Modulation In Anterior Cingulate Cortex Research Articles

The Effect of Optogenetic Inhibition of the Anterior Cingulate Cortex in Neuropathic Pain Following Sciatic Nerve Injury.

Cortical disinhibition is the underlying pathological alteration contributing to neuropathic pain associated with peripheral nerve injury. Nerve injury resulting in disinhibition of the anterior cingulate cortex has been reported. However, the effect of optogenetic inhibition of the anterior cingulate cortex (ACC) on the sensory component of nerve injury-induced neuropathic pain has not been well studied. To investigate the feasibility of optogenetic ACC modulation, we injected an optogenetic virus or a null virus into the ACC of a nerve injury-induced neuropathic pain model. The unilateral ACC was modulated, and the optogenetic effect was measured by mechanical and thermal sensitivity tests. The assessment was performed in "pre-light off," "stimulation-yellow light on," and "post-light off" states. Optogenetic inhibition of the ACC in injury models revealed improved mechanical and thermal latencies with profound pain-relieving effects against nerve injury-induced neuropathic pain. The sensory thalamic discharge in electrophysiological in vivo recordings was also altered during laser stimulation. This finding indicates that hyperactivity of the ACC in nerve injury increases output to the spinothalamic tract through direct or indirect pathways. The direct photoinhibition of ACC neurons could play a vital role in restoring equilibrium and provide novel insight into techniques that can assuage peripheral nerve injury-induced neuropathic pain.

Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain

It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP receptor in nociceptive modulation in ACC in naïve rats and inflammatory rats. Administration of different does of CGRP in ACC induced significant antinociception in a dose-dependent manner in both naïve rats and rats with inflammatory pain. The CGRP-induced antinociception was attenuated by injection of the CGRP receptor antagonist CGRP8-37 in ACC. Interestingly, both CGRP-induced antinociception and CGRP receptor expression decreased in ACC in rats with inflammatory pain compared with naïve rats. Knockdown of CGRP receptor in ACC by siRNA targeting to CGRP receptor attenuated both the CGRP receptor expression and the CGRP-induced antinociception significantly in rats. These findings demonstrate that CGRP and CGRP receptor participate in nociceptive modulation in ACC in rats, inhibiting CGRP receptor expression induces decrease in CGRP-induced antinociception in ACC.

Role of mu-opioid receptor in nociceptive modulation in anterior cingulate cortex of rats.

Lots of studies have demonstrated that anterior cingulate cortex plays important roles in the pain perception and pain modulation. The present study explored the role of mu-opioid receptor in nociceptive modulation in anterior cingulate cortex of rats with neuropathic pain. Neuropathic pain model was set up by chronic constriction injury of the left sciatic nerve of rats. The hindpaw withdrawal latency to thermal and mechanical stimulation, by hot plate and Randall Selitto Test respectively, was used to evaluate the rat’s responses to noxious stimulation. Results showed that intra-anterior cingulate cortex injection of morphine could induce the antinociception dose-dependently. By intra-anterior cingulate cortex injection of opioid receptor antagonist, the morphine-induced antinociception could be attenuated by naloxone, as well as much significantly by the selective mu-opioid receptor antagonist β-funaltrexamine, indicating that mu-opioid receptor is involved in the morphine-induced antinociception in anterior cingulate cortex of rats with neuropathic pain. The morphine-induced antinociception was much more decreased in rats with neuropathic pain than that in normal rats, and there was a significant decrease in mu-opioid receptor messenger RNA levels in anterior cingulate cortex of rats with neuropathic pain, indicating that there may be a down-regulation in mu-opioid receptor expression in anterior cingulate cortex of rats with neuropathic pain. To further confirm the role of mu-opioid receptor in morphine-induced antinociception in anterior cingulate cortex, normal rats were received intra-anterior cingulate cortex administration of small interfering RNA targeting mu-opioid receptor and it was found that there was a down-regulation in mu-opioid receptor messenger RNA levels, as well as a down-regulation in mu-opioid receptor expression in anterior cingulate cortex tested by real-time polymerase chain reaction and western blotting. Furthermore, the morphine-induced antinociceptive effect decreased significantly in rats with small interfering RNA targeting mu-opioid receptor, which indicated that knockdown mu-opioid receptor in anterior cingulate cortex could also attenuate morphine-induced antinociceptive effect. These results strongly suggest that mu-opioid receptor plays a significant role in nociceptive modulation in anterior cingulate cortex of rats.

Developmental frontal brain activation differences in overcoming heuristic bias

Since reasoning is often biased by intuitive heuristics, the development of sound reasoning has long been postulated to depend on successful bias monitoring and inhibition. The present fMRI study aimed to identify neural correlates of developmental changes in these processes. A group of adults and young adolescents were presented with ratio-bias problems in which an intuitively cued heuristic response could be incongruent (conflict item) or congruent (no-conflict item) with the correct response. Results showed that successfully avoiding biased responding on conflict items across both age groups was associated with increased activation in Anterior Cingulate Cortex (ACC) and the right Lateral Prefrontal Cortex (LPFC) regions of interest. Critically, the right LPFC activation decreased with age. Biased responding did not result in right LPFC or ACC modulation and failed to show any developmental activation changes. We discuss implications for ongoing debates on the nature of heuristic bias and its development.

