The Neurobiology of long COVID

A number of my friends have reported, having caught break thru Covid even after 3-5 vaccinations, and are having symptoms of long Covid such as brain fog, anosmia, and cognitive impairment. (I am extremely grateful, after five vaccinations, to still be Covid free.) For these friends as well as Mind Blog readers, I want to point to a special issue of Neuron and in particular one open source article "The neurobiology of long Covid," which describes the array of neurological symptoms and their possible causes.

New Perspectives on how our Minds Work

I want to pass on to MindBlog readers this link to a lecture I gave this past Friday (10/21/22) to the Univ. of Texas OLLI (Osher Lifelong Learning Institute) UT FORUM group on Oct. 21, 2022. Here is the brief description of the talk:  

Abstract

Recent research shows that much of what we thought we knew about how our minds work is wrong. Rather than rising from our essential natures, our emotional and social realities are mainly invented by each of us. Modern and ancient perspectives allow us to have some insight into what we have made.

Description

This talk offers a description of how our predictive brains work to generate our perceptions, actions, emotions, concepts, language, and social structures. Our experience that a self or "I" inside our heads is responsible for these behaviors is a useful illusion, but there is in fact no homunculus or discrete place inside our heads where “It all comes together.” Starting before we are born diffuse networks of brain cells begin generating actions and perceiving their consequences to build an internal library of sensing and acting correlations that keep us alive and well, a library that is the source of predictions about what we might expect to happen next in our worlds. Insights from both modern neuroscience research and ancient meditative traditions allow us to partially access and sometimes change this archive that manages our behaviors.

The brain chemistry underlying mental exhaustion.

Emily Underwood does a review of work by Wiehler et al. (open source) on the brain chemistry underlying mental fatigue, also describing several reservations expressed by other researchers. From her description:

The researchers divided 39 paid study participants into two groups, assigning one to a series of difficult cognitive tasks that were designed to induce mental exhaustion. In one, participants had to decide whether letters and numbers flashing on a computer screen in quick succession were green or red, uppercase or lowercase, and other variations. In another, volunteers had to remember whether a number matched one they’d seen three characters earlier...As the day dragged on, the researchers repeatedly measured cognitive fatigue by asking participants to make choices that required self-control—deciding to forgo cash that was immediately available so they could earn a larger amount later, for example. The group that had been assigned to more difficult tasks made about 10% more impulsive choices than the group with easier tasks, the researchers observed. At the same time, their glutamate levels rose by about 8% in the lateral prefrontal cortex—a pattern that did not show up in the other group...

Here is the Wiehler et al. abstract:  

Highlights

• Cognitive fatigue is explored with magnetic resonance spectroscopy during a workday 

• Hard cognitive work leads to glutamate accumulation in the lateral prefrontal cortex 

• The need for glutamate regulation reduces the control exerted over decision-making 

• Reduced control favors the choice of low-effort actions with short-term rewards

Summary

Behavioral activities that require control over automatic routines typically feel effortful and result in cognitive fatigue. Beyond subjective report, cognitive fatigue has been conceived as an inflated cost of cognitive control, objectified by more impulsive decisions. However, the origins of such control cost inflation with cognitive work are heavily debated. Here, we suggest a neuro-metabolic account: the cost would relate to the necessity of recycling potentially toxic substances accumulated during cognitive control exertion. We validated this account using magnetic resonance spectroscopy (MRS) to monitor brain metabolites throughout an approximate workday, during which two groups of participants performed either high-demand or low-demand cognitive control tasks, interleaved with economic decisions. Choice-related fatigue markers were only present in the high-demand group, with a reduction of pupil dilation during decision-making and a preference shift toward short-delay and little-effort options (a low-cost bias captured using computational modeling). At the end of the day, high-demand cognitive work resulted in higher glutamate concentration and glutamate/glutamine diffusion in a cognitive control brain region (lateral prefrontal cortex [lPFC]), relative to low-demand cognitive work and to a reference brain region (primary visual cortex [V1]). Taken together with previous fMRI data, these results support a neuro-metabolic model in which glutamate accumulation triggers a regulation mechanism that makes lPFC activation more costly, explaining why cognitive control is harder to mobilize after a strenuous workday.

