ReviewA revised limbic system model for memory, emotion and behaviour
Introduction
The limbic system is a group of interconnected cortical and subcortical structures dedicated to linking visceral states and emotion to cognition and behaviour (Mesulam, 2000). The use of the term ‘limbic’ has changed over time. Initially introduced by Thomas Willis (1664) to designate a cortical border encircling the brainstem (limbus, Latin for ‘border’) (Fig. 1) the term has been used in more recent times to indicate a progressively increasing number of regions dedicated to a wide range of functions (Marshall and Magoun, 1998, Mega et al., 1997). Paul Broca (1878) held the view that ‘le grand lobe limbique’ was mainly an olfactory structure common to all mammalian brains, although he argued that its functions were not limited to olfaction (Fig. 2). After Broca's publication the accumulation of experimental evidence from ablation studies in animals broadened the role of the limbic structures to include other aspects of behaviour such as controlling social interactions and behaviour (Brown and Schäfer, 1888), consolidating memories (Bechterew, 1900), and forming emotions (Cannon, 1927).
Anatomical and physiological advancements in the field led Christfield Jakob (1906) (Fig. 3) and James Papez (1937) (Fig. 4) to formulate the first unified network model for linking action and perception to emotion. According to Papez emotion arises either from cognitive activity entering the circuit through the hippocampus or from visceral and somatic perceptions entering the circuit through the hypothalamus. In the case of emotion arising from cognitive activity, for example, ‘incitations of cortical origin would pass first to the hippocampal formation and then down by way of the fornix to the mammillary body. From this they would pass upward through the mammillo-thalamic tract, or the fasciculus of Vicq d’Azyr, to the anterior nuclei of the thalamus and thence by the medial thalamocortical radiation [or anterior thalamic projections] to the cortex of the gyrus cinguli […] The cortex of the cingular gyrus may be looked on as the receptive region for the experiencing of emotion as the result of impulses coming from the hypothalamic region [or the hippocampal formation][…] Radiation of the emotive process from the gyrus cinguli to other regions in the cerebral cortex would add emotional colouring to psychic processes occurring elsewhere (Papez, 1937)’
A decade later, Paul Yakovlev (1948), proposed that the orbitofrontal cortex, insula, amygdala, and anterior temporal lobe form a network underlying emotion and motivation (Fig. 5). In two seminal papers published in 1949 and 1952, Paul. MacLean crystallised previous works by incorporating both Papez and Yakovlev view into a model of the limbic system that has remained almost unchanged since (MacLean, 1949, MacLean, 1952). MacLean concluded that the limbic cortex, together with the limbic subcortical structures, is a functionally integrated system interconnected by short- and long-range fibre bundles (Fig. 6).
The development of tracing methods for studying long axonal pathways added details to the anatomical model of the limbic system (Crosby et al., 1962). These methods allowed, for example, the description of long and short connections of the cingulate cortex in animals. Further, the combination of anatomical methods with experimental procedures was used to demonstrate a direct link between specific limbic structures and behavioural response (e.g. amygdala and aggressive response). Unfortunately, axonal tracing could not be applied to human anatomy for the study of the biological underpinnings of those abilities that characterise human mind (e.g. emotions; empathy). Also animal models were not suitable for studying anatomical differences in psychiatric conditions such as autism and schizophrenia.
In the 1990s the use of functional neuroimaging methods (e.g. PET, fMRI) and later diffusion tractography offered the possibility of studying the functional anatomy of the limbic system in the living human brain. A major finding that emerged initially from PET studies and later confirmed with fMRI was the identification of a ‘default network’, consisting of a set of regions that activate under resting-state condition and deactivate during task-related functions (Buckner et al., 2008, Raichle et al., 2001, Raichle and Snyder, 2007, Shulman et al., 1997) (Fig. 7). The most medial regions of the default network correspond to the most dorsal portion of the Papez circuit and are interconnected through the dorsal cingulum.
