Reduced Integrity of Right Lateralized White Matter in Patients with Primary Insomnia: A Diffusion-Tensor Imaging Study

Abstract

Purpose To analyze the integrity of white matter (WM) tracts in primary insomnia patients and provide better characterization of abnormal WM integrity and its relationship with disease duration and clinical features of primary insomnia. Materials and Methods This prospective study was approved by the ethics committee of the Guangdong No. 2 Provincial People's Hospital. Tract-based spatial statistics were used to compare changes in diffusion parameters of WM tracts from 23 primary insomnia patients and 30 healthy control (HC) participants, and the accuracy of these changes in distinguishing insomnia patients from HC participants was evaluated. Voxel-wise statistics across subjects was performed by using a 5000-permutation set with family-wise error correction (family-wise error, P < .05). Multiple regressions were used to analyze the associations between the abnormal fractional anisotropy (FA) in WM with disease duration, Pittsburgh Sleep Quality Index, insomnia severity index, self-rating anxiety scale, and the self-rating depression scale in primary insomnia. Characteristics for abnormal WM were also investigated in tract-level analyses. Results Primary insomnia patients had lower FA values mainly in the right anterior limb of the internal capsule, right posterior limb of the internal capsule, right anterior corona radiata, right superior corona radiata, right superior longitudinal fasciculus, body of the corpus callosum, and right thalamus (P < .05, family-wise error correction). The receiver operating characteristic areas for the seven regions were acceptable (range, 0.60-0.74; 60%-74%). Multiple regression models showed abnormal FA values in the thalamus and body corpus callosum were associated with the disease duration, self-rating depression scale, and Pittsburgh Sleep Quality Index scores. Tract-level analysis suggested that the reduced FA values might be related to greater radial diffusivity. Conclusion This study showed that WM tracts related to regulation of sleep and wakefulness, and limbic cognitive and sensorimotor regions, are disrupted in the right brain in patients with primary insomnia. The reduced integrity of these WM tracts may be because of loss of myelination. (©) RSNA, 2016.

Resting state functional connectivity in primary insomnia, generalized anxiety disorder and controls

“…These investigators suggest that such reduced structural connectivity may represent a basis for reduced top-down control of negative emotions in GAD. Similarly, in PI, reduced FA has been reported in multiple white matter tracts, and reduced FA correlated with both PSQI and duration of PI (Li et al, 2016b). Hence GAD and PI may share disruption of axonal connectivity resulting in diminished top-down emotional regulation.…”

Increased interhemispheric resting-state functional connectivity in healthy participants with insomnia symptoms

“…[30–32] Zhu et al [21] reveal a significant increase in VMHC in the thalamus in 28 healthy participants after a total night of sleep deprivation. Li et al [18] find reduced fractional anisotropy in the thalamus, as well as negative correlation between fractional anisotropy in the thalamus and disease duration, in primary insomnia. Allen et al [33] find increased thalamic Gln plus Glu (Glx)/creatine/phosphocreatine (Cr) in patients with restless legs, which is correlated with the wake time during the sleep period.…”

“…Further, it has also been found that the gray matter density in the left inferior orbitofrontal cortex bordering the insula is negatively associated with earlier morning awakening in healthy subjects with insomnia symptoms, suggesting that the salience network may be related to the compromised ability to judge thermal comfort. [17] Using tract-based spatial statistics to analyze the integrity of white matter tracts, Li et al [18] observe that the fractional anisotropy in the thalamus and body corpus callosum is associated with the Pittsburgh Sleep Quality Index scores, supporting the notion that white matter tracts related to hyperarousal networks are affected in patients with primary insomnia. The above network abnormalities may in part be due to disruptions in the interhemispheric functional coordination communication between the bilateral cerebral hemispheres.…”

Associations between self‐reported sleep quality and white matter in community‐dwelling older adults: A prospective cohort study

“…Gene expression studies have shown that brain transcripts involved in myelin synthesis or maintenance are up‐regulated during sleep [Bellesi, ], with the proliferation of oligodendrocyte precursor cells doubling during sleep [Bellesi et al, ]. Diffusion tensor imaging (DTI) studies have documented reduced fractional anisotropy (FA) and increased radial diffusivity (RD) within fronto‐subcortical tracts in insomnia [Li et al, ; Spiegelhalder et al, ]. Although the relationship between DTI metrics is complex, a signature of reduced FA and increased RD can reflect microstructural changes associated with white matter degeneration, such as reduced axon density or reduced myelin [Zatorre et al, ].…”