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Uncovering brainheart
information through advanced
signal and image processing
Gaetano Valenza1,2,3 , Nicola Toschi4,5 and

Introduction

Riccardo Barbieri2,3,6

Cite this article: Valenza G, Toschi N, Barbieri

R. 2016 Uncovering brainheart information
through advanced signal and image
processing. Phil. Trans. R. Soc. A 374: 20160020.
http://dx.doi.org/10.1098/rsta.2016.0020

1 Research Center E. Piaggio, and Department of Information

Accepted: 8 February 2016

One contribution of 16 to a theme issue
Uncovering brainheart information through
advanced signal and image processing.
Subject Areas:
image processing, medical physics

Engineering, School of Engineering, University of Pisa, 56122 Pisa,

Italy
2 Department of Anesthesia, Critical Care and Pain Medicine,
Massachusetts General Hospital, Harvard Medical School, Boston,
MA 02114, USA
3 Massachusetts Institute of Technology, Cambridge, MA 02139, USA
4 Department of Biomedicine and Prevention, University of Rome
Tor Vergata, 00133 Rome, Italy
5 A.A. Martinos Center for Biomedical Imaging (MGH), Harvard
Medical School, Charlestown, MA 02129, USA
6 Department of Electronics, Informatics and Bioengineering,
Politecnico di Milano, 20133 Milan, Italy
GV, 0000-0001-6574-1879

Keywords:
brainheart interaction, advanced signal
and image processing, brainheart physiology
and physiopathology
Author for correspondence:
Gaetano Valenza
e-mail: g.valenza@ieee.org

Through their dynamical interplay, the brain and the

heart ensure fundamental homeostasis and mediate
a number of physiological functions as well as
their disease-related aberrations. Although a vast
number of ad hoc analytical and computational tools
have been recently applied to the non-invasive
characterization of brain and heart dynamic
functioning, little attention has been devoted to
combining information to unveil the interactions
between these two physiological systems. This theme
issue collects contributions from leading experts
dealing with the development of advanced analytical
and computational tools in the field of biomedical
signal and image processing. It includes perspectives
on recent advances in 7 T magnetic resonance imaging
as well as electroencephalogram, electrocardiogram
and cerebrovascular flow processing, with the
specific aim of elucidating methods to uncover novel
biological and physiological correlates of brainheart
physiology and physiopathology.

2016 The Author(s) Published by the Royal Society. All rights reserved.

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Over the past few years, there has been increasing evidence for the potential clinical implications
of dysfunctional brainheart interactions. For instance, cerebrovascular accidents and transient
ischaemic attacks (transient episodes of neurological dysfunction caused by the loss of blood flow)
are frequently caused by cardiac arrhythmias [1], and atrial fibrillation may also result in cognitive
disorders [2], even in the absence of manifest stroke [36]. On the other hand, brain disorders,
including stroke, epilepsy and others thought to be secondary to environmental stress (e.g. panic
disorders and emotional distress), may lead to cardiovascular disorders and have been shown to
result in cardiac arrhythmias both experimentally and clinically [7]. A recent article in Scientific
American (A new idea for treating Alzheimers) [8] begins with the following sentence: If its
good for the heart, it could also be good for the neurons, astrocytes and oligodendrocytes, cells
that make up the main items on the brains parts list, suggesting that Alzheimers disease may
be a candidate for combined brainheart therapeutic approaches. Furthermore, a wide variety
of changes in the electrocardiogram, mainly referring to arrhythmias and repolarization, is often
observed in the context of neurological disease [9].
In this context, a significant part of the current knowledge on brainheart interaction as
applied to the medical field refers to neurocardiology (see [9] also for a historical review). While
this discipline is inherently multidimensional, it may be conceptualized as divided into three
major categories: the hearts effects on the brain (e.g. cardiac source embolic stroke), the brains
effects on the heart (e.g. neurogenic heart disease) and neurocardiac syndromes (e.g. Friedreichs
ataxia [10,11]).
Modern neuroimaging data, including positron emission tomography and functional magnetic
resonance imaging (fMRI), have revealed that a network consisting of the insular cortex, anterior
cingulate gyrus and amygdala plays a crucial role in the regulation of the central autonomic
nervous system (ANS) [12]. More specifically, insular cortex damage has been associated with
cardiac arrhythmia, disruption of physiological diurnal blood pressure variations (e.g. a nondipper or riser pattern), myocardial injury and breathing-related sleep disorders, as well as
higher plasma levels of brain natriuretic peptide, catecholamines and glucose [12,13]. Moreover,
the paraventricular nucleus of the hypothalamus was seen to be one of the most important
central sites involved in regulating sympathetic tone and is, in part, responsible for the evident
dysregulation of the sympathetic nervous system in heart failure [1].
Despite the above-mentioned observations, current clinical practice in evaluating patients
suffering from conditions that involve the central nervous system often does not take into account
the concomitant autonomic/cardiovascular effects. This could possibly be due to a preferential
emphasis, in current medical training programmes, on expertise in single physiological systems
at the expense of interdisciplinary skills. Similar considerations result from examining the current
scientific literature, and while increased funding from the principal western agencies (European
Commission in Europe and National Institutes of Health in the USA) has been granted for the
study of the brain (the European Human Brain Project and the American Human Connectome
Project), the heart as a physiological subsystem is not explicitly taken into account in these
projects.
Another prominent reason why poor attention is devoted to the interaction between brain and
heart is the current lack of data analysis methodologies able to reliably handle such information.
It is not straightforward to obtain estimates of the bidirectional control effected through the
brainheart axis and, therefore, most experimental investigations of brain and cardiovascular
dynamics are simply based on simultaneous observation. Given that recent advances in data
collection techniques (such as high-resolution electroencephalogram (EEG) and ultra-high field
7 T MRI [14]) are providing access to a wealth of currently underexploited information,
the development of novel, evidence-based, ad hoc methodologies for biomedical signal and
image processing is expected to greatly advance the understanding of the pathophysiology of
brainheart interactions. In this context, purposeful mathematical modelling is a key player,
which can greatly aid in quantitatively characterizing complex heartbrain interactions, hence
allowing an improved understanding of physiological and clinical measurements related to both
domains [15]. In particular, novel methodological advancements have succeeded in combining

