Ignite Creation Date:
2024-05-06 @ 7:01 PM
Last Modification Date:
2024-10-26 @ 2:58 PM
Study NCT ID:
NCT05863169
Status:
COMPLETED
Last Update Posted:
2023-05-17
First Post:
2022-10-17
Brief Title:
fNIRS Neurofeedback in Highly Impulsive Participants With ROI Regions DLPFC and IFG
Sponsor:
University Hospital Tuebingen
Organization:
University Hospital Tuebingen
Study Overview
Official Title:
Determining the Most Effective Training Region in ADHD Neurofeedback NF Therapy - Functional Near-infrared Spectroscopy NF of the Dorsolateral Prefrontal Cortex DLPFC vs Inferior Frontal Gyrus IFG in Healthy Participants
Status:
COMPLETED
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The aim of the following study is to investigate which is the best region of interest ROI for a functional near-infrared spectroscopy fNIRS-based neurofeedback NF training for highly-impulsive individuals and consequently also patients with attention-deficithyperactivity disorder ADHD the dorsolateral prefrontal cortex DLPFC or the inferior frontal gyrus IFG Generally NF trainings aim to improve the neurophysiological as well as cognitive-behavioral deficits observed in many neuropsychiatric disorders and were shown to constitute an effective complementary treatment option for patients with ADHD Some previous studies used the DLPFC as a ROI for NF training while others focused on the IFG as the main target region However so far no study has directly compared the effectiveness of NF trainings targeting the DLPFC vs IFG using the same protocol or the specificity of regulation efforts between these two areas using fNIRS Therefore the aim of the current study is to compare the effectiveness of fNIRS-NF using the DLPFC as a ROI with fNIRS-NF using the IFG as a ROI in a randomized controlled study design with highly-impulsive healthy participants
Furthermore the investigators aim to test the effect of fNIRS-NF training in the context of stress Previous studies reported that there is a strong connection between ADHD and stress However the effect of fNIRS-NF training for the adaptation to stressful situations is uncertain
To this end the investigators will assess the brain activity of participants before and after an fNIRS-NF training period during performance of a GoNoGo task an n-back task and The Trier Social Stress Test TSST It is hypothesized that both trainings will be successful in reducing impulsive behavior however in the prepost testing specific effects of fNIRS-based NF of the DLPFC are expected on working memory function and of fNIRS-based NF of the IFG on inhibitory control GoNoGo task Correlations between both functions and impulsive symptoms will give an indication which training ROI may be more promising for the treatment of specific subgroups of ADHD Correlations between regulation of different training ROIs will indicate the specificity of feedback regulation of circumscribed cortical areas
Furthermore the investigators aim to test the effect of fNIRS-NF training in the context of stress Previous studies reported that there is a strong connection between ADHD and stress However the effect of fNIRS-NF training for the adaptation to stressful situations is uncertain
To this end the investigators will assess the brain activity of participants before and after an fNIRS-NF training period during performance of a GoNoGo task an n-back task and The Trier Social Stress Test TSST It is hypothesized that both trainings will be successful in reducing impulsive behavior however in the prepost testing specific effects of fNIRS-based NF of the DLPFC are expected on working memory function and of fNIRS-based NF of the IFG on inhibitory control GoNoGo task Correlations between both functions and impulsive symptoms will give an indication which training ROI may be more promising for the treatment of specific subgroups of ADHD Correlations between regulation of different training ROIs will indicate the specificity of feedback regulation of circumscribed cortical areas
Detailed Description:
Aims
The investigators will assess the effects - and specificity - of two fNIRS-based NF protocols one targeting the DLPFC and one targeting the IFG Both groups will also be compared to a sham training group with regulation of the fNIRS signal outside of the frontal lobes Prepost testing will be conducted in all three groups ie measures of brain activity cognition and impulsive behavior will be obtained before the start of the NF training phase as well as following the last training session Thereby a GoNogo task and an n-back task will be applied to evaluate training-related changes in brain activity and neuropsychological performance The study population will be highly impulsive healthy individuals who were previously found to show a reduced DLPFC and IFG activity similar to patients with ADHD and the investigators expect their DLPFC and IFG function to increase after fNIRS-NF training Our hypothesis is that both active NF groups DLPFC and IFG will improve more than the placebo sham training group on all relevant measures Thereby specific advantages are expected in the DLPFC group for working memory data n-back task and in the IFG group for measures of inhibitory control GoNogo task Further the investigators will test the effect of fNIRS-NF on the stress response using the TSST as a standardized stress test It is hypothesized that fNIRS-NF training is also effective in reducing stress by strengthening stress-related regulation that has also been related to the frontal lobe
