Efficacy and safety of celecoxib monotherapy for treatment of moderate depressive symptoms following COVID-19 infection: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Celecoxib, a nonsteroidal anti-inflammatory agent, was found to be an effective add-on treatment for unipolar and bipolar depression. We investigated the potential beneficial effect of celecoxib monotherapy on depressive symptoms after Coronavirus disease (COVID-19). METHODS: This was a randomized, double-blind, placebo-controlled clinical trial investigating the therapeutic effects of celecoxib monotherapy in patients with moderate depressive symptoms following COVID-19 infection. Patients were randomized to receive either a celecoxib capsule (100 mg) twice daily or a placebo capsule twice daily for 6 weeks. Participants were assessed with the Hamilton Depression Rating Scale (HDRS) and the side effect checklist at baseline and weeks 3 and 6. RESULTS: A total of 62 patients were included. GLM repeated-measures showed a significant effect of time × treatment (F = 12.95, df = 1.98, p < 0.001) for celecoxib, suggesting superior improvement of depressive symptoms in celecoxib compared to placebo from baseline to the study endpoint. HDRS scores in the celecoxib group showed a greater decline from baseline to both week 3 (t = 4.12, p < 0.001, Cohen's d = 1.10) and week 6 (t = 4.76, p < 0.001, Cohen's d = 1.27), compared to the placebo group. Rate of response to treatment (70% vs 9%, p < 0.001) and remission (67% vs 0%, p < 0.001) was significantly higher in celecoxib compared to the placebo group at week 6. Adverse event frequencies were not significantly different between the two groups. CONCLUSION: We demonstrated that treatment with celecoxib significantly improved depression scores of patients with depressive symptoms following COVID-19 infection. Further trials with larger sample sizes and longer study periods should assess our findings before any suggestion for clinical use. The trial was prospectively registered at the Iranian registry of clinical trials (www.irct.ir; registration number: IRCT20090117001556N142).

Resting-state functional magnetic resonance imaging alterations in borderline personality disorder: A systematic review.

BACKGROUND: Borderline personality disorder (BPD) is a severe psychiatric disorder characterized by emotion dysregulation, impulsivity, and interpersonal disturbances. Several structural and functional neuroimaging abnormalities have been described in BPD. In particular, resting-state functional magnetic resonance imaging (rs-fMRI) studies have recently suggested various connectivity alterations within and between large-scale brain networks in BPD. This review aimed at providing an updated summary of the evidence reported by the available rs-fMRI studies in BPD individuals. METHODS: A search on PubMed, Scopus, and Web of Science was performed to identify rs-fMRI alterations in BPD. A total of 15 studies met our inclusion criteria. RESULTS: Overall, aberrant resting-state functional connectivity (rs-FC) within and between default mode network (DMN), salience network (SN), and central executive network (CEN) were observed in BPD compared to healthy controls, as well as selective functional impairments in bilateral amygdala, anterior and posterior cingulate cortex, hippocampus, and prefrontal cortex. LIMITATIONS: The observational design, small sample size, prevalence of females, high rates of concurrent comorbidities and medications, and heterogeneity across imaging methodologies limit the generalizability of the results. CONCLUSIONS: The identification of altered patterns of rs-FC within and between selective brain networks, including DMN, SN, and CEN, could further our knowledge of the clinical symptoms of BPD, and therefore, future studies with multimodal methodologies and longitudinal designs are warranted to further explore the neural correlates of this disorder.

Machine learning applied to functional magnetic resonance imaging in anxiety disorders.

BACKGROUND: Brain functional abnormalities have been commonly reported in anxiety disorders, including generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, and specific phobias. The role of functional abnormalities in the discrimination of these disorders can be tested with machine learning (ML) techniques. Here, we aim to provide a comprehensive overview of ML studies exploring the potential discriminating role of functional brain alterations identified by functional magnetic resonance imaging (fMRI) in anxiety disorders. METHODS: We conducted a search on PubMed, Web of Science, and Scopus of ML investigations using fMRI as features in patients with anxiety disorders. A total of 12 studies (resting-state fMRI n = 5, task-based fMRI n = 6, resting-state and task-based fMRI n=1) met our inclusion criteria. RESULTS: Overall, the studies showed that, regardless of the classifiers, alterations in functional connectivity and aberrant neural activation involving the amygdala, anterior cingulate cortex, hippocampus, insula, orbitofrontal cortex, temporal pole, cerebellum, default mode network, dorsal attention network, sensory network, and affective network were able to discriminate patients with anxiety from controls, with accuracies spanning from 36 % to 94 %. LIMITATIONS: The small sample size, different ML approaches and heterogeneity in the selection of regions included in the multivariate pattern analyses limit the conclusions of the present review. CONCLUSIONS: ML methods using fMRI as features can distinguish patients with anxiety disorders from healthy controls, indicating that these techniques could be used as a helpful tool for the diagnosis and the development of more targeted treatments for these disorders.

