DOCSLIB.ORG

The Cingulate Cortex and Limbic Systems for Emotion, Action, and Memory

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Brain Structure and Function https://doi.org/10.1007/s00429-019-01945-2 REVIEW The cingulate cortex and limbic systems for emotion, action, and memory Edmund T. Rolls1,2 Received: 19 April 2019 / Accepted: 19 August 2019 © The Author(s) 2019 Abstract Evidence is provided for a new conceptualization of the connectivity and functions of the cingulate cortex in emotion, action, and memory. The anterior cingulate cortex receives information from the orbitofrontal cortex about reward and non-reward outcomes. The posterior cingulate cortex receives spatial and action-related information from parietal cortical areas. It is argued that these inputs allow the cingulate cortex to perform action–outcome learning, with outputs from the midcingulate motor area to premotor areas. In addition, because the anterior cingulate cortex connects rewards to actions, it is involved in emotion; and because the posterior cingulate cortex has outputs to the hippocampal system, it is involved in memory. These apparently multiple diferent functions of the cingulate cortex are related to the place of this proisocortical limbic region in brain connectivity. Keywords Cingulate cortex · Limbic systems · Hippocampus · Orbitofrontal cortex · Emotion · Memory · Depression Introduction: the cingulate cortex and other stream processing areas that decode ‘what’ the stimulus is limbic structures (Rolls 2014b, 2016a, 2019a, b). The hippocampus is a key structure in episodic memory with inputs from the dorsal A key area included by Broca in his limbic lobe (Broca stream cortical areas about space, action, and ‘where’ events 1878) is the cingulate cortex, which hooks around the cor- occur, as well as from the ‘what’ ventral processing stream pus callosum. The term limbic used by Broca referred to (Kesner and Rolls 2015; Rolls 2018b). Because of the dif- structures that are at the border or edge (the literal meaning ferent connectivity and functions of these limbic structures of limbic) of the hemispheres (when seen in medial view), (amygdala, orbitofrontal cortex, and hippocampus) in emo- and led to the development of the concept of a limbic system tion and in memory, it has been suggested that the concept of (Pessoa and Hof 2015). Other limbic structures include the a single ‘limbic system’ is not realistic, and that we should hippocampus, and the amygdala (which has major connec- consider separately the connectivity and functions of difer- tions with the orbitofrontal cortex). These structures appear ent limbic structures in emotion and memory (Rolls 2015). to have very diferent connections and functions. The amyg- However, that leaves the cingulate cortex in an interesting dala and orbitofrontal cortex are key structures involved in position straddling the emotional and memory domains. The emotion and reward value with connections from ventral anterior cingulate cortex receives inputs from the orbitofron- tal cortex and amygdala which receive from ventral stream areas. The posterior cingulate cortex receives from dorsal Electronic supplementary material The online version of this stream areas including the parietal cortex and has connec- article (https ://doi.org/10.1007/s0042 9-019-01945 -2) contains tions to the hippocampal memory system. Moreover, there supplementary material, which is available to authorized users. is evidence relating the cingulate cortex to what is appar- * Edmund T. Rolls ently something else, action–outcome learning, in which [email protected] actions are learned to obtain goals based on the outcomes, http://www.oxcns.org the rewards and punishers, received for diferent actions (Rushworth et al. 2012; Kolling et al. 2016; Rolls 2019a). 1 Oxford Centre for Computational Neuroscience, Oxford, UK In this paper, I provide a framework for understanding 2 Department of Computer Science, University of Warwick, the connectivity and functions of the cingulate cortex, and Coventry CV4 7AL, UK Vol.:(0123456789)1 3 Brain Structure and Function how the cingulate cortex can be involved in at least three important functions, emotion, action–outcome learning, and memory. I consider the evidence on the connectivity and 6 5 7 4 1 ips functions of the diferent parts of the cingulate cortex, and 2 LIP 9 cs 3 ls then in the synthesis I produce an integrated conceptual- ps 46 MT ization of how the cingulate cortex, with its proisocortical as V1 structure and type of connectivity, fts in to our overall con- V2 ceptual understanding of the functions performed by dif- V4 22 ferent cortical areas, and by other limbic structures (Rolls PIT AIT 2016a). Proisocortical areas can be understood in terms of brain structure and function as forming connectional bridges between neocortical areas and areas such as the hippocam- pus (which is termed allocortex) (Pandya et