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1.
Hippocampus ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39268888

RESUMEN

Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (-24%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

2.
NPJ Biodivers ; 3(1): 6, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-39242842

RESUMEN

The Convention on Biological Biodiversity (CBD) exists as a major multilateral environmental agreement to safeguard biodiversity and "live in harmony with nature". To deliver it, strategies and frameworks are set out in regular agreements that are then implemented at the national scale. However, we are not on track to achieve overall goals, and frameworks so far have not been successful. This could be due to unambitious targets, low follow-through on commitments, or desired outcomes for nature not being achieved when action is taken. Here, we focus on national planning and reporting documents from a set of 30% of Parties to the CBD. We found that nearly half of the commitments mentioned in national planning documents did not appear in the Sixth National Reports and that further losses emerged due to measures reported as incomplete or ineffective. There were differences between commitments to each of the Aichi Targets, with more losses in high-profile and "institutionally challenging" Targets. Commitments from Parties in different Human Development Index categories had different outcomes among Targets, and Parties self-identifying as "megadiverse countries" had overall higher rates of reported success. Our results are important for informing the monitoring of commitment implementation in the Kunming-Montreal "global biodiversity package".

3.
Elife ; 122024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037765

RESUMEN

Hippocampal place cells in freely moving rodents display both theta phase precession and procession, which is thought to play important roles in cognition, but the neural mechanism for producing theta phase shift remains largely unknown. Here, we show that firing rate adaptation within a continuous attractor neural network causes the neural activity bump to oscillate around the external input, resembling theta sweeps of decoded position during locomotion. These forward and backward sweeps naturally account for theta phase precession and procession of individual neurons, respectively. By tuning the adaptation strength, our model explains the difference between 'bimodal cells' showing interleaved phase precession and procession, and 'unimodal cells' in which phase precession predominates. Our model also explains the constant cycling of theta sweeps along different arms in a T-maze environment, the speed modulation of place cells' firing frequency, and the continued phase shift after transient silencing of the hippocampus. We hope that this study will aid an understanding of the neural mechanism supporting theta phase coding in the brain.


Asunto(s)
Potenciales de Acción , Células de Lugar , Ritmo Teta , Animales , Ritmo Teta/fisiología , Células de Lugar/fisiología , Potenciales de Acción/fisiología , Modelos Neurológicos , Hipocampo/fisiología , Hipocampo/citología , Adaptación Fisiológica , Ratas
4.
Curr Biol ; 34(10): 2256-2264.e3, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38701787

RESUMEN

The hippocampal formation contains neurons responsive to an animal's current location and orientation, which together provide the organism with a neural map of space.1,2,3 Spatially tuned neurons rely on external landmark cues and internally generated movement information to estimate position.4,5 An important class of landmark cue are the boundaries delimiting an environment, which can define place cell field position6,7 and stabilize grid cell firing.8 However, the precise nature of the sensory information used to detect boundaries remains unknown. We used 2-dimensional virtual reality (VR)9 to show that visual cues from elevated walls surrounding the environment are both sufficient and necessary to stabilize place and grid cell responses in VR, when only visual and self-motion cues are available. By contrast, flat boundaries formed by the edges of a textured floor did not stabilize place and grid cells, indicating only specific forms of visual boundary stabilize hippocampal spatial firing. Unstable grid cells retain internally coherent, hexagonally arranged firing fields, but these fields "drift" with respect to the virtual environment over periods >5 s. Optic flow from a virtual floor does not slow drift dynamics, emphasizing the importance of boundary-related visual information. Surprisingly, place fields are more stable close to boundaries even with floor and wall cues removed, suggesting invisible boundaries are inferred using the motion of a discrete, separate cue (a beacon signaling reward location). Subsets of place cells show allocentric directional tuning toward the beacon, with strength of tuning correlating with place field stability when boundaries are removed.