Central nervous system microstructural alterations in Type 1 diabetes mellitus: A systematic review of diffusion Tensor imaging studies.

AIMS: Type 1 diabetes mellitus (T1DM) is a chronic childhood disease with potentially persistent CNS disruptions. In this study, we aimed to systematically review diffusion tensor imaging studies in patients with T1DM to understand the microstructural effects of this entity on individuals' brains METHODS: We performed a systematic search and reviewed the studies to include the DTI studies in individuals with T1DM. The data for the relevant studies were extracted and a qualitative synthesis was performed. RESULTS: A total of 19 studies were included, most of which showed reduced FA widespread in optic radiation, corona radiate, and corpus callosum, as well as other frontal, parietal, and temporal regions in the adult population, while most of the studies in the juvenile patients showed non-significant differences or a non-persistent pattern of changes. Also, reduced AD and MD in individuals with T1DM compared to controls and non-significant differences in RD were noted in the majority of studies. Microstructural alterations were associated with clinical profile, including age, hyperglycemia, diabetic ketoacidosis and cognitive performance. CONCLUSION: T1DM is associated with microstructural brain alterations including reduced FA, MD, and AD in widespread brain regions, especially in association with glycemic fluctuations and in adult age.

Trail Making Test Could Predict Impairment in Cognitive Domains in Patients with Multiple Sclerosis: A Study of Diagnostic Accuracy.

OBJECTIVE: Cognitive impairment (CI) and executive dysfunction (ED) are prevalent in patients with multiple sclerosis (PwMS). The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is the gold standard neuropsychological battery (NPB) for detecting CI. Delis-Kaplan Executive Function System (DKEFS) NPB evaluates ED. We aimed to find practical test(s) from DKEFS with acceptable diagnostic utility for early detection of impairment in cognitive and executive domains. METHODS: Cognitive and executive tasks, physical disability, and depression scores of 30 PwMS were assessed (17 women, age: 38.1). Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Controlled Oral Word Association Test (COWAT) from MACFIMS and Trail Making Test (TMT), Design Fluency Test (DFT), and Verbal Fluency Test (VFT) from DKEFS were selected. The association between patients' characteristics and performance in tests, and diagnostic accuracy of DKEFS tests in detecting impairment in cognitive tasks were evaluated, using Pearson correlation and receiver operator characteristic curve analyses, respectively. RESULTS: A significant correlation was found between disease duration and SDMT and TMT subtests. Expanded Disability Status Scale was significantly related to SDMT, VFT-switching, and TMT subtests. Beck Depression Inventory was significantly related to DFT. TMT-switching detected abnormalities in SDMT and PASAT with 100% sensitivity, 93.3% (for SDMT), and 85.7% specificity (for PASAT). TMT-letter showed 100% sensitivity and 90% specificity in identifying abnormalities in COWAT. CONCLUSIONS: TMT, particularly the switching condition, is a practical paper-based test that could predict impairment in cognitive tasks. Clinicians may use TMT as a screening tool among PwMS.

Efficacy of Spironolactone as an Adjunctive Therapy to Risperidone to Improve Symptoms of Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled, Clinical Trial.

