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Background: Apathy, characterized by a quantifiable reduction in motivation or goal-directed behavior, is a multidimensional syndrome that has been observed across many neurodegenerative diseases.
Objective: To develop a novel task measuring spontaneous action initiation (ie, a nonverbal equivalent to spontaneous speech tasks) and to investigate the association between apathy and executive functions such as the voluntary initiation of speech and actions and energization (ie, ability to initiate and sustain a response).
Method: We compared the energization and executive functioning performance of 10 individuals with neurodegenerative disease and clinically significant apathy with that of age-matched healthy controls (HC). We also investigated the association between self-reported scores on the Apathy Evaluation Scale (AES) and performance on energization tasks.
Results: The individuals with apathy made significantly fewer task-related actions than the HC on the novel spontaneous action task, and their scores on the AES were negatively correlated with spontaneous task-related actions, providing preliminary evidence for the task's construct validity. In addition, the individuals with apathy performed more poorly than the HC on all of the energization tasks, regardless of task type or stimulus modality, suggesting difficulty in sustaining voluntary responding over time. Most of the tasks also correlated negatively with the AES score. However, the individuals with apathy also performed more poorly on some of the executive function tasks, particularly those involving self-monitoring.
Conclusion: Our work presents a novel experimental task for measuring spontaneous action initiation-a key symptom of apathy-and suggests a possible contribution of apathy to neuropsychological deficits such as poor energization.
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http://dx.doi.org/10.1097/WNN.0000000000000345 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240.
Major depressive disorder affects millions worldwide, yet current treatments require prolonged administration. In contrast, ketamine produces rapid antidepressant effects by blocking spontaneous N-Methyl-D-Aspartate (NMDA) receptor signaling, which lifts the suppression of protein synthesis and triggers homeostatic synaptic plasticity. Here, we identify a parallel signaling pathway involving metabotropic glutamate receptor 5 (mGluR5) that promotes rapid antidepressant-like effects.
View Article and Find Full Text PDFJACC Case Rep
September 2025
Cardiovascular Diseases Section, Interdisciplinary Department of Medicine (DIM), University of Bari "Aldo Moro," Bari, Italy.
Background: Brugada syndrome (BrS) is a rare inherited arrhythmia disease carrying a variable risk of sudden cardiac death. Diagnosis requires the type 1 Brugada electrocardiographic pattern, which can either be spontaneous or induced by sodium channel-blocking drugs. Ranolazine is an antianginal drug acting on the late sodium current with emerging antiarrhythmic properties; no information is available on the safety of ranolazine use in patients with BrS.
View Article and Find Full Text PDFJCI Insight
September 2025
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Patients with Dravet syndrome (DS) present with severe, spontaneous seizures and ataxia. While most patients with DS have variants in the sodium channel Nav1.1 α subunit gene, SCN1A, variants in the sodium channel β1 subunit gene, SCN1B, are also linked to DS.
View Article and Find Full Text PDFAdv Physiol Educ
September 2025
Swansea University Medical School, Swansea University, Swansea, UK.
The chick embryo ventricular cardiomyocyte model provides students easy access to experiments involving fundamental features of cardiac cell physiology and pharmacology. Using standard physiology teaching laboratories and basic cell culture equipment, spontaneously beating colonies of electrically-connected cardiomyocytes can be obtained by the students themselves. Students learn, aseptic techniques and cell culture alongside experiments illustrating, at the simplest level of experimentation, how beating rate can be altered physiologically or pharmacologically.
View Article and Find Full Text PDFFront Neurosci
August 2025
Cell Signaling Laboratory, Institute of Experimental Medicine, Universidad Central de Venezuela, Caracas, Venezuela.
In our current view of reality, free will hangs on two opposing forces. On one side, we have determinism, which states that everything is already determined by our inner constituents, the atoms and molecules that form our bodies. On the other side, we have quantum mechanics and its view that everything in the quantum world is inherently random and probabilistic.
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