 51-100% stance, p < 0.01), lower rectus femoris activity (1-50% stance, p = 0.04), higher semimembranosus activity (1-50% stance, p=0.01), higher gluteus medius activity (51-100% stance, p = 0.01), and higher vastus medialis:semimembranosus co-contraction (1-50% stance, p = 0.02). While the altered muscle activity strategies observed in the ACL group may act to increase joint stability, these strategies may alter joint loading and contribute to post-traumatic knee osteoarthritis often observed in this population. Our results warrant further investigation to determine the longterm effects of altered muscle activity on the knee joint following ACL reconstruction.

  12. Influences of unconscious priming on voluntary actions: Role of the rostral cingulate zone.

    PubMed

    Teuchies, Martyn; Demanet, Jelle; Sidarus, Nura; Haggard, Patrick; Stevens, Michaël A; Brass, Marcel

    2016-07-15

    The ability to make voluntary, free choices is fundamental to what it means to be human. A key brain region that is involved in free choices is the rostral cingulate zone (RCZ), which is part of the medial frontal cortex. Previous research has shown that activity in this brain region can be modulated by bottom-up information while making free choices. The current study extends those findings, and shows, for the first time, that activation in the RCZ can also be modulated by subliminal information. We used a subliminal response priming paradigm to bias free and cued choices. We observed more activation in the RCZ when participants made a choice that went against the prime's suggestion, compared to when they chose according to the prime. This shows that the RCZ plays an important role in overcoming externally-triggered conflict between different response options, even when the stimuli triggering this conflict are not consciously perceived. Our results suggest that an important mechanism of endogenous action in the RCZ may therefore involve exerting an internally-generated action choice against conflicting influences, such as external sensory evidence. We further found that subliminal information also modulated activity in the anterior insula and the supramarginal gyrus.

  13. Training-stage related neuronal plasticity in limbic thalamus and cingulate cortex during learning: a possible key to mnemonic retrieval.

    PubMed

    Gabriel, M; Vogt, B A; Kubota, Y; Poremba, A; Kang, E

    1991-12-20

    This study is part of an ongoing project concerned with the analysis of the neural substrates of discriminative avoidance learning in rabbits. Multi-unit activity was recorded in 5 anterior and lateral thalamic nuclei and in 4 layers of 2 posterior cingulate cortical areas (29c/d and 29b) during learning. The rabbits learned to step in response to a warning tone to avoid a foot-shock, and to ignore a different tone not followed by shock. Excitatory training-induced unit activity (TIA, increased tone-elicited activity during training relative to a pretraining session with unpaired tone-shock presentations) and/or discriminative TIA (greater discharges to the warning than to the safe tone) developed during training in 11 of the 13 areas. Discriminative TIA in the thalamic nuclei increased monotonically as learning occurred. Anterodorsal (AD) thalamic excitatory TIA peaked in an early stage (the first session of training), laterodorsal thalamic and parvocellular anteroventral (AVp) excitatory TIA peaked in an intermediate stage (the session of the first behavioral discrimination), and magnocellular anteroventral (AVm) and anteromedial (AM) thalamic excitatory TIA peaked in a late stage (the session in which asymptotic behavioral discrimination first occurred). The excitatory TIA in these nuclei declined as training continued beyond the stage in which the peak occurred. Peaks of excitatory TIA developed in area 29c/d of posterior cingulate cortex in the early (layer IV), intermediate (layers I-III and V) and late (layer IV) training stages, as just defined. Only layer IV in area 29b of posterior cingulate cortex exhibited a peak of excitatory TIA, which occurred in the early and intermediate training stages. As in limbic thalamus, discriminative TIA increased monotonically over training stages in layers V and VI of areas 29c/d and in layer VI of area 29b. However, layers I-III and IV in area 29c exhibited peak discriminative TIA in the intermediate and late training

  14. Increased muscle activation following motor imagery during the rehabilitation of the anterior cruciate ligament.

    PubMed

    Lebon, Florent; Guillot, Aymeric; Collet, Christian

    2012-03-01

    Motor imagery (MI) is the mental representation of an action without any concomitant movement. MI has been used frequently after peripheral injuries to decrease pain and facilitate rehabilitation. However, little is known about the effects of MI on muscle activation underlying the motor recovery. This study aimed to assess the therapeutic effects of MI on the activation of lower limb muscles, as well as on the time course of functional recovery and pain after surgery of the anterior cruciate ligament (ACL). Twelve patients with a torn ACL were randomly assigned to a MI or control group, who both received a series of physiotherapy. Electromyographic activity of the quadriceps, pain, anthropometrical data, and lower limb motor ability were measured throughout a 12-session therapy. The data provided evidence that MI elicited greater muscle activation, even though imagery practice did not result in pain decrease. Muscle activation increase might originate from a redistribution of the central neuronal activity, as there was no anthropometric change in lower limb muscles after imagery practice. This study confirmed the effectiveness of integrating MI in a rehabilitation process by facilitating muscular properties recovery following motor impairment. MI may thus be considered a reliable adjunct therapy to help injured patients to recover motor functions after reconstructive surgery of ACL.

  15. Altered Cingulate Sub-Region Activation Accounts for Task-Related Dissociation in ERN Amplitude as a Function of Obsessive-Compulsive Symptoms

    ERIC Educational Resources Information Center

    Cavanagh, James F.; Grundler, Theo O. J.; Frank, Michael J.; Allen, John J. B.

    2010-01-01

    Larger error-related negativities (ERNs) have been consistently found in obsessive-compulsive disorder (OCD) patients, and are thought to reflect the activities of a hyperactive cortico-striatal circuit during action monitoring. We previously observed that obsessive-compulsive (OC) symptomatic students (non-patients) have larger ERNs during errors…

  16. Anterior insula activity reflects the effects of intentionality on the anticipation of aversive stimulation.

    PubMed

    Liljeholm, Mimi; Dunne, Simon; O'Doherty, John P

    2014-08-20

    If someone causes you harm, your affective reaction to that person might be profoundly influenced by your inferences about the intentionality of their actions. In the present study, we aimed to understand how affective responses to a biologically salient aversive outcome administered by others are modulated by the extent to which a given individual is judged to have deliberately or inadvertently delivered the outcome. Using fMRI, we examined how neural responses to anticipation and receipt of an aversive stimulus are modulated by this fundamental social judgment. We found that affective evaluations about an individual whose actions led to either noxious or neutral consequences for the subject did indeed depend on the perceived intentions of that individual. At the neural level, activity in the anterior insula correlated with the interaction between perceived intentionality and anticipated outcome valence, suggesting that this region reflects the influence of mental state attribution on aversive expectations.

  17. Role of abnormal anterior pituitary hormones-growth hormone and prolactin in active systemic lupus erythematosus

    PubMed Central

    Zhu, Xiaohua; Xu, Jinhua; Li, Shujuan; Huang, Wen; Li, Feng

    2015-01-01

    Background: The role of anterior pituitary hormones in systemic lupus erythematosus (SLE) remains controversial. Aims and Objectives: We determined the expression levels of human growth hormone (GH), prolactin (PRL), and their receptors in subjects presenting with SLE, and modulation of disease severity. Materials and methods: Forty-seven subjects and ten healthy controls were assessed for possible association between SLE disease activity and levels of serum PRL, GH and thyrotropin-releasing hormone (TRH). In peripheral blood mononuclear cells (PBMC), specific binding and mRNA expression of receptors for GH (GHR), and PRL (PRLR) were determined by receptor-ligand binding assay (RLBA) and RT-PCR. PBMC of recruited subjects were treated with hPRL and rhGH to assess IgG production and antibodies against dsDNA. Results: In active SLE subjects we found elevated PRL and GH levels. Study subject PBMCs displayed augmented GHR and PRLR protein and mRNA expression. Study subjects also showed a positive correlation in serum PRL levels and specific antibodies against dsDNA, SLE disease activity index (SLEDAI), and proteinuria. However, a negative correlation was found between serum PRL levels and complement component C3. We found a positive correlation between specific binding rates of PRLR and GHR and both SLE activity and dsDNA antibody titers. Enhanced IgG and anti-dsDNA secretion was observed in cultured PBMC stimulated by PRL or GH with/without PHA, PWM, IL-2 or IL-10. In active SLE, a close association was found between augmented PRL and GH levels, expression and specific binding activities of PRLR and GHR, and changes in the specific titer of anti-dsDNA. Conclusion: Anterior pituitary hormones play an important role in the pathogenesis of SLE. High levels of growth hormone (GH) and prolactin (PRL) play a role in pathogenesis of SLE, which is correlated with SLE disease activity and antibodies against dsDNA. The mechanism of GH and PRL in SLE was complicated and should

  18. Effect of knee angle on quadriceps strength and activation after anterior cruciate ligament reconstruction

    PubMed Central

    Theuerkauf, Paul

    2015-01-01

    Quadriceps strength and activation deficits after anterior cruciate ligament (ACL) injury or surgery are typically evaluated at joint positions that are biomechanically advantageous to the quadriceps muscle. However, the effect of knee joint position and the associated changes in muscle length on strength and activation is currently unknown in this population. Here, we examined the effect of knee angle on quadriceps strength, activation, and electrically evoked torque in individuals with ACL reconstruction. Furthermore, we evaluated whether knee angle mediated the relationship between quadriceps weakness and functional performance after ACL reconstruction. Knee strength and activation were tested bilaterally at 90° and 45° of knee flexion in 11 subjects with ACL reconstruction using an interpolated triplet technique. The magnitude of electrically evoked torque at rest was used to quantify peripheral muscle contractile property changes, and the single-leg hop for distance test was used to evaluate functional performance. The results indicated that although quadriceps strength deficits were similar between knee angles, voluntary activation deficits were significantly higher in the reconstructed leg at 45° of knee flexion. On the contrary, the side-to-side evoked torque at rest ratio [i.e., (reconstructed/nonreconstructed) × 100] was significantly lower at 90° than at 45° of knee flexion. The association between quadriceps strength and functional performance was stronger at 45° of knee flexion. The results provide novel evidence that quadriceps activation is selectively affected at 45° of knee flexion and emphasize the importance of assessing quadriceps strength and activation at this position when feasible because it better captures activation deficits. PMID:25997949

  19. Effect of knee angle on quadriceps strength and activation after anterior cruciate ligament reconstruction.

    PubMed

    Krishnan, Chandramouli; Theuerkauf, Paul

    2015-08-01

    Quadriceps strength and activation deficits after anterior cruciate ligament (ACL) injury or surgery are typically evaluated at joint positions that are biomechanically advantageous to the quadriceps muscle. However, the effect of knee joint position and the associated changes in muscle length on strength and activation is currently unknown in this population. Here, we examined the effect of knee angle on quadriceps strength, activation, and electrically evoked torque in individuals with ACL reconstruction. Furthermore, we evaluated whether knee angle mediated the relationship between quadriceps weakness and functional performance after ACL reconstruction. Knee strength and activation were tested bilaterally at 90° and 45° of knee flexion in 11 subjects with ACL reconstruction using an interpolated triplet technique. The magnitude of electrically evoked torque at rest was used to quantify peripheral muscle contractile property changes, and the single-leg hop for distance test was used to evaluate functional performance. The results indicated that although quadriceps strength deficits were similar between knee angles, voluntary activation deficits were significantly higher in the reconstructed leg at 45° of knee flexion. On the contrary, the side-to-side evoked torque at rest ratio [i.e., (reconstructed/nonreconstructed) × 100] was significantly lower at 90° than at 45° of knee flexion. The association between quadriceps strength and functional performance was stronger at 45° of knee flexion. The results provide novel evidence that quadriceps activation is selectively affected at 45° of knee flexion and emphasize the importance of assessing quadriceps strength and activation at this position when feasible because it better captures activation deficits.

  20. Neurochemical, morphologic, and laminar characterization of cortical projection neurons in the cingulate motor areas of the macaque monkey

    NASA Technical Reports Server (NTRS)

    Nimchinsky, E. A.; Hof, P. R.; Young, W. G.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1996-01-01

    The primate cingulate gyrus contains multiple cortical areas that can be distinguished by several neurochemical features, including the distribution of neurofilament protein-enriched pyramidal neurons. In addition, connectivity and functional properties indicate that there are multiple motor areas in the cortex lining the cingulate sulcus. These motor areas were targeted for analysis of potential interactions among regional specialization, connectivity, and cellular characteristics such as neurochemical profile and morphology. Specifically, intracortical injections of retrogradely transported dyes and intracellular injection were combined with immunocytochemistry to investigate neurons projecting from the cingulate motor areas to the putative forelimb region of the primary motor cortex, area M1. Two separate groups of neurons projecting to area M1 emanated from the cingulate sulcus, one anterior and one posterior, both of which furnished commissural and ipsilateral connections with area M1. The primary difference between the two populations was laminar origin, with the anterior projection originating largely in deep layers, and the posterior projection taking origin equally in superficial and deep layers. With regard to cellular morphology, the anterior projection exhibited more morphologic diversity than the posterior projection. Commissural projections from both anterior and posterior fields originated largely in layer VI. Neurofilament protein distribution was a reliable tool for localizing the two projections and for discriminating between them. Comparable proportions of the two sets of projection neurons contained neurofilament protein, although the density and distribution of the total population of neurofilament protein-enriched neurons was very different in the two subareas of origin. Within a projection, the participating neurons exhibited a high degree of morphologic heterogeneity, and no correlation was observed between somatodendritic morphology and

  1. Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex

    PubMed Central

    Walter, Susanna A.; Forsgren, Mikael; Lundengård, Karin; Simon, Rozalyn; Torkildsen Nilsson, Maritha; Söderfeldt, Birgitta; Lundberg, Peter; Engström, Maria

    2016-01-01

    Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms. PMID:26930498

  2. Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex.

    PubMed

    Walter, Susanna A; Forsgren, Mikael; Lundengård, Karin; Simon, Rozalyn; Torkildsen Nilsson, Maritha; Söderfeldt, Birgitta; Lundberg, Peter; Engström, Maria

    2016-01-01

    Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.

  3. Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex.

    PubMed

    Walter, Susanna A; Forsgren, Mikael; Lundengård, Karin; Simon, Rozalyn; Torkildsen Nilsson, Maritha; Söderfeldt, Birgitta; Lundberg, Peter; Engström, Maria

    2016-01-01

    Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms. PMID:26930498

  4. Behavioral Regulation and the Modulation of Information Coding in the Lateral Prefrontal and Cingulate Cortex.

    PubMed

    Khamassi, Mehdi; Quilodran, René; Enel, Pierre; Dominey, Peter F; Procyk, Emmanuel

    2015-09-01

    To explain the high level of flexibility in primate decision-making, theoretical models often invoke reinforcement-based mechanisms, performance monitoring functions, and core neural features within frontal cortical regions. However, the underlying biological mechanisms remain unknown. In recent models, part of the regulation of behavioral control is based on meta-learning principles, for example, driving exploratory actions by varying a meta-parameter, the inverse temperature, which regulates the contrast between competing action probabilities. Here we investigate how complementary processes between lateral prefrontal cortex (LPFC) and dorsal anterior cingulate cortex (dACC) implement decision regulation during exploratory and exploitative behaviors. Model-based analyses of unit activity recorded in these 2 areas in monkeys first revealed that adaptation of the decision function is reflected in a covariation between LPFC neural activity and the control level estimated from the animal's behavior. Second, dACC more prominently encoded a reflection of outcome uncertainty useful for control regulation based on task monitoring. Model-based analyses also revealed higher information integration before feedback in LPFC, and after feedback in dACC. Overall the data support a role of dACC in integrating reinforcement-based information to regulate decision functions in LPFC. Our results thus provide biological evidence on how prefrontal cortical subregions may cooperate to regulate decision-making.

  5. Behavioral Regulation and the Modulation of Information Coding in the Lateral Prefrontal and Cingulate Cortex.

    PubMed

    Khamassi, Mehdi; Quilodran, René; Enel, Pierre; Dominey, Peter F; Procyk, Emmanuel

    2015-09-01

    To explain the high level of flexibility in primate decision-making, theoretical models often invoke reinforcement-based mechanisms, performance monitoring functions, and core neural features within frontal cortical regions. However, the underlying biological mechanisms remain unknown. In recent models, part of the regulation of behavioral control is based on meta-learning principles, for example, driving exploratory actions by varying a meta-parameter, the inverse temperature, which regulates the contrast between competing action probabilities. Here we investigate how complementary processes between lateral prefrontal cortex (LPFC) and dorsal anterior cingulate cortex (dACC) implement decision regulation during exploratory and exploitative behaviors. Model-based analyses of unit activity recorded in these 2 areas in monkeys first revealed that adaptation of the decision function is reflected in a covariation between LPFC neural activity and the control level estimated from the animal's behavior. Second, dACC more prominently encoded a reflection of outcome uncertainty useful for control regulation based on task monitoring. Model-based analyses also revealed higher information integration before feedback in LPFC, and after feedback in dACC. Overall the data support a role of dACC in integrating reinforcement-based information to regulate decision functions in LPFC. Our results thus provide biological evidence on how prefrontal cortical subregions may cooperate to regulate decision-making. PMID:24904073

  6. Time course of regional brain activation associated with onset of auditory/verbal hallucinations

    PubMed Central

    Hoffman, Ralph E.; Anderson, Adam W.; Varanko, Maxine; Gore, John C.; Hampson, Michelle

    2008-01-01

    The time course of brain activation prior to onset of auditory/verbal hallucinations was characterised using functional magnetic resonance imaging in six dextral patients with schizophrenia. Composite maps of pre-hallucination periods revealed activation in the left anterior insula and in the right middle temporal gyrus, partially replicating two previous case reports, as well as deactivation in the anterior cingulate and parahippocampal gyri. These findings may reflect brain events that trigger or increase vulnerability to auditory/verbal hallucinations. PMID:18978327

  7. fMRI Activation in Late-Life Anxious Depression: a Potential Biomarker

    PubMed Central

    Andreescu, Carmen; Butters, Meryl; Lenze, Eric J.; Venkatraman, Vijay K; Nable, Megan; Reynolds, Charles F.; Aizenstein, Howard J.

    2009-01-01

    Objective and Methods The neurobiology of late-life anxious depression (LLAD) is poorly characterized despite evidence that this is a common and severe subtype of late-life depression. To identify the neuroanatomical substrate of late-life anxious depression, we examined event-related fMRI data collected in 8 subjects with late-life depression, half of whom had high levels of comorbid anxiety. Subjects were trained on the Preparing to Overcome Prepotency (POP) task, which is an executive control task that reliably activates the lateral prefrontal cortex - anterior cingulate cortex cognitive control circuit. Results Time series analysis showed that, when compared with elderly depressed subjects, elderly subjects with anxious depression performing the POP task produced a significantly greater and more sustained signal in three regions: BA 24 (dorsal anterior cingulate), BA31 (posterior cingulate) and BA6 (prefrontal cortex). While elderly subjects with pure depression presented a bimodal activation curve in the dorsal anterior cingulate and the posterior cingulate, elderly subjects with anxious depression presented a sustained unimodal activation pattern. Conclusions Our preliminary results suggest specific activation patterns unique to anxious depression that may suggest greater and more sustained efforts of the ACC to carry out cognitive control tasks. Further research is needed to clarify the neuroanatomical basis of late-life anxious depression. PMID:19575412

  8. Resting State Functional Connectivity within the Cingulate Cortex Jointly Predicts Agreeableness and Stressor-Evoked Cardiovascular Reactivity

    PubMed Central

    Ryan, John P.; Sheu, Lei K.; Gianaros, Peter J.