Alcohol, neuronal plasticity, and mitochondrial trafficking

Hernandez and Kaun provide a nice description of work by Knabbe et al. with summary graphics. Here is the start of their text:

Consumption of alcohol creates a sense of euphoria, reduces inhibition, and increases sociability and impulsivity. The age at which alcohol is first experienced is a key factor contributing to the likelihood to misuse alcohol. However, the impacts of the first experience of alcohol on the molecules in the brain at these key developmental stages are not well understood. Knabbe et al. endeavored to address the neuromolecular alterations resulting from acute alcohol by combining hippocampal proteomics with somatosensory and motor cortex protein, dendrite, axon, and mitochondrial analysis in adolescent mice. Evidence from this array of preparations led to the hypothesis that alcohol disrupted mitochondrial trafficking, and using Drosophila they demonstrated a functional role for mitochondrial trafficking in cue-induced alcohol preference.

The cross-assay and cross-species approach outlined in Knabbe et al. proved to be an effective way of discovering how alcohol hijacks brain mechanisms. Animals from flies to humans maintain functionally consistent neurotransmitter systems, neural circuit mechanisms, and molecular pathways underlying reward.

And here is the abstract from Knabbe et al.:

Alcohol intoxication at early ages is a risk factor for the development of addictive behavior. To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope-labeled mice combined with quantitative mass spectrometry to screen more than 2,000 hippocampal proteins, of which 72 changed synaptic abundance up to twofold after ethanol exposure. Among those were mitochondrial proteins and proteins important for neuronal morphology, including MAP6 and ankyrin-G. Based on these candidate proteins, we found acute and lasting molecular, cellular, and behavioral changes following a single intoxication in alcohol-naïve mice. Immunofluorescence analysis revealed a shortening of axon initial segments. Longitudinal two-photon in vivo imaging showed increased synaptic dynamics and mitochondrial trafficking in axons. Knockdown of mitochondrial trafficking in dopaminergic neurons abolished conditioned alcohol preference in Drosophila flies. This study introduces mitochondrial trafficking as a process implicated in reward learning and highlights the potential of high-resolution proteomics to identify cellular mechanisms relevant for addictive behavior.

A systematic review of microdosing - research on low dose psychedelics

I pass on the link to this review by Polito and Liknaitzky. Their abstract:

The use of low doses of psychedelic substances (microdosing) is attracting increasing interest. This systematic review summarises all empirical microdosing research to date, including a set of infrequently cited studies that took place prior to prohibition. Specifically, we reviewed 44 studies published between 1955 and 2021, and summarised reported effects across six categories: mood and mental health; wellbeing and attitude; cognition and creativity; personality; changes in conscious state; and neurobiology and physiology. Studies showed a wide range in risk of bias, depending on design, age, and other study characteristics. Laboratory studies found changes in pain perception, time perception, conscious state, and neurophysiology. Self-report studies found changes in cognitive processing and mental health. We review data related to expectation and placebo effects, but argue that claims that microdosing effects are largely due to expectancy are premature and possibly wrong. In addition, we attempt to clarify definitional inconsistencies in the microdosing literature by providing suggested dose ranges across different substances. Finally, we provide specific design suggestions to facilitate more rigorous future research.

fNIRS - Functional near Iinfrared spectroscopy as a monitor of brain activity

Functional magnetic resonance imaging, or fMRI, requires that a subject remain still for an extended period within the confines of a large, noisy magnet available only at a dedicated facility. Sakai does an accessible review of recent work on functional near-infrared spectroscopy, or fNIRS, which affords a view into the brain based on blood oxygenation without the need for a big, immobile scanner. This optical imaging technique detects changes in how hemoglobin absorbs near-infrared light—usually wavelengths between 750 and 1,200 nanometers. Like fMRI, fNIRS provides an indirect measure of localized brain activity. It has now advanced from relatively simple measures of blood-oxygen changes to a sophisticated method of recording real-time brain responses associated with a wide variety of activities and cognitive tasks. fNIRS offers much better temporal resolution than fMRI, but light scattering limits fNIRS signals to the outer two centimeters of the brain, with a spatial resolution of about two to three centimeters—lower than fMRI but higher than EEG. The portability of fNIRS systems is allowing researchers to scrutinize the brain activity of subjects who are on the move, and observe brain changes associated with language recovery after a stroke.