Role of Mu-Opioid Receptor in Nociceptive Modulation in the Anterior Cingulate Cortex of Rats with Inflammatory Pain

Objective: The present study was performed to explore the role of mu opioid receptor (MOR) in nociceptive modulation in anterior cingulate cortex (ACC) of rats with inflammatory pain. Methods: To set up an inflammatory pain model, rats received a subcutaneous injection of 0.1 ml of 2% carrageenan into the left hindpaw. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation, by hot plate and Randall Selitto Test respectively, was used to evaluate the rat's responses to noxious stimulation. The effects induced by intra-ACC administration of morphine and opioid receptor antagonists were observed. The influence of inflammatory pain on MOR mRNA level and MOR expression in ACC were assayed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) and western blot. Results: We found that intra-ACC administration of morphine induced significant antinociceptive effects in a dose-dependent manner in rats with inflammatory pain. Furthermore, the antinociceptive effects induced by morphine were attenuated by intra-ACC injection of the opioid receptor antagonist naloxone, indicating an involvement of opioid receptor in nociceptive modulation in ACC in rats with inflammatory pain. Moreover, intra-ACC administration of the MOR antagonist β-funaltrexamine (β-FNA) attenuated the morphine-induced antinociception significantly in rats with inflammatory pain. The results demonstrated that blockade MOR by β-FNA inhibited the morphine-induced antinociception, indicating that MOR plays an important role in nociceptive modulation in ACC in rats with inflammatory pain. We further found that the morphine-induced antinociception was lower in rats with inflammatory pain than that in normal rats. Interestingly, we found that there were significant decreases in MOR mRNA level and MOR expression in ACC in rats with inflammatory pain compared with intact rats tested by RT-PCR and western blot, indicating that there is a down regulation in MOR expression in rats with inflammatory pain, which support our above results that morphine-induced antinociception was lower in rats with inflammatory pain than that in normal rats. Conclusion: These findings suggest that MOR plays an important role in nociceptive modulation in ACC in rats with inflammatory pain and there is a down-regulation in MOR expression in rats with inflammatory pain.

Decreased anterior cingulate activation in a motor task in youths with bipolar disorder.

Bipolar disorder (BP) is characterized by abnormal shifts in mood between episodes of mania and severe depression, both of which have been linked with psychomotor disturbances. This study compares brain activation patterns in motor networks between euthymic youths with BP and healthy controls (HC) during the completion of a simple motor task. Thirty-five youths with BP and 35 HC (aged 10-19) completed a self-paced sequential bilateral finger-tapping task, consisting of a 4-minute scan block with alternating 20-second periods of either the tapping task (six blocks) or rest (six blocks), while undergoing functional magnetic resonance imaging. Clinical and behavioral symptoms were assessed using the Child Behavior Checklist (CBCL). A between-group whole-brain analysis compared activation pattern differences while controlling for effects of age and sex. Clusters meeting whole-brain false discovery rate (FDR) correction (qFDR<.05) were considered statistically significant. Post hoc analyses evaluating comorbid attention-deficit/hyperactivity disorder (ADHD) in the BP group were also conducted. Significantly decreased activation was found in the anterior cingulate cortex (ACC) in youths with BP compared to HC. Furthermore, ACC activation was negatively correlated with CBCL mood dysregulation profile scores in the BP group. No significant differences in functional activation patterns were found between youths with BP and comorbid ADHD and those with only BP. These findings suggest a potential common mechanism of impaired ACC modulation between emotion dysregulation and motor processing in youths with BP.

Involvement of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex of normal rats and rats with mononeuropathy

The present study was performed to explore the role of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex (ACC) of normal rats and rats with mononeuropathy. Intra-ACC injection of galanin induced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in both normal rats and rats with mononeuropathy, the increased HWLs were attenuated significantly by intra-ACC injection of galanin receptor 2 antagonist M871, indicating an involvement of galanin receptor 2 in nociceptive modulation in ACC. Interestingly, the galanin-induced HWL was significant higher in rats with mononeuropathy than that in normal rats tested by Randall Selitto test. Furthermore, both the galanin mRNA expression and galanin content increased significantly in ACC in rats with mononeuropathy than that in normal rats. Moreover, both the mRNA levels of galanin receptor 2 and the content of galanin receptor 2 in ACC increased significantly in rats with mononeuropathy than that in normal rats. These results found that galanin induced antinociception in ACC in both normal rats and rats with mononeuropathy. And there may be plastic changes in the expression of galanin and galanin receptor 2 in rats with mononeuropathy, as well as in the galanin-induced antinociception.

