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Post-traumatic stress disorder is characterized by exaggerated threat response, and theoretical accounts to date have focused on impaired threat processing and dysregulated prefrontal-cortex-amygdala circuitry. Nevertheless, evidence is accruing for broad, threat-neutral sensory hyperactivity in post-traumatic stress disorder. As low-level, sensory processing impacts higher-order operations, such sensory anomalies can contribute to widespread dysfunctions, presenting an additional aetiological mechanism for post-traumatic stress disorder. To elucidate a sensory pathology of post-traumatic stress disorder, we examined intrinsic visual cortical activity (based on posterior alpha oscillations) and bottom-up sensory-driven causal connectivity (Granger causality in the alpha band) during a resting state (eyes open) and a passive, serial picture viewing state. Compared to patients with generalized anxiety disorder (n = 24) and healthy control subjects (n = 20), patients with post-traumatic stress disorder (n = 25) demonstrated intrinsic sensory hyperactivity (suppressed posterior alpha power, source-localized to the visual cortex-cuneus and precuneus) and bottom-up inhibition deficits (reduced posterior→frontal Granger causality). As sensory input increased from resting to passive picture viewing, patients with post-traumatic stress disorder failed to demonstrate alpha adaptation, highlighting a rigid, set mode of sensory hyperactivity. Interestingly, patients with post-traumatic stress disorder also showed heightened frontal processing (augmented frontal gamma power, source-localized to the superior frontal gyrus and dorsal cingulate cortex), accompanied by attenuated top-down inhibition (reduced frontal→posterior causality). Importantly, not only did suppressed alpha power and bottom-up causality correlate with heightened frontal gamma power, they also correlated with increased severity of sensory and executive dysfunctions (i.e. hypervigilance and impulse control deficits, respectively). Therefore, sensory aberrations help construct a vicious cycle in post-traumatic stress disorder that is in action even at rest, implicating dysregulated triangular sensory-prefrontal-cortex-amygdala circuitry: intrinsic sensory hyperactivity and disinhibition give rise to frontal overload and disrupt executive control, fuelling and perpetuating post-traumatic stress disorder symptoms. Absent in generalized anxiety disorder, these aberrations highlight a unique sensory pathology of post-traumatic stress disorder (ruling out effects merely reflecting anxious hyperarousal), motivating new interventions targeting sensory processing and the sensory brain in these patients.

Growing evidence of transcranial alternating current stimulation (tACS) modulating intrinsic neural oscillations has spawned interest in applying tACS to treat psychiatric disorders associated with aberrant neural oscillations. The alpha rhythmic activity is known to dominate neural oscillations at the awake, restful state, while attenuated resting-state alpha activity has been implicated in anxious mood. Administering repeated alpha-frequency tACS (-tACS; at individual peak alpha frequency; 8–12 Hz) over four consecutive days (in the experiment group, sham stimulation in the control group), we demonstrated immediate and lasting (>24 h) increases in resting-state posterior ➔frontal connectivity in the alpha frequency, quantified by Granger causality. Critically, this connectivity enhancement was accompanied by sustained reductions in both anxious arousal and negative perception of sensory stimuli. Resting-state alpha power also increased, albeit only transiently, reversing to the baseline level within 24 h after tACS. Therefore, the lasting enhancement of long-range alpha connectivity due to -tACS differs from local alpha activity that is nonetheless conserved, highlighting the adaptability of alpha oscillatory networks. In light of increasing recognition of large-scale network dysfunctions as a transdiagnostic pathophysiology of psychiatric disorders, this enduring connectivity plasticity, along with the behavioral improvements, paves the way for tACS applications in clinical interventions of psychiatric ‘oscillopathies’.

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain’s functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous electroencephalography and functional MRI (EEG-fMRI), we demonstrated that α-tACS (versus Sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can up-regulate the DMN further highlights an effective noninvasive intervention to normalize DMN functioning in various disorders.

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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.

Distress intolerance (DI), a trait-like individual difference reflective of the inability to endure aversive affective states, is relevant to multiple forms of psychopathology, but its relations to theoretically relevant neurobiological systems have received little attention. Altered cognitive control-related neurobiology has been theorized to underlie individual differences in DI, but little empirical work has been conducted. To test this hypothesis, baseline data from a large community sample with elevated high levels of emotional psychopathology and comorbidity was utilized (N = 256). Participants completed a complex go/no-go task while EEG was recorded, and P2, N2, and P3 amplitudes were measured. Based upon prior findings on the relations between these components and response inhibition, a core cognitive control function, we hypothesized that DI would predict reduced no-go N2 and P3 amplitude while controlling for current anxious/depressive symptom severity (i.e., negative affect). Peak amplitudes from the raw data and principal components analysis were used to quantify amplitude of ERP components. Partially consistent with predictions, high DI was independently associated with reduced no-go N2 peak amplitude in the raw ERP data, and was significantly related to a frontal positivity factor in the N2 time window across no-go and go trials. Contrary to predictions, no relations between DI and the P3 were found. Overall, results support the theorized relevance of cognitive control-linked neurobiology to individual differences in tolerance of distress over and above distress severity itself, and suggest specific relations between DI and alterations in early controlled attention/conflict-monitoring but not response inhibition or response inhibition-related sequelae. (PsycINFO Database Record