Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: neuroscience – Page 12

Temporal Variability in the Spiking Activity of Neurons in the External Globus Pallidus in Healthy and Parkinsonian Monkeys

The first report of in vivo extracellular recordings in the external segment of the globus pallidus (GPe) of awake monkeys described that most GPe neurons show high-frequency spiking activity, interspersed with pauses (high-frequency discharge with pauses, HFD-P), while a smaller proportion was said to show low-frequency discharge with bursts (LFD-B; DeLong, 1971). Similar patterns of pallidal discharge have been demonstrated by other authors, both in primates (Katabi et al., 2022) and rodents (Bugaysen et al., 2010; Benhamou et al., 2012).

There is evidence, however, that the HFD-P and LFD-B subtypes of GPe neurons are only the most recognizable extremes of a continuous spectrum of properties of GPe neurons. This view is supported by in vivo and in vitro recordings in rodents which found that the firing properties of the population of GPe neurons distribute along a continuum, with specific cells firing within more limited boundaries of firing rates and patterns (Abdi et al., 2015; Cui et al., 2021). Furthermore, observations in rodents showed that GPe neurons display a wide range of firing rates and patterns (Deister et al., 2013). The firing pattern heterogeneity in in vivo recordings may arise, at least in part, due to shifts in firing behavior of the same neurons, as has been reported in rodent studies (Deister et al., 2013). Such variations in firing patterns may only be detectable when recordings extend over long time periods (Elias et al., 2008).

The loss of nigrostriatal dopamine fibers associated with parkinsonism induces multiple alterations in GPe, where neuronal firing becomes slower, may show more frequent bursts, and becomes more synchronized (Galvan et al., 2015; Courtney et al., 2023). However, the stability of firing patterns of GPe neurons in the parkinsonian state has not yet been investigated.

Liad Mudrik: Using Prediction Maps to Guide Theory Testing and the Search for the NCC

This talk is part of the “New Ideas in NCC Research” workshop of the Bamberg Mathematical Consciousness Science Initiative (BAMΞ). For more talks and details, see https://www.uni-bamberg.de/en/bamxi/r…

Abstract: In recent years, the search for the neural correlates of consciousness (NCC) has been complemented, and influenced, by the ongoing efforts to test neuroscientific theories of consciousness. A key insight from these efforts, though, is that many theories remain underdeveloped and not fully specified, making it harder to establish stringent tests for their predictions. In this talk, I will present a novel methodological approach that represents scientific theories as networks of beliefs structured in a core-periphery manner. These Prediction Maps visualize theoretical claims and empirical predictions, and illustrate their inferential relations. This framework further facilitates systematic theory testing by allowing researchers to evaluate the evidential weight of different components of a theory, and to identify which experimental results would constitute the most informative tests. To do so, we apply graph-theoretic and network analysis metrics, quantifying the centrality of specific predictions. I argue that this approach can advance efforts to arbitrate between theories of consciousness and to identify their most promising candidate mechanisms as NCCs.

Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial

A personalized vaccine to treat glioblastoma, a fast-growing and incurable brain cancer that affects four in 100,000 people in the U.S., is safe and elicits robust and broad immune responses that appears to increase recurrence-free survival in a subset of patients after surgery, according to an early-stage clinical trial co-led by researchers at Washington University School of Medicine in St. Louis.

In patients with an especially aggressive form of glioblastoma, the vaccine caused no serious side effects and prolonged patients’ overall survival compared to historical outcomes after standard-of-care surgery and chemo-radiotherapy. One long-term survivor remains recurrence-free nearly five years later.

The results of the phase 1 trial, conducted at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, were published May 12 in Nature Cancer. The study was led jointly by Mass General Brigham and Geneos Therapeutics, a Philadelphia-based biotechnology company.

“We are extremely encouraged by these results,” said Tanner M. Johanns, MD, PhD, lead author of the study and an assistant professor in the Division of Oncology in the John T. Milliken Department of Medicine at WashU Medicine. “This kind of vaccine is a first for glioblastoma, and it is exciting to think how we can leverage this individualized therapeutic DNA cancer vaccine platform to make a positive impact on the lives of patients who are fighting this disease. Additionally, combination therapies leveraging this personalized platform are currently being investigated at WashU to test if outcomes may be improved further.”

