Fluctuation in cortical excitation/inhibition modulates capability of attention across time scales ranging from hours to seconds.

Sustained attention, as the basis of general cognitive ability, naturally varies across different time scales, spanning from hours, e.g. from wakefulness to drowsiness state, to seconds, e.g. trial-by-trail fluctuation in a task session. Whether there is a unified mechanism underneath such trans-scale variability remains unclear. Here we show that fluctuation of cortical excitation/inhibition (E/I) is a strong modulator to sustained attention in humans across time scales. First, we observed the ability to attend varied across different brain states (wakefulness, postprandial somnolence, sleep deprived), as well as within any single state with larger swings. Second, regardless of the time scale involved, we found highly attentive state was always linked to more balanced cortical E/I characterized by electroencephalography (EEG) features, while deviations from the balanced state led to temporal decline in attention, suggesting the fluctuation of cortical E/I as a common mechanism underneath trans-scale attentional variability. Furthermore, we found the variations of both sustained attention and cortical E/I indices exhibited fractal structure in the temporal domain, exhibiting features of self-similarity. Taken together, these results demonstrate that sustained attention naturally varies across different time scales in a more complex way than previously appreciated, with the cortical E/I as a shared neurophysiological modulator.

Impact of Acute High-intensity Interval Training on Cortical Excitability, M1-related Cognitive Functions, and Myokines: A Randomized Crossover Study.

High-intensity interval training (HIIT) is a time-efficient, safe, and feasible exercise type that can be utilized across different ages and health status. This randomized cross-over study aimed to investigate the effect of acute HIIT on cortical excitability, M1-related cognitive functions, cognition-related myokines, brain-derived neurotrophic factor (BDNF), and Cathepsin B (CTSB). Twenty-three sedentary young adults (mean age: 22.78 years ± 2.87; 14 female) participated in a cross-over design involving two sessions: either 23 min of HIIT or seated rest. Before and after the sessions, cortical excitability was measured using transcranial magnetic stimulation, and M1-related cognitive functions were assessed by the n-back test and mental rotation test. Serum levels of BDNF and CTSB were assessed using the ELISA method before and after the HIIT intervention. We demonstrated that HIIT improved mental rotation and working memory, and increased serum levels of BDNF and CTSB, whereas cortical excitability did not change. Our findings provide evidence that one session of HIIT is effective on M1-related cognitive functions and cognition-related myokines. Future research is warranted to determine whether such findings are transferable to different populations, such as cognitively at-risk children, adults, and older adults, and to prescribe effective exercise programs.

Mapping cortical excitability in the human dorsolateral prefrontal cortex.

BACKGROUND: Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an effective treatment for depression, but the neural effects after TMS remains unclear. TMS paired with electroencephalography (TMS-EEG) can causally probe these neural effects. Nonetheless, variability in single pulse TMS-evoked potentials (TEPs) across dlPFC subregions, and potential artifact induced by muscle activation, necessitate detailed mapping for accurate treatment monitoring. OBJECTIVE: To characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and specifically that conditions with larger muscle artifact may exhibit lower observed EL-TEPs due to over-rejection during preprocessing. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach. METHODS: In 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses. RESULTS: Stimulation location significantly influenced observed EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%. SIGNIFICANCE: EL-TEPs can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols.

Exercise effects on cortical excitability in pain populations: A systematic review and meta-analysis.

BACKGROUND: Transcranial Magnetic Stimulation (TMS) studies examining exercise-induced neuroplasticity in pain populations have produced contradictory findings. We conducted a systematic review to explore how exercise impacts cortical excitability in pain populations using TMS metrics. This review aims to summarize the effect sizes and to understand their sources of heterogeneity. METHODS: We searched multiple databases from inception to December 2022. We included randomized controlled trials (RCTs) with any type of pain population, including acute and chronic pain; exercise interventions were compared to sham exercise or other active interventions. The primary outcomes were TMS metrics, and pain intensity was the secondary outcome. Risk of bias assessment was conducted using the Cochrane tool. RESULTS: This review included five RCTs (n = 155). The main diagnoses were fibromyalgia and cervical dystonia. The interventions included submaximal contractions, aerobic exercise, physical therapy, and exercise combined with transcranial direct current stimulation. Three studies are considered to have a high risk of bias. All five studies showed significant pain improvement with exercise. The neurophysiological data revealed improvements in cortical excitability measured by motor-evoked potentials; standardized mean difference = 2.06, 95% confidence interval 1.35-2.78, I2 = 19%) but no significant differences in resting motor threshold. The data on intracortical inhibition/facilitation (ICI/ICF) was not systematically analyzed, but one study (n = 45) reported higher ICI and lower ICF after exercise. CONCLUSIONS: These findings suggest that exercise interventions positively affect pain relief by modifying corticospinal excitability, but their effects on ICI/ICF are still unclear. While the results are inconclusive, they provide a basis for further exploration in this area of research; future studies should focus on establishing standardized TMS measurements and exercise protocols to ensure consistent and reliable findings. A large-scale RCT that examines various exercise interventions and their effects on cortical excitability could offer valuable insights to optimize its application in promoting neuroplasticity in pain populations.

Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study.

BACKGROUND: Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. MATERIALS AND METHODS: TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. RESULTS: Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50-160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220-560 ms; 190-420 ms). Patients showed a reduction of both early (50-110 ms) gamma increase and later (180-230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. CONCLUSION: Our findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics.

Phosphene and motor transcranial magnetic stimulation thresholds are correlated: A meta-analytic investigation.

Transcranial magnetic stimulation (TMS) is commonly delivered at an intensity defined by the resting motor threshold (rMT), which is thought to represent cortical excitability, even if the TMS target area falls outside of the motor cortex. This approach rests on the assumption that cortical excitability, as measured through the motor cortex, represents a 'global' measure of excitability. Another common approach to measure cortical excitability relies on the phosphene threshold (PT), measured through the visual cortex of the brain. However, it remains unclear whether either estimate can serve as a singular measure to infer cortical excitability across different brain regions. If PT and rMT can indeed be used to infer cortical excitability across brain regions, they should be correlated. To test this, we systematically identified previous studies that measured PT and rMT to calculate an overall correlation between the two estimates. Our results, based on 16 effect sizes from eight studies, indicated that PT and rMT are correlated (ρ = 0.4), and thus one measure could potentially serve as a measure to infer cortical excitability across brain regions. Three exploratory meta-analyses revealed that the strength of the correlation is affected by different methodologies, and that PT intensities are higher than rMT. Evidence for a PT-rMT correlation remained robust across all analyses. Further research is necessary for an in-depth understanding of how cortical excitability is reflected through TMS.

Always expect the unexpected: eye position modulates visual cortex excitability in a stimulus-free environment.

Stimuli that potentially require a rapid defensive or avoidance action can appear from the periphery at any time in natural environments. de Wit et al. (Cortex 127: 120-130, 2020) recently reported novel evidence suggestive of a fundamental neural mechanism that allows organisms to effectively deal with such situations. In the absence of any task, motor cortex excitability was found to be greater whenever gaze was directed away from either hand. If modulation of cortical excitability as a function of gaze location is a fundamental principle of brain organization, then one would expect its operation to be present outside of motor cortex, including brain regions involved in perception. To test this hypothesis, we applied single-pulse transcranial magnetic stimulation (TMS) to the right lateral occipital lobe while participants directed their eyes to the left, straight-ahead, or to the right, and reported the presence or absence of a phosphene. No external stimuli were presented. Cortical excitability as reflected by the proportion of trials on which phosphenes were elicited from stimulation of the right visual cortex was greater with eyes deviated to the right as compared with the left. In conjunction with our previous findings of change in motor cortex excitability when gaze and effector are not aligned, this eye position-driven change in visual cortex excitability presumably serves to facilitate the detection of stimuli and subsequent readiness to act in nonfoveated regions of space. The existence of this brain-wide mechanism has clear adaptive value given the unpredictable nature of natural environments in which human beings are situated and have evolved.NEW & NOTEWORTHY For many complex tasks, humans focus attention on the site relevant to the task at hand. Humans evolved and live in dangerous environments, however, in which threats arise from outside the attended site; this fact necessitates a process by which the periphery is monitored. Using single-pulse transcranial magnetic stimulation (TMS), we demonstrated for the first time that eye position modulates visual cortex excitability. We argue that this underlies at least in part what we term "surveillance attention."

Acute aerobic exercise at different intensities modulates inhibitory control and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD).

BACKGROUND: This study aimed to investigate the effects of different aerobic exercise intensities on inhibitory control and cortical excitability in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: The study was conducted in a within-subject design. Twenty-four adults with ADHD completed a stop signal task and received cortical excitability assessment by transcranial magnetic stimulation (TMS) before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. RESULTS: Acute moderate-, and high-intensity aerobic exercise improved inhibitory control in adults with ADHD. Moreover, the improving effect was similar between moderate-, and high-intensity aerobic exercise conditions. As shown by the brain physiology results, short interval intracortical inhibition was significantly increased following both, moderate- and high-intensity aerobic exercise intervention conditions. Additionally, the alteration of short interval intracortical inhibition and inhibitory control improvement were positively correlated. CONCLUSIONS: The moderate-, and high-intensity aerobic exercise-dependent alterations of cortical excitability in adults with ADHD might partially explain the inhibitory control-improving effects of aerobic exercise in this population.

Assessing cortical excitability with electroencephalography: A pilot study with EEG-iTBS.

