Parenting links to parent-child interbrain synchrony: a real-time fNIRS hyperscanning study.

Parent-child interaction is crucial for children's cognitive and affective development. While bio-synchrony models propose that parenting influences interbrain synchrony during interpersonal interaction, the brain-to-brain mechanisms underlying real-time parent-child interactions remain largely understudied. Using functional near-infrared spectroscopy, we investigated interbrain synchrony in 88 parent-child dyads (Mage children = 8.07, 42.0% girls) during a collaborative task (the Etch-a-Sketch, a joint drawing task). Our findings revealed increased interbrain synchrony in the dorsolateral prefrontal cortex and temporo-parietal areas during interactive, collaborative sessions compared to non-interactive, resting sessions. Linear regression analysis demonstrated that interbrain synchrony in the left temporoparietal junction was associated with enhanced dyadic collaboration, shared positive affect, parental autonomy support, and parental emotional warmth. These associations remained significant after controlling for demographic variables including child age, child gender, and parent gender. Additionally, differences between fathers and mothers were observed. These results highlight the significant association between brain-to-brain synchrony in parent-child dyads, the quality of the parent-child relationship, and supportive parenting behaviors. Interbrain synchrony may serve as a neurobiological marker of real-time parent-child interaction, potentially underscoring the pivotal role of supportive parenting in shaping these interbrain synchrony mechanisms.

Using normative modeling to assess pharmacological treatment effect on brain state in patients with schizophrenia.

Quantifying individual differences in neuroimaging metrics is attracting interest in clinical studies with mental disorders. Schizophrenia is diagnosed exclusively based on symptoms, and the biological heterogeneity makes it difficult to accurately assess pharmacological treatment effects on the brain state. Using the Cambridge Centre for Ageing and Neuroscience data set, we built normative models of brain states and mapped the deviations of the brain characteristics of each patient, to test whether deviations were related to symptoms, and further investigated the pharmacological treatment effect on deviation distributions. Specifically, we found that the patients can be divided into 2 groups: the normalized group had a normalization trend and milder symptoms at baseline, and the other group showed a more severe deviation trend. The baseline severity of the depression as well as the overall symptoms could predict the deviation of the static characteristics for the dorsal and ventral attention networks after treatment. In contrast, the positive symptoms could predict the deviations of the dynamic fluctuations for the default mode and dorsal attention networks after treatment. This work evaluates the effect of pharmacological treatment on static and dynamic brain states using an individualized approach, which may assist in understanding the heterogeneity of the illness pathology as well as the treatment response.

Autistic children's visual sensitivity to face movement.

There is a pressing need for studies of large sample sizes and variable age ranges to delineate the mechanism underlying reduced visual attention to biological motion in autism. Here we focused on the basic movement of the eyes or mouth in guiding attention. The stimuli face blinked continuously or moved the mouth silently. In a large sample (145 autistic and 132 non-autistic participants) ranging from 3 to 17 years old, we assessed whether autistic participants showed reduced visual attention to basic movement of the eyes or mouth using a free-viewing eye-tracking task. We found that, like non-autistic participants, autistic participants increased their eye-looking time when viewing the blinking face and increased mouth-looking time when viewing the mouth-moving face. Furthermore, these effects were stable across ages, suggesting the presence of a developmentally stable attentional capture by basic face movements in both groups. We also found that autistic participants looked less at basic face movement than non-autistic participants. Our results suggest that autistic children and adolescents could modulate their visual attention to the basic face movements, but their modulation effect is weaker than non-autistic participants. These results further our understanding of the mechanism underlying visual attention-to-face movement in autistic people.

Heterogeneous brain dynamic functional connectivity patterns in first-episode drug-naive patients with major depressive disorder.

