Supplemental material for:
Whole blood Serotonin Levels in Healthy Elderly are Negatively Associated with the Functional Activity of Emotion-related Brain Regions
Yacila I. Deza-Araujoa,b, Sebastian Baez-Lugoa,b, Patrik Vuilleumiera,b, Anne Chocatc,Gaël Chételatc, Géraldine Poisnelc, Olga M. Klimeckia,d
a Swiss Center for Affective Sciences, University of Geneva, Geneva, Switzerland.
b Laboratory for Behavioral Neurology and Imaging of Cognition, Department of Neuroscience, Medical School, University of Geneva, Geneva, Switzerland.
c Inserm, UMR-S U1237, Université de Caen-Normandie, GIP Cyceron, Caen, France.
d Clinical Psychology and Behavioral Neuroscience, Faculty of Psychology, Technische Universität Dresden, 01187, Dresden, Germany.
Correspondence concerning this article should be addressed to:
Yacila I. Deza-Araujo, Ph.D.
Swiss Center for Affective Sciences, University of Geneva, Campus Biotech
Chemin des Mines 9, 1202 Geneva, Switzerland.
Phone: +41 (0) 223790228
E-mail address: yacila.dezaaraujo@unige.ch
S1. Recruitment process
This study included data from the baseline assessment (V1) of the Age-Well randomized Clinical Trial (See Poisnel et al. (2018) for a complete description). Participants were recruited between end of 2016 and May 2018 from the general population in and around the town of Caen (Normandy, France), in three successive cohorts of 43, 50 and 44 participants, respectively, 6 months apart. Advertisement for recruitment was carried out through a communication campaign which included advertisement in media outlets and social media, and distribution of flyers in relevant places. Interested citizens were invited to attend a public conference in which the researchers gave written and oral information about the clinical trial and to potential participants. At this point, eligibility was assessed by means of a pre-screening questionnaire. Prescreened participants were then invited to the screening visit (V0) at which a neuropsychological assessment was performed. After this, participants who fulfilled eligibility criteria were invited to the baseline pre-intervention (V1), and then randomized to one of the three arms (groups) at a ratio of 1:1:1. A graphical depiction of the recruitment process is provided in Figure S1.
Fig S1. Flow diagram of participant’s recruitment
S2. Inclusion and exclusion criteria
Participants were included in the study if they met the following criteria: age ≥64 years, autonomous and living at home, native French speaker, retired for at least one year, educational level ≥7 years (from the Preparatory Course, 1st grade, included), registered to the social security system, motivated to participate in the project, available to attend the intervention for the total trial duration (24 months), performance within the normal range on standardized cognitive tests according to agreed study-specific standards (age, sex and education level when available. For details, see (Poisnel et al., 2018), no strong preference or aversion for an intervention group, no present or past regular or intensive practice of meditation or comparable practices (i.e. more than one day per week for more than six consecutive months over the last 10 years, and/or in case of more than five consecutive days of intensive practice such as internship or retreat, over the past 10 years, and/or of more than 25 days of retreats (cumulatively) within the last 10 years) and not fluent in English.
Exclusion criteria included: Being under legal guardianship or incapacitation, diagnosis of major neurological or psychiatric disorder (including an addiction to alcohol or drugs), history of cerebral disease (vascular, degenerative, physical malformation, tumour, or head trauma with loss of consciousness for more than an hour), presence of a chronic disease or acute unstable illness (respiratory, cardiovascular, digestive, renal, metabolic, hematologic, endocrine or infectious), current or recent medication that may interfere with cognitive functioning (psychotropic, antihistaminic with anticholinergic action, anti- Parkinson's, benzodiazepines, steroidal anti-inflammatory long-term treatment, antiepileptic or analgesic drugs), safety concerns in relation to MR scanning (claustrophobia, ferromagnetic object) or PET scanning (blood sampling to check hepatic and renal functions are performed before the PET scans; known hypersensibility to Amyvid or Glucotep), participation in another biomedical research protocol including the injection of radiopharmaceuticals, physical or behavioral inability to perform the follow-up visits as planned in the study protocol.
S3. Development of the SoVT-Rest
The Socio-affective Video Task (SoVT) consists of three parallel video sets (V1, V2, V3) with 12 high emotion (HE) and 12 low emotion (LE) videos (Klimecki, Leiberg, Lamm, &
Singer, 2013). HE videos depict people in distress (i.e., due to catastrophes, diseases or physical pain) and LE videos depict people in everyday activities (i.e., talking or walking).
The videos were selected from documentaries and unedited material cast for news. The functional paradigm used in our study is a modified version of the SoVT, which includes resting periods after each block of high emotion (HE) or low emotion (LE) videos (SoVT- Rest; Baez-Lugo et al., under review). Specifically, each block of either HE or LE videos was followed by a resting period of 90 seconds to observe potential carryover effects of the previous set of videos in the resting-state activity (Eryilmaz, Van De Ville, Schwartz, &
Vuilleumier, 2011). During the SoVT-Rest, the videos are presented in two separate runs in a randomized order (i.e. half of the participants started the experiment by a HE block and the other half by a LE block). Each run was followed by a thought probe to determine what participants were thinking during the last resting period (following LE videos in one run and following HE videos in the other run). The total duration of the SoVT-Rest in the scanner was approximately 21 minutes from which 9.5 minutes corresponded to the duration of a single run and one minute corresponded to the though probe.
