About

Brenda Rapp is a Research Professor in the Department of Cognitive Science at Johns Hopkins University. Her primary research interests lie in understanding the cognitive processes and neural substrates that support written and spoken word production and comprehension. Her work includes examining questions such as what is known when individuals know the spellings of words, the independence and interaction of lexical phonological, orthographic, semantic, and syntactic processes, and the manner in which these processes interact at different levels of processing. Most of her research involves detailed examination of language performance in individuals who have suffered neural injury, typically from stroke, affecting language functions. This cognitive neuropsychological approach provides insights into the organization and internal structure of lexical processing mechanisms, with a particular focus on written word production (spelling) and dysgraphia. At the neural level, she investigates the neural substrates supporting written language production and comprehension in the intact system, as well as neuroplastic changes associated with orthographic learning and recovery of language functions following neural injury or neurodegenerative disease. Her work on recovery employs fMRI to understand the complex neural network changes that support re-learning and recovery in the face of damage and disruption.

Research topics

• Neuroscience
• Psychology
• Computer Science
• Anatomy
• Artificial Intelligence
• Linguistics
• Radiology
• Cognitive psychology
• Communication
• Medicine
• Developmental psychology
• Biology

Selected publications

• Protocol for a multisite study on the efficacy of transcranial direct current stimulation as an adjuvant to naming and spelling therapy in the treatment of oral and written naming in individuals with primary progressive aphasia

  Frontiers in Human Neuroscience · 2025-09-02 · 1 citations

  articleOpen access

  Primary progressive aphasia (PPA) is a neurological syndrome characterized by the gradual deterioration of language capabilities. Due to its neurodegenerative nature, PPA is marked by a continuous decline, necessitating ongoing and adaptive therapeutic interventions. Recent studies have demonstrated that behavioral therapies, particularly when combined with neuromodulation techniques such as transcranial direct current stimulation (tDCS), can improve treatment outcomes, including the long-term maintenance and generalization of therapeutic effects. However, there has yet to be a phase II multisite study examining the efficacy of tDCS in individuals with PPA. This paper reports the methods and analyses for the clinical trial NCT05386394. A total of 120 adults with non-fluent and logopenic variant PPA will receive a novel spoken Naming and Spelling (NaSp), individuals with semantic variant PPA will be excluded from this trial. Participants will receive NASP therapy over two periods of 3 weeks (Monday through Friday, for a total of 15 non-consecutive days) combined with anodal (a-tDCS) and sham tDCS (s-tDCS). They will be randomly allocated to receive a-tDCS either during the first or second intervention period. The study will be conducted at four sites across the United States and Canada. Outcome measures will be recorded immediately before and after each intervention period, as well as 3 months after each period. Primary outcome measures will be the change in phonemic accuracy in spoken picture naming and letter accuracy in spelling for trained nouns and verbs. Changes from the a-tDCS and s-tDCS periods will be compared to determine the efficacy of tDCS. Primary outcomes will be analyzed using statistical methods that account for repeated measures within participants (namely generalized estimating equations). A significant adjuvant effect of tDCS will be determined if differences in phonemic accuracy and/or letter accuracy immediately following a-tDCS intervention and/or at the 3-month follow-up are greater (at p < 0.05) than those of the s-tDCS intervention. This trial is the first multisite, fully powered, randomized, double-blind, sham-controlled, crossover study of the effectiveness of tDCS as an adjuvant to behavioral treatment for spoken naming and spelling deficits in individuals with PPA. Specific challenges in designing the protocol are considered.

  PublisherOA PDFDOI

• Longitudinal changes in functional connectivity networks in the first year following stroke

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-13 · 2 citations

  preprintOpen accessSenior author

  Abstract The functional organization of the brain consists of multiple subsystems, or modules, with dense functional communication within modules (i.e., visual, attention) and relatively sparse but vital communications between them. The two hemispheres also have strong functional communications, which presumably supports hemispheric lateralization and specialization. Subsequent to stroke, the functional organization undergoes neuroplastic changes over time. However, empirical longitudinal studies of human subjects are lacking. Here we analyzed three large-scale, whole-brain resting-state functional MRI connectivity measures: modularity , hemispheric symmetry (based on system segregation ), and homotopic connectivity in a group of 17 participants at 1-month, 3-months, and 12-months after a single left-hemisphere stroke. These measures were also compared to a group of 13 age-matched healthy controls. The three measures exhibited different trajectories of change: (1) modularity steadily decreased across the 12-month period and became statistically inferior to control values at 12 months, indicating a less modular organization; (2) hemispheric symmetry values were abnormally low at 1-month and then increased significantly in the first 6 months, leveling off at levels not significantly below control levels by 12 months, suggesting that the two hemispheres diverged initially after the unilateral damage, but improved over time; and (3) homotopic connectivity exhibited a U-shaped function with a significant decrease from 1-6 months and then an increase from 6-12 months, to levels that were not significantly different from controls. The results revealed a complex picture of the dynamic changes the brain undergoes as it responds to abrupt onset damage.

