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Browse the failure-mode index

258 real negative results, null findings, and replication failures in Neuroscience. Search the index →

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record compiled from open scholarly databases; the abstract is shown in full only where the paper is openly licensed, otherwise a short excerpt under fair use. Classifications are automated and approximate.

Negative / Null Result ReportOpen accessNeuroscience

Music and Language Processing Share Behavioral and Cerebral Features

Clara E. James · 2012 · Frontiers in Psychology

A commentary on Musical expertise and statistical learning of musical and linguistic structures by Schön, D., and François, C. (2011). Front. Psychology 2:167. doi: 10.3389/ fpsyg.2011.00167 Both language and music consist of discrete elements organized in embedded hierarchical structures. Schön and François nicely expose in this review that musical expertise facilitates learning of both linguistic and musical structures. At the behavioral level, the musicians did not outperform the nonmusicians. However, ERP analyses showed that acquisition of boundary perception (segmentation) between units

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Negative / Null Result ReportOpen accessNeuroscience

Predicting ‘Brainage’ in late childhood to adolescence (6-17yrs) using structural MRI, morphometric similarity, and machine learning

Daniel Griffiths-King, Amanda Wood, Jan Novák · 2023 · Scientific Reports

Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy children to predict an individual's age from structural MRI. This data-driven, predicted 'Brainage' typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this Brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI t

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Negative / Null Result ReportOpen accessNeuroscience

Target Size Manipulations Affect Error-Processing Duration and Success Perceptions but not Behavioural Indices of Learning

Nicole T. Ong, Jamie Hawke, Nicola J. Hodges · 2019 · Brain Sciences

We evaluated if and how success perceptions, through target size manipulations, impact processes related to motor learning. This work was based on recent literature suggesting that expectations and self-efficacy exert a direct impact on learning. We measured arousal, kinematics, learner expectancies, motivation, and outcomes in a dart-throwing task. Novices (n = 29) were assigned to either a “Large-target” (horizontal target, 10-cm high) or “Small-target” (2-cm high) group for practice (t = 90), and both groups completed 24-h retention tests. The Small-target group took longer to plan and proc

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Negative / Null Result ReportOpen accessNeuroscience

FMR1, circadian genes and depression: suggestive associations or false discovery?

Daniel F. Kripke, Caroline M. Nievergelt, Gregory J. Tranah et al. · 2013 · Journal of Circadian Rhythms

BACKGROUND: There are several indications that malfunctions of the circadian clock contribute to depression. To search for particular circadian gene polymorphisms associated with depression, diverse polymorphisms were genotyped in two samples covering a range of depressed volunteers and participants with normal mood. METHODS: Depression mood self-ratings and DNA were collected independently from a sample of patients presenting to a sleep disorders center (1086 of European origin) and from a separate sample consisting of 399 participants claiming delayed sleep phase symptoms and 406 partly-matc

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Negative / Null Result ReportOpen accessNeuroscience

Quantitative and Qualitative Exploration of Meaningful Change on the Vineland Adaptive Behavior Scales (Vineland™-II) in Children and Adolescents with Autism Without Intellectual Disability Following Participation in a Clinical Trial

Susanne Clinch, Stacie Hudgens, Elizabeth Gibbons et al. · 2023 · Patient Related Outcome Measures

Purpose: Adaptive Behavior Scale is often used in autism spectrum disorder (ASD) trials. The Adaptive Behavior Composite Score (VABS-ABC) is the standardized overall score (the average of the Socialization, Communication and Daily Living…

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Negative / Null Result ReportOpen accessNeuroscience

Adaptive scaling of reward in episodic memory: a replication study

Alice Mason, Casimir J. H. Ludwig, Simon Farrell · 2016 · Quarterly Journal of Experimental Psychology

Reward is thought to enhance episodic memory formation via dopaminergic consolidation. Bunzeck, Dayan, Dolan, and Duzel [(2010). A common mechanism for adaptive scaling of reward and novelty. Human Brain Mapping, 31, 1380-1394] provided functional magnetic resonance imaging (fMRI) and behavioural evidence that reward and episodic memory systems are sensitive to the contextual value of a reward-whether it is relatively higher or lower-as opposed to absolute value or prediction error. We carried out a direct replication of their behavioural study and did not replicate their finding that memory p

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Negative / Null Result ReportOpen accessNeuroscience

Visual Perceptual Load Does Not Affect the Frequency Mismatch Negativity

Stefan Wiens, Erik van Berlekom, Malina Szychowska et al. · 2019 · Frontiers in Psychology

The mismatch negativity (MMN) has been of particular interest in auditory perception because of its sensitivity to auditory change. It is typically measured in an oddball task and is computed as the difference of deviant minus standard tones. Previous studies suggest that the oddball MMN can be reduced by crossmodal attention to a concurrent, difficult visual task. However, more recent studies did not replicate this effect. Because previous findings seem to be biased, we preregistered the present study and used Bayesian hypothesis testing to measure the strength of evidence for or against an e

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Negative / Null Result ReportOpen accessNeuroscience

Higher visual areas act like domain-general filters with strong selectivity and functional specialization

Meenakshi Khosla, Leila Wehbe · 2026 · Nature Communications

Neuroscientific studies rely heavily on a-priori hypotheses, which can bias results toward existing theories. Here, we use a hypothesis-neutral approach to study category selectivity in higher visual cortex. Using only stimulus images and their associated fMRI activity, we constrain randomly initialized neural networks to predict voxel activity. Despite no category-level supervision, units in the trained networks act as detectors for semantic concepts like 'faces' or 'words', providing solid empirical support for categorical selectivity. Importantly, this selectivity is mostly maintained when

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Negative / Null Result ReportOpen accessNeuroscience

Comparing fear and anxiety chemosignals: Do they modulate facial muscle activity and facilitate identifying facial expressions?