It is hypothesized that both trainings will be successful in reducing impulsive behavior however in a prepost testing specific effects of fNIRS-based NF of the DLPFC on working memory function and of fNIRS-based NF of the IFG on inhibitory control is expected Correlations between both functions and impulsive symptoms will give an indication which training ROI may be more promising for the treatment of specific subgroups of ADHD Correlations between regulation of different training ROIs will indicate the specificity of feedback regulation of circumscribed cortical areas
Functional near-infrared spectroscopy fNIRS
An fNIRS system ETG-4000 Hitachi Medical Corporation Japan will be used to measure hemodynamic responses within the prefrontal cortex PFC
All experiments will be conducted at the Department of Psychiatry and Psychotherapy University of Tübingen Calwerstraße 14Osianderstraße 24 72076 Tübingen All medical-technical devices are CE certified and approved for application in patients and will only be used according to their approved purpose by persons who have the knowledge and experience to operate apply and maintain the devices
Neurofeedback
One NF session comprises 2 feedback blocks each lasting 12 min and one transfer block lasting 8 min A feedback block consists of 12 regulation trials One regulation trial consists of 20 s resting time and 30 s regulation time The task is to increase or decrease the hemodynamic activity in the DLPFC or IFG or for the sham control group 4 channels of the temporal cortex which is putatively not involved in impulsivityADHD symptomatology furthermore in an unpublished pilot study these 4 channels were found to be inactive during a Stroop task involving cognitive control functions with 50 activation trials and 50 deactivation trials which were presented in random order As a feedback of hemodynamic brain activation a ball is shown to the participant on a screen moving from left to right and depicting concentration changes in oxygenated hemoglobin by moving below or above a line in the middle of the screen An arrow in the middle of the screen indicates if activation pointing upwards or deactivation pointing downwards is expected on a given trial In activation trials the concentration of oxygenated hemoglobin should increase in comparison to the baseline in deactivation trials it should decrease At the end of a successful trial the ball moved in the expected direction for at least 7 s of the last 15 s regulation time a rewarding feedback Gut gemacht weiter so which is German for Well done continue like this is shown on the screen A transfer block consists of 8 regulation trials in which the moving ball is not shown but the reward at the end of the trial still indicates whether the participant was successful The transfer blocks are included in order to facilitate transfer of the learned regulation strategies into everyday life
Study population
Participants will be recruited from the local student population via advertisementsemail and from existing databases An online system will be used to have potential participants fill out the ASRS in order to classify them as highly- or low-impulsive During this online screening procedure they confirm with a button press that they read the study information and the informed consent and that they agree with the usage of their data They continue by a further button press and will be informed about their rights Appropriate potential participants highly-impulsive healthy subjects with ASRS scores 15 but 23 are contacted again for a study appointment The complete study information informed consent and data safety form will be sent to the potential participant at that time When they arrive for the actual laboratory appointment they will again receive explanations on all procedures and possible risks verbally and in written form They are included in the study when they give their written informed consent
Sample Size Estimation
The proposed project is planned as a randomized controlled trial and comprises a total of 60 participants divided into an IFG- a DLPFC and a placebo training group receiving either IFG-based DLPFC-based or a sham temporal cortex NF control training Based on the effect sizes of NF interventions typically observed in patients with ADHD around d08 for attention-related symptom improvements as compared to different control groups including waiting list EMG biofeedback and cognitive training see eg Arns de Ridder Strehl Breteler Coenen 2009 subgroup sample sizes of n20 would be the result of a formal power calculation with a pre-defined α of 005 and an intended power of at least 80 Closely related to the currently planned training protocol recent own data confirm effect sizes of at least 08 for pre-post comparisons within a control group design In detail following eight training sessions with a frontal-lobe focused fNIRS-based NF training highly-impulsive subjects showed positive changes in both target cognitive measures standard deviation of RTs in a stop signal task and cortical activation left DLPFC that were significantly stronger than in an EMG-based control training group Hudak et al 2017 with effect sizes of dcorr 0981 and 161 respectively formula according to Klauer 2001 for pre-post control design studies Taken together and relying on the more conservative estimation of NF effects on the symptom level itself see above a sample size of n20 per group and treatment arm thus seems to be adequate for the different aims and questions of the proposed study