  PublisherOA PDFDOI

• The role of structural and functional parameters in designing pathology-specific tDCS protocols for primary progressive aphasia

  Alzheimer s Research & Therapy · 2025-07-14

  articleOpen access

  BACKGROUND: The two subtypes of primary progressive aphasia (PPA) associated with Frontotemporal Lobar Degeneration (FTLD)-non-fluent (nfvPPA) and semantic (svPPA)-have distinct structural and functional abnormalities. Transcranial direct current stimulation (tDCS) targets the language network to address deficits, yet a single, arbitrary montage is often applied despite pathophysiological differences. Since tDCS current distribution depends on brain structure and function, variant-specific montages are essential. This study presents a pathology-specific approach for tDCS montage selection, identifying the optimal montage for each PPA variant. METHOD: T1-weighted and resting-state fMRI data from 38 healthy, 31 nfvPPA and 32 svPPA subjects were obtained. Grey matter volume and functional entropy were analysed across 116 brain regions. Patients and controls were compared to identify significant differences in atrophy and entropy. Electric-field modelling of three widely used dorsal, ventral, and frontal tDCS montages provided current intensity estimates in the language network. Canonical Correlation Analysis examined the relationship between current intensity, atrophy, and entropy. RESULTS: Structural and functional changes differed between the two PPA variants: nfvPPA showed left frontal atrophy and reduced entropy in the left parietal/cerebellar areas, while svPPA exhibited left temporal atrophy and reduced entropy in the left frontal and right temporal regions. Atrophy distribution primarily influenced tDCS current spread, determining montage suitability. In nfvPPA, the frontal montage showed a strong association between delivered current and grey mettwr volume of atrophied areas, whereas in svPPA, a similar pattern was observed for the ventral montage. CONCLUSION: The study identifies the frontal montage as the most suitable for nfvPPA and the ventral montage for svPPA. This study highlights the importance of pathology-specific tDCS montage selection, emphasizing the need for variant-based modulation of the language network in PPA.

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• Cerebello-Cerebral Pathways Contribute to Written Word Production

  Neurobiology of Language · 2025-01-01

  articleOpen access

  Written language production is a fundamental aspect of daily communication, yet the neural pathways supporting it are far less studied than those for spoken language production. This study evaluated the contributions of speech-production pathways to written word production, specifically focusing on the central processes of word spelling rather than the motor production processes that support handwriting. Seventy-three English-speaking, neurotypical adults completed a spelling-to-dictation task and underwent diffusion MRI scans. The bilateral cerebello-thalamo-cortical pathways (CTC) and frontal aslant tract (FAT) were identified in individual participants using probabilistic tractography and automated segmentation tools. Fractional anisotropy (FA) values were computed along the trajectory of each tract and entered into correlation analyses with the spelling accuracy scores. A significant correlation was found between spelling accuracy scores and FA in the left CTC, which connects the left cerebellar hemisphere with the right cerebral hemisphere. This effect remained significant after controlling for spoken production measures. A similar trend was observed in the right homologous tract. In contrast, no significant correlations were identified between spelling accuracy scores and FA in the bilateral FAT. These findings demonstrate, for the first time, the involvement of cerebello-cerebral connections in spelling processes, aligning with the growing recognition regarding the role of the cerebellum in higher-order language functions. This effect did not generalize to the FAT, which may be relevant for more peripheral aspects of language production.

  PublisherOA PDFDOI

• Written picture descriptions distinguish variants of primary progressive aphasia

  Journal of Alzheimer s Disease · 2025-09-23 · 1 citations

  article

  BackgroundFew studies have examined written discourse in primary progressive aphasia (PPA), a clinical syndrome due to frontotemporal lobar degeneration (FTLD) or Alzheimer's disease (AD).ObjectiveWe aim to: (1) determine differences in written discourse in PPA variants and controls using three approaches for analyzing narratives, and (2) make recommendations regarding the clinical utility of these approaches.MethodsIndividuals with PPA and healthy controls wrote descriptions of the Boston Diagnostic Aphasia Examination Cookie Theft Picture (CTP). We hypothesized that written narratives would be characterized by: (1) fewer total words, lower percentages of CTP content units (CUs) and Core Lexicon Words, and lower communication efficiency in all PPA variants compared to controls; (2) fewer content words in semantic variant PPA (svPPA) than in logopenic variant PPA (lvPPA), nonfluent variant PPA (nfvPPA), and controls; and (3) fewer function words in nfvPPA than in lvPPA and controls.ResultsParticipants with svPPA had significantly lower percentages of total CTP CUs, CTP noun and verb phrase CUs, and Core Lexicon Words than lvPPA. Overall content unit (CU) profile of lvPPA was more similar to controls than to the other two variants. Written narratives of participants with nfvPPA and svPPA had significantly lower percentages of particles, a class of function words, than lvPPA participants.ConclusionsPart of speech analysis showed a deficit in function words in nfvPPA. Content unit analysis distinguished svPPA and lvPPA, and is easily incorporated into the clinical environment when spoken data are scarce or difficult to obtain because of speech production impairments.

