Effects of tDCS on Verbal Short-term Memory in PPA
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Cognitive Studies, Cognitive Studies, Neurology, Neurology, Neurology |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 45 - 80 |
| Updated: | 4/5/2019 |
| Start Date: | April 2019 |
| End Date: | June 2025 |
| Contact: | Kyrana Tsapkini, PhD |
| Email: | tsapkini@jhmi.edu |
| Phone: | 410-736-2940 |
Rehabilitating Verbal Short-term Memory (STM) in Primary Progressive Aphasia (PPA) Using Transcranial Direct Current Stimulation (tDCS)
Short-term memory (STM)—the ability for a person to temporarily hold and access a small
amount of information—strongly correlates with people's ability to learn new information at
both the word and the sentence level. People with primary progressive aphasia are shown to
have reduced verbal STM capacity and all variants are affected. Transcranial Direct Current
Stimulation (tDCS) is a safe, non-invasive, non-painful electrical stimulation of the brain
that has resulted in improved language abilities in post-stroke aphasia as well as in primary
progressive aphasia, when administered along with behavioral (language) therapy. However, no
studies have assessed the efficacy of short-term memory treatments paired with tDCS in PPA or
other neurodegenerative disorders. In this research project, the investigators aim to fill
this gap by investigating the behavioral and neuromodulatory effects of tDCS during STM
therapy over time in people with primary progressive aphasia and related neurodegenerative
conditions, such as mild cognitive impairment (MCI). The investigators will follow a novel
STM intervention developed for post-stroke aphasia that has been modified for PPA in which
participants will be trained in a series of word sequences. The investigators also aim to
investigate whether tDCS alters brain volume, structural and functional connectivity,
perfusion, or neuropeptide concentrations, using magnetic resonance imaging (MRI)
spectroscopy (MRS). Study results may help optimize future intervention in individuals with
neurodegenerative disorders by providing treatment alternatives. A better understanding of
the therapeutic and neuromodulatory effects of tDCS in PPA will offer insight into means of
impeding neurodegeneration that may improve patients' quality of life and augment therapies.
amount of information—strongly correlates with people's ability to learn new information at
both the word and the sentence level. People with primary progressive aphasia are shown to
have reduced verbal STM capacity and all variants are affected. Transcranial Direct Current
Stimulation (tDCS) is a safe, non-invasive, non-painful electrical stimulation of the brain
that has resulted in improved language abilities in post-stroke aphasia as well as in primary
progressive aphasia, when administered along with behavioral (language) therapy. However, no
studies have assessed the efficacy of short-term memory treatments paired with tDCS in PPA or
other neurodegenerative disorders. In this research project, the investigators aim to fill
this gap by investigating the behavioral and neuromodulatory effects of tDCS during STM
therapy over time in people with primary progressive aphasia and related neurodegenerative
conditions, such as mild cognitive impairment (MCI). The investigators will follow a novel
STM intervention developed for post-stroke aphasia that has been modified for PPA in which
participants will be trained in a series of word sequences. The investigators also aim to
investigate whether tDCS alters brain volume, structural and functional connectivity,
perfusion, or neuropeptide concentrations, using magnetic resonance imaging (MRI)
spectroscopy (MRS). Study results may help optimize future intervention in individuals with
neurodegenerative disorders by providing treatment alternatives. A better understanding of
the therapeutic and neuromodulatory effects of tDCS in PPA will offer insight into means of
impeding neurodegeneration that may improve patients' quality of life and augment therapies.
A. Evaluation Tasks
Language Tasks:
Participants will be administered baseline language and cognitive tasks, including 1 or more
of the following, depending on participant's residual language and cognitive skills:
(a) writing to dictation, (b) oral spelling, (c) oral and written naming of pictures, (d)
word-picture matching, (f) written and oral picture description, (g) digit span, (h) spatial
span, (i) verbal learning, (j) grammatical sentence production, (k) oral word repetition, (l)
sentence comprehension, (m) verbal fluency (category and letter), (n) verbal short-term
memory battery.
Quality of Life questionnaires:
Participants will be administered standardized and non-standardized quality-of-life
questionnaires before, after, and at follow-up intervals of each experimental period. The
purpose of these questionnaires is to assess whether the proposed interventions have affected
participants' well-being and the general quality of participant's life.
B. Assessment of Verbal Short-term Memory Therapy Tasks:
Follow-up assessment will probe all sets of trained words, or other stimuli (e.g. sentences)
to identify whether or not the patient has retained knowledge of the trained items.
Differences in baseline measures in pre- and post-therapy accuracy for each patient will be
evaluated using the following: percentages of total number of points correct, arithmetic
differences between percentage scores, and permutation tests (Pearson's chi-square test;
Fisher's exact test).