Diffusion imaging is an advanced MRI technique based on optimised pulse sequences, which permits the quantification of the diffusion characteristics of water molecules inside biological tissues (Le Bihan and Breton, 1985). Given that cerebral white matter contains axons, and that water molecules diffuse more freely along axons than across them (Moseley et al., 1990), it is possible to obtain in vivo estimates of white matter fibre orientation by measuring the diffusivity of water molecules along different directions (Basser et al., 1994). By following the orientation of the water molecules displacement, diffusion imaging tractography reconstructs 3D trajectories of white matter pathways closely resembling tracts described in post-mortem animal tracing studies (Dauguet et al., 2007, Thiebaut de Schotten et al., 2011a, Thiebaut de Schotten et al., 2012) and human brain dissections (Basser et al., 2000, Catani et al., 2012a, Dell’Acqua and Catani, 2012, Dell’Acqua et al., 2010, Dell’Acqua et al., 2012, Jones, 2008, Lawes et al., 2008, Thiebaut de Schotten et al., 2011b, Forkel et al., 2012). One of the advantages of tractography is the ability to study the interindividual variability of white matter tracts in the healthy population and correlate white matter abnormalities with symptoms severity in patients with neurological and psychiatric disorders that involve the limbic system (Catani et al., 2012b, Catani et al., 2013a). In the following paragraphs we will use integrated information from animal studies and tractography findings in human to describe in detail the anatomy of the main limbic pathways (Fig. 8).
Section snippets
Fornix
The fornix is mainly a projection tract connecting the hippocampus with the mammillary body, the anterior thalamic nuclei, and the hypothalamus; it also has a small commissural component known as the hippocampal commissure (Aggleton, 2008, Crosby et al., 1962, Nieuwenhuys et al., 2008). Fibres arise from the hippocampus (subiculum and entorhinal cortex) of each side, run through the fimbria, and join beneath the splenium of the corpus callosum to form the body of the fornix. Other fimbrial
Functional anatomy of the limbic system
The limbic system has always been considered as a complex arrangement of transitional structures situated between a visceral ‘primitive’ subcortical brain and a more evolved cortical one (MacLean, 1952, Yakovlev, 1948). The subcortical limbic structures include the amygdala, mammillary bodies, hypothalamus, some thalamic nuclei (i.e. anterior, intralaminar, and medial dorsal groups) and the ventral striatum (i.e. nucleus accumbens). The neurons and fibres composing the subcortical limbic
Limbic syndromes
The limbic system is affected by a wide range of disorders, including neurodevelopmental conditions, traumatic brain injury and neurodegeneration. In most psychiatric conditions a dysfunction of the limbic structures involved with emotion regulation, social interaction and behaviour has been implicated. In the older population neurodegenerative disorders affect primarily limbic systems dedicated to memory. These disorders take a heavy tall on affected individuals, families and society at large.
Conclusions and future directions
In this review we propose an update of the limbic model based on the work of pioneer anatomists and more recent findings from functional imaging and tractography. In the revised circuit we identify three distinct but partially overlapping networks.
The hippocampal-diencephalic and parahippocampal-retrosplenial network is dedicated to memory and spatial orientation and lesions to this division cause severe anterograde and spatial disorientation. The temporo-amygdala-orbitofrontal network
Acknowledgment
We thank the Natbrainlab (http://www.natbrainlab.com), Emilio Verche, Guy's and St. Thomas’ Charity and the French Agence Nationale de la Recherche (project CAFORPFC, no. ANR-09-RPDOC-004-01 and project HM-TC, no. ANR-09-EMER-006).
References (164)
- et al.
The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations
Neurosci. Biobehav. Rev.
(2008) - et al.
Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP)
Lancet
(2006) - et al.
White matter structure in autism: preliminary evidence from diffusion tensor imaging
Biol. Psychiatry
(2004) - et al.
MR diffusion tensor spectroscopy and imaging
Biophys. J.
(1994) - et al.
Neuroanatomic observations of the brain in autism: a review and future directions
Int. J. Dev. Neurosci.
(2005) - et al.
Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia
Schizophr. Res.
(1995) The amygdala and ventromedial prefrontal cortex in morality and psychopathy
Trends Cogn. Sci.
(2007)- et al.
Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study
Neuroimage
(2004) - et al.
Default-mode brain dysfunction in mental disorders: a systematic review
Neurosci. Biobehav. Rev.
(2009) - et al.
