Impact of Theta Burst Stimulation Over the Left DLPFC on Language Switching

• Sponsor: Jean-Marie Annoni (Other)
• Overall Status: Completed
• CT.gov ID: NCT03148470
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Actual Duration (Months): 33.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate whether theta burst stimulation (TBS) over the left dorsolateral prefrontal cortex (DLPFC) influences language switching and cognitive flexibility. The experimental paradigm will assess the impact of inhibitory and excitatory prefrontal stimulation by TBS versus sham-TBS over the DLPFC in healthy bilinguals.

Condition or Disease	Intervention/Treatment	Phase
Languages	Device: Sham iTBS; Device: Sham cTBS; Device: intermittent theta burst stimulation (iTBS); Device: continuous theta burst stimulation (cTBS)	N/A

Detailed Description

Background:

Clinical observations and neuroimaging studies seem to confirm the role of executive functions and frontal structures in language processing in bilingual subjects.

Repetitive transcranial magnetic stimulation, such as for example theta burst stimulation (TBS), is increasingly being used as a valuable tool for neuroscientists investigating the underlying mechanisms of cognitive functions. Case studies have shown a change in language switching after bilingual patients received repetitive magnetic stimulation to the left DLPFC. However, there is no study investigating the effect of TBS applied to the DLPFC on language switching in healthy participants.

Procedure:

A planned total of 40 unbalanced bilingual participants will be included. Half of the participants will receive inhibitory theta burst stimulation (continuous TBS), the other half excitatory theta burst stimulation (intermittent TBS). After TBS, different language and nonverbal tasks will be performed while an EEG is measured. Before being stimulated, each subject will conduct the same tasks with a sham-TBS as a baseline measure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Impact of Theta Burst Stimulation Over the Left Dorsolateral Prefrontal Cortex on Language Switching and Cognitive Flexibility
• Actual Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Jul 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: intermittent theta burst stimulation intermittent theta burst stimulation (iTBS) + Sham iTBS	Device: Sham iTBS; Placebo stimulation for the iTBS group; Device: intermittent theta burst stimulation (iTBS); Excitatory theta burst stimulation
Experimental: continuous theta burst stimulation continuous theta burst stimulation (cTBS) + Sham cTBS	Device: Sham cTBS; Placebo stimulation for the cTBS group; Device: continuous theta burst stimulation (cTBS); inhibitory theta burst stimulation

Outcome Measures

Primary Outcome Measures

1. RTs for Picture Naming With the Factors Language (L1, L2) and Block (Switching, Non-Switching) [Within 30 minutes after intervention]

   Picture naming with the factors Language (L1, L2) and Block (Switching, Non-Switching): Speech onset times (msec) L1 refers to the mother tongue. L2 refers to the late acquired (> age 7) second language. Switching Block refers to a language switching block with picture naming alternated between the mother tongue and the second language. Non-Switching Block refers to a block of picture naming either only in the mother or only in the second language.

Secondary Outcome Measures

1. Nonverbal Switching [Within 30 minutes after intervention]

   Nonverbal Switching: response times

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• L1 (Swiss)German, knowledge of English as a foreign language

• 18-45 years of age

• right-handedness

Exclusion Criteria:

• epilepsy / family history of epilepsy

• brain surgery, traumatic brain injuries

• cardiac pacemaker, metallic objects in the head

• history of neurological diseases or severe psychiatric disorders

• drug use (alcohol, psychoactive medication)

• strong headache

• pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Laboratory for Cognitive and Neurological Sciences	Fribourg		Switzerland	1700

Sponsors and Collaborators

• Jean-Marie Annoni

Investigators

• Principal Investigator: Jean-Marie Annoni, Prof. Dr., University of Fribourg

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 6, 2016

More Information

Publications

• Holtzheimer P, Fawaz W, Wilson C, Avery D. Repetitive transcranial magnetic stimulation may induce language switching in bilingual patients. Brain Lang. 2005 Sep;94(3):274-7.
• Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipović SR, Hummel FC, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5. Review.
• Nardone R, De Blasi P, Bergmann J, Caleri F, Tezzon F, Ladurner G, Golaszewski S, Trinka E. Theta burst stimulation of dorsolateral prefrontal cortex modulates pathological language switching: A case report. Neurosci Lett. 2011 Jan 10;487(3):378-82. doi: 10.1016/j.neulet.2010.10.060. Epub 2010 Oct 29.

