Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study.

Background: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Findings: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found. Interpretation: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection. Funding: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.

Impact of dietary sucralose and sucrose-sweetened water intake on lipid and glucose metabolism in male mice.

AIMS: Overconsumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of metabolic disorders, including obesity and diabetes. However, accumulating evidence also suggests the potential negative impact of consuming nonnutritive sweeteners (NNSs) on weight and glycaemic control. The metabolic effects of sucralose, the most widely used NNS, remain controversial. This study aimed to compare the impact of intake of dietary sucralose (acceptable daily intake dose, ADI dose) and sucrose-sweetened water (at the same sweetness level) on lipid and glucose metabolism in male mice. MATERIALS AND METHODS: Sucralose (0.1 mg/mL) or sucrose (60 mg/mL) was added to the drinking water of 8-week-old male C57BL/6 mice for 16 weeks, followed by oral glucose and intraperitoneal insulin tolerance tests, and measurements of bone mineral density, plasma lipids, and hormones. After the mice were sacrificed, the duodenum and ileum were used for examination of sweet taste receptors (STRs) and glucose transporters. RESULTS: A significant increase in fat mass was observed in the sucrose group of mice after 16 weeks of sweetened water drinking. Sucrose consumption also led to increased levels of plasma LDL, insulin, lipid deposition in the liver, and increased glucose intolerance in mice. Compared with the sucrose group, mice consuming sucralose showed much lower fat accumulation, hyperlipidaemia, liver steatosis, and glucose intolerance. In addition, the daily dose of sucralose only had a moderate effect on T1R2/3 in the intestine, without affecting glucose transporters and plasma insulin levels. CONCLUSION: Compared with mice consuming sucrose-sweetened water, daily drinking of sucralose within the ADI dose had a much lower impact on glucose and lipid homeostasis.

The roles of the LpSTS and DLPFC in self-prioritization: A transcranial magnetic stimulation study.

The Self-Attention Network (SAN) has been proposed to describe the underlying neural mechanism of the self-prioritization effect, yet the roles of the key nodes in the SAN-the left posterior superior temporal sulcus (LpSTS) and the dorsolateral prefrontal cortex (DLPFC)-still need to be clarified. One hundred and nine participants were randomly assigned into the LpSTS group, the DLPFC group, or the sham group. We used the transcranial magnetic stimulation (TMS) technique to selectively disrupt the functions of the corresponding targeted region, and observed its impacts on self-prioritization effect based on the difference between the performance of the self-matching task before and after the targeted stimulation. We analyzed both model-free performance measures and HDDM-based performance measures for the self-matching task. The results showed that the inhibition of LpSTS could lead to reduced performance in processing self-related stimuli, which establishes a causal role for the LpSTS in self-related processing and provide direct evidence to support the SAN framework. However, the results of the DLPFC group from HDDM analysis were distinct from the results based on response efficiency. Our investigation further the understanding of the differentiated roles of key nodes in the SAN in supporting the self-salience in information processing.

Prioritization of personally relevant stimuli in male abstinent heroin users.

The prioritization of the processing of highly relevant personal stimuli pervades various cognitive domains and is vital to our survival and normal functioning. However, the extent to which this process is altered by drug addiction remains to be elucidated. The present study examined the self-prioritization effect in abstinent heroin users (AHUs) using the perceptual matching task, which controls for the confounding effect of familiarity, and further modified it to revalidate the drug-prioritization effect (DPE). Eighty male AHUs and forty healthy control (HC) participants were recruited for this study. Participants filled in the questionnaire and completed two perceptual matching tasks. The questionnaire included demographic information (e.g., age, education) and characteristics of drug use, whereas the HC participants only completed the demographic information. AHUs exhibited a robust self-advantage in the self-perceptual matching task, and that the magnitude of the self-prioritization effect (MSPE) was comparable to that in HCs. Only AHUs prioritized the processing of drug-related stimuli in the drug-perceptual matching task, and showed similar prioritization effects during self- and drug-related processing. The MSPE and magnitude of the drug-prioritization effect (MDPE) were correlated with the heroin consumption behavior in AHUs. The process of self-prioritization is intact in drug users, and they uniquely prioritize the processing of drug cues. The similar pattern between the self- and drug-related processing provided behavioral evidence to support that drug cues are likely to be associated with heightened personal relevance in drug users. These prioritization processes may play critical roles in addiction and provide a promising route for intervention.

Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Impulse Inhibition in Abstinent Patients With Methamphetamine Addiction: A Randomized Clinical Trial.