Asunto(s)
Señales (Psicología) , Células de Red , Realidad Virtual , Animales , Células de Red/fisiología , Masculino , Hipocampo/fisiología , Percepción Espacial/fisiología , Ratas , Células de Lugar/fisiología , Percepción Visual/fisiología , Ratas Long-Evans , Orientación/fisiología
5.
PLoS One ; 19(5): e0300371, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753613

RESUMEN

Chameleons (family Chamaeleonidae) are a distinctive group of reptiles, mainly found in Africa, which have high local endemism and face significant threats from the international wildlife trade. We review the scale and structure of international chameleon trade, with a focus on collection in and exports from Tanzania; a hotspot of chameleon diversity. Analysis used data from the CITES Trade Database 2000-2019, combined with assessment of online trade, and on-the-ground surveys in Tanzania in 2019. Between 2000 and 2019, 1,128,776 live chameleons from 108 species were reported as exported globally, with 193,093 of these (from 32 species) exported by Tanzania. Both global and Tanzanian chameleon exports declined across the study period, driven by decreased trade in generalist genera. Whilst the proportion of captive-bred individuals increased across time for the generalist taxa, the majority of range-restricted taxa in trade remained largely wild-sourced. For Tanzanian exports, 41% of chameleons were from one of the 23 endemic species, and 10 of the 12 Tanzanian endemic species in trade are categorised as threatened with extinction by IUCN. In terms of online trade, of the 42 Tanzanian species assessed, there was evidence of online sale for 83.3% species, and 69% were actively for sale with prices listed. Prices were on average highest for Trioceros species, followed by Kinyongia, Rieppeleon, Rhampholeon, and Chameleo. Field work in Tanzania provided evidence that the historic harvest of endemic chameleon species has been higher than the quantities of these species reported as exported by Tanzania in their annual trade reports to CITES. However, we found no field evidence for trade in 2020 and 2021, in line with Tanzanian regulations that applied a blanket ban on all exports of live wild animals. Literature evidence, however, suggests that illegal trade continued to Europe from seizures of Tanzanian chameleon species in Austria in 2021.


Asunto(s)
Animales Salvajes , Comercio , Conservación de los Recursos Naturales , Lagartos , Animales , Tanzanía , Especies en Peligro de Extinción/estadística & datos numéricos , Especies en Peligro de Extinción/tendencias , Biodiversidad , Comercio de Vida Silvestre
6.
Nat Commun ; 15(1): 982, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302455

RESUMEN

Boundaries to movement form a specific class of landmark information used for navigation: Boundary Vector Cells (BVCs) are neurons which encode an animal's location as a vector displacement from boundaries. Here we characterise the prevalence and spatial tuning of subiculum BVCs in adult and developing male rats, and investigate the relationship between BVC spatial firing and boundary geometry. BVC directional tunings align with environment walls in squares, but are uniformly distributed in circles, demonstrating that environmental geometry alters BVC receptive fields. Inserted barriers uncover both excitatory and inhibitory components to BVC receptive fields, demonstrating that inhibitory inputs contribute to BVC field formation. During post-natal development, subiculum BVCs mature slowly, contrasting with the earlier maturation of boundary-responsive cells in upstream Entorhinal Cortex. However, Subiculum and Entorhinal BVC receptive fields are altered by boundary geometry as early as tested, suggesting this is an inherent feature of the hippocampal representation of space.


Asunto(s)
Hipocampo , Percepción Espacial , Ratas , Masculino , Animales , Percepción Espacial/fisiología , Hipocampo/fisiología , Corteza Entorrinal/fisiología , Neuronas/fisiología , Movimiento
7.
Alzheimers Dement ; 20(4): 2779-2793, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38421123

RESUMEN

INTRODUCTION: Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)-based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD. METHODS: We compared immersive virtual reality (VR) PI ability to other cognitive domains in 100 asymptomatic midlife adults stratified by hereditary and physiological AD risk factors. In some participants, behavioral data were compared to 7T magnetic resonance imaging (MRI) measures of brain structure and function. RESULTS: Midlife PI impairments predicted both hereditary and physiological AD risk, with no corresponding multi-risk impairment in episodic memory or other spatial behaviors. Impairments associated with altered functional MRI signal in the posterior-medial EC. DISCUSSION: Altered PI may represent the transition point from at-risk state to disease manifestation in AD, prior to impairment in other cognitive domains.


