Empathy-related differences in the anterior cingulate functional connectivity of regular cannabis users when compared to controls.

It has been reported that cannabis consumption affects the anterior cingulate cortex (ACC), a structure with a central role in mediating the empathic response. In this study, we compared psychometric scores of empathy subscales, between a group of regular cannabis users (85, users) and a group of non-consumers (51, controls). We found that users have a greater Emotional Comprehension, a cognitive empathy trait involving the understanding of the "other" emotional state. Resting state functional MRI in a smaller sample (users = 46, controls = 34) allowed to identify greater functional connectivity (FC) of the ACC with the left somatomotor cortex (SMC), in users when compared to controls. These differences were also evident within the empathy core network, where users showed greater within network FC. The greater FC showed by the users is associated with emotional representational areas and empathy-related regions. In addition, the differences in psychometric scores suggest that users have more empathic comprehension. These findings suggest a potential association between cannabis use, a greater comprehension of the other's affective state and the functional brain organization of the users. However, further research is needed to explore such association, since many other factors may be at play.

Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation.

OBJECTIVE: To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR). METHODS: The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis. RESULTS: BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; ß = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; ß = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; ß = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA. CONCLUSION: Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone.

Increased Glucose Activity in Subgenual Anterior Cingulate and Hippocampus of High Performing Older Adults, Despite Amyloid Burden.

BACKGROUND: Individuals at 80 years of age or above with exceptional memory are considered SuperAgers (SA), an operationalized definition of successful cognitive aging. SA showed increased thickness and altered functional connectivity in the anterior cingulate cortex as a neurobiological signature. However, their metabolic alterations are yet to be uncovered. OBJECTIVE: Herein, a metabolic (FDG-PET), amyloid (PIB-PET), and functional (fMRI) analysis of SA were conducted. METHODS: Ten SA, ten age-matched older adults (C80), and ten cognitively normal middle-aged (C50) adults underwent cognitive testing and multimodal neuroimaging examinations. Anterior and posterior regions of the cingulate cortex and hippocampal areas were primarily examined, then subregions of anterior cingulate were segregated. RESULTS: The SA group showed increased metabolic activity in the left and right subgenual anterior cingulate cortex (sACC, p < 0.005 corrected, bilateral) and bilateral hippocampi (right: p < 0.0005 and left: p < 0.005, both corrected) as compared to that in the C80 group. Amyloid deposition was above threshold in 30% of SA and C80 (p > 0.05). The SA group also presented decreased connectivity between right sACC and posterior cingulate (p < 0.005, corrected) as compared to that of the C80 group. CONCLUSION: These results support the key role of sACC and hippocampus in SA, even in the presence of amyloid deposition. It also suggests that sACC may be used as a potential biomarker in older adults for exceptional memory ability. Further longitudinal studies measuring metabolic biomarkers may help elucidate the interaction between these areas in the cognitive aging process.

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

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

ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization.

Bipolar disorder (BD) is characterized by unstable mood states ranging from mania to depression. Although there is some evidence that mood instability may result from an imbalance between excitatory glutamatergic and inhibitory GABA-ergic neurotransmission, few proton magnetic resonance spectroscopy (1H-MRS) studies have measured these two neurometabolites simultaneously in BD. The enzyme glutamic acid decarboxylase (GAD1) catalyzes the decarboxylation of glutamate (Glu) to GABA, and its single nucleotide polymorphisms (SNPs) might influence Glu/GABA ratio. Thus, we investigated Glu/GABA ratio in the dorsal anterior cingulate cortex (dACC) of euthymic BD type I patients and healthy controls (HC), and assessed the influence of both mood stabilizers and GAD1 SNPs on this ratio. Eighty-eight subjects (50 euthymic BD type I patients and 38 HC) underwent 3T 1H-MRS in the dACC (2 × 2 × 4.5 cm3) using a two-dimensional JPRESS sequence and all subjects were genotyped for 4 SNPs in the GAD1 gene. BD patients had lower dACC Glu/GABA ratio compared to HC, where this was influenced by anticonvulsant and antipsychotic medications, but not lithium. The presence of GAD1 rs1978340 allele A was associated with higher Glu/GABA ratio in BD, while patients without this allele taking mood stabilizers had a lower Glu/GABA ratio. The lowering of dACC Glu/GABA could be one explanation for the mood stabilizing action of anticonvulsants and antipsychotics in BD type I euthymia. Therefore, this putative role of Glu/GABA ratio and the influence of GAD1 genotype interacting with mood stabilization medication should be confirmed by further studies involving larger samples and other mood states.ClincalTrials.gov registration: NCT01237158.