    2010-01-01

    Exaggerated cardiovascular reactivity to stress confers risk for cardiovascular disease. Further, individual differences in stressor-evoked cardiovascular reactivity covary with the functionality of cortical and limbic brain areas, particularly within the cingulate cortex. What remains unclear, however, is how individual differences in personality traits interact with cingulate functionality in the prediction of stressor-evoked cardiovascular reactivity. Accordingly, we tested the associations between (i) a particular personality trait, Agreeableness, which is associated with emotional reactions to conflict, (ii) resting state functional connectivity within the cingulate cortex, and (iii) stressor-evoked blood pressure (BP) reactivity. Participants (N=39, 19 men, aged 20–37 yrs) completed a resting functional connectivity MRI protocol, followed by two standardized stressor tasks that engaged conflict processing and evoked BP reactivity. Agreeableness covaried positively with BP reactivity across individuals. Moreover, connectivity analyses demonstrated that a more positive functional connectivity between the posterior cingulate (BA31) and the perigenual anterior cingulate (BA32) covaried positively with Agreeableness and with BP reactivity. Finally, statistical mediation analyses demonstrated that BA31–BA32 connectivity mediated the covariation between Agreeableness and BP reactivity. Functional connectivity within the cingulate appears to link Agreeableness and a risk factor for cardiovascular disease, stressor-evoked BP reactivity. PMID:21130172

  9. Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Roy, R. R.; Edgerton, V. R.

    1995-01-01

    The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data

  10. Anterior cruciate ligament injury after more than 20 years: I. Physical activity level and knee function.

    PubMed

    Tengman, E; Brax Olofsson, L; Nilsson, K G; Tegner, Y; Lundgren, L; Häger, C K

    2014-12-01

    Little is known about physical activity level and knee function including jump capacity and fear of movement/reinjury more than 20 years after injury of the anterior cruciate ligament (ACL). Seventy persons with unilateral ACL injury participated (23 ± 2 years post-injury): 33 treated with physiotherapy in combination with surgical reconstruction (ACLR ), and 37 treated with physiotherapy alone (ACLPT ). These were compared with 33 age- and gender-matched controls. Assessment included knee-specific and general physical activity level [Tegner activity scale, International Physical Activity Questionnaire (IPAQ)], knee function [Lysholm score, Knee injury and Osteoarthritis Outcome Score (KOOS)], jump capacity (one-leg hop, vertical jump, side hops), and fear of movement/reinjury [Tampa Scale for Kinesiophobia (TSK)]. Outcomes were related to degree of osteoarthritis (OA). ACL-injured had lower Lysholm, KOOS, and Tegner scores than controls (P < 0.001), while IPAQ score was similar. ACL-injured demonstrated inferior jump capacity in injured compared with noninjured leg (6-25%, P < 0.001-P = 0.010 in the different jumps), while noninjured leg had equal jump capacity as controls. ACL groups scored 33 ± 7 and 32 ± 7 of 68 on TSK. Lower scores on Lysholm and KOOS symptom were seen for persons with moderate-to-high OA than for no-or-low OA, while there were no differences for physical activity and jump capacity. Regardless of treatment, there are still negative knee-related effects of ACL injury more than 20 years later.

  11. Altered functional connectivity between the insula and the cingulate cortex in patients with TMD – a pilot study

    PubMed Central

    Ichesco, Eric; Quintero, Andres; Clauw, Daniel J.; Peltier, Scott; Sundgren, Pia M.; Gerstner, Geoffrey E.; Schmidt-Wilcke, Tobias

    2011-01-01

    Background Amongst the most common chronic pain conditions, yet poorly understood, are temporomandibular disorders (TMDs), with a prevalence estimate of 3 – 15% for Western populations. Although it is increasingly acknowledged that central nervous system mechanisms contribute to pain amplification and chronicity in TMDs, further research is needed to unravel neural correlates that might abet the development of chronic pain. Objective The insular cortex (IC) and cingulate cortex (CC) are both critically involved in the experience of pain. The current study sought specifically to investigate IC-CC functional connectivity in TMD patients and healthy controls (HCs), both during resting state and during the application of a painful stimulus. Method Eight patients with TMD, and 8 age and sex matched healthy controls (HCs) were enrolled in the present study. FMRI data during resting state and during the performance of a pressure pain stimulus to the temple were acquired. Predefined seed regions were placed in the IC (anterior and posterior insular cortices) and the extracted signal was correlated with brain activity throughout the whole brain. Specifically we were interested whether TMD patients and HCs would show differences in IC – CC connectivity, both during resting state and during the application of a painful stimulus to the face. Results As a main finding functional connectivity analyses revealed an increased functional connectivity between the left anterior IC and pregenual ACC in TMD patients, during both resting state and applied pressure pain. Within the patient group there was a negative correlation between the anterior IC - ACC connectivity and clinical pain intensity as measured by a VAS. Conclusions Since the pregenual region of the ACC is critically involved in antinociception, we hypothesize that an increase in anterior IC – ACC connectivity is indicative of an adaptation of the pain modulatory system early in the chronification process. PMID

  12. Fear avoidance beliefs in back pain-free subjects are reflected by amygdala-cingulate responses.

    PubMed

    Meier, Michael L; Stämpfli, Phillipp; Vrana, Andrea; Humphreys, Barry K; Seifritz, Erich; Hotz-Boendermaker, Sabina

    2015-01-01

    In most individuals suffering from chronic low back pain, psychosocial factors, specifically fear avoidance beliefs (FABs), play central roles in the absence of identifiable organic pathology. On a neurobiological level, encouraging research has shown brain system correlates of somatic and psychological factors during the transition from (sub) acute to chronic low back pain. The characterization of brain imaging signatures in pain-free individuals before any injury will be of high importance regarding the identification of relevant networks for low back pain (LBP) vulnerability. Fear-avoidance beliefs serve as strong predictors of disability and chronification in LBP and current research indicates that back pain related FABs already exist in the general and pain-free population. Therefore, we aimed at investigating possible differential neural functioning between high- and low fear-avoidant individuals in the general population using functional magnetic resonance imaging. Results revealed that pain-free individuals without a history of chronic pain episodes could be differentiated in amygdala activity and connectivity to the pregenual anterior cingulate cortex by their level of back pain related FABs. These results shed new light on brain networks underlying psychological factors that may become relevant for enhanced disability in a future LBP episode. PMID:26257635

  13. A COMPARISON OF TWO TAPING TECHNIQUES (KINESIO AND MCCONNELL) AND THEIR EFFECT ON ANTERIOR KNEE PAIN DURING FUNCTIONAL ACTIVITIES

    PubMed Central

    Babu, Jenie; Dmochowska, Katarzyna; Scariah, Shiju; Varughese, Jincy

    2013-01-01

    Background: Anterior knee pain is a clinical syndrome characterized by pain experienced perceived over the anterior aspect of the knee that can be aggravated by functional activities such as stair climbing and squatting. Two taping techniques commonly used for anterior knee pain in the clinic include the McConnell Taping Technique (MT) and the Kinesio Taping® Method (KT®). Objective: The purpose of this study was to compare the effectiveness of KT® and the MT versus no tape in subjects with anterior knee pain during a squat lift and stair climbing. Design: Pretest‐ posttest design. Participants: A total of 20 subjects (15 female, 5 male) with unilateral anterior knee pain were recruited. The mean age of the subjects was 24 (+/–3) years, with a mean weight of 160 (+/–28) pounds. Methods: Each participant was tested during two functional activities; a squat lift with a weighted box (10% of his/her body weight, plus the weight [8.5 pounds] of the box) and stair climbing under three conditions: 1) no tape, 2) MT and 3) KT®. Pain levels were assessed (verbally) using the 0‐10 Numeric Pain Intensity Scale. Results: The median (interquartile range [IQR]) pain during squat lift was 2 (2.75) for no tape, 1 (1) for KT®, and 0.5 (2) for McConnell, with no significant differences between the groups. During the stair activity the median (IQR) pain was 1.5 (2.75) for no tape, 1 (1.75) for KT®, and 1 (1.75) for MT with a significant difference (p=0.024) between the groups. Further analysis determined that the only a significant difference was (p=0.034) between the no tape and the KT® conditions. Conclusion: The results of this study found that both the KT® and the MT may be effective in reducing pain during stair climbing activities. Level of Evidence: Level 2, Prospective Cohort study PMID:23593548

  14. Cannabis use and brain structural alterations of the cingulate cortex in early psychosis.

    PubMed

    Rapp, Charlotte; Walter, Anna; Studerus, Erich; Bugra, Hilal; Tamagni, Corinne; Röthlisberger, Michel; Borgwardt, Stefan; Aston, Jacqueline; Riecher-Rössler, Anita

    2013-11-30

    As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors.

  15. Knee functions and a return to sports activity in competitive athletes following anterior cruciate ligament reconstruction.

    PubMed

    Nakayama, Y; Shirai, Y; Narita, T; Mori, A; Kobayashi, K

    2000-06-01

    We investigated knee functions and a return to sports in 50 competitive athlete patients treated with arthroscopic anterior cruciate ligament reconstruction using double-looped STG augmented by woven polyester at a 1-year follow-up. There were 25 males and 25 females with a mean age of 24.3 years (range: 19-39 years). The majority of preinjury sports were basketball, volleyball and soccer. Athletic rehabilitation including agility training and sports-specific training was started at 12 weeks. Fourty patients (80%) was rated as normal or nearly normal on the assessment of International Knee Documentation Commitee postoperatively. Fourty-eight patients (96%) obtained full range of motion, and the mean quadriceps muscle strength of the injured side was 91.3%of that of the uninjured side. As for a return to sports, 46 patients (92%) were able to do fully competitive sports at a mean of 8.1 postoperative months. These results suggest that arthroscopic reconstruction using augmented double-looped STG allows early athletic rehabilitation, and lead satisfactory outcome as well as a reliable and early return to preinjury level of sport activity for the majority of the competitive athlete patients.

  16. Glucocorticoids Inhibit CRH/AVP-Evoked Bursting Activity of Male Murine Anterior Pituitary Corticotrophs

    PubMed Central

    Duncan, Peter J.; Tabak, Joël; Ruth, Peter; Bertram, Richard

    2016-01-01

    Corticotroph cells from the anterior pituitary are an integral component of the hypothalamic-pituitary-adrenal (HPA) axis, which governs the neuroendocrine response to stress. Corticotrophs are electrically excitable and fire spontaneous single-spike action potentials and also display secretagogue-induced bursting behavior. The HPA axis function is dependent on effective negative feedback in which elevated plasma glucocorticoids result in inhibition at the level of both the pituitary and the hypothalamus. In this study, we have used an electrophysiological approach coupled with mathematical modeling to investigate the regulation of spontaneous and CRH/arginine vasopressin-induced activity of corticotrophs by glucocorticoids. We reveal that pretreatment of corticotrophs with 100 nM corticosterone (CORT; 90 and 150 min) reduces spontaneous activity and prevents a transition from spiking to bursting after CRH/arginine vasopressin stimulation. In addition, previous studies have identified a role for large-conductance calcium- and voltage-activated potassium (BK) channels in the generation of secretagogue-induced bursting in corticotrophs. Using the dynamic clamp technique, we demonstrated that CRH-induced bursting can be switched to spiking by subtracting a fast BK current, whereas the addition of a fast BK current can induce bursting in CORT-treated cells. In addition, recordings from BK knockout mice (BK−/−) revealed that CORT can also inhibit excitability through BK-independent mechanisms to control spike frequency. Thus, we have established that glucocorticoids can modulate multiple properties of corticotroph electrical excitability through both BK-dependent and BK-independent mechanisms. PMID:27254001

  17. Posterior cingulate cortex: adapting behavior to a changing world.

    PubMed

    Pearson, John M; Heilbronner, Sarah R; Barack, David L; Hayden, Benjamin Y; Platt, Michael L

    2011-04-01

    When has the world changed enough to warrant a new approach? The answer depends on current needs, behavioral flexibility and prior knowledge about the environment. Formal approaches solve the problem by integrating the recent history of rewards, errors, uncertainty and context via Bayesian inference to detect changes in the world and alter behavioral policy. Neuronal activity in posterior cingulate cortex - a key node in the default network - is known to vary with learning, memory, reward and task engagement. We propose that these modulations reflect the underlying process of change detection and motivate subsequent shifts in behavior.

  18. Cross-modal representations of first-hand and vicarious pain, disgust and fairness in insular and cingulate cortex

    PubMed Central

    Corradi-Dell'Acqua, Corrado; Tusche, Anita; Vuilleumier, Patrik; Singer, Tania

    2016-01-01

    The anterior insula (AI) and mid-anterior cingulate cortex (mACC) have repeatedly been implicated in first-hand and vicarious experiences of pain, disgust and unfairness. However, it is debated whether these regions process different aversive events through a common modality-independent code, reflecting the shared unpleasantness of the experiences or through independent modality-specific representations. Using functional magnetic resonance imaging, we subjected 19 participants (and 19 confederates) to equally unpleasant painful and disgusting stimulations, as well as unfair monetary treatments. Multivoxel pattern analysis identified modality-independent activation maps in the left AI and mACC, pointing to common coding of affective unpleasantness, but also response patterns specific for the events' sensory properties and the person to whom it was addressed, particularly in the right AI. Our results provide evidence of both functional specialization and integration within AI and mACC, and support a comprehensive role of this network in processing aversive experiences for self and others. PMID:26988654

  19. Coordinated electromyographic activity of the human masseter and temporalis anterior muscles during mastication.

    PubMed

    Ferrario, V F; Sforza, C

    1996-01-01

    The present report aimed at evaluating the within- and between-subject electromyographic coordination between the masseter (M) and temporalis anterior (T) muscles during the performance of a standardized chewing task. Electromyographic activity of M and T muscles was recorded in 60 young healthy adults (30 men, 30 women) during two 15-s unilateral mastications of gum. Left-right differential potentials (delta M = MR-ML, delta T = TR-TL) were computed and the square root of (delta M2 + delta T2) moduli were calculated. The maximum modulus relative to each masticatory cycle was located, and each modulus and differential potential were expressed as a % of the maximum modulus for each subject and chewing trial. For each subject and chewing side, the masticatory frequency was computed, and statistics of the moduli as %s of the maximum were determined by means of bivariate analysis. Within-subject repeatability of the unilateral chewing patterns was good. Mean population values for the modulus position (bivariate analysis), chewing frequency, and maximum modulus of the differential potentials (univariate statistics) were computed. A significant gender difference was found for the masticatory frequency, with larger values in men than in women. Conversely, no gender or side differences were found for the mean values of the maximum modulus or for the mean position of the percentage moduli. The chewing test applied allowed the evaluation of the neuromuscular coordination during the performance of a standardized physiologic activity. In particular, it quantified the within-subject and chewing side repeatability of the muscular pattern.

  20. Is anterior cruciate ligament surgery technique important in rehabilitation and activity scores?

    PubMed Central

    Kilinc, Bekir Eray; Kara, Adnan; Celik, Haluk; Oc, Yunus; Camur, Savas

    2016-01-01

    To compare the two different anterior cruciate ligament surgery techniques’ effect in rehabilitation and activity performance. Fifty-five patients were evaluated. Twenty-seven patients with transtibial technique (TT), 28 with anatomic single-bundle technique (AT) included. Tegner Activity Scale (TAS) was performed at preoperation and follow-up. The returning time of the sport and work was evaluated at follow-up. Single-leg hop test was performed at follow-up. Outcomes were compared between the two groups. The determined length difference between the operated knee and the intact knee was compared between the two groups. Average age of TT and AT was 27.9±6.4 yr, 28.3±6 yr, respectively. There was a significant difference between the two groups in duration of returning to sport. TT group had higher duration to return to sport (P<0.01). No difference between the two groups in duration of returning to work (P>0.05). There was a significant difference between the two groups. TT group had significantly higher values than AT group (P<0.01). No difference in TAS between the two techniques at preoperation and at last follow-up (P>0.05). The increase of TAS in patients who had AT was higher than the patients who had TT (P>0.05). No difference in single-leg hop test at 55%–65%, 65%–75%, and 85%–95% level (P>0.05). In this test at 75%–85% TT group had higher values than AT group (P<0.05), AT group had higher values at 95%–105% level (P<0.05). Good short and long-term knee outcome scores depend on rehabilitation protocol after surgery. Surgery technique should provide the adequate stability in rehabilitation period. AT obtains better outcomes in rehabilitation. PMID:27419120

  1. Spatial Representations in Local Field Potential Activity of Primate Anterior Intraparietal Cortex (AIP)

    PubMed Central

    Lehmann, Sebastian J.; Scherberger, Hansjörg

    2015-01-01

    The execution of reach-to-grasp movements in order to interact with our environment is an important subset of the human movement repertoire. To coordinate such goal-directed movements, information about the relative spatial position of target and effector (in this case the hand) has to be continuously integrated and processed. Recently, we reported the existence of spatial representations in spiking-activity of the cortical fronto-parietal grasp network (Lehmann & Scherberger 2013), and in particular in the anterior intraparietal cortex (AIP). To further investigate the nature of these spatial representations, we explored in two rhesus monkeys (Macaca mulatta) how different frequency bands of the local field potential (LFP) in AIP are modulated by grip type, target position, and gaze position, during the planning and execution of reach-to-grasp movements. We systematically varied grasp type, spatial target, and gaze position and found that both spatial and grasp information were encoded in a variety of frequency bands (1–13Hz, 13–30Hz, 30–60Hz, and 60–100Hz, respectively). Whereas the representation of grasp type strongly increased towards and during movement execution, spatial information was represented throughout the task. Both spatial and grasp type representations could be readily decoded from all frequency bands. The fact that grasp type and spatial (reach) information was found not only in spiking activity, but also in various LFP frequency bands of AIP, might significantly contribute to the development of LFP-based neural interfaces for the control of upper limb prostheses. PMID:26554592

  2. Systematic regional variations of GABA, glutamine, and glutamate concentrations follow receptor fingerprints of human cingulate cortex.

