In the present study, we investigated the difference in the topological organization of white matter networks between MAUD and HUD patients. The major findings are as follows:(1) MAUD patients demonstrated significantly increased anxiety, hostility, and schizophrenia nuclear symptoms score. (2) HUD patients showed significantly increased Sp and Eglob than HC, and significantly increased Sp than MAUD. (3) MAUD patients had significantly decreased nodal strength and Enod than HUD. (4)Compared with HC, MAUD had reduced Hubs, while HUD had increased Hubs. (5) Nodal strength in the right superior temporal gyrus was positively correlated with the psychological scores in MAUD patients. These findings enhanced our understanding of the potential neurobiological foundation underlying the difference of psychological symptoms between MAUD and HUD patients.
The most important behavioral effects of MA are the mood-altering properties. Psychosis is indued more commonly by MA than by any other stimulants, perhaps because of the longer duration of action produced by MA when compared with the shorter half-life of other stimulants [34]. In this study, we found significantly increased scores in anxiety, hostility, and schizophrenia nuclear symptoms in MAUD patients. The hostility score in MAUD was higher than HUD. These findings are consistent with the previous. After large doses or/and long-term abuse, MAUD patients may experience violent behavior than any other psychoactive drugs, and they had higher scores on affective and positive symptoms, such as hostility, anxiety, depression and hallucinations [35].
The strength of a network (Sp) is the average of the strength across all of the nodes in the network [22]. Sp is related to the connection density or the “wiring cost” of the brain networks, the larger of the Sp, the more expensive of the “wiring cost” of the network [23]. Eglob is defined as the average of efficiency for all node pairs, measures the global efficiency of parallel information transfer in the network [36]. Several graph theoretic studies have revealed abnormal topological organization of structural networks in HUD patients. Zhang et al. found HUD patients showed significantly increased Eglob and Sp compared with HC [23], which is consistent with the present study. Increased Sp and Eglob means increased global integration, this may indicate that the white matter networks in HUD patients may keep high “wiring cost” or break up the trade-off between the efficiency and cost and may shift towards a random network [23]. However, there is an inconsistent finding in Sun’s study, they found no significant differences in any global parameter of the whole brain white matter networks between HUD and HC [22]. This may be caused by the abstinent from heroin use of their HUD patients, the functional and structural recovery during heroin abstinence had been identified in our previous studies [37–39].
Increased positive symptoms score in stimulant-induced psychosis were believed to reflect the dysregulation of the mesolimbic dopamine pathway [40, 41], and which may be mediated by frontal, striatal and limbic regions [42]. In this study, we found significantly increased positive symptoms in MAUD patients present as increased schizophrenia nuclear symptoms score. Meanwhile, MAUD group showed significantly decreased nodal strength and Enod in cingulum, parietal, temporal, and occipital regions than HUD. Decreased nodal strength and Enod in these regions may imply that the essentiality of these brain regions and the information transformation in the network were decreased. The significant correlation between the nodal strength in the right superior temporal gyrus and the psychological scores may indicate the essential function of the temporal cortices or limbic related regions underlying the MAUD related psychological symptoms.
The role of the parietal cortices in the development of psychological symptoms in schizophrenia has been established previously, and especially in the role of monitoring of internally generated thoughts and actions [43, 44]. And this abnormal self-monitoring has been proposed as the neural basis for hallucinations and delusions [45]. Reduced nodal strength in parietal regions may play an important role in the higher incidence of hallucinations and delusions in MAUD patients. A role for parietal cortices may be an early-onset risk factor for both MAUD and schizophrenia [7]. And it has been reported that the gray matter atrophy would begin in the parietal cortices and progress to the temporal and finally the frontal cortices accompany by the progress of schizophrenia [44, 46]. We found significantly decreased nodal strength and Enod in extensive temporal and parietal regions in MAUD patients when compared with HUD. The previous study has also found the smaller volume in left parietal/temporal lobe in schizophrenia patients with concurrent stimulant dependence [41], reduced gray matter in the parietal cortices in MAUD patients [47]. The disconnection within the parietal, temporal and occipital regions or with other regions, may be related to the abnormal neural response to visual and/or auditory stimuli in MAUD patients [48].
On the contrary, we found HUD patients have significantly increased nodal strength and Enod in some frontal, temporal and occipital regions compared with HC. Which was similar with the previous studies. Zhang et al. found significantly increased Enod in the frontal regions, altered white matter connectivity in frontal regions may lead to the reduced cognitive control on craving and motivation in heroin users [23, 49]. Another study found increased structural connectivity within the DMN, attentional and visual systems, and specific within-frontal and within-temporal connections were significantly correlated with the heroin dosage and the non-planning impulsivity in HUD patients [22]. These findings may reveal the topological characteristic of heroin related white matter structure connectivity alterations, and suggested a potential neural-foundation of heroin caused craving and cognitive impairment.
The regions with high centrality values are structural cores of the brain and usually defined as Hubs [50], which plays a particularly important role toward integrating information across the system by accessing different modules. Brain Hubs are central to brain disorders in general [51]. The largest declines in function may occur when disease impinges on a Hub regions [52]. In the present study, nine Hubs were identified in HC group, the result was similar with previous studies [50]. We found two brain regions located in right supplementary motor area (SMA) and right calcarine turn into nonHubs in MAUD group. Network Hub has been considered important in how a disease spreads in a network [53]. We speculate that the loss of Hubs in the medial frontal and visual regions in MAUD patients may mean the originally disconnected in the network. Interestingly, we found three Hubs specific to HUD patients located in the right middle frontal cortex, left middle cingulum and right paracentral lobule. Increased Hubs in frontal/parietal regions was accompanied by increased nodal strength and Enod in these regions in HUD patients, these findings may relate to abnormally enhanced heroin craving and impaired function in cognition and decisions.
Some limitations should be noticed. Firstly, only males were included in this study, the potential gender related influence to the white matter network and the course of psychological symptoms were not identified. Studies found that females showed more rapid progression from initial drug use to MAUD, and female MAUD patients had smaller and thinner frontal cortices than males [54, 55]. Female substances use disorder patients may experience a greater relative impact on the course of psychological symptoms than males [56]. Thus, further studies include the gender related influence should be considered. Secondly, the psychological evaluation is unspecific. More detailed evaluations such as the assessment of auditory and visual hallucinations as well as the positive and negative symptoms should be included in the future study. Thirdly, Future studies may be needed to investigate the relationship between the changes of structural network and functional network.