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rsta.royalsocietypublishing.org Phil. Trans. R. Soc. A 374: 20160020

imaging techniques with physiological measurements in order to map the central autonomic
network dynamics initiating peripheral autonomic control mechanisms [1620].
To this extent, this theme issue is focused on the application of advanced signal and
image processing algorithms to characterize brainheart interactions. The proposed contributions
include several novel key elements concerning the brainheart axis, from both experimental and
theoretical points of view.
In detail, this theme issue includes both extensive reviews (which critically report on the
current knowledge about brainheart physiology) and original research articles (which present
novel analysis methods targeted to extracting physiologically relevant information about brain
heart interactions).
Specifically, Silvani et al. [21] illustrate the functional and anatomical links between the brain
and the heart, as well as their possible disease-related alterations. Perspectives on the potential
clinical implications of advanced signal and image processing methods that are able to quantify
these links are also included. Chang et al. [22] critically discuss the recent improvements and
trade-offs in brain imaging at high and ultra-high field strengths (7 T MRI), also in the context
of distinguishing non-neural physiological effects from neural signals of interest that reflect
cardiorespiratory function. Recently developed data analysis methods to uncover novel heart
brain interactions are also covered. Rossi et al. [23] review current brain stimulation techniques
and the mechanisms underlying their neuromodulatory action on brain networks, including the
function of brainstem centres controlling vital functions as well as acute and long-term effects
on brain sympathetic outflow controlling heart function and blood pressure. Rossi et al. also
provide a critical perspective on how brain neuromodulation may enhance our understanding
of the cortical/subcortical mechanisms of autonomic cardiovascular regulation, and discuss how
such techniques may open a therapeutic window in patients with otherwise intractable autonomic
dysfunctions.
These reviews are complemented by 12 research articles providing original perspectives
on brainheart interactions. The latter are studied by measuring electrical activity (EEG) and
haemodynamic activity (cerebral blood flow and fMRI) while employing novel multivariate
modelling methodologies to analyse experimental brainheart-related findings in healthy subjects
as well as in patients with mental or neurological disorders.
In detail, five research articles describe novel methodologies for uncovering brainheart
information using EEG signals in conjunction with peripheral signals related to ANS activity.
Faes et al. [24] introduce a framework to study the network formed by the autonomic
component of heart-rate variability and the amplitude of the different EEG waves during healthy
and pathological sleep using multivariate linear models, whereas Lin et al. [25] propose a
generalized time-delay approach to quantifying dynamical interactions between physiologically
relevant brain rhythms and heart rate in healthy subjects during night-time sleep.
Furthermore, Stankovski et al. [26] study cross-frequency coupling functions between
neuronal, cardiac and respiratory oscillations, revealing how these relationships are altered
by anaesthesia, and Valenza et al. [27] describe brainheart dynamics during visual
emotion elicitation in healthy subjects, considering linear and nonlinear coupling measures
between instantaneous heart-rate estimates and EEG oscillations. Finally, Schulz et al. [28]
study brainheart interactions in paranoid schizophrenic patients, as compared with age
gender-matched healthy subjects, using high-resolution joint symbolic dynamics to analyse
EEG signals.
In view of the crucial role that haemodynamics plays in brainheart information exchange,
Marmarelis et al. [29] combine information gathered from heart-rate variability, arterial blood
pressure and cerebral blood flow velocity in healthy subjects through the concept of principal
dynamic modes, whereas Bari et al. [30] investigate cardiovascular and cerebrovascular control
systems through joint symbolic analysis, selectively conditioned on respiration, in subjects
experiencing recurrent syncope episodes when compared with healthy individuals.
Five further research articles describe novel methodologies for combining MRI data with
cardiovascular dynamics. Specifically, Bianciardi et al. [31] perform an initial validation of a

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