Cerebral hyperactivation across the Alzheimer’s disease pathological cascade

Brain Communications, Год журнала: 2024, Номер 6(6)

Опубликована: Янв. 1, 2024

Neuronal dysfunction in specific brain regions or across distributed networks is a known feature of Alzheimer's disease. An often reported finding the early stage disease presence increased functional MRI (fMRI) blood oxygenation level-dependent signal under task conditions relative to cognitively normal controls, phenomenon as 'hyperactivation'. However, research past decades yielded complex, sometimes conflicting results. The magnitude and topology fMRI hyperactivation patterns have been found vary preclinical clinical spectrum disease, including concomitant 'hypoactivation' some cases. These incongruences are likely due range factors, at which cohort examined, areas studied paradigm utilized evoke these abnormalities. Additionally, perennial question pertains nature context Some propose it reflects compensatory mechanisms sustain cognitive performance, while others suggest linked pathological disruption highly regulated homeostatic cycle that contributes to, even drives, progression. Providing coherent narrative for empirical conceptual discrepancies paramount develop models, understand synergy between cascade tailor effective interventions. We first provide comprehensive overview changes spanning course from ageing then highlight evidence supporting close relationship

Язык: Английский

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Single-value brain activity scores reflect both severity and risk across the Alzheimer’s continuum

Brain, Год журнала: 2024, Номер 147(11), С. 3789 - 3803

Опубликована: Май 14, 2024

Abstract Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME prototypical novelty-related and memory-related functional MRI activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive ageing. Here, we tested utility these potential diagnostic prognostic markers Alzheimer’s disease (AD) risk states like mild cognitive impairment (MCI) subjective decline (SCD). To this end, analysed subsequent memory data individuals SCD, MCI AD dementia well controls first-degree relatives patients (AD-rel) who participated multi-centre DELCODE study (n = 468). Based on individual participants’ whole-brain novelty responses, calculated FADE SAME assessed their association stage, neuropsychological test scores, CSF amyloid positivity APOE genotype. Memory-based showed a considerably larger reference sample groups compared to controls, SCD AD-rel. In addition, novelty-based significantly differed between groups. Across entire sample, single-value correlated performance. The score further Aβ-positive Aβ-negative AD-rel, ApoE ɛ4 carriers non-carriers Hence, are associated both performance factors for AD. Their warrants exploration, particularly patients.

Язык: Английский

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Cognitive reserve against Alzheimer’s pathology is linked to brain activity during memory formation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 13, 2024

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) AD dementia using longitudinal data 490 participants of DELCODE multicentric observational study. Brain measured task fMRI visual memory encoding. Using a multivariate moderation analysis, identify CR-related activity pattern underlying successful encoding moderates detrimental effect pathological load on performance. CR mainly represented more pronounced expression task-active network encompassing deactivation default mode (DMN) activation inferior temporal regions including fusiform gyrus. We devise personalized fMRI-based scores moderate impact performance are positively years education. Furthermore, higher attenuate decline over time. Our findings primarily provide evidence maintenance core circuits DMN as neural basis CR. Individual levels these areas during have prognostic value future decline.

Язык: Английский

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Have you been there before? Decoding recognition of spatial scenes from fMRI signals in precuneus

Human Brain Mapping, Год журнала: 2024, Номер 45(7)

Опубликована: Май 1, 2024

Abstract One potential application of forensic “brain reading” is to test whether a suspect has previously experienced crime scene. Here, we investigated it possible decode real life autobiographic exposure spatial locations using fMRI. In the first session, participants visited four out eight rooms on university campus. During subsequent scanning subjects passively viewed pictures and videos from these (four old, novel) without giving any responses. A multivariate searchlight analysis was employed that trained classifier distinguish between “seen” versus “unseen” stimuli subset six rooms. We found bilateral precuneus encoded information can be used seen unseen also generalized two left training. conclude activity in associated with memory rooms, irrespective identity room, thus supporting parietal contribution episodic for locations. Importantly, could room need explicit judgments about This suggests recognition an automatic response decoded fMRI data, potentially applications concealed tests scene recognition.

Язык: Английский

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Moderating effects of cortical thickness, volume, and memory performance on age differences in neural reinstatement of scene information

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

Abstract The strength of neural reinstatement, a correlate episodic memory retrieval, reportedly reflects the amount and fidelity mnemonic content is weaker in older than younger adults, especially for scene memoranda. Given evidence that age-related declines cortical thickness volume contribute to cognitive decline, we analyzed fMRI data acquired from healthy young adults examine relationships between thickness, volume, age, scene- related reinstatement parahippocampal place area (PPA) medial (MPA), two regions implicated processing. A ‘reinstatement index’ was estimated collected during tests source images, multiple regression analyses were employed effects variables interest on reinstatement. There robust age differences volume. In both interest, fully mediated Additionally, PPA predicted performance independently or age. These findings suggest are by associated with unique components variance strength.