Objective: Spironolactone (C24H32O4S), a potent mineralocorticoid receptor (MR) inhibitor, is a potassium-sparing diuretic that is traditionally used to treat fluid build-up in the body or for its anti-androgenic properties. This study is a double-blind, placebo-controlled, randomized clinical trial assessing the beneficial effects of spironolactone in addition to risperidone in improving negative symptoms of schizophrenia. Method: 40 patients with chronic schizophrenia, aged 18-60 years, were assigned to two groups: risperidone + spironolactone or risperidone + placebo. Risperidone was administered to both the spironolactone and placebo groups with a dose up to 6 mg/day throughout the trial. Spironolactone (C24H32O4S) was ordered 100 mg/day for the full 8-week course of the study. Patients were rated on the Positive and Negative Syndrome Scale (PANSS) at four time points: baseline, weeks two, four, and eight. The PANSS negative subscale score was the main objective. Results: PANSS negative, positive, and total scores showed significantly greater improvements in the spironolactone relative to the placebo group from baseline to the trial endpoint (P (Cohen's d): 0.004 (0.96), 0.007 (0.90), and 0.042 (0.66), respectively). Similarly, ANOVA also presented significant time × treatment interaction effect for spironolactone on PANSS negative (F = 9.04; ηp2 = 0.19; df = 1.38; P = 0.002), positive (F = 3.43; ηp2 = 0.08; df = 2.72; P = 0.023), and total (F = 3.94; ηp2 = 0.09; df = 2.05; P = 0.022) scores. However, spironolactone did not cause significant decrease in the general psychiatric pathology score of PANSS. Conclusion: Our findings suggest the efficacy and safety of spironolactone as an adjunctive therapy to risperidone in improving the symptoms of schizophrenia.

Risperidone combination therapy with adalimumab for treatment of chronic schizophrenia: a randomized, double-blind, placebo-controlled clinical trial.

This study aimed to investigate the efficacy and safety of antitumor necrosis factor-alpha (TNF-α) therapy using adalimumab in patients with chronic schizophrenia. This is a randomized, double-blind, placebo-controlled clinical trial carried out at Roozbeh Hospital (Tehran, Iran) from June 2020 to October 2021. The patients were randomly divided into two parallel adalimumab + risperidone and placebo + risperidone groups. Participants in the intervention group received adalimumab subcutaneous injection (40 mg) by pen-injector at weeks 0 and 4. Using the Positive and Negative Symptoms Scale (PANSS), patients' positive and negative symptoms were assessed at weeks 0, 4, and 8. Forty patients (20 in each group) were included. PANSS total (t = 4.43, df = 38, P < 0.001), negative (t = 2.88, df = 38, P = 0.006), and general psychopathology (t = 4.06, df = 38, P < 0.001) scores demonstrated a significantly greater decline in adalimumab compared with the placebo group from baseline study endpoint. However, improvement of PANSS positive subscale scores showed no significant difference from the baseline study endpoint. There was no significant between-group difference regarding levels of C-reactive protein, interleukin (IL)-1ß, TNF-α, IL-6, and IL-8 at baseline and also at the week 8 visit (P > 0.05 for all). The current study found adalimumab adjunctive therapy effective in treating schizophrenia, particularly its negative and general psychopathology symptoms, with no side effects.

Psychometric evaluation of Persian version of Seizure Severity Questionnaire.

BACKGROUND AND PURPOSE: Seizure severity has been increasingly gaining attention as a complementary assessment to seizure frequency for the measurement of treatment responses. This study aimed to assess the reliability and external validity and of the Persian version of the Seizure Severity Questionnaire (SSQ). METHODS: The study sample was recruited from 126 patients with epilepsy who attended the neurology outpatient clinic at Imam Khomeini and Roozbeh hospitals, Tehran, Iran. The Forward-Backward technique was applied to translate the questionnaire. The reliability of SSQ was assessed by Cronbach's alpha coefficient. The external validity of SSQ was assessed by correlating SSQ scores with Quality of Life in Epilepsy Inventory-31 (QOLIE-31) subscales. RESULTS: The sample comprised 63 women (50%) and 63 men (50%) aged 13-76 years. The mean scores of SSQ items ranged from 3.46 to 5.48. Distribution was skewed for all component scores, with a tendency for the item scores to concentrate toward the highest scores. Reliability for almost all domains were moderate to good, with Cronbach's alpha ranging from 0.615 to 0.770. Component B to D and total score of SSQ had weak-to-moderate inverse correlation with QOLIE-31 subscale scores. However, the result showed no significant correlation with age, sex, or education. CONCLUSION: With some limitations, the Persian version of the SSQ shows relatively good reliability and content validity, supporting its use as a specific measure of seizure severity in epilepsy in Iran.