  PublisherDOI

• Personalized Transcranial Direct Current Stimulation for Behavioral and Neurophysiologic Outcomes

  JAMA Network Open · 2025-08-25 · 3 citations

  articleOpen access

  Importance: Transcranial direct current stimulation (tDCS) is emerging as a home-based intervention for neuropsychiatric conditions and cognitive enhancement. However, its effectiveness is limited by interindividual variability, as fixed-dose protocols have failed to account for anatomic differences influencing current delivery to targeted regions and treatment outcome. While computational modeling supports individualized dosing to improve consistency, experimental validation remains limited. Objective: To compare the behavioral and neurophysiologic outcomes of fixed-dose vs individualized-dose tDCS. Design, Setting, and Participants: This comparative effectiveness study using a within-participant, double-masked, crossover design was conducted from January 1, to March 31, 2024, at the National Institute of Mental Health and Neurosciences in India. Adult participants (aged 21-35 years) received 3 sessions of tDCS (fixed-dose, individualized-dose, and sham stimulation) in counterbalanced order. Individualized doses were calculated using a custom-built simulation toolbox. Main Outcomes and Measures: Behavioral performance was measured using reaction time during a rapid naming task. Neurophysiologic effects were assessed using motor-evoked potentials (MEPs) recorded before and after stimulation. Linear mixed-effects models were used for the statistical analysis. Results: Sixteen right-hand-dominant, bilingual English-Dravidian speakers (mean [SD] age, 23.1 [3.9] years; 8 female [50%]) were included. Individualized-dose tDCS associated with significantly greater reaction time improvement over sham (estimated marginal mean [SD]: before, 753.0 [41.1] ms; after, 619.0 [41.1] ms; change [Δ] = 133.6 ms; SE, 10.2 ms; z score ratio, 13.09) compared with fixed-dose tDCS (before, 694.0 [41.1] ms; after, 680.0 [41.1] ms; Δ = 14.6 ms; SE, 10.1 ms; z score ratio, 1.45). Variability was lower with individualized-dose stimulation (coefficient of variation, -1.14 vs 0.39 fixed vs individualized dose, respectively). Sex-stratified analyses showed that women had improvements with both fixed (Δ = 58.0 ms; P = .003) and individualized (Δ = 113.8 ms; P < .001) stimulation, while men had improvement only with individualized tDCS (Δ = 153.4 ms; P < .001). Seven participants (5 men and 2 women) converted from nonresponders to responders with individualized dosing. For MEPs, individualized-dose tDCS showed greater poststimulation amplitude increases over sham (β [SE], 0.91 [0.23]), although fixed-dose tDCS poststimulation amplitude was smaller, but significant (β [SE], 0.56 [0.23]; P = .02) and showed a higher percentage change (β [SE], 144.26% [55.74%]; P = .01) and reduced variability (coefficient of variation, -0.79 vs 1.12 [fixed]). Conclusions and Relevance: In this comparative effectiveness study, dose-controlled tDCS was associated with consistent behavioral and neurophysiologic improvement, highlighting its translational importance in the treatment of neuropsychiatric disorders.

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• Alignment of behaviour and tDCS stimulation site induces maximum response: evidence from online tDCS and ERP

  Scientific Reports · 2024-08-24 · 8 citations

  articleOpen access

  tDCS modulates the activity of the neuronal networks to induce the desired behavioural changes. Two factors determine its effectiveness- (1) whether the network being stimulated is relevant to the task, and (2) if there is a scope for improvement in behavioral performance. To explore this, both dorsal (sub-lexical) and ventral (lexical) reading networks were stimulated (20 min, 2 mA) in 25 healthy young volunteers. Participants performed two reading tasks with different levels of lexical involvement: word fragment completion tasks (WCT) and word association tasks (WAT), while event-related potentials (ERPs) were recorded simultaneously. The study used a within-subject design over three sessions, comparing various electrode montages targeting the dorsal pathway's left inferior parietal lobule or the ventral reading pathway's left middle temporal lobule, as well as sham stimulation. The impact of tDCS sessions (dorsal, ventral, & sham) and task type (WCT & WAT) on priming effects (primed vs. unprimed) of behavioral performance (accuracy and reaction times), and ERP parameters (N400 amplitudes and latencies) were statistically analyzed.It was found that tDCS modulated the performance of WAT only (a task with a lower priming effect). The failure to modulate WCT (larger priming effect) indicated that tDCS was effective for conditions with room for improvement compared to a task where performance has reached the ceiling. Ventral stimulation enhanced accuracy in the WAT condition and shortened the N400 latency of the priming effect. In contrast, dorsal stimulation delayed the priming effect reaction time in the WAT condition and enhanced the N400 amplitude. To conclude, enhancement in performance due to tDCS occurs when the network (ventral) being stimulated aligns with the cognitive demands of the task and there is a scope for improvement.