How stress focuses brain integration

From Wang et al.(open source, with good graphics):

Despite the prevalence of stress, how brains reconfigure their multilevel, hierarchical functional organization in response to acute stress remains unclear. We examined changes in brain networks after social stress using whole-brain resting-state functional MRI (fMRI) by extending our recently published nested-spectral partition method, which quantified the functional balance between network segregation and integration. Acute stress was found to shift the brain into a more integrated and less segregated state, especially in frontal-temporal regions. Stress also stabilized brain states by reducing the variability of dynamic transition between segregated and integrated states. Transition frequency was associated with the change of cortisol, and transition variability was correlated with cognitive control. Our results show that brain networks tend to be more integrated and less variable after acute stress, possibly to enable efficient coping.

Reduction of stress and inflammatory responses by transcutaneous cervical vagal nerve stimulation

I want to point to an article by Caron that reviews work investigating therapeutic effects of stimulating our vagus nerve, two large nerve fiber bundles that run down both sides of our neck from the brain stem to our internal organs to regulate our parasympathetic 'calming' nervous system (as distinguished from the 'arousing' sympathetic part of our autonomic nervous system.) In the work by Bremmer et al. (open source) cited by Caron I was struck by the simplicity and accessibility of the simple technique used to stimulate the neck vagus nerves and suppress inflammatory and stress responses.

 

Figure 3. Diagram showing placement of tcVNS device on the neck to target the vagus nerve as it travels through the carotid sheath.

For technically inclined readers like myself, I pass on the following details of the vagal stimulation:

Both active tcVNS and sham stimuli were administered using hand-held devices that target the cervical portion of the vagus nerve from the skin (GammaCore, ElectroCore, Basking Ridge, New Jersey). Stimulation was applied using collar, stainless steel electrodes with a conductive electrode gel placed on the left side of the neck over the carotid sheath as determined by palpation of the carotid artery (Figure 3). Active tcVNS devices produced an alternating voltage signal consisting of five 5kHz sine bursts (1 ms of five sine waves with pulse width of 40 ms) repeating at a rate of 25 Hz envelopes. The frequency of 25 Hz was chosen based on prior studies showing optimization of effects on autonomic function and other measures at this frequency...The sham devices produce an alternating biphasic voltage signal consisting of 0.2 Hz square pulses (pulse width of 5 s) eliciting a mild sensation...Both active and sham devices delivered two minutes of stimulation. The stimulation intensity (amplitude of the voltage wavefront) was adjustable using a roll switch that ranged from 0 to 5 a.u. (arbitrary units) with a corresponding peak output ranging from 0 to 30V for active tcVNS, and from 0 to 14 V for the sham device. During each application, the amplitude of the voltage waveform was increased to the maximum the subject could tolerate, without pain. The stimulation continued at the selected intensity...The rationale behind the frequency difference between active (5kHz) and sham (0.2Hz) device waveforms is based on the fact that high frequency voltage signals (such as the active stimulus, 5kHz) pass through the skin with minimal power dissipation due to the low skin-electrode impedance at kHz frequencies. In contrast, lower frequency signals (such as the sham stimulus, 0.2Hz) are mainly attenuated at the skin-electrode interface due to the high impedance (Rosell et al., 1988). Accordingly, the active device operating at higher frequencies can deliver substantial energy to the vagus nerve to facilitate stimulation, while the voltage levels appearing at the vagus would be expected to be orders of magnitude lower for the sham device and thus stimulation is unlikely. Nevertheless, since the sham device does deliver relatively high voltage levels directly to the skin, it activates skin nociceptors, causing a similar feeling to a pinch. This sensation is considered to be necessary for blinding of the participants, particularly longitudinal protocols such as in this manuscript.

Magnetic stimulation of the brain can improve cognitive impairment

An open source article from Liu et al. in the journal Cerebral Cortex reports that repetitive transcranial magnetic stimulation (rTMS) over the bilateral angular gyrus in patients with probable Alzheimer’s disease resulted in up to 8 weeks of significantly improved cognitive function.:

