The current study aims to systematically assess and compare the antidepressant outcomes of repetitive transcranial magnetic stimulation (rTMS) with the figure-of-eight (F8)-coil and deep transcranial ...magnetic stimulation (DTMS) with the H1-coil in studies matched on stimulation frequency in unipolar major depressive disorder (MDD).
Electronic search of Medline and PsycInfo identified 19 studies with stimulation frequency of 18-20 Hz using F8-coil (k = 8 randomised sham-controlled trials, RCTs, k = 3 open-label; n = 168 patients) or H1-coil (k = 1 RCT, k = 7 open-label; n = 200). Depression severity (the primary outcome) and response/remission rates (the secondary outcomes) were assessed at session 10.
Effects pooled with random-effects meta-analysis showed a large reduction in depression severity, 29% response, and 15% remission rates after 10 sessions of active stimulation with either coil relative to baseline. Reduction in depression severity was greater in studies with younger patients using either coil. The comparison between coils showed a larger reduction in depression severity in H1-coil vs. F8-coil studies (independent of the study design or the concurrent pharmacotherapy) and a trend towards higher remission rates in F8-coil vs. H1-coils studies. These effects are based on a low volume of studies, are not controlled for placebo, and may not be clinically-relevant. The stimulation protocols differed systematically because stimulation was more focal but less intense (80-110% of the resting motor threshold, MT) in the F8-coil studies and less focal but more intense (120% MT) in the H1-coil studies. Two seizures occurred in the H1-coil studies relative to none in the F8-coil studies.
When matched on frequency, the higher-intensity and less focal stimulation with the H1-coil reduces depression more than the lower-intensity and more focal stimulation with the F8-coil. Head-to-head trials should compare the antidepressant outcomes of F8-coil and H1-coil to identify the most optimal stimulation protocols for acute and longer-lasting efficacy.
•We compared cerebellar grey matter loss in Alzheimer’s disease and normal aging.•Posterior cerebellum was affected by both healthy aging and Alzheimer’s disease.•Healthy aging showed bilateral grey ...matter loss, while AD was right lateralized.•Affected regions participate in default, frontoparietal and attention networks.•AD and aging show partly divergent and convergent cerebellar functional profiles.
Recent findings challenge the prior notion that the cerebellum remains unaffected by Alzheimer’s disease (AD). Yet, it is unclear whether AD exacerbates age-related cerebellar grey matter decline or engages distinct structural and functional territories. We performed a meta-analysis of cerebellar grey matter loss in normal ageing and AD. We mapped voxels with structural decline onto established brain networks, functional parcellations, and along gradients that govern the functional organisation of the cerebellum. Importantly, these gradients track continuous changes in cerebellar specialisation providing a more nuanced measure of the functional profile of regions vulnerable to ageing and AD. Gradient 1 progresses from motor to cognitive territories; Gradient 2 isolates attentional processing; Gradient 3 captures lateralisation differences in cognitive functions. We identified bilateral and right-lateralised posterior cerebellar atrophy in ageing and AD, respectively. Age- and AD-related structural decline only showed partial spatial overlap in right lobule VI/Crus I. Despite the seemingly distinct patterns of AD- and age-related atrophy, the functional profiles of these regions were similar. Both participate in the same macroscale networks (default mode, frontoparietal, attention), support executive functions and language processing, and did not exhibit a difference in relative positions along Gradients 1 or 2. However, Gradient 3 values were significantly different in ageing vs. AD, suggesting that the roles of left and right atrophied cerebellar regions exhibit subtle functional differences despite their membership in similar macroscale networks. These findings provide an unprecedented characterisation of structural and functional differences and similarities in cerebellar grey matter loss between normal ageing and AD.
The cerebellum has strong cortical and subcortical connectivity, but is rarely taken into account for clinical diagnosis in many neurodegenerative conditions, particularly in the absence of clinical ...ataxia. The current meta-analysis aims to assess patterns of cerebellar grey matter atrophy in seven neurodegenerative conditions (Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), progressive supranuclear palsy (MSP)).
We carried out a systematic search in PubMed (any date: 14 July 2016) and a hand search of references from pertinent articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors were contacted to provide missing coordinate data. Peer-reviewed studies with direct comparison of patient and control groups, and availability of coordinate data of grey matter cerebellar atrophy in patients were included. These coordinates were used in an anatomical likelihood estimation meta-analysis.