C. tDCS Methods:
Participants will take part in 15 consecutive training sessions (5 per week), separated by 2
months. Anodal tDCS has typically been shown to up-regulate neuronal excitability and produce
enhancement of behavioral performance. A Soterix-CT device will be delivering current at an
intensity of 1-2 milliamperes (mA) (estimated current density 0.04 mA/cm2; estimated total
charge 0.048 Coulombs/cm2) for a maximum of 20 minutes over the left IFG in the tDCS
condition and for a maximum of 30 seconds in the Sham condition. For both interventions (tDCS
and Sham) the electrical current will be increased in a ramp-like fashion at the onset of the
stimulation eliciting a transient tingling sensation on the scalp that usually disappears
over seconds.
E. Imaging Methods:
Imaging will be performed at the beginning of enrollment, before and after each 12-to-15-day
tDCS treatment, and at follow-up intervals for up to 8 time points per individual on a
3-Tesla (3T) Philips system, and will include resting-state fMRI (rsfMRI),
magnetization-prepared rapid acquisition with gradient echo (MPRAGE), and diffusion tensor
imaging (DTI). Each scanning session will last approximately 1 hour.
F. Statistical Analyses:
In the within-subject crossover protocol, each participant will be administered three
experimental conditions: Control (natural progression), inferior frontal gyrus (IFG)
tDCS+short-term memory therapy (henceforth abbr. tDCS treatment) and sham tDCS+short-term
memory therapy (henceforth abbr. sham treatment). To achieve an accurate estimate of
degeneration and rate of decline in each participant at participant's particular stage of the
disease progression, each participant will first be enrolled in the control condition
(natural progression), such that for the first 12 weeks participants will not receive any
therapy. Then the participant will receive either the tDCS treatment followed by sham, or
vice versa. All analyses, behavioral and imaging, will be under the oversight of the study
statisticians.
G. Study duration and number of study visits required of research participants.
Before any intervention, participants will be enrolled in a control condition for 12 weeks
during which no therapy will be provided to enable the investigators to assess participant's
personal decline rate. After this period participants will be randomly assigned to either
sham or tDCS experimental conditions. After 3 weeks of tDCS application (5 sessions in a
week, 15 sessions per stimulation site) there will be an interval of approximately 2 months
and then the investigators will implement the other two tDCS conditions in a within-subject
cross-over design. Participants will be followed-up at 2-week and 2-month follow-up
intervals.
H. Blinding, including justification for blinding or not blinding the trial, if applicable.
Participants will be blinded to the application of anodal or sham tDCS. To achieve blinding,
all participants will be fitted with the tDCS electrodes placed over the left inferior
frontal gyrus. The Soterix-CT device will be used for double-blinding purposes.
I. Justification of why participants will not receive routine care or will have current
therapy stopped
Participation in this study will not disrupt any current care or therapy.
J. Justification for inclusion of a placebo or non-treatment group
All participants will undergo active and sham conditions, thus serving as participant's own
control.
K. Definition of treatment failure or participant removal criteria
Participants will be removed from the study if participants are unable to comply with task
instructions or tolerate the tDCS procedure.
L. Description of what happens to participants receiving therapy when study ends or if a
participant's participation in the study ends prematurely
When the study ends participants will continue to receive management with participant's
neurologist as usual. If a patient's participation in the study ends prematurely s/he will
still receive care as before. In sum, termination of the study or termination of
participation in it will not affect regular therapy he or she may be receiving.
M. Qualification of investigators:
The PI and co-investigators have extensive research and clinical experience with all study
tasks: behavioral language therapy (including short-term memory, repetition, spelling and
naming therapy). The investigators have already published several tDCS studies on the
behavioral and imaging results for the improvement of spelling abilities.
Language Tasks:
Participants will be administered baseline language and cognitive tasks, including 1 or more
of the following, depending on participant's residual language and cognitive skills:
(a) writing to dictation, (b) oral spelling, (c) oral and written naming of pictures, (d)
word-picture matching, (f) written and oral picture description, (g) digit span, (h) spatial
span, (i) verbal learning, (j) grammatical sentence production, (k) oral word repetition, (l)
sentence comprehension, (m) verbal fluency (category and letter), (n) verbal short-term
memory battery.
Quality of Life questionnaires:
Participants will be administered standardized and non-standardized quality-of-life
questionnaires before, after, and at follow-up intervals of each experimental period. The
purpose of these questionnaires is to assess whether the proposed interventions have affected
participants' well-being and the general quality of participant's life.
B. Assessment of Verbal Short-term Memory Therapy Tasks:
Follow-up assessment will probe all sets of trained words, or other stimuli (e.g. sentences)
to identify whether or not the patient has retained knowledge of the trained items.
Differences in baseline measures in pre- and post-therapy accuracy for each patient will be
evaluated using the following: percentages of total number of points correct, arithmetic
differences between percentage scores, and permutation tests (Pearson's chi-square test;
Fisher's exact test).