Asunto(s)
Enfermedad de Alzheimer , Adulto , Humanos , Enfermedad de Alzheimer/patología , Corteza Entorrinal/patología , Encéfalo/patología , Imagen por Resonancia Magnética/métodos
8.
PLoS One ; 19(2): e0281408, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38315706

RESUMEN

Since 1997 Tanzania has undertaken a process to identify and declare a network of Nature Forest Reserves (NFRs) with high biodiversity values, from within its existing portfolio of national Forest Reserves, with 16 new NFRs declared since 2015. The current network of 22 gazetted NFRs covered 948,871 hectares in 2023. NFRs now cover a range of Tanzanian habitat types, including all main forest types-wet, seasonal, and dry-as well as wetlands and grasslands. NFRs contain at least 178 of Tanzania's 242 endemic vertebrate species, of which at least 50% are threatened with extinction, and 553 Tanzanian endemic plant taxa (species, subspecies, and varieties), of which at least 50% are threatened. NFRs also support 41 single-site endemic vertebrate species and 76 single-site endemic plant taxa. Time series analysis of management effectiveness tracking tool (METT) data shows that NFR management effectiveness is increasing, especially where donor funds have been available. Improved management and investment have resulted in measurable reductions of some critical threats in NFRs. Still, ongoing challenges remain to fully contain issues of illegal logging, charcoal production, firewood, pole-cutting, illegal hunting and snaring of birds and mammals, fire, wildlife trade, and the unpredictable impacts of climate change. Increased tourism, diversified revenue generation and investment schemes, involving communities in management, and stepping up control measures for remaining threats are all required to create a network of economically self-sustaining NFRs able to conserve critical biodiversity values.


Asunto(s)
Conservación de los Recursos Naturales , Bosques , Animales , Tanzanía , Conservación de los Recursos Naturales/métodos , Ecosistema , Biodiversidad , Mamíferos
9.
Nat Hum Behav ; 8(3): 526-543, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38242925

RESUMEN

Episodic memories are (re)constructed, share neural substrates with imagination, combine unique features with schema-based predictions and show schema-based distortions that increase with consolidation. Here we present a computational model in which hippocampal replay (from an autoassociative network) trains generative models (variational autoencoders) to (re)create sensory experiences from latent variable representations in entorhinal, medial prefrontal and anterolateral temporal cortices via the hippocampal formation. Simulations show effects of memory age and hippocampal lesions in agreement with previous models, but also provide mechanisms for semantic memory, imagination, episodic future thinking, relational inference and schema-based distortions including boundary extension. The model explains how unique sensory and predictable conceptual elements of memories are stored and reconstructed by efficiently combining both hippocampal and neocortical systems, optimizing the use of limited hippocampal storage for new and unusual information. Overall, we believe hippocampal replay training generative models provides a comprehensive account of memory construction, imagination and consolidation.


Asunto(s)
Memoria Episódica , Lóbulo Temporal , Humanos , Hipocampo/patología
10.
Psychol Rev ; 131(2): 578-597, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37166847

RESUMEN

Two of the main impediments to learning complex tasks are that relationships between different stimuli, including rewards, can be uncertain and context-dependent. Reinforcement learning (RL) provides a framework for learning, by predicting total future reward directly (model-free RL), or via predictions of future states (model-based RL). Within this framework, "successor representation" (SR) predicts total future occupancy of all states. A recent theoretical proposal suggests that the hippocampus encodes the SR in order to facilitate prediction of future reward. However, this proposal does not take into account how learning should adapt under uncertainty and switches of context. Here, we introduce a theory of learning SRs using prediction errors which includes optimally balancing uncertainty in new observations versus existing knowledge. We then generalize that approach to a multicontext setting, allowing the model to learn and maintain multiple task-specific SRs and infer which one to use at any moment based on the accuracy of its predictions. Thus, the context used for predictions can be determined by both the contents of the states themselves and the distribution of transitions between them. This probabilistic SR model captures animal behavior in tasks which require contextual memory and generalization, and unifies previous SR theory with hippocampal-dependent contextual decision-making. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Aprendizaje , Refuerzo en Psicología , Animales , Humanos , Recompensa , Incertidumbre , Generalización Psicológica
11.
bioRxiv ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-36789443

RESUMEN

Despite bilateral hippocampal damage dating to perinatal or early-childhood period, and severely-impaired episodic memory that unfolds in later childhood, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganise to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40% while the atrophy of the uncus was moderate (-23%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions, such that the greater the damage, the more likely it is that surrounding cortical areas will be recruited to rescue the putative functions of the damaged subregions. Our findings document for the first time not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