    PubMed

    Dou, Weiqiang; Palomero-Gallagher, Nicola; van Tol, Marie-José; Kaufmann, Jörn; Zhong, Kai; Bernstein, Hans-Gert; Heinze, Hans-Jochen; Speck, Oliver; Walter, Martin

    2013-07-31

    Magnetic resonance spectroscopy (MRS) of glutamatergic or GABAergic measures in anterior cingulate cortex (ACC) was found altered in psychiatric disorders and predictive of interindividual variations of functional responses in healthy populations. Several ACC subregions have been parcellated into receptor-architectonically different portions with heterogeneous fingerprints for excitatory and inhibitory receptors. Similarly, these subregions overlap with functionally distinct regions showing opposed signal changes toward stimulation or resting conditions. We therefore investigated whether receptor-architectonical and functional segregation of the cingulate cortex in humans was also reflected in its local concentrations of glutamate (Glu), glutamine (Gln), and GABA. To accomplish a multiregion estimation of all three metabolites in one robust and reliable session, we used an optimized 7T-stimulated echo-acquisition mode method with variable-rate selective excitation pulses. Our results demonstrated that, ensuring high data retest reliability, four cingulate subregions discerning e.g., pregenual ACC (pgACC) from anterior mid-cingulate cortex showed different metabolite concentrations and ratios reflective of regionally specific inhibition/excitation balance. These findings could be controlled for potential influences of local gray matter variations or MRS voxel-placement deviations. Pregenual ACC was found to have significantly higher GABA and Glu concentrations than other regions. This pattern was not paralleled by Gln concentrations, which for both absolute and relative values showed a rostrocaudal gradient with highest values in pgACC. Increased excitatory Glu and inhibitory GABA in pgACC were shown to follow a regional segregation agreeing with recently shown receptor-architectonic GABAB receptor distribution in ACC, whereas Gln distribution followed a pattern of AMPA receptors.

  3. Serratus Anterior and Lower Trapezius Muscle Activities During Multi-Joint Isotonic Scapular Exercises and Isometric Contractions

    PubMed Central

    Tsuruike, Masaaki; Ellenbecker, Todd S.

    2015-01-01

    Context: Proper scapular function during humeral elevation, such as upward rotation, external rotation, and posterior tilting of the scapula, is necessary to prevent shoulder injury. However, the appropriate intensity of rehabilitation exercise for the periscapular muscles has yet to be clarified. Objective: To identify the serratus anterior, lower trapezius, infraspinatus, and posterior deltoid muscle activities during 2 free-motion exercises using 3 intensities and to compare these muscle activities with isometric contractions during quadruped shoulder flexion and external rotation and abduction of the glenohumeral joint. Design: Cross-sectional study. Setting: Health Science Laboratory. Patients or Other Participants: A total of 16 uninjured, healthy, active, male college students (age = 19.5 ± 1.2 years, height = 173.1 ± 6.5 cm, weight = 68.8 ± 6.6 kg). Main Outcome Measure(s): Mean electromyographic activity normalized by the maximal voluntary isometric contraction was analyzed across 3 intensities and 5 exercises. Intraclass correlation coefficients were calculated for electromyographic activity of the 4 muscles in each free-motion exercise. Results: Significant interactions in electromyographic activity were observed between intensities and exercises (P < .05). The quadruped shoulder-flexion exercise activated all 4 muscles compared with other exercises. Also, the modified robbery free-motion exercise activated the serratus anterior, lower trapezius, and infraspinatus compared with the lawn-mower free-motion exercise. However, neither exercise showed a difference in posterior deltoid electromyographic activity. Conclusions: Three intensities exposed the nature of the periscapular muscle activities across the different exercises. The free-motion exercise in periscapular muscle rehabilitation may not modify serratus anterior, lower trapezius, and infraspinatus muscle activities unless knee-joint extension is limited. PMID:25689561

  4. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

    PubMed

    Morrison, T R; Sikes, R W; Melloni, R H

    2016-02-19

    Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure.

  5. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

    PubMed

    Morrison, T R; Sikes, R W; Melloni, R H

    2016-02-19

    Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure. PMID:26691962

  6. When your error becomes my error: anterior insula activation in response to observed errors is modulated by agency.

    PubMed

    Cracco, Emiel; Desmet, Charlotte; Brass, Marcel

    2016-03-01

    Research on error observation has focused predominantly on situations in which individuals are passive observers of errors. In daily life, however, we are often jointly responsible for the mistakes of others. In the current study, we examined how information on agency is integrated in the error observation network. It was found that activation in the anterior insula but not in the posterior medial frontal cortex or lateral prefrontal cortex differentiates between observed errors for which we are partly responsible or not. Interestingly, the activation pattern of the AI was mirrored by feelings of guilt and shame. These results suggest that the anterior insula is crucially involved in evaluating the consequences of our actions for other persons. Consequently, this region may be thought of as critical in guiding social behavior.

  7. Stress and Sucrose Intake Modulate Neuronal Activity in the Anterior Hypothalamic Area in Rats

    PubMed Central

    Mitra, Arojit; Guèvremont, Geneviève; Timofeeva, Elena

    2016-01-01

    The anterior hypothalamic area (AHA) is an important integrative relay structure for a variety of autonomic, endocrine, and behavioral responses including feeding behavior and response to stress. However, changes in the activity of the AHA neurons during stress and feeding in freely moving rats are not clear. The present study investigated the firing rate and burst activity of neurons in the central nucleus of the AHA (cAHA) during sucrose intake in non-stressful conditions and after acute stress in freely behaving rats. Rats were implanted with micro-electrodes into the cAHA, and extracellular multi-unit activity was recorded during 1-h access to 10% sucrose in non-stressful conditions or after acute foot shock stress. Acute stress significantly reduced sucrose intake, total sucrose lick number, and lick frequency in licking clusters, and increased inter-lick intervals. At the cluster start (CS) of sucrose licking, the cAHA neurons increased (CS-excited, 20% of the recorded neurons), decreased (CS-inhibited, 42% of the neurons) or did not change (CS-nonresponsive, 38% of the neurons) their firing rate. Stress resulted in a significant increase in the firing rate of the CS-inhibited neurons by decreasing inter-spike intervals within the burst firing of these neurons. This increase in the stress-induced firing rate of the CS-inhibited neurons was accompanied by a disruption of the correlation between the firing rate of CS-inhibited and CS-nonresponsive neurons that was observed in non-stressful conditions. Stress did not affect the firing rate of the CS-excited and CS-nonresponsive neurons. However, stress changed the pattern of burst firing of the CS-excited and CS-nonresponsive neurons by decreasing and increasing the burst number in the CS-excited and CS-nonresponsive neurons, respectively. These results suggest that the cAHA neurons integrate the signals related to stress and intake of palatable food and play a role in the stress- and eating-related circuitry

  8. Visual processing of optic flow and motor control in the human posterior cingulate sulcus.

    PubMed

    Field, David T; Inman, Laura A; Li, Li

    2015-10-01

    Previous studies have shown that the human posterior cingulate contains a visual processing area selective for optic flow (CSv). However, other studies performed in both humans and monkeys have identified a somatotopic motor region at the same location (CMA). Taken together, these findings suggested the possibility that the posterior cingulate contains a single visuomotor integration region. To test this idea we used fMRI to identify both visual and motor areas of the posterior cingulate in the same brains and to test the activity of those regions during a visuomotor task. Results indicated that rather than a single visuomotor region the posterior cingulate contains adjacent but separate motor and visual regions. CSv lies in the fundus of the cingulate sulcus, while CMA lies in the dorsal bank of the sulcus, slightly superior in terms of stereotaxic coordinates. A surprising and novel finding was that activity in CSv was suppressed during the visuomotor task, despite the visual stimulus being identical to that used to localize the region. This may provide an important clue to the specific role played by this region in the utilization of optic flow to control self-motion.

  9. Structural and functional changes of the cingulate gyrus following traumatic brain injury: relation to attention and executive skills.

    PubMed

    Merkley, Tricia L; Larson, Michael J; Bigler, Erin D; Good, Daniel A; Perlstein, William M

    2013-09-01

    Impairments of attention and executive functions are common sequelae of traumatic brain injury (TBI). The anterior cingulate is implicated in conflict-related task performance, such as the Stroop, and is susceptible to TBI-related injury due to its frontal location and proximity to the rough surface of the falx cerebri. We investigated the relationship between cingulate cortex volume and performance on tasks of selective attention and cognitive flexibility (single-trial Stroop and Auditory Consonant Trigrams [ACT]). Participants consisted of 12 adults with severe TBI and 18 controls. T1-weighted volumetric MRI data were analyzed using automated cortical reconstruction, segmentation, parcellation, and volume measurement. Cortical volume reductions were prominent bilaterally in frontal, temporal, and inferior parietal regions.Specific regional reduction of the cingulate cortex was observed only for cortical volume of right caudal anterior cingulate(cACC). The TBI group performed significantly worse than control participants on the Stroop and ACT tasks. Findings suggest that atrophy of the right cACC may contribute to reduced performance on executive function tasks, such as the Stroop and ACT, although this is likely but one node of an extensive brain network involved in these cognitive processes.

  10. Specialized core stability exercise: a neglected component of anterior cruciate ligament rehabilitation programs.

    PubMed

    Shi, Dong-liang; Li, Jing-long; Zhai, Hua; Wang, Hui-fang; Meng, Han; Wang, Yu-bin

    2012-01-01

    The incidence of anterior cruciate ligament injury has continued to increase over the last two decades. This injury is associated with abnormal gait patterns and osteoarthritis of the knee. In order to accelerate recovery, the introduction of core stability exercises into the rehabilitation program is proposed. The theory underlying the use of core stability exercise relates to the neuroplasticity that follows anterior cruciate ligament injury. Neuroplasticity in lumbar, thoracic, cervical and brain regions diminish activation in the contralateral thalamus, postparietal cortex, SM1, basal ganglia-external globus pallidus, SII, cingulated motor area, premotor cortex, and in the ipsilateral cerebellum and SM1 and increase activation in pre-SMA, SIIp, and pITG, indicating modifications of the CNS. In addition, the neuroplasticity can regulate the movement of trunk muscles, for example, sternocleidomastoid and lower trapezius muscles. Core stability also demonstrates a negative correlation with the incidence of anterior cruciate ligament injury. Therefore, we propose that core stability exercises may improve the rehabilitation of anterior cruciate ligament injuries by increasing core motor control. Specialized core stability exercises aimed at rectifying biomechanical problems associated with gait and core stability may play a key role in the management of anterior cruciate ligament injury.

  11. Dissociating patterns of anterior and posterior hippocampal activity and connectivity during distinct forms of category fluency.

    PubMed

    Sheldon, Signy; McAndrews, Mary Pat; Pruessner, Jens; Moscovitch, Morris

    2016-09-01

    Recent work has suggested that there are functionally distinct contributions from hippocampal subregions to episodic memory retrieval. One view of this dissociation is that the anterior and posterior hippocampus support gist-based/conceptual and fine-grained/spatial memory representations, respectively. It is not clear if such distinctions hold for other cognitive domains. To test this possibility, we examined anterior and posterior hippocampal contributions to a standard semantic retrieval task, category fluency. During fMRI scanning, participants generated exemplars to categories that were based on conceptual (autobiographical categories - 'movies that you have seen') or spatio-perceptual (spatial categories - 'items in a kitchen') information. Our main finding was that the autobiographical categories preferentially recruited the anterior hippocampus whereas the spatial categories preferentially recruited the posterior hippocampus. Differences were also evident when we examined the patterns of task-based hippocampal connectivity associated with these two forms of fluency. Our findings provide evidence for a functional organization along the long axis of the hippocampus that is based on conceptual and perceptual relational retrieval and indicate that this manner of organization is apparent outside the domain of episodic memory. PMID:27343687

  12. The effect of acute ethanol (EtOH) exposure on protein kinase C (PKC) activity in anterior pituitary.

    PubMed

    Steiner, J; Kirsteins, L; LaPaglia, N; Lawrence, A; Williams, D; Emanuele, N; Emanuele, M

    1997-01-01

    Alterations in the protein kinase C (PKC) pathway may interrupt anterior pituitary luteinizing hormone (LH) synthesis and/or secretion, which may impair normal reproductive function. Work by our laboratory and others has shown that EtOH has profound deleterious effects on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. The present study focuses on PKC translocation from the cytosol to the membrane of anterior pituitary after acute EtOH exposure. Serum levels of LH were measured at three time points (15, 30, and 90 min) after an IP injection of either saline or 3 g/kg EtOH in adult castrated male rats. LH levels dropped significantly (p < 0.03) in EtOH-injected compared to saline-injected control animals. In the same animals, EtOH significantly suppressed PKC localization at its active site at the pituitary cell membrane (p < 0.05). These findings suggest that the mechanism of EtOH's suppression of LH is mediated, at least in part, through a decrease in PKC translocation to the anterior pituitary cell membrane.

  13. Default-mode-like network activation in awake rodents.

    PubMed

    Upadhyay, Jaymin; Baker, Scott J; Chandran, Prasant; Miller, Loan; Lee, Younglim; Marek, Gerard J; Sakoglu, Unal; Chin, Chih-Liang; Luo, Feng; Fox, Gerard B; Day, Mark

    2011-01-01

    During wakefulness and in absence of performing tasks or sensory processing, the default-mode network (DMN), an intrinsic central nervous system (CNS) network, is in an active state. Non-human primate and human CNS imaging studies have identified the DMN in these two species. Clinical imaging studies have shown that the pattern of activity within the DMN is often modulated in various disease states (e.g., Alzheimer's, schizophrenia or chronic pain). However, whether the DMN exists in awake rodents has not been characterized. The current data provides evidence that awake rodents also possess 'DMN-like' functional connectivity, but only subsequent to habituation to what is initially a novel magnetic resonance imaging (MRI) environment as well as physical restraint. Specifically, the habituation process spanned across four separate scanning sessions (Day 2, 4, 6 and 8). At Day 8, significant (p<0.05) functional connectivity was observed amongst structures such as the anterior cingulate (seed region), retrosplenial, parietal, and hippocampal cortices. Prior to habituation (Day 2), functional connectivity was only detected (p<0.05) amongst CNS structures known to mediate anxiety (i.e., anterior cingulate (seed region), posterior hypothalamic area, amygdala and parabracial nucleus). In relating functional connectivity between cingulate-default-mode and cingulate-anxiety structures across Days 2-8, a significant inverse relationship (r = -0.65, p = 0.0004) was observed between these two functional interactions such that increased cingulate-DMN connectivity corresponded to decreased cingulate anxiety network connectivity. This investigation demonstrates that the cingulate is an important component of both the rodent DMN-like and anxiety networks.

  14. Neural activity predicts attitude change in cognitive dissonance.

    PubMed

    van Veen, Vincent; Krug, Marie K; Schooler, Jonathan W; Carter, Cameron S

    2009-11-01

    When our actions conflict with our prior attitudes, we often change our attitudes to be more consistent with our actions. This phenomenon, known as cognitive dissonance, is considered to be one of the most influential theories in psychology. However, the neural basis of this phenomenon is unknown. Using a Solomon four-group design, we scanned participants with functional MRI while they argued that the uncomfortable scanner environment was nevertheless a pleasant experience. We found that cognitive dissonance engaged the dorsal anterior cingulate cortex and anterior insula; furthermore, we found that the activation of these regions tightly predicted participants' subsequent attitude change. These effects were not observed in a control group. Our findings elucidate the neural representation of cognitive dissonance, and support the role of the anterior cingulate cortex in detecting cognitive conflict and the neural prediction of attitude change.

  15. Initial evidence of a failure to activate right anterior insula during affective set-shifting in PTSD

    PubMed Central

    Simmons, Alan; Strigo, Irina A.; Matthews, Scott C.; Paulus, Martin P.; Stein, Murray B.

    2010-01-01

    Objective Interoception is the perception of one's internal physiological, sensory, and emotional status. Extensive evidence supports a link between interoception and subjective experience. An altered ability to monitor or modulate interoception as it relates to subjective experience may provide a mechanistic explanation for the development of some forms of psychiatric illness. Methods We investigated which neural networks are activated when anticipating a change in affective (and thus interoceptive) state, which we term “affective set-shifting”, in women with posttraumatic stress disorder (PTSD) related to intimate partner violence, and in non-traumatized healthy volunteers. Results Although both groups activated the dorsolateral prefrontal cortex during affective set-shifting, the PTSD group showed significantly less activation in the right anterior insula than did the controls. Conclusions These findings may suggest that although individuals with PTSD are cognitively aware of the impending shift in interoceptive state, they fail to appropriately activate neural circuitry involved in modulating interoceptive responses. PMID:19398499

  16. Amygdala and cingulate structure is associated with stereotype on sex-role.

    PubMed

    Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-01-01

    Sex-role egalitarianism (SRE) is the belief that the sex of an individual should not influence the perception of his or her rights, abilities, obligations, and opportunities. Thus, low SRE reflects a more conservative stereotypical view on sex-role. Here we investigated anatomical correlates of individual differences in SRE in the present study. We used voxel-based morphometry, a questionnaire to determine an individual's SRE and associated psychological measures, and determined the association of SRE with gray matter structures and their cognitive nature in healthy individuals (375 men and 306 women; age, 20.6 ± 1.8 years). We demonstrated that higher SRE was associated with smaller regional gray matter density (rGMD) in the anterior part of the posterior cingulate cortex (PCC) and higher rGMD in the right amygdala. Post-hoc analyses revealed psychological measures characterized by contentious interpersonal orientations, such as contentious achievement motivation, were associated with lower SRE and higher rGMD in the anterior part of PCC. Depressive tendencies were associated with lower SRE and higher rGMD in the right amygdala. These findings suggest that variations in stereotype on sex role have roots in the limbic brain structures linked to contentious interpersonal orientation (cingulate) and negative mood (amygdala). PMID:26420574

  17. Amygdala and cingulate structure is associated with stereotype on sex-role

    PubMed Central

    Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-01-01

    Sex-role egalitarianism (SRE) is the belief that the sex of an individual should not influence the perception of his or her rights, abilities, obligations, and opportunities. Thus, low SRE reflects a more conservative stereotypical view on sex-role. Here we investigated anatomical correlates of individual differences in SRE in the present study. We used voxel-based morphometry, a questionnaire to determine an individual’s SRE and associated psychological measures, and determined the association of SRE with gray matter structures and their cognitive nature in healthy individuals (375 men and 306 women; age, 20.6 ± 1.8 years). We demonstrated that higher SRE was associated with smaller regional gray matter density (rGMD) in the anterior part of the posterior cingulate cortex (PCC) and higher rGMD in the right amygdala. Post-hoc analyses revealed psychological measures characterized by contentious interpersonal orientations, such as contentious achievement motivation, were associated with lower SRE and higher rGMD in the anterior part of PCC. Depressive tendencies were associated with lower SRE and higher rGMD in the right amygdala. These findings suggest that variations in stereotype on sex role have roots in the limbic brain structures linked to contentious interpersonal orientation (cingulate) and negative mood (amygdala). PMID:26420574

  18. WRM-1 activates the LIT-1 protein kinase to transduce anterior/posterior polarity signals in C. elegans.

    PubMed

    Rocheleau, C E; Yasuda, J; Shin, T H; Lin, R; Sawa, H; Okano, H; Priess, J R; Davis, R J; Mello, C C

    1999-06-11

    During C. elegans development, Wnt/WG signaling is required for differences in cell fate between sister cells born from anterior/posterior divisions. A beta-catenin-related gene, wrm-1, and the lit-1 gene are effectors of this signaling pathway and appear to downregulate the activity of POP-1, a TCF/LEF-related protein, in posterior daughter cells. We show here that lit-1 encodes a serine/threonine protein kinase homolog related to the Drosophila tissue polarity protein Nemo. We demonstrate that the WRM-1 protein binds to LIT-1 in vivo and that WRM-1 can activate the LIT-1 protein kinase when coexpressed in vertebrate tissue culture cells. This activation leads to phosphorylation of POP-1 and to apparent changes in its subcellular localization. Our findings provide evidence for novel regulatory avenues for an evolutionarily conserved Wnt/WG signaling pathway. PMID:10380924

  19. Greater anterior insula activation during anticipation of food images in women recovered from anorexia nervosa versus controls

    PubMed Central

    Oberndorfer, Tyson; Simmons, Alan; McCurdy, Danyale; Strigo, Irina; Matthews, Scott; Yang, Tony; Irvine, Zoe; Kaye, Walter

    2013-01-01

    Individuals with anorexia nervosa (AN) restrict food consumption and become severely emaciated. Eating food, even thinking of eating food, is often associated with heightened anxiety. However, food cue anticipation in AN is poorly understood. Fourteen women recovered from AN and 12 matched healthy control women performed an anticipation task viewing images of food and object images during functional magnetic resonance imaging. Comparing anticipation of food versus object images between control women and recovered AN groups showed significant interaction only in the right ventral anterior insula, with greater activation in recovered AN anticipating food images. These data support the hypothesis of a disconnect between anticipating and experiencing food stimuli in recovered AN. Insula activation positively correlated with pleasantness ratings of palatable foods in control women, while no such relationship existed in recovered AN, which is further evidence of altered interoceptive function. Finally, these findings raise the possibility that enhanced anterior insula anticipatory response to food cues in recovered AN could contribute to exaggerated sensitivity and anxiety related to food and eating. PMID:23993362

  20. Causal Interactions Within a Frontal-Cingulate-Parietal Network During Cognitive Control: Convergent Evidence from a Multisite-Multitask Investigation.

