EPS Mid-Career Award 2006: Understanding anterograde amnesia: Disconnections and hidden lesions

2008 ◽  
Vol 61 (10) ◽  
pp. 1441-1471 ◽  
Author(s):  
John P. Aggleton
Keyword(s):  
Anterograde Amnesia ◽  
Functional System ◽  
Brain Regions ◽  
Retrosplenial Cortex ◽  
Thalamic Nuclei ◽  
Neural Basis ◽  
Lesion Effect ◽  
Anterior Thalamic Nuclei ◽  
Colloid Cysts ◽  
The Many

Three emerging strands of evidence are helping to resolve the causes of the anterograde amnesia associated with damage to the diencephalon. First, new anatomical studies have refined our understanding of the links between diencephalic and temporal brain regions associated with amnesia. These studies direct attention to the limited numbers of routes linking the two regions. Second, neuropsychological studies of patients with colloid cysts confirm the importance of at least one of these routes, the fornix, for episodic memory. By combining these anatomical and neuropsychological data strong evidence emerges for the view that damage to hippocampal—mammillary body—anterior thalamic interactions is sufficient to induce amnesia. A third development is the possibility that the retrosplenial cortex provides an integrating link in this functional system. Furthermore, recent evidence indicates that the retrosplenial cortex may suffer “covert” pathology (i.e., it is functionally lesioned) following damage to the anterior thalamic nuclei or hippocampus. This shared indirect “lesion” effect on the retrosplenial cortex not only broadens our concept of the neural basis of amnesia but may also help to explain the many similarities between temporal lobe and diencephalic amnesia.

scholarly journals Hippocampal–diencephalic–cingulate networks for memory and emotion: An anatomical guide

2017 ◽  
Vol 1 ◽  
pp. 239821281772344 ◽  
Author(s):  
Emma J. Bubb ◽  
Lisa Kinnavane ◽  
John P. Aggleton
Keyword(s):  
Prefrontal Cortex ◽  
Medial Temporal Lobe ◽  
Current Knowledge ◽  
Hippocampal Formation ◽  
Retrosplenial Cortex ◽  
Thalamic Nuclei ◽  
Mammillary Bodies ◽  
Individual Site ◽  
Multi Stage ◽  
Anterior Thalamic Nuclei

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus.

scholarly journals Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by apical tuft-targeting CA1 neurons

2018 ◽  
Author(s):  
Naoki Yamawaki ◽  
Xiaojian Li ◽  
Laurie Lambot ◽  
Lynn Y. Ren ◽  
Jelena Radulovic ◽  
...  
Keyword(s):  
Long Range ◽  
Pyramidal Neurons ◽  
Dorsal Hippocampus ◽  
Retrosplenial Cortex ◽  
Molecular Profile ◽  
Thalamic Nuclei ◽  
Cellular Mechanisms ◽  
Ca1 Neurons ◽  
Apical Tuft ◽  
Anterior Thalamic Nuclei

AbstractDorsal hippocampus, retrosplenial cortex (RSC), and anterior thalamic nuclei (ATN) interact to mediate diverse cognitive functions, but the cellular basis for these interactions is unclear. We hypothesized a long-range circuit converging in layer 1 (L1) of RSC, based on the pathway anatomy of GABAergic CA1 retrosplenial-projecting (CA1-RP) neurons and thalamo-restrosplenial projections from ATN. We find that CA1→RSC projections stem from GABAergic neurons with a distinct morphology, electrophysiology, and molecular profile, likely corresponding to recently described Ntng1-expressing hippocampal interneurons. CA1-RP neurons monosynaptically inhibit L5 pyramidal neurons, principal outputs of RSC, via potent GABAergic synapses onto apical tuft dendrites in L1. These inhibitory inputs align precisely with L1-targeting thalamocortical excitatory inputs from ATN, particularly the anteroventral nucleus, forming a convergent circuit whereby CA1 inhibition can intercept ATN excitation to co-regulate RSC activity. Excitatory axons from subiculum, in contrast, innervate proximal dendrites in deeper layers. Short-term synaptic plasticity differs at each connection. Chemogenetically abrogating inhibitory CA1→RSC or excitatory ATN→RSC connections oppositely affects the encoding of contextual fear memory. Collectively, our findings identify multiple cellular mechanisms underlying hippocampo-thalamo-retrosplenial interactions, establishing CA1 RSC-projecting neurons as a distinct class with long-range axons that target apical tuft dendrites, and delineating an unusual cortical circuit in the RSC specialized for integrating long-range inhibition and thalamocortical excitation.

scholarly journals Individual Differences in Cognitive Performance Are Better Predicted by Global Rather Than Localized BOLD Activity Patterns Across the Cortex

