Resting-state Activity Research Articles

Macroscopic resting-state brain dynamics are best described by linear models

It is typically assumed that large networks of neurons exhibit a large repertoire of nonlinear behaviours. Here we challenge this assumption by leveraging mathematical models derived from measurements of local field potentials via intracranial electroencephalography and of whole-brain blood-oxygen-level-dependent brain activity via functional magnetic resonance imaging. We used state-of-the-art linear and nonlinear families of models to describe spontaneous resting-state activity of 700 participants in the Human Connectome Project and 122 participants in the Restoring Active Memory project. We found that linear autoregressive models provide the best fit across both data types and three performance metrics: predictive power, computational complexity and the extent of the residual dynamics unexplained by the model. To explain this observation, we show that microscopic nonlinear dynamics can be counteracted or masked by four factors associated with macroscopic dynamics: averaging over space and over time, which are inherent to aggregated macroscopic brain activity, and observation noise and limited data samples, which stem from technological limitations. We therefore argue that easier-to-interpret linear models can faithfully describe macroscopic brain dynamics during resting-state conditions.

A Blood-Based Lipid Profile Associated With Hippocampal Volume and Brain Resting-State Activation Within Obese Adults from the UK Biobank.

Objectives: Obesity and dyslipidemia may be associated with hippocampal alterations and may increase the risk of neurodegeneration. This study studied hippocampal anatomical and functional association with a lipid profile based on high-density lipoprotein, low-density lipoprotein, and triglyceride related to dyslipidemia in obese and nonobese adults. A whole-brain analysis was also conducted to examine the effect of dyslipidemia on resting-state function across the brain. Participants and Methods: In total, 553 UK Biobank participants comprised three groups based on body mass index (BMI) rankings: obese adults with high BMI (OHigh, n = 184, 32.7 kg/m2 ≤ BMI ≤53.4 kg/m2), obese adults with a lower BMI (OLow, n = 182, 30.3 kg/m2 ≤ BMI ≤32.6 kg/m2), and nonobese controls (n = 187). Structural MRI and functional MRI data were accessed. The fractional amplitude of low-frequency fluctuations (fALFFs) maps was calculated to reflect resting-state brain activity. A lipid health factor was created using principal component analysis. Linear models tested for associations between the lipid health score and hippocampal MRI readouts. Results: With a higher lipid health factor corresponding to a lower dyslipidemia risk, we found a positive correlation between hippocampal volume with the lipid health factor exclusively in group OLow (p = 0.01). We also found a positive association between the lipid health factor and hippocampal fALFF in group OHigh (p = 0.02). Additional fALFF voxel-wise analysis to group OHigh also implicated that the premotor cortex, amygdala, thalamus, subcallosal cortex, temporal fusiform cortex, and middle temporal gyrus brain regions are related with lipid. Conclusion: The study finds novel associations among circulating lipid, hippocampal structure, and hippocampal function exclusively in the obese adults.

Reduced evoked cortical beta and gamma activity and neuronal synchronization in succinic semialdehyde dehydrogenase deficiency, a disorder of γ-aminobutyric acid metabolism.

Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessively inherited metabolic disorder of γ-aminobutyric acid catabolism manifested by intellectual disability, expressive aphasia, movement disorders, psychiatric ailments and epilepsy. Subjects with succinic semialdehyde dehydrogenase deficiency are characterized by elevated γ-aminobutyric acid and related metabolites, such as γ-guanidinobutyric acid, and an age-dependent downregulation of cerebral γ-aminobutyric acid receptors. These findings indicate impaired γ-aminobutyric acid and γ-aminobutyric acid sub-type A (GABAA) receptor signalling as major factors underlying the pathophysiology of this neurometabolic disorder. We studied the cortical oscillation patterns and their relationship with γ-aminobutyric acid metabolism in 18 children affected by this condition and 10 healthy controls. Using high-density EEG, we recorded somatosensory cortical responses and resting-state activity. Using electrical source imaging, we estimated the relative power changes (compared with baseline) in both stimulus-evoked and stimulus-induced responses for physiologically relevant frequency bands and resting-state power. Stimulus-evoked oscillations are phase locked to the stimulus, whereas induced oscillations are not. Power changes for both evoked and induced responses as well as resting-state power were correlated with plasma γ-aminobutyric acid and γ-guanidinobutyric acid concentrations and with cortical γ-aminobutyric acid measured by proton magnetic resonance spectroscopy. Plasma γ-aminobutyric acid, γ-guanidinobutyric acid and cortical γ-aminobutyric acid were higher in patients than in controls (P < 0.001 for both). Beta and gamma relative power were suppressed for evoked responses in patients versus controls (P < 0.01). No group differences were observed for induced activity (P > 0.05). The mean gamma frequency of evoked responses was lower in patients versus controls (P = 0.002). Resting-state activity was suppressed in patients for theta (P = 0.011) and gamma (P < 0.001) bands. Evoked power changes were inversely correlated with plasma γ-aminobutyric acid and with γ-guanidinobutyric acid for beta (P < 0.001) and gamma (P < 0.001) bands. Similar relationships were observed between the evoked power changes and cortical γ-aminobutyric acid for all tested areas in the beta band (P < 0.001) and for the posterior cingulate gyrus in the gamma band (P < 0.001). We also observed a negative correlation between resting-state activity and plasma γ-aminobutyric acid and γ-guanidinobutyric acid for theta (P < 0.001; P = 0.003), alpha (P = 0.003; P = 0.02) and gamma (P = 0.02; P = 0.01) bands. Our findings indicate that increased γ-aminobutyric acid concentration is associated with reduced sensory-evoked beta and gamma activity and impaired neuronal synchronization in patients with succinic semialdehyde dehydrogenase deficiency. This further elucidates the pathophysiology of this neurometabolic disorder and serves as a potential biomarker for therapeutic trials.

Abnormal changes of dynamic topological characteristics in patients with major depressive disorder

BackgroundMost studies have detected abnormalities of static topological characteristics in major depressive disorder (MDD). However, whether dynamic alternations in brain topology are influenced by MDD remains unknown. MethodsAn approach was proposed to capture the dynamic topological characteristics with sliding-window and graph theory for a large data sample from the REST-meta-MDD project. ResultsIt was shown that patients with MDD were characterized by decreased nodal efficiency of the left orbitofrontal cortex. The temporal variability of topological characteristics was focused on the left opercular part of inferior frontal gyrus, and the right part of middle frontal gyrus, inferior parietal gyrus, precuneus and thalamus. LimitationsFuture studies need larger and diverse samples to explore the relationship between dynamic topological network characteristics and MDD symptoms. ConclusionsThe results support that the altered dynamic topology in cortex of frontal and parietal lobes and thalamus during resting-state activity may be involved in the neuropathological mechanism of MDD.

Depression recurrence is accompanied by longer periods in default mode and more frequent attentional and reward processing dynamic brain-states during resting-state activity.

Recurrence in major depressivedisorder (MDD) is common, but neurobiological models capturing vulnerability for recurrences are scarce. Disturbances in multiple resting-state networks have been linked to MDD, but most approaches focus on stable (vs. dynamic) network characteristics. We investigated how the brain's dynamical repertoire changes after patients transition from remission to recurrence of a new depressive episode. Sixty two drug-free, MDD-patients with ≥2 episodes underwent a baseline resting-state fMRI scan when in remission. Over 30-months follow-up, 11 patients with a recurrence and 17 matched-remitted MDD-patients without a recurrence underwent a second fMRI scan. Recurrent patterns of functional connectivity were characterized by applying Leading Eigenvector Dynamics Analysis (LEiDA). Differences between baseline and follow-up were identified for the 11 non-remitted patients, while data from the 17 matched-remitted patients was used as a validation dataset. After the transition into a depressive state, basal ganglia-anterior cingulate cortex (ACC) and visuo-attentional networks were detected significantly more often, whereas default mode network activity was found to have a longer duration. Additionally, the fMRI signal in the basal ganglia-ACC areas underlying the reward network, were significantly less synchronized with the rest of the brain after recurrence (compared to a state of remission). No significant changes were observed in the matched-remitted patients who were scanned twice while in remission. These findings characterize changes that may be associated with the transition from remission to recurrence and provide initial evidence of altered dynamical exploration of the brain's repertoire of functional networks when a recurrent depressive episode occurs.

Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model

Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while excessive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.

Altered Resting-State Activity and Connectivity in Late-Life Depression with Suicidal Ideation

Altered Resting-State Activity and Connectivity in Late-Life Depression with Suicidal Ideation

EEG Spatial-temporal Dynamics of Resting-state Activity in Young Women with Anorexia Nervosa: Preliminary Evidence.