    PubMed

    Cai, Weidong; Chen, Tianwen; Ryali, Srikanth; Kochalka, John; Li, Chiang-Shan R; Menon, Vinod

    2016-05-01

    Cognitive control plays an important role in goal-directed behavior, but dynamic brain mechanisms underlying it are poorly understood. Here, using multisite fMRI data from over 100 participants, we investigate causal interactions in three cognitive control tasks within a core Frontal-Cingulate-Parietal network. We found significant causal influences from anterior insula (AI) to dorsal anterior cingulate cortex (dACC) in all three tasks. The AI exhibited greater net causal outflow than any other node in the network. Importantly, a similar pattern of causal interactions was uncovered by two different computational methods for causal analysis. Furthermore, the strength of causal interaction from AI to dACC was greater on high, compared with low, cognitive control trials and was significantly correlated with individual differences in cognitive control abilities. These results emphasize the importance of the AI in cognitive control and highlight its role as a causal hub in the Frontal-Cingulate-Parietal network. Our results further suggest that causal signaling between the AI and dACC plays a fundamental role in implementing cognitive control and are consistent with a two-stage cognitive control model in which the AI first detects events requiring greater access to cognitive control resources and then signals the dACC to execute load-specific cognitive control processes. PMID:25778346

  1. Electromyographic activity of knee stabilizer muscles during six different balance board stimuli after anterior cruciate ligament surgery.

    PubMed

    Pereira, H M; Nowotny, A H; Santos, A B A N; Cardoso, J R

    2009-01-01

    The purpose of this study was to compare the electrical activity of the knee stabilizers, in patients with ACL (anterior cruciate ligament) reconstructed and uninjured individuals during different balance board stimuli. Eleven post-surgery individuals and eleven uninjured controls participated in the study. The muscular activity of the vastus medialis obliquus, vastus lateralis, semitendinosus, biceps femoris and gastrocnemius medial were analyzed by surface electromyography during the execution of six different balance board activities. All electromyographic data were reported as percentage of RMS mean values obtained in maximal voluntary isometric contractions (MVIC) for each muscle. When comparing the individuals with ACL reconstructed and uninjured controls, minor electromyographic activity was observed (MVIC %) for all the muscles in the surgery group (P < 0.05), however, when comparing each exercise between the groups, a statistically significant difference for vastus lateralis was demonstrated in the floor exercise (P = 0.02) and for gastrocnemius on the round board (P = 0.04). Individuals ACL reconstructed presented a decrease in muscular activity during different balance board stimuli, which suggests that compensatory alterations after ACL may still exist even after a surgery to repair an ACL rupture.

  2. Long-term potentiation and evoked spike responses in the cingulate cortex of freely mobile rats.

    PubMed

    Gorkin, A G; Reymann, K G; Aleksandrov, Yu I

    2003-10-01

    Long-term potentiation of synaptic efficiency is regarded as a major candidate for the role of the physiological mechanism of long-term memory. However, the limited development of concepts of the cellular and subcellular characteristics of the induction of long-term potentiation in animals in conditions of free behavior does not correspond to the importance of this question. The present study was undertaken to determine whether the characteristics of potentiation in the cingulate cortex in response to stimulation of fibers of the subiculo-cingulate tract are truly long-term, i.e., develop through all known phases and last at least 24 h, in freely moving animals. In addition, the study aims included identification of the effects of application of blockers of different types of glutamate receptors on the development of long-term potentiation and identification of the characteristics of spike responses of single cingulate cortex neurons to stimulation of the subiculo-cingulate tract. Long-term potentiation, lasting more than 24 h, was obtained in freely moving adult rats not treated with GABA blockers. Injection of glutamate NMDA synapse blockers led to significant decreases in evoked cingulate cortex potentials in response to test stimulation. Activatory short-latency spike responses were characterized by a low probability of spike generation, and this increased with increases in the stimulation current. These data demonstrated that it is methodologically possible to compare, in freely moving rats, the involvement of individual neurons in the mechanisms involved in learning one or another type of adaptive behavior and the dynamics of their evoked spike activity during the formation of long-term potentiation. PMID:14635990

  3. Correlations between social-emotional feelings and anterior insula activity are independent from visceral states but influenced by culture

    PubMed Central

    Immordino-Yang, Mary Helen; Yang, Xiao-Fei; Damasio, Hanna

    2014-01-01

    The anterior insula (AI) maps visceral states and is active during emotional experiences, a functional confluence that is central to neurobiological accounts of feelings. Yet, it is unclear how AI activity correlates with feelings during social emotions, and whether this correlation may be influenced by culture, as studies correlating real-time AI activity with visceral states and feelings have focused on Western subjects feeling physical pain or basic disgust. Given psychological evidence that social-emotional feelings are cognitively constructed within cultural frames, we asked Chinese and American participants to report their feeling strength to admiration and compassion-inducing narratives during fMRI with simultaneous electrocardiogram recording. Trial-by-trial, cardiac arousal and feeling strength correlated with ventral and dorsal AI activity bilaterally but predicted different variance, suggesting that interoception and social-emotional feeling construction are concurrent but dissociable AI functions. Further, although the variance that correlated with cardiac arousal did not show cultural effects, the variance that correlated with feelings did. Feeling strength was especially associated with ventral AI activity (the autonomic modulatory sector) in the Chinese group but with dorsal AI activity (the visceral-somatosensory/cognitive sector) in an American group not of Asian descent. This cultural group difference held after controlling for posterior insula (PI) activity and was replicated. A bi-cultural East-Asian American group showed intermediate results. The findings help elucidate how the AI supports feelings and suggest that previous reports that dorsal AI activation reflects feeling strength are culture related. More broadly, the results suggest that the brain's ability to construct conscious experiences of social emotion is less closely tied to visceral processes than neurobiological models predict and at least partly open to cultural influence and

  4. Comparison of functional magnetic resonance imaging in cerebral activation between normal Uygur and Mandarin participants in semantic identification task

    PubMed Central

    Xi, Yan-Ling; Tian, Qing; Tuerxun, Tuerhong; Kaheman, Kuerbannaimu; Jiang, Chun-Hui; Huang, Hai-Xia; Wang, Bao-Lan

    2015-01-01

    Purpose: This study utilized blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) technology to study the activated cerebral regions in normal participants whose native language was Uyghur or Chinese. Methods: We collected the fMRI data from 15 Uyghur-speaking volunteers and 15 Mandarin-speaking volunteers when executing the semantic identification task and compared the results of two groups. Results: Statistically significant difference of brain activation was found primarily in the left anterior cingulate gyrus (BA23) and the midline precuneus (P<0.05). When performing the semantic identification task, the Uyghur group exhibited significant activation in these two regions, whereas the Chinese group demonstrated relatively weak activation in these areas. Conclusion: The cerebral regions activated by Uyghur and Chinese semantic identification are not identical, the dominant hemisphere for both languages is the left cerebral hemisphere. The left anterior cingulate gyrus might have a language function in Uyghur semantic processing. PMID:26550318

  5. Reduced Maximal Force during Acute Anterior Knee Pain Is Associated with Deficits in Voluntary Muscle Activation

    PubMed Central

    Salomoni, Sauro; Tucker, Kylie; Hug, François; McPhee, Megan; Hodges, Paul

    2016-01-01

    Although maximal voluntary contraction (MVC) force is reduced during pain, studies using interpolated twitch show no consistent reduction of voluntary muscle drive. The present study aimed to test if the reduction in MVC force during acute experimental pain could be explained by increased activation of antagonist muscles, weak voluntary activation at baseline, or changes in force direction. Twenty-two healthy volunteers performed maximal voluntary isometric knee extensions before, during, and after the effects of hypertonic (pain) and isotonic (control) saline injections into the infrapatellar fat pad. The MVC force, voluntary activation, electromyographic (EMG) activity of agonist, antagonist, and auxiliary (hip) muscles, and pain cognition and anxiety scores were recorded. MVC force was 9.3% lower during pain than baseline (p < 0.001), but there was no systematic change in voluntary activation. Reduced MVC force during pain was variable between participants (SD: 14%), and was correlated with reduced voluntary activation (r = 0.90), baseline voluntary activation (r = − 0.62), and reduced EMG amplitude of agonist and antagonist muscles (all r > 0.52), but not with changes in force direction, pain or anxiety scores. Hence, reduced MVC force during acute pain was mainly explained by deficits in maximal voluntary drive. PMID:27559737

  6. Neuromuscular Fatigue Alters Postural Control and Sagittal Plane Hip Biomechanics in Active Females With Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Frank, Barnett S.; Gilsdorf, Christine M.; Goerger, Benjamin M.; Prentice, William E.; Padua, Darin A.

    2014-01-01

    Background: Females with history of anterior cruciate ligament (ACL) injury and subsequent ligament reconstruction are at high risk for future ACL injury. Fatigue may influence the increased risk of future injury in females by altering lower extremity biomechanics and postural control. Hypothesis: Fatigue will promote lower extremity biomechanics and postural control deficits associated with ACL injury. Study Design: Descriptive laboratory study. Methods: Fourteen physically active females with ACL reconstruction (mean age, 19.64 ± 1.5 years; mean height, 163.52 ± 6.18 cm; mean mass, 62.6 ± 13.97 kg) volunteered for this study. Postural control and lower extremity biomechanics were assessed in the surgical limb during single-leg balance and jump-landing tasks before and after a fatigue protocol. Main outcome measures were 3-dimensional hip and knee joint angles at initial contact, peak angles, joint angular displacements and peak net joint moments, anterior tibial shear force, and vertical ground reaction force during the first 50% of the loading phase of the jump-landing task. During the single-leg stance task, the main outcome measure was center of pressure sway speed. Results: Initial contact hip flexion angle decreased (t = −2.82, P = 0.01; prefatigue, 40.98° ± 9.79°; postfatigue, 36.75° ± 8.61°) from pre- to postfatigue. Hip flexion displacement (t = 2.23, P = 0.04; prefatigue, 45.19° ± 14.1°; postfatigue, 47.48° ± 14.21°) and center of pressure sway speed (t = 3.95, P < 0.05; prefatigue, 5.18 ± 0.96 cm/s; postfatigue, 6.20 ± 1.72 cm/s) increased from pre- to postfatigue. There was a trending increase in hip flexion moment (t = 2.14, P = 0.05; prefatigue, 1.66 ± 0.68 Nm/kg/m; postfatigue, 1.91 ± 0.62 Nm/kg/m) from pre- to postfatigue. Conclusion: Fatigue may induce lower extremity biomechanics and postural control deficits that may be associated with ACL injury in physically active females with ACL reconstruction. Clinical Relevance

  7. Brain Activation for Knee Movement Measured Days Before Second Anterior Cruciate Ligament Injury: Neuroimaging in Musculoskeletal Medicine

    PubMed Central

    Grooms, Dustin R.; Page, Stephen J.; Onate, James A.

    2015-01-01

    Background Anterior cruciate ligament (ACL) injury has multifactorial causes encompassing mechanical, hormonal, exposure, and anatomical factors. Alterations in the central nervous system also play a role, but their influence after injury, recovery, and recurrent injury remain unknown. Modern neuroimaging techniques can be used to elucidate the underlying functional and structural alterations of the brain that predicate the neuromuscular control adaptations associated with ACL injury. This knowledge will further our understanding of the neural adaptations after ACL injury and rehabilitation and in relation to injury risk. In this paper, we describe the measurement of brain activation during knee extension-flexion after ACL injury and reconstruction and 26 days before a contralateral ACL injury. Methods Brain functional magnetic resonance imaging data for an ACL-injured participant and a matched control participant were collected and contrasted. Results Relative to the matched control participant, the ACL-injured participant exhibited increased activation of motor-planning, sensory-processing, and visual-motor control areas. A similar activation pattern was present for the contralateral knee that sustained a subsequent injury. Conclusions Bilateral neuroplasticity after ACL injury may contribute to the risk of second injury, or aspects of neurophysiology may be predisposing factors to primary injury. Clinical Implications Sensory-visual-motor function and motor-learning adaptations may provide targets for rehabilitation. PMID:26509775

  8. The effects of shoulder joint abduction angles on the muscle activity of the serratus anterior muscle and the upper trapezius muscle while vibrations are applied

    PubMed Central

    Jung, Da-eun; Moon, Dong-chul

    2015-01-01

    [Purpose] The purpose of this study was to examine the ratio between the upper trapezius and the serratus anterior muscles during diverse shoulder abduction exercises applied with vibrations in order to determine the appropriate exercise methods for recovery of scapular muscle balance. [Subjects and Methods] Twenty-four subjects voluntarily participated in this study. The subjects performed shoulder abduction at various shoulder joint abduction angles (90°, 120°, 150°, 180°) with oscillation movements. [Results] At 120°, all the subjects showed significant increases in the muscle activity of the serratus anterior muscle in comparison with the upper trapezius muscle. However, no significant difference was found at angles other than 120°. [Conclusion] To selectively strengthen the serratus anterior, applying vibration stimuli at the 120° shoulder abduction position is considered to be appropriate. PMID:25642052

  9. Anterior Medial Temporal Lobe Activation during Encoding of Words: FMRI Methods to Optimize Sensitivity

    ERIC Educational Resources Information Center

    Parsons, Michael W.; Haut, Marc W.; Lemieux, Susan K.; Moran, Maria T.; Leach, Sharon G.

    2006-01-01

    The existence of a rostrocaudal gradient of medial temporal lobe (MTL) activation during memory encoding has historically received support from positron emission tomography studies, but less so from functional MRI (FMRI) studies. More recently, FMRI studies have demonstrated that characteristics of the stimuli can affect the location of activation…

  10. Unawareness of deficits in ischemic injury: role of the cingulate cortex.

    PubMed

    Palermo, S; Leotta, D; Bongioanni, M R; Amanzio, M

    2014-01-01

    Reduced awareness of illness is a well-known phenomenon that has been studied in patients with vascular disease, but the precise nature of their executive dysfunction is an intriguing question that still has to be resolved. It would be particularly interesting to study patients with reduced awareness of disease possibly related to vascular lesions of the prefrontal cortex. Due to the clinical importance of the case, here we present a patient with a selective right anterior cingulate ischemic injury and impaired awareness of deficits. We suggest that the cingulo-frontal area dysfunction may represent one of the corresponding neurobiological substrates of his persistent unawareness, which has not yet been evaluated in the literature on patients with acquired brain injury (ABI). PMID:23962086

  11. Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state.

    PubMed

    Strecker, R E; Morairty, S; Thakkar, M M; Porkka-Heiskanen, T; Basheer, R; Dauphin, L J; Rainnie, D G; Portas, C M; Greene, R W; McCarley, R W

    2000-11-01

    This review describes a series of animal experiments that investigate the role of endogenous adenosine (AD) in sleep. We propose that AD is a modulator of the sleepiness associated with prolonged wakefulness. More specifically, we suggest that, during prolonged wakefulness, extracellular AD accumulates selectively in the basal forebrain (BF) and cortex and promotes the transition from wakefulness to slow wave sleep (SWS) by inhibiting cholinergic and non-cholinergic wakefulness-promoting BF neurons at the AD A1 receptor. New in vitro data are also compatible with the hypothesis that, via presynaptic inhibition of GABAergic inhibitory input, AD may disinhibit neurons in the preoptic/anterior hypothalamus (POAH) that have SWS-selective activity and Fos expression. Our in vitro recordings initially showed that endogenous AD suppressed the discharge activity of neurons in the BF cholinergic zone via the AD A1 receptor. Moreover, in identified mesopontine cholinergic neurons, AD was shown to act post-synaptically by hyperpolarizng the membrane via an inwardly rectifying potassium current and inhibition of the hyperpolarization-activated current, I(h). In vivo microdialysis in the cat has shown that AD in the BF cholinergic zone accumulates during prolonged wakefulness, and declines slowly during subsequent sleep, findings confirmed in the rat. Moreover, increasing BF AD concentrations to approximately the level as during sleep deprivation by a nucleoside transport blocker mimicked the effect of sleep deprivation on both the EEG power spectrum and behavioral state distribution: wakefulness was decreased, and there were increases in SWS and REM sleep. As predicted, microdialyis application of the specific A1 receptor antagonist cyclopentyltheophylline (CPT) in the BF produced the opposite effects on behavioral state, increasing wakefulness and decreasing SWS and REM. Combined unit recording and microdialysis studies have shown neurons selectively active in wakefulness

  12. Early active extension after anterior cruciate ligament reconstruction does not result in increased laxity of the knee.

