Comparing neural response to painful electrical stimulation with functional MRI at 3 and 7 T
Introduction
Within the last decades, in vivo investigations by functional magnetic resonance imaging (fMRI) have substantially improved our knowledge of human brain function. This includes basic physiological processes and the response to external stimulation as well as pathological alterations. The continuous technical advancements of scanners, coils, imaging sequences and data analysis have further allowed to depict neural processing with increasing spatial specificity (Norris, 2003). A major step is the ongoing shift to higher field strength, from 1.5 T to 3 T and nowadays even to 7 T and above.
Although sophisticated acquisition techniques are required to overcome increased effects of geometric distortions (Sladky et al., 2013), physiological noise (Triantafyllou et al., 2005) and reduced T2* relaxation times (Bandettini et al., 2012), higher field strengths may offer great advantages. These include increases in image and time course signal to noise ratios (SNR, see also Discussion) and improved spatial resolution allowing for thinner slices which in turn reduces signal drop out, especially in basal brain areas (Bandettini et al., 2012, Moser et al., 2012, Norris, 2003, Sladky et al., 2013, Solano-Castiella et al., 2011). Accordingly, previous applications demonstrated robust advances in blood oxygen level dependent (BOLD) contrast and spatial specificity at 7 T during visual (Duong et al., 2003, Yacoub et al., 2001) and motor tasks (van der Zwaag et al., 2009) as well as emotional processing (Sladky et al., 2013). These comparisons, however, used rather simple paradigms and focused on the signal response of single brain regions. Hence, it is not clear whether the advantages of 7 T equally translate to the entire brain when investigating a complex set of areas activated by a task. Potential issues for such regional differences are physiological noise and artifacts caused by movement, since both also increase with the field strength (Hutton et al., 2011, Triantafyllou et al., 2005). As movement is also likely to increase with scan time, this may represent an important issue for the design of fMRI experiments regarding the paradigm length, especially in certain patient populations.
To compare the BOLD signal response between different field strengths in more detail we used painful and non-painful electrical stimulation during fMRI at 3 T and 7 T. The perception of nociceptive stimuli is a complex process including sensory, affective and cognitive domains (Friebel et al., 2011, Peyron et al., 2000). Hence, functional imaging studies may further improve our understanding of pain processing as well as the treatment of patients with chronic pain. Administration of painful stimuli elicits activation in several cortical brain regions (such as the primary and secondary somatosensory cortices, supplementary motor area, insula, midcingulate cortex) and in subcortical areas within the midbrain periaqueductal gray (PAG) and the thalamus (Apkarian et al., 2005, Duerden and Albanese, 2013, Friebel et al., 2011, Kong et al., 2010, Peyron et al., 2000). The PAG has been identified as a key region for the expression, control and modulation of pain (Eippert et al., 2009, Linnman et al., 2012). However from a methodological point of view, several difficulties have complicated imaging of this area by fMRI. First of all, accurate localization might be difficult to achieve at the whole-brain level since spatial normalization algorithms are designed to solve an overall optimization problem for the entire brain, whereas the registration results for brainstem nuclei might be less accurate (Beissner et al., 2011). Similarly, standard spatial smoothing (e.g., 8 mm Gaussian kernel) is optimized for larger cortical areas whereas this might introduce signal decreases and/or partial volume effects in small brainstem structures (Linnman et al., 2012). The brainstem is also subject to movement from cardiac and cerebrospinal fluid pulsations, which might further complicate robust identification of PAG activations due to motion artifacts. Considering the above mentioned advantages of 7 T regarding spatial resolution, specificity, increased BOLD contrast and SNR, functional imaging of small subcortical regions such as the PAG might be markedly improved at higher field strengths.
Therefore, we aimed to evaluate the BOLD signal response during the perception of painful transcutaneous electrical stimulation at 3 T and 7 T. The optimization of pain-induced activations was further addressed by variation of the paradigm length (i.e., varying the number of runs) for each scanner as well as assessment of the accompanied changes in motion. Moreover, we investigated whether differences between the two field strengths are similarly present when using the specific control condition of non-painful stimuli. In addition to activations in cortical areas, special attention was drawn to the midbrain PAG. Here an optimized preprocessing strategy was employed to improve the spatial registration of brainstem regions. This enables a thorough assessment of the potential advantages of higher field strengths regarding spatial specificity of small subcortical structures.