The aim of this study was to provide preliminary evidence on temporal dynamics of resting-state brain networks in youth with anorexia nervosa (AN) using electroencephalography (EEG). Resting-state EEG data were collected in 18 young women with AN and 18 healthy controls (HC). Between-group differences in brain networks were assessed using microstates analyses. Five microstates were identified across all subjects (A, B, C, D, E). Using a single set of maps representative of the whole dataset, group differences were identified for microstates A, C, and E. A common-for-all template revealed a relatively high degree of consistency in results for reduced time coverage of microstate C, but also an increased presence of microstate class E. AN and HC had different microstate transition probabilities, largely involving microstate A. Using LORETA, for microstate D, we found that those with AN had augmented activations in the left frontal inferior operculum, left insula, and bilateral paracentral lobule, compared with HC. For microstate E, AN had augmented activations in the para-hippocampal gyrus, caudate, pallidum, cerebellum, and cerebellar vermis. Our findings suggest altered microstates in young women with AN associated with integration of sensory and bodily signals, monitoring of internal/external mental states, and self-referential processes. Future research should examine how EEG-derived microstates could be applied to develop diagnostic and prognostic models of AN.

Similarities and differences between intermittent and continuous resting-state fMRI.

Functional Magnetic Resonance Imaging (fMRI) block-design experiments typically include active ON-blocks with presentation of cognitive tasks which are contrasted with OFF- blocks with no tasks presented. OFF-blocks in between ON-blocks can however, also be seen as a proxy for intermittent periods of resting, inducing temporary resting-states. We still do not know if brain activity during such intermittent periods reflects the same kind of resting-state activity as that obtained during a continuous period, as is typically the case in studies of the classic Default Mode Network (DMN). The purpose of the current study was therefore to investigate both similarities and differences in brain activity between intermittent and continuous resting conditions. There were 47 healthy participants in the 3T fMRI experiment. Data for the intermittent resting-state condition were acquired from resting-periods in between active task-processing periods in a standard ON-OFF block design, with three different cognitive tasks presented during ON-blocks. Data for the continuous resting-state condition were acquired during a 5 min resting period after the task-design had been presented. The results showed that activity was overall similar in the two conditions, but with some differences. These differences were within the DMN network, and for the interaction of DMN with other brain networks. DMN maps showed weak overlap between conditions in the medial prefrontal cortex (MPFC), and in particular for the intermittent compared to the continuous resting-state condition. Moreover, DMN showed strong connectivity with the salience network (SN) in the intermittent resting-state condition, particularly in the anterior insula and the supramarginal gyrus. The observed differences may reflect a "carry-over" effect from task-processing to the next resting-state period, not present in the continuous resting-state condition, causing interference from the ON-blocks. Further research is needed to fully understand the extent of differences between intermittent and continuous resting-state conditions.

Noncoding transcripts are linked to brain resting-state activity in non-human primates

Brain-derived transcriptomes are known to correlate with resting-state brain activity in humans. Whether this association holds in nonhuman primates remains uncertain. Here, we search for such molecular correlates by integrating 757 transcriptomes derived from 100 macaque cortical regions with resting-state activity in separate conspecifics. We observe that 150 noncoding genes explain variations in resting-state activity at a comparable level with protein-coding genes. In-depth analysis of these noncoding genes reveals that they are connected to the function of nonneuronal cells such as oligodendrocytes. Co-expression network analysis finds that the modules of noncoding genes are linked to both autism and schizophrenia risk genes. Moreover, genes associated with resting-state noncoding genes are highly enriched in human resting-state functional genes and memory-effect genes, and their links with resting-state functional magnetic resonance imaging (fMRI) signals are altered in the brains of patients with autism. Our results highlight the potential for noncoding RNAs to explain resting-state activity in the nonhuman primate brain.

Periodic and Aperiodic EEG Features as Potential Markers of Developmental Dyslexia.