al. 2015) (see “Connectivity of the cingulate cortex with the hippocampal medial 7 Precuneus memory system”). This is a conceptual review of the struc- Cingulatemid 24 Cingulatepost ture and functions of the cingulate cortex, and introduces Cingulateant 32 24 (23/31) new concepts on how it relates to other limbic and cortical Retrosplenial (29/30) V1 structures, rather than an exhaustive review. The cytoarchi- OFC25 tectural details of the human cingulate cortex are provided in Fig. S1 (Vogt 2009, 2016). Entorhinal TH Many previous contributions have been valuable in (28) TF leading towards an understanding of the cingulate cortex Perirhinal (35/36) (Devinsky et al. 1995; Vogt 2009, 2016; Rushworth et al. Medial view 2011). This paper focusses on research on the cingulate and The entorhinal cortex is the gateway into and from the hippocampus orbitofrontal cortex in primates including humans, rather than on research in rodents (Izquierdo 2017; Wikenheiser Fig. 1 and Schoenbaum 2016), because of the great development of The connections of the anterior and posterior cingulate cortex with their input areas, and their outputs to the hippocampal memory these regions in primates (Passingham and Wise 2012; Rolls system. A medial view of the macaque brain is shown below, and 2014a, 2018a, 2019a). For example, rodents have no poste- a lateral view is above. The green arrows show the convergence of rior cingulate cortex (Vogt 2009) and most of the orbito- reward or outcome information from the ACC and of information frontal cortex (apart from the agranular areas posteriorly) about actions from the posterior cingulate cortex to the midcingu- late motor area, which then projects to premotor areas including the may not be present in rodents (Passingham and Wise 2012; premotor cortex area 6 and the supplementary motor area. This pro- Rolls 2019a). vides connectivity for action–outcome learning. The anterior cin- An overview of the concepts about the cingulate cortex gulate cortex receives reward outcome information from the orbito- considered here follows, to provide a framework for under- frontal cortex (OFC). The posterior cingulate cortex (23 and 31) receives information about actions from the parietal cortex. This standing the evidence included in this paper. Some of the cingulate connectivity is compared with that of the hippocampus, connections and regions of the cingulate cortex are shown which receives information from the ventral ‘what’ processing stream in Figs. 1 and 2. (blue) and the dorsal ‘where’ or ‘action’ processing stream (red), as In humans, the pregenual anterior cingulate cortex described in the text. as, arcuate sulcus; cs, central sulcus; ips, intra- parietal sulcus; ios, inferior occipital sulcus; ls, lunate sulcus; ret- receives information related to reward from the medial orbit- rosplenial cortex (29, 30) is the small region in primates including ofrontal cortex, and related to punishment and not receiving humans behind the splenium of the corpus callosum shaded grey: it reward from the lateral orbitofrontal cortex. These orbito- is present in rodents, which do not have a posterior cingulate cortex frontal cortex areas represent information about value, not (Vogt 2009); sts, superior temporal sulcus; 4, 6, motor and premotor cortex. Developed from Rolls and Wirth (2018) about actions or responses, as shown by neuronal record- ings in macaques. The value representation received by the anterior cingulate cortex includes information about the particular, to actions. The subgenual cingulate cortex (area outcome of actions, that is, whether reward or punishment 25) may link rewards and punishers to autonomic output. has been received, and is used by the cingulate cortex for The posterior cingulate cortex receives information about learning the action to perform to obtain a reward or avoid actions from the parietal cortex, including areas 7a, VIP a punisher. This is termed ‘action–outcome learning’. The and LIP laterally, and area 7m medially (as well as some anterior cingulate cortex is implicated in emotion, because inputs from ventral stream temporal lobe areas) (Vogt and it is involved in linking reward and punishment informa- Laureys 2009). The posterior cingulate cortex is therefore tion, which elicit emotional responses, to behaviour, and, in implicated in spatial including visuospatial processing. A 1 3 Brain Structure and Function Midcingulate cortex Posterior cingulate cortex Retrosplenial Supracallosal ant cingulate cortex cortex cgs Pregenual ant cingulate cortex 24 Subgenual ant cingulate cortex T 10 cf Am TH TF 28 Medial View TE 12 lo s TG cs mos 13 as ips 11 51 ps os 10 S2 14 ls fros 46 Ventral view of INS Sylvian f orbitofrontal cortex 22 TPO ios STG TE 21 sts 38 Lateral View
Recommended publications
  • Lesions of Perirhinal and Parahippocampal Cortex That Spare the Amygdala and Hippocampal Formation Produce Severe Memory Impairment

