Trial reportNeuroImage. Clinical2015
Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance.
Trial report in NeuroImage. Clinical, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
167 citing papers in PubMed, 2 syntheses or guidelines pooled it, 291 citations in OpenAlex.
- Effect of levetiracetam on cognition in patients with cognitive decline: A systematic review and meta-analysis of randomized controlled trials.Epilepsia open · 2025Pooled it
- Effect of Levetiracetam on Cognition: A Systematic Review and Meta-analysis of Double-Blind Randomized Placebo-Controlled Trials.CNS drugs · 2024Pooled it
- Modulation of hippocampal activity in schizophrenia with levetiracetam: a randomized, double-blind, cross-over, placebo-controlled trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST).Journal of Alzheimer's disease : JAD · 2024Trial
- Characterizing hippocampal activation during pattern separation with multi-echo fMRI in cognitively normal older adults.Brain imaging and behavior · 2026Article
- Different functional connectivity gradients reflect aging and Alzheimer's disease.Nature neuroscience · 2026Article
- Structural Assessment of Fibrillated Beta Amyloid to Reveal the Potential Epitopes for Alzheimer's Disease.Cell biochemistry and biophysics · 2026Article
- New insights into synaptic vesicle dysfunction in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Excitation-inhibition homeostasis in Alzheimer's disease: a selective multiscale review of mechanisms, sex differences, and therapeutic opportunities.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- The rise and deceleration of neuronal excitability in aging and Alzheimer's disease: Mechanisms, implications, and therapeutic targets.Ageing research reviews · 2026Review
- Spike-wave discharges are uncoupled with cognitive outcome in aged Long-Evans rats.Psychopharmacology · 2025Article
- Restoration of sFRP3 Preserves the Neural Stem Cell Pool and Spatial Discrimination Ability in a Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Chronic optogenetic activation of hippocampal CA1 neurons triggers Alzheimer's disease-like proteomic remodeling.iScience · 2025Article
- Altered NPTX2 dynamics associated with impaired cognitive aging.bioRxiv : the preprint server for biology · 2025Article
- Cognitive outcomes of deep brain stimulation depend on age and hippocampal connectivity in Parkinson's and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Pharmacological reduction of reverse-translated hippocampal hyperactivity in mouse: relevance for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Age and Alzheimer's disease affect functional connectivity along separate axes of functional brain organization.bioRxiv : the preprint server for biology · 2025Article
- Longitudinal excitation-inhibition balance altered by sex and APOE-ε4.Communications biology · 2025Article
- Precuneus Activity during Retrieval Is Positively Associated with Amyloid Burden in Cognitively Normal OlderThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Impact of individual differences in cognitive reserve, stress, and busyness on episodic memory: an fMRI analysis of the Alabama Brain Study On Risk for Dementia.Cognitive, affective & behavioral neuroscience · 2025Article
107 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Studies of individuals with amnestic mild cognitive impairment (aMCI) have detected hyperactivity in the hippocampus during task-related functional magnetic resonance imaging (fMRI). Such elevated activation has been localized to the hippocampal dentate gyrus/CA3 (DG/CA3) during performance of a task designed to detect the computational contributions of those hippocampal circuits to episodic memory. The current investigation was conducted to test the hypothesis that greater hippocampal activation in aMCI represents a dysfunctional shift in the normal computational balance of the DG/CA3 regions, augmenting CA3-driven pattern completion at the expense of pattern separation mediated by the dentate gyrus. We tested this hypothesis using an intervention based on animal research demonstrating a beneficial effect on cognition by reducing excess hippocampal neural activity with low doses of the atypical anti-epileptic levetiracetam. In a within-subject design we assessed the effects of levetiracetam in three cohorts of aMCI participants, each receiving a different dose of levetiracetam. Elevated activation in the DG/CA3 region, together with impaired task performance, was detected in each aMCI cohort relative to an aged control group. We observed significant improvement in memory task performance under drug treatment relative to placebo in the aMCI cohorts at the 62.5 and 125 mg BID doses of levetiracetam. Drug treatment in those cohorts increased accuracy dependent on pattern separation processes and reduced errors attributable to an over-riding effect of pattern completion while normalizing fMRI activation in the DG/CA3 and entorhinal cortex. Similar to findings in animal studies, higher dosing at 250 mg BID had no significant benefit on either task performance or fMRI activation. Consistent with predictions based on the computational functions of the DG/CA3 elucidated in basic animal research, these data support a dysfunctional encoding mechanism detected by fMRI in individuals with aMCI and therapeutic intervention using fMRI to detect target engagement in response to treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.