2020 ◽  
Author(s):  
Weiqi Zhao ◽  
Clare E Palmer ◽  
Wesley K Thompson ◽  
Bader Chaarani ◽  
Hugh P Garavan ◽  
...  
Keyword(s):  
Effect Size ◽  
Activity Patterns ◽  
Size Variation ◽  
Prediction Method ◽  
Brain Regions ◽  
Summary Score ◽  
Neural Basis ◽  
Out Of Sample ◽  
The Many ◽  
Globally Distributed

Abstract Despite its central role in revealing the neurobiological mechanisms of behavior, neuroimaging research faces the challenge of producing reliable biomarkers for cognitive processes and clinical outcomes. Statistically significant brain regions, identified by mass univariate statistical models commonly used in neuroimaging studies, explain minimal phenotypic variation, limiting the translational utility of neuroimaging phenotypes. This is potentially due to the observation that behavioral traits are influenced by variations in neuroimaging phenotypes that are globally distributed across the cortex and are therefore not captured by thresholded, statistical parametric maps commonly reported in neuroimaging studies. Here, we developed a novel multivariate prediction method, the Bayesian polyvertex score, that turns a unthresholded statistical parametric map into a summary score that aggregates the many but small effects across the cortex for behavioral prediction. By explicitly assuming a globally distributed effect size pattern and operating on the mass univariate summary statistics, it was able to achieve higher out-of-sample variance explained than mass univariate and popular multivariate methods while still preserving the interpretability of a generative model. Our findings suggest that similar to the polygenicity observed in the field of genetics, the neural basis of complex behaviors may rest in the global patterning of effect size variation of neuroimaging phenotypes, rather than in localized, candidate brain regions and networks.

scholarly journals Anterior thalamic nuclei, but not retrosplenial cortex, lesions abolish latent inhibition in rats.

2018 ◽  
Vol 132 (5) ◽  
pp. 378-387 ◽  
Author(s):  
Andrew J. D. Nelson ◽  
Anna L. Powell ◽  
Lisa Kinnavane ◽  
John P. Aggleton
Keyword(s):  
Latent Inhibition ◽  
Retrosplenial Cortex ◽  
Thalamic Nuclei ◽  
Anterior Thalamic Nuclei

scholarly journals BIFURCATING NEURONS IN THE ANTERIOR THALAMIC NUCLEI

2021 ◽  
Author(s):  
Y Pei ◽  
S (Yee T) Tasananukorn ◽  
M Wolff ◽  
JC Dalrymple-Alford
Keyword(s):  
Hippocampal Formation ◽  
Nodal Point ◽  
Primary Source ◽  
Brain Structures ◽  
Retrosplenial Cortex ◽  
Thalamic Nuclei ◽  
Neural Ensembles ◽  
Multiple Structures ◽  
Anterior Thalamic Nuclei ◽  
New Perspective

AbstractThe anterior thalamic nuclei (ATN) form a nodal point within a hippocampal-cingulate-diencephalic memory system. ATN projections to different brain structures are conventionally viewed as distinct, but ATN neurons may send collaterals to multiple structures. The anteromedial subregion (AM) is the primary source of efferents to the medial prefrontal cortex (mPFC). Using a dual-retrograde neurotracer strategy, we discovered bifurcating AM neurons for tracers placed in the mPFC when paired with other regions. A semi-quantitative analysis found a high proportion of AM neurons (~36%) showed collateral projections when the mPFC was paired with dorsal subiculum (dSub); 20% were evident for mPFC paired with caudal retrosplenial cortex (cRSC); and 6% was found for mPFC and ventral hippocampal formation (vHF). About 10% of bifurcating AM neurons was also identified when the mPFC was not included, that is, for cRSC with dSub, and cRSC with vHF. Similar percentages of bifurcating neurons were also found within the anterior region of the adjacent nucleus reuniens (Re). The high frequency of bifurcating neurons suggests a new perspective for ATN function. These neurons would facilitate direct coordination among distal neural ensembles to support episodic memory and may explain why the ATN is a critical region for diencephalic amnesia.

scholarly journals Hippocampal CA1 pyramidal cells do not receive monosynaptic input from thalamic nucleus reuniens

2021 ◽  
Author(s):  
Lilya Andrianova ◽  
Erica S Brady ◽  
Gabriella Margetts-Smith ◽  
Shivali Kohli ◽  
Chris J McBain ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Thalamic Nucleus ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Brain Regions ◽  
Thalamic Nuclei ◽  
Nucleus Reuniens ◽  
Ca1 Pyramidal Cells ◽  
Local Inhibition ◽  
The Many