    Lesions of Perirhinal and Parahippocampal Cortex That Spare the Amygdala and Hippocampal Formation Produce Severe Memory Impairment

    The Journal of Neuroscience, December 1989, 9(12): 4355-4370 Lesions of Perirhinal and Parahippocampal Cortex That Spare the Amygdala and Hippocampal Formation Produce Severe Memory Impairment Stuart Zola-Morgan,’ Larry Ft. Squire,’ David G. Amaral,2 and Wendy A. Suzuki2J Veterans Administration Medical Center, San Diego, California, 92161, and Department of Psychiatry, University of California, San Diego, La Jolla, California 92093, The Salk Institute, San Diego, California 92136, and 3Group in Neurosciences, University of California, San Diego, La Jolla, California 92093 In monkeys, bilateral damage to the medial temporal region Moss, 1984). (In this notation, H refers to the hippocampus, A produces severe memory impairment. This lesion, which in- to the amygdala, and the plus superscript (+) to the cortical cludes the hippocampal formation, amygdala, and adjacent tissue adjacent to each structure.) This lesion appears to con- cortex, including the parahippocampal gyrus (the H+A+ le- stitute an animal model of medial temporal lobe amnesia like sion), appears to constitute an animal model of human me- that exhibited by the well-studied patient H.M. (Scoville and dial temporal lobe amnesia. Reexamination of histological Milner, 1957). material from previously studied monkeys with H+A+ lesions The H+A+ lesion produces greater memory impairment than indicated that the perirhinal cortex had also sustained sig- a lesion limited to the hippocampal formation and parahip- nificant damage. Furthermore, recent neuroanatomical stud- pocampal cortex-the H+ lesion (Mishkin, 1978; Mahut et al., ies show that the perirhinal cortex and the closely associated 1982; Zola-Morgan and Squire, 1985, 1986; Zola-Morgan et al., parahippocampal cortex provide the major source of cortical 1989a).
  • Sustained Activities and Retrieval in a Computational Model of Perirhinal