It remains challenging to identify depression accurately due to its biological heterogeneity. As people suffering from depression are associated with functional brain network alterations, we investigated subtypes of patients with first-episode drug-naive (FEDN) depression based on brain network characteristics. This study included data from 91 FEDN patients and 91 matched healthy individuals obtained from the International Big-Data Center for Depression Research. Twenty large-scale functional connectivity networks were computed using group information guided independent component analysis. A multivariate unsupervised normative modeling method was used to identify subtypes of FEDN and their associated networks, focusing on individual-level variability among the patients for quantifying deviations of their brain networks from the normative range. Two patient subtypes were identified with distinctive abnormal functional network patterns, consisting of 10 informative connectivity networks, including the default mode network and frontoparietal network. 16% of patients belonged to subtype I with larger extreme deviations from the normal range and shorter illness duration, while 84% belonged to subtype II with weaker extreme deviations and longer illness duration. Moreover, the structural changes in subtype II patients were more complex than the subtype I patients. Compared with healthy controls, both increased and decreased gray matter (GM) abnormalities were identified in widely distributed brain regions in subtype II patients. In contrast, most abnormalities were decreased GM in subtype I. The informative functional network connectivity patterns gleaned from the imaging data can facilitate the accurate identification of FEDN-MDD subtypes and their associated neurobiological heterogeneity.

Understanding the heterogeneity of dynamic functional connectivity patterns in first-episode drug naïve depression using normative models.

BACKGROUND: The heterogeneity of the clinical symptoms and presumptive neural pathologies has stunted progress toward identifying reproducible biomarkers and limited therapeutic interventions' effectiveness for the first episode drug-naïve major depressive disorders (FEDN-MDD). This study combined the dynamic features of fMRI data and normative modeling to quantitative and individualized metrics for delineating the biological heterogeneity of FEDN-MDD. METHOD: Two hundred seventy-four adults with FEDN-MDD and 832 healthy controls from International Big-Data Center for Depression Research were included. Subject-specific dynamic brain networks and network fluctuation characteristics were computed for each subject using the group information-guided independent component analysis. Then, we mapped the heterogeneity of the dynamic features (network fluctuation characteristics and dynamic functional connectivity within brain networks) in the patients group via normative modeling. RESULTS: The FEDN-MDD whose network fluctuation characteristics deviate from the normative model also showed significant differences within the default mode network, executive control network, and limbic network compared with healthy controls. Furthermore, the network fluctuation characteristics are significantly increased in patients with FEDN-MDD. About 4.74 % of the patients showed a deviation of dynamic functional connectivity, and only 3.35 % of the controls deviated from the normative model in above 100 connectivities. More patients than healthy controls showed extreme dynamic variabilities in above 100 connectivities. CONCLUSIONS: This work evaluates the efficacy of an individualized approach based on normative modeling for understanding the heterogeneity of abnormal dynamic functional connectivity patterns in FEDN-MDD, and could be used as complementary to classical case-control comparisons.

Increasing audiovisual speech integration in autism through enhanced attention to mouth.

Autistic children (AC) show less audiovisual speech integration in the McGurk task, which correlates with their reduced mouth-looking time. The present study examined whether AC's less audiovisual speech integration in the McGurk task could be increased by increasing their mouth-looking time. We recruited 4- to 8-year-old AC and nonautistic children (NAC). In two experiments, we manipulated children's mouth-looking time, measured their audiovisual speech integration by employing the McGurk effect paradigm, and tracked their eye movements. In Experiment 1, we blurred the eyes in McGurk stimuli and compared children's performances in blurred-eyes and clear-eyes conditions. In Experiment 2, we cued children's attention to either the mouth or eyes of McGurk stimuli or asked them to view the McGurk stimuli freely. We found that both blurring the speaker's eyes and cuing to the speaker's mouth increased mouth-looking time and increased audiovisual speech integration in the McGurk task in AC. In addition, we found that blurring the speaker's eyes and cuing to the speaker's mouth also increased mouth-looking time in NAC, but neither blurring the speaker's eyes nor cuing to the speaker's mouth increased their audiovisual speech integration in the McGurk task. Our findings suggest that audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the mouth. Our findings contribute to a deeper understanding of relations between face attention and audiovisual speech integration, and provide insights for the development of professional supports to increase audiovisual speech integration in AC. HIGHLIGHTS: The present study examined whether audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the speaker's mouth. Blurring the speaker's eyes increased mouth-looking time and audiovisual speech integration in the McGurk task in AC. Cuing to the speaker's mouth also increased mouth-looking time and audiovisual speech integration in the McGurk task in AC. Audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the speaker's mouth.

