This research study investigates the feasibility and efficacy of a personalized, closed-loop electroencephalogram-transcranial electrical stimulation (EEG-tES) intervention for individuals with Primary Progressive Aphasia (PPA), addressing the inconsistent results of generic brain stimulation protocols. By integrating artificial intelligence (AI)-derived insights with real-time data, the study aims to customize transcranial electrical stimulation (tES) parameters, including electrode placement, intensity, and frequency to target the specific brain regions responsible for abnormal signaling in each participant. Over the intervention period paired with computerized cognitive training, the project will evaluate improvements in learning, memory, and functional connectivity, while simultaneously identifying clinical and physiological predictors to determine the viability of transitioning this low-cost, non-invasive technology into a remotely supervised, home-based therapy setting. The study duration will be a total of 6-8 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
This three-week, closed-loop program integrates personalized tES with computerized cognitive training to drive neuroplasticity. Following baseline electroencephalogram (EEG) mapping, participants undergo daily 30-minute sessions consisting of four "loops." Each loop begins with an AI-analyzed EEG to calibrate stimulation parameters, followed by 5-minute stimulation periods.
In between tES treatment loops, the participants will be asked to complete cognitive exercises. By pairing real-time brain modulation with targeted executive function exercises, the intervention aims to improve language skills and clinical outcomes through precise, data-driven cortical targeting.
Johns Hopkins Hospital
Baltimore, Maryland, United States
Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically related - trained word-lists
Each trained word-list (practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in auditory delayed recall accuracy of semantically related - trained word-lists
Each trained word-list (practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - trained word-lists
Each trained word-list (practiced during the intervention period) will consist of 12 semantically unrelated words as in Rey Auditory-Verbal Learning Test (RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in auditory delayed recall accuracy of semantically unrelated - trained word-lists
Each trained word-list (practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in auditory recall accuracy based the sum of words recalled in Trials 1-5 of semantically related - untrained word-lists
Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in auditory delayed recall accuracy of semantically related - untrained word-lists
Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - untrained word-lists
Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in auditory delayed recall accuracy of semantically unrelated - untrained word-lists
Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in Rey Auditory-Verbal Learning Test (RAVLT) score
RAVLT is a well-established verbal memory test. RAVLT includes a 5-trial presentation of a 15-word list (List A), a single presentation of an interference list (List B)(Trial 6), two post-interference recall trials (one immediate - Trial 7, one delayed - Trial 8) and recognition of the target words in the orthographic modality with distractors (Trial 9). Scoring includes the percent score of Trial 1, Trial 5, Trial 8 and Trial 9 as well as the sum of Trial 1 through 5, and the difference between Trial 5 and Trial 1 computed as the percent difference between the scores before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in Mini Mental State Examination (MMSE)
MMSE is a well-established cognitive assessment test. It examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. The total raw score is out of 30 points. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in Mnemonic Similarity Task (MST) score
MST is a well-established test in order to assess high interference memory and general recognition memory via pattern separation. It involves differentiating between previously learned images and novel images. For the MST tasks, the Pattern Separation (PS) score will be calculated using two measures: a) the rate of similar items correctly identified minus the rate of similar items misidentified as new (S\|S-S\|N); b) the rate of similar items correctly identified minus the rate of similar items misidentified as old (S\|S-O\|S). The number of correct responses for each category of items (i.e., old, similar, new) and the type of errors (i.e., identifications of new items as similar; identification of similar items as old) will also be tracked. Change in outcome in percent difference will be computed between the scores before intervention and each time point after. Increase in scores is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
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Change in word repetition score
Temple Assessment of Language and Short-Term Memory in Aphasia (TALSA) tasks include word repetition, with sets of 1-6 words. Scoring will be based on percent of words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in non-word repetition score
TALSA tasks include non-word repetition, with sets of 1-6 non-words. Scoring will be based on percent of non-words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in sentence repetition score
Sentence repetition tasks come from the TALSA, with scoring based on percent of words in sentences correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in oral naming Boston Naming Test score
Accuracy in oral picture naming (30-item Boston Naming Test). The Boston Naming Test is a widely used picture naming test that detects lexical retrieval deficits in the oral modality. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in oral naming Philadelphia Naming Test score
Accuracy in oral picture naming (Philadelphia Naming Test). The Philadelphia Naming Test is an extensive picture naming test that comprises 275 items from a wide range of frequencies and other psycholinguistic characteristics. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in written naming as assessed by Boston Naming Test
Accuracy in written picture naming (30-item Boston Naming Test). The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in written naming as assessed by Philadelphia Naming Test
Accuracy in written picture naming (Philadelphia Naming Test). The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in oral naming of action as assessed by Hopkins Assessment of Naming Actions (HANA)
Accuracy in oral naming of actions. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in syntactic comprehension as assessed by Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery
The 40-item Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery of various sub-tests will be used to assess argument structure comprehension and production. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between baseline and each time point. Increase in score is considered benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in verbal fluency task score
Verbal fluency tasks (semantic and letter fluency) involve generating as many words as possible in one minute. Scoring will be based on number of words generated per minute. The investigators will compute the raw score of items correct and compute change in outcome between baseline and each time point. Increase in score is considered benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in spelling as assessed by the Johns Hopkins Dysgraphia battery
Accuracy in spelling will be analyzed using the Johns Hopkins Dysgraphia battery. The investigators will compute the raw score of items correct using a spelling scoring system accounting for additions, substitutions, and deletions, and transform to percent correct (range: 0-100%), computing change in outcome in percent difference before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in digit span forward score
Digit span forward involves the recall of a series of single digits (sets of 1-8 digits) in the same order the digits were presented. Scoring will be based on the number of consecutive digits correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in digit span backward score
Digit span backward involves the recall of a series of single digits (sets of 1-8 digits) in the reverse order than the digits were presented. Scoring will be based on the number of consecutive digits correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in spatial span forward score
Spatial span forward involves the recall of a series of positions on a board (sets of 1-9) in the same order the digits were presented. Scoring will be based on the number of consecutive positions correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in spatial span backward score
Spatial span backward involves the recall of a series of positions (sets of 1-8) in the reverse order than the digits were presented. Scoring will be based on the number of consecutive positions correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in semantic content of connected speech (Cookie Theft)
Using the Cookie Theft image from the Boston Diagnostic Aphasia Examination (BDAE) investigators will obtain representative language samples as participants describe the image. The investigators will combine the raw score of all items (semantics) correct from the image and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in semantic content of connected speech (Circus)
Using the Circus image from the Apraxia Battery for Adults (ABA) investigators will obtain representative language samples as participants describe the images. The investigators will combine the raw score of all items (semantics) correct from the image and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention
Change in attention and manipulation of information scores
Using the Trail Making Test (TMT) parts A and B, which include the sequential connection of letters/numbers in order to complete a trail, the investigators will obtain the time required by the participants to finish the tasks. Decrease in the time is considered a benefit.
Time frame: Before intervention, immediately after intervention and 1 month post intervention