Risks and side effects
FNIRS No medical risks are associated with a fNIRS recordings when laser diodes are used which is the case in the present study no significant tissue heating occurs In order to avoid any accidental problems all possible precautions will be taken Guidelines and protocols on how to handle the measurement applications eg comfortable adjustment of the NIRS cap will be followed strictly as suggested by experienced laboratories Moreover the experimenters will work under close supervision of Dr Ann-Christine Ehlis
FNIRS-based NF Risks associated with fNIRS-based NF treatment are few rare and quickly remediable For individuals who are highly sensitive or susceptible fNIRS-based NF may precipitate a migraine headache muscle tension induced hot flash or mild anxiety performance induced Potential problems can be minimized and averted by obtaining an adequate medical history prior to treatment Side effects are typically mild transient and quickly remediable allowing participants to continue with treatment
Data Privacy
All experimenters are bound to professional discretion Medical doctoral students master students potentially involved in the project will get detailed explanations of all procedures and will sign a contract for applying these guidelines The confidential treatment of the data according to the data privacy act is guaranteed As data is encoded on acquisition it is not possible to assign published results to individuals Recordings enabling a re-identification are locked and only accessible to staff members for further details see below The following rules will be applied for handling the data
Data acquisition and storage
Data will be stored by using codes These pseudonyms will be created for each participant german Pseudonymisierung The codes are composed out of the name of the used paradigm and the running number of the participant
There will be only three forms with the participants name on them First participants will write their name date of birth and signature on the consent form Second the experimenter will note down the participants name date of birth and study code on the protocol form This protocol will be the only way to link a participants study code with herhis identity Third participants will sign a form for having received participation fee All three documents will be stored apart from the other study documents in a lockable cupboard The keys for this cupboard and for the room will be accessible solely with a licence signed by Dr A-C Ehlis head of the research group Psychophysiology and Optical Imaging at the Department of Psychiatry and Psychotherapy in Tuebingen
The psychometric questionnaires will be stored in a cupboard in a lockable room Only participants study code is noted down on these questionnaires The keys for the room will also be accessible solely with a licence signed by Dr A-C Ehlis These documents will be destroyed after ten years Furthermore the questionnaire data and participants study codes will be entered into a data matrix of the programs Excel or SPSS for further analyses The imaging data are also labelled with participants study codes
The online questionnaire will be constructed and distributed using SoSciSurvey software SoSciSurvey saves all data on a German server located in Munich SoSciSurvey does not share any data with third parties does not save IP addresses and deletes all data if the project manager has not logged into the system for three months All data are encrypted during data transfer Thus SoSciSurvey offers a very high security standard Following the online assessment period the data will be downloaded and stored on a password-protected hard disk of the University Hospital Tübingen Psychophysiology Optical Imaging group All data will then be deleted from the SoSciSurvey server
Data analysis
The coded data will be analyzed and results will be published in specific scientific journals There will be no possibility to deduce information about single participants from these results
FNIRS data will be analyzed with the software package implemented in the ETG-4000 Topo software by Hitachi Medical Co Japan as well as MATLAB The MathWorks Inc a commercial software applied to the offline analysis of the change in haemoglobin concentration Additionally statistical analyses will be conducted with the software packages Excel Microsoft inc and SPSS For statistical analysis mainly ANOVAs for repeated measures and correlation analyses will be applied Post-hoc comparisons will be conducted using t-tests for matched or independent samples as well as correlation analyses
The investigators will assess the effects - and specificity - of two fNIRS-based NF protocols one targeting the DLPFC and one targeting the IFG Both groups will also be compared to a sham training group with regulation of the fNIRS signal outside of the frontal lobes Prepost testing will be conducted in all three groups ie measures of brain activity cognition and impulsive behavior will be obtained before the start of the NF training phase as well as following the last training session Thereby a GoNogo task and an n-back task will be applied to evaluate training-related changes in brain activity and neuropsychological performance The study population will be highly impulsive healthy individuals who were previously found to show a reduced DLPFC and IFG activity similar to patients with ADHD and the investigators expect their DLPFC and IFG function to increase after fNIRS-NF training Our hypothesis is that both active NF groups DLPFC and IFG will improve more than the placebo sham training group on all relevant measures Thereby specific advantages are expected in the DLPFC group for working memory data n-back task and in the IFG group for measures of inhibitory control GoNogo task Further the investigators will test the effect of fNIRS-NF on the stress response using the TSST as a standardized stress test It is hypothesized that fNIRS-NF training is also effective in reducing stress by strengthening stress-related regulation that has also been related to the frontal lobe