Mindfulness and Stress Among Parents of Children with Autism Spectrum Disorder in China.

Parenting a child with autism spectrum disorder (ASD) can be tremendously challenging. It is important to identify factors associated with parenting stress. This study examined the indirect effect of parental dispositional mindfulness on their anxiety and depressive symptoms and family quality of life (FQOL) through mindful parenting and then parenting stress. Seventy-nine Chinese parents (24.1% fathers) of children with ASD aged 3-13 years completed self-report questionnaires. Results indicated that higher dispositional mindfulness was associated with higher mindful parenting, which was related to lower parenting stress, and further related to lower anxiety and depressive symptoms and higher FQOL. The findings provide valuable insight into the potential pathways through which general mindfulness and mindful parenting may positively impact parental outcomes.

Early development of social attention in toddlers at high familial risk for autism spectrum disorder.

The present study explored the early development of social attention of toddlers at high familial risk (HR) for autism spectrum disorder (ASD). Eighteen HR toddlers and twenty-two toddlers at low familial risk for ASD (LR) between 11 and 24 months were asked to watch paired social and non-social videos. We found that: (1) the initial social preference in HR group decreased with age, but not in LR group; (2) both groups showed significant social habituation across trials, but HR group habituated slightly slower as age increased. These findings suggest that atypical social attention could be an early characteristic of toddlers at high familial risk for ASD.

Investigating intra-individual variability of face scanning in autistic children.

LAY ABSTRACT: Atypical face scanning is suggested to be related to social interactions and communicative deficits in autistic children. We systematically examined whether autistic and non-autistic children used consistent scanning patterns when performing different tasks and scanning different types of faces. We found that autistic children scanned faces more variably than non-autistic children: While non-autistic children used more consistent scanning patterns, autistic children's scanning patterns changed frequently when watching different faces. Autistic children's variable face scanning patterns might delay and impair face processing, resulting in a social interaction deficit. What's more, variable scanning patterns may create an unstable and unpredictable perception of the environment for autistic children. Developing in such an unstable environment might motivate autistic children to retract from the environment, avoid social interaction, and focus instead on the performance of repetitive behavior. Therefore, studying face scanning variability might represent a new avenue for understanding core symptoms in autistic people.

Vigilance or avoidance: How do autistic traits and social anxiety modulate attention to the eyes?

Introduction: Social anxiety disorder (SAD) and autism spectrum disorder (ASD) are highly overlapping in symptoms and have a high rate of comorbidity, posing challenges in diagnosis and intervention for both disorders. Both disorders are linked to abnormal attention to the eyes, yet how they interactively modulate the attentional process to the eyes remains unclear. Methods: In this study, we explored how autistic traits and social anxiety in college students separately and together affected different temporal stages of attention to the eyes. Participants were instructed to view virtual faces for 10 s and make an emotional judgment, while their eye movements were recorded. Results: We found that social anxiety and autistic traits affected different temporal stages of eye-looking. Social anxiety only affected the first fixation duration on the eyes, while autistic traits were associated with eye avoidance at several time points in the later stage. More importantly, we found an interactive effect of autistic traits and social anxiety on the initial attention to the eyes: Among people scoring high on autistic traits, social anxiety was related to an early avoidance of the eyes as well as attention maintenance once fixated on the eyes. Discussion: Our study suggests the separate and interactive roles of social anxiety and autistic traits in attention to the eyes. It contributes to a deeper understanding of the mechanisms of social attention in both SAD and ASD and highlights the application of psychiatric diagnoses using eye-tracking techniques.

Comparing visual preferences between autism spectrum disorder (ASD) and normal children to explore the characteristics of visual preference of ASD children by improved visual preference paradigm: a case-control study.

