Altered Fronto-Striatal and Fronto-Cerebellar Circuits in Heroin-Dependent Individuals: A Resting-State fMRI Study

Abstract

BackgroundThe formation of compulsive pattern of drug use is related to abnormal regional neural activity and functional reorganization in the heroin addicts’ brain, but the relationship between heroin-use-induced disrupted local neural activity and its functional organization pattern in resting-state is unknown.Methodology/Principal FindingsWith fMRI data acquired during resting state from 17 male heroin dependent individuals (HD) and 15 matched normal controls (NC), we analyzed the changes of amplitude of low frequency fluctuation (ALFF) in brain areas, and its relationship with history of heroin use. Then we investigated the addiction related alteration in functional connectivity of the brain regions with changed ALFF using seed-based correlation analysis. Compared with NC, the ALFF of HD was obviously decreased in the right caudate, right dorsal anterior cingulate cortex (dACC), right superior medial frontal cortex and increased in the bilateral cerebellum, left superior temporal gyrus and left superior occipital gyrus. Of the six regions, only the ALFF value of right caudate had a negative correlation with heroin use. Setting the six regions as “seeds”, we found the functional connectivity between the right caudate and dorsolateral prefrontal cortex (dlPFC) was reduced but that between the right caudate and cerebellum was enhanced. Besides, an abnormal lateral PFC-dACC connection was also observed in HD.ConclusionsThe observations of dysfunction of fronto-striatal and fronto-cerebellar circuit in HD implicate an altered balance between local neuronal assemblies activity and their integrated network organization pattern which may be involved in the process from voluntary to habitual and compulsive drug use.

The cerebellum in drug craving

“…Functional connectivity studies indicated increased connectivity between the cerebellum and several cortical zones in addicted patients presented with drug-related cues (Wang et al, 2013). However, impairment in functional connectivity between frontal cortex, midbrain, anterior cingulate cortex and the vermis (Tomasi et al, 2010) and between cerebellum and nucleus accumbens has also been described (Froeliger et al, 2015).…”

“…Indeed, very few studies have shown an involvement of the anterior cerebellum (Anderson et al, 2006;Filbey et al, 2009), whereas activation in the posterior cerebellum has been a common finding (Anderson et al, 2006;Bonson et al, 2002;Filbey et al, 2009;Kilts et al, 2001;Li et al, 2014;Olbrich et al, 2006;Schneider et al, 2001;Tomasi et al, 2015;Wang et al, 2013), even in the few studies that show activity in the anterior lobe. This is consistent with the sensory vs cognitive/affective dichotomy proposed for the cerebellar anterior-posterior lobes (Stoodley and Schmahmann, 2010).…”

Resting-state Abnormalities in Heroin-dependent Individuals

“…Recently the scientific community has witnessed an explosion in the study of functional connectivity modulations (Polunina et al, 2007;Ma et al, 2010Ma et al, , 2011Wang et al, 2010Wang et al, , 2013Yuan et al, 2010a;Xie et al, 2011;Zhang et al, 2011;Moreno-López et al, 2012), structural deficits (Liu et al, 2008(Liu et al, , 2009aYuan et al, 2009Yuan et al, , 2010bBora et al, 2010;Wang et al, 2012;Qiu et al, 2011Qiu et al, , 2013Wang et al, 2011;Lin et al, 2012;Denier et al, 2013a;Zhang et al, 2013;Li et al, 2013aLi et al, , 2013c and changes in topological properties (Liu et al, 2009bYuan et al, 2010c;Jiang et al, 2013) in heroin-dependent individuals at rest.Resting-state is defined as a state that is characterized by the absence of a specific goal-oriented activity or alternatively as a task-free state where the subjects rest quietly awake with their eyes closed, as it has been proposed by Raichle et al (2001). Nevertheless, a more complex baseline or control state such as visual fixation of a cross hair on a monitor or alternatively passive viewing of a stimulus (Greicius et al, 2003;Fox et al, 2005;Fransson, 2006;Fair et al, 2008;Fransson and Marrelec, 2008) is more frequently used.…”

“…The reduced GM intensity located in the DLPFC has been implicated in goal-oriented behavior dysfunctions and erroneous decisions (Yuan et al, 2010b). Dysfunctions in DLPFC have been further linked to heroin-conditioning (Moreno-López et al, 2012) that is carried out retrieving memories biased towards heroinrelated stimuli, maintaining and orientating representations inherited from other brain regions during craving as well as choosing direct rewarding responses Wang et al, 2013).The higher degree found in the DLPFC of the heroin-dependent group indicates that information transfer becomes more complicated in the addicted brain compared to the healthy one (Yuan et al, 2010c). Similar findings have been reported for the dorsal superior frontal gyrus that is a part of the DLPFC providing evidence for the poormonitoring in heroin-addicts' daily life (Liu et al, 2009b).…”

“…The reduced GM intensity located in the DLPFC has been implicated in goal-oriented behavior dysfunctions and erroneous decisions (Yuan et al, 2010b). Dysfunctions in DLPFC have been further linked to heroin-conditioning (Moreno-López et al, 2012) that is carried out retrieving memories biased towards heroinrelated stimuli, maintaining and orientating representations inherited from other brain regions during craving as well as choosing direct rewarding responses Wang et al, 2013).…”