It is hypothesized that both trainings will be successful in reducing impulsive behavior however in a prepost testing specific effects of fNIRS-based NF of the DLPFC on working memory function and of fNIRS-based NF of the IFG on inhibitory control is expected Correlations between both functions and impulsive symptoms will give an indication which training ROI may be more promising for the treatment of specific subgroups of ADHD Correlations between regulation of different training ROIs will indicate the specificity of feedback regulation of circumscribed cortical areas
Functional near-infrared spectroscopy fNIRS
An fNIRS system ETG-4000 Hitachi Medical Corporation Japan will be used to measure hemodynamic responses within the prefrontal cortex PFC
All experiments will be conducted at the Department of Psychiatry and Psychotherapy University of Tübingen Calwerstraße 14Osianderstraße 24 72076 Tübingen All medical-technical devices are CE certified and approved for application in patients and will only be used according to their approved purpose by persons who have the knowledge and experience to operate apply and maintain the devices
Neurofeedback
One NF session comprises 2 feedback blocks each lasting 12 min and one transfer block lasting 8 min A feedback block consists of 12 regulation trials One regulation trial consists of 20 s resting time and 30 s regulation time The task is to increase or decrease the hemodynamic activity in the DLPFC or IFG or for the sham control group 4 channels of the temporal cortex which is putatively not involved in impulsivityADHD symptomatology furthermore in an unpublished pilot study these 4 channels were found to be inactive during a Stroop task involving cognitive control functions with 50 activation trials and 50 deactivation trials which were presented in random order As a feedback of hemodynamic brain activation a ball is shown to the participant on a screen moving from left to right and depicting concentration changes in oxygenated hemoglobin by moving below or above a line in the middle of the screen An arrow in the middle of the screen indicates if activation pointing upwards or deactivation pointing downwards is expected on a given trial In activation trials the concentration of oxygenated hemoglobin should increase in comparison to the baseline in deactivation trials it should decrease At the end of a successful trial the ball moved in the expected direction for at least 7 s of the last 15 s regulation time a rewarding feedback Gut gemacht weiter so which is German for Well done continue like this is shown on the screen A transfer block consists of 8 regulation trials in which the moving ball is not shown but the reward at the end of the trial still indicates whether the participant was successful The transfer blocks are included in order to facilitate transfer of the learned regulation strategies into everyday life
Study population
Participants will be recruited from the local student population via advertisementsemail and from existing databases An online system will be used to have potential participants fill out the ASRS in order to classify them as highly- or low-impulsive During this online screening procedure they confirm with a button press that they read the study information and the informed consent and that they agree with the usage of their data They continue by a further button press and will be informed about their rights Appropriate potential participants highly-impulsive healthy subjects with ASRS scores 15 but 23 are contacted again for a study appointment The complete study information informed consent and data safety form will be sent to the potential participant at that time When they arrive for the actual laboratory appointment they will again receive explanations on all procedures and possible risks verbally and in written form They are included in the study when they give their written informed consent
Sample Size Estimation