BACKGROUND: One of features of Visual preference in autism spectrum disorder (ASD) is that they tend to social stimuli to nonsocial stimuli. Though it has been studied widely, until now the results are still not consistent. One of the most important reasons may be that the stimuli of the past visual preference paradigm have different movement patterns. Therefore, the present study aimed to improve the visual preference paradigm to reduce the bias caused by different movement of stimuli and explore the features of visual preference of ASD further. METHODS: Two hundred and seven children who met DSM-5 criteria for ASD and 125 typically developmental (TD) children were enrolled. They were matched in age and gender. Visual preference was measured by eye tracking technology. The subjects presented simultaneously with dynamic object images (DOI) and dynamic social images (DSI) with the same type and same speed of repetitive movement. Social interaction deficits of ASD were assessed by parents with Aberrant Behavior Checklist (ABC). RESULTS: Compared with TD children, the following findings were noted: (I) children with ASD paid less attention to social stimuli and more attention to nonsocial stimuli (t=6.417, P<0.001). (II) Increased preference to DSI was positively correlated with age (R=0.23, P=0.001). (III) No association was noted between visual preference and IQ in children with ASD (R=0.081, P=0.435). (IV) Reduced preference to DSI was negatively correlated with the severity of social interaction impairment rated by parents with ABC in children with ASD (R=0.237, P=0.010). CONCLUSIONS: Children with ASD exhibited abnormal visual preference for social and nonsocial stimuli.

Face-viewing patterns predict audiovisual speech integration in autistic children.

Autistic children show audiovisual speech integration deficits, though the underlying mechanisms remain unclear. The present study examined how audiovisual speech integration deficits in autistic children could be affected by their looking patterns. We measured audiovisual speech integration in 26 autistic children and 26 typically developing (TD) children (4- to 7-year-old) employing the McGurk task (a videotaped speaker uttering phonemes with her eyes open or closed) and tracked their eye movements. We found that, compared with TD children, autistic children showed weaker audiovisual speech integration (i.e., the McGurk effect) in the open-eyes condition and similar audiovisual speech integration in the closed-eyes condition. Autistic children viewed the speaker's mouth less in non-McGurk trials than in McGurk trials in both conditions. Importantly, autistic children's weaker audiovisual speech integration could be predicted by their reduced mouth-looking time. The present study indicated that atypical face-viewing patterns could serve as one of the cognitive mechanisms of audiovisual speech integration deficits in autistic children. LAY SUMMARY: McGurk effect occurs when the visual part of a phoneme (e.g., "ga") and the auditory part of another phoneme (e.g., "ba") uttered by a speaker were integrated into a fused perception (e.g., "da"). The present study examined how McGurk effect in autistic children could be affected by their looking patterns for the speaker's face. We found that less looking time for the speaker's mouth in autistic children could predict weaker McGurk effect. As McGurk effect manifests audiovisual speech integration, our findings imply that we could improve audiovisual speech integration in autistic children by directing them to look at the speaker's mouth in future intervention.

Circumscribed Interest Modulates Attention to Eyes in Boys With and Without Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) exhibit abnormal visual attention, such as diminished attention to eyes and enhanced attention to high-autism-interest objects. We tested whether high-autism-interest objects would modulate the attention to eyes in boys with ASD and typically developing (TD) boys. Twenty-two ASD and 22 TD children were presented simultaneously with human eyes and high/low-autism-interest objects (HAI/LAI) while their eye movements were recorded. We found that visual preference for eyes was influenced by competing objects in children with and without ASD. Specifically, both children with and without ASD showed reduced overall and first looking preference when eyes were paired with HAI objects relative to LAI objects. Children with ASD also showed reduced sustained viewing preference to the eyes after first looking at the eyes and late looking preference to the eyes after first looking at the objects in the HAI condition than the LAI condition, but these effects were absent in the TD group. Our study not only helps us understand some factors that impact attention to eyes, but also has implications for interventions aiming at improving eye contact in children with ASD.

Neural substrates of propranolol-induced impairments in the reconsolidation of nicotine-associated memories in smokers.

The majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).

Social synchronization during joint attention in children with autism spectrum disorder.