    PubMed

    Isberg, Jonas; Faxén, Eva; Brandsson, Sveinbjörn; Eriksson, Bengt I; Kärrholm, Johan; Karlsson, Jon

    2006-11-01

    If permission of full active and passive extension immediately after an anterior cruciate ligament (ACL) reconstruction will increase the post-operative laxity of the knee has been a subject of discussion. We investigated whether a post-operative rehabilitation protocol including active and passive extension without any restrictions in extension immediately after an ACL reconstruction would increase the post-operative anterior-posterior knee laxity (A-P laxity). Our hypothesis was that full active and passive extension immediately after an ACL reconstruction would have no effect on the A-P laxity and clinical results up to 2 years after the operation. Twenty-two consecutive patients (14 men, 8 women, median age 21 years, range 17-41) were included. All the patients had a unilateral ACL rupture and no other ligament injuries or any other history of previous knee injuries. The surgical procedure was identical in all patients and one experienced surgeon operated on all the patients, using the bone-patellar tendon-bone autograft. The post-operative rehabilitation programme was identical in both groups, except for extension training during the first 4 weeks post-operatively. The patients were randomly allocated to post-operative rehabilitation programmes either allowing (Group A, n=11) or not allowing [Group B (30 to -10 degrees ), n=11] full active and passive extension immediately after the operation. They were evaluated pre-operatively and at 6 months and 2 years after the reconstruction. To evaluate the A-P knee laxity, radiostereometric analysis (RSA) and KT-1000 arthrometer (KT-1000) measurements were used, range of motion, Lysholm score, Tegner activity level, the International Knee Documentation Committee (IKDC) evaluation system and one-leg-hop test quotient were used. Pre-operatively, the RSA measurements revealed side-to-side differences in Group A of 8.6 mm (2.3-15.4), median (range) and in Group B of 7.2 mm (2.2-17.4) (n.s.). The corresponding KT-1000

  13. Empathic Responsiveness in Amygdala and Anterior Cingulate Cortex in Youths with Psychopathic Traits

    ERIC Educational Resources Information Center

    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…

  14. Electrocortical activity distinguishes between uphill and level walking in humans.

    PubMed

    Bradford, J Cortney; Lukos, Jamie R; Ferris, Daniel P

    2016-02-01

    The objective of this study was to determine if electrocortical activity is different between walking on an incline compared with level surface. Subjects walked on a treadmill at 0% and 15% grades for 30 min while we recorded electroencephalography (EEG). We used independent component (IC) analysis to parse EEG signals into maximally independent sources and then computed dipole estimations for each IC. We clustered cortical source ICs and analyzed event-related spectral perturbations synchronized to gait events. Theta power fluctuated across the gait cycle for both conditions, but was greater during incline walking in the anterior cingulate, sensorimotor and posterior parietal clusters. We found greater gamma power during level walking in the left sensorimotor and anterior cingulate clusters. We also found distinct alpha and beta fluctuations, depending on the phase of the gait cycle for the left and right sensorimotor cortices, indicating cortical lateralization for both walking conditions. We validated the results by isolating movement artifact. We found that the frequency activation patterns of the artifact were different than the actual EEG data, providing evidence that the differences between walking conditions were cortically driven rather than a residual artifact of the experiment. These findings suggest that the locomotor pattern adjustments necessary to walk on an incline compared with level surface may require supraspinal input, especially from the left sensorimotor cortex, anterior cingulate, and posterior parietal areas. These results are a promising step toward the use of EEG as a feed-forward control signal for ambulatory brain-computer interface technologies.

  15. Choice, uncertainty and value in prefrontal and cingulate cortex.

    PubMed

    Rushworth, Matthew F S; Behrens, Timothy E J

    2008-04-01

    Reinforcement learning models that focus on the striatum and dopamine can predict the choices of animals and people. Representations of reward expectation and of reward prediction errors that are pertinent to decision making, however, are not confined to these regions but are also found in prefrontal and cingulate cortex. Moreover, decisions are not guided solely by the magnitude of the reward that is expected. Uncertainty in the estimate of the reward expectation, the value of information that might be gained by taking a course of action and the cost of an action all influence the manner in which decisions are made through prefrontal and cingulate cortex.

  16. Anterior insular cortex and emotional awareness.

    PubMed

    Gu, Xiaosi; Hof, Patrick R; Friston, Karl J; Fan, Jin

    2013-10-15

    This paper reviews the foundation for a role of the human anterior insular cortex (AIC) in emotional awareness, defined as the conscious experience of emotions. We first introduce the neuroanatomical features of AIC and existing findings on emotional awareness. Using empathy, the awareness and understanding of other people's emotional states, as a test case, we then present evidence to demonstrate: 1) AIC and anterior cingulate cortex (ACC) are commonly coactivated as revealed by a meta-analysis, 2) AIC is functionally dissociable from ACC, 3) AIC integrates stimulus-driven and top-down information, and 4) AIC is necessary for emotional awareness. We propose a model in which AIC serves two major functions: integrating bottom-up interoceptive signals with top-down predictions to generate a current awareness state and providing descending predictions to visceral systems that provide a point of reference for autonomic reflexes. We argue that AIC is critical and necessary for emotional awareness.

  17. Anterior Insular Cortex and Emotional Awareness

    PubMed Central

    Gu, Xiaosi; Hof, Patrick R.; Friston, Karl J.; Fan, Jin

    2014-01-01

    This paper reviews the foundation for a role of the human anterior insular cortex (AIC) in emotional awareness, defined as the conscious experience of emotions. We first introduce the neuroanatomical features of AIC and existing findings on emotional awareness. Using empathy, the awareness and understanding of other people’s emotional states, as a test case, we then present evidence to demonstrate: 1) AIC and anterior cingulate cortex (ACC) are commonly coactivated as revealed by a meta-analysis, 2) AIC is functionally dissociable from ACC, 3) AIC integrates stimulus-driven and top-down information, and 4) AIC is necessary for emotional awareness. We propose a model in which AIC serves two major functions: integrating bottom-up interoceptive signals with top-down predictions to generate a current awareness state and providing descending predictions to visceral systems that provide a point of reference for autonomic reflexes. We argue that AIC is critical and necessary for emotional awareness. PMID:23749500

  18. 38 CFR 3.379 - Anterior poliomyelitis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Anterior poliomyelitis. 3... Specific Diseases § 3.379 Anterior poliomyelitis. If the first manifestations of acute anterior poliomyelitis present themselves in a veteran within 35 days of termination of active military service, it...

  19. Muscle Activity Onset Prior to Landing in Patients after Anterior Cruciate Ligament Injury: A Systematic Review and Meta-Analysis

    PubMed Central

    Theisen, Daniel; Rada, Isabel; Brau, Amélie; Gette, Paul; Seil, Romain

    2016-01-01

    Muscle activation during landing is paramount to stabilise lower limb joints and avoid abnormal movement patterns. Delayed muscle activity onset measured by electromyography (EMG) has been suggested to be associated with anterior cruciate ligament (ACL) injury. Therefore, the aim of this systematic review and meta-analysis was to test the hypothesis if ACL-injured patients display different results for muscle onset timing during standard deceleration tasks compared to healthy control participants. PubMed, Embase, Scopus and ScienceDirect databases were systematically searched over the period from January 1980 to February 2015, yielding a total of 1461 citations. Six studies meeting inclusion criteria underwent quality assessment, data extraction and re-computing procedures for the meta-analysis. The quality was rated “moderate” for 2 studies and “poor” for 4. Patients included and procedures used were highly heterogeneous. The tasks investigated were single leg hopping, decelerating from running or walking, tested on a total of 102 ACL-injured participants and 86 controls. EMG analyses of the muscles vastus lateralis, vastus medialis, lateral and medial hamstrings revealed trivial and non-significant standardised mean differences (SMD<0.20; p>0.05) between patients and control participants. Furthermore, no differences were found between the contralateral leg of patients and controls for muscle activity onset of the medial and lateral gastrocnemius (SMD<0.20; p>0.05). Based on 3 studies, the involved legs of ACL-injured patients showed overall earlier muscle activity onset compared to control participants for the medial gastrocnemius (SMD = 0.5; p = 0.05). Similar results were found for the lateral gastrocnemius (SMD = 2.1; p<0.001), with a greater effect size but based only on a single study. We conclude that there are no differences between leg muscles of ACL-injured patients and healthy controls regarding the muscle activity onset during landing. However

  20. Anterior Knee Pain (Chondromalacia Patellae).

    ERIC Educational Resources Information Center

    Garrick, James G.

    1989-01-01

    This article presents a pragmatic approach to the definition, diagnosis, and management of anterior knee pain. Symptoms and treatment are described. Emphasis is on active involvement of the patient in the rehabilitation exercise program. (IAH)

  1. Lower extremity muscle activation onset times during the transition from double-leg stance to single-leg stance in anterior cruciate ligament injured subjects.

    PubMed

    Dingenen, Bart; Janssens, Luc; Luyckx, Thomas; Claes, Steven; Bellemans, Johan; Staes, Filip F

    2015-12-01

    The goal of this study was to evaluate muscle activation onset times (MAOT) of both legs during a transition task from double-leg stance (DLS) to single-leg stance (SLS) in anterior cruciate ligament injured (ACLI) (n=15) and non-injured control subjects (n=15) with eyes open and eyes closed. Significantly delayed MAOT were found in the ACLI group compared to the control group for vastus lateralis, vastus medialis obliquus, hamstrings medial, hamstrings lateral, tibialis anterior, peroneus longus and gastrocnemius in both vision conditions, for gluteus maximus and gluteus medius with eyes open and for tensor fascia latae with eyes closed. Within the ACLI group, delayed MAOT of tibialis anterior with eyes open and gastrocnemius with eyes closed were found in the injured leg compared to the non-injured leg. All other muscles were not significantly different between legs. In conclusion, the ACLI group showed delayed MAOT not only around the knee, but also at the hip and ankle muscles compared to the non-injured control group. No differences between both legs of the ACLI group were found, except for tibialis anterior and gastrocnemius. These findings indirectly support including central nervous system re-education training to target the underlying mechanisms of these altered MAOT after ACL injury.

  2. Tasting calories differentially affects brain activation during hunger and satiety.

    PubMed

    van Rijn, Inge; de Graaf, Cees; Smeets, Paul A M

    2015-02-15

    An important function of eating is ingesting energy. Our objectives were to assess whether oral exposure to caloric and non-caloric stimuli elicits discriminable responses in the brain and to determine in how far these responses are modulated by hunger state and sweetness. Thirty women tasted three stimuli in two motivational states (hunger and satiety) while their brain responses were measured using functional magnetic resonance imaging in a randomized crossover design. Stimuli were solutions of sucralose (sweet, no energy), maltodextrin (non-sweet, energy) and sucralose+maltodextrin (sweet, energy). We found no main effect of energy content and no interaction between energy content and sweetness. However, there was an interaction between hunger state and energy content in the median cingulate (bilaterally), ventrolateral prefrontal cortex, anterior insula and thalamus. This indicates that the anterior insula and thalamus, areas in which hunger state and taste of a stimulus are integrated, also integrate hunger state with caloric content of a taste stimulus. Furthermore, in the median cingulate and ventrolateral prefrontal cortex, tasting energy resulted in more activation during satiety compared to hunger. This finding indicates that these areas, which are known to be involved in processes that require approach and avoidance, are also involved in guiding ingestive behavior. In conclusion, our results suggest that energy sensing is a hunger state dependent process, in which the median cingulate, ventrolateral prefrontal cortex, anterior insula and thalamus play a central role by integrating hunger state with stimulus relevance.

  3. Elongation of the active anterior wall of the uro-genital pelvic diaphragm, a late unusual complication of paraplegia.

    PubMed

    Jurascheck, F; Dollfus, P; Jacob-Chia, D

    1980-08-01

    The situation of the usual bladder, prostate, membranous urethra channel, can vary, according to the morphology of the perineum which can be overstretched. A case of a young man with a T10 complete upper motor neurone lesion is presented. The normal anterior angulation at the prostate and membranous urethra junction was reduced anteriorly and pushed backwards, thus causing an added indirect factor of dysuria. The mechanism is discussed in comparison with other such late, but often overlooked consequences of alterations of the pelvic floor during micturition. PMID:7422341

  4. Targeted Overexpression of TGF-α in the Corneal Epithelium of Adult Transgenic Mice Induces Changes in Anterior Segment Morphology and Activates Noncanonical Wnt Signaling

    PubMed Central

    Yuan, Yong; Yeh, Lung-Kun; Liu, Hongshan; Yamanaka, Osamu; Hardie, William D.; Kao, Winston W.-Y.; Liu, Chia-Yang

    2013-01-01

    Purpose. Transforming growth factor-alpha (TGF-α) transduces its signal through the epidermal growth factor receptor and is essential for corneal epithelial homeostasis. Previous studies have demonstrated that overexpression of TGF-α in the developing eye leads to anterior segment dysgenesis. However, the underlying mechanisms remain unclear. Here we examined the effects of TGF-α overexpression on adult ocular surface homeostasis. Methods. Binary Tet-On transgenic Krt12rtTA/tet-O-TGF-α mice were subjected to doxycycline (Dox) induction to overexpress TGF-α in the corneal epithelium. Intraocular pressure (IOP) was measured by noninvasive tonometry. The enucleated eyes of the experimental mice were subjected to histopathology, immunohistochemistry, and biochemistry examination. Results. Histologic and immunofluorescent examination showed that double-transgenic mice overexpressing TGF-α manifested peripheral anterior synechiae. Elevation of IOP, activation of glial cells, and loss of retinal ganglion cells were also observed. Quantitative real-time PCR revealed that the expressions of genes (RXRα, PITX2, and FOXC1) related to anterior segment dysgenesis were downregulated. Canonical Wnt signaling was suppressed, whereas noncanonical Wnt ligands (Wnt4 and Wnt5a) were upregulated. Increased myosin light chain phosphorylation suggested that noncanonical Wnt signaling is activated in affected eyes. Conclusions. Overexpression of TGF-α in the corneal epithelium induces changes in anterior segment morphology. Corneal endothelial abnormalities are associated with the activation of the noncanonical Wnt and RhoA/ROCK signaling axis, indicating a potential application of RhoA/ROCK inhibitors as a therapeutic strategy for certain types of secondary angle-closure glaucoma. PMID:23412089

  5. Changes in cue-induced, prefrontal cortex activity with video-game play.

    PubMed

    Han, Doug Hyun; Kim, Yang Soo; Lee, Yong Sik; Min, Kyung Joon; Renshaw, Perry F

    2010-12-01

    Brain responses, particularly within the orbitofrontal and cingulate cortices, to Internet video-game cues in college students are similar to those observed in patients with substance dependence in response to the substance-related cues. In this study, we report changes in brain activity between baseline and following 6 weeks of Internet video-game play. We hypothesized that subjects with high levels of self-reported craving for Internet video-game play would be associated with increased activity in the prefrontal cortex, particularly the orbitofrontal and anterior cingulate cortex. Twenty-one healthy university students were recruited. At baseline and after a 6-week period of Internet video-game play, brain activity during presentation of video-game cues was assessed using 3T blood oxygen level dependent functional magnetic resonance imaging. Craving for Internet video-game play was assessed by self-report on a 7-point visual analogue scale following cue presentation. During a standardized 6-week video-game play period, brain activity in the anterior cingulate and orbitofrontal cortex of the excessive Internet game-playing group (EIGP) increased in response to Internet video-game cues. In contrast, activity observed in the general player group (GP) was not changed or decreased. In addition, the change of craving for Internet video games was positively correlated with the change in activity of the anterior cingulate in all subjects. These changes in frontal-lobe activity with extended video-game play may be similar to those observed during the early stages of addiction.

  6. Anterior insula coordinates hierarchical processing of tactile mismatch responses.

    PubMed

    Allen, Micah; Fardo, Francesca; Dietz, Martin J; Hillebrandt, Hauke; Friston, Karl J; Rees, Geraint; Roepstorff, Andreas

    2016-02-15

    The body underlies our sense of self, emotion, and agency. Signals arising from the skin convey warmth, social touch, and the physical characteristics of external stimuli. Surprising or unexpected tactile sensations can herald events of motivational salience, including imminent threats (e.g., an insect bite) and hedonic rewards (e.g., a caressing touch). Awareness of such events is thought to depend upon the hierarchical integration of body-related mismatch responses by the anterior insula. To investigate this possibility, we measured brain activity using functional magnetic resonance imaging, while healthy participants performed a roving tactile oddball task. Mass-univariate analysis demonstrated robust activations in limbic, somatosensory, and prefrontal cortical areas previously implicated in tactile deviancy, body awareness, and cognitive control. Dynamic Causal Modelling revealed that unexpected stimuli increased the strength of forward connections along a caudal to rostral hierarchy-projecting from thalamic and somatosensory regions towards insula, cingulate and prefrontal cortices. Within this ascending flow of sensory information, the AIC was the only region to show increased backwards connectivity to the somatosensory cortex, augmenting a reciprocal exchange of neuronal signals. Further, participants who rated stimulus changes as easier to detect showed stronger modulation of descending PFC to AIC connections by deviance. These results suggest that the AIC coordinates hierarchical processing of tactile prediction error. They are interpreted in support of an embodied predictive coding model where AIC mediated body awareness is involved in anchoring a global neuronal workspace. PMID:26584870

  7. Anterior insula coordinates hierarchical processing of tactile mismatch responses.

    PubMed

    Allen, Micah; Fardo, Francesca; Dietz, Martin J; Hillebrandt, Hauke; Friston, Karl J; Rees, Geraint; Roepstorff, Andreas

    2016-02-15

    The body underlies our sense of self, emotion, and agency. Signals arising from the skin convey warmth, social touch, and the physical characteristics of external stimuli. Surprising or unexpected tactile sensations can herald events of motivational salience, including imminent threats (e.g., an insect bite) and hedonic rewards (e.g., a caressing touch). Awareness of such events is thought to depend upon the hierarchical integration of body-related mismatch responses by the anterior insula. To investigate this possibility, we measured brain activity using functional magnetic resonance imaging, while healthy participants performed a roving tactile oddball task. Mass-univariate analysis demonstrated robust activations in limbic, somatosensory, and prefrontal cortical areas previously implicated in tactile deviancy, body awareness, and cognitive control. Dynamic Causal Modelling revealed that unexpected stimuli increased the strength of forward connections along a caudal to rostral hierarchy-projecting from thalamic and somatosensory regions towards insula, cingulate and prefrontal cortices. Within this ascending flow of sensory information, the AIC was the only region to show increased backwards connectivity to the somatosensory cortex, augmenting a reciprocal exchange of neuronal signals. Further, participants who rated stimulus changes as easier to detect showed stronger modulation of descending PFC to AIC connections by deviance. These results suggest that the AIC coordinates hierarchical processing of tactile prediction error. They are interpreted in support of an embodied predictive coding model where AIC mediated body awareness is involved in anchoring a global neuronal workspace.

  8. Anterior insula coordinates hierarchical processing of tactile mismatch responses

    PubMed Central

    Allen, Micah; Fardo, Francesca; Dietz, Martin J.; Hillebrandt, Hauke; Friston, Karl J.; Rees, Geraint; Roepstorff, Andreas

    2016-01-01

    The body underlies our sense of self, emotion, and agency. Signals arising from the skin convey warmth, social touch, and the physical characteristics of external stimuli. Surprising or unexpected tactile sensations can herald events of motivational salience, including imminent threats (e.g., an insect bite) and hedonic rewards (e.g., a caressing touch). Awareness of such events is thought to depend upon the hierarchical integration of body-related mismatch responses by the anterior insula. To investigate this possibility, we measured brain activity using functional magnetic resonance imaging, while healthy participants performed a roving tactile oddball task. Mass-univariate analysis demonstrated robust activations in limbic, somatosensory, and prefrontal cortical areas previously implicated in tactile deviancy, body awareness, and cognitive control. Dynamic Causal Modelling revealed that unexpected stimuli increased the strength of forward connections along a caudal to rostral hierarchy—projecting from thalamic and somatosensory regions towards insula, cingulate and prefrontal cortices. Within this ascending flow of sensory information, the AIC was the only region to show increased backwards connectivity to the somatosensory cortex, augmenting a reciprocal exchange of neuronal signals. Further, participants who rated stimulus changes as easier to detect showed stronger modulation of descending PFC to AIC connections by deviance. These results suggest that the AIC coordinates hierarchical processing of tactile prediction error. They are interpreted in support of an embodied predictive coding model where AIC mediated body awareness is involved in anchoring a global neuronal workspace. PMID:26584870

  9. Self-efficacy, symptoms and physical activity in patients with an anterior cruciate ligament injury: a prospective study.