A systematic review of resting-state and task-based fmri in juvenile myoclonic epilepsy.

Functional neuroimaging modalities have enhanced our understanding of juvenile myoclonic epilepsy (JME) underlying neural mechanisms. Due to its non-invasive, sensitive and analytical nature, functional magnetic resonance imaging (fMRI) provides valuable insights into relevant functional brain networks and their segregation and integration properties. We systematically reviewed the contribution of resting-state and task-based fMRI to the current understanding of the pathophysiology and the patterns of seizure propagation in JME Altogether, despite some discrepancies, functional findings suggest that corticothalamo-striato-cerebellar network along with default-mode network and salience network are the most affected networks in patients with JME. However, further studies are required to investigate the association between JME's main deficiencies, e.g., motor and cognitive deficiencies and fMRI findings. Moreover, simultaneous electroencephalography-fMRI (EEG-fMRI) studies indicate that alterations of these networks play a role in seizure modulation but fall short of identifying a causal relationship between altered functional properties and seizure propagation. This review highlights the complex pathophysiology of JME, which necessitates the design of more personalized diagnostic and therapeutic strategies in this group.

Effect of parental depressive symptoms on offspring's brain structure and function: A systematic review of neuroimaging studies.

Perinatal Depression (PND) is a severe mental disorder that appears during pregnancy or in the post-partum. Although PND has been associated with behavioral problems in the offspring, its effects on brain development are unclear. With this review we aimed at summarizing the existing literature on the effects of perinatal depressive symptoms on children's brains. A search on PubMed and Embase of structural, functional Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) studies exploring the effect of PND on offspring's brain was conducted. We selected twenty-six studies, ten structural MRI, five DTI, six fMRI and five with combined techniques. Overall, the studies showed: a) gray matter alterations in amygdala and fronto-temporal lobes; b) microstructural alterations in amygdala, frontal lobe, cingulum, longitudinal fasciculus and fornix; and c) functional alterations between limbic and mesocortical networks. The small sample size and the heterogeneity in populations and methodologies limit this review. In conclusion, PND seems to influence structure and function of offspring, that may contribute to the risk of behavioral disturbances later in life.

Brain microstructural abnormalities in 22q11.2 deletion syndrome: A systematic review of diffusion tensor imaging studies.

22q11.2 deletion syndrome (22q11DS) is a severe genetic syndrome characterized by cognitive deficits and neuropsychiatric disorders, particularly schizophrenia. Neuroimaging alterations have been extensively reported in 22q11DS, both in gray and white matter structures. However, a considerable variability among the results affects the generalizability of the findings to date. Herein, we reviewed diffusion tensor imaging (DTI) findings in 22q11DS, their association with psychosis and cognition, and the implications of DTI studies on neurodevelopment in 22q11DS. We also investigated differences between 22q11DS and schizophrenic patients without 22q11DS. Using an online search of PubMed and Embase, we identified studies investigating DTI findings in 22q11DS. After selecting eligible studies in accordance with the preferred reporting items for systematic reviews and meta-analyses guideline, we included thirty-one studies. Overall, 22q11DS patients show altered structural connectivity and disrupted microstructural organization of most cortical and subcortical structures and white matter tracts. Moreover, despite a significant heterogeneity in the results, reduced diffusivity measures and elevated fractional anisotropy were observed. However controversial, compared to typically developing children, 22q11DS patients reached the peak of fractional anisotropy (FA) and the trough of radial diffusivity (RD) at an older age, which shows neurodevelopmental delay. DTI measures were also associated with psychotic symptoms and cognitive deficits. In conclusion, this study provides a comprehensive review of microstructural alterations in 22q11DS. Future larger investigations on this syndrome could potentially lead to the detection of early diagnostic imaging markers for genetically induced schizophrenia, thus improving the treatment and, ultimately, the outcome.

Cognitive Impairment in Opium Use Disorder.