Developmental Dyslexia (DD) is a neurobiological condition affecting the ability to read fluently and/or accurately. Analyzing resting-state electroencephalographic (EEG) activity in DD may provide a deeper characterization of the underlying pathophysiology and possible biomarkers. So far, studies investigating resting-state activity in DD provided limited evidence and did not consider the aperiodic component of the power spectrum. In the present study, adults with (n = 26) and without DD (n = 31) underwent a reading skills assessment and resting-state EEG to investigate potential alterations in aperiodic activity, their impact on the periodic counterpart and reading performance. In parieto-occipital channels, DD participants showed a significantly different aperiodic activity as indexed by a flatter and lower power spectrum. These aperiodic measures were significantly related to text reading time, suggesting a link with individual differences in reading difficulties. In the beta band, the DD group showed significantly decreased aperiodic-adjusted power compared to typical readers, which was significantly correlated to word reading accuracy. Overall, here we provide evidence showing alterations of the endogenous aperiodic activity in DD participants consistently with the increased neural noise hypothesis. In addition, we confirm alterations of endogenous beta rhythms, which are discussed in terms of their potential link with magnocellular-dorsal stream deficit.

The development of oscillatory and aperiodic resting state activity is linked to a sensitive period in humans

Congenital blindness leads to profound changes in electroencephalographic (EEG) resting state activity. A well-known consequence of congenital blindness in humans is the reduction of alpha activity which seems to go together with increased gamma activity during rest. These results have been interpreted as indicating a higher excitatory/inhibitory (E/I) ratio in visual cortex compared to normally sighted controls. Yet it is unknown whether the spectral profile of EEG during rest would recover if sight were restored. To test this question, the present study evaluated periodic and aperiodic components of the EEG resting state power spectrum. Previous research has linked the aperiodic components, which exhibit a power-law distribution and are operationalized as a linear fit of the spectrum in log-log space, to cortical E/I ratio. Moreover, by correcting for the aperiodic components from the power spectrum, a more valid estimate of the periodic activity is possible. Here we analyzed resting state EEG activity from two studies involving (1) 27 permanently congenitally blind adults (CB) and 27 age-matched normally sighted controls (MCB); (2) 38 individuals with reversed blindness due to bilateral, dense, congenital cataracts (CC) and 77 age-matched sighted controls (MCC). Based on a data driven approach, aperiodic components of the spectra were extracted for the low frequency (Lf-Slope 1.5 to 19.5 Hz) and high frequency (Hf-Slope 20 to 45 Hz) range. The Lf-Slope of the aperiodic component was significantly steeper (more negative slope), and the Hf-Slope of the aperiodic component was significantly flatter (less negative slope) in CB and CC participants compared to the typically sighted controls. Alpha power was significantly reduced, and gamma power was higher in the CB and the CC groups. These results suggest a sensitive period for the typical development of the spectral profile during rest and thus likely an irreversible change in the E/I ratio in visual cortex due to congenital blindness. We speculate that these changes are a consequence of impaired inhibitory circuits and imbalanced feedforward and feedback processing in early visual areas of individuals with a history of congenital blindness.

The time scales of irreversibility in spontaneous brain activity are altered in obsessive compulsive disorder.

We study how obsessive-compulsive disorder (OCD) affects the complexity and time-reversal symmetry-breaking (irreversibility) of the brain resting-state activity as measured by magnetoencephalography (MEG). Comparing MEG recordings from OCD patients and age/sex matched control subjects, we find that irreversibility is more concentrated at faster time scales and more uniformly distributed across different channels of the same hemisphere in OCD patients than in control subjects. Furthermore, the interhemispheric asymmetry between homologous areas of OCD patients and controls is also markedly different. Some of these differences were reduced by 1-year of Kundalini Yoga meditation treatment. Taken together, these results suggest that OCD alters the dynamic attractor of the brain's resting state and hint at a possible novel neurophysiological characterization of this psychiatric disorder and how this therapy can possibly modulate brain function.

