Quantitative Assessment of the Activation of Brain Areas With Positive and Negative Emotional Stimuli and Its Correlation With Degrees of Emotional Disorder.
Conditions: Emotional Disorder
Sponsor: Instituto del Corazon, Argentina

                                 PROTOCOL N ° 2 
 
Title: Quantitative assessment of the activation of brain areas 
with positive and negative emotional stimuli and its correlation 
with degrees of emotional disorder. 
 
NCT number: not yet assigned 
 
Document date: 06/01/2021 
 
Updated: 10/11/2021 
 
 
INCOR IMAGES - Bazan y Bustos 132. La Rioja (5300) 
 
Main investigator: Ruben Novoa, MD Head of Magnetic Resonance Imaging at Incor Images. 
rubennnovoa@gmail.com Tel: 3804509777 
 
Collaborators: Graduates in production of Bioimages Maribel Oliva, Ivana Ceressa and Paolo 
Paez from the Magnetic Resonance Imaging Area of Incor Images. 
 
REFERENTIAL FRAME 
The technology applied in functional magnetic resonance imaging allows us to visualize on a 
color scale the changes in the blood flow of those sectors of the brain that increase their 
metabolic activity during a given action. This is achieved by mapping the volume of cerebral 
blood, known by its acronym in English as CBV (cerebral blood volume), which increases or 
decreases according to the metabolic activity in a certain region of the brain. This indirect 
method of measuring the metabolic activity of brain areas is very useful for anatomically 
identifying motor areas and critical functions in individual patients prior to neurosurgery, to 
allow better surgical planning. Currently this is its main application in healthcare practice. In 
the field of research it is applied in clinical neurology, psychiatry and psychology. Studies have 
been conducted on the activations of brain regions in basic emotions. There is less data on the 
quantitative differences of these activations in the Argentine population according to the 
degree of emotional disorder, this being the object of study of this project. 
 
JUSTIFICATION 
By comparing the findings of clinically of participants with different degrees of emotional 
disorder, treatment strategies can be developed based on the functional findings obtained. 
 
PROBLEM STATEMENT 
The diversity of feelings derived from basic emotions and the many possible combinations of 
their effects in emotional disorders, may mean that generic treatments for different clinical 
syndromes do not have the same efficacy in all patients. A more detailed study of the type and 
magnitude of brain activation related to the degree of emotional disorder will allow the 
development of personalized treatment strategies focused on obtaining better therapeutic 
results. 
 
RESEARCH QUESTION 
Are there differences in the activation of brain areas whith positive and negative emotional 
stimuli that are related to the degree of emotional disorder that can be used in symptomatic 
patients to develop personalized treatment strategies? 
 

GENERAL AND SPECIFIC OBJECTIVE 
The general objective is to demonstrate the relationship between the activation of brain areas 
and its intensity with the degree of emotional disturbance. In turn, the recognized patterns will 
be compared with the different degrees of emotional disorder determined by a validated 
survey, to try to determine the weight of the emotional disorder on each type of activation 
according to the stimulus received as a specific objective on each one of them in particular. 
 
HYPOTHESIS 
The activation of specific brain areas follows common patterns for basic emotions and their 
derived feelings depending on whether they are positive or negative emotions, while in 
patients with emotional deficits the activation patterns are different and this difference can 
manifest itself in specific emotions. 
 
METHODOLOGY TYPE OF STUDY 
Initial exploratory, observational, cross-sectional study. 
 
UNIVERSE 
Population of the City of La Rioja. 
 
SAMPLE 
We estimate that 13 participants would give the study more than 80% power to detect a change 
between measures of 5% or more, using a linear mixed model for repeated measures, with a type I 
error of 5% (3).  
 
INCLUSION, EXCLUSION AND ELIMINATION CRITERIA 
Volunteers who express their informed consent to participate in the research protocol will be 
included. The exclusion criteria will be the impossibility of the patient to actively collaborate 
with the tests to be carried out for the measurement of emotional responses and / or the 
conditions that represent contraindications for carrying out MRI studies in general. The 
elimination criterion will be the appearance of any of the two exclusion criteria mentioned at 
any time during the development of the research. 
 
OPERATIONALIZATION OF VARIABLES 
Variable: increased metabolism of a brain area before the application of an emotional 
stimulus. The stimuli will be generated by paradigms designed to generate positive and 
negative emotional responses, using audiovisual material c constituted by fragments of films 
validated for the local population (9), following in all cases the quality requirements of 
paradigms defined by the American Society of Functional Neuroradiology (ASFNR). 
 
Type of variable: dependent, controlled. 
 
Origin of the variable: attributive. 
 
Operational definition: the increase in metabolism in a given brain area is indirectly quantified 
through mapping the brain blood volume in that area in relation to a stimulus. Indicator: The 
comparative mapping will be the input to determine the indicator in the comparative 
assessment of patients according to their score in the variable on emotional disorders. 
Measurement level: ratio or proportion. 
 
Variable: The categorization of the volunteers by score for levels of emotional disturbance 
using the 37-question version of the CESIM, validated for the local population (10). 
 

MEASUREMENT TOOLS 
Philips Prodiva resonator, year of manufacture 2018, with 1.5 Tesla magnetic field, BOLD 
sequence, for the measurement of blood flow variations as an indirect parameter of the 
metabolic activation of specific brain areas, post-processing software incorporated in the 
resonator, sound circuit compatible with the resonance room for auditory stimuli and external 
projection of images with mirror system for visual stimuli. 
 