    PubMed

    Thomeé, P; Währborg, P; Börjesson, M; Thomeé, R; Eriksson, B I; Karlsson, J

    2007-06-01

    Self-efficacy belief may be of major importance for the outcome of rehabilitation after sports-related injuries. A new instrument, the Knee Self-Efficacy Scale (K-SES), was used to evaluate the role of perceived self-efficacy in patients with an anterior cruciate ligament (ACL) injury. The purpose of this prospective exploratory study was to describe the patients' perceived self-efficacy at various times post-injury and surgery, respectively, for responsiveness of the K-SES and to correlate the K-SES score with the patients' subjective symptoms. The purpose was also to describe the influence of gender, age and physical activity on the patients' perceived self-efficacy. Thirty recently injured patients with an ACL-deficient knee and 33 patients who had undergone ACL reconstruction reported their physical activity level and their perceived self-efficacy on four test occasions during a 1-year period. The patients' subjective knee symptoms were documented on two of the test occasions. A significant increase in the K-SES score was seen after injury as well as after surgery, during the course of rehabilitation. Pre-operatively, men's perceived self-efficacy was significantly (P=0.013) higher compared with women's self-efficacy. Patients with a high baseline (pre-injury) physical activity level (Tegner 7-10) perceived their self-efficacy as being significantly (P=0.005) higher pre-operatively compared with patients with a low baseline activity level (Tegner 3-6). "Younger" (age 17-29), recently injured patients, perceived their self-efficacy as being significantly (P=0.034) higher compared with "older" patients (age 30-54). At the 12-month test, 15 of 30 patients with an ACL-deficient knee and 15 of 33 patients who had undergone ACL reconstruction reported that they had returned or nearly returned to their baseline physical activity level. The subjective knee outcome score, as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS), improved significantly (P<0

  10. Single- vs. double-bundle anterior cruciate ligament reconstruction: a new aspect of knee assessment during activities involving dynamic knee rotation.

    PubMed

    Czamara, Andrzej; Królikowska, Aleksandra; Szuba, Łukasz; Widuchowski, Wojciech; Kentel, Maciej

    2015-02-01

    Few studies have compared single-bundle (SB) and double-bundle (DB) anterior cruciate ligament reconstruction (ACLR) in the knee joint during activities involving change-of-direction maneuvers and knee rotation. This study examined whether the type of ACLR contributes to postphysiotherapy outcomes, with an emphasis on knee function assessment during activities involving dynamic knee rotation. Fifteen male patients after SB ACLR and 15 male patients after DB ACLR took part in the same physiotherapy program. Twenty-four weeks after ACLR, both groups underwent anterior laxity measurement, pivot shift tests, range of movement and joint circumference measurements, subjective assessment of pain and stability levels in the knee joint, peak torque measurement of the muscles rotating the tibia toward the femur, and a run test with maximal speed and change-of-direction maneuvers. Comparative analysis did not show any differences between the results of anterior tibial translation, pivot shift test, range of movement and joint circumference, and subjective assessment of pain and knee joint stability levels. No differences were noted between the groups in peak torque values obtained from the muscles responsible for internal and external tibial rotation or results of the run test. The data obtained from this study can be used by research teams to monitor and compare the effectiveness of various study protocols involving surgical and physiotherapy treatment. The data are especially useful when combined with the clinical assessment of patients who would like to return to sport.

  11. Single- vs. double-bundle anterior cruciate ligament reconstruction: a new aspect of knee assessment during activities involving dynamic knee rotation.

    PubMed

    Czamara, Andrzej; Królikowska, Aleksandra; Szuba, Łukasz; Widuchowski, Wojciech; Kentel, Maciej

    2015-02-01

    Few studies have compared single-bundle (SB) and double-bundle (DB) anterior cruciate ligament reconstruction (ACLR) in the knee joint during activities involving change-of-direction maneuvers and knee rotation. This study examined whether the type of ACLR contributes to postphysiotherapy outcomes, with an emphasis on knee function assessment during activities involving dynamic knee rotation. Fifteen male patients after SB ACLR and 15 male patients after DB ACLR took part in the same physiotherapy program. Twenty-four weeks after ACLR, both groups underwent anterior laxity measurement, pivot shift tests, range of movement and joint circumference measurements, subjective assessment of pain and stability levels in the knee joint, peak torque measurement of the muscles rotating the tibia toward the femur, and a run test with maximal speed and change-of-direction maneuvers. Comparative analysis did not show any differences between the results of anterior tibial translation, pivot shift test, range of movement and joint circumference, and subjective assessment of pain and knee joint stability levels. No differences were noted between the groups in peak torque values obtained from the muscles responsible for internal and external tibial rotation or results of the run test. The data obtained from this study can be used by research teams to monitor and compare the effectiveness of various study protocols involving surgical and physiotherapy treatment. The data are especially useful when combined with the clinical assessment of patients who would like to return to sport. PMID:25148470

  12. Combined Posterior and Anterior Ankle Arthroscopy

    PubMed Central

    Scholten, Peter E.; van Dijk, C. Niek

    2012-01-01

    Treatment of combined anterior and posterior ankle pathology usually consists of either combined anterior and posterior arthrotomies or anterior ankle arthroscopy with an additional posterolateral portal. The first technique bears the risk of complications associated with the extensive exposure, the latter technique provides limited access to the posterior ankle joint. A case is described of combined anterior and posterior arthroscopy, with the patient lying prone and then turned supine, addressing both anterior and posterior ankle pathologies in one tempo. This minimally invasive combined approach allows quick recovery and early return to work and sports activities. PMID:23227391

  13. Event-related potentials recorded from the cingulate gyrus during attentional tasks: a study in patients with implanted electrodes.

    PubMed

    Turak, Baris; Louvel, Jacques; Buser, Pierre; Lamarche, Michel

    2002-01-01

    Recent neuroimaging data suggests that the cingulate gyrus is involved in a variety of cognitive tasks. In this study sensory field potentials were directly recorded from the cingulate gyrus in order to investigate its implication in attentional processes associated or not with a motor task. Evoked potentials recordings were performed in 29 epileptic patients with multilead electrodes implanted for presurgical evaluation, who agreed to participate in an experimental protocol consisting of a series of paradigms designed using a warning auditory tone, two distinct visual patterns and various attentional, memory, motor and decisional tasks. Our data shows that evoked potentials could be recorded from various parts of the cingulate gyrus. The inclusion of an instruction in the experimental paradigm resulted in an increase in the amplitude of the late, intrinsic component of the visual evoked potential culminating at about 450 ms. Several variations of response patterns across individuals were identified. We conclude that the cingulate gyrus appears to be a multimodal area involved in several types of cognitive activity, including attention. Variations in response patterns are probably related to differences in the strategy adopted by each subject when faced with a particular cognitive task.

  14. EMG activity of the serratus anterior and trapezius muscles during the different phases of the push-up plus exercise on different support surfaces and different hand positions

    PubMed Central

    Gioftsos, George; Arvanitidis, Michail; Tsimouris, Dimitrios; Kanellopoulos, Assimakis; Paras, George; Trigkas, Panagiotis; Sakellari, Vasiliki

    2016-01-01

    [Purpose] The appropriate exercise prescription is crucial for achieving scapular stability and providing successful rehabilitation, and the Push-up Plus (PuP) exercise has an important role in shoulder rehabilitation. Consequently, this study examined the effect of support surface stability, hand positioning, and phase of exercise, on the trapezius and serratus anterior muscle contractions as well as on the EMG ratio of the upper/lower trapezius. [Subjects and Methods] Thirteen healthy male volunteers participated in this study. The subjects performed the PuP exercise on stable and unstable supporting surfaces with three different hand orientations. During the PuP exercise, the muscle activities of the upper (UT) and lower (LT) trapezius, as well as the serratus anterior (SA) were measured and expressed as percentages of maximum voluntary isometric contraction (%MVIC). [Results] The EMG activities of UT and LT were statistically greater during the push-up phase compared to the plus phase of the exercise. The contrary was recorded for the activity of the SA. SA was affected by the support surface as well as by the hand positioning. [Conclusion] The results suggest that different phases of the PuP exercise require different muscle stability actions with corresponding activations of appropriate muscle fibers. A detailed prescription of the required phase of the exercise can more effectively activate the scapula-thoracic musculature. PMID:27512278

  15. Connectivity-based parcellation increases network detection sensitivity in resting state fMRI: An investigation into the cingulate cortex in autism.

    PubMed

    Balsters, Joshua H; Mantini, Dante; Apps, Matthew A J; Eickhoff, Simon B; Wenderoth, Nicole

    2016-01-01

    Although resting state fMRI (RS-fMRI) is increasingly used to generate biomarkers of psychiatric illnesses, analytical choices such as seed size and placement can lead to variable findings. Seed placement especially impacts on RS-fMRI studies of Autism Spectrum Disorder (ASD), because individuals with ASD are known to possess more variable network topographies. Here, we present a novel pipeline for analysing RS-fMRI in ASD using the cingulate cortex as an exemplar anatomical region of interest. Rather than using seeds based on previous literature, or gross morphology, we used a combination of structural information, task-independent (RS-fMRI) and task-dependent functional connectivity (Meta-Analytic Connectivity Modeling) to partition the cingulate cortex into six subregions with unique connectivity fingerprints and diverse behavioural profiles. This parcellation was consistent between groups and highly replicable across individuals (up to 93% detection) suggesting that the organisation of cortico-cingulo connections is highly similar between groups. However, our results showed an age-related increase in connectivity between the anterior middle cingulate cortex and right lateral prefrontal cortex in ASD, whilst this connectivity decreased in controls. There was also a Group × Grey Matter (GM) interaction, showing increased connectivity between the anterior cingulate cortex and the rectal gyrus in concert with increasing rectal gyrus GM in controls. By comparing our approach to previously established methods we revealed that our approach improves network detection in both groups, and that the ability to detect group differences using 4 mm radius spheres varies greatly with seed placement. Using our multi-modal approach we find disrupted cortico-cingulo circuits that, based on task-dependent information, may contribute to ASD deficits in attention and social interaction. Moreover, we highlight how more sensitive approaches to RS-fMRI are crucial for establishing

  16. Connectivity-based parcellation increases network detection sensitivity in resting state fMRI: An investigation into the cingulate cortex in autism

    PubMed Central

    Balsters, Joshua H.; Mantini, Dante; Apps, Matthew A.J.; Eickhoff, Simon B.; Wenderoth, Nicole

    2016-01-01

    Although resting state fMRI (RS-fMRI) is increasingly used to generate biomarkers of psychiatric illnesses, analytical choices such as seed size and placement can lead to variable findings. Seed placement especially impacts on RS-fMRI studies of Autism Spectrum Disorder (ASD), because individuals with ASD are known to possess more variable network topographies. Here, we present a novel pipeline for analysing RS-fMRI in ASD using the cingulate cortex as an exemplar anatomical region of interest. Rather than using seeds based on previous literature, or gross morphology, we used a combination of structural information, task-independent (RS-fMRI) and task-dependent functional connectivity (Meta-Analytic Connectivity Modeling) to partition the cingulate cortex into six subregions with unique connectivity fingerprints and diverse behavioural profiles. This parcellation was consistent between groups and highly replicable across individuals (up to 93% detection) suggesting that the organisation of cortico-cingulo connections is highly similar between groups. However, our results showed an age-related increase in connectivity between the anterior middle cingulate cortex and right lateral prefrontal cortex in ASD, whilst this connectivity decreased in controls. There was also a Group × Grey Matter (GM) interaction, showing increased connectivity between the anterior cingulate cortex and the rectal gyrus in concert with increasing rectal gyrus GM in controls. By comparing our approach to previously established methods we revealed that our approach improves network detection in both groups, and that the ability to detect group differences using 4 mm radius spheres varies greatly with seed placement. Using our multi-modal approach we find disrupted cortico-cingulo circuits that, based on task-dependent information, may contribute to ASD deficits in attention and social interaction. Moreover, we highlight how more sensitive approaches to RS-fMRI are crucial for establishing

  17. Reduction of type IIb myosin and IIB fibers in tibialis anterior muscle of mini-muscle mice from high-activity lines.

    PubMed

    Bilodeau, Geneviève M; Guderley, Helga; Joanisse, Denis R; Garland, Theodore

    2009-03-01

    Selective breeding of laboratory house mice (Mus domesticus) for high voluntary wheel running has generated four replicate lines that show an almost threefold increase in daily wheel-running distances as compared with four nonselected control lines. An unusual hindlimb "mini-muscle" phenotype (small muscles, increased mitochondrial enzyme levels, disorganized fiber distribution) has increased in frequency in two of the four replicate selected lines. The gene of major effect that accounts for this phenotype is an autosomal recessive that has been mapped to a 2.6335 Mb interval on MMU11, but not yet identified. This study examined the tibialis anterior muscle to determine whether changes in muscle fiber types could explain such modifications in muscle size and properties. Although selected and control lines did not exhibit systematic differences in the fiber types present in the tibialis anterior muscle, as assessed by electrophoresis of myosin heavy chains (MHC) and by histochemistry, mini-muscle mice lacked type IIB fibers and the corresponding MHCs. Mini-muscle tibialis show increased activities of hexokinase and citrate synthase compared with the normally sized muscles, likely the result of the modified fiber types in the muscle. The mini-muscle phenotype is the major means through which selective breeding for high wheel running has modified the functional capacities of the hindlimb muscles, as normally sized tibialis anterior muscles from control and selected lines did not show general differences in their enzymatic capacities, MHC profiles or fiber type composition, with the exception of an elevated hexokinase activity and a reduced GPa activity in the selected lines. PMID:19177556

  18. Functional lateralization in cingulate cortex predicts motor recovery after basal ganglia stroke.

    PubMed

    Li, Yao; Chen, Zengai; Su, Xin; Zhang, Xiaoliu; Wang, Ping; Zhu, Yajing; Xu, Qun; Xu, Jianrong; Tong, Shanbao

    2016-02-01

    The basal ganglia (BG) is involved in higher order motor control such as movement planning and execution of complex motor synergies. Neuroimaging study on stroke patients specifically with BG lesions would help to clarify the consequence of BG damage on motor control. In this paper, we performed a longitudinal study in the stroke patients with lesions in BG regions across three motor recovery stages, i.e., less than 2week (Session 1), 1-3m (Session 2) and more than 3m (Session 3). The patients showed an activation shift from bilateral hemispheres during early sessions (<3m) to the ipsilesional cortex in late session (>3m), suggesting a compensation effect from the contralesional hemisphere during motor recovery. We found that the lateralization of cerebellum(CB) for affected hand task correlated with patients' concurrent Fugl-Meyer index (FMI) in Session 2. Moreover, the cingulate cortex lateralization index in Session 2 was shown to significantly correlate with subsequent FMI change between Session 3 and Session 2, which serves as a prognostic marker for motor recovery. Our findings consolidated the close interactions between BG and CB during the motor recovery after stroke. The dominance of activation in contralateral cingulate cortex was associated with a better motor recovery, suggesting the important role of ipsilesional attention modulation in the early stage after BG stroke. PMID:26742641

  19. Precuneus and Cingulate Cortex Atrophy and Hypometabolism in Patients with Alzheimer's Disease and Mild Cognitive Impairment: MRI and 18F-FDG PET Quantitative Analysis Using FreeSurfer

    PubMed Central

    Bailly, Matthieu; Destrieux, Christophe; Hommet, Caroline; Mondon, Karl; Cottier, Jean-Philippe; Beaufils, Emilie; Vierron, Emilie; Vercouillie, Johnny; Ibazizene, Méziane; Voisin, Thierry; Payoux, Pierre; Barré, Louisa; Camus, Vincent; Guilloteau, Denis; Ribeiro, Maria-Joao

    2015-01-01

    Objective. The objective of this study was to compare glucose metabolism and atrophy, in the precuneus and cingulate cortex, in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), using FreeSurfer. Methods. 47 individuals (17 patients with AD, 17 patients with amnestic MCI, and 13 healthy controls (HC)) were included. MRI and PET images using 18F-FDG (mean injected dose of 185 MBq) were acquired and analyzed using FreeSurfer to define regions of interest in the hippocampus, amygdala, precuneus, and anterior and posterior cingulate cortex. Regional volumes were generated. PET images were registered to the T1-weighted MRI images and regional uptake normalized by cerebellum uptake (SUVr) was measured. Results. Mean posterior cingulate volume was reduced in MCI and AD. SUVr were different between the three groups: mean precuneus SUVr was 1.02 for AD, 1.09 for MCI, and 1.26 for controls (p < 0.05); mean posterior cingulate SUVr was 0.96, 1.06, and 1.22 for AD, MCI, and controls, respectively (p < 0.05). Conclusion. We found graduated hypometabolism in the posterior cingulate cortex and the precuneus in prodromal AD (MCI) and AD, whereas atrophy was not significant. This suggests that the use of 18F-FDG in these two regions could be a neurodegenerative biomarker. PMID:26346648

  20. Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making.

    PubMed

    Amemori, Ken-ichi; Graybiel, Ann M

    2012-05-01

    The pregenual anterior cingulate cortex (pACC) has been implicated in human anxiety disorders and depression, but the circuit-level mechanisms underlying these disorders are unclear. In healthy individuals, the pACC is involved in cost-benefit evaluation. We developed a macaque version of an approach-avoidance decision task used to evaluate anxiety and depression in humans and, with multi-electrode recording and cortical microstimulation, we probed pACC function as monkeys performed this task. We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value. Spatial distribution of these two neuronal populations overlapped in the pACC, except in one subzone, where neurons with negative coding were more numerous. Notably, microstimulation in this subzone, but not elsewhere in the pACC, increased negative decision-making, and this negative biasing was blocked by anti-anxiety drug treatment. This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making. PMID:22484571

  1. A role for primate subgenual cingulate cortex in sustaining autonomic arousal.

    PubMed

    Rudebeck, Peter H; Putnam, Philip T; Daniels, Teresa E; Yang, Tianming; Mitz, Andrew R; Rhodes, Sarah E V; Murray, Elisabeth A

    2014-04-01

    The subgenual anterior cingulate cortex (subgenual ACC) plays an important role in regulating emotion, and degeneration in this area correlates with depressed mood and anhedonia. Despite this understanding, it remains unknown how this part of the prefrontal cortex causally contributes to emotion, especially positive emotions. Using Pavlovian conditioning procedures in macaque monkeys, we examined the contribution of the subgenual ACC to autonomic arousal associated with positive emotional events. After such conditioning, autonomic arousal increases in response to cues that predict rewards, and monkeys maintain this heightened state of arousal during an interval before reward delivery. Here we show that although monkeys with lesions of the subgenual ACC show the initial, cue-evoked arousal, they fail to sustain a high level of arousal until the anticipated reward is delivered. Control procedures showed that this impairment did not result from differences in autonomic responses to reward delivery alone, an inability to learn the association between cues and rewards, or to alterations in the light reflex. Our data indicate that the subgenual ACC may contribute to positive affect by sustaining arousal in anticipation of positive emotional events. A failure to maintain positive affect for expected pleasurable events could provide insight into the pathophysiology of psychological disorders in which negative emotions dominate a patient's affective experience. PMID:24706828

  2. Effect of low dose acetylsalicylic acid on the frequency and hematologic activity of left ventricular thrombus in anterior wall acute myocardial infarction

    SciTech Connect

    Kuepper, A.J.V.; Verheugt, F.W.; Peels, C.H.; Galema, T.W.; den Hollander, W.; Roos, J.P.