Abstract: Nature Cancer

Johanns and colleagues report the results (including safety, efficacy and immunogenicity) of a phase 1 clinical trial of a DNA-based personalized therapeutic cancer vaccine administered following surgical resection and radiation in patients with MGMT unmethylated glioblastoma.

Continue reading “Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial” | >

Hippocampal ripples and replay reveal how brain recombines past knowledge for flexible planning

When facing new situations or problems, humans typically rely on knowledge they acquired in the past. Specifically, neuroscience studies suggest that the brain reorganizes past experiences and previously acquired knowledge, creating mental frameworks that can help humans to solve the problems they are facing. The recombination of past knowledge into new mental structures also allows humans to flexibly plan future actions in changing environments. Past studies suggest that two key brain regions contribute to this process, the hippocampus and the medial prefrontal cortex (mPFC).

The hippocampus is a brain structure that plays a key role in the formation of memories and spatial navigation. The mPFC, on the other hand, is known to support decision-making, planning, reasoning and the integration of information.

Researchers at Beijing Normal University, the Chinese Academy of Medical Sciences, University College London (UCL) and other institutes recently set out to investigate how the hippocampus and mPFC work together to combine past knowledge into new configurations. Their findings, published in Nature Neuroscience, suggest that this process is supported by brief bursts of high-frequency neural activity in the hippocampus, called hippocampal ripples, and the replay (i.e., re-activation) of past experiences in the brain.

Decoding intended speech with an intracortical brain-computer interface in a person with long-standing anarthria and locked-in syndrome

This study aimed to explore the alleviating effects of fisetin, a polyphenolic flavonoid, on ovarian dysfunction in a D-galactose (D-gal)-induced aging mouse model, as well as the underlying mechanisms, using both in vivo and in vitro experiments. Mice were subcutaneously injected with D-gal (100 mg/kg/day) for 60 days to establish the ovarian aging model; during the final 30 days, fisetin (10, 20, 30 mg/kg/day) was given orally. In addition, a senescent model of granulosa cell (GC) was established using D-gal and treated with fisetin. Fisetin supplementation improved ovarian endocrine function and reproductive capacity in aging mice, as reflected by regularized estrous cycles, elevated estradiol levels, and increased embryo numbers. Furthermore, fisetin reduced the number of atretic follicles and the extent of ovarian fibrosis and senescence, while simultaneously restoring the proliferation-apoptosis balance in follicular GCs, as well as alleviating oxidative stress. RNA-sequencing revealed that AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling and mitophagy were involved in the protective effects of fisetin against ovarian aging. Consistently, fisetin treatment promoted mitophagy, accompanied by AMPK/mTOR activation in ovarian tissues and GCs following D-gal exposure. Inhibition of AMPK attenuated the effect of fisetin on mitophagy. Additionally, blockage of mitophagy also reversed the beneficial effects of fisetin on mitochondrial injury, oxidative stress, cell cycle arrest, and cellular senescence in D-gal-induced senescent GCs. These findings indicate that fisetin prevents ovarian aging by suppressing follicular GC oxidative damage and ameliorating cell cycle arrest via activation of AMPK/mTOR-mediated mitophagy, thereby preserving female fertility.

Sleep Duration Linked to Accelerated Aging

The relationship between sleep and disease suggests that there exists a connection between the brain and the body that extends beyond merely influencing the brain itself.

Among brain-related disorders, short sleep was significantly associated with depressive episodes and anxiety disorders, as seen in other studies of sleep and mental health. Short sleep was also associated with obesity, type 2 diabetes, hypertension, ischemic heart disease, and heart arrhythmias.

Short and long sleep were associated with chronic obstructive pulmonary disease, asthma, and a cluster of digestive disorders, including gastritis and gastroesophageal reflux disease.

/* */