Review article
Self-awareness and the medial temporal lobe in neurodegenerative diseases

https://doi.org/10.1016/j.neubiorev.2017.04.015Get rights and content

Highlights

  • Most studies on self-awareness point to involvement of cortical midline structures.

  • Medial temporal lobe changes also occur in patients unaware of their disabilities.

  • The medial temporal lobe structures involved depend on the self-awareness domain.

  • The findings are discussed in view of the connectivity of the medial temporal lobe.

  • They are also discussed in the context of theoretical models of self-awareness.

Abstract

Accurate self-awareness is essential for adapting one’s behaviour to one’s actual abilities, to avoid risky behaviour. Impaired self-awareness of deficits is common in neurodegenerative diseases. Numerous studies show an involvement of midline cortical areas in impaired self-awareness. Among the other brain regions implicated stand the medial temporal lobe (MTL) structures (i.e. hippocampus, amygdala, and temporopolar, entorhinal, perirhinal and posterior parahippocampal cortices). This review aims at evaluating the role of those structures in self-awareness in neurodegenerative diseases. To this aim, we briefly review impaired self-awareness in neurodegenerative diseases, give a neuroanatomical background on the MTL structures, and report those identified in neuroimaging studies on self-awareness. The MTL shows neuropathological, and structural or functional changes in patients who overestimate their abilities in the cognitive, socio-emotional or daily life activities domains. The structures implicated differ depending on the domain considered, suggesting a modality-specific involvement. The functional significance of the findings is discussed in view of the neuroanatomical networks of the MTL and in the context of theoretical models of self-awareness.

Introduction

Awareness can be defined as “a reasonable or realistic perception or appraisal of one’s situation, functioning or performance, or of the resulting implications, expressed explicitly or implicitly” (Clare et al., 2011). Accurate self-awareness is essential for optimal daily life activities, as it allows adapting individual behaviour to different situations according to one’s actual abilities. Accurate self-awareness thus prevents from risky or withdrawal behaviour.

Impaired self-awareness may have significant adverse effects. For instance, overestimation of one’s driving or postural abilities increases the risk of driving or fall accident (Morone et al., 2014, Horrey et al., 2015), and overestimation of one’s cognitive abilities may negatively impact numerous daily life activities such as managing finances or shopping (Hoofien et al., 2004); likewise, inaccurate estimation of one’s social skills may affect social communication. Conversely, underestimation of these same abilities may lead to a loss of autonomy and social isolation. However, overestimation is more common than underestimation of one’s abilities (e.g. Michon et al., 1994, Okonkwo et al., 2008). Unawareness of deficits can be detrimental to the rehabilitation of brain damage. It also affects the patient’s family and friends’ quality of life, namely by increasing the caregivers’ burden (Rymer et al., 2002). Although impaired self-awareness should thus be considered as a symptom of great importance, it is often neglected, mainly because of the lack of knowledge of its pathophysiology, treatment and prevention.

Impaired self-awareness has been reported in a number of neurological and neuropsychiatric disorders (e.g. stroke, neurodegenerative diseases, traumatic brain injury, schizophrenia), and in various domains (e.g. sensori-motor, cognitive, socio-emotional, and daily life activities). This clearly demonstrates that there is no “awareness centre” in the brain, but rather suggests that self-awareness implies several areas likely organized in specific networks.

Attempts to unravel the brain networks involved in impaired self-awareness have been the focus of a number of studies. The medial prefrontal cortex is the most constantly identified region within this network. Other cortical and sub-cortical areas have been implicated. However, their role in self-awareness remains obscure (see Northoff et al., 2006 for meta-analysis). Among them, the medial temporal lobe (MTL) structures stand out, namely the hippocampus, amygdala, and surrounding cortices, i.e. the temporopolar, entorhinal, perirhinal and posterior parahippocampal cortices.

This review aims at providing an in depth analysis of the putative role of MTL in impaired self-awareness in neurodegenerative diseases, because this symptom is common in these conditions that are often associated with MTL damage albeit to varying degrees. Moreover, involvement of MTL in impaired self-awareness has never been explored specifically. Thus, we will focus on five of such neurodegenerative diseases: Alzheimer’s disease (AD), frontotemporal dementia (FTD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). Mild cognitive impairment (MCI) has also been included in the review because many symptoms are shared and quite a few individuals will convert to AD.

Section snippets

Methodological assessment procedures

The most frequently used method of assessing self-awareness is to compare the participant’s judgments about its own abilities and behaviour with parallel ratings made by an informant (e.g. spouse and caregiver). Several validated questionnaires and standardized procedures have been developed (eg, Wilson et al., 1989, Clare et al., 2002, Starkstein et al., 2006, Bramham et al., 2009). This method, however, lacks direct measurement of performance, and a range of psychological and social factors

Medial temporal lobe and awareness in neurodegenerative diseases

Brain networks of self-awareness in neurodegenerative diseases were mainly investigated by assessing the brain correlates of self-awareness (using structural MRI or metabolic FDG-PET imaging for instance) or in participants performing a self-awareness task (e.g. fMRI). Up to date, there is only one postmortem anatomical study (Marshall et al., 2004), and it provided little significant information due to various methodological limitations (e.g. only four areas investigated, etc.).