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• White matter associations with spelling performance

  Brain Structure and Function · 2024-03-25 · 6 citations

  articleOpen access

  Multiple neurocognitive processes are involved in the highly complex task of producing written words. Yet, little is known about the neural pathways that support spelling in healthy adults. We assessed the associations between performance on a difficult spelling-to-dictation task and microstructural properties of language-related white matter pathways, in a sample of 73 native English-speaking neurotypical adults. Participants completed a diffusion magnetic resonance imaging scan and a cognitive assessment battery. Using constrained spherical deconvolution modeling and probabilistic tractography, we reconstructed dorsal and ventral white matter tracts of interest, bilaterally, in individual participants. Spelling associations were found in both dorsal and ventral stream pathways. In high-performing spellers, spelling scores significantly correlated with fractional anisotropy (FA) within the left inferior longitudinal fasciculus, a ventral stream pathway. In low-performing spellers, spelling scores significantly correlated with FA within the third branch of the right superior longitudinal fasciculus, a dorsal pathway. An automated analysis of spelling errors revealed that high- and low- performing spellers also differed in their error patterns, diverging primarily in terms of the orthographic distance between their errors and the correct spelling, compared to the phonological plausibility of their spelling responses. The results demonstrate the complexity of the neurocognitive architecture of spelling. The distinct white matter associations and error patterns detected in low- and high- performing spellers suggest that they rely on different cognitive processes, such that high-performing spellers rely more on lexical-orthographic representations, while low-performing spellers rely more on phoneme-to-grapheme conversion.

  PublisherOA PDFDOI

• Cortical and Subcortical Mechanisms of Orthographic Word-form Learning

  Journal of Cognitive Neuroscience · 2024-01-01 · 3 citations

  articleSenior author

  We examined the initial stages of orthographic learning in real time as literate adults learned spellings for spoken pseudowords during fMRI scanning. Participants were required to learn and store orthographic word forms because the pseudoword spellings were not uniquely predictable from sound to letter mappings. With eight learning trials per word form, we observed changes in the brain's response as learning was taking place. Accuracy was evaluated during learning, immediately after scanning, and 1 week later. We found evidence of two distinct learning systems-hippocampal and neocortical-operating during orthographic learning, consistent with the predictions of dual systems theories of learning/memory such as the complementary learning systems framework [McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychological Review, 102, 419-457, 1995]. The bilateral hippocampus and the visual word form area (VWFA) showed significant BOLD response changes over learning, with the former exhibiting a rising pattern and the latter exhibiting a falling pattern. Moreover, greater BOLD signal increase in the hippocampus was associated with better postscan recall. In addition, we identified two distinct bilateral brain networks that mirrored the rising and falling patterns of the hippocampus and VWFA. Functional connectivity analysis revealed that regions within each network were internally synchronized. These novel findings highlight, for the first time, the relevance of multiple learning systems in orthographic learning and provide a paradigm that can be used to address critical gaps in our understanding of the neural bases of orthographic learning in general and orthographic word-form learning specifically.

  PublisherDOI

• The neurocognitive mechanisms of spelling

  Elsevier eBooks · 2024-05-20 · 1 citations

  book-chapterSenior authorCorresponding
  PublisherDOI

Recent grants

• NIH Grant R29MH055758

  NIH · $569k · 2002

• NIH Grant R01DC006740

  NIH · $2.6M · 2011

Frequent coauthors

• David Caplan

  50 shared

• Swathi Kıran

  Boston University

  36 shared

• Robert W. Wiley

  Johns Hopkins University

  31 shared

• Cynthia K. Thompson

  28 shared

• Argye E. Hillis

  Johns Hopkins University

  26 shared

• Kyrana Tsapkini

  Johns Hopkins University

  25 shared

• John E. Desmond

  23 shared

• Todd B. Parrish

  Northwestern University

  23 shared

Labs

• Cognitive and Brain Sciences LabPI

Awards & honors

• Dysgraphia: Cognitive Processes, Remediation, and Neural Sub…
• Handbook of Cognitive Neuropsychology: What Deficits Reveal…