    Sustained Activities and Retrieval in a Computational Model of Perirhinal

    Sustained activities and retrieval in a computational model of perirhinal cortex Julien Vitay and Fred H. Hamker∗ Abstract Perirhinal cortex is involved in object recognition and novelty detection, but also in multimodal in- tegration, reward association and visual working memory. We propose a computational model that focuses on the role of perirhinal cortex in working memory, particularly with respect to sustained activities and memory retrieval. This model describes how different partial informations are inte- grated into assemblies of neurons that represent the identity of an object. Through dopaminergic modulation, the resulting clusters can retrieve the global information with recurrent interactions between neurons. Dopamine leads to sustained activities after stimulus disappearance that form the basis of the involvement of perirhinal cortex in visual working memory processes. The infor- mation carried by a cluster can also be retrieved by a partial thalamic or prefrontal stimulation. Thus, we suggest that areas involved in planning and memory coordination encode a pointer to access the detailed information encoded in associative cortex such as perirhinal cortex. ∗Allgemeine Psychologie, Psychologisches Institut II, Westf. Wilhelms-Universit¨at M¨unster, Germany 1 Introduction Perirhinal cortex (PRh), composed of cortical areas 35 and 36, is located in the ventromedial part of the temporal lobe. It receives its major inputs from areas TE and TEO of inferotemporal cortex, as well as from entorhinal cortex (ERh), parahippocampal cortex, insular cortex and orbitofrontal cortex (Suzuki & Amaral, 1994). As part of the medial temporal lobe system (with hippocampus and ERh), its primary role is considered to be object-recognition memory, as shown by impairements in delayed matching-to-sample (DMS) or delayed nonmatching-to-sample (DNMS) tasks following PRh cooling or removal (Horel, Pytko-Joiner, Voytko, & Salsbury, 1987; Zola-Morgan, Squire, Amaral, & Suzuki, 1989; Meunier, Bachevalier, Mishkin, & Murray, 1993; Buffalo, Reber, & Squire, 1998).
  • Anatomy of the Temporal Lobe

    Anatomy of the Temporal Lobe

    Hindawi Publishing Corporation Epilepsy Research and Treatment Volume 2012, Article ID 176157, 12 pages doi:10.1155/2012/176157 Review Article AnatomyoftheTemporalLobe J. A. Kiernan Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, Canada N6A 5C1 Correspondence should be addressed to J. A. Kiernan, [email protected] Received 6 October 2011; Accepted 3 December 2011 Academic Editor: Seyed M. Mirsattari Copyright © 2012 J. A. Kiernan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Only primates have temporal lobes, which are largest in man, accommodating 17% of the cerebral cortex and including areas with auditory, olfactory, vestibular, visual and linguistic functions. The hippocampal formation, on the medial side of the lobe, includes the parahippocampal gyrus, subiculum, hippocampus, dentate gyrus, and associated white matter, notably the fimbria, whose fibres continue into the fornix. The hippocampus is an inrolled gyrus that bulges into the temporal horn of the lateral ventricle. Association fibres connect all parts of the cerebral cortex with the parahippocampal gyrus and subiculum, which in turn project to the dentate gyrus. The largest efferent projection of the subiculum and hippocampus is through the fornix to the hypothalamus. The choroid fissure, alongside the fimbria, separates the temporal lobe from the optic tract, hypothalamus and midbrain. The amygdala comprises several nuclei on the medial aspect of the temporal lobe, mostly anterior the hippocampus and indenting the tip of the temporal horn. The amygdala receives input from the olfactory bulb and from association cortex for other modalities of sensation.
  • Prefrontal and Posterior Parietal Contributions to the Perceptual Awareness of Touch M

    Prefrontal and Posterior Parietal Contributions to the Perceptual Awareness of Touch M

    www.nature.com/scientificreports OPEN Prefrontal and posterior parietal contributions to the perceptual awareness of touch M. Rullmann1,2,5, S. Preusser1,5 & B. Pleger1,3,4* Which brain regions contribute to the perceptual awareness of touch remains largely unclear. We collected structural magnetic resonance imaging scans and neurological examination reports of 70 patients with brain injuries or stroke in S1 extending into adjacent parietal, temporal or pre-/frontal regions. We applied voxel-based lesion-symptom mapping to identify brain areas that overlap with an impaired touch perception (i.e., hypoesthesia). As expected, patients with hypoesthesia (n = 43) presented lesions in all Brodmann areas in S1 on postcentral gyrus (BA 1, 2, 3a, 3b). At the anterior border to BA 3b, we additionally identifed motor area BA 4p in association with hypoesthesia, as well as further ventrally the ventral premotor cortex (BA 6, BA 44), assumed to be involved in whole-body perception. At the posterior border to S1, we found hypoesthesia associated efects in attention-related areas such as the inferior parietal lobe and intraparietal sulcus. Downstream to S1, we replicated previously reported lesion-hypoesthesia associations in the parietal operculum and insular cortex (i.e., ventral pathway of somatosensory processing). The present fndings extend this pathway from S1 to the insular cortex by prefrontal and posterior parietal areas involved in multisensory integration and attention processes. Te primary somatosensory cortex (S1) in monkeys can be divided into four Brodmann areas: (BA) 1, 2, 3a, and 3b. Each BA consists of a somatotopically organized map that subserves distinct somatosensory functions1–3.
  • Toward a Common Terminology for the Gyri and Sulci of the Human Cerebral Cortex Hans Ten Donkelaar, Nathalie Tzourio-Mazoyer, Jürgen Mai