Lisdexamfetamine Alters BOLD-fMRI Activations Induced by Odor Cues in Impulsive Children.

INTRODUCTION: Lisdexamfetamine (LDX) is a drug used to treat ADHD/impulsive patients. Impulsivity is known to affect inhibitory, emotional and cognitive function. On the other hand, smell and odor processing are known to be affected by neurological disorders, as they are modulators of addictive and impulsive behaviors specifically. We hypothesize that, after LDX ingestion, inhibitory pathways of the brain would change, and complementary behavioral regulation mechanisms would appear to regulate decision-making and impulsivity. METHODS: 20 children were studied in an aleatory crossover study. Imaging of BOLD-fMRI activity, elicited by olfactory stimulation in impulsive children, was performed after either LDX or placebo ingestion. RESULTS: Findings showed that all subjects who underwent odor stimulation presented activations of similar intensities in the olfactory centers of the brain. This contrasted with inhibitory regions of the brain such as the cingulate cortex and frontal lobe regions, which demonstrated changed activity patterns and intensities. While some differences between the placebo and medicated states were found in motor areas, precuneus, cuneus, calcarine, supramarginal, cerebellum and posterior cingulate cortex, the main changes were found in frontal, temporal and parietal cortices. When comparing olfactory cues separately, pleasant food smells like chocolate seemed not to present large differences between the medicated and placebo scenarios, when compared to non-food-related smells. CONCLUSION: It was demonstrated that LDX, first, altered the inhibitory pathways of the brain, secondly it increased activity in several brain regions which were not activated by smell in drug-naïve patients, and thirdly, it facilitated a complementary behavioral regulation mechanism, run by the cerebellum, which regulated decision-making and impulsivity in motor and frontal structures.

Effects of semantic categorization strategy training on episodic memory in children and adolescents.

Episodic memory is the ability to learn, store and recall new information. The prefrontal cortex (PFC) is a crucial area engaged in this ability. Cognitive training has been demonstrated to improve episodic memory in adults and older subjects. However, there are no studies examining the effects of cognitive training on episodic memory encoding in typically developing children and adolescents. This study investigated the behavioral effects and neural correlates of semantic categorization strategy training in children and adolescents during verbal episodic memory encoding using functional magnetic resonance imaging (fMRI). Participants with age range: 7-18 years were scanned before and after semantic categorization training during encoding of word lists. Results showed improved memory performance in adolescents, but not in children. Deactivation of the anterior medial PFC/anterior cingulate and higher activation of the right anterior and lateral orbital gyri, right frontal pole and right middle frontal gyrus activation were found after training in adolescents when compared to children. These findings suggest different maturational paths of brain regions, especially in the PFC, and deactivation of default mode network areas, which are involved in successful memory and executive processes in the developing brain.

Methylphenidate Alters Functional Connectivity of Default Mode Network in Drug-Naive Male Adults With ADHD.

Objective: This study evaluated the hypothesis that methylphenidate immediate release (MPH-IR) treatment would improve Default Mode Network (DMN) within-connectivity. Method: Resting-state functional connectivity of the main nodes of DMN was evaluated in a highly homogeneous sample of 18 drug-naive male adult participants with ADHD. Results: Comparing resting-state functional connectivity functional magnetic resonance imaging (R-fMRI) scans before and after MPH treatment focusing exclusively on within-DMN connectivity, we evidenced the strengthening of functional connectivity between two nodes of the DMN: posterior cingulate cortex (PCC) and left lateral parietal cortex (LLP). Conclusion: Our results contribute to the further understanding on how MPH affects functional connectivity within DMN of male adults with ADHD and corroborate the hypothesis of ADHD being a delayed neurodevelopmental disorder.

Increased posterior cingulate cortex efficiency may predict cognitive impairment in asymptomatic HIV patients.