Dementia causes a substantial global economic burden, but effective treatment is lacking. Recently, studies have revealed that gamma-band waves of electrical brain activity, particularly 40 Hz oscillations, are closely associated with high-order cognitive functions and can activate microglia to clear amyloid-β deposition. Here, we found that compared with sham stimulation, applying 40-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) over the bilateral angular gyrus in patients with probable Alzheimer’s disease (AD; n = 37) resulted in up to 8 weeks of significantly improved cognitive function. Power spectral density analysis of the resting-state electroencephalography (EEG) demonstrated that 40-Hz rTMS modulated gamma-band oscillations in the left posterior temporoparietal region. Further testing with magnetic resonance imaging and TMS-EEG revealed the following: 40-Hz rTMS 1) prevented gray matter volume loss, 2) enhanced local functional integration within bilateral angular gyrus, as well as global functional integration in bilateral angular gyrus and the left middle frontal gyrus, 3) strengthened information flow from the left posterior temporoparietal region to the frontal areas and strengthened the dynamic connectivity between anterior and posterior brain regions. These findings demonstrate that modulating gamma-band oscillations effectively improves cognitive function in patients with probable AD by promoting local, long-range, and dynamic connectivity within the brain.

Effortless training of attention and self-control

I pass on the highlights statement from a fascinating opinion piece by Tang et al. (motivated readers can obtain a copy of the text from me). 

Highlights

A long-held belief in cognitive science is that training attention and self-control must recruit effort. Therefore, various effortful training programs such as attention or working memory training have been developed to improve attention and self-control (or executive function). However, effortful training has limited far-transfer effects.

A growing literature suggests a new way of effortless training for attention and self-control. Effortless training – such as nature exposure, flow experience, and effortless practices – has shown promising effects on improving attention and self-control.

Effortful training requires cognitive control supported by the frontoparietal network to sustain mental effort over the course of training. Effortless training engages autonomic control with less effort, and is supported by the anterior and posterior cingulate cortex, striatum, and parasympathetic nervous system (PNS).

For the past 50 years, cognitive scientists have assumed that training attention and self-control must be effortful. However, growing evidence suggests promising effects of effortless training approaches such as nature exposure, flow experience, and effortless practice on attention and self-control. This opinion article focuses on effortless training of attention and self-control. We begin by introducing our definitions of effortful and effortless training and reviewing the growing literature on these two different forms of training. We then discuss the similarities and differences in their respective behavioral outcomes and neural correlates. Finally, we propose a putative neural mechanism of effortless training. We conclude by highlighting promising directions for research, development, and application of effortless training.

Figure Legend: Core brain regions and their functions during effortless training.

Three colored areas represent the anterior cingulate cortex–posterior cingulate cortex (ACC–PCC)–striatum (APS) and their corresponding functions during training. The broken line arrows indicate that these regions actively communicate with each other during effortless training.

How stress might help reduce dementia and alzheimer’s.

The post today (my 80th birthday) points to experimental results relevant to my interest in not losing my marbles anytime soon. Fauzia points to work by Avezov and collaborators (open source) showing that the accumulation of aggregates of misfolded proteins in the endoplasmic reticulum of brain cells that is associated with dementia and Alzheimer's can be reversed by stressing cells with chemicals or heat, activating molecular chaperones that in turn untangle or remove protein aggregates. How much stress is just enough, but not to much, isn't clear. The abstract of the work:

Protein synthesis is supported by cellular machineries that ensure polypeptides fold to their native conformation, whilst eliminating misfolded, aggregation prone species. Protein aggregation underlies pathologies including neurodegeneration. Aggregates’ formation is antagonised by molecular chaperones, with cytoplasmic machinery resolving insoluble protein aggregates. However, it is unknown whether an analogous disaggregation system exists in the Endoplasmic Reticulum (ER) where ~30% of the proteome is synthesised. Here we show that the ER of a variety of mammalian cell types, including neurons, is endowed with the capability to resolve protein aggregates under stress. Utilising a purpose-developed protein aggregation probing system with a sub-organellar resolution, we observe steady-state aggregate accumulation in the ER. Pharmacological induction of ER stress does not augment aggregates, but rather stimulate their clearance within hours. We show that this dissagregation activity is catalysed by the stress-responsive ER molecular chaperone – BiP. This work reveals a hitherto unknow, non-redundant strand of the proteostasis-restorative ER stress response.

Magic mind therapy….. Moving your body.

Gretchen Reynolds interviews Jennifer Heisz about the contents of her new book "Move the Body, Heal the Mind," which details the latest science about exercise and mental health, especially its potential to reduce anxiety and stress. The brief reprieve from anxiety than can sometimes be experienced after a workout is due to the release of neuropeptide Y, known to dampen hyperactivity of the anxious amygdala. Exercise also can reduce stress-induced body inflammation that damages cells and affects mood. These effects require only about a quarter of the normally recommended 150 minutes of moderate to vigorous exercise a week, so the exercise prescription for mental health seems to be less than that for physical health.