Structural or

Functional interpretation of neuroimaging findings on self-awareness in neurodegenerative diseases

Three main salient points emerge from the review of the above neuroimaging studies. First, despite the numerous differences in the methodological procedure used in the different studies (e.g. population, awareness assessment, imaging techniques, statistical analyses), the MTL structures that show structural or functional changes in patients who overestimate their abilities are essentially consistent from one study to the other, especially when analysed by awareness domain. Second, structural or

Future directions and conclusion

In view of the present review, there is a need for further neuroimaging investigations focusing on MTL in the various domains of self-awareness and in the different neurodegenerative diseases. In addition, the search for other brain centres involved in self-awareness, as the present endeavour regarding the role played by the MTL, is a potentially fruitful avenue for future studies designed to advance in the knowledge of the biological basis of self-awareness. Special attention should in

Acknowledgements

The authors wish to thank the personnel of the Human Neuroanatomy Laboratory of the University of Castilla-La Mancha as well as E Monfardini (INSERM U1028, CNRS UMR5292) for their valuable help in neuroanatomy and neuroimaging analyses. Supported by grants BFU-06-12964 and BFU09-14705 from MINECO, Spain.

References (102)

  • J.P. Jacus et al.

    Awareness disorders in Alzheimer’s disease and in mild cognitive impairment

    Encephale

    (2014)
  • K. Juottonen et al.

    Volumes of the entorhinal and perirhinal cortices in Alzheimer’s disease

    Neurobiol. Aging

    (1998)
  • F. Maier et al.

    Behavioural and neuroimaging correlates of impaired self-awareness of hypo- and hyperkinesia in Parkinson’s disease

    Cortex

    (2016)
  • W.B. Marlowe et al.

    Complete Kluver-Bucy syndrome in man

    Cortex

    (1975)
  • G. Morone et al.

    Can overestimation of walking ability increase the risk of falls in people in the subacute stage after stroke on their return home?

    Gait Posture

    (2014)
  • R.G. Morris et al.

    Anosognosia, autobiographical memory and self-knowledge in Alzheimer’s disease

    Cortex

    (2013)
  • G. Northoff et al.

    Self-referential processing in our brain–a meta-analysis of imaging studies on the self

    Neuroimage

    (2006)
  • O.C. Okonkwo et al.

    Awareness of deficits in financial abilities in patients with mild cognitive impairment: going beyond self-informant discrepancy

    Am. J. Geriatr. Psychiatry

    (2008)
  • S. Pietracupa et al.

    Poor self-awareness of levodopa-induced dyskinesias in Parkinson’s disease: clinical features and mechanisms

    Parkinsonism Relat. Disord.

    (2013)
  • F. Piras et al.

    Self-awareness in Mild Cognitive Impairment: quantitative evidence from systematic review and meta-analysis

    Neurosci. Biobehav. Rev.

    (2016)
  • M.L. Ries et al.

    Medial prefrontal functional connectivity–relation to memory self-appraisal accuracy in older adults with and without memory disorders

    Neuropsychologia

    (2012)
  • R.S. Rosenbaum et al.

    The case of K.C.: contributions of a memory-impaired person to memory theory

    Neuropsychologia

    (2005)
  • S.E. Starkstein

    Anosognosia in Alzheimer’s disease: diagnosis, frequency, mechanism and clinical correlates

    Cortex

    (2014)
  • J.P. Aggleton

    The contribution of the amygdala to normal and abnormal emotional states

    Trends Neurosci.

    (1993)
  • M. Amanzio et al.

    Unawareness of deficits in Alzheimer’s disease: role of the cingulate cortex

    Brain

    (2011)
  • D.G. Amaral et al.

    Retrograde transport of d-[3H]-aspartate injected into the monkey amygdaloid complex

    Exp. Brain. Res.

    (1992)
  • D.G. Amaral et al.

    Amygdalo-cortical projections en the monkey (Macaca fascicularis)

    J. Comp. Neurol.

    (1984)
  • X. Blaizot et al.

    Mapping the visual recognition memory network with PET in the behaving baboon

    J. Cereb. Blood Flow Metab.

    (2000)
  • X. Blaizot et al.

    Correlations between visual recognition memory and neocortical and hippocampal glucose metabolism after bilateral rhinal cortex lesions in the baboon: implications for Alzheimer’s disease

    J. Neurosci.

    (2002)
  • X. Blaizot et al.

    The parahippocampal gyrus in the baboon: anatomical, cytoarchitectonic and MRI studies

    Cereb. Cortex

    (2004)
  • X. Blaizot et al.

    The human parahippocampal region: I. Temporal pole cytoarchitectonic and MRI correlation

    Cereb. Cortex

    (2010)
  • H. Braak et al.

    Neuropathological stageing of Alzheimer-related changes

    Acta Neuropathol.

    (1991)
  • H. Braak et al.

    Pattern of brain destruction in Parkinson's and Alzheimer’s diseases

    J. Neural Transm.

    (1996)
  • J. Bramham et al.

