Differences In Anterior Cingulate Cortex Research Articles

Transcranial Ultrasound Stimulation of the Anterior Cingulate Cortex Reduces Neuropathic Pain in Mice.

Focused ultrasound (FUS) is a potential tool for treating chronic pain by modulating the central nervous system. Herein, we aimed to determine whether transcranial FUS stimulation of the anterior cingulate cortex (ACC) effectively improved chronic pain in the chronic compress injury mice model at different stages of neuropathic pain. The mechanical threshold of pain was recorded in the nociceptive tests. We found FUS stimulation elevated the mechanical threshold of pain in both short-term (p < 0.01) and long-term (p < 0.05) experiments. Furthermore, we determined protein expression differences in ACC between the control group, the intervention group, and the Sham group to analyze the underlying mechanism of FUS stimulation in improving neuropathic pain. Additionally, the results showed FUS stimulation led to alterations in differential proteins in long-term experiments, including cellular processes, cellular signaling, and information storage and processing. Our findings indicate FUS may effectively alleviate mechanical neuropathic pain via the ACC's stimulation, especially in the chronic state.

Evaluation of fronto-striatal networks during cognitive control in unmedicated patients with schizophrenia and the effect of antipsychotic medication

To understand the mechanism of cognitive control dysfunction in schizophrenia, it is critical to characterize brain function without the confounding effect of medication. It is also important to establish the extent to which antipsychotic medication restores brain function and whether those changes are related to psychosis improvement. Twenty-two patients with schizophrenia, initially unmedicated and after a 6-week course of risperidone, and 20 healthy controls (HC) studied twice, 6 weeks apart, performed an fMRI task. We examined group and longitudinal differences in anterior cingulate cortex (ACC), striatum, and midbrain functional activity during performance of a Stroop color task as well as activity patterns associated with improvement in psychosis symptoms. Unmedicated patients showed reduced functional activity in the ACC, striatum, and midbrain compared to HC. Post hoc contrasts from significant group-by-time interactions indicated that, in patients, drug administration was associated with both activity increases and decreases. In unmedicated patients, greater baseline functional activity in the striatum and midbrain predicted subsequent better treatment response. Greater changes in functional activity in ACC and ventral putamen over the course of 6 weeks positively correlated with better treatment response. Unmedicated patients show reduced activity in brain networks pivotal for cognitive control and medication is associated with functional changes in these regions. These results suggest a mechanism by which antipsychotic medication has a beneficial effect on cognition. Our results also support the notion that treatment response is determined by a combination of the baseline pattern of brain function and by the pharmacological modulation of these regions.

T173. GABA AND GLUTAMATE IN PATIENTS WITH 22Q11.2 DELETION SYNDROME AND HEALTHY VOLUNTEERS AND THE RELATION WITH COGNITION: A RANDOMIZED DOUBLE-BLIND 7TESLA PHARMACOLOGICAL MRS STUDY