S4. ROI analysis using anatomical masks
We performed additional analyses as a “sanity check” and to confirm the specificity of our results. First, we created our ROIs again, this time based on binary anatomical masks.
Briefly, we defined the amygdalae and the insulae from the Harvard-Oxford atlas (Desikan et al., 2006) and the dACC and sgCG from the Brainetomme Atlas (Fan et al., 2016) using FSLeyes (https://git.fmrib.ox.ac.uk/fsl/fsleyes/fsleyes/).
As illustrated below in Fig. S2, the results of these analyses confirmed the main findings reported in our study. Specifically, correlations between whole blood 5-HT and difference in activity (i.e. HE-LE) during videos in the bilateral insula, dACC and sgCG yielded significant results. However, one potential limitation of these analyses is the size of anatomical masks, which comprise adjacent regions. Due to the lower specificity of these regions, we favoured analyses using spheres located at the peak of activations for each selected region in the Neurosynth database.
Fig. S2. Correlations between whole blood 5-HT and brain activity in response to HE-LE videos in the selected ROIs (bilateral amygdala, bilateral insula, dorsal anterior cingulate cortex and subgenual gyrus. Significant Pearson’s partial correlations (controlled for age and sex) are highlighted in bold letters.
Supplemental Table S1. Relationships between whole blood 5-HT levels and behavioral variables.
PSWQ RRS STAI-trait GDS SoVT-
positive LE
SoVT- negative
LE
SoVT- positive
HE
SoVT- negative
HE Zero - order correlations
5 ρ = .05 ρ = -.02 ρ = -.07 ρ = -.07 ρ = -.02 ρ = .07 ρ = -.09 ρ =.12 H p =.54 p =.82 p =.42 p =.40 p =.77 p =.43 p =.31 p =.18 T
Partial correlations
5 ρ = .04 ρ = -.03 ρ = -.07 ρ = -.08 ρ = -.02 ρ = .07 ρ = -.07 ρ =.10 H p =.59 p =.73 p =.39 p =.34 p =.77 p =.38 p =.43 p =.25 T
PSWQ = Penn State Worry Questionnaire; RRS = Rumination Response Scale; STAI-trait = State-Trait anxiety Inventory; GDS = Geriatric Depression Scale; SoVT = Socio-affective Video Task, LE = Low Emotion, HE = High Emotion.
5-HT= 5-hydroxytryptamine – Serotonin.
ρ = Spearman’s zero-order correlation and partial correlation, controlled for age and sex.
p-values uncorrected for multiple comparisons.
Supplemental Table S2. Relationships between whole blood 5-HT levels and behavioral measures of empathy and prosocialness.
SoVT- Empathy
LE
SoVT- Empathy
HE
IRI-
Fantasy IRI- Perspective
taking
IRI- Empathic
concern
IRI-
Distress Prosocialness Zero-Order correlations
5 ρ = .06 ρ = .14 ρ = -.03 ρ = .10 ρ = .07 ρ = .06 ρ = -.03
H p =.49 p =.15 p =.54 p =.30 p =.43 p =.60 p =.85
T
Partial correlations
5 ρ = -.003 ρ = .14 ρ = -.07 ρ = .03 ρ = .06 ρ = .03 ρ = .01
H p =.97 p =.11 p =.40 p =.72 p =.46 p =.74 p =.87
T
SoVT = Socio-affective Video Task, LE = Low Emotion, HE = High Emotion; IRI = Interpersonal Reactivity Index.
5-HT= 5-hydroxytryptamine – Serotonin
ρ = Spearman’s zero-order correlation and partial correlation, controlled for age and sex p - values uncorrected for multiple comparisons.
Supplemental Table S3. Relationship between HE-LE brain reactivity in target ROIs and behavioral measures of emotion.
