Working memory capacity has traditionally been thought to be constant. Recent studies, however, suggest that working memory can be improved by training. In this study, we have investigated the changes in brain activity that are induced by working memory training. Two experiments were carried out in which healthy, adult human subjects practiced working memory tasks for 5 weeks. Brain activity was measured with functional magnetic resonance imaging (fMRI) before, during and after training. After training, brain activity that was related to working memory increased in the middle frontal gyrus and superior and inferior parietal cortices. The changes in cortical activity could be evidence of training-induced plasticity in the neural systems that underlie working memory.
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http://dx.doi.org/10.1038/nn1165 | DOI Listing |
Alzheimers Dement
December 2024
Centre for Addiction and Mental Health, Toronto, ON, Canada.
Background: Dysregulated GABA/somatostatin (SST) signaling has been implicated in psychiatric and neurodegenerative disorders. The inhibition of excitatory neurons by SST+ interneurons, particularly through α5-containing GABAA receptors (α5-GABAAR), plays a crucial role in mitigating cognitive functions. Previous research demonstrated that an α5-positive allosteric modulator (α5-PAM) mitigates working memory deficits and reverses neuronal atrophy in aged mice.
View Article and Find Full Text PDFBackground: Selecting the optimal dose for clinical development is especially problematic for drugs directed at CNS-specific targets. For drugs with a novel mechanism of action, these problems are often greater. We describe Xanamem's clinical pharmacology, including the approach to dose selection and proof-of-concept studies.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a neurodegenerative disorder without a cure. Targeting this multifactorial disease by repurposing FDA approved drugs serves as a faster mode of treatment due to its pre-established human safety. We tested terazosin (TZ), an a-1 adrenergic receptor (AR) antagonist and phosphoglycerate kinase-1 (PGK1) activator as having potential to treat AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Background: Acetylcholine, a neurotransmitter critical for cognitive functions, including attention, memory, and sociability, is essential for maintaining synaptic integrity. Deficits in acetylcholine levels are linked to cognitive impairments. Heterozygous VAChT KD (VAChT KDHET) mice, characterized by reduced vesicular acetylcholine transporter protein production, exhibit cognitive impairments due to diminished acetylcholine release.
View Article and Find Full Text PDFBackground: The increased incidence of Alzheimer's disease (AD) rate represent an unmet medical need and thus critical for the development of novel molecular therapeutics. Recent work focusing on patients with apoE4 alleles has highlighted the association of brain cholesterol dysregulation with elevated pathological burden and neurodegeneration. These studies have highlighted the importance of the nuclear receptor Liver X receptor (LXR) for developing AD therapies.
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