Purpose Despite antiretroviral therapy, approximately half of individuals with human immunodeficiency virus (HIV) will develop HIV-associated neurocognitive disorder (HAND). Efficiency of brain networks is of great importance for cognitive functioning, since functional networks may reorganize or compensate to preserve normal cognition. This study aims to compare efficiency of the posterior cingulate cortex (PCC) between patients with and without HAND and controls. We hypothesize HAND negative (HAND-) patients will show higher PCC efficiency than HAND positive (HAND+) patients. Methods A total of 10 HAND + patients were compared with 9 HAND- patients and 17 gender-, age-, and education-matched controls. Resting-state functional MRI was acquired with a 3 Tesla scanner. Local efficiency, a measure of network functioning, was investigated for PCC. Network differences among HAND + , HAND- patients and controls were tested as well as correlations between network parameters and cognitive test performance in different domains. Results HAND- patients showed significantly increased PCC efficiency compared with healthy controls ( p = 0.015). No differences were observed between HAND + patients and either controls ( p = 0.327) or HAND- patients ( p = 0.152). In HAND- patients, PCC efficiency was positively related with cognitive performance in the attention/working memory domain ( p = 0.003). Conversely, in HAND + patients, PCC efficiency was negatively correlated with performance in the abstraction/executive domain ( p = 0.002). Conclusion HAND- patients showed a higher level of PCC efficiency compared with healthy subjects, and PCC efficiency was positively related to cognitive performance. These results support the functional reorganization hypothesis, that increased PCC efficiency is a compensation technique to maintain cognitive functioning.

Migraine improvement correlates with posterior cingulate cortical thickness reduction.

Objective The main goal of this study was to correlate migraine improvement, after prophylactic therapy, with cortical thickness changes. Methods Cortical thickness maps were obtained with magnetic resonance imaging (MRI) from 19 patients with migraine before (first scan) and after (second scan) prophylactic treatment, and these were compared with controls using the FreeSurfer MRI tool. Cortical changes were correlated with the headache index (HI). Results Anincrease incortical thickness was found in the right cuneus and precuneus, somatosensory and superior parietal cortices in both patient scans, compared with the controls. No changes were observed in the left hemisphere. Following correction for multiple comparisons, no areas changed from the first to the second scan. Regression analysis showed a significant negative correlation between the HI improvement and cortical thickness changes in the left posterior cingulate, a region involved with nociception and, possibly, the development of chronic pain. Conclusion There were changes in cortical thickness in patients with migraine relative to controls in areas involved with vision and pain processing. Left posterior cingulate cortical changes correlated with headache frequency and intensity.

Migraine improvement correlates with posterior cingulate cortical thickness reduction / Variação da espessura cortical no cíngulo posterior em pacientes com enxaqueca. Correlação com a melhora pós-tratamento profilático

ABSTRACT Objective The main goal of this study was to correlate migraine improvement, after prophylactic therapy, with cortical thickness changes. Methods Cortical thickness maps were obtained with magnetic resonance imaging (MRI) from 19 patients with migraine before (first scan) and after (second scan) prophylactic treatment, and these were compared with controls using the FreeSurfer MRI tool. Cortical changes were correlated with the headache index (HI). Results Anincrease incortical thickness was found in the right cuneus and precuneus, somatosensory and superior parietal cortices in both patient scans, compared with the controls. No changes were observed in the left hemisphere. Following correction for multiple comparisons, no areas changed from the first to the second scan. Regression analysis showed a significant negative correlation between the HI improvement and cortical thickness changes in the left posterior cingulate, a region involved with nociception and, possibly, the development of chronic pain. Conclusion There were changes in cortical thickness in patients with migraine relative to controls in areas involved with vision and pain processing. Left posterior cingulate cortical changes correlated with headache frequency and intensity.

RESUMO Objetivos Correlacionar a melhora de pacientes enxaquecosos após tratamento preventivo com alterações na espessura do córtex cerebral. Métodos Espessura cortical foi determinada a partir de imagens de ressonância magnética (RM)em 19 pacientes com enxaqueca, antes (1ᵃ RM) e após (2ᵃ RM) o tratamento profilático, e comparada com controles, usando o programa FreeSurfer. Mudanças corticais foram correlacionadas com o índice de cefaleia (HI). Resultados O hemisfério direito apresentou aumento da espessura no córtex do cúneus e pré-cúneus, parietal superior e somatossensitivo na primeira RM e na segunda RM, em comparação aos controles. Após correção para comparações múltiplas, nenhuma região cortical se mostrou estatisticamente diferente entre a primeira e a segunda RM. A regressão mostrou correlação (negativa) significativa entre melhora do HI e mudanças na espessura cortical do cíngulo posterior esquerdo. Conclusão Existem alterações de espessura cortical em pacientes com enxaqueca em relação a controles em áreas envolvidas com processamento visual e com a dor. As alterações corticais no cíngulo posterior esquerdo variaram de acordo com a frequência e intensidade das crises.