Altered integrity of perisylvian language pathways in schizophrenia: relationship to auditory hallucinations
Biol. Psychiatry
(2011)
Short frontal lobe connections of the human brain
Cortex
Beyond cortical localization in clinico-anatomical correlation
Cortex
Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection
Curr. Opin. Neurobiol.
The hippocampus, a time machine that makes errors
Trends Cogn. Sci.
Comparison of fiber tracts derived from in-vivo DTI tractography with 3D histological neural tract tracer reconstruction on a macaque brain
Neuroimage
A modified damped Richardson-Lucy algorithm to reduce isotropic background effects in spherical deconvolution
Neuroimage
Meta-analysis of diffusion tensor imaging studies in schizophrenia
Schizophr. Res.
Anterior cingulate pathology and social cognition in schizophrenia: a study of gray matter, white matter and sulcal morphometry
Neuroimage
Medial temporal and prefrontal function: recent behavioural disconnection studies in the macaque monkey
Cortex
Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses
Biol. Psychiatry
Studying connections in the living human brain with diffusion MRI
Cortex
Microstructural organization of cerebellar tracts in schizophrenia
Biol. Psychiatry
Diffusion tensor imaging in schizophrenia
Biol. Psychiatry
Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging
Biol. Psychiatry
Fornix integrity and hippocampal volume in male schizophrenic patients
Biol. Psychiatry
Atlas-based segmentation of white matter tracts of the human brain using diffusion tensor tractography and comparison with classical dissection
Neuroimage
Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism
Neurosci. Lett.
A study of diffusion tensor imaging by tissue-specific, smoothing-compensated voxel-based analysis
Neuroimage
Into the mind of a killer
Nature
Absolute diffusivities define the landscape of white matter degeneration in Alzheimer's disease
Brain
Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study
Bipolar Disord.
EPS Mid-Career Award 2006. Understanding anterograde amnesia: disconnections and hidden lesions
Q. J. Exp. Psychol. (Colchester)
Language networks in semantic dementia
Brain
Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients
Arch. Gen. Psychiatry
T2 hyperintensities in bipolar disorder: magnetic resonance imaging comparison and literature meta-analysis
Am. J. Psychiatry
Early-Onset Dementia: A National Challenge, A Future Crisis
2012 Alzheimer's Disease Facts and Figures
Meeting of minds: the medial frontal cortex and social cognition
Nat. Rev. Neurosci.
Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder
Mol. Psychiatry
In vivo fiber tractography using DT-MRI data
Magn. Reson. Med.
Demonstration eines gehirns mit Zestörung der vor- deren und inneren Theile der Hirnrinde beider Schläfenlappen
Neurol. Centralbl.
Neural basis of confabulation
Neurology
A selective impairment in the processing of sad and fearful expressions in children with psychopathic tendencies
J. Abnorm. Child Psychol.
The Psychopath: Emotion and the Brain
Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia
Arch. Neurol.
Anterior cingulate cortex pathology in schizophrenia and bipolar disorder
Acta Neuropathol.
Anatomie comparée des circonvolutions cérébrales: le grand lobe limbique
Rev. Anthropol.
An investigation into the functions of the occipital and temporal lobes of the monkey's brain
Philos. Trans. R. Soc. Lond. B
A study of bipolar disorder using magnetization transfer imaging and voxel-based morphometry
Brain
The brain's default network: anatomy, function, and relevance to disease
Ann. N.Y. Acad. Sci.
Cited by (482)
Unveiling the muscle-brain axis: A bidirectional mendelian randomization study investigating the causal relationship between sarcopenia-related traits and brain aging
2024, Archives of Gerontology and GeriatricsSystemic lupus erythematosus-related brain abnormalities in the default mode network and the limbic system: A resting-state fMRI meta-analysis
2024, Journal of Affective DisordersThe role of income and emotional engagement in the efficacy of a brief help-seeking video intervention for essential workers
2024, Journal of Psychiatric ResearchDistinctive intrinsic functional connectivity alterations of anterior cingulate cortex subdivisions in major depressive disorder: A systematic review and meta-analysis
2024, Neuroscience and Biobehavioral ReviewsThe mediodorsal thalamus in executive control
2024, Neuron