Язык: Английский

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Differential effects of aging, Alzheimer's pathology, and APOE4 on longitudinal functional connectivity and episodic memory in older adults

Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 25, 2025

Abstract Background Both aging and Alzheimer's disease (AD) affect brain networks, with early disruptions occurring in regions involved episodic memory. Few studies have, however, focused on distinguishing region-specific effects of AD-biomarker negative “normal” amyloid- tau pathology functional connectivity. Further, longitudinal combining imaging, biomarkers, cognition are rare. Methods We assessed resting-state connectivity (rsFC) strength graph measures the memory network including medial temporal lobe (MTL), posteromedial cortex (PMC), prefrontal alongside over two years. For this preregistered study, we included 100 older adults who were tau-negative using CSF PET measurements to investigate aging, 70 had data available changes related AD pathology. All participants cognitively unimpaired from PREVENT-AD cohort. used region interest (ROI)-to-ROI bivariate correlations, analysis, multiple regression models. Results In sample, rsFC within PMC, between parahippocampal inferomedial precuneus, posterior hippocampus precuneus decreased time. Additionally, observed a decrease global efficiency. there was steeper efficiency higher baseline age particularly parahippocampal-gyrus regions. lower PMC associated poorer performance. sample data, increase anterior superior Higher MTL-PMC differentially trajectories depending APOE4 genotype. Conclusions Our findings suggest differential Hypoconnectivity cognitive decline. hyperconnectivity decline carriers. Future should more diverse samples, nonetheless, our approach allowed us identify pathology, enhancing cross-sectional research. Hyperconnectivity has been proposed as mechanism before, now contribute specific connections focus future Graphical A ) “Normal aging” tau- biomarker status characterized by strength. B Cognitively Alzheimer’s at (measured via cerebrospinal fluid) exhibited

Язык: Английский

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Frequency-specific directed connectivity between the hippocampus and parietal cortex during verbal and spatial episodic memory: an intracranial EEG replication

Cerebral Cortex, Год журнала: 2024, Номер 34(7)

Опубликована: Июль 1, 2024

Abstract Hippocampus-parietal cortex circuits are thought to play a crucial role in memory and attention, but their neural basis remains poorly understood. We employed intracranial electroencephalography (iEEG) investigate the neurophysiological underpinning of these across three tasks spanning verbal spatial domains. uncovered consistent pattern higher causal directed connectivity from hippocampus both lateral parietal (supramarginal angular gyrus) medial (posterior cingulate cortex) delta–theta band during encoding recall. This was independent activation or suppression states cortex. Crucially, supramarginal gyrus enhanced participants with recall, highlighting its behavioral significance. Our findings align attention-to-memory model, which posits that attention directs cognitive resources toward pertinent information formation. The robustness results demonstrated through Bayesian replication analysis recall periods tasks. study sheds light on casual signaling within hippocampus–parietal circuits, broadening our understanding critical roles human cognition.

Язык: Английский

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Reduced expression of fMRI subsequent memory effects with increasing severity across the Alzheimer’s disease risk spectrum

Imaging Neuroscience, Год журнала: 2024, Номер 2, С. 1 - 23

Опубликована: Янв. 1, 2024

Abstract In functional magnetic resonance imaging (fMRI) studies, episodic memory is commonly investigated with the subsequent paradigm in which brain activity recorded during encoding and analyzed as a function of remembering forgetting. Impaired common individuals or at risk for Alzheimer’s disease (AD), but only few studies have reported effects AD its states like mild cognitive impairment (MCI). One reason this might be that responses may blunted MCI thus less likely to manifest fMRI signal differences. Here, we used Bayesian model selection single-subject general linear models (GLMs) visual novelty experiment compare performance categorical parametric well memory-invariant clinical cohort (N = 468) comprising healthy controls (HC) subjective decline (SCD), MCI, AD, plus relatives patients (AD-rel). We could replicate previously superiority over (Soch, Richter, Schütze, Kizilirmak, Assmann, Knopf, et al., 2021) HC also SCD AD-rel groups. However, outperformed any assuming group, additionally found substantially lower preference compared not differentiating between novel familiar stimuli. Our results suggest voxel-wise memory-related patterns should interpreted caution point need additional alternative approaches investigate function.

Язык: Английский

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Reduced expression of fMRI subsequent memory effects with increasing severity across the Alzheimer’s disease risk spectrum

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 11, 2023

Abstract In functional magnetic resonance imaging (fMRI) studies, episodic memory is commonly investigated with the subsequent paradigm in which brain activity recorded during encoding and analyzed as a function of remembering forgetting. Impaired common individuals or at risk for Alzheimer’s disease (AD), but only few studies have reported effects AD its states like mild cognitive impairment (MCI). One reason this might be that responses may blunted MCI thus less likely to manifest fMRI signal differences. Here, we used Bayesian model selection single-subject general linear models (GLMs) visual novelty experiment compare performance categorical parametric well memory-invariant clinical cohort (N = 468) comprising healthy controls (HC) subjective decline (SCD), MCI, AD, plus relatives patients (AD-rel). We could replicate previously superiority over (Soch et al., 2021a) HC also SCD AD-rel groups. However, outperformed any assuming group, additionally found substantially lower preference compared not differentiating between novel familiar stimuli. Our results suggest voxel-wise memory-related patterns should interpreted caution point need additional alternative approaches investigate function.

Язык: Английский

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Neural Representations of Emotions in Visual, Auditory, and Modality‐Independent Regions Reflect Idiosyncratic Conceptual Knowledge

Human Brain Mapping, Год журнала: 2024, Номер 45(14)

Опубликована: Окт. 1, 2024

ABSTRACT Growing evidence suggests that conceptual knowledge influences emotion perception, yet the neural mechanisms underlying this effect are not fully understood. Recent studies have shown brain representations of facial categories in visual‐perceptual areas predicted by knowledge, but it remains to be seen if auditory regions similarly affected. Moreover, is clear whether these operate at a modality‐independent level. To address questions, we conducted functional magnetic resonance imaging study presenting participants with both and vocal emotional stimuli. This dual‐modality approach allowed us investigate effects on modality‐specific regions. Using univariate representational similarity analyses, found visual (middle lateral occipital cortices) (superior temporal gyrus) were understanding emotions for faces voices, respectively. Additionally, discovered also influenced supra‐modal superior sulcus. Dynamic causal modeling revealed network showing bottom‐up top‐down flows, suggesting complex interplay processing. These findings collectively indicate sensory‐perceptual likely shaped each individual's knowledge.

Язык: Английский

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