    1989-04-15

    In this prospective, randomized, placebo-controlled trial the effect of 100 mg acetylsalicylic acid (ASA) once daily on the incidence, hematologic activity and embolic potential of left ventricular (LV) thrombosis was studied in 100 consecutive patients with a first anterior wall acute myocardial infarction (AMI). Patients were randomized to ASA or placebo less than 12 hours after onset of symptoms. Heparin, 5,000 IU subcutaneously twice daily, was given to all patients during immobilization. Echocardiography was performed less than 24 hours, 48 to 72 hours and 1, 2, and 12 weeks after AMI. LV thrombosis was detected by echocardiography in 30 (33%) of the 92 evaluable patients (15 patients given ASA and 15 given placebo). Indium-111 platelet scintigraphy was done in 17 of the 22 patients with an LV thrombus at the second week echocardiogram. Among 7 ASA-treated patients, 4 had positive images; among 10 placebo patients, 5 had positive images. LV thrombus resolution was noted in 3 of 9 patients with a positive scan and in 5 of 8 patients with a negative platelet scan. In 7 of 10 ASA-treated patients and 5 of 12 placebo-treated patients thrombus resolution was observed (difference not significant). Systemic embolism occurred in 2 patients, both given ASA, during the first week after AMI. Thus, low dose ASA has no effect on the incidence, hematologic activity and embolic potential of LV thrombosis in anterior wall AMI.

  3. Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex.

    PubMed

    Littlefield, Melissa M; Dietz, Martin J; Fitzgerald, Des; Knudsen, Kasper J; Tonks, James

    2015-01-01

    "Truth" has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person's mental state, a phenomenon known as Theory of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in-group and out-group members. Participants were asked to be honest and were told that their evaluations would be made public. We found increased BOLD responses in the medial prefrontal cortex, bilateral anterior insula and precuneus when participants were asked to tell social truths compared to simple truths about another person. At the behavioral level, participants were slower at responding to social compared to simple questions about another person. These findings suggest that telling the truth is a nuanced cognitive operation that is dependent on the degree of mentalizing. Importantly, we show that the cortical regions engaged by truth telling show a distinct pattern when the task requires social reasoning.

  4. Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex

    PubMed Central

    Littlefield, Melissa M.; Dietz, Martin J.; Fitzgerald, Des; Knudsen, Kasper J.; Tonks, James

    2015-01-01

    “Truth” has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person's mental state, a phenomenon known as Theory of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in-group and out-group members. Participants were asked to be honest and were told that their evaluations would be made public. We found increased BOLD responses in the medial prefrontal cortex, bilateral anterior insula and precuneus when participants were asked to tell social truths compared to simple truths about another person. At the behavioral level, participants were slower at responding to social compared to simple questions about another person. These findings suggest that telling the truth is a nuanced cognitive operation that is dependent on the degree of mentalizing. Importantly, we show that the cortical regions engaged by truth telling show a distinct pattern when the task requires social reasoning. PMID:26539094

  5. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    PubMed Central

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee

    2016-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. Materials and Methods We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. Results During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Conclusion Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism. PMID:26632397

  6. Subgenual cingulate cortex and personality in chimpanzees (Pan troglodytes)

    PubMed Central

    Blatchley, Barbara J.; Hopkins, William D.

    2012-01-01

    Animals vary in their dispositions, abilities, and moods and demonstrate characteristic behavior patterns that remain consistent across situation and time. This study describes the relationship between measures of personality in the chimpanzee and the structure of the subgenual cingulate cortex (SGCC). Measures of individual traits and personality factors (dominance, extraversion, conscientiousness, and agreeableness) and assessments of percentage of SGCC gray matter (PGM) and asymmetry taken from MRI scans were obtained for 74 chimpanzees housed at the Yerkes National Primate Research Center. PGM in the SGCC was significantly higher for females than for males and was significantly correlated with two personality factors (dominance and conscientiousness) in male apes. There was also a population-level leftward asymmetry in the SGCC. These results are discussed in terms of current models of SGCC function, which suggest that this area may play a role in the biological foundation of personality. PMID:20805542

  7. Left insula activation: a marker for language attainment in bilinguals.

    PubMed

    Chee, Michael W L; Soon, Chun Siong; Lee, Hwee Ling; Pallier, Christophe

    2004-10-19

    Several lines of evidence suggest the importance of phonological working memory (PWM) in language acquisition. We investigated the neural correlates of PWM in young adults who were under compelling social pressure to be bilingual. Equal bilinguals had high proficiency in English and Chinese as measured by a standardized examination, whereas unequal bilinguals were proficient in English but not Chinese. Both groups were matched on several measures of nonverbal intelligence and working memory. In-scanner behavioral results did not show between-group differences. Of the regions showing load-dependent increments in activation, the left insula showed greater activation in equal bilinguals. Unequal bilinguals showed greater task-related deactivation in the anterior medial frontal region and greater anterior cingulate activation. Although unequal bilinguals kept apace with equal bilinguals in the simple PWM task, the differential cortical activations suggest that more optimal engagement of PWM in the latter may correlate with better second-language attainment. PMID:15469927

  8. Left insula activation: A marker for language attainment in bilinguals

    PubMed Central

    Chee, Michael W. L.; Soon, Chun Siong; Lee, Hwee Ling; Pallier, Christophe

    2004-01-01

    Several lines of evidence suggest the importance of phonological working memory (PWM) in language acquisition. We investigated the neural correlates of PWM in young adults who were under compelling social pressure to be bilingual. Equal bilinguals had high proficiency in English and Chinese as measured by a standardized examination, whereas unequal bilinguals were proficient in English but not Chinese. Both groups were matched on several measures of nonverbal intelligence and working memory. In-scanner behavioral results did not show between-group differences. Of the regions showing load-dependent increments in activation, the left insula showed greater activation in equal bilinguals. Unequal bilinguals showed greater task-related deactivation in the anterior medial frontal region and greater anterior cingulate activation. Although unequal bilinguals kept apace with equal bilinguals in the simple PWM task, the differential cortical activations suggest that more optimal engagement of PWM in the latter may correlate with better second-language attainment. PMID:15469927

  9. Left insula activation: a marker for language attainment in bilinguals.

    PubMed

    Chee, Michael W L; Soon, Chun Siong; Lee, Hwee Ling; Pallier, Christophe

    2004-10-19

    Several lines of evidence suggest the importance of phonological working memory (PWM) in language acquisition. We investigated the neural correlates of PWM in young adults who were under compelling social pressure to be bilingual. Equal bilinguals had high proficiency in English and Chinese as measured by a standardized examination, whereas unequal bilinguals were proficient in English but not Chinese. Both groups were matched on several measures of nonverbal intelligence and working memory. In-scanner behavioral results did not show between-group differences. Of the regions showing load-dependent increments in activation, the left insula showed greater activation in equal bilinguals. Unequal bilinguals showed greater task-related deactivation in the anterior medial frontal region and greater anterior cingulate activation. Although unequal bilinguals kept apace with equal bilinguals in the simple PWM task, the differential cortical activations suggest that more optimal engagement of PWM in the latter may correlate with better second-language attainment.

  10. Patterns of cortico-limbic activations during visual processing of sad faces in depression patients: a coordinate-based meta-analysis.

    PubMed

    Lai, Chien-Han

    2014-01-01

    The author retrieved 10 functional magnetic resonance imaging studies about visual tasks for emotional faces in subjects with depression. The activation foci were then summarized and entered into a coordinate-based meta-analysis. The depression group showed significantly increased activations in the left striatum and left parahippocampal gyrus; the control group showed increased activations in the left medial frontal gyrus, left middle frontal gyrus, right thalamus, left anterior cingulate, and superior frontal gyrus. The study suggests that depression patients have limbic activations, and controls have fronto-thalamic activations with visual processing of emotional faces.

  11. Emotion recognition from dynamic emotional displays following anterior cingulotomy and anterior capsulotomy for chronic depression.

    PubMed

    Ridout, Nathan; O'Carroll, Ronan E; Dritschel, Barbara; Christmas, David; Eljamel, Muftah; Matthews, Keith

    2007-04-01

    Four patients that had received an anterior cingulotomy (ACING) and five patients that had received both an ACING and an anterior capsulotomy (ACAPS) as an intervention for chronic, treatment refractory depression were presented with a series of dynamic emotional stimuli and invited to identify the emotion portrayed. Their performance was compared with that of a group of non-surgically treated patients with major depression (n=17) and with a group of matched, never-depressed controls (n=22). At the time of testing, four of the nine neurosurgery patients had recovered from their depressive episode, whereas five remained depressed. Analysis of emotion recognition accuracy revealed no significant differences between depressed and non-depressed neurosurgically treated patients. Similarly, no significant differences were observed between the patients treated with ACING alone and those treated with both ACING and ACAPS. Comparison of the emotion recognition accuracy of the neurosurgically treated patients and the depressed and healthy control groups revealed that the surgically treated patients exhibited a general impairment in their recognition accuracy compared to healthy controls. Regression analysis revealed that participants' emotion recognition accuracy was predicted by the number of errors they made on the Stroop colour-naming task. It is plausible that the observed deficit in emotion recognition accuracy was a consequence of impaired attentional control, which may have been a result of the surgical lesions to the anterior cingulate cortex.

  12. Bilateral Anterior Shoulder Dislocation

    PubMed Central

    Siu, Yuk Chuen; Lui, Tun Hing

    2014-01-01

    Introduction: Unilateral anterior shoulder dislocation is one of the most common problems encountered in orthopedic practice. However, simultaneous bilateral anterior dislocation of the shoulders is quite rare. Case Presentation: We report a case of a 75-year-old woman presented with simultaneous bilateral anterior shoulder dislocation following a trauma, complicated with a traction injury to the posterior cord of the brachial plexus. Conclusions: Bilateral anterior shoulder dislocation is very rare. The excessive traction force during closed reduction may lead to nerve palsy. Clear documentation of neurovascular status and adequate imaging before and after a reduction should be performed. PMID:25685749

  13. The neural mechanisms of affect infusion in social economic decision-making: a mediating role of the anterior insula.

    PubMed

    Harlé, Katia M; Chang, Luke J; van 't Wout, Mascha; Sanfey, Alan G

    2012-05-15

    Though emotions have been shown to have sometimes dramatic effects on decision-making, the neural mechanisms mediating these biases are relatively unexplored. Here, we investigated how incidental affect (i.e. emotional states unrelated to the decision at hand) may influence decisions, and how these biases are implemented in the brain. Nineteen adult participants made decisions which involved accepting or rejecting monetary offers from others in an Ultimatum Game while undergoing functional magnetic resonance imaging (fMRI). Prior to each set of decisions, participants watched a short video clip aimed at inducing either a sad or neutral emotional state. Results demonstrated that, as expected, sad participants rejected more unfair offers than those in the neutral condition. Neuroimaging analyses revealed that receiving unfair offers while in a sad mood elicited activity in brain areas related to aversive emotional states and somatosensory integration (anterior insula) and to cognitive conflict (anterior cingulate cortex). Sad participants also showed a diminished sensitivity in neural regions associated with reward processing (ventral striatum). Importantly, insular activation uniquely mediated the relationship between sadness and decision bias. This study is the first to reveal how subtle mood states can be integrated at the neural level to influence decision-making.

  14. Proprioceptive deficit in individuals with unilateral tearing of the anterior cruciate ligament after active evaluation of the sense of joint position☆☆☆

    PubMed Central

    Cossich, Victor; Mallrich, Frédéric; Titonelli, Victor; de Sousa, Eduardo Branco; Velasques, Bruna; Salles, José Inácio

    2014-01-01

    Objective To ascertain whether the proprioceptive deficit in the sense of joint position continues to be present when patients with a limb presenting a deficient anterior cruciate ligament (ACL) are assessed by testing their active reproduction of joint position, in comparison with the contralateral limb. Methods Twenty patients with unilateral ACL tearing participated in the study. Their active reproduction of joint position in the limb with the deficient ACL and in the healthy contralateral limb was tested. Meta-positions of 20% and 50% of the maximum joint range of motion were used. Proprioceptive performance was determined through the values of the absolute error, variable error and constant error. Results Significant differences in absolute error were found at both of the positions evaluated, and in constant error at 50% of the maximum joint range of motion. Conclusion When evaluated in terms of absolute error, the proprioceptive deficit continues to be present even when an active evaluation of the sense of joint position is made. Consequently, this sense involves activity of both intramuscular and tendon receptors. PMID:26229869

  15. Involvement of nitric oxide pathways in short term modulation of tyrosine hydroxylase activity by endothelins 1 and 3 in the rat anterior hypothalamus.

    PubMed

    Morgazo, Carolina; Perfume, Guadalupe; Legaz, Guillermina; di Nunzio, Andrea; Hope, Sandra I; Bianciotti, Liliana G; Vatta, Marcelo S

    2005-09-01

    The ability of endothelins 1 and 3 (ET-1 and ET-3) to reduce neuronal norepinephrine release through ETB receptor activation involving nitric oxide (NO) pathways in the rat anterior hypothalamus region (AHR) was previously reported. In the present work, we studied the effects of ET-1 and -3 on tyrosine hydroxylase (TH) activity and the possible involvement of NO pathways. Results showed that ET-1 and -3 (10 nM) diminished TH activity in AHR and this effect was blocked by a selective ETB receptor antagonist (100 nM BQ-788), but not by a ET(A) receptor antagonist (BQ-610). To confirm these results, 1 microM IRL-1620 (ET(B) agonist) reduced TH activity whereas 300 nM sarafotoxin S6b falled to modify it. N(omega)-Nitro-L-arginine methyl ester (10 microM), 7-nitroindazole (10 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-ona (10 microM), KT5823 (2 microM), inhibitors of nitric oxide synthase, neuronal nitric oxide synthase, NO-sensitive-guanylyl cyclase, and protein kinase G, respectively, did not modify the reduction of TH activity produced by ETs. In addition, both 100 microM sodium nitroprusside and 50 microM 8-bromoguanosine-3',5'-cyclic monophosphate (NO donor and guanosine-3',5'-cyclic monophosphate analog, respectively) diminished TH activity. Present results showed that ET-1 and ET-3 diminished TH activity through the activation of ET(B) receptors involving the NO/guanosine-3',5'-cyclic monophosphate/protein kinase G pathway. Taken jointly present and previous results it can be concluded that both ETs play an important role as modulators of norepinephrine neurotransmission in the rat AHR.

  16. Surgical treatment of anterior cruciate ligament injury in adults.

    PubMed

    Alazzawi, Sulaiman; Sukeik, Mohamed; Ibrahim, Mazin; Haddad, Fares S

    2016-04-01

    Anterior cruciate ligament injury is among the most common soft tissue injuries of the knee joint and reconstruction of the anterior cruciate ligament is the gold standard treatment for young active symptomatic patients. This review summarizes the surgical treatment of anterior cruciate ligament injury.

  17. Self-determined, but not non-self-determined, motivation predicts activations in the anterior insular cortex: an fMRI study of personal agency.

    PubMed

    Lee, Woogul; Reeve, Johnmarshall

    2013-06-01

    Neuroscientific studies on agency focus rather exclusively on the notion of who initiates and regulates actions, not on the notion of why the person does. The present study focused on the latter to investigate two different reasons underlying personal agency. Using event-related functional magnetic resonance imaging, we scanned 16 healthy human subjects while they imagined the enactment of volitional, agentic behavior on the same task but either for a self-determined and intrinsically motivated reason or for a non-self-determined and extrinsically motivated reason. Results showed that the anterior insular cortex (AIC), known to be related to the sense of agency, was more activated during self-determined behavior while the angular gyrus, known to be related to the sense of loss of agency, was more activated during non-self-determined behavior. Furthermore, AIC activities during self-determined behavior correlated highly with participants' self-reported intrinsic satisfactions. We conclude that self-determined behavior is more agentic than is non-self-determined behavior and that personal agency arises only during self-determined, intrinsically motivated action.

  18. Long-term outcome of operative or nonoperative treatment of anterior cruciate ligament rupture--is sports activity a determining variable?

    PubMed

    Fink, C; Hoser, C; Hackl, W; Navarro, R A; Benedetto, K P

    2001-05-01

    The purpose of this study was to evaluate the long-term clinical outcome of operative versus nonoperative treatment of anterior cruciate ligament (ACL) deficiency and to define its relationship with sports activity. Forty-six patients (37 male, 9 female, mean age, 33.6 +/- 8.0 years) who underwent open ACL reconstruction using patellar tendon autograft and 25 patients (18 male, 7 female, mean age, 32.3 +/- 9.9 years) who were treated nonoperatively were evaluated by the same two examiners at 5 - 7 and 10 - 13 years following injury. The evaluations included objective and subjective scoring (Lysholm, OAK, IKDC), instrumented testing (Cybex, KT 1000), radiographic evaluation, and assessments of sports activity, with respect to type, frequency and associated symptoms. According to Lysholm, OAK and IKDC scores, the operative group performed significantly (p < 0.05) better and was able to maintain increased involvement in sports, although both groups participated less over time. However, risks for degenerative joint changes were similar for both the operative and the nonoperative group. A significant (p < 0.05) correlation between participation in high-risk pivoting sports, such as soccer or basketball and osteoarthritic changes could be found for the nonoperative group, only. Sports activity represents an important variable not only affecting the outcome, but also influencing treatment decisions following ACL injuries.

  19. [Subcortical infarcts (caudate nucleus) in a case of bilateral anterior cerebral artery occlusion].

    PubMed

    Halicka, D; Jankowicz, E; Drozdowski, W; Kochanowicz, J

    1999-01-01

    The authors describe a patient with bilateral anterior cerebral artery (ACA) occlusion. CT and MRI revealed bilateral encephalomalacia in the regions supplied by Heubner arteries and/or by perforating branches of ACA. The patient presented mainly with frontal symptomatology resulting from caudate nuclei lesion. Frontal symptomatology due to caudate impairment is discussed in the sense of frontal-subcortical circuits: lateral orbitofrontal and anterior cingulate ones. We emphasise a similarity of behavioural and cognitive disorders in early Huntington's disease and in frontal lobe lesion.

  20. Increasing pre-activation of the quadriceps muscle protects the anterior cruciate ligament during the landing phase of a jump: an in vitro simulation.