Across 54 studies, clusters of cerebellar atrophy were found for AD, ALS, FTD, MSA, and PSP. Atrophy patterns were largely disease-specific, with overlap in certain areas of the cerebellar hemisphere, which showed marked atrophy in AD, ALS, FTD and PSP (Crus I/II), and MSA and PSP (lobules I-IV), respectively. Atrophy colocated with cerebellar areas implicated for motor (PSP, MSA) or cognitive symptoms (FTD, ALS, PSP) in the diseases.
Our findings suggest that cerebellar changes are largely disease-specific and correspond to cortical or subcortical changes in neurodegenerative conditions. High clinical variability in PD and HD samples may explain the absence of findings for consistent grey matter loss across studies. Our results have clinical implications for diagnosis and cerebellar neuroimaging referencing approaches.
Aging results in less detailed memories, reflecting reduced fidelity of remembered compared to real-world representations. We tested whether poorer representational fidelity across perception, ...short-term memory (STM), and long-term memory (LTM) are among the earliest signs of cognitive aging. Our paradigm probed target-lure object mnemonic discrimination and precision of object-location binding. Across the lifespan, cognitive deficits were observed in midlife when detailed stimulus representations were required for perceptual and short/long-term forced choice mnemonic discrimination. A continuous metric of object-location source memory combined with computational modeling demonstrated that errors in STM and LTM in middle-aged adults were largely driven by a loss of precision for retrieved memories, not necessarily by forgetting. On a trial-by-trial basis, fidelity of item and spatial information was more tightly bound in LTM compared to STM with this association being unaffected by age. Standard neuropsychological tests without demands on memory quality (digit span, verbal learning) were less sensitive to age effects than STM and LTM precision. Perceptual discrimination predicted mnemonic discrimination. Neuropsychological proxies for prefrontal executive functions correlated with STM, but not LTM fidelity. Conversely, neuropsychological indicators of hippocampal integrity correlated with mnemonic discrimination and precision of both STM and LTM, suggesting partially dissociable mechanisms of interindividual variability in STM and LTM fidelity. These findings suggest that reduced representational fidelity is a hallmark of cognitive aging across perception, STM, and LTM and can be observed from midlife onward. Continuous memory precision tasks may be promising for the early detection of subtle age-related cognitive decline.
Public Significance StatementMemories can vary widely in terms of fidelity, that is how accurately they represent previous experiences. Using measures of memory fidelity, this study demonstrates that a key determinant of whether middle-aged and older adults show memory deficits is whether a task requires memories to be highly detailed. Across the domains of perception, short-term memory, and long-term memory, middle-aged and older adults show poorer performance whenever they need to keep in mind highly detailed information, but largely maintain the ability to form less fine-grained representations. Tasks taxing the fidelity of perceptual and memory representations are therefore particularly sensitive to subtle changes in cognition in aging, providing a potential avenue for their use as tools for early detection of cognitive decline.
Decreased fidelity of mnemonic representations plays a critical role in age-related episodic memory deficits, yet the brain mechanisms underlying such reductions remain unclear. Using functional and ...structural neuroimaging, we examined how changes in two key nodes of the posterior-medial network, the hippocampus and the angular gyrus (AG), might underpin loss of memory precision in older age. Healthy young and older adults completed a memory task that involved reconstructing object features on a continuous scale. Investigation of blood-oxygen-level-dependent (BOLD) activity during retrieval revealed an age-related reduction in activity reflecting successful recovery of object features in the hippocampus, whereas trial-wise modulation of BOLD signal by graded memory precision was diminished in the AG. Gray matter volume of the AG further predicted individual differences in memory precision in older age, beyond likelihood of successful retrieval. These findings provide converging evidence for a role of functional and structural integrity of the AG in constraining the fidelity of episodic remembering in older age, yielding new insights into parietal contributions to age-related episodic memory decline.
Abstract Functional interactions between brain regions can be viewed as a network, enabling neuroscientists to investigate brain function through network science. Here, we systematically evaluate 768 ...data-processing pipelines for network reconstruction from resting-state functional MRI, evaluating the effect of brain parcellation, connectivity definition, and global signal regression. Our criteria seek pipelines that minimise motion confounds and spurious test-retest discrepancies of network topology, while being sensitive to both inter-subject differences and experimental effects of interest. We reveal vast and systematic variability across pipelines’ suitability for functional connectomics. Inappropriate choice of data-processing pipeline can produce results that are not only misleading, but systematically so, with the majority of pipelines failing at least one criterion. However, a set of optimal pipelines consistently satisfy all criteria across different datasets, spanning minutes, weeks, and months. We provide a full breakdown of each pipeline’s performance across criteria and datasets, to inform future best practices in functional connectomics.
