Measurement of excitation-inhibition ratio in autism spectrum disorder using critical brain dynamics.

Balance between excitation (E) and inhibition (I) is a key principle for neuronal network organization and information processing. Consistent with this notion, excitation-inhibition imbalances are considered a pathophysiological mechanism in many brain disorders including autism spectrum disorder (ASD). However, methods to measure E/I ratios in human brain networks are lacking.

An EEG nicotinic acetylcholine index to assess the efficacy of pro-cognitive compounds.

Objectives: Cognitive impairment models are used in clinical studies aimed at proving pharmacology of drugs being developed for Alzheimer's disease and other cognitive disorders. Due to rising interest in nicotinic agonists, we aimed to establish a method to monitor neurophysiological effects of modulating the nicotinic cholinergic system.

Methods: In a four-way cross-over study, eyes-closed rest EEG was recorded in 28 healthy subjects receiving mecamylamine-a nicotinic acetylcholine receptor (nAChR) antagonist, which induces temporary cognitive dysfunction in healthy subjects-with co-administration of placebo, nicotine or galantamine.

Long-Range Temporal Correlations in Alpha Oscillations Stabilize Perception of Ambiguous Visual Stimuli.

Ongoing brain dynamics have been proposed as a type of "neuronal noise" that can trigger perceptual switches when viewing an ambiguous, bistable stimulus. However, no prior study has directly quantified how such neuronal noise relates to the rate of percept reversals. Specifically, it has remained unknown whether individual differences in complexity of resting-state oscillations-as reflected in long-range temporal correlations (LRTC)-are associated with perceptual stability.

Bumetanide As a Candidate Treatment for Behavioral Problems in Tuberous Sclerosis Complex.

Background: Recent studies indicate excitatory GABA action in and around tubers in patients with tuberous sclerosis complex (TSC). This may contribute to recurrent seizures and behavioral problems that may be treated by agents that enhance GABAergic transmission by influencing chloride regulation.

Case Presentation: Here, we used the chloride transporter antagonist bumetanide to treat a female adolescent TSC patient with refractory seizures, sensory hyper-reactivity, and a variety of repetitive and compulsive behaviors.

Strong long-range temporal correlations of beta/gamma oscillations are associated with poor sustained visual attention performance.

Neuronal oscillations exhibit complex amplitude fluctuations with autocorrelations that persist over thousands of oscillatory cycles. Such long-range temporal correlations (LRTC) are thought to reflect neuronal systems poised near a critical state, which would render them capable of quick reorganization and responsive to changing processing demands. When we concentrate, however, the influence of internal and external sources of distraction is better reduced, suggesting that neuronal systems involved with sustained attention could benefit from a shift toward the less volatile sub-critical state.

EEG machine learning for accurate detection of cholinergic intervention and Alzheimer's disease.

Monitoring effects of disease or therapeutic intervention on brain function is increasingly important for clinical trials, albeit hampered by inter-individual variability and subtle effects. Here, we apply complementary biomarker algorithms to electroencephalography (EEG) recordings to capture the brain's multi-faceted signature of disease or pharmacological intervention and use machine learning to improve classification performance. Using data from healthy subjects receiving scopolamine we developed an index of the muscarinic acetylcholine receptor antagonist (mAChR) consisting of 14 EEG biomarkers.

Age-dependent and -independent changes in attention-deficit/hyperactivity disorder (ADHD) during spatial working memory performance.

Objectives: Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities.

Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion.

Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion.

Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?

The diuretic agent bumetanide has recently been put forward as a novel, promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate γ-aminobutyric acid (GABA)-ergic inhibition in patients with neurodevelopmental disorders. However, strategies to select appropriate candidates for bumetanide treatment are lacking.

Subcortical glutamate mediates the reduction of short-range functional connectivity with age in a developmental cohort.

Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults.

Integrative EEG biomarkers predict progression to Alzheimer's disease at the MCI stage.