    PubMed

    Hashemi, Javad; Breighner, Ryan; Jang, Taek-Hyun; Chandrashekar, Naveen; Ekwaro-Osire, Stephen; Slauterbeck, James R

    2010-06-01

    We hypothesize that application of an unopposed quadriceps force coupled with an impulsive ground reaction force may induce anterior cruciate ligament (ACL) injury. This situation is similar to landing from a jump if only the quadriceps muscle is active; an unlikely but presumably dangerous circumstance. The purpose of this study was to test our hypothesis using in vitro simulation of jump landing. A jump-landing simulator was utilized. Nine cadaveric knees were tested at an initial flexion angle of 20 degrees . Each ACL was instrumented with a differential variable reluctance transducer (DVRT). Quadriceps pre-activation forces (QPFs) ranging from 25N to 700N were applied to each knee, followed by an impulsive ground reaction force produced by a carriage-mounted drop weight (7kg) that impulsively drove the ankle upward. ACL strain was monitored before landing due to application of QPF (pre-activation strain) and at landing due to application of the ground reaction force (landing strain). No ACLs were injured. Pre-activation strains exhibited a positive correlation with QPF (r=0.674, p<0.001) while landing strains showed a negative correlation (r=-0.235, p=0.032). Total ACL strain (pre-activation+landing strain) showed no correlation with QPF (r=0.023, p=0.428). Our findings indicate that elevated QPF increases pre-activation strain but reduces the landing strain and is therefore protective post-landing. Overall, there is a complete lack of correlation between "total" ACL strain and QPF suggesting that the total strain in the ACL is independent of the QPF under the simulated conditions.

  1. Cortical control of thermoregulatory sympathetic activation.

    PubMed

    Fechir, M; Klega, A; Buchholz, H G; Pfeifer, N; Balon, S; Schlereth, T; Geber, C; Breimhorst, M; Maihöfner, C; Birklein, F; Schreckenberger, M

    2010-06-01

    Thermoregulation enables adaptation to different ambient temperatures. A complex network of central autonomic centres may be involved. In contrast to the brainstem, the role of the cortex has not been clearly evaluated. This study was therefore designed to address cerebral function during a whole thermoregulatory cycle (cold, neutral and warm stimulation) using 18-fluordeoxyglucose-PET (FDG-PET). Sympathetic activation parameters were co-registered. Ten healthy male volunteers were examined three times on three different days in a water-perfused whole-body suit. After a baseline period (32 degrees C), temperature was either decreased to 7 degrees C (cold), increased to 50 degrees C (warm) or kept constant (32 degrees C, neutral), thereafter the PET examination was performed. Cerebral glucose metabolism was increased in infrapontine brainstem and cerebellar hemispheres during cooling and warming, each compared with neutral temperature. Simultaneously, FDG uptake decreased in the bilateral anterior/mid-cingulate cortex during warming, and in the right insula during cooling and warming. Conjunction analyses revealed that right insular deactivation and brainstem activation appeared both during cold and warm stimulation. Metabolic connectivity analyses revealed positive correlations between the cortical activations, and negative correlations between these cortical areas and brainstem/cerebellar regions. Heart rate changes negatively correlated with glucose metabolism in the anterior cingulate cortex and in the middle frontal gyrus/dorsolateral prefrontal cortex, and changes of sweating with glucose metabolism in the posterior cingulate cortex. In summary, these results suggest that the cerebral cortex exerts an inhibitory control on autonomic centres located in the brainstem or cerebellum. These findings may represent reasonable explanations for sympathetic hyperactivity, which occurs, for example, after hemispheric stroke.

  2. Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus.

    PubMed

    Perfume, Guadalupe; Nabhen, Sabrina L; Barrera, Karla Riquelme; Otero, María G; Bianciotti, Liliana G; Vatta, Marcelo S

    2008-03-01

    Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ET(B) receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ET(C) receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.

  3. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism

    PubMed Central

    Klampfl, Stefanie M.; Brunton, Paula J.; Bayerl, Doris S.; Bosch, Oliver J.

    2016-01-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5 h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum. PMID:26630389

  4. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism.

    PubMed

    Klampfl, Stefanie M; Brunton, Paula J; Bayerl, Doris S; Bosch, Oliver J

    2016-02-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum.

  5. Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus.

    PubMed

    Perfume, Guadalupe; Nabhen, Sabrina L; Barrera, Karla Riquelme; Otero, María G; Bianciotti, Liliana G; Vatta, Marcelo S

    2008-03-01

    Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ET(B) receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ET(C) receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain. PMID:18094067

  6. Using a combination of fMRI and anterior temporal lobe rTMS to measure intrinsic and induced activation changes across the semantic cognition network

    PubMed Central

    Binney, Richard J.; Lambon Ralph, Matthew A.

    2015-01-01

    By developing and applying a method which combines fMRI and rTMS to explore semantic cognition, we identified both intrinsic (related to automatic changes in task/stimulus-related processing) and induced (i.e., associated with the effect of TMS) activation changes in the core, functionally-coupled network elements. Low-frequency rTMS applied to the human anterior temporal lobe (ATL) induced: (a) a local suppression at the site of stimulation; (b) remote suppression in three other ipsilateral semantic regions; and (c) a compensatory up-regulation in the contralateral ATL. Further examination of activity over time revealed that the compensatory changes appear to be a modulation of intrinsic variations that occur within the unperturbed network. As well as providing insights into the dynamic collaboration between core regions, the ability to observe intrinsic and induced changes in vivo may provide an important opportunity to understand the key mechanisms that underpin recovery of function in neurological patient groups. PMID:25448851

  7. The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention

    PubMed Central

    Chaddock-Heyman, Laura; Erickson, Kirk I.; Voss, Michelle W.; Knecht, Anya M.; Pontifex, Matthew B.; Castelli, Darla M.; Hillman, Charles H.; Kramer, Arthur F.

    2013-01-01

    This study used functional magnetic resonance imaging (fMRI) to examine the influence of a 9-month physical activity program on task-evoked brain activation during childhood. The results demonstrated that 8- to 9-year-old children who participated in 60+ min of physical activity, 5 days per week, for 9 months, showed decreases in fMRI brain activation in the right anterior prefrontal cortex coupled with within-group improvements in performance on a task of attentional and interference control. Children assigned to a wait-list control group did not show changes in brain function. Furthermore, at post-test, children in the physical activity group showed similar anterior frontal brain patterns and incongruent accuracy rates to a group of college-aged young adults. Children in the wait-list control group still differed from the young adults in terms of anterior prefrontal activation and performance at post-test. There were no significant changes in fMRI activation in the anterior cingulate cortex (ACC) for either group. These results suggest that physical activity during childhood may enhance specific elements of prefrontal cortex function involved in cognitive control. PMID:23487583

  8. Threonine deprivation rapidly activates the system A amino acid transporter in primary cultures of rat neurons from the essential amino acid sensor in the anterior piriform cortex.

    PubMed

    Blais, Anne; Huneau, Jean-François; Magrum, Linda J; Koehnle, Thomas J; Sharp, James W; Tomé, Daniel; Gietzen, Dorothy W

    2003-07-01

    Omnivores show recognition of essential (indispensable) amino acid deficiency by changing their feeding behavior within 20 min, yet the cellular mechanisms of amino acid sensation in eukaryotes are poorly understood. The anterior piriform cortex (APC) of the brain in rats or its analog in birds likely houses the in vivo amino acid chemosensor. Because amino acid transporters adapt rapidly to essential amino acid deficiency in several cell models, we hypothesized that activation of electrogenic amino acid transport in APC neurons might contribute to the function of the amino acid sensor. We evaluated transport systems in primary cultures of neurons from the APC, hippocampus and cerebellum, or glia, incubated in complete or threonine-devoid (deficient) medium. After 10 min in deficient medium, uptake of threonine or a system A-selective substrate, methyl amino-isobutyric acid, was increased 60% in APC neurons only (P < 0.05). These results demonstrated upregulation of system A, an electrogenic amino acid-sodium symporter. This depletion-induced activation required sodium, intact intracellular trafficking, and phosphorylation of signal transduction-related kinases. Efflux studies showed that other transporter types were functional in the APC; they appeared to be altered dynamically in threonine-deficient cells in response to rapid increases in system A activity. The present data provided support for the chemical sensitivity of the APC and its role as the brain area housing the indispensable amino acid chemosensor. They also showed a region-specific, phosphorylation-dependent activation of the system A transporter in the brain in response to threonine deficiency.

  9. A prospective study of the survival of chemically activated anterior resin composite restorations in general dental practice: 5-year results.

    PubMed

    van Noort, R; Davis, L G

    1993-08-01

    The principals of 26 general dental practices agreed to use six chemically activated resin composite restorative materials to restore Class III and Class V lesions and record information concerning their performance over a period of 5 years. The information collected was analysed by actuarial methods to assess the clinical longevity and reasons for replacement as perceived by the dentists operating in the General Dental Service in England. At the end of 5 years, 14 dentists provided sufficient returns for their data to be considered suitable for analysis. The database consisted of 2399 Class III and 1093 Class V restorations. The overall probability of survival at 5 years of Class III and Class V restorations was 62.9% and 71.8% respectively. The difference in performance between the six restorative materials was small, with the probability of survival varying from 70.4 +/- 2.9% to 56.3 +/- 2.9% for the Class III restorations and 78.6 +/- 3.7% to 67.7 +/- 4.2% for the Class V restorations. The main reasons for replacement were general surface discoloration, secondary caries and fracture. The chemically activated composite restorative materials available at the time of initiating this study produced comparable performances in general dental practice when used without enamel and dentine bonding techniques. This suggests that more general practice-based clinical studies are needed to determine whether or not improvements in materials and techniques are effectively transferred to the general practice situation.

  10. Ventromedial prefrontal cortex activation is critical for preference judgments.

    PubMed

    Paulus, Martin P; Frank, Lawrence R

    2003-07-18

    Preference judgment, the process of selecting a response from several alternatives based on which alternative the subject likes best, is an important aspect of daily life. The current study examined whether neural substrates that are thought to be critical for generating somatic markers are involved in preference judgments. Fifteen healthy, right-handed subjects performed a preference judgment task during functional magnetic resonance imaging. The medial frontal gyrus was significantly more activated during the preference judgment trials, relative to visual discrimination trials. Other areas that were also differentially activated included the posterior parietal cortex, the anterior cingulate and the left anterior insula. These findings are consistent with the role of the ventromedial prefrontal cortex in the representation of complex appetitive states. PMID:12876463

  11. Anterior knee pain

    MedlinePlus

    ... as running, jumping or twisting, skiing, or playing soccer). You have flat feet. Anterior knee pain is ... to the kneecap Runners, jumpers, skiers, bicyclists, and soccer players who exercise often Teenagers and healthy young ...

  12. Lesions of either anterior orbitofrontal cortex or ventrolateral prefrontal cortex in marmoset monkeys heighten innate fear and attenuate active coping behaviors to predator threat

    PubMed Central

    Shiba, Yoshiro; Kim, Charissa; Santangelo, Andrea M.; Roberts, Angela C.

    2015-01-01

    The ventral prefrontal cortex is an integral part of the neural circuitry that is dysregulated in mood and anxiety disorders. However, the contribution of its distinct sub-regions to the regulation of negative emotion are poorly understood. Recently we implicated both the ventrolateral prefrontal cortex (vlPFC) and anterior orbitofrontal cortex (antOFC) in the regulation of conditioned fear and anxiety responses to a social stimulus, i.e., human intruder, in the marmoset monkey. In the present study we extend our investigations to determine the role of these two regions in regulating innate responses and coping strategies to a predator stimulus, i.e., a model snake. Both the vlPFC and antOFC lesioned groups exhibited enhanced anxiety-related responses to the snake in comparison to controls. Both groups also showed a reduction in active coping behavior. These results indicate that the vlPFC and antOFC contribute independently to the regulation of both innate fear and, as previously reported, conditioned fear, and highlight the importance of these regions in producing stimulus-appropriate coping responses. The finding that dysregulation in two distinct prefrontal regions produces the apparently similar behavioral phenotype of heightened negative emotion provides insight into the varied etiology that may underlie this symptom across a wide variety of neuropsychiatric conditions with implications for personalized treatment strategies. PMID:25653599

  13. Mechanisms of the Anterior Cruciate Ligament Injury in Sports Activities: A Twenty-Year Clinical Research of 1,700 Athletes

    PubMed Central

    Kobayashi, Hirokazu; Kanamura, Tomonao; Koshida, Sentaro; Miyashita, Koji; Okado, Tsuruo; Shimizu, Takuya; Yokoe, Kiyoshi

    2010-01-01

    The mechanisms of anterior cruciate ligament (ACL) injuries are still inconclusive from an epidemiological standpoint. An epidemiological approach in a large sample group over an appropriate period of years will be necessary to enhance the current knowledge of the ACL injury mechanism. The objective of the study was to investigate the ACL injury occurrence in a large sample over twenty years and demonstrate the relationships between the ACL injury occurrence and the dynamic knee alignment at the time of the injury. We investigated the activity, the injury mechanism, and the dynamic knee alignment at the time of the injury in 1,718 patients diagnosed as having the ACL injuries. Regarding the activity at the time of the injury, “competition ”was the most common, accounting for about half of all the injuries. The current result also showed that the noncontact injury was the most common, which was observed especially in many female athletes. Finally, the dynamic alignment of “Knee-in & Toe- out ”(i.e. dynamic knee valgus) was the most common, accounting for about half. These results enhance our understanding of the ACL injury mechanism and may be used to guide future injury prevention strategies. Key points We investigated the situation of ACL injury occurrence, especially dynamic alignments at the time of injury, in 1,718 patients who had visited our institution for surgery and physical therapy for twenty years. Our epidemiological study of the large patient group revealed that “knee-in & toe-out ”alignment was the most frequently seen at the time of the ACL injury. From an epidemiological standpoint, we need to pay much attention to avoiding “Knee-in & Toe-out ”alignment during sports activities. PMID:24149795

  14. SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex.

    PubMed

    Thompson, Peter M; Cruz, Dianne A; Fucich, Elizabeth A; Olukotun, Dianna Y; Takahashi, Masami; Itakura, Makoto

    2015-12-01

    SNAP-25 is a neurotransmitter vesicular docking protein which has been associated with brain disorders such as attention deficit hyperactivity disorder, bipolar disorder and schizophrenia. In this project, we were interested if clinical factors are associated with differential SNAP-25 expression. We examined the SNAP-25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9) and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical variables including mood state in the last week of life and lifetime impulsiveness. We found affected subjects with a diagnosis of alcohol use disorder (AUD) had a lower level of SNAP-25b BA24 protein compared to those without AUD. Hispanic subjects had lower levels of SNAP-25a, b and BA9 mRNA than Anglo-American subjects. Subjects who smoked had a total pan (total) SNAP-25 BA9/BA24 ratio. Subjects in the group with a low level of anxious-psychotic symptoms had higher SNAP-25a BA24 mRNA compared to normal controls, and both the high and low symptoms groups had higher pan (total) SNAP-25 BA9/BA24 ratios than normal controls. These data expand our understanding of clinical factors associated with SNAP-25. They suggest that SNAP-25 total and isoform levels may be useful biomarkers beyond limited neurological and psychiatric diagnostic categories. PMID:27606314

  15. SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex.

    PubMed

    Thompson, Peter M; Cruz, Dianne A; Fucich, Elizabeth A; Olukotun, Dianna Y; Takahashi, Masami; Itakura, Makoto

    2015-12-01

    SNAP-25 is a neurotransmitter vesicular docking protein which has been associated with brain disorders such as attention deficit hyperactivity disorder, bipolar disorder and schizophrenia. In this project, we were interested if clinical factors are associated with differential SNAP-25 expression. We examined the SNAP-25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9) and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical variables including mood state in the last week of life and lifetime impulsiveness. We found affected subjects with a diagnosis of alcohol use disorder (AUD) had a lower level of SNAP-25b BA24 protein compared to those without AUD. Hispanic subjects had lower levels of SNAP-25a, b and BA9 mRNA than Anglo-American subjects. Subjects who smoked had a total pan (total) SNAP-25 BA9/BA24 ratio. Subjects in the group with a low level of anxious-psychotic symptoms had higher SNAP-25a BA24 mRNA compared to normal controls, and both the high and low symptoms groups had higher pan (total) SNAP-25 BA9/BA24 ratios than normal controls. These data expand our understanding of clinical factors associated with SNAP-25. They suggest that SNAP-25 total and isoform levels may be useful biomarkers beyond limited neurological and psychiatric diagnostic categories.

  16. Meditation leads to reduced default mode network activity beyond an active task

    PubMed Central

    Garrison, Kathleen A.; Zeffiro, Thomas A.; Scheinost, Dustin; Constable, R. Todd; Brewer, Judson A.

    2015-01-01

    Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest despite other studies reporting differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, this study compared meditation to another active cognitive task, both to replicate findings that meditation is associated with relatively reduced default mode network activity, and to extend these findings by testing whether default mode activity was reduced during meditation beyond the typical reductions observed during effortful tasks. In addition, prior studies have used small groups, whereas the current study tested these hypotheses in a larger group. Results indicate that meditation is associated with reduced activations in the default mode network relative to an active task in meditators compared to controls. Regions of the default mode showing a group by task interaction include the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that suppression of default mode processing may represent a central neural process in long-term meditation, and suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task. PMID:25904238

  17. Meditation leads to reduced default mode network activity beyond an active task.

    PubMed

    Garrison, Kathleen A; Zeffiro, Thomas A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2015-09-01

    Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.

  18. Electrocortical activity is coupled to gait cycle phase during treadmill walking.

    PubMed

    Gwin, Joseph T; Gramann, Klaus; Makeig, Scott; Ferris, Daniel P

    2011-01-15

    Recent findings suggest that human cortex is more active during steady-speed unperturbed locomotion than previously thought. However, techniques that have been used to image the brain during locomotion lack the temporal resolution necessary to assess intra-stride cortical dynamics. Our aim was to determine if electrocortical activity is coupled to gait cycle phase during steady-speed human walking. We used electroencephalography (EEG), motion capture, and a force-measuring treadmill to record brain and body dynamics while eight healthy young adult subjects walked on a treadmill. Infomax independent component analysis (ICA) parsed EEG signals into maximally independent component (IC) processes representing electrocortical sources, muscle sources, and artifacts. We calculated a spatially fixed equivalent current dipole for each IC using an inverse modeling approach, and clustered electrocortical sources across subjects by similarities in dipole locations and power spectra. We then computed spectrograms for each electrocortical source that were time-locked to the gait cycle. Electrocortical sources in the anterior cingulate, posterior parietal, and sensorimotor cortex exhibited significant (p<0.05) intra-stride changes in spectral power. During the end of stance, as the leading foot was contacting the ground and the trailing foot was pushing off, alpha- and beta-band spectral power increased in or near the left/right sensorimotor and dorsal anterior cingulate cortex. Power increases in the left/right sensorimotor cortex were more pronounced for contralateral limb push-off (ipsilateral heel-strike) than for ipsilateral limb push-off (contralateral heel-strike). Intra-stride high-gamma spectral power changes were evident in anterior cingulate, posterior parietal, and sensorimotor cortex. These data confirm cortical involvement in steady-speed human locomotion. Future applications of these techniques could provide critical insight into the neural mechanisms of movement

  19. Altered post