Validating MEG source imaging of resting state oscillatory patterns with an intracranial EEG atlas

BackgroundMagnetoencephalography (MEG) is a widely used non-invasive tool to estimate brain activity with high temporal resolution. However, due to the ill-posed nature of the MEG source imaging (MSI) problem, the ability of MSI to identify accurately underlying brain sources along the cortical surface is still uncertain and requires validation. MethodWe validated the ability of MSI to estimate the background resting state activity of 45 healthy participants by comparing it to the intracranial EEG (iEEG) atlas (https://mni-open-ieegatlas.research.mcgill.ca/). First, we applied wavelet-based Maximum Entropy on the Mean (wMEM) as an MSI technique. Next, we converted MEG source maps into intracranial space by applying a forward model to the MEG-reconstructed source maps, and estimated virtual iEEG (ViEEG) potentials on each iEEG channel location; we finally quantitatively compared those with actual iEEG signals from the atlas for 38 regions of interest in the canonical frequency bands. ResultsThe MEG spectra were more accurately estimated in the lateral regions compared to the medial regions. The regions with higher amplitude in the ViEEG than in the iEEG were more accurately recovered. In the deep regions, MEG-estimated amplitudes were largely underestimated and the spectra were poorly recovered. Overall, our wMEM results were similar to those obtained with minimum norm or beamformer source localization. Moreover, the MEG largely overestimated oscillatory peaks in the alpha band, especially in the anterior and deep regions. This is possibly due to higher phase synchronization of alpha oscillations over extended regions, exceeding the spatial sensitivity of iEEG but detected by MEG. Importantly, we found that MEG-estimated spectra were more comparable to spectra from the iEEG atlas after the aperiodic components were removed. ConclusionThis study identifies brain regions and frequencies for which MEG source analysis is likely to be reliable, a promising step towards resolving the uncertainty in recovering intracerebral activity from non-invasive MEG studies.

A parahippocampal-sensory Bayesian vicious circle generates pain or tinnitus: a source-localized EEG study.

Pain and tinnitus share common pathophysiological mechanisms, clinical features, and treatment approaches. A source-localized resting-state EEG study was conducted in 150 participants: 50 healthy controls, 50 pain, and 50 tinnitus patients. Resting-state activity as well as functional and effective connectivity was computed in source space. Pain and tinnitus were characterized by increased theta activity in the pregenual anterior cingulate cortex, extending to the lateral prefrontal cortex and medial anterior temporal lobe. Gamma-band activity was increased in both auditory and somatosensory cortex, irrespective of the pathology, and extended to the dorsal anterior cingulate cortex and parahippocampus. Functional and effective connectivity were largely similar in pain and tinnitus, except for a parahippocampal-sensory loop that distinguished pain from tinnitus. In tinnitus, the effective connectivity between parahippocampus and auditory cortex is bidirectional, whereas the effective connectivity between parahippocampus and somatosensory cortex is unidirectional. In pain, the parahippocampal-somatosensory cortex is bidirectional, but parahippocampal auditory cortex unidirectional. These modality-specific loops exhibited theta-gamma nesting. Applying a Bayesian brain model of brain functioning, these findings suggest that the phenomenological difference between auditory and somatosensory phantom percepts result from a vicious circle of belief updating in the context of missing sensory information. This finding may further our understanding of multisensory integration and speaks to a universal treatment for pain and tinnitus-by selectively disrupting parahippocampal-somatosensory and parahippocampal-auditory theta-gamma activity and connectivity.

In-silico EEG biomarkers of reduced inhibition in human cortical microcircuits in depression.

Reduced cortical inhibition by somatostatin-expressing (SST) interneurons has been strongly associated with treatment-resistant depression. However, due to technical limitations it is impossible to establish experimentally in humans whether the effects of reduced SST interneuron inhibition on microcircuit activity have signatures detectable in clinically-relevant brain signals such as electroencephalography (EEG). To overcome these limitations, we simulated resting-state activity and EEG using detailed models of human cortical microcircuits with normal (healthy) or reduced SST interneuron inhibition (depression), and found that depression microcircuits exhibited increased theta, alpha and low beta power (4-16 Hz). The changes in depression involved a combination of an aperiodic broadband and periodic theta components. We then demonstrated the specificity of the EEG signatures of reduced SST interneuron inhibition by showing they were distinct from those corresponding to reduced parvalbumin-expressing (PV) interneuron inhibition. Our study thus links SST interneuron inhibition level to distinct features in EEG simulated from detailed human microcircuits, which can serve to better identify mechanistic subtypes of depression using EEG, and non-invasively monitor modulation of cortical inhibition.

Resting-State Activity in Children: Replicating and Extending Findings of Early Maturation of Alpha Rhythms in Autism Spectrum Disorder.