Importance: Impulsivity during periods of abstinence is a critical symptom of patients who use methamphetamine (MA). Objective: To evaluate changes in impulse inhibition elicited by repetitive transcranial magnetic stimulation (rTMS) in patients with MA addiction. Design, Setting, and Participants: This randomized clinical trial was conducted in Da Lian Shan Addiction Rehabilitation Center, Nanjing, China, from December 1, 2018, to April 20, 2019. Effects of the intervention were examined at 3 time points: after a single session (day 1), 24 hours after 10 repeated sessions (day 11), and at 3 weeks of follow-up (day 31). Men with MA addiction and healthy male control participants were recruited for this study. Data analysis was performed from March 2019 to October 2019. Interventions: Patients who use MA were randomized to undergo sham rTMS (36 patients) and or 1-Hz rTMS (37 patients) to the left prefrontal cortex, receiving daily TMS treatments for 10 consecutive days. Main Outcomes and Measures: The primary outcome was impulse inhibition, which is primarily embodied by accuracy reduction (ie, accuracy cost) from standard to deviant trials in a 2-choice oddball task (80% standard and 20% deviant trials). Result: The study included 73 men with MA addiction (mean [SD] age, 38.49 [7.69] years) and 33 male healthy control participants without MA addiction (mean [SD] age, 35.15 [9.68] years). The mean (SD) duration of abstinence for the men with MA addiction was 9.27 (4.61) months. Compared with the control group, patients with MA addiction exhibited greater impulsivity (accuracy cost, 3.3% vs 6.2%). The single session of 1-Hz rTMS over the left prefrontal cortex significantly increased accuracy from 91.4% to 95.7% (F1,36 = 9.58; P < .001) and reaction time delay from 50 milliseconds to 77 milliseconds (F1,36 = 22.66; P < .001) in deviant trials. These effects were seen consistently after 10 sessions of 1-Hz rTMS treatment (day 11 vs day 1, t26 = 1.59; P = .12), and the behavioral improvement was maintained at least for 3 weeks after treatment (day 31 vs day 1, t26 = 0.26; P = .80). These improvement effects of impulse inhibition were coupled with a reduction in addictive symptoms as measured by cue-induced craving. The pretest accuracy cost was positively correlated with the change in impulse inhibition (r = 0.615; P < .001) and change in craving (r = 0.334; P = .01), suggesting that these 2 behaviors may be modified simultaneously. Conclusions and Relevance: These findings suggest that repeated rTMS sessions have sustained effects on impulse inhibition in patients with MA addiction and provide novel data on impulsivity management strategies for addiction rehabilitation. Trial Registration: ChiCTR-ROC-16008541.

Assessing the severity of methamphetamine use disorder beyond the subjective craving report: the role of an attention bias test.

BACKGROUND: Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA use disorder, the indicator of addiction severity is mainly limited to subjective craving score to drug-related cues, which is influenced by many factors such as social approval and self-masking. AIM: The present study investigates whether self-reported craving for drug use in response to MA cues is a reliable indicator for addiction severity in MA users, and then tests the validity of the cue-induced attention bias test in addiction severity assessment. METHODS: Fifty-two male MA users completed the cue-induced craving test and attention bias task, and were required to report clinical characteristics of addiction severity. For the attention bias test, subjects were required to discriminate the letter superimposed onto MA use-related or neutral scenes. The reaction time delay during MA-use condition relative to neutral condition was used as an index of the attention bias. RESULTS: The results showed that 24 of the 52 MA users rated non-zero in cue-induced craving test, and they showed a significant attention bias to drug-related pictures. However, the other 28 users who rated zero in cue-induced craving evaluation showed a similar attention bias to drug-related cues. In addition, the attention bias to MA use-related cues was significantly and positively correlated with the clinical indexes of addiction severity, but the relationship was absent between subjective craving evaluation and the indexes of addiction severity. CONCLUSION: These results suggest that attention bias to MA cues may be a more reliable indicator than experiential craving report, especially when subjective craving is measured in the compulsory rehabilitation centre.

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex restores attention bias to negative information in methamphetamine addicts.

Methamphetamine (hereafter, meth) addiction results in various emotional problems linked to structural impairments in the prefrontal cortex (PFC). In this paper, we investigated whether high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral PFC (DLPFC) can improve emotional attention. Thirty-one meth addicts were randomly assigned to a 10 Hz or sham rTMS group; additionally, 31 healthy participants were enrolled, who were required to respond as correctly and quickly as possible to a yellow arrow embedded in an image depicting emotional content (neutral, fear, sadness, or disgust). Results showed that the healthy participants responded more rapidly to negative compared to neutral stimuli, while meth addicts responded indiscriminately to stimuli representing disgust, fear, and neutral content. The randomization check showed no significant differences in the pretest of emotional attention measures between the 10 Hz and sham groups. However, 10 Hz rTMS yielded faster response to negative pictures than to neutral pictures, which was similar to the performance of healthy participants but Sham not. However, this attention bias effect persisted in the 10 Hz group 2 weeks later. These results demonstrate that high-frequency rTMS of the left DLPFC can improve the emotional attention of meth addicts.

Intervention Effect of Repetitive TMS on Behavioral Adjustment After Error Commission in Long-Term Methamphetamine Addicts: Evidence From a Two-Choice Oddball Task.

Behavioral adjustment plays an important role in the treatment and relapse of drug addiction. Nonetheless, few studies have examined behavioral adjustment and its plasticity following error commission in methamphetamine (METH) dependence, which is detrimental to human health. Thus, we investigated the behavioral adjustment performance following error commission in long-term METH addicts and how it varied with the application of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Twenty-nine male long-term METH addicts (for > 3 years) were randomly assigned to high-frequency (10 Hz, n = 15) or sham (n = 14) rTMS of the left DLPFC during a two-choice oddball task. Twenty-six age-matched, healthy male adults participated in the two-choice oddball task pretest to establish normal performance for comparison. The results showed that 10 Hz rTMS over the left DLPFC significantly decreased the post-error slowing effect in response times of METH addicts. In addition, the 10 Hz rTMS intervention remarkably reduced the reaction times during post-error trials but not post-correct trials. While the 10 Hz rTMS group showed a more pronounced post-error slowing effect than the healthy participants during the pretest, the post-error slowing effect in the posttest of this sample was similar to that in the healthy participants. These results suggest that high-frequency rTMS over the left DLPFC is a useful protocol for the improvement of behavioral adjustment after error commission in long-term METH addicts.