INFORMATION ACQUISITION 
The training of Graduates in Production of Bioimages for the application of the fRMI paradigms 
will be in charge of the principal investigator. The design of the paradigms will be carried out 
by the principal investigator. At the time of the study, the acquisitions during the 
implementation of the paradigms will be made by the Graduates in Bioimagenes Production 
under the supervision of the researchers. The CESIM 37 questionnaires will be filled out by the 
participants prior to obtaining the fMRI images. 
The technical parameters in the acquisition of the fMRI images will be the following: 
Volumetric acquisition in T1 will be made with a 1.2 mm slice thickness without gap, with TR 
7000.0 and TE 154.9. 
Two BOLD acquisitions will be made, the first with a positive stimulus and the second with a 
negative stimulus, obtaining in each one the slices with a 4 mm slice thickness without gap, 
TR 3000.0 and TE 50.0 
The positive and negative paradigms have duration of 250 seconds each, with an initial rest 
period of 80 seconds, a validated video projection for 140 seconds and a final rest period of 30 
seconds for the positive stimulus and 80-130-40 seconds for the negative stimuus. 
 
STATISTICAL ANALYSIS PROGRAM 
 
The final data processing will be carried out with statistical tools to quantitatively compare the 
activation areas in the different clinical scenarios according to the type of stimulus 
administered. The activation areas before the positive and negative stimulus will be quantified 
in cm³ and fMRI Z-score and correlated with the score of the emotional questionnaire. Pierson's 
correlation coefficient will be used for data of normal distribution or Spearman in case of not 
having normal distribution. 
 
PLAN FOR THE PRESENTATION OF THE INFORMATION 
Starting on July 1, 2021, it is planned to provide the Committee with information on the 
progress of the project every 30 days, namely on 8/1, 9/1, 10/1 and 11/1, 2021 to later 
present the final report. 
 
SCHEDULE OF ACTIVITIES 
Calibration and fine-tuning of the enabled software and tests in healthy volunteers of the 
auditory and visual paradigms developed by the researchers. From 7/1/21 to 7/25/21. 
fMRI sessions for the quantification of emotions in different parameters with healthy 
volunteers. From 7/28/21 to 10/30/21. 
Statistical post-processing of results from 11/01/21 to 11/22/21. Presentation of the final report 
on 11/30/21 and subsequent submission to a scientific journal for consideration of its 
publication. 
 
BUDGET 
The use of the BOLD sequence to perform fRMI is provided free of charge by Philips for a 
limited period of time for the purposes of carrying out this research protocol. No disposables 
or medications are used. The necessary elements for the construction of paradigms, 
stationery, etc. they will be contributed by the researchers. No expenses are generated for 

Incor, except for the use of the room, light, etc., during the MRI acquisitions that will be 
carried out at specific times without interfering with the healthcare task. 
ETHICAL CONSIDERATIONS 
The informed consent of each volunteer participant will be requested, including a personal 
interview to clarify any doubts that may arise and explain in detail and clearly the 
characteristics of the study. Attached is a letter of adherence to the 2013 Declaration of 
Helsinki. The researcher's Certificate of Ethics issued by the La Rioja Council of Physicians is 
attached. The protocol is presented for evaluation by INCOR's Ethics Committee. 
 
BIBLIOGRAPHY 
1-Ríos, M. Neurosychology and Functional Magnetic Resonance. Radiology. Volume 50, 
Issue 5, October 2008 ,, pages 351-365. doi: 10.1016 / S0033-8338 (08) 76050-8 
2-Posner, J. The neurophysiological bases of emotion: An fMRI study of the affective 
circumplex using emotion-denoting words. Hum Brain Mapp. 2009 Mar; 30 (3): 883– 
895. 
3-Gur RE, Gur RC. Functional magnetic resonance imaging in schizophrenia. Dialogues 
Clin Neurosci. 2010; 12 (3): 333-343. doi: 10.31887 / DCNS.2010.12.3 / rgur 
4-Kassam, K. Identifying Emotions on the Basis of Neural Activation. PLOS ONE 
Published: June 19, 2013 https://doi.org/10.1371/journal.pone.0066032 5-Kragel PA, 
5-Kevin S. LaBar: Multivariate neural biomarkers of emotional states are categorically 
distinct. Social Cognitive and Affective Neuroscience (2015). DOI: 10.1093 / scan / 
nsv032 
6-Kragel PA, Knodt AR, Hariri AR, LaBar KS (2016) Decoding Spontaneous Emotional 
States in the Human Brain. PLOS Biology 14 (9): e2000106. 
https://doi.org/10.1371/journal.pbio.2000106 
7-Gu, S. An Integrative Way for Studying Neural Basis of Basic Emotions With fMRI. 
Front. Neurosci., June 19, 2019 | https://doi.org/10.3389/fnins.2019.00628 
8-Shunta - Cocha, F. Validation of an abstract reasoning paradigm for Functional 
Magnetic Resonance (fMRI). Ecuadorian Journal Neurology Vol. 29, No 2, 2020. 
9-Michelini, Y. Characteristics of the emotional experience induced by film fragments 
in a sample of young Argentines. Interdisciplinary, 2015, 32, 2, 367-382. 
10-Muñoz Rodriguez M, Korzeniowski C (2019) Validation of the epidemiological 
questionnaire in mental symptoms -CESIM- in the Argentine population. Journal of 
Public Health, (XXIII) 2: 8-24 June 2019