We explored the social synchronization of gaze-shift behaviors when responding to joint attention in children with autism spectrum disorder (ASD). Forty-one children aged 5 to 8 with ASD and 43 typically developing (TD) children watched a video to complete the response to joint attention (RJA) tasks, during which their gaze data were collected. The synchronization of gaze-shift behaviors between children and the female model in the video was measured with the cross-recurrence quantification analysis (CRQA). Ultimately, we discovered that children with ASD had the ability to synchronize their gaze shifts with the female model in the video during RJA tasks. Compared to the TD children, they displayed lower levels of synchronization and longer latency in this synchronized behavior. These findings provide a new avenue to deepen our understanding of the impairments of social interaction in children with ASD. Notably, the analytic method can be further applied to explore the social synchronization of numerous other social interactive behaviors in ASD. LAY SUMMARY: This study explored how autistic children synchronized their gazed shifts with others' gaze cues during joint attention. We found that compared to typical children, autistic children synchronized their gazed shifts less and needed more time to follow others' gaze. These findings provide a new avenue to deepen our understanding of the impairments of social interaction in children with ASD.

Automatic classification of children with autism spectrum disorder by using a computerized visual-orienting task.

Early screening and diagnosis of autism spectrum disorder (ASD) primarily rely on behavioral observations by qualified clinicians whose decision process can benefit from the combination of machine learning algorithms and sensor data. We designed a computerized visual-orienting task with gaze-related or non-gaze-related directional cues, which triggered participants' gaze-following behavior. Based on their eye-movement data registered by an eye tracker, we applied the machine learning algorithms to classify high-functioning children with ASD (HFA), low-functioning children with ASD (LFA), and typically developing children (TD). We found that TD children had higher success rates in obtaining rewards than HFA children, and HFA children had higher rates than LFA children. Based on raw eye-tracking data, our machine learning algorithm could classify the three groups with an accuracy of 81.1% and relatively high sensitivity and specificity. Classification became worse if only data from the gaze or nongaze conditions were used, suggesting that "less-social" directional cues also carry useful information for distinguishing these groups. Our findings not only provide insights about visual-orienting deficits among children with ASD but also demonstrate the promise of combining classical behavioral paradigms with machine learning algorithms for aiding the screening for individuals with ASD.

Characteristics of Multimodal Brain Connectomics in Patients With Schizophrenia and the Unaffected First-Degree Relatives.

OBJECTIVE: Increasing pieces of evidence suggest that abnormal brain connectivity plays an important role in the pathophysiology of schizophrenia. As an essential strategy in psychiatric neuroscience, the research of brain connectivity-based neuroimaging biomarkers has gained increasing attention. Most of previous studies focused on a single modality of the brain connectomics. Multimodal evidence will not only depict the full profile of the brain abnormalities of patients but also contribute to our understanding of the neurobiological mechanisms of this disease. METHODS: In the current study, 99 schizophrenia patients, 69 sex- and education-matched healthy controls, and 42 unaffected first-degree relatives of patients were recruited and scanned. The brain was parcellated into 246 regions and multimodal network analyses were used to construct brain connectivity networks for each participant. RESULTS: Using the brain connectomics from three modalities as the features, the multi-kernel support vector machine method yielded high discrimination accuracies for schizophrenia patients (94.86%) and for the first-degree relatives (95.33%) from healthy controls. Using an independent sample (49 patients and 122 healthy controls), we tested the model and achieved a classification accuracy of 64.57%. The convergent pattern within the basal ganglia and thalamus-cortex circuit exhibited high discriminative power during classification. Furthermore, substantial overlaps of the brain connectivity abnormality between patients and the unaffected first-degree relatives were observed compared to healthy controls. CONCLUSION: The current findings demonstrate that decreased functional communications between the basal ganglia, thalamus, and the prefrontal cortex could serve as biomarkers and endophenotypes for schizophrenia.

Truthful but Misleading: Advanced Linguistic Strategies for Lying Among Children.

