Posttraumatic Stress Disorder Is Associated with α Dysrhythmia across the Visual Cortex and the Default Mode Network

Abstract

Visual-cortex-DMN alpha dysrhythmia in PTSD p. 3 3 Posttraumatic stress disorder is associated with alpha dysrhythmia across the visual cortex and the default mode network ABSTRACT Anomalies in default mode network (DMN) activity and alpha (8-12 Hz) oscillations have been independently observed in posttraumatic stress disorder (PTSD). Recent spatiotemporal analyses suggest that alpha oscillations support DMN functioning via interregional synchronization and sensory cortical inhibition. Therefore, we examined a unifying pathology of alpha deficits in the visual-cortex-DMN system in PTSD. Human patients with PTSD (N = 25) and two control groups-patients with Generalized Anxiety Disorder (GAD; N = 24) and healthy controls (HC; N = 20)-underwent a standard eyes-open resting state (S-RS) and a modified resting state (M-RS) of passively viewing salient images (known to deactivate the DMN). High-density electroencephalogram (hdEEG) were recorded, from which intracortical alpha activity (power and connectivity/Granger causality) was extracted using the exact low-resolution electromagnetic tomography (eLORETA). Patients with PTSD (vs. GAD/HC) demonstrated attenuated alpha power in the visual cortex and key hubs of the DMN (posterior cingulate cortex/PCC and medial prefrontal cortex/mPFC) at both states, the severity of which further correlated with hypervigilance symptoms. With increased visual input (at M-RS vs. S-RS), patients with PTSD further demonstrated reduced alpha-frequency directed connectivity within the DMN (PCC mPFC) and, importantly, from the visual cortex (VC) to both DMN hubs (VC PCC and VC mPFC), linking alpha deficits in the two systems. These interrelated alpha deficits align with DMN hypoactivity/hypoconnectivity, sensory disinhibition, and hypervigilance in PTSD, representing a unifying neural underpinning of these anomalies. The Visual-cortex-DMN alpha dysrhythmia in PTSD p. 4 4 identification of visual-cortex-DMN alpha dysrhythmia in PTSD further presents a novel therapeutic target, promoting network-based intervention of neural oscillations. SIGNIFICANCE STATEMENT Alpha (8-12 Hz) oscillations and the default mode network (DMN) both dominate the restingstate brain activity and are found to be closely related. In addition, aberrant alpha and DMN activities are both implicated in the pathophysiology of posttraumatic stress disorder (PTSD). Linking alpha and DMN aberrations in PTSD, our high-density EEG source analysis reveals that PTSD is associated with alpha power deficits across the DMN and visual cortex (VC) and deficient alpha-frequency connectivity from the VC to the DMN. That this visual-cortex-DMN alpha dysrhythmia further underpins hypervigilance symptoms in PTSD highlights a temporalspatial network pathology, promoting network-based neural oscillatory interventions.

Transcranial stimulation of alpha oscillations up-regulates the default mode network

“…While mounting evidence indicates the physiological coupling and functional similarity between alpha oscillations and the DMN, they have been correlational in nature ( 1 , 13 , 16 – 20 , 23 , 24 , 26 ). Our experimental manipulation of alpha oscillations via tACS lends mechanistic support for the DMN–alpha association, reinforcing the hypothesis that the intrinsic connectivity networks have an electrophysiological origin ( 4 ) and, specifically, that alpha oscillations underpin the DMN ( 15 ).…”

“…We thus extracted masks for the vPCC and dPCC subdivisions individually from the Brainnetome Atlas ( 60 ). Since these masks were not applicable for low-resolution source EEG tomography (as in eLORETA), we applied 10-mm spheres around their respective coordinates established in the literature ( 26 , 61 ). The tACS site was also included as an ROI, represented by a 10-mm sphere centered on the voxel with the maximal electric field (x, y, z = 16, −86, 36; Fig.…”

“…Of particular relevance, akin to its role in long-range neural communication, alpha oscillations are found to be the primary neural synchrony linking the posterior and anterior hubs of the DMN (the posterior cingulate cortex [PCC] and medial prefrontal cortex [mPFC], respectively) ( 15 , 19 , 21 , 22 ). Functionally, alpha oscillations and the DMN are both involved in disengaging the brain from the sensory environment and maintaining the RS ( 1 , 13 , 23 ), while alpha desynchrony and DMN dysconnectivity, including specific disruption of alpha-oscillatory PCC-mPFC connectivity, co-occur in several major neuropsychiatric disorders (e.g., Alzheimer’s disease, schizophrenia, and posttraumatic stress disorder) ( 24 – 26 ).…”

Transcranial stimulation of alpha oscillations upregulates the default mode network

“…While mounting evidence indicates the physiological coupling and functional similarity between alpha oscillations and the DMN, they have been correlational in nature (1, 12, 15-19, 22, 23, 25). Our experimental manipulation of alpha oscillations via tACS lends mechanistic support for the DMN-alpha association, reinforcing the hypothesis that the intrinsic connectivity networks have an electrophysiological origin (4) and, specifically, that alpha oscillations underpin the DMN (14).…”

“…Of particular relevance, alpha oscillations are found to be the primary neural synchrony linking the posterior and anterior hubs of the DMN (the posterior cingulate cortex/PCC and medial prefrontal cortex/mPFC, respectively) (14, 18, 20, 21). Functionally, alpha oscillations and the DMN are both involved in disengaging the brain from the sensory environment and maintaining the resting state (1, 12, 22) while alpha desynchrony and DMN dysconnectivity, including specific disruption of alpha-oscillatory PCC-mPFC connectivity, often co-occur in major neuropsychiatric disorders (23-25).…”