Brain Imaging and Behavior

, Volume 12, Issue 6, pp 1622–1630 | Cite as

Structural and functional papez circuit integrity in amyotrophic lateral sclerosis

  • Ana Paula Arantes Bueno
  • Walter Hugo L. Pinaya
  • Luciana M. Moura
  • Maxime Bertoux
  • Ratko Radakovic
  • Matthew C. Kiernan
  • Antonio Lucio Teixeira
  • Leonardo Cruz de Souza
  • Michael HornbergerEmail author
  • João Ricardo Sato


Cognitive impairment in amyotrophic lateral sclerosis (ALS) is heterogeneous but now recognized as a feature in non-demented patients and no longer exclusively attributed to executive dysfunction. However, despite common reports of temporal lobe changes and memory deficits in ALS, episodic memory has been less explored. In the current study, we examined how the Papez circuit—a circuit known to participate in memory processes—is structurally and functionally affected in ALS patients (n = 20) compared with healthy controls (n = 15), and whether these changes correlated with a commonly used clinical measure of episodic memory. Our multimodal MRI approach (cortical volume, voxel-based morphometry, diffusion tensor imaging and resting state functional magnetic resonance) showed reduced gray matter in left hippocampus, left entorhinal cortex and right posterior cingulate as well as increased white matter fractional anisotropy and decreased mean diffusivity in the left cingulum bundle (hippocampal part) of ALS patients compared with controls. Interestingly, thalamus, mammillary bodies and fornix were preserved. Finally, we report a decreased functional connectivity in ALS patients in bilateral hippocampus, bilateral anterior and posterior parahippocampal gyrus and posterior cingulate. The results revealed that ALS patients showed statistically significant structural changes, but more important, widespread prominent functional connectivity abnormalities across the regions comprising the Papez circuit. The decreased functional connectivity found in the Papez network may suggest these changes could be used to assess risk or assist early detection or development of memory symptoms in ALS patients even before structural changes are established.


Multimodal MRI Papez circuit Episodic memory Cognitive deficits Amyotrophic lateral sclerosis 



The authors gratefully acknowledge the contribution of the patients and their families. The authors thank Prof. Paulo Caramelli for his valuable comments on early versions of the manuscript.


This work was supported by the National Health and Medical Research Council of Australia Program Grant to Forefront (1,037,746) and the Brain Foundation Australia grant to MH. MH is further supported by Alzheimer’s Research UK and the Wellcome trust. AB is supported by FAPESP. Grant 2016/19376-9, São Paulo Research Foundation (FAPESP). RR is supported by the Motor Neuron Disease Association (MNDA).

Compliance with ethical standards

Conflict of interest

All authors report no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee (Human Research Ethics Committee of South Eastern Sydney/Illawarra Area Health Service) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from all individual participants included in the study or from a close relative.

Supplementary material

11682_2018_9825_MOESM1_ESM.docx (27 kb)
Supplementary material 1 (DOCX 27 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ana Paula Arantes Bueno
    • 1
  • Walter Hugo L. Pinaya
    • 1
  • Luciana M. Moura
    • 1
  • Maxime Bertoux
    • 2
  • Ratko Radakovic
    • 3
    • 4
    • 5
  • Matthew C. Kiernan
    • 6
  • Antonio Lucio Teixeira
    • 7
  • Leonardo Cruz de Souza
    • 7
  • Michael Hornberger
    • 2
    Email author
  • João Ricardo Sato
    • 1
  1. 1.Center of Mathematics, Computation and CognitionUniversidade Federal do ABCSanto AndréBrazil
  2. 2.Department of Medicine, Norwich Medical SchoolUniversity of East AngliaNorwichUK
  3. 3.School of Health Sciences, Norwich Medical SchoolUniversity of East AngliaNorwichUK
  4. 4.Alzheimer Scotland Dementia Research CentreUniversity of EdinburghEdinburghUK
  5. 5.Centre for Cognitive Ageing and Cognitive EpidemiologyUniversity of EdinburghEdinburghUK
  6. 6.Brain & Mind Centre and Sydney Medical SchoolUniversity of SydneySydneyAustralia
  7. 7.Department of Internal MedicineUniversidade Federal de Minas GeraisBelo HorizonteBrazil

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