    Social and emotional functioning following bilateral and unilateral neurosurgical prefrontal cortex lesions

    J. Neuropsychol.

    (2009)
  • C. Chavoix et al.

    Excitotoxic lesions of the rhinal cortex in the baboon differentially affect visual recognition memory, habit memory and spatial executive functions

    Eur. J. Neurosci.

    (2002)
  • L. Clare et al.

    Assessing awareness in early-stage Alzheimer’s disease: development and piloting of the Memory Awareness Rating Scale

    Neuropsychol. Rehabil.

    (2002)
  • L. Clare et al.

    Awareness in Alzheimer’s disease and associated dementias: theoretical framework and clinical implications

    Aging Mental Health

    (2011)
  • L. Clare et al.

    Memory awareness profiles differentiate mild cognitive impairment from early-stage dementia: evidence from assessments of performance monitoring and evaluative judgement

    Dement. Geriatr. Cogn. Disord.

    (2013)
  • S. Corkin et al.

    H.M.’s medial temporal lobe lesion: findings from magnetic resonance imaging

    J. Neurosci.

    (1997)
  • S. Corkin

    Permanent Present Tense: the Unforgettable Life of the Amnesic Patient

    (2013)
  • G. Dalla Barba et al.

    Anosognosia, intrusions and ‘frontal’ functions in Alzheimer’s disease and depression

    Neuropsychologia

    (1995)
  • P. Eslinger et al.

    Metacognitive deficits in frontotemporal dementia

    J. Neurol. Neurosurg. Psychiatry

    (2005)
  • L.A. Flashman

    Disorders of awareness in neuropsychiatric syndromes: an update

    Curr. Psychiatry Rep.

    (2002)
  • E. Frankó et al.

    Identification of the human medial temporal lobe regions on magnetic resonance images

    Hum. Brain Mapp.

    (2014)
  • J.M. Fuster et al.

    Neuron activity related to short-term memory

    Science (New York, NY)

    (1971)
  • P.S. Goldman-Rakic

    Working memory and the mind

    Sci. Am.

    (1992)
  • D. Hoofien et al.

    Unawareness of cognitive deficits and daily functioning among persons with traumatic brain injuries

    J. Clin. Exp. Neuropsychol.

    (2004)
  • M. Hornberger et al.

    Ventromedial-frontopolar prefrontal cortex atrophy correlates with insight loss in frontotemporal dementia and Alzheimer’s disease

    Hum. Brain Mapp.

    (2014)
  • B.T. Hyman et al.

    Alzheimers’s disease: cell-speciphic pathology isolates the hippocampal formation

    Science

    (1984)
  • H. Ichikawa et al.

    Self-rated anosognosia score may be a sensitive and predictive indicator for progressive brain atrophy in amyotrophic lateral sclerosis: an X-ray computed tomographic study

    Eur. Neurol.

    (2013)
  • Cited by (33)

    • Self-awareness and underestimation of cognitive abilities in patients with adult temporal lobe epilepsy after surgical treatment

      2020, Epilepsy and Behavior
      Citation Excerpt :

      These brain networks are connected to the temporal lobe through projections from the entorhinal cortex. Moreover, studies on cognitive self-awareness and neurodegenerative disease affecting the temporal lobe have reported a tendency toward the engagement of bilateral hippocampus and parahippocampal cortices [80]. Our findings indicate that episodic memory performance is not correlated with self-awareness or self-reports of cognitive function in patients with TLE.

    • Neuroanatomical and cognitive correlates of domain-specific anosognosia in early Alzheimer's disease

      2020, Cortex
      Citation Excerpt :

      Similarly, other studies postulate that memory anosognosia could find its pathological substrates in regions responsible for autobiographical conceptual memory such as medial temporal lobe structures that are damaged by the characteristic pathophysiology of AD (Morris & Mograbi, 2013; Tondelli et al., 2018). The clinical manifestations of memory or executive anosognosia are associated with degeneration of densely interconnected fronto-temporal structures which are thought to be responsible for the integrity of the cognitive awareness system (Chavoix & Insausti, 2017). Moreover, since anosognosia in AD can be expressed in multiple clinical domains, it is unknown whether the mechanisms are the same for each domain affected by the trait.

    • Altered neural basis of self-reflective processing in schizophrenia: An fMRI study

      2019, Asian Journal of Psychiatry
      Citation Excerpt :

      In the present study, only the patient group exhibited hyperactivation in the left hippocampus and right external capsule associated with the other-evaluation task. Although previous fMRI of self/other evaluation tasks in schizophrenia patients revealed no such findings (e.g., Murphy et al., 2010; Pankow et al., 2016), the hippocampus plays an essential role in the self-memory system, especially episodic memory (Martinelli et al., 2013), and may have a significant role in impaired self-awareness in neurodegenerative/neuropsychiatric diseases (Chavoix and Insausti, 2017). Recent diffusion tensor image (DTI) studies demonstrated white matter abnormality in the CMS-related area, including the cingulate, hippocampus, and external capsule, in first-episode schizophrenia (Lee et al., 2013; Asmal et al., 2017).

    View all citing articles on Scopus
    View full text