Nuno Gomes, Bettina M. Pause, Monique A. M. Smeets et al. · 2023 · Chemical Senses

Fear and anxiety are the most frequently studied emotional states in chemosignal research. Despite differences between these two emotional states, findings from research using fear and anxiety body odors (BOs) are often treated as part of…

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Negative / Null Result ReportOpen accessNeuroscience

TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism

Astrid Feiten, Kilian Dahm, Kai Schlepckow et al. · 2026 · Nature Communications

Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol met

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Negative / Null Result ReportOpen accessNeuroscience

Tactile processing in mouse cortex depends on action context

Eric A. Finkel, Yi-Ting Chang, Rajan Dasgupta et al. · 2024 · Cell Reports

The brain receives constant tactile input, but only a subset guides ongoing behavior. Actions associated with tactile stimuli thus endow them with behavioral relevance. It remains unclear how the relevance of tactile stimuli affects…

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Negative / Null Result ReportOpen accessNeuroscience

Accelerated transcranial magnetic stimulation for psychological distress in advanced cancer: A phase 2a feasibility and preliminary efficacy clinical trial

James Downar, James Downar, Julie Lapenskie et al. · 2024 · Palliative Medicine

Background: Psychological and existential suffering affects many people with advanced illness, and current therapeutic options have limited effectiveness. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective therapy…

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Negative / Null Result ReportOpen accessNeuroscience

Null effect of perceived drum pattern complexity on the experience of groove

Olivier Senn, Florian Hoesl, Toni Bechtold et al. · 2024 · PLoS ONE

There is a broad consensus in groove research that the experience of groove, understood as a pleasurable urge to move in response to music, is to some extent related to the complexity of the rhythm. Specifically, music with medium rhythmic complexity has been found to motivate greater urge to move compared to low or high complexity music (inverted-U hypothesis). Studies that confirmed the inverted-U hypothesis usually based their measure of complexity on the rhythmic phenomenon of syncopation, where rhythms with more and/or stronger syncopation are considered to be more complex than less synco

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Replication FailureOpen accessNeuroscience

Pridopidine in early-stage manifest Huntington’s disease: a phase 3 trial

Ralf Reilmann, Andrew Feigin, Anne Rosser et al. · 2025 · Nature Medicine

Huntington's disease (HD) is a rare, neurodegenerative disorder for which only symptomatic treatments are available. The PROOF-HD study was a randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of pridopidine, a selective Sigma-1 receptor agonist, in HD. The primary and key secondary endpoints, change in total functional capacity (TFC) and composite Unified Huntington's Disease Rating Scale (cUHDRS) score at week 65, were not met in the overall population. The TFC least-squares mean difference between pridopidine and placebo was -0.18 (95% confidence i

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Negative / Null Result ReportNeuroscience

Does testing impair relational processing? Failed attempts to replicate the negative testing effect.

Katherine A. Rawson, Kathryn T. Wissman, Kalif E. Vaughn · 2015 · Journal of Experimental Psychology Learning Memory and Cognition

Recent research on testing effects (i.e., practice tests are more effective than restudy for enhancing subsequent memory) has focused on explaining when and why testing enhances memory. Of particular interest for present purposes, Zaromb…

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Negative / Null Result ReportOpen accessNeuroscience

Precision fMRI reveals that the language network exhibits adult-like left-hemispheric lateralization by 4 years of age

Ola Ozernov‐Palchik, Amanda O’Brien, Elizabeth Jiachen Lee et al. · 2026 · Nature Communications

In adults, left hemisphere (LH) damage often leads to aphasia, but many cases of early damage leave linguistic processing intact, with a functional language system developing in the right hemisphere. To explain this early apparent equipotentiality of the two hemispheres for language, some have proposed that the language system is more bilateral during early development and becomes increasingly left-lateralized with age. We examined language lateralization using fMRI in two large developmental cohorts (total n=273 children aged 4-16 years; n=107 adults). Strong, adult-like LH lateralization (in

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Failed Experiment ReportOpen accessNeuroscience

Microglia-derived nanovesicles synchronize macroautophagy and chaperone-mediated autophagy for Alzheimer’s disease therapy

Min Li, Min Li, Shuang Chen et al. · 2025 · Signal Transduction and Targeted Therapy