BACKGROUND: Cortical excitability measures neural reactivity to stimuli, usually delivered via Transcranial Magnetic Stimulation (TMS). Excitation/inhibition balance (E/I) is the ongoing equilibrium between excitatory and inhibitory activity of neural circuits. According to some studies, E/I could be estimated in-vivo and non-invasively through the modeling of electroencephalography (EEG) signals and termed 'intrinsic excitability' measures. Several measures have been proposed (phase consistency in the gamma band, sample entropy, exponent of the power spectral density 1/f curve, E/I index extracted from detrend fluctuation analysis, and alpha power). Intermittent theta burst stimulation (iTBS) of the primary motor cortex (M1) is a non-invasive neuromodulation technique allowing controlled and focal enhancement of TMS cortical excitability and E/I of the stimulated hemisphere. OBJECTIVE: Investigating to what extent E/I estimates scale with TMS excitability and how they relate to each other. METHODS: M1 excitability (TMS) and several E/I estimates extracted from resting state EEG recordings were assessed before and after iTBS in a cohort of healthy subjects. RESULTS: Enhancement of TMS M1 excitability, as measured through motor-evoked potentials (MEPs), and phase consistency of the cortex in high gamma band correlated with each other. Other measures of E/I showed some expected results, but no correlation with TMS excitability measures or strong consistency with each other. CONCLUSIONS: EEG E/I estimates offer an intriguing opportunity to map cortical excitability non-invasively, with high spatio-temporal resolution and with a stimulus independent approach. While different EEG E/I estimates may reflect the activity of diverse excitatory-inhibitory circuits, spatial phase synchrony in the gamma band is the measure that best captures excitability changes in the primary motor cortex.

Effect of neuronavigated repetitive Transcranial Magnetic Stimulation on pain, cognition and cortical excitability in fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep. METHODS: Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy (n = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy. RESULTS: Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity (P < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham. CONCLUSIONS: Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity.

Environmental enrichment reduces brain excitability in adult rats overnourished during lactation / Enriquecimento ambiental reduz excitabilidade cerebral em ratos adultos hipernutridos durante a lactação

ABSTRACT Objective: This study aimed to analyze whether exposure to environmental enrichment (EE) during the juvenile phase of life interferes with the electrical activity of the adult rat brain. In addition, the present research also investigated whether this putative effect on brain electrical activity could be affected by prior overnutrition during lactation. Electrophysiology was measured through cortical spreading depression (CSD), a phenomenon related to brain excitability. Methods: Wistar rats were suckled in litters of either nine or three pups, forming the nourished (N) or overnourished (ON) groups, respectively. At 36 days old, half of the animals from each nutritional condition were exposed to EE. The other half was kept in the standard environment (SE). At 90-120 days of life, each animal was anesthetized for CSD recordings. Results: Overnutrition during lactation caused increases (p < 0.05) in body and brain weights. The EE decelerated CSD propagation velocity regardless of nutritional state during lactation (p < 0.001). The CSD deceleration in the N-EE group was 23.8% and in the ON-EE group was 15% in comparison with the N-SE and ON-SE groups, respectively. Conclusion: Our data demonstrated that EE exposure in the juvenile phase of the rat's life reduced brain excitability, and this effect was observed even if animals were overnourished during lactation. An EE could be considered an adjuvant therapeutic resource to modulate brain excitability.

RESUMO Objetivo: Este estudo analisou se a exposição ao ambiente enriquecido durante a fase juvenil da vida interferiria na atividade elétrica do cérebro de ratos adultos. Além disso, a presente pesquisa também investigou se esse provável efeito na atividade elétrica cerebral poderia ser afetado pela hipernutrição durante a lactação. A eletrofisiologia foi medida através da depressão alastrante cortical, um fenômeno relacionado à excitabilidade cerebral. Métodos: Ratos Wistar foram amamentados em ninhadas de nove ou três filhotes, formando os grupos nutridos ou hipernutridos, respectivamente. Aos 36 dias, metade dos animais de cada condição nutricional foram expostos ao ambiente enriquecido. A outra metade foi mantida na condição de ambiente padrão. Aos 90-120 dias de vida, foram obtidos os registros da depressão alastrante cortical. Resultados: A hipernutrição durante a lactação causou incrementos (p < 0,05) nos pesos corporal e cerebral.O Ambiente Enriquecido desacelerou a velocidade de propagação da depressão alastrante cortical independentemente do estado nutricional durante a lactação (p < 0,001). A desaceleração da depressão alastrante cortical no grupo nutrido/ambiente enriquecido foi de 23,8% e no grupo hipernutrido/ambiente enriquecido foi de 15% em comparação com os grupos nutrido/ambiente padrão e hipernutrido/ambiente padrão, respectivamente. Conclusão: Nossos dados demonstram que a exposição ao ambiente enriquecido na fase juvenil da vida do rato reduz a excitabilidade cerebral, e esse efeito pode ser observado mesmo se os animais estiverem hipernutridos durante a lactação. O ambiente enriquecido pode ser considerado um recurso terapêutico adjuvante para modular a excitabilidade cerebral.