This cross-sectional study is aimed at assessing the effects of opium use disorder (OUD) on attention, working memory, and information-processing speed. Thirty outpatients with OUD and 20 healthy controls (HCs) were assessed using a neuropsychological battery consisted of Auditory Verbal Learning Test-Revised (AVLT-R), Brief Visuospatial Memory Test-Revised (BVMT-R), Digit Forward and Backward Tests (DFT and DBT), and WAIS-R Digit Symbol Substitution Test (DSST). The most affected cognitive functions in patients with OUD were detected by DBT and DSST. However, we found no significant difference between patients according to the route of administration. Within patients with OUD, DBT score was associated with opium use quantity (OUQ) (r = -0.385), and DBT (r = 0.483) and DSST (r = 0.542) scores were correlated with duration of use. Our findings indicated that working memory and information-processing speed are the most affected domains of cognitive functioning. DBT and DSST could be used as brief assessments in clinical settings to screen for cognitive deficits in patients with OUD.

Sex Differences are Reflected in Microstructural White Matter Alterations of Musical Sophistication: A Diffusion MRI Study.

Background: The human-specified ability to engage with different kinds of music in sophisticated ways is named "Musical Sophistication." Herein, we investigated specific white matter (WM) tracts that are associated with musical sophistication and musicality in both genders, separately, using Diffusion MRI connectometry approach. We specifically aimed to explore potential sex differences regarding WM alterations correlated with musical sophistication. Methods: 123 healthy participants [70 (56.9%) were male, mean age = 36.80 ± 18.86 year], who were evaluated for musical sophistication using Goldsmiths Musical Sophistication Index (Gold-MSI) self-assessment instrument from the LEMON database, were recruited in this study. The WM correlates of two Gold-MSI subscales (active engagement and music training) were analyzed. Images were prepared and analyzed with diffusion connectometry to construct the local connectome. Multiple regression models were then fitted to address the correlation of local connectomes with Gold-MSI components with the covariates of age and handedness. Results: a significant positive correlation between WM integrity in the corpus callosum (CC), right corticospinal tract (CST), cingulum, middle cerebellar peduncle (MCP), bilateral parieto-pontine tract, bilateral cerebellum, and left arcuate fasciculus (AF) and both active engagement [false discovery rate (FDR) = 0.008] and music training (FDR = 0.057) was detected in males. However, WM integrity in the body of CC, MCP, and cerebellum in females showed an inverse association with active engagement (FDR = 0.046) and music training (FDR = 0.032). Conclusion: WM microstructures with functional connection with motor and somatosensory areas (CST, cortico-pontine tracts, CC, cerebellum, cingulum, and MCP) and language processing area (AF) have significant correlation with music engagement and training. Our findings show that these associations are different between males and females, which could potentially account for distinctive mechanisms related to musical perception and musical abilities across genders.

Effects of Prenatal Methamphetamine Exposure on the Developing Human Brain: A Systematic Review of Neuroimaging Studies.

Methamphetamine (MA) can cross the placenta in pregnant women and cause placental abruption and developmental alterations in offspring. Previous studies have found prenatal MA exposure effects on the social and cognitive performance of children. Recent studies reported some alterations in structural and functional magnetic resonance imaging (MRI) of prenatal MA-exposed offspring. In this study, we aimed to investigate the effect of prenatal MA exposure on brain development using recently published structural, metabolic, and functional MRI studies. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and SCOPUS databases for articles that used each brain imaging modality in prenatal MA-exposed children. Seventeen studies were included in this study. We investigated brain imaging alterations using 17 articles with four different modalities, including structural MRI, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI). The participants' age range was from infancy to 15 years. Our findings demonstrated that prenatal MA exposure is associated with macrostructural, microstructural, metabolic, and functional deficits in both cortical and subcortical areas. However, the most affected regions were the striatum, frontal lobe, thalamus and the limbic system, and white matter (WM) fibers connecting these regions. The findings from our study might have valuable implications for targeted treatment of neurocognitive and behavioral deficits in children with prenatal MA exposure. Even so, our results should be interpreted cautiously due to the heterogeneity of the included studies in terms of study populations and methods of analysis.

Sex differences in microstructural white matter alterations of mathematics anxiety based on diffusion MRI connectometry.

