About

John Desmond is a Professor of Neurology at the Johns Hopkins School of Medicine, affiliated with The Solomon H. Snyder Department of Neuroscience. His research focuses on systems, cognitive, and computational neuroscience, with particular interest in cerebellar contributions to cognition, including verbal working memory performance. He investigates the role of the cerebellum and cerebro-cerebellar circuits beyond motor coordination, exploring their involvement in cognitive performance through neuroimaging and patient studies. His work also examines the effects of chronic heavy alcohol consumption on cognition and brain activation, as well as neurovascular changes, brain structure, and functional connectivity. Additionally, he studies how aging affects neural systems involved in associative learning and stimulus awareness, with a focus on neural systems important for classical eyeblink conditioning in the cerebellum and medial temporal lobe, along with attention-related structures in the parietal lobe. Desmond has developed methods integrating transcranial magnetic stimulation with functional MRI to assess brain connectivity non-invasively, utilizing concurrent TMS and fMRI to reveal brain activation patterns and their necessity for cognitive performance.

Research topics

• Neuroscience
• Psychology
• Anatomy
• Medicine
• Physical medicine and rehabilitation
• Radiology
• Pathology
• Communication
• Biology
• Developmental psychology
• Audiology
• Linguistics

Selected publications

• White matter predictors of cerebellar tDCS treatment effects in aphasia rehabilitation

  Frontiers in Neurology · 2026-02-20

  articleOpen access

  Introduction: Cerebellar transcranial direct current stimulation (tDCS) combined with language therapy can aid in chronic aphasia recovery, but the neural mechanisms and biomarkers of treatment efficacy remain uncertain. Methods: In this secondary analysis of data from a previously conducted clinical trial, we used a randomized, double-blind, sham-controlled, within-subject crossover design with a study sample of 19 participants with post-stroke aphasia. We assessed the degree to which baseline properties of cerebro-cerebellar white matter tracts can predict or moderate longitudinal treatment effects at three time points: post-treatment, 2 weeks post-treatment, and 2 months post-treatment. Tract properties were measured by fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI). We also tested whether there are differential effects between trained and untrained language tasks and between cerebellar tDCS polarity (anodal and cathodal). Results: Baseline measures of tracts connecting the left lesioned cortex to the right posterolateral cerebellum (stimulation target) influenced treatment gains for untrained tasks, relative to sham control. In contrast, for the trained task, treatment gains were influenced by baseline measures of tracts connecting the non-stimulated left cerebellum with the contralateral right cerebral cortex. Although there were no consistent effects from cerebellar tDCS polarity, a highly consistent pattern emerged across all tasks and tracts. Specifically, language improvements were predicted by a baseline tract profile (i.e., higher FA and lower MD) typically associated with higher white matter integrity, especially within the context of stroke-induced white matter decline. Discussion: These findings corroborate the potential for baseline tract properties as a biomarker of treatment efficacy and support the notion that adjuvant (cerebellar tDCS + language) therapy preferentially benefits individuals with relatively preserved structural connections within functionally relevant networks. Clinical trial registration: ClinicalTrials.gov, identifier (NCT02901574).

  PublisherOA PDFDOI

• Baseline Functional Connectivity Predicts Who Will Benefit From Neuromodulation: Evidence From Primary Progressive Aphasia