Altered salience network connectivity predicts macronutrient intake after sleep deprivation.

Although insufficient sleep is a well-recognized risk factor for overeating and weight gain, the neural mechanisms underlying increased caloric (particularly fat) intake after sleep deprivation remain unclear. Here we used resting-state functional magnetic resonance imaging and examined brain connectivity changes associated with macronutrient intake after one night of total sleep deprivation (TSD). Compared to the day following baseline sleep, healthy adults consumed a greater percentage of calories from fat and a lower percentage of calories from carbohydrates during the day following TSD. Subjects also exhibited increased brain connectivity in the salience network from the dorsal anterior cingulate cortex (dACC) to bilateral putamen and bilateral anterior insula (aINS) after TSD. Moreover, dACC-putamen and dACC-aINS connectivity correlated with increased fat and decreased carbohydrate intake during the day following TSD, but not during the day following baseline sleep. These findings provide a potential neural mechanism by which sleep loss leads to increased fat intake.

Cardiovascular risk in cognitively preserved elderlies is associated with glucose hypometabolism in the posterior cingulate cortex and precuneus regardless of brain atrophy and apolipoprotein gene variations.

Cardiovascular risk factors (CVRF) possibly contribute to the emergence of Alzheimer's disease (AD). Fluorodeoxyglucose-positron emission tomography (FDG-PET) has been widely used to demonstrate specific patterns of reduced cerebral metabolic rates of glucose (CMRgl) in subjects with AD and in non-demented carriers of the apolipoprotein ε4 (APOE ε4) allele, the major genetic risk factor for AD. However, functional neuroimaging studies investigating the impact of CVRF on cerebral metabolism have been scarce to date. The present FDG-PET study investigated 59 cognitively preserved elderlies divided into three groups according to their cardiovascular risk based on the Framingham 10-year risk Coronary Heart Disease Risk Profile (low-, medium-, and high-risk) to examine whether different levels of CVRF would be associated with reduced CMRgl, involving the same brain regions affected in early stages of AD. Functional imaging data were corrected for partial volume effects to avoid confounding effects due to regional brain atrophy, and all analyses included the presence of the APOE ε4 allele as a confounding covariate. Significant cerebral metabolism reductions were detected in the high-risk group when compared to the low-risk group in the left precuneus and posterior cingulate gyrus. This suggests that findings of brain hypometabolism similar to those seen in subjects with AD can be detected in association with the severity of cardiovascular risk in cognitively preserved individuals. Thus, a greater knowledge about how such factors influence brain functioning in healthy subjects over time may provide important insigths for the future development of strategies aimed at delaying or preventing the vascular-related triggering of pathologic brain changes in the AD.

Ultrasonographic description of brain cortex and cingulate sulcus development in Mexican neonates and infants with congenital hypothyroidism.

BACKGROUND: Ultrasonography of cortical and cingulum maturity patterns, were studied in newborns and infants with congenital hypothyroidism (CH). METHOD: Transversal study of 29 newborns and infants with CH, detected by neonatal screening and confirmed with thyroid function test, thyroid ultrasonography, and thyroid scintigraphy. During the first 2 months of life, transfontanelar brain ultrasonography was performed. Brain cortex maturity was assessed by normality referents provided by Slagle and Timor methods. RESULTS: Cortical immaturity signs were observed in 69% of infants (20 patients with Slage's method brain cortex development delay (Pearson's p=0.05). Logistic nominal analysis for normality prediction demonstrated a correlation between brain cortex development and age, bone age, treatment duration, and type of CH. The most sensitive detecting technique was sagittal sight by Slagle's method. CONCLUSIONS: Brain cortex delayed development is frequent in children with CH. Bone age, postnatal age at treatment start, and time since treatment start, correlates with neurological development, but not athyreosis or sublingual nodule.

Localized cerebral blood flow reductions in patients with heart failure: a study using 99mTc-HMPAO SPECT.

