Memory Part 3: The Role of the Fornix and Clinical Cases

Raslau, Flavius D.; Augustinack, Jean C.; Klein, Andrew P.; Ulmer, John L.; Mathews, Vincent P.; Mark, Leighton P.

doi:10.3174/ajnr.a4371

Cited by 25 publications

(17 citation statements)

References 15 publications

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“…As MS progresses, multifocal white matter (WM) damage ranging from demyelination to axonal loss may result in disconnection between cortical and subcortical grey matter (GM) areas, involving key structures for cognitive and memory processes even early in the disease course (Dineen et al, 2009; Ontaneda et al, 2021). The limbic system includes crucial WM and GM regions that are involved in aspects of emotions and cognition (Aggleton & Brown, 1999; Thomas et al, 2011), such as the fornix, which is the major efferent WM pathway from the hippocampus with indirect connections to the thalamic nuclei (Raslau et al, 2015; Thomas et al, 2011). The fornix as a part of this extended hippocampal–diencephalic system (i.e., hippocampus, fornix, mamillary bodies and anterior thalamus) (Aggleton & Brown, 1999; Papez, 1995) is crucial for effective encoding, and therefore, new episodic information recalling (Aggleton & Brown, 1999; Thomas et al, 2011) and its damage as well as any other components of this system can cause anterograde amnesia or related memory impairments (Goetz & Pappert, 1999).…”

Section: Introductionmentioning

confidence: 99%

Diffusion imaging of fornix and interconnected limbic deep grey matter is linked to cognitive impairment in multiple sclerosis

Cabrera

Smyth

Blevins

et al. 2021

Eur J of Neuroscience

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Diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) have shown white matter (WM) and deep grey matter (GM) abnormalities in the limbic system of multiple sclerosis (MS) participants. Structures like the fornix have been associated with cognitive impairment (CI) in MS, but the diffusion metrics are often biased by partial volume effects from cerebrospinal fluid (CSF) due to its small bundle size and intraventricular location. These errors in DTI parameter estimation worsen with atrophy in MS. The goal here was to evaluate DTI parameters and volumes of the fornix, as well as associated deep GM structures like the thalamus and hippocampus, with high‐resolution fluid‐attenuated inversion recovery (FLAIR)‐DTI at 3T in 43 MS patients, with and without CI, versus 43 controls. The fornix, thalamus and hippocampus displayed atrophy and/or abnormal diffusion metrics, with the fornix showing the most extensive changes within the structures studied here, mainly in CI MS. The affected fornix volumes and diffusion metrics were associated with thalamic atrophy and atypical diffusion metrics in interconnected limbic GM, larger total lesion volume and global brain atrophy. Lower fractional anisotropy (FA) and higher mean and radial diffusivity in the fornix, lower hippocampus FA and lower thalamus volume were strongly correlated with CI in MS. Hippocampus FA and thalamus atrophy were negatively correlated with fatigue and longer time since MS symptoms onset, respectively. FLAIR‐DTI and volumetric analyses provided methodologically superior evidence for microstructural abnormalities and extensive atrophy of the fornix and interconnected deep GM in MS that were associated with cognitive deficits.

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Section: Introductionmentioning

confidence: 99%

Diffusion imaging of fornix and interconnected limbic deep grey matter is linked to cognitive impairment in multiple sclerosis

Cabrera

Smyth

Blevins

et al. 2021

Eur J of Neuroscience

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“…Our previous study (Ross et al, 2016) showed both ipsilateral and contralateral somatosensory BOLD responses, which indicated circuit involvement between the hippocampus and PSC. In terms of the functional distribution of the forniceal fibers, part of the fornix carries fibers from the caudal hippocampus that process exteroceptive signals (Raslau et al, 2015), and lesion or damage to the fornix lead to visual discrimination deficits (Lech et al, 2016). Another possible explanation of the decreases is that electrical stimulation affected not only the fornix but also brain regions near the fornix such as the hypothalamic area.…”

Section: Discussionmentioning

confidence: 99%

Fornix Stimulation Induces Metabolic Activity and Dopaminergic Response in the Nucleus Accumbens

et al. 2019

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The Papez circuit, including the fornix white matter bundle, is a well-known neural network that is involved in multiple limbic functions such as memory and emotional expression. We previously reported a large-animal study of deep brain stimulation (DBS) in the fornix that found stimulation-induced hemodynamic responses in both the medial limbic and corticolimbic circuits on functional resonance imaging (fMRI) and evoked dopamine responses in the nucleus accumbens (NAc), as measured by fast-scan cyclic voltammetry (FSCV). The effects of DBS on the fornix are challenging to analyze, given its structural complexity and connection to multiple neuronal networks. In this study, we extend our earlier work to a rodent model wherein we characterize regional brain activity changes resulting from fornix stimulation using fludeoxyglucose (18F-FDG) micro positron emission tomography (PET) and monitor neurochemical changes using FSCV with pharmacological confirmation. Both global functional changes and local changes were measured in a rodent model of fornix DBS. Functional brain activity was measured by micro-PET, and the neurochemical changes in local areas were monitored by FSCV. Micro-PET images revealed increased glucose metabolism within the medial limbic and corticolimbic circuits. Neurotransmitter efflux induced by fornix DBS was monitored at NAc by FSCV and identified by specific neurotransmitter reuptake inhibitors. We found a significant increase in the metabolic activity in several key regions of the medial limbic circuits and dopamine efflux in the NAc following fornix stimulation. These results suggest that electrical stimulation of the fornix modulates the activity of brain memory circuits, including the hippocampus and NAc within the dopaminergic pathway.