Videos PSWQ RRS STAI-
trait
GDS SoVT- positive HE - LE
SoVT- negative HE - LE Right
Amygdala ρ = .12 ρ = .20 ρ = .20 ρ = .08 ρ = -.00 ρ = .04 p =.17 p =.02* p =.02* p =.37 p =.99 p =.62 Left
Amygdala ρ = .12 ρ = .22 ρ = .20 ρ = .05 ρ = -.10 ρ = .14 p =.17 p =.01* p =.02* p =.54 p =.23 p =.11 Right
Insula ρ = .04 ρ = .11 ρ = .10 ρ =.05 ρ = .08 ρ = .03 p =.59 p =.20 p =.27 p =.53 p =.33 p =.71 Left
Insula ρ = -.08 ρ = .06 ρ = .07 ρ = .15 ρ = -.03 ρ = .03 p =.35 p =.51 p =.44 p =.10 p =.69 p =.69 dACC ρ = .05 ρ = .17 ρ = .05 ρ = -.01 ρ = .01 ρ = .13 p =.53 p =.05 p =.51 p =.91 p =.89 p =.14 sgCG ρ = .01 ρ = -.00 ρ = -.03 ρ = -.11 ρ = .03 ρ =.04 p =.89 p =.92 p =.72 p =.21 p =.71 p =.66 Rest
Right
Amygdala ρ = .12 ρ = .05 ρ =.12 ρ =.04 ρ = -.04 ρ = -.14 p =.18 p =.58 p =.15 p =.62 p =.65 p =.12 Left
Amygdala ρ = .01 ρ = .03 ρ =-.01 ρ =-.00 ρ =-.04 ρ =-.14 p =.86 p =.68 p =.88 p =.93 p =.65 p =.12 Right
Insula ρ = .13 ρ =.01 ρ =.11 ρ =.02 ρ = -.07 ρ =.11
p =.14 p =.85 p =.21 p =.82 p =.41 p =.23 Left
Insula ρ =.16 ρ =.07 ρ =.08 ρ =-.01 ρ =-.01 ρ =.12
p =.07 p =38 p =.36 p =.88 p =.90 p =.81
dACC ρ =-.06 ρ =-.02 ρ =.02 ρ =.15 ρ =.56 ρ =-.01
p =.45 p =.78 p =.77 p =.08 p =-.05 p =.86
sgCG ρ =.01 ρ =.03 ρ =.07 ρ =.00 ρ =-.01 ρ =-.02
p =.88 p =.70 p =.40 p =.99 p =.88 p =.79
PSWQ = Penn State Worry Questionnaire; RRS = Rumination Response Scale; STAI-trait = State-Trait anxiety Inventory; GDS = Geriatric Depression Scale; SoVT = Socio-affective Video Task, HE - LE = High Emotion ratings minus Low Emotion ratings.
dACC = Dorsal anterior cingulate cortex; sgCG = Subgenual cingulate gyrus.
ρ = Spearman’s zero-order correlation.
*p < 0.05, uncorrected for multiple comparisons.
Supplemental Table S4. Relationship between brain reactivity in target ROIs and behavioral measures of empathy and prosocialness.
Videos SoVT- Empathy
HE - LE
IRI-
Fantasy IRI- Perspective
taking
IRI- Empathic
concern
IRI-
Distress Prosocialness Right
Amygdal a
ρ =.05 ρ = .13 ρ = .02 ρ = -.06 ρ =-.01 ρ = -.02 p =.58 p =.13 p =.80 p =.50 p =.89 p =.80
Left Amygdal a
ρ =.10 ρ = .13 ρ = -.06 ρ = -.08 ρ =-.01 ρ = .01 p =.25 p =.14 p =.48 p =.36 p =.90 p =.87
Right
Insula ρ =.07 ρ = .03 ρ = -.05 ρ = -.13 ρ = .00 ρ = -.10 p =.39 p =.73 p =.54 p =.13 p =.98 p =.24 Left
Insula ρ = -.07 ρ = .07 ρ = .04 ρ = -.04 ρ =-.05 ρ = -.03 p =.43 p =.39 p =.66 p =.62 p =.51 p =.73 dACC ρ =.01 ρ = .06 ρ = -.02 ρ = -.12 ρ =-.01 ρ = -.01
p =.90 p =.51 p =.80 p =.16 p =.86 p =.86 sgCG ρ = .04 ρ = -.03 ρ = -.03 ρ = -.05 ρ = .01 ρ = .08 p =.66 p =.70 p =.73 p =.58 p =.86 p =.37 Rest
Right Amygdal
a
ρ = -.00 ρ =.08 ρ =.01 ρ =.18 ρ =.13 ρ =.07 p =.94 p =.38 p =.84 p =.04 p =.14 p =.41
Left ρ =.00 ρ =.02 ρ =.02 ρ =.17 ρ =.06 ρ =.06 Amygdal
a p =.97 p =.77 p =.82 p =.05 p =.49 p =.51
Right ρ =.04 ρ =.21 ρ =.03 ρ =.17 ρ =.16 ρ =.07
Insula p =.66 p =.01* p =.70 p =.05 p =.07 p =.40
Left ρ =.09 ρ =.12 ρ =-.05 ρ = .23 ρ =.18 ρ =.10
Insula p =.32 p =.19 p =.52 p =.01* p =.04* p =.27
dACC ρ =-.09 ρ =.07 ρ =-.09 ρ =.08 ρ =.02 ρ =.07 p =.32 p =.44 p =.32 p =.36 p =.80 p =.42 sgCG ρ =-.08 ρ =-.06 ρ =-.00 ρ =-.05 ρ =.06 ρ =-.11
p =.80 p =.50 p =.93 p =.56 p =.46 p =.21
SoVT = Socio-affective Video Task, HE - LE = High Emotion ratings minus Low Emotion ratings; IRI = Interpersonal Reactivity Index.
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