12.
Nat Commun ; 14(1): 7397, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38036557

RESUMEN

Slow waves of neuronal activity are a fundamental component of sleep that are proposed to have homeostatic and restorative functions. Despite this, their interaction with pathology is unclear and there is only indirect evidence of their presence during wakefulness. Using intracortical recordings from the temporal lobe of 25 patients with epilepsy, we demonstrate the existence of local wake slow waves (LoWS) with key features of sleep slow waves, including a down-state of neuronal firing. Consistent with a reduction in neuronal activity, LoWS were associated with slowed cognitive processing. However, we also found that LoWS showed signatures of a homeostatic relationship with interictal epileptiform discharges (IEDs): exhibiting progressive adaptation during the build-up of network excitability before an IED and reducing the impact of subsequent IEDs on network excitability. We therefore propose an epilepsy homeostasis hypothesis: that slow waves in epilepsy reduce aberrant activity at the price of transient cognitive impairment.


Asunto(s)
Epilepsias Parciales , Epilepsia , Humanos , Electroencefalografía , Sueño/fisiología , Cognición
13.
Curr Biol ; 33(21): 4650-4661.e7, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37827151

RESUMEN

Path integration (PI) is impaired early in Alzheimer's disease (AD) but reflects multiple sub-processes that may be differentially sensitive to AD. To characterize these sub-processes, we developed a novel generative linear-angular model of PI (GLAMPI) to fit the inbound paths of healthy elderly participants performing triangle completion, a popular PI task, in immersive virtual reality with real movement. The model fits seven parameters reflecting the encoding, calculation, and production errors associated with inaccuracies in PI. We compared these parameters across younger and older participants and patients with mild cognitive impairment (MCI), including those with (MCI+) and without (MCI-) cerebrospinal fluid biomarkers of AD neuropathology. MCI patients showed overestimation of the angular turn in the outbound path and more variable inbound distances and directions compared with healthy elderly. MCI+ were best distinguished from MCI- patients by overestimation of outbound turns and more variable inbound directions. Our results suggest that overestimation of turning underlies the PI errors seen in patients with early AD, indicating specific neural pathways and diagnostic behaviors for further research.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Anciano , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Pruebas Neuropsicológicas , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/patología , Disfunción Cognitiva/psicología , Biomarcadores
14.
Neural Netw ; 167: 473-488, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37688954

RESUMEN

We introduce a large-scale neurocomputational model of spatial cognition called 'Spacecog', which integrates recent findings from mechanistic models of visual and spatial perception. As a high-level cognitive ability, spatial cognition requires the processing of behaviourally relevant features in complex environments and, importantly, the updating of this information during processes of eye and body movement. The Spacecog model achieves this by interfacing spatial memory and imagery with mechanisms of object localisation, saccade execution, and attention through coordinate transformations in parietal areas of the brain. We evaluate the model in a realistic virtual environment where our neurocognitive model steers an agent to perform complex visuospatial tasks. Our modelling approach opens up new possibilities in the assessment of neuropsychological data and human spatial cognition.


Asunto(s)
Cognición , Memoria Espacial , Humanos , Visión Ocular , Percepción Espacial , Atención , Percepción Visual
15.
Lancet Psychiatry ; 10(10): 760-767, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37739583