    Toward a Common Terminology for the Gyri and Sulci of the Human Cerebral Cortex Hans Ten Donkelaar, Nathalie Tzourio-Mazoyer, Jürgen Mai

    Toward a Common Terminology for the Gyri and Sulci of the Human Cerebral Cortex Hans ten Donkelaar, Nathalie Tzourio-Mazoyer, Jürgen Mai To cite this version: Hans ten Donkelaar, Nathalie Tzourio-Mazoyer, Jürgen Mai. Toward a Common Terminology for the Gyri and Sulci of the Human Cerebral Cortex. Frontiers in Neuroanatomy, Frontiers, 2018, 12, pp.93. 10.3389/fnana.2018.00093. hal-01929541 HAL Id: hal-01929541 https://hal.archives-ouvertes.fr/hal-01929541 Submitted on 21 Nov 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. REVIEW published: 19 November 2018 doi: 10.3389/fnana.2018.00093 Toward a Common Terminology for the Gyri and Sulci of the Human Cerebral Cortex Hans J. ten Donkelaar 1*†, Nathalie Tzourio-Mazoyer 2† and Jürgen K. Mai 3† 1 Department of Neurology, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands, 2 IMN Institut des Maladies Neurodégénératives UMR 5293, Université de Bordeaux, Bordeaux, France, 3 Institute for Anatomy, Heinrich Heine University, Düsseldorf, Germany The gyri and sulci of the human brain were defined by pioneers such as Louis-Pierre Gratiolet and Alexander Ecker, and extensified by, among others, Dejerine (1895) and von Economo and Koskinas (1925).
  • Connection Interfaces Between Neuronal Elements and Structures Inside Greater Limbic System

    Connection Interfaces Between Neuronal Elements and Structures Inside Greater Limbic System

    Rom J Leg Med [21] 137-148 [2013] DOI: 10.4323/rjlm.2013.137 © 2013 Romanian Society of Legal Medicine Connection interfaces between neuronal elements and structures inside greater limbic system. Evaluation in forensic psycho-affective pathology Gheorghe S. Dragoi1, Petru Razvan Melinte2, Liviu Radu3 _________________________________________________________________________________________ Abstract: The authors achieved a macroanatomic analysis on the location and relations of neuronal structures and elements inside transitional mesocortex and archicortex in order to visualize the connection interfaces of greater limbic system. The analysis was performed on human encephalon using subsystems generally homologated by neuroanatomists: lobus limbicus, hippocampal formation, prefrontal cortex, lobus insularis and subcortical structures. Equally, they performed a research of the literature on the implication of connection interfaces from paralimbic, limbic and archicortex areas, into forensic psycho-affective ortology and pathology. The study draws the attention to time and space development of terminology and homologation of some new concepts bound to multifunctional subsystems such as: medial temporal lobe memory system, prefrontal cortex and limbic midbrain area. Key Words: greater limbic system, transitional mesocortex, archicortex euroanatomy registered remarkable progress (proneocortical or paralimbic zone and periarchicortical or by the diversity of morph-functional and limbic zone); hippocampal formation (with two regions: N anatomic-clinical
  • Metabolic Reduction in the Posterior Cingulate Cortex in Very Early Alzheimer’S Disease