Mnemonic discrimination deficits, or impaired ability to discriminate between similar events in memory, is a hallmark of cognitive aging, characterised by a stark age-related increase in false ...recognition. While individual differences in mnemonic discrimination have gained attention due to potential relevance for early detection of Alzheimer's disease, our understanding of the component processes that contribute to variability in task performance across older adults remains limited. The present investigation explores the roles of representational quality, indexed by perceptual discrimination of objects and scenes with overlapping features, and strategic retrieval ability, indexed by standardised tests of executive function, to mnemonic discrimination in a large cohort of older adults (N=124). We took an individual differences approach and characterised the contributions of these factors to performance under Forced Choice (FC) and Yes/No (YN) recognition memory formats, which place different demands on strategic retrieval. Performance in both test formats declined with age. Accounting for age, individual differences in FC memory performance were best explained by perceptual discrimination score, whereas YN memory performance was best explained by executive functions. A linear mixed model and dominance analyses confirmed the relatively greater importance of perceptual discrimination over executive functioning for FC performance, while the opposite was true for YN. These findings highlight parallels between perceptual and mnemonic discrimination in aging, the importance of considering demands on executive functions in the context of mnemonic discrimination, and the relevance of test format for modulating the impact of these factors on performance in older adults.
•Executive functions and perceptual discrimination impact mnemonic discrimination in aging.•The relative contribution of these factors depends on demands placed on strategic retrieval.•In a Forced Choice task, perceptual discrimination explains individual differences in memory.•In a Yes/No task, executive functions best explain individual variability in performance.•Studies should consider choice of task format when aiming to isolate specific mnemonic processes.
Cognitive tests sensitive to the integrity of the medial temporal lobe (MTL), such as mnemonic discrimination of perceptually similar stimuli, may be useful early markers of risk for cognitive ...decline in older populations. Perceptual discrimination of stimuli with overlapping features also relies on MTL but remains relatively unexplored in this context. We assessed mnemonic discrimination in two test formats (Forced Choice, Yes/No) and perceptual discrimination of objects and scenes in 111 community-dwelling older adults at different risk status for cognitive impairment based on neuropsychological screening. We also investigated associations between performance and MTL sub-region volume and thickness. The at-risk group exhibited reduced entorhinal thickness and impaired perceptual and mnemonic discrimination. Perceptual discrimination impairment partially explained group differences in mnemonic discrimination and correlated with entorhinal thickness. Executive dysfunction accounted for Yes/No deficits in at-risk adults, demonstrating the importance of test format for the interpretation of memory decline. These results suggest that perceptual discrimination tasks may be useful tools for detecting incipient cognitive impairment related to reduced MTL integrity in nonclinical populations.
Introduction
Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia.
Methods
We systematically reviewed studies reporting AI for neuroimaging in ...diagnosis and/or prognosis of cognitive neurodegenerative diseases.
Results
A total of 255 studies were identified. Most studies relied on the Alzheimer's Disease Neuroimaging Initiative dataset. Algorithmic classifiers were the most commonly used AI method (48%) and discriminative models performed best for differentiating Alzheimer's disease from controls. The accuracy of algorithms varied with the patient cohort, imaging modalities, and stratifiers used. Few studies performed validation in an independent cohort.
Discussion
The literature has several methodological limitations including lack of sufficient algorithm development descriptions and standard definitions. We make recommendations to improve model validation including addressing key clinical questions, providing sufficient description of AI methods and validating findings in independent datasets. Collaborative approaches between experts in AI and medicine will help achieve the promising potential of AI tools in practice.
Highlights
There has been a rapid expansion in the use of machine learning for diagnosis and prognosis in neurodegenerative disease
Most studies (71%) relied on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with no other individual dataset used more than five times
There has been a recent rise in the use of more complex discriminative models (e.g., neural networks) that performed better than other classifiers for classification of AD vs healthy controls
We make recommendations to address methodological considerations, addressing key clinical questions, and validation
We also make recommendations for the field more broadly to standardize outcome measures, address gaps in the literature, and monitor sources of bias
Systems consolidation theory (SCT) proposes that the hippocampus is not required for retrieval of remote memories. In this issue, Tallman and colleagues observe reduced hippocampal-cortical ...connectivity in recognition memory as a function of memory age, which they interpret as supportive of SCT. We suggest that research seeking to inform this debate would benefit from using perceptually rich stimuli that promote the recollection of high-fidelity contextual details. Tests of recognition alone may not be capable of discerning whether reductions in hippocampal activity or connectivity reflect remote memory retrieval independent of hippocampus (consistent with SCT) or a time-dependent decline in episodic detail.
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