Baroreceptor Sensitivity is Optimized by Deep Brain Stimulation in
Humans
Jonathan Hyam, Tipu Aziz and Alexander Green
Nuffield Department of Surgical Sciences, Department of Physiology, Anatomy & Genetics, University of Oxford,
Oxford, U.K.
1 OBJECTIVES
Dysautonomia can be debilitating and
predominantly manifests as postural hypotension.
Sympathetic myocardial denervation and deranged
arterial baroreceptor reflex are among the
abnormalities described in Parkinson's disease
(PD) in which dysautonomia can affect up to 50%
of patients. Deep brain stimulators placed within
the brainstem or hypothalamus have been shown to
modulate cardiorespiratory function and many of
these stimulated sites are components of the central
autonomic network and the baroreceptor circuit.
Electrical stimulation is provided chronically
through an implanted electrode, across the brain-
machine interface. In humans, we have previously
demonstrated a resistance to postural drop in blood
pressure on standing and during head-up tilt with
deep brain stimulation (DBS) of the periventricular
grey matter of the midbrain and pedunculopontine
nucleus at the junction of the midbrain and pons.
This mirrors results found in animal studies. We
investigated whether DBS could improve Valsalva
response, an index of dysautonomia, using PD as
the model of dysautonomia.
2 METHODS
Design: Prospective Controlled StudySubjects:
Eight PD patients tested and stimulation On and
Off in random order.
Valsalva manoeuvre to achieve a pressure of
30-40mmHg was sustained for 15 seconds.
Portapress continuous non-invasive
plethysmography to record blood pressure and
electrocardiogram were recorded. Baroreceptor
sensitivity (BRS) was calculated from the transfer
function of systolic BP and R-R interval using
autoregressive modelling. Valsalva ratio (VR) was
calculated as the ratio between the quickest heart
rate during Phase II against the slowest heart rate
of Phase IV of the Valsalva manoeuvre (normal
VR>1.21).
3 RESULTS
Six patients could be successfully tested. Valsalva
ratio increased with stimulation from median 1.15
(SE +/- 0.06) Off to 1.20 (SE +/- 0.06) On
(p=0.028). BRS increased significantly during
Valsalva compared to rest with stimulation On
versus Off (p=0.028). BRS increase had a major
correlation with mean depth of PPN stimulating
electrode contacts whereby it explained 89% of its
variance (Spearman’s rho=0.943, n=6, p=0.005).
4 DISCUSSION
Pathological cardiovascular response to Valsalva
manoeuvre in PD, characteristic of dysautonomia,
shifted towards normal. There was a direct effect
on BRS itself suggesting central cardiovascular
modulation by DBS. This adds to the body of
human data supporting the beneficial
cardiovascular modulation provided by DBS and
this is the first study to show significant
improvements in autonomic function in patients
with existing dysautonomia.
Hyam J., Aziz T. and Green A..
Baroreceptor Sensitivity is Optimized by Deep Brain Stimulation in Humans.
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 2013 SCITEPRESS (Science and Technology Publications, Lda.)