1. Neuroscience
Download icon

Causal manipulation of functional connectivity in a specific neural pathway during behaviour and at rest

  1. Vanessa M Johnen  Is a corresponding author
  2. Franz-Xaver Neubert
  3. Ethan R Buch
  4. Lennart M Verhagen
  5. Jill O'Reilly
  6. Rogier B Mars
  7. Matthew F S Rushworth
  1. Oxford University, United Kingdom
  2. National Institutes of Health, United States
Research Article
  • Cited 24
  • Views 3,154
  • Annotations
Cite this article as: eLife 2015;4:e04585 doi: 10.7554/eLife.04585

Abstract

Correlations in brain activity between two areas (functional connectivity) have been shown to relate to their underlying structural connections. We examine the possibility that functional connectivity also reflects short-term changes in synaptic efficacy. We demonstrate that paired transcranial magnetic stimulation (TMS) near ventral premotor cortex (PMv) and primary motor cortex (M1) with a short 8ms inter-pulse interval evoking synchronous pre- and post-synaptic activity and which strengthens interregional connectivity between the two areas in a pattern consistent with Hebbian plasticity, leads to increased functional connectivity between PMv and M1 as measured with functional magnetic resonance imaging (fMRI). Moreover, we show that strengthening connectivity between these nodes has effects on a wider network of areas, such as decreasing coupling in a parallel motor programming stream. A control experiment revealed that identical TMS pulses at identical frequencies caused no change in fMRI-measured functional connectivity when the inter-pulse-interval was too long for Hebbian-like plasticity.

Article and author information

Author details

  1. Vanessa M Johnen

    Department of Experimental Psychology, Oxford University, Oxford, United Kingdom
    For correspondence
    vanessa.johnen@psy.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Franz-Xaver Neubert

    Department of Experimental Psychology, Oxford University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Ethan R Buch

    Human Cortical Physiology and Neurorehabilitation Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lennart M Verhagen

    Department of Experimental Psychology, Oxford University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Jill O'Reilly

    Functional Magnetic Resonance Imaging of the Brain Centre, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Rogier B Mars

    Department of Experimental Psychology, Oxford University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Matthew F S Rushworth

    Department of Experimental Psychology, Oxford University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Human subjects: Human subjects: Informed consent, including consent to publish was obtained from all subjects. The study was performed in accordance with local ethics committee approval (MKREC REF 07/Q1603/11 and Berkshire REC 11/SC/0537).

Reviewing Editor

  1. Jody C Culham, University of Western Ontario, Canada

Publication history

  1. Received: September 3, 2014
  2. Accepted: February 8, 2015
  3. Accepted Manuscript published: February 9, 2015 (version 1)
  4. Version of Record published: March 10, 2015 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 3,154
    Page views
  • 687
    Downloads
  • 24
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Genetics and Genomics
    2. Neuroscience
    Radhia Kacher et al.
    Research Article

    Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD mutation carriers over a twenty-year period, along with post-mortem tissue from 15 adults and 7 fetal mutation carriers, to examine somatic expansions at different stages of life. Post-mortem brains, as previously reported, had the greatest expansions, but fetal cortex had virtually none. Somatic instability in blood increased with age, despite blood cells being short-lived compared to neurons, and was driven mostly by CAG repeat length, then by age at sampling and by interaction between these two variables. Expansion rates were higher in symptomatic subjects. These data lend support to a previously proposed computational model of somatic instability-driven disease.

    1. Neuroscience
    Kara A Fulton, Kevin L Briggman
    Tools and Resources

    A dense reconstruction of neuronal synaptic connectivity typically requires high-resolution 3D electron microscopy (EM) data, but EM data alone lacks functional information about neurons and synapses. One approach to augment structural EM datasets is with the fluorescent immunohistochemical (IHC) localization of functionally relevant proteins. We describe a protocol that obviates the requirement of tissue permeabilization in thick tissue sections, a major impediment for correlative pre-embedding IHC and EM. We demonstrate the permeabilization-free labeling of neuronal cell types, intracellular enzymes, and synaptic proteins in tissue sections hundreds of microns thick in multiple brain regions from mice while simultaneously retaining the ultrastructural integrity of the tissue. Finally, we explore the utility of this protocol by performing proof-of-principle correlative experiments combining two-photon imaging of protein distributions and 3D EM.