Regional homogeneity of resting-state brain abnormalities in violent juvenile offenders: A biomarker of brain immaturity?

The authors investigated whether male violent juvenile offenders demonstrate any differences in local functional connectivity indicative of delayed maturation of the brain that may serve as a biomarker of violence. Twenty-nine violent juvenile offenders and 28 age-matched controls were recruited. Regional homogeneity (ReHo) method was used to analyze resting-state magnetic resonance images. Violent offenders showed significantly lower ReHo values in the right caudate, right medial prefrontal cortex, and left precuneus, and higher values in the right supramarginal gyrus than the controls. These regions had both high sensitivity and specificity in distinguishing between the two groups suggesting that dysfunction in these regions can be used to correctly classify those individuals who are violent. Dysfunction in the right medial prefrontal-caudate circuit may, therefore, represent an important biomarker of violence juvenile males.

Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions

The current study, in parallel experiments, evaluated the impact of chronic psychological stress on physiological and behavioural measures, and on the activation status of microglia in 15 stress-responsive brain regions. Rats were subjected, for 14 days, to two 30 min sessions of restraint per day, applied at random times each day. In one experiment the effects of stress on sucrose preference, weight gain, core body temperature, and struggling behaviour during restraint, were determined. In the second experiment we used immunohistochemistry to investigate stress-induced changes in ionized calcium-binding adaptor molecule-1 (Iba1), a marker constitutively expressed by microglia, and major histocompatibility complex-II (MHC-II), a marker often expressed on activated microglia, in a total of 15 stress-responsive nuclei. We also investigated cellular proliferation in these regions using Ki67 immunolabelling, to check for the possibility of microglial proliferation. Collectively, the results we obtained showed that chronic stress induced a significant increase in anhedonia, a decrease in weight gain across the entire observation period, a significant elevation in core body temperature during restraint, and a progressive decrease in struggling behaviour within and over sessions. With regard to microglial activation, chronic stress induced a significant increase in the density of Iba1 immunolabelling (nine of 15 regions) and the number of Iba1-positive cells (eight of 15 regions). Within the regions that exhibited an increased number of Iba1-positive cells after chronic stress, we found no evidence of a between group difference in the number of MHC-II or Ki67 positive cells. In summary, these results clearly demonstrate that chronic stress selectively increases the number of microglia in certain stress-sensitive brain regions, and also causes a marked transition of microglia from a ramified-resting state to a non-resting state. These findings are consistent with the view that microglial activation could play an important role in controlling and/or adapting to stress.

Cocaine-specific neuroplasticity in the ventral striatum network is linked to delay discounting and drug relapse

AIMS: To contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling, via a resting-state functional connectivity approach; and to determine the association between cocaine dependence-related neuroadaptations indexed by functional connectivity and impulsivity, compulsivity and drug relapse. DESIGN: Cross-sectional study of 20 individuals with cocaine dependence (CD), 19 individuals with pathological gambling (PG) and 21 healthy controls (HC), and a prospective cohort study of 20 CD followed-up for 12 weeks to measure drug relapse. SETTING AND PARTICIPANTS: CD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment (Centro Provincial de Drogodependencias) and a public clinic specialized in gambling treatment (AGRAJER), respectively; HC were recruited through community advertisement in the same area in Granada (Spain). MEASUREMENTS: Seed-based functional connectivity in the ventral striatum (ventral caudate and ventral putamen) and dorsal striatum (dorsal caudate and dorsal putamen), the Kirby delay-discounting questionnaire, the reversal-learning task and a dichotomous measure of cocaine relapse indicated with self-report and urine tests. FINDINGS: CD relative to PG exhibit enhanced connectivity between the ventral caudate seed and subgenual anterior cingulate cortex, the ventral putamen seed and dorsomedial pre-frontal cortex and the dorsal putamen seed and insula (P≤0.001, kE=108). Connectivity between the ventral caudate seed and subgenual anterior cingulate cortex is associated with steeper delay discounting (P≤0.001, kE=108) and cocaine relapse (P≤0.005, kE=34). CONCLUSIONS: Cocaine dependence-related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse.

Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.