Section snippets
Participants
Twenty-nine healthy right-handed participants were recruited via poster notice, whereas 7 dropped out during the study due to technical reasons and/or non-compliance with the study protocol, resulting in 22 subjects for the final analysis (mean age ± SD = 24.3 ± 3.8 years, 10 females). All subjects underwent medical examination and an interview with an experienced psychiatrist including the Structural Clinical Interview for DSM-IV (SCID) to rule out any psychiatric, neurological and physical
Results
The analysis of motion parameters showed a significant interaction between field strength and the number of runs (F1,21 = 19.5) as well as main effects of field strength (F1,21 = 22.5) and runs (F1,21 = 16.3, all p < 0.001). Post-hoc paired t-tests revealed that the average displacement was higher for all 4 runs as compared to the 1st run at 3 T (t = 4.3, p < 0.001) but not at 7 T (t = 0.4, p = 0.72). Furthermore, increased displacement was observed at 3 T compared to 7 T, which was slightly lower for the 1st run
Discussion
Evaluating the BOLD signal response to painful transcutaneous electrical stimulation showed stronger activations for 7 T as compared to 3 T in various brain regions involved in pain processing, except the SII. However, increasing the number of runs resulted in decreased activations for both field strengths, whereas motion parameters increased for 3 T but not at 7 T. Contrasting painful against non-painful stimuli yielded differences between the two field strengths only within the PAG at uncorrected
Conclusions
To summarize, 7 T fMRI yielded stronger BOLD signal response to transcutaneous electrical stimulation as compared to 3 T in a number of brain areas associated with pain processing. The advantage of higher field strength however depends on the region, the control condition and the contrast of interest. For the small subcortical area of the periaqueductal gray, 7 T showed marked improvements in localization of activation foci due to increased spatial specificity.
The following are the supplementary
Acknowledgments
This research was supported by an intramural grant of the research cluster between the Medical University of Vienna and the University of Vienna (FA103FC001) to C. Lamm and R. Lanzenberger as well as a grant from the Austrian National Bank to S. Kasper (OeNB14577). This project received partial funding from the Viennese Science and Technology Fund (projects CS11-016 and CS11-005). We would like to thank the native speaker M. Spies for English proofreading.
Conflict of interest
The authors declare
References (37)
- et al.
Human brain mechanisms of pain perception and regulation in health and disease
Eur. J. Pain
(2005) - et al.
fMRI of the brainstem using dual-echo EPI
NeuroImage
(2011) - et al.
Classical fear conditioning in functional neuroimaging
Curr. Opin. Neurobiol.
(2000) - et al.
Activation of the opioidergic descending pain control system underlies placebo analgesia
Neuron
(2009) - et al.
Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain
NeuroImage
(2011) - et al.
The amygdala response to emotional stimuli: a comparison of faces and scenes
NeuroImage
(2002) - et al.
The impact of physiological noise correction on fMRI at 7 T
NeuroImage
(2011) - et al.
Exploring the brain in pain: activations, deactivations and their relation
Pain
(2010) - et al.
Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study
Neuron
(1998) - et al.
Neuroimaging of the periaqueductal gray: state of the field
NeuroImage
(2012)
Automated brainstem co-registration (ABC) for MRI
NeuroImage
Functional imaging of brain responses to pain. A review and meta-analysis (2000)
Neurophysiol. Clin.
Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion
NeuroImage
The organization and function of endogenous antinociceptive systems
Prog. Neurobiol.
High-resolution functional MRI of the human amygdala at 7 T
Eur. J. Radiol
Slice-timing effects and their correction in functional MRI
NeuroImage
Parcellation of human amygdala in vivo using ultra high field structural MRI
NeuroImage
Comparison of physiological noise at 1.5 T, 3 T and 7 T and optimization of fMRI acquisition parameters
NeuroImage
Cited by (43)
Cerebral effects of gender-affirming hormone treatments in transgender persons
2023, Principles of Gender-Specific Medicine: Sex and Gender-Specific Biology in the Postgenomic EraRegional hypothalamic, amygdala, and midbrain periaqueductal gray matter recruitment during acute pain in awake humans: A 7-Tesla functional magnetic resonance imaging study
2022, NeuroImageCitation Excerpt :Since experimental animal studies have shown that the hypothalamus, amygdala, and PAG contain many discrete subnuclei with varying connections and functions, limitations in the spatial acuity of most human brain imaging studies has meant that very few studies have attempted detailed exploration of these regions in humans. Ultra-high field strength magnetic resonance imaging (MRI) scanners, with greater signal-to-noise and higher spatial resolution, have improved our ability to explore small brain structures such as the brainstem, in more detail (Crawford et al., 2021; Faull et al., 2015; Hahn et al., 2013; Sclocco et al., 2019, 2016). Specifically, the human equivalents of the sub-nuclei identified in animal models may be detectable.
Detached empathic experience of others’ pain in remitted states of depression – An fMRI study
2021, NeuroImage: Clinical