    Metabolic Reduction in the Posterior Cingulate Cortex in Very Early Alzheimer’S Disease

    Metabolic Reduction in the Posterior Cingulate Cortex in Very Early Alzheimer’s Disease Satoshi Minoshima, MD, PhD,* Bruno Giordani, PhD,t Stanley Berent, PhD,t$ Kirk A. Frey, MD, PhD,*$ Norman L. Foster, MD,$ and David E. Kuhl, MD* This study investigated cerebral glucose metabolism in very early Alzheimer’s disease, before a clinical diagnosis of probable Alzheimer’s disease is possible, using [ ‘8F]flu~r~de~xygluc~~epositron emission tomography. First, 66 patients with probable Alzheimer’s disease with a spectrum of dementia severity (Mini-Mental State Examination score, 0-23) were recruited and studied. Cortical metabolic activity was analyzed topographically using three-dimensional stereotactic surface projections. Regression analysis was performed for each brain pixel to predict metabolic patterns of very early disease. Predictions were tested prospectively in a group of 8 patients who complained only of memory impairment without general cognitive decline (Mini-Mental State Examination score, 25 Ifr 1) at the time of scanning but whose condition later progressed to probable Alzheimer’s disease. Both results were compared to cerebral metabolic activity in 22 age-similar normal control subjects. Prediction and analysis of actual patients consistently indicated marked metabolic reduction (21-22%) in the posterior cingulate cortex and cinguloparietal transitional area in patients with very early Alzheimer’s disease. Mean metabolic reduction in the posterior cingulate cortex was significantly greater than that in the lateral neocortices or parahippocampal cortex. The result suggests a functional importance for the posterior cingulate cortex in impairment of learning and memory, which is a feature of very early Alzheimer’s disease. Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE.
  • A Hypothesis for the Evolution of the Upper Layers of the Neocortex Through Co-Option of the Olfactory Cortex Developmental Program

    A Hypothesis for the Evolution of the Upper Layers of the Neocortex Through Co-Option of the Olfactory Cortex Developmental Program

    HYPOTHESIS AND THEORY published: 12 May 2015 doi: 10.3389/fnins.2015.00162 A hypothesis for the evolution of the upper layers of the neocortex through co-option of the olfactory cortex developmental program Federico Luzzati 1, 2* 1 Department of Life Sciences and Systems Biology (DBIOS), University of Turin, Turin, Italy, 2 Neuroscience Institute Cavalieri Ottolenghi, Orbassano, Truin, Italy The neocortex is unique to mammals and its evolutionary origin is still highly debated. The neocortex is generated by the dorsal pallium ventricular zone, a germinative domain that in reptiles give rise to the dorsal cortex. Whether this latter allocortical structure Edited by: contains homologs of all neocortical cell types it is unclear. Recently we described a Francisco Aboitiz, + + Pontificia Universidad Catolica de population of DCX /Tbr1 cells that is specifically associated with the layer II of higher Chile, Chile order areas of both the neocortex and of the more evolutionary conserved piriform Reviewed by: cortex. In a reptile similar cells are present in the layer II of the olfactory cortex and Loreta Medina, the DVR but not in the dorsal cortex. These data are consistent with the proposal that Universidad de Lleida, Spain Gordon M. Shepherd, the reptilian dorsal cortex is homologous only to the deep layers of the neocortex while Yale University School of Medicine, the upper layers are a mammalian innovation. Based on our observations we extended USA Fernando Garcia-Moreno, these ideas by hypothesizing that this innovation was obtained by co-opting a lateral University of Oxford, UK and/or ventral pallium developmental program. Interestingly, an analysis in the Allen brain *Correspondence: atlas revealed a striking similarity in gene expression between neocortical layers II/III Federico Luzzati, and piriform cortex.
  • Differential Cortical Atrophy in Subgroups of Mild Cognitive Impairment