Antinociception induced by galanin in anterior cingulate cortex in rats with acute inflammation

The present study was performed to explore the role of galanin in nociceptive modulation in anterior cingulate cortex (ACC) of rats with acute inflammation, and the changes in galanin and galanin receptor 2 (Gal R2) expressions in rats with acute inflammation. Intra-ACC injection of galanin induced antinociception in rats with acute inflammation, the antinociceptive effects induced by galanin were attenuated significantly by intra-ACC injection of the Gal R2 antagonist M871, indicating an involvement of Gal R2 in nociceptive modulation in ACC in rats with acute inflammation. Furthermore, we found that both the galanin mRNA expression and galanin content increased significantly in ACC in rats with acute inflammation than that in normal rats. Moreover, both the mRNA levels of Gal R2 and the content of Gal R2 in ACC increased significantly in rats with acute inflammation than that in normal rats. These results demonstrated that galanin induced antinociception in ACC in rats with acute inflammation. And there were changes in the expression of galanin and Gal R2 in rats with acute inflammation.

Reward valence modulates conflict-driven attentional adaptation: Electrophysiological evidence

Recent findings suggest that, relative to negative feedback, positive feedback counteracts conflict processing and subsequent attentional adaptation. Here we hypothesize that this interaction may direct adjustments in perception and action via the anterior cingulate cortex (ACC). We recorded EEG while participants performed an arrow flanker task with monetary gain or loss as arbitrary reward feedback between trials. As predicted, we found a reduction in conflict-driven adaptation for trials in which conflict was followed by monetary gain (vs. monetary loss), a behavioral effect accompanied by a modulation in early visual processing related to the processing of the distracters. Moreover, time-frequency analyses showed that ongoing fronto-central theta oscillations induced by previous conflict sustained longer after loss than after gain, an interaction presumably reflecting ACC modulation. These data provide a first important step toward understanding the neural mechanism underlying the affective regulation of conflict-driven behavior.

Increased Anterior Cingulate Regional Homogeneity After Duloxetine Therapy in First-Episode, Drug-Naïve, Major Depressive Disorder With Panic Disorder Patients: A Case Series

Increased Anterior Cingulate Regional Homogeneity After Duloxetine Therapy in First-Episode, Drug-Naïve, Major Depressive Disorder With Panic Disorder Patients: A Case Series

Affective modulation of anterior cingulate cortex in young people at increased familial risk of depression

We previously found that children of parents with depression showed impaired performance on a task of emotional categorisation. To test the hypothesis that children of parents with depression would show abnormal neural responses in the anterior cingulate cortex, a brain region involved in the integration of emotional and cognitive information. Eighteen young people (mean age 19.8 years) with no personal history of depression but with a biological parent with a history of major depression (FH+ participants) and 16 controls (mean age 19.9 years) underwent functional magnetic resonance imaging while completing an emotional counting Stroop task. Controls showed significant activation in the pregenual anterior cingulate cortex to both positive and negative words during the emotional Stroop task. This activation was absent in FH+ participants. Our findings show that people at increased familial risk of depression demonstrate impaired modulation of the anterior cingulate cortex in response to emotionally valenced stimuli.

Pathways for fear perception: modulation of amygdala activity by thalamo-cortical systems

Effective perception of fear signals is crucial for human survival and the importance of the amygdala in this process is well documented. Animal, lesion and neuroimaging studies indicate that incoming sensory signals of fear travel from thalamus to amygdala via two neural pathways: a direct subcortical route and an indirect pathway via the sensory cortex. Other lines of research have demonstrated prefrontal modulation of the amygdala. However, no study to date has examined the prefrontal modulation of the thalamo-cortico-amygdala pathways in vivo. We used psychophysiological and physiophysiological interactions to examine the functional connectivity within thalamus, amygdala and sensory (inferior occipital, fusiform) cortices, and the modulation of these networks by the anterior cingulate cortex (ACC). Functional magnetic resonance imaging (fMRI) data were acquired for 28 healthy control subjects during a fear perception task, with neutral as the ‘baseline’ control condition. Main effect analysis, using a region of interest (ROI) approach, confirmed that these regions are part of a distributed neural system for fear perception. Psychophysiological interactions revealed an inverse functional connectivity between occipito-temporal visual regions and the left amygdala, but a positive connectivity between these visual region and the right amygdala, suggesting that there is a hemispheric specialization in the transfer of fear signals from sensory cortices to amygdala. Physiophysiological interactions revealed a dorsal–ventral division in ACC modulation of the thalamus–sensory cortex pathway. While the dorsal ACC showed a positive modulation of this pathway, the ventral ACC exhibited an inverse relationship. In addition, both the dorsal and ventral ACC showed an inverse interaction with the direct thalamus–amygdala pathway. These findings suggest that thalamo-amygdala and cortical regions are involved in a dynamic interplay, with functional differentiation in both lateralized and ventral/dorsal gradients. Breakdowns in these interactions may give rise to affect-related symptoms seen in a range of neuropsychiatric disorders.