Re-energizing the aged brain

Alderton does a brief summary of work by Brakedal et al.:

Nicotinamide adenine dinucleotide (NAD) is an important cofactor in numerous metabolic reactions. NAD concentrations decline with age, which may contribute to age-associated conditions such as Parkinson’s disease. Preclinical studies show that replenishing NAD by supplementation with nicotinamide riboside (NR), a biosynthetic precursor to NAD, can promote health span and neuroprotection. Brakedal et al. performed a randomized, double-blind phase 1 clinical trial of NR supplementation in 30 patients newly diagnosed with Parkinson’s disease. They found that NR supplementation was safe and that concentrations of NAD in the brain increased in most patients receiving NR. These patients had signs of altered cerebral metabolism and mild clinical improvement, although further testing is needed with a larger cohort to confirm any clinical benefit.

Added note: I realized I had bought a jar of nicotinamide riboside some time ago ("TRU - Niagen" at an outrageious price), decided not to take it after reading about possible side effects, but relented after reading the Brakedal et al. article. I've been taking a 150 mg capsule daily for the past 10 days, half the recommended dosage. I haven't detected any noticable effects on my general energy levels.

How exercise supports the brain

From Leiter et al. "Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging":

Highlights 

• Selenium mediates the exercise-induced increase in adult hippocampal neurogenesis 

• Selenium increases hippocampal precursor proliferation and adult neurogenesis 

• Selenium reverses cognitive decline in aging and in hippocampal injury 

Summary 

Although the neurogenesis-enhancing effects of exercise have been extensively studied, the molecular mechanisms underlying this response remain unclear. Here, we propose that this is mediated by the exercise-induced systemic release of the antioxidant selenium transport protein, selenoprotein P (SEPP1). Using knockout mouse models, we confirmed that SEPP1 and its receptor low-density lipoprotein receptor-related protein 8 (LRP8) are required for the exercise-induced increase in adult hippocampal neurogenesis. In vivo selenium infusion increased hippocampal neural precursor cell (NPC) proliferation and adult neurogenesis. Mimicking the effect of exercise through dietary selenium supplementation restored neurogenesis and reversed the cognitive decline associated with aging and hippocampal injury, suggesting potential therapeutic relevance. These results provide a molecular mechanism linking exercise-induced changes in the systemic environment to the activation of quiescent hippocampal NPCs and their subsequent recruitment into the neurogenic trajectory.

Listening to our bodies can make us more resilient to stress

Jane Brody points to work from Haas et al. suggesting that resilience is more about body awareness than rational thinking. In their experiments subjects who had more subjective awareness of their internal feelings were less emotionally reactive to stress (showing less heart rate increase, shallow breathing, blood adrenaline increase), and recovered more quickly from it. Increased awareness of interoceptive stress signals from the body appears to enable stronger top-down suppression of the stress response. Here is the abstract from the Haas et al. article:

This study examined neural processes of resilience during aversive interoceptive processing. Forty-six individuals were divided into three groups of resilience Low (LowRes), high (HighRes), and normal (NormRes), based on the Connor-Davidson Resilience Scale (2003). Participants then completed a task involving anticipation and experience of loaded breathing during functional magnetic resonance imaging (fMRI) recording. Compared to HighRes and NormRes groups, LowRes self-reported lower levels of interoceptive awareness and demonstrated higher insular and thalamic activation across anticipation and breathing load conditions. Thus, individuals with lower resilience show reduced attention to bodily signals but greater neural processing to aversive bodily perturbations. In low resilient individuals, this mismatch between attention to and processing of interoceptive afferents may result in poor adaptation in stressful situations.

Predictions help neurons, and the brain, learn

From the PNAS Journal Club, a review of a publication by Luczak et. al. that suggest that neurons might be able to predict their own future activity, and learn to improve the accuracy of those predictions. The review expands on the Luczak et al abstract, which I pass on here:

Understanding how the brain learns may lead to machines with human-like intellectual capacities. It was previously proposed that the brain may operate on the principle of predictive coding. However, it is still not well understood how a predictive system could be implemented in the brain. Here we demonstrate that the ability of a single neuron to predict its future activity may provide an effective learning mechanism. Interestingly, this predictive learning rule can be derived from a metabolic principle, whereby neurons need to minimize their own synaptic activity (cost) while maximizing their impact on local blood supply by recruiting other neurons. We show how this mathematically derived learning rule can provide a theoretical connection between diverse types of brain-inspired algorithm, thus offering a step towards the development of a general theory of neuronal learning. We tested this predictive learning rule in neural network simulations and in data recorded from awake animals. Our results also suggest that spontaneous brain activity provides ‘training data’ for neurons to learn to predict cortical dynamics. Thus, the ability of a single neuron to minimize surprise—that is, the difference between actual and expected activity—could be an important missing element to understand computation in the brain.