Dysregulated autophagy is a hallmark of Alzheimer's disease (AD), yet the extent of impairment in macroautophagy and chaperone-mediated autophagy (CMA) remains unclear. Here, we show that both pathways are disrupted in AD model mice, preceding β-amyloid accumulation and driving disease progression. However, therapeutic autophagy modulation is severely restricted by the blood-brain barrier (BBB). To overcome this, we developed Microglia-Liposome Fusion Extrusion (MiLi-FE), a method to engineer microglia-derived nanovesicles (AR@ENV) for the codelivery of AR7 (a CMA inducer) and rapamycin (a mac

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Negative / Null Result ReportOpen accessNeuroscience

Neuroinflammation in Schizophrenia: An Overview of Evidence and Implications for Pathophysiology

Evgeny A. Ermakov, Irina A. Mednova, Anastasiia S. Boiko et al. · 2025 · Journal of Integrative Neuroscience

Neuroinflammation, meaning an inflammatory process primarily occurring within the central nervous system (CNS), is thought to be associated with the pathogenesis of psychiatric disorders including schizophrenia (SC), although existing evidence is sometimes contradictory. This review critically summarizes the existing data on neuroinflammation and possible neuroinflammatory mechanisms in the pathogenesis of SC. Despite heterogeneity and inconsistency, the existing evidence indicates dysregulation of inflammatory genes and infiltration of the CNS parenchyma by immune cells, disturbances in the b

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Negative / Null Result ReportOpen accessNeuroscience

Exploring Bottom-Up Visual Processing and Visual Hallucinations in Parkinson's Disease With Dementia

Nicholas Murphy, Alison Killen, Rajnish Kumar Gupta et al. · 2021 · Frontiers in Neurology

Visual hallucinations (VH) are a common symptom of Parkinson's disease with dementia (PDD), affecting up to 65% of cases. Integrative models of their etiology posit that a decline in executive control of the visuo-perceptual system is a primary mechanism of VH generation. The role of bottom-up processing in the manifestation of VH in this condition is still not clear although visual evoked potential (VEP) differences have been associated with VH at an earlier stage of PD. Here we compared the amplitude and latency pattern reversal VEPs in healthy controls ( n = 21) and PDD patients ( n = 34) w

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Negative / Null Result ReportOpen accessNeuroscience

EEG-based classification of alzheimer’s disease and frontotemporal dementia using functional connectivity

Tjaša Mlinarič, Arne Van Den Kerchove, Zoe I. Barinaga et al. · 2026 · Scientific Reports

Abstract Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are two major causes of dementia, with overlapping clinical and pathophysiological characteristics. We investigated whether resting-state EEG functional connectivity could distinguish AD, FTD, and healthy controls (HC) using a stacked ensemble learning approach. A publicly available dataset (openneuro.org/datasets/ds004504) was used to extract multiple connectivity metrics across frequency bands. Base classifiers were trained using the Fisher’s Geodesic Minimum Distance to Mean (FgMDM) approach with Euclidean or Riemannian dis

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Negative / Null Result ReportOpen accessNeuroscience

Hierarchical interactions between sensory cortices defy predictive coding

Jacob A. Westerberg, Pieter R. Roelfsema · 2025 · Trends in Cognitive Sciences

Perceptual experience depends on recurrent interactions between lower and higher cortices. One theory, predictive coding, posits that feedback from higher to lower brain regions decreases neuronal activity predicted by higher-level representations. Despite the widespread adoption of predictive coding in neuroscience, the correspondence to neurophysiological findings in sensory cortices remains elusive. Here, we review how the canonical patterns of intra- and inter-cortical interactions that occur during perception and shifts of attention deviate from those predicted by predictive coding. We ar

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Negative / Null Result ReportNeuroscience

Failure to replicate talker-specific syntactic adaptation.

Linda Liu, Zachary Burchill, Michael K. Tanenhaus et al. · 2017 · eScholarship (California Digital Library)

Sentence understanding is affected by recent experience. Animportant open question is whether this reflects adaptationto the statistics of the input. Support for this hypothesiscomes from the recent finding that listeners can…

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Negative / Null Result ReportOpen accessNeuroscience

The myth of the Bayesian brain

Madhur Mangalam · 2025 · European Journal of Applied Physiology

The Bayesian brain hypothesis-the idea that neural systems implement or approximate Bayesian inference-has become a dominant framework in cognitive neuroscience over the past two decades. While mathematically elegant and conceptually unifying, this paper argues that the hypothesis occupies an ambiguous territory between useful metaphor and testable, biologically plausible mechanistic explanation. We critically examine the key claims of the Bayesian brain hypothesis, highlighting issues of unfalsifiability, biological implausibility, and inconsistent empirical support. The framework's remarkabl

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Negative / Null Result ReportNeuroscience

Combined lipid emulsion and ACLS resuscitation following bupivacaine- and hypoxia-induced cardiovascular collapse in unanesthetized swine.

Brent A Bushey, Victor H Auld, John E Volk et al. · 2011 · PubMed

This study examined whether combining lipid emulsion and advanced cardiac life support (ACLS) improves survival in an unanesthetized swine model of bupivacaine- and hypoxia-induced cardiovascular collapse. Arterial and venous catheters and…

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