Alterations in functional cortical hierarchy in hemiparkinsonian rats.
J. Neurosci.. 2017-07-07; 37(32): 7669-7681
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1. J Neurosci. 2017 Aug 9;37(32):7669-7681. doi: 10.1523/JNEUROSCI.3257-16.2017.
Epub 2017 Jul 7.
Alterations in Functional Cortical Hierarchy in Hemiparkinsonian Rats.
Jávor-Duray BN(1), Vinck M(2), van der Roest M(1), Bezard E(3)(4), Berendse
HW(5), Boraud T(3)(4), Voorn P(6).
(1)Department of Anatomy and Neurosciences, VU University Medical Center,
Amsterdam Neuroscience, 1081 BT Amsterdam, The Netherlands.
(2)Ernst Strüngmann Institut for Neuroscience in Cooperation with Max Planck
Society, 60528 Frankfurt am Main, Germany.
(3)Université de Bordeaux, Institut des Maladies Neurodégénératives, Unité Mixte
de Recherche 5293, F-33000 Bordeaux, France.
(4)Centre National de la Recherche Scientifique, Institut des Maladies
Neurodégénératives, Unité Mixte de Recherche 5293, F-33000 Bordeaux, France, and.
(5)Department of Neurology, VU University Medical Center, Amsterdam Neuroscience,
1081 HV Amsterdam, The Netherlands.
(6)Department of Anatomy and Neurosciences, VU University Medical Center,
Amsterdam Neuroscience, 1081 BT Amsterdam, The Netherlands, .
Parkinson’s disease and experimentally induced hemiparkinsonism are characterized
by increased beta synchronization between cortical and subcortical areas. This
change in beta connectivity might reflect either a symmetric increase in
interareal influences or asymmetric changes in directed influences among brain
areas. We assessed patterns of functional and directed connectivity within and
between striatum and six cortical sites in each hemisphere of the
hemiparkinsonian rat model. LFPs were recorded in resting and walking states,
before and after unilateral 6-hydroxydopamine lesion. The hemiparkinsonian state
was characterized by increased oscillatory activity in the 20-40 Hz range in
resting and walking states, and increased interhemispheric coupling (phase lag
index) that was more widespread at rest than during walking. Spectral
Granger-causality analysis revealed that the change in symmetric functional
connectivity comprised profound reorganization of hierarchical organization and
directed influence patterns. First, in the lesioned hemisphere, the more
anterior, nonprimary motor areas located at the top of the cortical hierarchy
(i.e., receiving many directed influences) tended to increase their directed
influence onto the posterior primary motor and somatosensory areas. This enhanced
influence of “higher” areas may be related to the loss of motor control due to
the 6-OHDA lesion. Second, the drive from the nonlesioned toward the lesioned
hemisphere (in particular to striatum) increased, most prominently during
walking. The nature of these adaptations (disturbed signaling or compensation) is
discussed. The present study demonstrates that hemiparkinsonism is associated
with a profound reorganization of the hierarchical organization of directed
influence patterns among brain areas, perhaps reflecting compensatory
processes.SIGNIFICANCE STATEMENT Parkinson’s disease classically first becomes
manifest in one hemibody before affecting both sides, suggesting that
degeneration is asymmetrical. Our results suggest that asymmetrical degeneration
of the dopaminergic system induces an increased drive from the nonlesioned toward
the lesioned hemisphere and a profound reorganization of functional cortical
hierarchical organization, leading to a stronger directed influence of
hierarchically higher placed cortical areas over primary motor and somatosensory
cortices. These changes may represent a compensatory mechanism for loss of motor
control as a consequence of dopamine depletion.
Copyright © 2017 the authors 0270-6474/17/377669-13$15.00/0.
PMID: 28687605 [Indexed for MEDLINE]