The proposed project is planned as a randomized controlled trial and comprises a total of 60 participants divided into an IFG- a DLPFC and a placebo training group receiving either IFG-based DLPFC-based or a sham temporal cortex NF control training Based on the effect sizes of NF interventions typically observed in patients with ADHD around d08 for attention-related symptom improvements as compared to different control groups including waiting list EMG biofeedback and cognitive training see eg Arns de Ridder Strehl Breteler Coenen 2009 subgroup sample sizes of n20 would be the result of a formal power calculation with a pre-defined α of 005 and an intended power of at least 80 Closely related to the currently planned training protocol recent own data confirm effect sizes of at least 08 for pre-post comparisons within a control group design In detail following eight training sessions with a frontal-lobe focused fNIRS-based NF training highly-impulsive subjects showed positive changes in both target cognitive measures standard deviation of RTs in a stop signal task and cortical activation left DLPFC that were significantly stronger than in an EMG-based control training group Hudak et al 2017 with effect sizes of dcorr 0981 and 161 respectively formula according to Klauer 2001 for pre-post control design studies Taken together and relying on the more conservative estimation of NF effects on the symptom level itself see above a sample size of n20 per group and treatment arm thus seems to be adequate for the different aims and questions of the proposed study
Risks and side effects
FNIRS No medical risks are associated with a fNIRS recordings when laser diodes are used which is the case in the present study no significant tissue heating occurs In order to avoid any accidental problems all possible precautions will be taken Guidelines and protocols on how to handle the measurement applications eg comfortable adjustment of the NIRS cap will be followed strictly as suggested by experienced laboratories Moreover the experimenters will work under close supervision of Dr Ann-Christine Ehlis
FNIRS-based NF Risks associated with fNIRS-based NF treatment are few rare and quickly remediable For individuals who are highly sensitive or susceptible fNIRS-based NF may precipitate a migraine headache muscle tension induced hot flash or mild anxiety performance induced Potential problems can be minimized and averted by obtaining an adequate medical history prior to treatment Side effects are typically mild transient and quickly remediable allowing participants to continue with treatment
Data Privacy
All experimenters are bound to professional discretion Medical doctoral students master students potentially involved in the project will get detailed explanations of all procedures and will sign a contract for applying these guidelines The confidential treatment of the data according to the data privacy act is guaranteed As data is encoded on acquisition it is not possible to assign published results to individuals Recordings enabling a re-identification are locked and only accessible to staff members for further details see below The following rules will be applied for handling the data
Data acquisition and storage
Data will be stored by using codes These pseudonyms will be created for each participant german Pseudonymisierung The codes are composed out of the name of the used paradigm and the running number of the participant
There will be only three forms with the participants name on them First participants will write their name date of birth and signature on the consent form Second the experimenter will note down the participants name date of birth and study code on the protocol form This protocol will be the only way to link a participants study code with herhis identity Third participants will sign a form for having received participation fee All three documents will be stored apart from the other study documents in a lockable cupboard The keys for this cupboard and for the room will be accessible solely with a licence signed by Dr A-C Ehlis head of the research group Psychophysiology and Optical Imaging at the Department of Psychiatry and Psychotherapy in Tuebingen
The psychometric questionnaires will be stored in a cupboard in a lockable room Only participants study code is noted down on these questionnaires The keys for the room will also be accessible solely with a licence signed by Dr A-C Ehlis These documents will be destroyed after ten years Furthermore the questionnaire data and participants study codes will be entered into a data matrix of the programs Excel or SPSS for further analyses The imaging data are also labelled with participants study codes
The online questionnaire will be constructed and distributed using SoSciSurvey software SoSciSurvey saves all data on a German server located in Munich SoSciSurvey does not share any data with third parties does not save IP addresses and deletes all data if the project manager has not logged into the system for three months All data are encrypted during data transfer Thus SoSciSurvey offers a very high security standard Following the online assessment period the data will be downloaded and stored on a password-protected hard disk of the University Hospital Tübingen Psychophysiology Optical Imaging group All data will then be deleted from the SoSciSurvey server
Data analysis
The coded data will be analyzed and results will be published in specific scientific journals There will be no possibility to deduce information about single participants from these results
FNIRS data will be analyzed with the software package implemented in the ETG-4000 Topo software by Hitachi Medical Co Japan as well as MATLAB The MathWorks Inc a commercial software applied to the offline analysis of the change in haemoglobin concentration Additionally statistical analyses will be conducted with the software packages Excel Microsoft inc and SPSS For statistical analysis mainly ANOVAs for repeated measures and correlation analyses will be applied Post-hoc comparisons will be conducted using t-tests for matched or independent samples as well as correlation analyses
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None