Background22q11.2 deletion syndrome (22q11DS) is characterized by a microdeletion on the long arm of chromosome 22. The clinical phenotype of this syndrome is highly variable but symptoms include cognitive impairment, heart malformations, auto-immune problems and a high risk of developing a psychotic disorder. One of the genes located in the deleted region is PRODH which encodes proline dehydrogenase (PRODH). This enzyme is involved in converting proline to glutamate (GLU). GLU is involved in the pathophysiology of psychosis, particularly in cognitive symptoms (Lewis and Moghaddam 2006). Gamma-aminobutyric acid (GABA) is involved in cognition and psychosis as well (Vinkers et al. 2010). With this study we aimed to investigate GLUergic and GABAergic reactivity in the anterior cingulate cortex (ACC) and striatum in medication-free patients with 22q11DS with no psychiatric history and healthy controls (HC).MethodsThis was a randomized double-blind placebo controlled cross-over study. Groups were matched for age and gender. 12 patients with 22q11DS (mean age 35 years) and 20 HCs (mean age 31 years) were enrolled in the study. GABA and GLU, levels in the ACC and striatum were obtained twice with 7Tesla Magnetic Resonance Spectroscopy (MRS, STEAM): once after placebo and once after oral administration of 50 mg. riluzole (agent with anti-glutamate and pro-GABA action). Striatal and ACC GLU/GABA ratios were computed as well as GLUergic and GABAergic reactivity (placebo minus riluzole). In addition, within the 22q11DS group, the relationship between cognitive functions (memory and attention) measured with the CANTAB and GABA, GLU, GLU/GABA ratio, GABAergic reactivity and GLUergic in the ACC and striatum were examined.ResultsAnalyses of Covariance (ANCOVA) showed no baseline group differences in glutamate and GABA levels and GLU/GABA ratios (corrected for fraction of cerebral spinal fluid, CSF) in both brain regions. A repeated measures ANCOVA showed a trend level significant increase in striatal GABA concentrations after (p= 0.065). Riluzole had no significant effect on GLU (p= 0.303) and GLU/GABA ratios (p= 0.150) in the striatum. No medication X group interaction effects were found. Riluzole had no significant effect on GABA (p= 0.101), GLU (p= 0.847) and GLU/GABA ratio (p= 0.108) in the ACC. No group main effects and no medication X group interactions effects were found. However, a significant negative correlation was found between verbal memory (r= -0.650, p= 0.030) and ACC GLU levels, as well as GLUergic reactivity (r= -0.733, p= 0.010). Moreover, in the 22q11DS group, a significant negative correlation was found between attention (target sequence detection) and ACC GLU levels (r= -0.704, p= 0.016) as well as GLU/GABA ratio (r= -0.602, p= 0.050). Furthermore, sustained attention was positively associated with ACC GABA levels (r= 0.700, p= 0.024) and negatively associated with GLU/GABA ratio r= -0.639, p= 0.047) in these patients. Finally, a positive correlation was found between visual memory and striatal GLU levels (r= 0.616, p= 0.043).DiscussionThe present study did not demonstrate differences in ACC and striatal GLU and GABA levels, nor in GLUergig or GABAergic reactivity in response to riluzole between 22q11DS patients and controls. However, these results suggest a role for GLU and GABA in cognition in the 22q11DS group. Therefore, influencing these neurotransmitter systems might enhance cognitive functioning in these patients. More studies are required to replicate these findings.

S172. BRAIN METABOLITES AND THE RELATION WITH COGNITION AND PSYCHOTIC SYMPTOMS IN MEDICATION-FREE PSYCHOSIS AND CONTROLS: A PHARMACOLOGICAL MAGNETIC RESONANCE SPECTROSCOPY STUDY

BackgroundPsychotic disorders are complex neuropsychiatric disorders characterized by positive, negative and cognitive symptoms. Over the recent years, several neurotransmitter systems and neurometabolites have been related to psychotic disorders but the exact underlying neurobiological mechanisms are still not well understood. One neurotransmitter system that has been increasingly related to psychosis is the cholinergic muscarinic system. Increased choline concentrations and reduced muscarinic M1 receptor expression have been reported in schizophrenia. Therefore, the present study investigated brain metabolite concentrations, their responsivity to M1 receptor blockage, and their relation to cognitive, positive and negative symptoms in psychosis.Methods31 medication-free subjects with a psychotic disorder (mean age 27 years) and 31 gender, age and IQ-matched healthy control subjects (mean age 25 years) were enrolled in the study. 1H-proton magnetic resonance spectroscopy (1H-MRS, PRESS) was used to measure brain metabolites in the anterior cingulate cortex (ACC) and striatum. Metabolites measured included choline (Cho), glutamate (Glu), glutamine (Gln), GLX, myoinositol (MI), N-acetylaspartate (NAA) and gluthatione (GSH) (metabolite to creatine ratios were analyzed). All subjects were measured twice: once after placebo and once after a pharmacological challenge (4 mg. biperiden, a M1 receptor antagonist). The order of drug – challenge was counterbalanced. In addition, cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and psychotic symptom severity was assessed with the Positive and Negative Syndrome Scale (PANSS) to examine the relation between brain metabolites and cognition and psychosis symptoms.ResultsNo significant differences were found in both ACC and striatal brain metabolite levels between subjects with a psychotic disorder and controls after placebo. Moreover, M1 blockade did not significantly affect brain metabolite levels in these regions and no group x challenge interaction effects were found. In addition, in both groups, no correlation was found between cognitive functioning and any of the brain metabolites. In subjects with a psychotic disorder, a positive correlation was found between striatal choline levels (after placebo) and negative symptom severity (p = 0.024).DiscussionThese results suggest that there are no differences in ACC and striatal brain metabolites between medication-free subjects with a psychotic disorder and healthy controls and that these metabolites are not influences by acute muscarinic M1 receptor antagonism. The significant correlation between striatal choline and negative symptom severity in the psychosis group could indicate that the cholinergic system is involved in negative symptom pathology. This is the first study that examined the influence of M1 receptor blockade on brain metabolites and therefore these results warrant replication.

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

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.

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

ObjectiveThere is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity.MethodStructural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects.ResultsWhole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms.ConclusionsThe depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.