Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(12), P. e0278412 - e0278412

Published: Dec. 1, 2022

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) cognitively normal volunteers (n = 25), patients with mild AD dementia 16), epilepsy who underwent intracranial electrode monitoring 2) to assess safety single brief GENUS session induce entrainment (2) single-blinded, randomized, placebo-controlled 2A pilot (NCT04055376) probable 15) safety, compliance, entrainment, exploratory clinical outcomes after chronic daily sensory for 3 months. Our showed that was safe effectively induced both cortical regions other subcortical structures the hippocampus, amygdala, insula, gyrus rectus. demonstrated light sound well-tolerated compliance equally high control active groups, participants inaccurate guessing their group assignments prior unblinding. Electroencephalography recordings show our device safely dementia. After months stimulation, receiving (i) lesser ventricular dilation hippocampal (ii) increased functional connectivity default mode network well medial visual network, (iii) better on face-name association delayed recall test, (iv) improved measures activity rhythmicity compared group. These results support further evaluation pivotal trial evaluate its potential novel disease-modifying therapeutic

Language: Английский

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Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer’s disease model mice

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(4), P. 570 - 578

Published: March 6, 2023

Language: Английский

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The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: July 29, 2022

Gamma oscillation is the synchronization with a frequency of 30-90 Hz neural oscillations, which are rhythmic electric processes neuron groups in brain. The inhibitory interneuron network necessary for production gamma but certain disruptions such as brain inflammation, oxidative stress, and metabolic imbalances can cause this to malfunction. oscillations specifically control connectivity between different regions, crucial perception, movement, memory, emotion. Studies have linked abnormal conditions central nervous system, including Alzheimer's disease, Parkinson's schizophrenia. Evidence suggests that entrainment using sensory stimuli (GENUS) provides significant neuroprotection. This review discusses function advanced activities from both physiological pathological standpoint, it emphasizes potential therapeutic approach range neuropsychiatric diseases.

Language: Английский

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Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression

Frontiers in Synaptic Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 9, 2023

The synapse has consistently been considered a vulnerable and critical target within Alzheimer’s disease, loss is, to date, one of the main biological correlates cognitive decline disease. This occurs prior neuronal with ample evidence that synaptic dysfunction precedes this, in support idea failure is crucial stage disease pathogenesis. two pathological hallmarks abnormal aggregates amyloid or tau proteins, have had demonstrable effects on physiology animal cellular models There also growing these proteins may synergistic effect neurophysiological dysfunction. Here, we review some findings alterations what know from models. First, briefly summarize human suggest synapses are altered, including how this relates network activity. Subsequently, considered, highlighting mouse pathology role play dysfunction, either isolation examining pathologies interact specifically focuses function observed models, typically measured using electrophysiology calcium imaging. Following loss, it would be impossible imagine not alter oscillatory activity brain. Therefore, discusses underpin aberrant patterns seen patients. Finally, an overview key directions considerations field covered. includes current therapeutics targeted at but methods modulate rescue patterns. Other important future avenues note include non-neuronal cell types such as astrocytes microglia, mechanisms independent will certainly continue for foreseeable future.

Language: Английский

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Neuroprosthetics: from sensorimotor to cognitive disorders

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Jan. 6, 2023

Abstract Neuroprosthetics is a multidisciplinary field at the interface between neurosciences and biomedical engineering, which aims replacing or modulating parts of nervous system that get disrupted in neurological disorders after injury. Although neuroprostheses have steadily evolved over past 60 years sensory motor disorders, their application to higher-order cognitive functions still relatively preliminary stage. Nevertheless, recent series proof-of-concept studies suggest electrical neuromodulation strategies might also be useful alleviating some memory deficits, particular context dementia. Here, we review evolution neuroprosthetics from sensorimotor highlighting important common principles such as need for neuroprosthetic systems enable multisite bidirectional interactions with system.

Language: Английский

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Fast-spiking parvalbumin-positive interneurons in brain physiology and Alzheimer’s disease

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(12), P. 4954 - 4967

Published: July 7, 2023

Abstract Fast-spiking parvalbumin (PV) interneurons are inhibitory with unique morphological and functional properties that allow them to precisely control local circuitry, brain networks memory processing. Since the discovery in 1987 PV is expressed a subset of fast-spiking GABAergic neurons, our knowledge complex molecular physiological these cells has been expanding. In this review, we highlight specific neurons fire at high frequency reliability, enabling network oscillations shape encoding, consolidation retrieval memories. We next discuss multiple studies reporting neuron impairment as critical step neuronal dysfunction cognitive decline mouse models Alzheimer’s disease (AD). Finally, propose potential mechanisms underlying AD argue early changes activity could be causal AD-associated significant contributor pathogenesis.