RESUMEN

BACKGROUND: Childhood maltreatment is a risk factor for the development of post-traumatic stress disorders and psychosis. However, the association between post-traumatic stress disorder (PTSD), including complex PTSD, and psychotic symptoms is unknown. We investigated whether the presence of PTSD and complex PTSD was associated with psychotic symptom severity within survivors of developmental trauma. METHODS: As part of the Investigating Mechanisms underlying Psychosis Associated with Childhood Trauma (IMPACT) study, from Aug 20, 2020, to Jan 24, 2021, and from Sept 9, 2022, to Feb 21, 2023, using study advertisement on online platforms we recruited adult (≥18 years) participants who had experienced developmental trauma without a psychiatric diagnosis in the UK and South Korea. We measured whether participants met diagnostic thresholds for PTSD and complex PTSD using the self-reported International Trauma Questionnaire, and psychotic symptoms using the self-reported Community Assessment of Psychic Experiences. We used linear regression, adjusting for sociodemographic variables such as age, sex, ethnicity, educational attainment, and socioeconomic status, to examine whether there was an association between PTSD and complex PTSD and psychotic symptoms. The study is registered in the UK (University College London Research Ethics Committee [14317/001] and the National Health Service Research Ethics Committee [22/YH/0096]) and South Korea (Institutional Review Board of Seoul National University Bundang Hospital [B-2011-648-306]), and is ongoing. FINDINGS: Of the 2675 participants who took part in the study, 1273 had experienced developmental trauma and were included in the study in the UK (n=475) and South Korea (n=798), comprising 422 (33%) men and 851 (67%) women with a mean age of 26·9 years (SD 6, range 18-40), mostly of White British (n=328) or South Korean (n=798) ethnicity. We found no significant association between PTSD and psychotic symptom severity (total severity ß=-2·40 [SE 3·28], p=0·47), compared with participants who did not meet PTSD or complex PTSD caseness. We found a significant relationship between complex PTSD and psychotic symptom severity (total severity ß=22·62 [SE 1·65], p<0·0001), including for positive (ß=12·07 [SE 0·99], p<0·0001) and negative symptoms (ß=10·5 [SE 0·95], p<0·0001), compared with participants who did not meet PTSD or complex PTSD caseness. INTERPRETATION: Health systems must assess individuals with previous developmental trauma for complex PTSD and treat those affected. These individuals should also be assessed for psychotic symptoms, and if necessary, preventative measures should be taken to reduce risk of conversion. Further work should assess whether treating complex PTSD modifies the risk of conversion to psychosis. FUNDING: UKRI Future Leaders Fellowship, British Medical Association Margaret Temple Award for Schizophrenia Research, and the National Research Foundation of Korea-Korea Government.


Asunto(s)
Trastornos Psicóticos , Trastornos por Estrés Postraumático , Masculino , Adulto , Femenino , Humanos , Adolescente , Adulto Joven , Trastornos por Estrés Postraumático/epidemiología , Estudios Transversales , Medicina Estatal , Trastornos Psicóticos/epidemiología , República de Corea/epidemiología , Reino Unido/epidemiología
16.
Cereb Cortex ; 33(13): 8792-8802, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37160345

RESUMEN

Hippocampal theta oscillations have been implicated in associative memory in humans. However, findings from electrophysiological studies using scalp electroencephalography or magnetoencephalography, and those using intracranial electroencephalography are mixed. Here we asked 10 pre-surgical epilepsy patients undergoing intracranial electroencephalography recording, along with 21 participants undergoing magnetoencephalography recordings, to perform an associative memory task, and examined whether hippocampal theta activity during encoding was predictive of subsequent associative memory performance. Across the intracranial electroencephalography and magnetoencephalography studies, we observed that theta power in the hippocampus increased during encoding, and that this increase differed as a function of subsequent memory, with greater theta activity for pairs that were successfully retrieved in their entirety compared with those that were not remembered. This helps to clarify the role of theta oscillations in associative memory formation in humans, and further, demonstrates that findings in epilepsy patients undergoing intracranial electroencephalography recordings can be extended to healthy participants undergoing magnetoencephalography recordings.


Asunto(s)
Epilepsia , Ritmo Teta , Humanos , Ritmo Teta/fisiología , Hipocampo/fisiología , Electroencefalografía , Recuerdo Mental/fisiología , Epilepsia/cirugía
17.
JAMA Psychiatry ; 80(7): 700-709, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37223934