Resting-state alpha brain rhythms provide a foundation for basic as well as higher-order brain processes. Research suggests atypical maturation of the peak frequency of resting-state alpha activity (= PAF) in autism spectrum disorder (ASD). The present study examined resting-state alpha activity in young school-aged children, obtaining magnetoencephalographic (MEG) eyes-closed resting-state data from 47 typically developing (TD) males and 45 ASD males 6.0 to 9.3 years old. Results confirmed a higher PAF in ASD versus TD, and demonstrated that alpha power differences between groups were linked to the shift of PAF in ASD. Additionally, a higher PAF was associated with better cognitive performance in TD but not ASD. Finding thus suggested functional consequences of group differences in resting-state alpha activity.

Laparoscopic sleeve gastrectomy induces simultaneous changes in brain functions and structures that are associated with weight loss

Introduction Laparoscopic sleeve gastrectomy (LSG) is one of the most effective interventions to promote weight-loss and induce reversal of brain functional and structural abnormalities. However, it is unclear whether these brain alterations occur simultaneously as well as the relationship with weight-loss.Methods We employed magnetic resonance imaging to investigate brain changes in 35 patients with obesity (OB), 36 normal-weight (NW) individuals, and 22 OB who received LSG and were studied at baseline and 1 month after LSG.Results Comparisons between OB and NW and between pre- and post-LSG showed (1) Resting-state activity differences in amplitude of low frequency fluctuation (ALFF) in the orbitofrontal cortex (OFC), caudate, hippocampus (HIPP), amygdala, thalamus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex. (2) Structural differences in fractional anisotropy (FA) in the middle cerebellar peduncle (MCP), genu corpus collosum (GCC), cingulate (Cin), and superior longitudinal fasciculus. Correlation analysis showed that (1) Reduced BMI/waist-circumference was positively correlated with decreased ALFF in the OFC and negatively associated with increased FA in the GCC following LSG. (2) Increased ALFF in the ACC was positively correlated with increased FA in the GCC and MCP. ALFF in the HIPP was negatively correlated with FA in the Cin at post-LSG.Conclusions These findings provide evidence that LSG induces simultaneous changes in brain function and structure which are associated with weight-loss.

P-124 Development of oscillatory and aperiodic resting state activity is linked to a sensitive period in humans

P-124 Development of oscillatory and aperiodic resting state activity is linked to a sensitive period in humans

Homeostatic normalization of alpha brain rhythms within the default-mode network and reduced symptoms in post-traumatic stress disorder following a randomized controlled trial of electroencephalogram neurofeedback.

Collective research has identified a key electroencephalogram signature in patients with post-traumatic stress disorder, consisting of abnormally reduced alpha (8-12 Hz) rhythms. We conducted a 20-session, double-blind, randomized controlled trial of alpha desynchronizing neurofeedback in patients with post-traumatic stress disorder over 20 weeks. Our objective was to provide mechanistic evidence underlying potential clinical improvements by examining changes in aberrant post-traumatic stress disorder brain rhythms (namely, alpha oscillations) as a function of neurofeedback treatment. We randomly assigned participants with a primary diagnosis of post-traumatic stress disorder (n = 38) to either an experimental group (n = 20) or a sham-control group (n = 18). A multichannel electroencephalogram cap was used to record whole-scalp resting-state activity pre- and post-neurofeedback treatment, for both the experimental and sham-control post-traumatic stress disorder groups. We first observed significantly reduced relative alpha source power at baseline in patients with post-traumatic stress disorder as compared to an age/sex-matched group of neurotypical healthy controls (n = 32), primarily within regions of the anterior default mode network. Post-treatment, we found that only post-traumatic stress disorder patients in the experimental neurofeedback group demonstrated significant alpha resynchronization within areas that displayed abnormally low alpha power at baseline. In parallel, we observed significantly decreased post-traumatic stress disorder severity scores in the experimental neurofeedback group only, when comparing baseline to post-treatment (Cohen's d = 0.77) and three-month follow-up scores (Cohen's d = 0.75), with a remission rate of 60.0% at the three-month follow-up. Overall, our results indicate that neurofeedback training can rescue pathologically reduced alpha rhythmicity, a functional biomarker that has repeatedly been linked to symptoms of hyperarousal and cortical disinhibition in post-traumatic stress disorder. This randomized controlled trial provides long-term evidence suggesting that the 'alpha rebound effect' (i.e. homeostatic alpha resynchronization) occurs within key regions of the default mode network previously implicated in post-traumatic stress disorder.