BACKGROUND AND PURPOSE: Reduced resting global cerebral blood flow has been previously detected in association with heart failure (HF), but it is not clear whether there are brain regions that could be specifically affected by those brain perfusion deficits. The authors used a fully automated, voxel-based image analysis method to investigate, across the entire cerebral volume, the presence of resting regional cerebral blood flow (rCBF) abnormalities in HF patients compared to healthy controls. METHODS: rCBF was evaluated with 99mTc-single-photon emission computed tomography in 17 HF patients (New York Heart Association functional class II or III) and 18 elderly healthy volunteers. Voxel-based analyses of rCBF data were conducted using the statistical parametric mapping software. RESULTS: Significant rCBF reductions in HF patients relative to controls (P<.05, corrected for multiple comparisons) were detected in 2 foci, encompassing, respectively, the left and right precuneus and cuneus and the right lateral temporoparietal cortex and posterior cingulated gyrus. In the HF group, there was also a significant direct correlation between the degree of cognitive impairment as assessed using the Cambridge Mental Disorders of the Elderly Examination and rCBF on a voxel cluster involving the right posterior cingulate cortex and precuneus, located closely to the site where between-group rCBF differences had been identified. CONCLUSIONS: These preliminary findings indicate that posterior cortical areas of the brain may be particularly vulnerable to brain perfusion reductions associated with HF and suggest that functional deficits in these regions might be relevant to the pathophysiology of the cognitive impairments presented by HF patients.

Correlation between cerebral blood flow and items of the Hamilton Rating Scale for Depression in antidepressant-naive patients.

BACKGROUND: The purpose of this study was to correlate the basal cerebral blood flow (CBF) in patients with major depressive disorder (MDD) with the score for each of the 21 questions in the Hamilton Rating Scale for Depression (HRSD), in order to determine the cerebral regions associated with each item. METHODS: Fourteen antidepressant-naive patients with unipolar depression (DSM-IV criteria for MDD) participated in this study with a HRSD score of >/=20 points. CBF images obtained by SPECT were analyzed by SPM99 software. The significant correlation threshold for a priori regions (frontocortical and limbic regions) was a Z value of at least 2.25 and clusters formed by more than 10 voxels. RESULTS: Items 1, 6, 11 and 20 were positively correlated with right medial frontal gyrus; item 7 was negatively correlated with bilateral medial frontal gyrus. Items 2 and 10 were positively correlated with right anterior and medial cingulate, respectively. Item 5 was negatively correlated with the left amygdala. Item 9 was negatively correlated with bilateral insula, and item 16 with right insula. Items 12 and 14 were positively correlated with right and left precentral frontal gyrus, respectively. LIMITATIONS: The small sample size and only out-patients included in the study. CONCLUSIONS: The frontal cortex plays an important role in the expression of MDD symptoms. Not all the symptoms evaluated correlated with one single structure, which may explain the diverse results reported in the literature. These preliminary results support the necessity of further analyses by symptoms that could provide more specific information on the pathophysiology of MDD.

Psychotic symptoms in major depressive disorder are associated with reduced regional cerebral blood flow in the subgenual anterior cingulate cortex: a voxel-based single photon emission computed tomography (SPECT) study.

BACKGROUND: Delusions and/or hallucinations are not an uncommon feature in severe major depressive episodes. Functional imaging studies of depression have been widely reported in the literature, but few of these have attempted to investigate the neurophysiological correlates of psychotic symptoms. METHODS: We measured resting regional cerebral blood flow (rCBF) with the (99m)Tc-ECD SPECT technique in patients with major depressive disorder with (n=9) and without (n=12) psychotic features, as well as in a group of healthy volunteers (n=12). Between-group rCBF comparisons were performed using the voxel-based statistical parametric mapping method. RESULTS: Major depressed patients with psychotic features showed decreased rCBF in the left subgenual anterior cingulate cortex relative to both non-psychotic patients and healthy controls (P<0.001 one-tailed, uncorrected for multiple comparisons). Relative to the non-psychotic group, depressed patients with psychotic symptoms also had a focus of decreased rCBF in the right inferior frontal cortex, with the voxel of maximal significance in the insula (P<0.031, corrected for multiple comparisons). A similar pattern of significant between-group rCBF differences between psychotic and non-psychotic patients emerged after covarying the analysis for the confounding influence of overall illness severity. CONCLUSIONS: These results provide preliminary evidence that psychotic symptoms in major depression may be associated with abnormalities in ventral paralimbic regions previously implicated in mood regulation and depression.