We explored whether children could apply linguistic strategies for lying, i.e., manipulating linguistic content of speech to mislead others. We announced a knowledge-test entailing prizes in the classrooms of a primary school and a middle school. Altogether 79 Chinese children (6-18 years) voluntarily participated in the test: listening to a series of animal sounds before guessing the names of the animals. Meanwhile, behind the participants, a video was playing images that ostensibly corresponded to the sounds being played. In fact, this was not necessarily the case, i.e., some items cannot be solved because the sounds played are not from any animal but machine-synthesized. Participants were instructed not to look back at the video. However, 51 children peeked at the video for the unsolvable items, although the peeking behavior decreased with age. Moreover, when explaining how they correctly guessed the unsolvable items, children as young as 6 years old were able to apply a linguistic strategy (i.e., "capability attribution") for lying. Besides "capability attribution," Children also applied "fortune attribution" and "topic shift" for lying. Finally, "fortune attribution" and "topic shift" increased with age. Therefore, educators need to be aware that children are able to apply verbal strategies for lying that could involve truthful statements (i.e., "topic shift") or statements that are difficult to be proved as untruthful (i.e., "fortune attribution").

Effect of ADRA2A gene polymorphisms on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women with cesarean section.

It is well known that differences in drug reactions among individuals are widespread, and therefore the study of genetic polymorphisms of drug targets has become a research hotspot. Dexmedetomidine is clinically effective by acting on α2 adrenergic receptor and the impact of the adrenoceptor α2A gene (ADRA2A) polymorphisms on the anesthetic and analgesic effects of dexmedetomidine is related to the clinical application of dexmedetomidine. The present study aimed to analyze the effects of the rs1800035, rs201376588 and rs775887911 locus single-nucleotide polymorphisms of the ADRA2A on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women. A total of 434 Chinese women undergoing cesarean section were enrolled in this study. A 3-ml fasting venous blood sample was collected from all subjects for genomic DNA extraction and genotype detection. The pre-anesthetic and post-anesthetic pain threshold (PTh), pain tolerance threshold (PTTh), mean arterial pressure, heart rate, blood oxygen saturation, cortisol (Cor) content, blood glucose (Glu) content, opioid usage, patient-controlled analgesia pressing times, surgical satisfaction and postoperative adverse reactions were recorded. The visual analogue scale (VAS) and Ramsay sedation score were evaluated. PTh and PTTh in the wild-type women were higher than those in the women with mutations (P<0.05). The postoperative VAS scores of wild-type women were lower than those of mutants (P<0.05). The Ramsay sedation scores of wild-type patients at 12 h after the operation were significantly higher than in those with mutations (P<0.05). The levels of Cor and Glu in women with mutations were significantly higher than those of wild-type women at 12, 24 and 48 h after surgery (P<0.05). The satisfaction with surgery of wild-type patients was higher than that of patients with mutations (P<0.05). Gene mutations of rs1800035, rs201376588 and rs775887911 loci in the ADRA2A gene reduced the anesthetic and analgesic effect during and after cesarean section in Chinese Han women. Postoperative analgesia of mothers with mutations may require higher doses of analgesics.

Neural substrates of smoking and reward cue reactivity in smokers: a meta-analysis of fMRI studies.

Smoking is partly attributed to alterations of reward processing. However, findings on the neurobiological mechanisms that underlie smoking-related and smoking-unrelated reward processing in smokers have been inconsistent. Neuroimaging experiments that used functional magnetic resonance imaging (fMRI) and reported brain responses to smoking-related cues and nonsmoking reward-related cues in smokers and healthy controls as coordinates in a standard anatomic reference space were identified by searching the PubMed, Embase, and Web of Science databases up to December 2018. Three meta-analyses were performed using random-effect nonparametric statistics with Seed-based d Mapping software, with brain activity contrast from individual studies as the input. The striatum showed higher activation in response to smoking-related cues compared with neutral cues in 816 smokers from 28 studies and lower activation in response to nonsmoking reward-related cues in 275 smokers compared with 271 healthy control individuals from 13 studies. The relative reactivity of the putamen to smoking-related cues increased in 108 smokers compared with 107 healthy controls from seven studies. Meta-regression showed that smokers with a greater severity of nicotine dependence exhibited less engagement of the striatum in response to both smoking-related cues and nonsmoking reward-related cues. The present results reveal the disruption of reward system function in smokers and provide new insights into diverging theories of addiction. With the escalation of nicotine dependence, nicotine appears to exert dynamic effects on reward processing, based on incentive sensitization theory and reward deficiency syndrome theory.