• Responsible Party: Jean-Marie Annoni, Prof. Dr. med., University of Fribourg
• ClinicalTrials.gov Identifier: NCT03148470
• Other Study ID Numbers: SNF325130_156937_4
• First Posted: May 11, 2017
• Last Update Posted: Apr 22, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jean-Marie Annoni, Prof. Dr. med., University of Fribourg: theta burst stimulation; Language switching; dorsolateral prefrontal cortex

Study Results

Participant Flow

Arm/Group Title	iTBS Group	cTBS Group
Arm/Group Description	intermittent theta burst stimulation (iTBS) + Sham iTBS Sham iTBS: Placebo stimulation (3 Min) Tasks (30 Min) Pause (10Min) iTBS: Excitatory stimulation (3Min) Tasks (30Min)	continuous theta burst stimulation (cTBS) + Sham cTBS Sham cTBS: Placebo stimulation (40Sec) Tasks (30min) Pause (10Min) cTBS: inhibitory stimulation (40 Sec) Tasks (30Min)
Period Title: Overall Study
STARTED	21	20
COMPLETED	20	20
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Intermittent Theta Burst Stimulation	Continuous Theta Burst Stimulation	Total
Arm/Group Description	intermittent theta burst stimulation (iTBS) + Sham iTBS Sham iTBS: Placebo stimulation intermittent theta burst stimulation (iTBS): Excitatory rTMS	continuous theta burst stimulation (cTBS) + Sham cTBS Sham cTBS: Placebo stimulation continuous theta burst stimulation (cTBS): inhibitory rTMS	Total of all reporting groups
Overall Participants	21	20	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.1 (2.7)	22.8 (5.36)	22.4 (4.2)
Sex: Female, Male (Count of Participants)
Female	15 71.4%	16 80%	31 75.6%
Male	6 28.6%	4 20%	10 24.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Switzerland	21 100%	20 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	RTs for Picture Naming With the Factors Language (L1, L2) and Block (Switching, Non-Switching)
Description	Picture naming with the factors Language (L1, L2) and Block (Switching, Non-Switching): Speech onset times (msec) L1 refers to the mother tongue. L2 refers to the late acquired (> age 7) second language. Switching Block refers to a language switching block with picture naming alternated between the mother tongue and the second language. Non-Switching Block refers to a block of picture naming either only in the mother or only in the second language.
Time Frame	Within 30 minutes after intervention

Outcome Measure Data

Analysis Population Description

As a primary outcome we compared RTs following iTBS vs cTBS. Sham-TBS is only used to have a baseline control between the two groups

Arm/Group Title	RTs for PN After Intermittent Theta Burst Stimulation	RTs for PN After Continuous Theta Burst Stimulation	RTs for Picture Naming in L1	RTs for Picture Naming in L2	RTs for Picture Naming in the Non-switching Blocks	RTs for Picture Naming in the Switching Blocks
Arm/Group Description	intermittent theta burst stimulation (iTBS) - across switching and non-switching blocks and across L1 and L2.	continuous theta burst stimulation (cTBS) - across switching and non-switching blocks and across L1 and L2.	Voice onset times for Picture Naming in L1 - across switching and non-switching blocks and across iTBS and cTBS.	Voice onset times for Picture Naming in L2 - across switching and non-switching blocks and across iTBS and cTBS.	Voice onset times for Picture Naming in the non-switching blocks - across L1 and L2 and across iTBS and cTBS.	Voice onset times for Picture Naming in the switching blocks - across L1 and L2 and across iTBS and cTBS.
Measure Participants	20	20	40	40	40	40
Mean (Standard Deviation) [Milliseconds]	1103.32 (126)	1107.26 (131)	1098.82 (405)	1158.91 (432)	1081.14 (414)	1175.24 (420)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RTs for PN After Intermittent Theta Burst Stimulation, RTs for PN After Continuous Theta Burst Stimulation, RTs for Picture Naming in L1, RTs for Picture Naming in L2, RTs for Picture Naming in the Non-switching Blocks, RTs for Picture Naming in the Switching Blocks
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.932
	Comments	This p-value refers to the effect of stimulation (cTBS vs iTBS).
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Nonverbal Switching
Description	Nonverbal Switching: response times
Time Frame	Within 30 minutes after intervention

Outcome Measure Data

Analysis Population Description

Data are compared between iTBS and cTBS Sham-TBS is only used to have a baseline control between the two groups

Arm/Group Title	Intermittent Theta Burst Stimulation	Continuous Theta Burst Stimulation
Arm/Group Description	intermittent theta burst stimulation (iTBS)	continuous theta burst stimulation (cTBS)
Measure Participants	20	20
Mean (Standard Deviation) [Milliseconds]	772.07 (159.28)	739.32 (137.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RTs for PN After Intermittent Theta Burst Stimulation, RTs for PN After Continuous Theta Burst Stimulation
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.642
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	3 hours
Arm/Group Title	cTBS		iTBS		Sham iTBS		Sham cTBS
Arm/Group Description	continuous theta burst stimulation (cTBS)		intermittent theta burst stimulation (iTBS)		Placebo (baseline) stimulation for iTBS group		Placebo (baseline) stimulation for cTBS group
All Cause Mortality
	cTBS		iTBS		Sham iTBS		Sham cTBS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/21 (0%)		0/20 (0%)
Serious Adverse Events
	cTBS		iTBS		Sham iTBS		Sham cTBS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/21 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	cTBS		iTBS		Sham iTBS		Sham cTBS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		1/21 (4.8%)		0/20 (0%)
Cardiac disorders
Nausea	0/20 (0%)		0/20 (0%)		1/21 (4.8%)	1	0/20 (0%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.