Language: Английский

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Ultrasound-Triggered In Situ Photon Emission for Noninvasive Optogenetics

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(2), P. 1097 - 1107

Published: Jan. 6, 2023

Optogenetics has revolutionized neuroscience understanding by allowing spatiotemporal control over cell-type specific neurons in neural circuits. However, the sluggish development of noninvasive photon delivery brain limited clinical application optogenetics. Focused ultrasound (FUS)-derived mechanoluminescence emerged as a promising tool for situ emission, but there is not yet biocompatible liquid-phase system To achieve optogenetics with high temporal resolution and desirable biocompatibility, we have developed liposome (Lipo@IR780/L012) nanoparticles FUS-triggered delivery. Synchronized stable blue light emission was generated solution under FUS irradiation due to cascade reactions liposomes. In vitro tests revealed that Lipo@IR780/L012 could be triggered at different stimulation frequencies, resulting activation opsin-expressing spiking HEK cells irradiation. vivo optogenetic further demonstrated motor cortex noninvasively reversibly activated repetitive after intravenous injection lipid limb movements.

Language: Английский

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Cross-Frequency Coupling and Intelligent Neuromodulation

Cyborg and Bionic Systems, Journal Year: 2023, Volume and Issue: 4

Published: Jan. 1, 2023

Cross-frequency coupling (CFC) reflects (nonlinear) interactions between signals of different frequencies. Evidence from both patient and healthy participant studies suggests that CFC plays an essential role in neuronal computation, interregional interaction, disease pathophysiology. The present review discusses methodological advances challenges the computation with particular emphasis on potential solutions to spurious coupling, inferring intrinsic rhythms a targeted frequency band, causal interferences. We specifically focus literature exploring context cognition/memory tasks, sleep, neurological disorders, such as Alzheimer's disease, epilepsy, Parkinson's disease. Furthermore, we highlight implication for optimization invasive noninvasive neuromodulation rehabilitation. Mainly, could support advancing understanding neurophysiology cognition motor control, serve biomarker symptoms, leverage therapeutic interventions, e.g., closed-loop brain stimulation. Despite evident advantages investigative translational tool neuroscience, further improvements are required facilitate practical correct use cyborg bionic systems field.

Language: Английский

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Dopamine neuron degeneration in the Ventral Tegmental Area causes hippocampal hyperexcitability in experimental Alzheimer’s Disease

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(5), P. 1265 - 1280

Published: Jan. 16, 2024

Abstract Early and progressive dysfunctions of the dopaminergic system from Ventral Tegmental Area (VTA) have been described in Alzheimer’s Disease (AD). During long pre-symptomatic phase, alterations function Parvalbumin interneurons (PV-INs) are also observed, resulting cortical hyperexcitability represented by subclinical epilepsy aberrant gamma-oscillations. However, it is unknown whether deficits contribute to brain AD. Here, using Tg2576 mouse model AD, we prove that reduced hippocampal innervation, due VTA dopamine neuron degeneration, impairs PV-IN firing gamma-waves, weakens inhibition pyramidal neurons induces via lower D2-receptor-mediated activation CREB-pathway. These coincide with numbers Perineuronal Net density. Importantly, L-DOPA selective D2-receptor agonist quinpirole rescue p -CREB levels improve PV-IN-mediated inhibition, thus reducing hyperexcitability. Moreover, similarly quinpirole, sumanirole – another a known anticonvulsant not only increases PV-INs but restores gamma-oscillations mice. Conversely, blocking transmission sulpiride (a D2-like receptor antagonist) WT mice reduces PV-INs, mimicking what occurs Tg2576. Overall, these findings support hypothesis integrity plays key role survival, disclosing relevant contribution tone epileptiform activity early

Language: Английский

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Slow Wave Sleep Is a Promising Intervention Target for Alzheimer’s Disease

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: June 30, 2020

Alzheimer’s disease (AD) is the major cause of dementia, characterized by presence amyloid-beta plaques and neurofibrillary tau tangles. Plaques tangles are associated with sleep-wake cycle disruptions, including disruptions in non-rapid eye movement (NREM) slow wave sleep. patients spend less time NREM sleep exhibit decreased activity. Consistent critical role memory consolidation, reduced activity impaired consolidation AD patients. The aberrant can be modeled transgenic mouse models amyloidosis tauopathy. Animal exhibited impairments early progression, prior to deposition however abundant oligomeric amyloid-beta. Optogenetic rescue successfully halted amyloid accumulation restored intraneuronal calcium levels mice. On other hand, optogenetic acceleration frequency exacerbated disrupted neuronal homeostasis. In this review, we summarize evidence mechanisms underlying existence a positive feedback loop between amyloid/tau pathology that lead further accumulations AD. Moreover, since occur plaque deposition, provide an biomarker for disease. Finally, propose therapeutic targeting might effective treatment

Language: Английский

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