Accelerated intermittent theta-burst stimulation broadly ameliorates symptoms and cognition in Alzheimer's disease: A randomized controlled trial

Wu, Xingqi; Ji, Gong‐Jun; Geng, Zhi; Wang, Lu; Yan, Yibing; Wu, Yue; Xiao, Guixian; Gao, Lina; Wei, Qiang; Zhou, Shi‐Ping; Wei, Ling; Tian, Yanghua; Wang, Kai

doi:10.1016/j.brs.2021.11.007

Cited by 36 publications

(27 citation statements)

References 82 publications

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“…Such findings provide a potential mechanism for the oscillatory disruption induced by CSF-tau incubation in this study and imply such network alterations to represent an element of the core, initial neuropathology of AD. Indeed, recent studies are now evaluating the therapeutic implementation of theta entrainment for AD patients [ 40 , 84 , 133 , 134 ].…”

Section: Discussionmentioning

confidence: 99%

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations

Brown

Camporesi

Lantero‐Rodriguez

et al. 2023

acta neuropathol commun

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Alzheimer’s disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. While in animal models of AD pathology, soluble tau aggregates have been shown to disrupt neuronal function, it is unclear whether the tau species present in CSF will modulate neural activity. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. The method involves incubation of acutely-isolated wild-type mouse hippocampal brain slices with small volumes of diluted human CSF, followed by a suite of electrophysiological recording methods to evaluate their effects on neuronal function, from single cells through to the network level. Comparison of the toxicity profiles of the same CSF samples, with and without immuno-depletion for tau, has enabled a pioneering demonstration that CSF-tau potently modulates neuronal function. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input–output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations

Brown

Camporesi

Lantero‐Rodriguez

et al. 2023

acta neuropathol commun

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations

Brown

Camporesi

Lantero‐Rodriguez

et al. 2023

Preprint

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Alzheimer's disease (AD) is the leading cause of dementia worldwide. In AD animal models, soluble tau aggregates have been shown to disrupt neuronal function, alter synaptic plasticity and impair cognitive function. In humans, small fractions of these toxic tau species are secreted into cerebrospinal fluid (CSF), some of which can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. However, the mechanisms of how these tau forms alter neuronal and network function are not fully understood. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. The method involves incubation of acutely-isolated wild-type mouse hippocampal brain slices with small volumes of diluted human CSF, followed by a suite of electrophysiological recording methods to evaluate their effects on neuronal function from single cells through to the network level. Comparison of the toxicity profiles of the same CSF samples, with and without immuno-depletion for tau, has enabled a pioneering demonstration that CSF-tau potently modulates neuronal function. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input-output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future.

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“…Others reported that stimulation of the DLPFC by high‐frequency TMS can substantially enhance the cognition, memory function, working memory, attention function, and emotional state of PSCI patients. 27 , 28 , 29 Low‐frequency TMS stimulation of contralateral DLPFC can effectively promote the recovery of attention function in PSCI patients, 30 and intermittent theta‐burst stimulation (iTBS) can improve the symptoms and cognitive function of Alzheimer's disease, 31 which is consistent with our findings. Unlike the studies mentioned above, the present study was limited to the specific disease of PISEI, which is more targeted, and not all of the studies mentioned above conducted TMS targeting by navigation systems, and no relevant brain function changes have been explored.…”

Section: Discussionmentioning

confidence: 99%

Screening diagnosis of executive dysfunction after ischemic stroke and the effects of transcranial magnetic stimulation: A prospective functional near‐infrared spectroscopy study

Liu

Luo

Fang³

et al. 2023

CNS Neurosci Ther

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Background Post‐ischemic stroke executive impairment (PISEI) is a serious obstacle for patients to returning to their society and is currently difficult to screen early and clinically ineffective. Aim The aim of the study was to clarify whether functional near‐infrared spectroscopy (fNIRS) can be used as a rapid screening tool for PISEI and to explore the efficacy of transcranial magnetic stimulation (TMS) in PISEI patients and the changes in brain function. Methods A single‐blind, randomized controlled study design was used to detect hemodynamic differences by fNIIRS in 16 PISEI patients and 16 healthy subjects during the resting state and Stroop task, respectively. After 3 days, all subjects received a single TMS intervention and underwent simultaneous fNIRS testing for the Stroop task before and 3 days after the TMS intervention. Results PISEI patients had significantly higher HbO 2 content in the left dorsolateral prefrontal cortex (DLPFC), the right pre‐motor cortex (PMC) and the right primary sensorimotor cortex (SM1) during the Stroop task compared to the resting state ( F = 141.966, p < 0.001), but significantly lower than healthy subjects ( T = −3.413, p = 0.002). After TMS intervention, PISEI patients' time and error number scores on the Stroop test were significantly enhanced, and the functional activity of the above‐mentioned brain regions was significantly more active than at baseline, while the strength of their functional connections with each other was markedly increased. Conclusions fNIRS helped screen and diagnose PISEI. A single TMS session benefited PISEI patients with effects lasting 3 days, which may be attributed to activation of the left DLPFC, right PMC and right SM1 brain regions.

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Accelerated intermittent theta-burst stimulation broadly ameliorates symptoms and cognition in Alzheimer's disease: A randomized controlled trial

Cited by 36 publications

References 82 publications

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations

Screening diagnosis of executive dysfunction after ischemic stroke and the effects of transcranial magnetic stimulation: A prospective functional near‐infrared spectroscopy study

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