Alzheimer's disease (AD) is a devastating disorder of increasing prevalence in modern society. Mild cognitive impairment (MCI) is considered a transitional stage between normal aging and AD; however, not all subjects with MCI progress to AD. Prediction of conversion to AD at an early stage would enable an earlier, and potentially more effective, treatment of AD.

The Amsterdam Resting-State Questionnaire reveals multiple phenotypes of resting-state cognition.

Resting-state neuroimaging is a dominant paradigm for studying brain function in health and disease. It is attractive for clinical research because of its simplicity for patients, straightforward standardization, and sensitivity to brain disorders. Importantly, non-sensory experiences like mind wandering may arise from ongoing brain activity.

Individual differences in white matter diffusion affect sleep oscillations.

The characteristic oscillations of the sleeping brain, spindles and slow waves, show trait-like, within-subject stability and a remarkable interindividual variability that correlates with functionally relevant measures such as memory performance and intelligence. Yet, the mechanisms underlying these interindividual differences are largely unknown. Spindles and slow waves are affected by the recent history of learning and neuronal activation, indicating sensitivity to changes in synaptic strength and thus to the connectivity of the neuronal network.

Detrended fluctuation analysis: a scale-free view on neuronal oscillations.

Recent years of research have shown that the complex temporal structure of ongoing oscillations is scale-free and characterized by long-range temporal correlations. Detrended fluctuation analysis (DFA) has proven particularly useful, revealing that genetic variation, normal development, or disease can lead to differences in the scale-free amplitude modulation of oscillations. Furthermore, amplitude dynamics is remarkably independent of the time-averaged oscillation power, indicating that the DFA provides unique insights into the functional organization of neuronal systems.

External drive to inhibitory cells induces alternating episodes of high- and low-amplitude oscillations.

Electrical oscillations in neuronal network activity are ubiquitous in the brain and have been associated with cognition and behavior. Intriguingly, the amplitude of ongoing oscillations, such as measured in EEG recordings, fluctuates irregularly, with episodes of high amplitude alternating with episodes of low amplitude. Despite the widespread occurrence of amplitude fluctuations in many frequency bands and brain regions, the mechanisms by which they are generated are poorly understood.

Critical-state dynamics of avalanches and oscillations jointly emerge from balanced excitation/inhibition in neuronal networks.

Criticality has gained widespread interest in neuroscience as an attractive framework for understanding the character and functional implications of variability in brain activity. The metastability of critical systems maximizes their dynamic range, storage capacity, and computational power. Power-law scaling-a hallmark of criticality-has been observed on different levels, e.

Fast network oscillations in vitro exhibit a slow decay of temporal auto-correlations.

Ongoing neuronal oscillations in vivo exhibit non-random amplitude fluctuations as reflected in a slow decay of temporal auto-correlations that persist for tens of seconds. Interestingly, the decay of auto-correlations is altered in several brain-related disorders, including epilepsy, depression and Alzheimer's disease, suggesting that the temporal structure of oscillations depends on intact neuronal networks in the brain. Whether structured amplitude modulation occurs only in the intact brain or whether isolated neuronal networks can also give rise to amplitude modulation with a slow decay is not known.

Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease.

Encoding and retention of information in memory are associated with a sustained increase in the amplitude of neuronal oscillations for up to several seconds. We reasoned that coordination of oscillatory activity over time might be important for memory and, therefore, that the amplitude modulation of oscillations may be abnormal in Alzheimer disease (AD). To test this hypothesis, we measured magnetoencephalography (MEG) during eyes-closed rest in 19 patients diagnosed with early-stage AD and 16 age-matched control subjects and characterized the autocorrelation structure of ongoing oscillations using detrended fluctuation analysis and an analysis of the life- and waiting-time statistics of oscillation bursts.

Avalanche dynamics of human brain oscillations: relation to critical branching processes and temporal correlations.

Human brain oscillations fluctuate erratically in amplitude during rest and exhibit power-law decay of temporal correlations. It has been suggested that this dynamics reflects self-organized activity near a critical state. In this framework, oscillation bursts may be interpreted as neuronal avalanches propagating in a network with a critical branching ratio.