The impact of physiological noise on hemodynamic-derived estimates of directed functional connectivity

  • F. Konrad Schumacher
  • Carmen Steinborn
  • Cornelius Weiller
  • Björn O. Schelter
  • Matthias Reinhard
  • Christoph P. KallerEmail author
Original Article


Measuring the strength of directed functional interactions between brain regions is fundamental to understand neural networks. Functional near-infrared spectroscopy (fNIRS) is a suitable method to map directed interactions between brain regions but is based on the neurovascular coupling. It, thus, relies on vasomotor reactivity and is potentially biased by non-neural physiological noise. To investigate the impact of physiological noise on fNIRS-based estimates of directed functional connectivity within the rostro-caudal hierarchical organization of the prefrontal cortex (PFC), we systematically assessed the effects of pathological perturbations of vasomotor reactivity and of externally triggered arterial blood pressure (aBP) fluctuations. Fifteen patients with unilateral stenosis of the internal carotid artery (ICA) underwent multi-channel fNIRS during rest and during metronomic breathing, inducing aBP oscillations at 0.1 Hz. Comparisons between the healthy and pathological hemispheres served as quasi-experimental manipulation of the neurovascular system’s capability for vasomotor reactivity. Comparisons between rest and breathing served as experimental manipulation of two different levels of physiological noise that were expected to differ between healthy and pathological hemispheres. In the hemisphere affected by ICA stenosis, the rostro-caudal hierarchical organization of the PFC was compromised reflecting the pathological effect on the vascular and neural level. Breathing-induced aBP oscillations biased the magnitude of directed interactions in the PFC, but could be adjusted using either the aBP time series (intra-individual approach) or the aBP-induced fNIRS signal variance (inter-individual approach). Multi-channel fNIRS, hence, provides a sound basis for analyses of directed functional connectivity as potential bias due to physiological noise can be effectively controlled for.


Prefrontal cortex Hierarchical organization Directed interactions Near-infrared spectroscopy Physiological noise Stenosis 



Arterial blood pressure


Functional magnetic resonance imaging


Functional near-infrared spectroscopy


Prefrontal cortex


Internal carotid artery


(partial) Directed coherence


Power spectral density


Vector autoregressive



This work was supported by a grant of the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation (DFG, Grant Number EXC 1086).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the local Ethics Committee.

Informed consent

All patients gave written informed consent prior to participation

Supplementary material

429_2019_1954_MOESM1_ESM.docx (555 kb)
Supplementary material 1 (DOCX 556 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, Medical CenterUniversity of FreiburgFreiburgGermany
  2. 2.Freiburg Brain Imaging CenterUniversity of FreiburgFreiburgGermany
  3. 3.Faculty of BiologyUniversity of FreiburgFreiburgGermany
  4. 4.Faculty of MedicineUniversity of FreiburgFreiburgGermany
  5. 5.BrainLinks-BrainTools Cluster of ExcellenceUniversity of FreiburgFreiburgGermany
  6. 6.Institute for Complex Systems and Mathematical BiologyUniversity of AberdeenAberdeenUK
  7. 7.Department of Neurology, Medical Center EsslingenTeaching Hospital of the University of TübingenEsslingenGermany
  8. 8.Department of Neuroradiology, Medical CenterUniversity of FreiburgFreiburgGermany

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