A special issue of Social Cognitive and Affective Neuroscience on tDCS

I want to point to this special open source issue of Social Cognitive and Affective Neuroscience. Paulo Boggio provides an interesting historical introduction, staring in Roman times with the use of the electrical discharge of the torpedo fish to treat headaches (imagine being treated with fish applications over your head!). The articles in the issue consider the effects of low-intensity direct current stimulation of the surface of the scalp on prosocial behavior, aggression, impulsivity, etc. A review article by Galli et al. considers the use of tDCS to relieve the symptomatology of individuals with affective or social cognition disorders. (DIY kits for home experimentrs - which I would not recommend - abound on the internet, regular flashlight batteries being a sufficient source of the low currents used.)

Can monitoring brain waves boost mental health?

David Dodge does an interesting article asking whether neurofeedback has delivered the mental health revolution it has been promising for decades. The bottom line is that no experiments with proper double-blind controls have been convincing, and positive results obtained in less rigorous experiments with small numbers of subjects could be due to placebo effects.

Well-heeled investors, including the former secretary of education, Betsy DeVos, continue to pour millions into neurofeedback companies that promise dramatic improvements to the ways our brains function...However, neurofeedback is still not accepted as a mainstream treatment within mental health circles — and the most robust research into the intervention so far suggests it is no more effective than a placebo.

Practitioners across the country use neurofeedback to treat conditions like attention deficit hyperactivity disorder, major depressive disorder, anxiety disorder, epilepsy and traumatic brain injuries. The Food and Drug Administration has cleared a wide range of neurofeedback devices to treat these and other conditions, and the Centers for Disease Control and Prevention list it as an option in cases of ADHD in children, though they stop short of endorsing it.

Robert Thibault, a postdoctoral scholar at the Meta-Research Innovation Center at Stanford University, notes that neurofeedback advocates point to peer-reviewed research that have “impressive results,” but most are not rigorous double-blind, placebo-controlled trials. Of the dozen or so such trials, all but one concluded that fake neurofeedback works just as well as real neurofeedback...neurofeedback therapy success stories are likely caused by the placebo effect and not the treatment. He suggested that the therapy’s success may have something to do with the “healing environment” that practitioners create in their clinics or the allure of using sophisticated brain-monitoring technology.

In many instances, an online course is all that is needed to earn the certificate required to operate one of the dozens of neurofeedback devices on the market...Some companies skip the practitioner entirely by selling pricey neurofeedback devices directly to consumers...While its effectiveness is still debated, neurofeedback is generally thought to be safe. Even critics admit there are few side effects or downsides for those who have the time and money.

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

Interesting work from Clancy et al. on the brain's default mode network that carries out our self referential rumination: Significance

In the brain’s functional organization, the default mode network (DMN) represents a key architecture, whose dysregulation is involved in a host of major neuropsychiatric disorders. However, insights into the regulation of the DMN remain scarce. Through neural synchrony, the alpha-frequency oscillation represents another key underpinning of the brain’s organization and is thought to share an inherent interdependence with the DMN. Here, we demonstrated that transcranial alternating current stimulation of alpha oscillations (α-tACS) not only augmented alpha activity but also strengthened connectivity of the DMN, with the former serving as a mediator of the latter. These findings reveal that alpha oscillations can support DMN functioning. In addition, they identify an effective noninvasive approach to regulate the DMN via α-tACS.

Abstract

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.

New articles on exercise and the brain

Gretchen Reynolds has done two recent brief reviews:

 The Quiet Brain of the Athlete describes work showing that the brains of fit, young athletes dial down extraneous noise and attend to important sounds better than those of other young people. 

And, 

 Staying physically active may protect the aging brain. Simple activities like walking boost immune cells in the brain that may help to keep memory sharp and even ward off Alzheimer’s disease.