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“…The DHC is frequently described as a component of the fornix that supports inter-hemispheric 512 connections between the hippocampi (Raslau et al 2015;Tubbs et al 2015). Whilst consistent with 513 the DHC reconstructions shown here, this anatomical interpretation is potentially misleading.…”

Section: Ex Vivo Non-human Primate Mr Data 353mentioning

confidence: 97%

“…Given that these regions play a key role in successful 55 learning and memory (Zola-Morgan et al 1989; Squire and Zola-Morgan 1991; Aggleton and Brown 56 1999; Aggleton 2012), their ability to communicate effectively with contralateral homologous regions 57 via the DHC may also be important for performance in these cognitive domains. 58There have, however, been few studies of the function of the DHC, potentially due to 59 misunderstanding around the cross-species anatomy of the DHC, as distinct from other local fiber 60 populations such as the VHC, fornix, and corpus callosum (Demeter et al 1985;Raslau et al 2015; 61 Tubbs et al 2015). In rodents, the VHC supports dense inter-hemispheric connections between the 62 hippocampi, which originate throughout the long-axis of the hippocampus; in nonhuman primates, 63 VHC connections are reduced so that only the uncal and genual subdivisions of the hippocampal 64 formation are connected to those in the contralateral hemisphere (Demeter et al 1985; Gloor et al 65 1993).…”

mentioning

confidence: 99%

Uncovering a role for the dorsal hippocampal commissure in episodic memory

Postans

Parker

Lundell

et al. 2018

Preprint

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32The dorsal hippocampal commissure (DHC) is a white matter tract that provides inter-hemispheric 33 connections between temporal lobe brain regions. Despite the importance of these regions for 34 learning and memory, there is scant evidence of a role for the DHC in successful memory performance. 35 We used diffusion-weighted MRI (DW-MRI) and white matter tractography to reconstruct the DHC 36 across both humans (in vivo) and nonhuman primates (ex vivo). Across species, our findings 37 demonstrate close consistency between the known anatomy and tract reconstructions of the DHC. 38Anterograde tract-tracer techniques also highlighted the parahippocampal origins of DHC fibers in 39 nonhuman primates. Finally, we derived Diffusion Tensor MRI (DT-MRI) metrics from the DHC in a 40 large sample of human subjects to investigate whether inter-individual variation in DHC 41 microstructure is predictive of memory performance. The mean diffusivity of the DHC was correlated 42 with performance in a standardised episodic memory task; an effect that was not reproduced in a 43 comparison commissure tract -the anterior commissure. These findings highlight a role for the DHC 44 in episodic memory, and our tract reconstruction approach has the potential to generate further novel 45 insights into the role of this previously understudied white matter tract in both health and disease. 46 47 48 The two hemispheres of the brain are connected by commissural fiber systems that include the corpus 50 callosum, anterior commissure (AC), posterior commissure, ventral hippocampal commissure (VHC), 51 and dorsal hippocampal commissure (DHC) (Demeter et al. 1985). The DHC (alternatively the 'dorsal 52 psaltarium') provides inter-hemispheric connections between functionally-related structures in the 53 medial temporal lobes (MTL), including the presubiculum, entorhinal and parahippocampal cortex 54 (Demeter et al. 1985(Demeter et al. , 1990Gloor et al. 1993). Given that these regions play a key role in successful 55 learning and memory (Zola-Morgan et al. 1989; Squire and Zola-Morgan 1991; Aggleton and Brown 56 1999; Aggleton 2012), their ability to communicate effectively with contralateral homologous regions 57 via the DHC may also be important for performance in these cognitive domains. 58There have, however, been few studies of the function of the DHC, potentially due to 59 misunderstanding around the cross-species anatomy of the DHC, as distinct from other local fiber 60 populations such as the VHC, fornix, and corpus callosum (Demeter et al. 1985;Raslau et al. 2015; 61 Tubbs et al. 2015). In rodents, the VHC supports dense inter-hemispheric connections between the 62 hippocampi, which originate throughout the long-axis of the hippocampus; in nonhuman primates, 63 VHC connections are reduced so that only the uncal and genual subdivisions of the hippocampal 64 formation are connected to those in the contralateral hemisphere (Demeter et al. 1985; Gloor et al. 65 1993). By contrast, the DHC remains a substantial tract in nonhuman prima...

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Memory Part 3: The Role of the Fornix and Clinical Cases

Cited by 25 publications

References 15 publications

Diffusion imaging of fornix and interconnected limbic deep grey matter is linked to cognitive impairment in multiple sclerosis

Diffusion imaging of fornix and interconnected limbic deep grey matter is linked to cognitive impairment in multiple sclerosis

Fornix Stimulation Induces Metabolic Activity and Dopaminergic Response in the Nucleus Accumbens

Uncovering a role for the dorsal hippocampal commissure in episodic memory

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