    Differential Cortical Atrophy in Subgroups of Mild Cognitive Impairment

    ORIGINAL CONTRIBUTION Differential Cortical Atrophy in Subgroups of Mild Cognitive Impairment Sandra Bell-McGinty, PhD; Oscar L. Lopez, MD; Carolyn Cidis Meltzer, MD; Joelle M. Scanlon, PhD; Ellen M. Whyte, MD; Steven T. DeKosky, MD; James T. Becker, PhD Objective: To compare gray matter brain volumes in jects. Compared with patients with MCI-MCD, patients patients diagnosed with subtypes of mild cognitive im- with MCI-A had significant volume loss of the left ento- pairment (MCI) (those with a focal amnestic disorder and rhinal cortex and inferior parietal lobe. Compared with those with more diffuse cognitive dysfunction) with those patients with MCI-A, patients with MCI-MCD had sig- of elderly controls. nificantly reduced volume of the right inferior frontal gy- rus, right middle temporal gyrus, and bilateral superior Design: Magnetic resonance imaging volumetric study temporal gyrus. Patients with MCI who progressed to Alz- of MCI subgroups (MCI-amnestic [MCI-A], and MCI- heimer disease during follow-up (mean interval 2 years, multiple cognitive domain [MCI-MCD]) using a whole maximum 4.5 years), showed greater atrophy in the left brain voxel-based analysis. entorhinal cortex, bilateral superior temporal gyri, and right inferior frontal gyrus compared with those who did Setting: Referral dementia clinic. not progress. Patients: Thirty-seven patients with MCI (age range, Conclusions: These data provide evidence of distinct 49-85 years; MCI-A, n=9; MCI-MCD, n=28) and 47 con- brain structural abnormalities in 2 groups of patients with trol subjects (age range, 55-81 years). MCI. While both have mesial temporal and cortical vol- ume loss, those with a focal memory deficit have more Main Outcome Measures: Volumetric anatomical mag- involvement of the mesial temporal structures and less netic resonance imaging differences between MCI sub- involvement of the neocortical heteromodal association groups and normal controls, and between patients with areas than those patients with MCI with diffuse cogni- MCI who progressed to dementia.
  • Neocortex and Allocortex Respond Differentially to Cellular Stress in Vitro and Aging in Vivo

    Neocortex and Allocortex Respond Differentially to Cellular Stress in Vitro and Aging in Vivo

    Neocortex and Allocortex Respond Differentially to Cellular Stress In Vitro and Aging In Vivo Jessica M. Posimo, Amanda M. Titler, Hailey J. H. Choi, Ajay S. Unnithan, Rehana K. Leak* Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, Pennsylvania, United States of America Abstract In Parkinson’s and Alzheimer’s diseases, the allocortex accumulates aggregated proteins such as synuclein and tau well before neocortex. We present a new high-throughput model of this topographic difference by microdissecting neocortex and allocortex from the postnatal rat and treating them in parallel fashion with toxins. Allocortical cultures were more vulnerable to low concentrations of the proteasome inhibitors MG132 and PSI but not the oxidative poison H2O2. The proteasome appeared to be more impaired in allocortex because MG132 raised ubiquitin-conjugated proteins and lowered proteasome activity in allocortex more than neocortex. Allocortex cultures were more vulnerable to MG132 despite greater MG132-induced rises in heat shock protein 70, heme oxygenase 1, and catalase. Proteasome subunits PA700 and PA28 were also higher in allocortex cultures, suggesting compensatory adaptations to greater proteasome impairment. Glutathione and ceruloplasmin were not robustly MG132-responsive and were basally higher in neocortical cultures. Notably, neocortex cultures became as vulnerable to MG132 as allocortex when glutathione synthesis or autophagic defenses were inhibited. Conversely, the glutathione precursor N-acetyl cysteine rendered allocortex resilient to MG132. Glutathione and ceruloplasmin levels were then examined in vivo as a function of age because aging is a natural model of proteasome inhibition and oxidative stress. Allocortical glutathione levels rose linearly with age but were similar to neocortex in whole tissue lysates.
  • Entorhinal Cortex Stimulation Induces Dentate Gyrus Neurogenesis Through Insulin Receptor Signaling T

