• insomnia
• neuroimaging
• systematic review

Insomnia shows a worldwide prevalence which varies from 3.9% to 22.1%; this range classifies this sleep disorder as a major public health concern, which is associated with several negative outcomes both for individual patients and health care in the mental health area, also due to it several comorbidities. The development of neuroimaging techniques has permitted to investigate brain mechanisms more deeply at a structural and functional level. The present systematic review aims at shedding light on functional, structural, and metabolic substrates of insomnia disorder by integrating all the available neuroimaging studies conducted on insomnia populations meeting specific inclusion criteria. The research was made on the databases PubMed, PsycARTICLES, PsycINFO, CINAHL and Web of Science, which were searched for case-control studies comparing neuroimaging findings in insomnia patients and healthy controls. Neuroimaging investigation was conducted with the following paradigms and techniques: resting-state functional magnetic resonance imaging (rs-fMRI), fMRI, structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), nuclear magnetic resonance (NMR), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and electroencephalography-fMRI (EEG-fMRI). At least one of these methods had to be involved in the screened articles. 620 papers were screened, and 119 studies remained for the full text evaluation. One study was manually added following the author’s answer. After the checking the full-texts and writing to the authors, 51 more reports were excluded. Finally, 69 articles (3728 subjects) met inclusion criteria and were included in the review. During data extraction, nine different neuroimaging methods were identified: 29 studies used resting-state fMRI as a paradigm, and 6 of them also used structural MRI investigation; 9 studies assessed structural data with MRI and 6 studies with DTI; 11 studies used a task to detect activation in insomnia patients compared to the control group with fMRI, and one of them also did a structural investigation with MRI and DTI; 6 studies used MRS to examine area-related presence of metabolites; 4 studies used the combined technique of EEG-fMRI; 3 studies investigated brain glucose metabolism with PET; finally, 1 study used SPECT as a neuroimaging technique. A result extraction step by step as well as a risk of bias assessment using the Newcastle-Ottawa-Scale (NOS; Wells et al., 2000) were performed, highlighting some shortcomings especially in the domains of selection and comparability. A hierarchy of involved areas mentioned as a result in the current literature was made, ordering them from those mentioned most frequently to those mentioned least frequently. According to the selected cut-off, the anterior cingulate cortex appears to be the most mentioned area followed by the right precuneus, the right thalamus, the left insula, the left thalamus, the posterior cingulate cortex, the left middle frontal gyrus and the left precuneus. The right insula and the right middle frontal gyrus were also included and systematically analysed here, as they represent the contralateral component of areas mentioned a number of times above the cut-off threshold, which was arbitrarily set at seven mentions. From the qualitative results of this review, ID seems to show a major involvement of the two main networks present in the human brain, that is to say the SN and the DMN. The involvement of these networks does not only concern those that are their main nodes, but also regions that are considered to be included in these networks from a connectivity point of view. The networks impairment is therefore related to the hyperarousal perspective, as well as to the SSM feature. Further investigations are needed to try to understand if the interoceptive sensitivity, which is determined by neuro-endocrino-immunologic systems alongside by inner affective, cognitive and arousal states of the subject, may have a role in all of the disrupted mechanisms known to participate in ID.