C. tDCS Methods:
Participants will take part in 15 consecutive training sessions (5 per week), separated by 2
months. Anodal tDCS has typically been shown to up-regulate neuronal excitability and produce
enhancement of behavioral performance. A Soterix-CT device will be delivering current at an
intensity of 1-2 milliamperes (mA) (estimated current density 0.04 mA/cm2; estimated total
charge 0.048 Coulombs/cm2) for a maximum of 20 minutes over the left IFG in the tDCS
condition and for a maximum of 30 seconds in the Sham condition. For both interventions (tDCS
and Sham) the electrical current will be increased in a ramp-like fashion at the onset of the
stimulation eliciting a transient tingling sensation on the scalp that usually disappears
over seconds.
E. Imaging Methods:
Imaging will be performed at the beginning of enrollment, before and after each 12-to-15-day
tDCS treatment, and at follow-up intervals for up to 8 time points per individual on a
3-Tesla (3T) Philips system, and will include resting-state fMRI (rsfMRI),
magnetization-prepared rapid acquisition with gradient echo (MPRAGE), and diffusion tensor
imaging (DTI). Each scanning session will last approximately 1 hour.
F. Statistical Analyses:
In the within-subject crossover protocol, each participant will be administered three
experimental conditions: Control (natural progression), inferior frontal gyrus (IFG)
tDCS+short-term memory therapy (henceforth abbr. tDCS treatment) and sham tDCS+short-term
memory therapy (henceforth abbr. sham treatment). To achieve an accurate estimate of
degeneration and rate of decline in each participant at participant's particular stage of the
disease progression, each participant will first be enrolled in the control condition
(natural progression), such that for the first 12 weeks participants will not receive any
therapy. Then the participant will receive either the tDCS treatment followed by sham, or
vice versa. All analyses, behavioral and imaging, will be under the oversight of the study
statisticians.
G. Study duration and number of study visits required of research participants.
Before any intervention, participants will be enrolled in a control condition for 12 weeks
during which no therapy will be provided to enable the investigators to assess participant's
personal decline rate. After this period participants will be randomly assigned to either
sham or tDCS experimental conditions. After 3 weeks of tDCS application (5 sessions in a
week, 15 sessions per stimulation site) there will be an interval of approximately 2 months
and then the investigators will implement the other two tDCS conditions in a within-subject
cross-over design. Participants will be followed-up at 2-week and 2-month follow-up
intervals.
H. Blinding, including justification for blinding or not blinding the trial, if applicable.
Participants will be blinded to the application of anodal or sham tDCS. To achieve blinding,
all participants will be fitted with the tDCS electrodes placed over the left inferior
frontal gyrus. The Soterix-CT device will be used for double-blinding purposes.
I. Justification of why participants will not receive routine care or will have current
therapy stopped
Participation in this study will not disrupt any current care or therapy.
J. Justification for inclusion of a placebo or non-treatment group
All participants will undergo active and sham conditions, thus serving as participant's own
control.
K. Definition of treatment failure or participant removal criteria
Participants will be removed from the study if participants are unable to comply with task
instructions or tolerate the tDCS procedure.
L. Description of what happens to participants receiving therapy when study ends or if a
participant's participation in the study ends prematurely
When the study ends participants will continue to receive management with participant's
neurologist as usual. If a patient's participation in the study ends prematurely s/he will
still receive care as before. In sum, termination of the study or termination of
participation in it will not affect regular therapy he or she may be receiving.
M. Qualification of investigators:
The PI and co-investigators have extensive research and clinical experience with all study
tasks: behavioral language therapy (including short-term memory, repetition, spelling and
naming therapy). The investigators have already published several tDCS studies on the
behavioral and imaging results for the improvement of spelling abilities.
Inclusion Criteria:
- Must be clinically diagnosed with semantic variant primary progressive aphasia
(svPPA), nonfluent/agrammatic variant PPA (nfvPPA) or logopenic variant PPA (lvPPA),
unclassifiable PPA, frontotemporal dementia (FTD), mild Alzheimer's disease (AD), or
mild cognitive impairment (MCI).
- Diagnosis will be based on neuropsychological testing, language testing (most commonly
the Western Aphasia Battery), MRI and clinical assessment.
- Must be right-handed.
- Must be native speakers of English.
- Must have at least 12th grade education.
Exclusion Criteria:
- Uncorrected visual or hearing impairment by self report.
- Stroke/other premorbid neurological disorder affecting the brain.
- Any other language-based learning disorder other than PPA.
- Inability to follow directions for baseline tasks.
- Western Aphasia Battery Aphasia Quotient (AQ) <30 (indicating severe language
impairment).
Exclusion Criteria for MRI Participation:
- People with severe claustrophobia.
- People with cardiac pacemakers or ferromagnetic implants.
- Pregnant women.
We found this trial at
1
site
1800 Orleans St.
Baltimore, Maryland 21287
Baltimore, Maryland 21287
410-955-5000
Principal Investigator: Kyrana Tsapkini, PhD
Phone: 410-736-2940
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