    Entorhinal Cortex Stimulation Induces Dentate Gyrus Neurogenesis Through Insulin Receptor Signaling T

    Brain Research Bulletin 144 (2019) 75–84 Contents lists available at ScienceDirect Brain Research Bulletin journal homepage: www.elsevier.com/locate/brainresbull Research report Entorhinal cortex stimulation induces dentate gyrus neurogenesis through insulin receptor signaling T Abdolaziz Ronaghia, Mohammad Ismail Zibaiib, Sareh Pandamooza, Nasrin Nourzeia, ⁎ Fereshteh Motamedia, Abolhassan Ahmadiania, Leila Dargahic, a Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran b Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran c Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran ARTICLE INFO ABSTRACT Keywords: Deep brain stimulation (DBS) has been established as a therapeutically effective method to treat pharmacological Deep brain stimulation resistant neurological disorders. The molecular and cellular mechanisms underlying the beneficial effects of DBS Entorhinal cortex on the brain are not yet fully understood. Beside numerous suggested mechanisms, regulation of neurogenesis is Neurogenesis an attractive mechanism through which DBS can affect the cognitive functions. Considering the high expression Insulin receptor of insulin receptors in hippocampus and also impaired neurogenesis in diabetic brain, the present study aimed to examine the role of insulin receptor signaling in DBS induced neurogenesis. High frequency stimulation was applied on the entorhinal cortex of rats and then neurogenesis markers in the dentate gyrus region of the hip- pocampus were examined using molecular and histological methods in the sham, DBS and insulin receptor antagonist-treated groups. In parallel, the changes in insulin receptor signaling in the hippocampus and spatial learning and memory performance were also assessed. DBS promoted adult hippocampal neurogenesis and fa- cilitated the spatial memory concomitant with changes in insulin receptor signaling parameters including IR, IRS2 and GSK3β.
  • The Structural Model: a Theory Linking Connections, Plasticity, Pathology, Development and Evolution of the Cerebral Cortex

    The Structural Model: a Theory Linking Connections, Plasticity, Pathology, Development and Evolution of the Cerebral Cortex

    Brain Structure and Function https://doi.org/10.1007/s00429-019-01841-9 REVIEW The Structural Model: a theory linking connections, plasticity, pathology, development and evolution of the cerebral cortex Miguel Ángel García‑Cabezas1 · Basilis Zikopoulos2,3 · Helen Barbas1,3 Received: 11 October 2018 / Accepted: 29 January 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract The classical theory of cortical systematic variation has been independently described in reptiles, monotremes, marsupials and placental mammals, including primates, suggesting a common bauplan in the evolution of the cortex. The Structural Model is based on the systematic variation of the cortex and is a platform for advancing testable hypotheses about cortical organization and function across species, including humans. The Structural Model captures the overall laminar structure of areas by dividing the cortical architectonic continuum into discrete categories (cortical types), which can be used to test hypotheses about cortical organization. By type, the phylogenetically ancient limbic cortices—which form a ring at the base of the cerebral hemisphere—are agranular if they lack layer IV, or dysgranular if they have an incipient granular layer IV. Beyond the dysgranular areas, eulaminate type cortices have six layers. The number and laminar elaboration of eulaminate areas differ depending on species or cortical system within a species. The construct of cortical type retains the topology of the systematic variation of the cortex and forms the basis for a predictive Structural Model, which has successfully linked cortical variation to the laminar pattern and strength of cortical connections, the continuum of plasticity and stability of areas, the regularities in the distribution of classical and novel markers, and the preferential vulnerability of limbic areas to neurodegenerative and psychiatric diseases.