BACKGROUND: Mathematics Anxiety (MA) is a feeling of stress, tension, and fear in situations engaging with math-related tasks. Herein, we utilized Diffusion Magnetic Resonance Imaging (DMRI) connectometry approach to tracking white matter (WM) fibers with a significant correlation with the severity of MA. METHODS: A total of 77 healthy adult participants (50 males, mean age ± SD = 26.00 ± 3.54) were included from the Leipzig Study for Mind-Body-Emotion Interactions (LEMON) database. Abbreviated Math Anxiety Scale (AMAS) questionnaire was used for assessing the participant's feelings when facing a math-related activity. DMRI data were prepared and analyzed with the connectometry approach. Multiple regression models were then carried out to examine the correlation of WM microstructural connectivity with AMAS score. RESULTS: DMRI connectometry showed a significant association between AMAS score and increased microstructural connectivity in left arcuate fasciculus (AF), the body of corpus callosum (CC), right cingulum, and left inferior longitudinal fasciculus (ILF) in male participants with moderate effect size false discovery rate (FDR = 0.040). Furthermore, DMRI connectometry in females identified a positive correlation between AMAS score and microstructural connectivity in the genu of CC, right ILF, and bilateral fornices with small-to-moderate effect size (FDR = 0.012) and a negative correlation between AMAS score and microstructural connectivity in the bilateral cingulum with small-to-moderate effect size (FDR = 0.032) Conclusion: Our findings support that structures with functional relation to language processing areas (e.g., AF) or limbic system (cingulum, CC, fornix, and ILF) play a significant role in MA. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Efficacy and safety of pentoxifylline combination therapy in major depressive disorder: a randomized, double-blind, placebo-controlled clinical trial.

In this randomized, double-blind, placebo-controlled clinical trial, we assessed the efficacy and safety of pentoxifylline combination therapy with sertraline in treatment of major depressive disorder (MDD). A total of 56 patients with MDD were assigned into two parallel groups to receive sertraline (100 mg/day) plus placebo or sertraline (100 mg/day) plus pentoxifylline (400 mg three times daily) for six weeks. Patients were evaluated with the Hamilton rating scale for depression (HAM-D) at baseline and weeks 2, 4 and 6. The sertraline plus pentoxifylline group demonstrated greater improvement in HAM-D scores from baseline to all three study time points (P = 0.013, 0.007 and 0.016 for week 2, 4 and 6, respectively). Response to treatment rate was also significantly higher in the sertraline plus pentoxifylline group compared to the sertraline plus placebo group at week 4 [57.1 vs. 21.4%, P = 0.013] and the study endpoint [96.4 vs. 57.1%, P = 0.001]. However, the remission rate, time to remission and time to treatment response did not show any significant difference between trial groups. Our findings support the efficacy and safety of pentoxifylline combination therapy in patients with MDD.

White matter microstructural abnormalities in primary insomnia: A systematic review of diffusion tensor imaging studies.

Primary insomnia (PI), the most common sleep disorder, is primarily characterized by difficulties in initiating and maintaining sleep and deficits in daytime functioning. Study of white matter (WM) connections of the brain might provide valuable information regarding the underlying neural mechanism of PI. Diffusion tensor imaging (DTI) provides non-invasive access to the microstructural and network properties of brain WM, and thus, a great opportunity to quantitatively and sensitively study the human brain. The current literature of PI does not provide a consistent explanation of the etiology and pathology of the disorder; thus, we searched PubMed, EMBASE, and SCOPUS for DTI studies that compared WM integrity or network organization between PI patients and healthy controls to integrate all existing literature as an insight for further studies, and, hopefully, effective prevention and management of the disorder. English peer-reviewed full-text publications that investigated the diffusion indices of PI patients or those with insomnia symptoms compared with a group of healthy controls were included. We included 11 studies and extracted the data for qualitative synthesis. Except for one study, all studies were rated as high-quality, based on quality assessment. In aggregation, a total of 541 patients with PI and 679 healthy controls were included in this study. Our review of DTI studies suggests that WM disruptions in PI are better characterized in the context of neural networks. Frontostriatal, frontothalamic, and corticocortiscal networks, as well as the limbic system, seem to be the main neural networks with microstructural and network alterations in patients with PI. To illustrate, different parts of corona radiate and internal capsule within the corticosubcortical networks and superior longitudinal fasciculus within the corticocortical networks showed altered microstructural properties in PI patients. In view of the fact that the findings from individual studies are heterogeneous, it is difficult to derive consistent findings from the results, and the divergence of the findings must not be disregarded. Thus, this study is a starting point for future studies, and its implications for etiology and pathogenesis of insomnia should be regarded cautiously.