Midline thalamic nuclei play a critical role in cognitive functions such as memory, decision-making and spatial navigation, by facilitating communication between the many brain regions involved in these processes. One canonical feature of thalamic interactions with the cortex or hippocampus appears to be that the thalamus receives input from, and projects to, excitatory neurons. Thalamic nucleus reuniens (NRe) is located on the midline and is viewed primarily as a relay from prefrontal cortex to hippocampal and entorhinal areas, although these connections are poorly defined at the cellular and synaptic level. Using electrophysiology and monosynaptic circuit-tracing, we found that pyramidal cells in CA1 receive no direct input from NRe. This contrasts starkly with prefrontal cortex, subiculum and entorhinal cortex, and indicates that NRe inputs to CA1 primarily drive local inhibition and not excitation they do in the other regions. The NRe to CA1 projection is thus a unique thalamic projection and as such is raising important questions about the function of NRe-mediated prefrontal control of the hippocampus.

scholarly journals Global and Local Head Direction Coding in the Human Brain

2021 ◽  
Author(s):  
J. P. Shine ◽  
T. Wolbers
Keyword(s):  
Reference Frames ◽  
Brain Regions ◽  
Retrosplenial Cortex ◽  
Specific Reference ◽  
Head Direction ◽  
Imaging Data ◽  
Neural Basis ◽  
Local Environments ◽  
Human Participants ◽  
Global And Local

AbstractOrientation-specific head direction (HD) cells increase their firing rate to indicate one’s facing direction in the environment. Rodent studies suggest HD cells in distinct areas of thalamus and retrosplenial cortex (RSC) code either for global (relative to the wider environment) or local (e.g., room-specific) reference frames. To investigate whether similar neuroanatomical dissociations exist in humans, we reanalysed functional magnetic resonance imaging data in which participants learned the orientation of unique images in separate local environments relative to distinct global landmarks (Shine, Valdés-Herrera, Hegarty, & Wolbers, 2016). The environment layout meant that we could establish two separate multivariate analysis models in which the HD on individual trials was coded relative either to global (North, South, East, West) or local (Front, Back, Right, Left) reference frames. Examining the data first in key regions of interest (ROI) for HD coding, we replicated our previous results and found that global HD was decodable in the thalamus and precuneus; the RSC, however, was sensitive only to local HD. Extending recent findings in both humans and rodents, V1 was sensitive to both HD reference frames. Additional small volume-corrected searchlight analyses supported the ROI results and indicated that the anatomical locus of the thalamic global HD coding was located in the medial thalamus, bordering the anterior thalamus, a region critical for global HD coding in rodents. Our findings elucidate further the putative neural basis of HD coding in humans, and suggest that distinct brain regions code for different frames of reference in HD.Significance statementHead direction (HD) cells provide a neural signal as to one’s orientation in the environment. HD can be coded relative to global or local (e.g., room-specific) reference frames, with studies suggesting that distinct areas of thalamus and retrosplenial cortex (RSC) code for this information. We reanalysed fMRI data where human participants associated images with global HDs before undergoing scanning. The design enabled us to examine both global and local HD coding. Supporting previous findings, global HD was decodable in thalamus, however the RSC coded only for local HD. We found evidence also for both reference frames in V1. These findings elucidate the putative neural basis of HD coding in humans, with distinct brain regions coding for different HD reference frames.

scholarly journals Episodic memory, amnesia, and the hippocampal–anterior thalamic axis

1999 ◽  
Vol 22 (3) ◽  
pp. 425-444 ◽  
Author(s):  
John P. Aggleton ◽  
Malcolm W. Brown
Keyword(s):  
Episodic Memory ◽  
Temporal Lobe ◽  
Gene Activation ◽  
Temporal Cortex ◽  
Anterograde Amnesia ◽  
Thalamic Nuclei ◽  
Medial Dorsal ◽  
New Information ◽  
Subsequent Recall ◽  
Anterior Thalamic Nuclei

By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an “extended hippocampal system” comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon. These are necessary for the encoding and, hence, the effective subsequent recall of episodic memory. An additional feature of this hippocampal–anterior thalamic axis is the presence of projections back from the diencephalon to the temporal cortex and hippocampus that also support episodic memory. In contrast, this hippocampal system is not required for tests of item recognition that primarily tax familiarity judgements. Familiarity judgements reflect an independent process that depends on a distinct system involving the perirhinal cortex of the temporal lobe and the medial dorsal nucleus of the thalamus. In the large majority of amnesic cases both the hippocampal–anterior thalamic and the perirhinal–medial dorsal thalamic systems are compromised, leading to severe deficits in both recall and recognition.

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