RESUMEN

Importance: Understanding the mechanisms of delusion formation in Alzheimer disease (AD) could inform the development of therapeutic interventions. It has been suggested that delusions arise as a consequence of false memories. Objective: To investigate whether delusions in AD are associated with false recognition, and whether higher rates of false recognition and the presence of delusions are associated with lower regional brain volumes in the same brain regions. Design, Setting, and Participants: Since the Alzheimer's Disease Neuroimaging Initiative (ADNI) launched in 2004, it has amassed an archive of longitudinal behavioral and biomarker data. This cross-sectional study used data downloaded in 2020 from ADNI participants with an AD diagnosis at baseline or follow-up. Data analysis was performed between June 24, 2020, and September 21, 2021. Exposure: Enrollment in the ADNI. Main Outcomes and Measures: The main outcomes included false recognition, measured with the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13) and the Rey Auditory Verbal Learning Test (RAVLT) and volume of brain regions corrected for total intracranial volume. Behavioral data were compared for individuals with delusions in AD and those without using independent-samples t tests or Mann-Whitney nonparametric tests. Significant findings were further explored using binary logistic regression modeling. For neuroimaging data region of interest analyses using t tests, Poisson regression modeling or binary logistic regression modeling and further exploratory, whole-brain voxel-based morphometry analyses were carried out to explore the association between regional brain volume and false recognition or presence of delusions. Results: Of the 2248 individuals in the ADNI database, 728 met the inclusion criteria and were included in this study. There were 317 (43.5%) women and 411 (56.5%) men. Their mean (SD) age was 74.8 (7.4) years. The 42 participants with delusions at baseline had higher rates of false recognition on the ADAS-Cog 13 (median score, 3; IQR, 1 to 6) compared with the 549 control participants (median score, 2; IQR, 0 to 4; U = 9398.5; P = .04). False recognition was not associated with the presence of delusions when confounding variables were included in binary logistic regression models. An ADAS-Cog 13 false recognition score was inversely associated with left hippocampal volume (odds ratio [OR], 0.91 [95% CI, 0.88-0.94], P < .001), right hippocampal volume (0.94 [0.92-0.97], P < .001), left entorhinal cortex volume (0.94 [0.91-0.97], P < .001), left parahippocampal gyrus volume (0.93 [0.91-0.96], P < .001), and left fusiform gyrus volume (0.97 [0.96-0.99], P < .001). There was no overlap between locations associated with false recognition and those associated with delusions. Conclusions and Relevance: In this cross-sectional study, false memories were not associated with the presence of delusions after accounting for confounding variables, and no indication for overlap of neural networks for false memories and delusions was observed on volumetric neuroimaging. These findings suggest that delusions in AD do not arise as a direct consequence of misremembering, lending weight to ongoing attempts to delineate specific therapeutic targets for treatment of psychosis.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Masculino , Humanos , Femenino , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Deluciones , Estudios Transversales , Imagen por Resonancia Magnética , Neuroimagen/métodos , Disfunción Cognitiva/psicología
19.
bioRxiv ; 2023 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-36778428

RESUMEN

The entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration, we predicted that path integration impairment would represent the first behavioural change in adults at-risk of AD. Using immersive virtual reality, we found that midlife path integration impairments predicted both hereditary and physiological AD risk, with no corresponding impairment on tests of episodic memory or other spatial behaviours. Impairments related to poorer angular estimation and were associated with hexadirectional grid-like fMRI signal in the posterior-medial EC. These results indicate that altered path integration may represent the transition point from at-risk state to disease onset in AD, prior to impairment in other cognitive domains.

20.
Sci Total Environ ; 860: 160464, 2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36427741

RESUMEN

Mercury (Hg) is a globally distributed heavy metal, with negative effects on wildlife. Its most toxic form, methylmercury (MeHg), predominates in aquatic systems. Levels of MeHg in marine predators can vary widely among individuals and populations. Leach's storm-petrels (Hydrobates leucorhous) have elevated levels of Hg but the role of Hg in storm-petrel population declines is unknown. In this study, we used egg and blood samples to study variation in Hg exposure among several northwest Atlantic colonies during breeding seasons, thereby evaluating relative toxicity risk within and among colonies. Total mercury (THg) concentrations were higher with increasing colony latitude, and were more pronounced in blood than in eggs. THg concentrations in blood were mostly associated with low toxicity risk in birds from the southern colonies and moderate risks in birds from the northern colonies; however, those values did not affect hatching or fledging success. THg concentrations in both eggs and blood were positively correlated with δ34S, emphasizing the role of sulfate-reducing bacteria in methylation of THg acquired through marine food webs, which is consistent with enriched δ34S profiles. By associating tracking data from foraging trips with THg from blood, we determined that blood THg levels were higher when storm-petrel's intensive search locations were over deeper waters. We conclude that spatial variation in THg concentrations in Leach's storm-petrels is attributable to differences in ocean depth at foraging locations, both at individual and colony levels. Differences in diet among colonies observed previously are the most likely cause for observed blood THg differences. As one of the few pelagic seabird species breeding in Atlantic Canada, with limited overlap in core foraging areas among colonies, Leach's storm-petrels can be used as biomonitors for less sampled offshore pelagic regions. The global trend in Hg emissions combined with legacy levels warrant continued monitoring for toxicity effects in seabirds.


Asunto(s)
Mercurio , Compuestos de Metilmercurio , Humanos , Animales , Aves , Mercurio/análisis , Animales Salvajes , Canadá , Monitoreo del Ambiente
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