Time to retire the serial Papez circuit: Implications for space, memory, and attention

Aggleton, John P.; Nelson, Andrew John Dudley; O’Mara, Shane M.

doi:10.1016/j.neubiorev.2022.104813

Cited by 21 publications

(10 citation statements)

References 227 publications

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“…The decreased latency of the limbic H-wave after ANT stimulation suggests an anterior route of propagation, potentially traveling from HC, through the fornix to the ANT, and later through the parolfactory cingulum bundle to the PCC, (Wu et al, 2016;Wang et al, 2020). By looking at the visual match between the electrode positions, estimated bundles and their endpoints, in addition to the presence of the limbic H-wave after ANT stimulation, we hypothesize that the limbic H-wave is generated by the circuit between the hippocampus, ANT, and the PCC, consistent with the previous reports on the hippocampal limbic system (Rolls, 2015;Wang et al, 2020;Aggleton et al, 2022). Interestingly, limbic H-waves in the PCC are not as clearly observed in subject 7 under HC stimulation (Figure 7A, orange traces), whereas ANT stimulation evoked clear limbic H-waves.…”

Section: Variability In Latency Of Responsessupporting

confidence: 88%

“…There are two possible pathways from the HC to the PCC, the posterior and the anterior. The posterior, connecting through the parahippocampal cingulum bundle (ph cin ) [Figure 7A, orange tract] (Jones et al, 2013; Wu et al, 2016); and the anterior, connecting through the thalamic portion of the limbic system, where hippocampus projects through the fornix (fx), to the mammillary bodies (MB), which project through the mammillothalamic tract (Grewal et al, 2018) to the ANT, that further projects to the PCC through the parolfactory cingulum (po cin ) bundle (Mufson and Pandya, 1984; Jones et al, 2013; Wu et al, 2016; Wang et al, 2020; Gregg et al,2021; Aggleton et al, 2022). DSI studio software tool can separately estimate different subsegments of the cingulum bundle (Wu et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

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Signatures of electrical stimulation driven network interactions in the human limbic system

Valencia

Gregg

Worrell

et al. 2022

Preprint

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Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomical, neurophysiological, and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Previous studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In seven patients with drug-resistant epilepsy, we stimulated the limbic system with single-pulse electrical stimulation (SPES). Reliable cortico-cortical evoked potentials (CCEPs) were measured between the hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the limbic H-wave. This limbic H-wave was visually distinct and separately decoded from the amygdala to ACC waveform. Diffusion MRI data show that the measured endpoints in the PCC overlap with the endpoints of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic H-wave may travel through the fornix, mammillary bodies, and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic H-wave but with a shorter latency. Limbic subsystems have unique stimulation-evoked signatures that may be used in the future to help develop stimulation therapies.

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Section: Variability In Latency Of Responsessupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Signatures of electrical stimulation driven network interactions in the human limbic system

Valencia

Gregg

Worrell

et al. 2022

Preprint

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“…Furthermore, our analysis revealed atrophy in the posterior cingulate cortex (PCC) among AD patients carrying the APOE ε4 allele compared to non-carriers. The PCC is an integral part of the Papez circuit, which also includes the hippocampus, mammillary bodies, thalamus, and parahippocampal gyrus (Aggleton et al 2022). This circuit plays a pivotal role in memory formation, emotional regulation, and is implicated in the episodic memory and spatial navigation challenges seen in AD (Forno et al 2021).…”

Section: Discussionmentioning

confidence: 99%

The impact of APOE ε4 in Alzheimer’s disease: a meta-analysis of voxel-based morphometry studies

Bailey,

Ilchovska,

Hosseini

et al. 2024

Preprint

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BackgroundAlzheimer’s disease (AD) is the most prevalent form of dementia, exerting substantial personal and societal impacts. The apolipoprotein E (APOE) ε4 allele is a known genetic factor that increases the risk of AD, contributing to more severe brain atrophy and exacerbated symptoms.PurposeWe aim to provide a comprehensive review of the impacts of the APOE ε4 allele on brain atrophy in AD and mild cognitive impairment (MCI) as a transitional stage of AD.MethodsWe performed a coordinate-based meta-analysis of voxel-based morphometry (VBM) studies to identify the patterns of grey matter atrophy in APOE ε4 carriers vs. non-carriers. We obtained coordinate-based structural magnetic resonance imaging (MRI) data for 1135 individuals from 12 studies on PubMed and Google Scholar that met our inclusion criteria.ResultsWe found significant atrophy in the hippocampus and parahippocampus of APOE ε4 carriers compared to non-carriers, especially within the AD and MCI groups, while healthy controls showed no significant atrophy in these regions.ConclusionOur meta-analysis sheds light on the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, emphasizing the allele’s critical influence on neurodegeneration, especially in the hippocampus. Our findings contribute to the understanding of the disease’s pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals with the APOE ε4 allele who are at risk for Alzheimer’s Disease.

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“…The anatomical circuit also contains the hypothalamus and the mamillary bodies in the original proposal by Papez [80]. This circuit has progressively been separated from its hypothesized function in emotion [83] and its anatomical study has made it evolve into a more complex network that is relevant for several neurologic conditions, such as Alzheimer’s disease, and their treatments [81, 84]. Additional structures have been incorporated into the Papez circuit based on their anatomical connections, including the amygdala, which is a brain region of the meta-analytical default mode network in healthy adults and altered brain site in Alzheimer’s disease [85].…”

Section: Discussionmentioning

confidence: 99%

The Subcortical Default Mode Network and Alzheimer’s Disease: A systematic review and Activation Likelihood Estimation Meta-Analysis

Seoane,

van den Heuvel,

Acebes

et al. 2023

Preprint

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The default mode network is a central cortical brain network suggested to play a major role in several disorders, and to be particularly vulnerable to the neuropathological hallmarks of Alzheimer’s disease. Subcortical involvement in the default mode network and its alteration in Alzhimer’s disease remains largely unknown. We performed a systematic review, meta-analysis, and empirical validation of the subcortical default mode network in healthy adults, combined with a systematic review, meta-analysis, and network analysis of the involvement of subcortical default mode areas in Alzheimer’s disease. Our results show that, besides the well-known cortical default mode network brain regions, the default mode network consistently includes subcortical regions, namely the thalamus, lobule and vermis IX and right Crus I/II of the cerebellum, and the amygdala. Network analysis also suggests the involvement of the caudate nucleus. In Alzheimer’s disease, we observed a left-lateralized cluster of decrease in functional connectivity which covered the medial temporal lobe and amygdala and showed overlap with the default mode network in a portion covering parts of the left anterior hippocampus and left amygdala. An increase in functional connectivity was also found in the right anterior insula. These results confirm the consistency of subcortical contributions to the default mode network in healthy adults and highlight the relevance of the subcortical default mode network alteration in Alzheimer’s disease.

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Time to retire the serial Papez circuit: Implications for space, memory, and attention

Cited by 21 publications

References 227 publications

Signatures of electrical stimulation driven network interactions in the human limbic system

Signatures of electrical stimulation driven network interactions in the human limbic system

The impact of APOE ε4 in Alzheimer’s disease: a meta-analysis of voxel-based morphometry studies

The Subcortical Default Mode Network and Alzheimer’s Disease: A systematic review and Activation Likelihood Estimation Meta-Analysis

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