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Neurosurgery
Review
Anatomy and function of the fornix in the context of its potential as a therapeutic target
  1. Suhan Senova1,
  2. Anton Fomenko2,3,
  3. Elise Gondard3,
  4. Andres M Lozano2,3
  1. 1 Neurosurgery, Institut Mondor de recherche biomedicale, Créteil, Île-de-France, France
  2. 2 Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada
  3. 3 University Health Network, Toronto, Ontario, Canada
  1. Correspondence to Dr Andres M Lozano, Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, ON M5T2S8, Canada; lozano{at}uhnresearch.ca

Abstract

The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play a key role in cognition and episodic memory recall. As the most prevalent cause of dementia, Alzheimer’s disease (AD) dramatically impairs the quality of life of patients and imposes a significant societal burden on the healthcare system. As an established treatment for movement disorders, deep brain stimulation (DBS) is currently being investigated in preclinical and clinical studies for treatment of memory impairment in AD by modulating fornix activity. Optimal target and stimulation parameters to potentially rescue memory deficits have yet to be determined. The aim of this review is to consolidate the structural and functional aspects of the fornix in the context of neuromodulation for memory deficits. We first present an anatomical and functional overview of the fibres and structures interconnected by the fornix. Recent evidence from preclinical models suggests that the fornix is subdivided into two distinct functional axes: a septohippocampal pathway and a subiculothalamic pathway. Each pathway’s target and origin structures are presented, followed by a discussion of their oscillatory dynamics and functional connectivity. Overall, neuromodulation of each pathway of the fornix is discussed in the context of evidence-based forniceal DBS strategies. It is not yet known whether driving fornix activity can enhance cognition—optimal target and stimulation parameters to rescue memory deficits have yet to be determined.

  • alzheimer's disease
  • electrical stimulation
  • neurosurgery
  • limbic system
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jnnp-2019-322375

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    Footnotes

    • SS and AF are joint first authors.

    • SS and AF contributed equally.

    • Contributors SS and AF are joint first authors and contributed equally to the manuscript. SS conceived the manuscript and wrote the first draft. AF created figures, wrote the anatomy and pathology chapters and revised the manuscript. EG contributed the imaging and clinical trials chapter. AL oversaw revisions and approved the final manuscript.

    • Funding This review was made possible by the R.R. Tasker Chair in Functional Neurosurgery, University Health Network (AML) and the University of Manitoba Clinician Investigator Program (AF)

    • Competing interests AML is a consultant to Medtronic, St Jude, Boston Scientific, Functional Neuromodulation and Insightec.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.