Reducing craving and consumption in individuals with drug addiction, obesity or overeating through neuromodulation intervention: a systematic review and meta-analysis of its follow-up effects.

BACKGROUND AND AIMS: Non-invasive brain stimulation has shown potential in clinical applications aiming at reducing craving and consumption levels in individuals with drug addiction or overeating behaviour. However, it is unclear whether these intervention effects are maintained over time. This study aimed to measure the immediate, short- and long-term effects of excitatory transcranial direct current stimulation (tDCS) and high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting at dorsolateral prefrontal cortex (dlPFC) in people with drug addiction or overeating. METHODS: A systematic review and random effects meta-analysis. We included 20 articles (total of 22 studies using randomized controlled trials: 3 alcohol dependence, 3 drug dependence, 12 smoking, 4 overeating; total: 720 participants) from January 2000 to June 2020, which reported at least one follow-up assessment of craving, consumption or abstinence levels after the intervention. We compared effects of active versus sham stimulation immediately after the intervention and at the last follow-up assessment, as compared with baseline. RESULTS: Excitatory neuromodulation of dlPFC activity reduced craving and consumption immediately after the intervention (craving: g = 0.734, CI = 0.447-1.021, P < 0.001; consumption: g = 0.527, CI = 0.309-0.745; P < 0.001), as well as during short-, mid- and long-term abstinence (craving: g = 0.677, CI = 0.440-0.914, P < 0.001; consumption: g = 0.445, CI = 0.245-0.645, P < 0.001; abstinence levels: g = 0.698, CI = 0.433-0.963, P < 0.001; average time of follow-up: 84 ± 83 days after last stimulation). Additional analysis demonstrated that the intervention effects were sustained in all populations studied (food, nicotine, alcohol or drug abuse) and with both stimulation techniques used (rTMS, tDCS). Interventions targeting at the left (vs right) hemisphere may be more effective. CONCLUSIONS: Excitatory neuromodulation targeting the dorsolateral prefrontal cortex appears to lead to a sustained reduction of craving and consumption in individuals with addiction or overeating behaviour.

A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood.

BACKGROUND: The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood. METHODS: In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using a graph-theoretical approach) in 5-year-old children (n = 34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent-report questionnaire (BRIEF-P) (n = 106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems. RESULTS: Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (ß's = .01, FDR-corrected p's ≤ .05); (b) more reported EF problems (ß's = .001, FDR-corrected p's ≤ .05). Higher global efficiency of brain areas involved in visual attention was associated with more EF problems (ß's = .01, FDR-corrected p's < .05). CONCLUSIONS: Intrinsic functional network organization of visual attention brain areas linked prenatal PBDE concentrations to EF problems in childhood. Visual attention may contribute to the development of higher-order cognitive functions, such as EF, which could be explored in future studies.

Cocaine addiction severity exacerbates the negative association of lifetime lead exposure with blood pressure levels: Evidence from a pilot study.

BACKGROUND: High blood pressure (BP) is associated independently with cocaine use and lead exposure. It is not known whether cocaine use and lead exposure act jointly to disrupt cardiovascular health. OBJECTIVE: To determine whether cocaine use modifies the association between cumulative lead levels and elevated BP. MATERIALS AND METHODS: We measured cumulative tibia lead levels in 35 adults: 20 with cocaine use disorder (CUD) and 15 non-CUD controls using in vivo K-shell X-ray fluorescence. Generalized estimating equation regression determined associations between log2-transformed lead and BP (systolic, diastolic, and mean arterial pressure) and assessed the modifying association of cocaine use (as addiction severity) on the lead-BP relationship, adjusting for age, sex, smoking, and education. Sensitivity analyses included correction for potential selection bias. RESULTS: Cases and controls differed by sex (%male: 90% vs. 67%), age (50.7 vs. 39.9 years), education (12.8 vs. 14.4 years), and tibia lead (3.50 vs. 2.35 µg/g). Lead was positively associated with systolic (P = 0.01) and diastolic BP (P = 0.01). We observed an interaction between lead and addiction severity on BP (P values for systolic BP: 0.01, diastolic BP: 0.003, and mean arterial BP: <0.0001); the association was stronger among individuals with more severe cocaine addiction: Systolic BP: Est.: 17.89, 95% confidence interval (CI): 9.52; 26.26, diastolic BP Est.: 17.89, 95% CI: 7.33; 13.79, mean arterial BP: Est.: 13.09, 95% CI: 10.34; 15.83. CONCLUSIONS: Lead was adversely associated with BP. This association was strongest among individuals with more severe cocaine addiction. The results from this small pilot study suggest that the interaction between lead and cocaine should be considered in studies of substance abuse-related health outcomes.

Neuroimaging Impaired Response Inhibition and Salience Attribution in Human Drug Addiction: A Systematic Review.

The impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six large-scale brain networks (reward, habit, salience, executive, memory, and self-directed networks) during drug cue exposure, decision making, inhibitory control, and social-emotional processing. Addicted individuals demonstrated increased recruitment of these networks during drug-related processing but a blunted response during non-drug-related processing, with the same networks also being implicated during resting state. Associations with real-life drug use, relapse, therapeutic interventions, and the relevance to initiation of drug use during adolescence support the clinical relevance of the results. Whereas the salience and executive networks showed impairments throughout the addiction cycle, the reward network was dysregulated at later stages of abuse. Effects were similar in alcohol, cannabis, and stimulant addiction.