  Neurorehabilitation and neural repair · 2026-01-01

  articleOpen access

  BackgroundUnderstanding individual variability in response to interventions is essential for developing personalized treatment strategies. In rare and clinically heterogeneous conditions like primary progressive aphasia (PPA), predicting treatment response is particularly challenging due to varying clinical manifestations. In this study, we aimed to identify and analyze predictors of individual language response to transcranial direct current stimulation (tDCS) of the left inferior frontal gyrus (IFG), using a novel, robust analytic approach focused on treatment effect heterogeneity.MethodsWe compared the ability of predicting individual effect (active vs sham tDCS during 20-minute sessions on weekdays for 3 weeks; active: 2 mA current across electrodes; sham: current ramped down after 30 seconds), using demographic and clinical patient characteristics (eg, PPA variant and disease progression, baseline language performance) or volumetric fMRI data versus functional connectivity (from resting-state fMRI) in the cohort of 36 patients.ResultsFunctional connectivity alone had the highest predictive value for outcomes, explaining 62% of the variance of the tDCS effect in generalization (semantic fluency) and 75% of the main outcome (written naming), contrasted with <15% (for semantic fluency) and <23% (for written naming) of variance predicted by demographic and clinical patient characteristics or volumetric data. Patients with higher baseline functional connectivity within the left IFG (between pars opercularis and pars triangularis) were most likely to benefit from tDCS both in generalization (semantic fluency) as well as in the main outcome (written naming). In addition, patients with higher baseline FC between the middle temporal pole and superior temporal gyrus, were most likely to show generalization effects of tDCS.ConclusionsThe present study showcases the importance of a baseline functional connectivity scan in predicting tDCS outcomes, and points toward a precision medicine approach in neuromodulation studies. The study has important implications for clinical trials and practice, providing a statistical method that addresses heterogeneity in patient populations and allowing accurate prediction and enrollment of those who will most likely benefit from specific interventions.

  PublisherOA PDFDOI

• Consistent cerebellar pathway-cognition associations across pre-adolescents &amp; young adults: a diffusion MRI study of 9000+ participants

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-06 · 2 citations

  preprintOpen access

  Abstract The cerebellum, long implicated in movement, is now recognized as a contributor to higher-order cognition. The cerebellar pathways provide key structural links between the cerebellum and cerebral regions integral to language, memory, and executive function. Here, we present a large-scale, cross-sectional diffusion MRI (dMRI) analysis investigating the relationships between cerebellar pathway microstructure and cognitive performance in over 9,000 participants spanning pre-adolescence (n&gt;8,000 from the ABCD dataset) and young adulthood (n&gt;900 from the HCP-YA dataset). We assessed the microstructure of five cerebellar pathways—the inferior, middle, and superior cerebellar peduncles; the parallel fibers; and input/Purkinje fibers—using three dMRI measures of fractional anisotropy, mean diffusivity, and number of streamlines. Cognitive performance was evaluated using seven NIH Toolbox assessments of language, executive function, and memory. In both datasets, we found numerous significant associations between cerebellar pathway microstructure and cognitive performance. These associations showed a strong correlation across the two datasets (r = 0.47, p &lt; 0.0001), underscoring the reliability of cerebellar dMRI-cognition relationships in pre-adolescents and young adults. In both datasets, the strongest associations were found between the superior cerebellar peduncle and performance on language assessments, suggesting this pathway plays an important role in language function across age groups. In young adults, but not pre-adolescents, parallel fiber microstructure was linked to inhibitory control, suggesting that contributions to attentional processes may emerge or strengthen with maturation. Overall, our findings highlight the important role of cerebellar pathways in cognition and the utility of large-scale datasets for advancing our understanding of brain-cognition relationships. Significance This study provides strong evidence linking cerebellar pathway tissue microstructure to cognition across large populations of preadolescent children and young adults. By leveraging diffusion MRI tractography and cognitive performance data from two major datasets, we identify significant relationships between cerebellar pathway microstructure and cognitive performance. Importantly, findings are significantly correlated across datasets, pointing to the consistency of these relationships, bridging age groups and acquisitions. These results highlight the cerebellar pathways’ integral role in cognitive functioning and underscore the value of large-scale, population-based studies in advancing our understanding of brain-cognition relationships. Classification 1) Biological Sciences, Neuroscience; 2) Social Sciences, Psychological and Cognitive Sciences

  PublisherDOI

• 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.

  PublisherOA PDFDOI

• Longitudinal evaluation of common and unique brain-networks in variants of primary progressive aphasia

  Alzheimer s Research & Therapy · 2025-08-19 · 1 citations

  articleOpen access

  BACKGROUND AND OBJECTIVES: The two variants of primary progressive aphasia (PPA) with Frontotemporal dementia pathology- semantic (svPPA) and non-fluent (nfvPPA) exhibit both shared and distinct features. The phenotypic heterogeneity stems from alterations in underlying brain networks. Investigating the common network (CN) and variant-specific unique network (UN) is critical to understanding the pathology of these conditions. Additionally, examining the evolution of these networks is key to elucidating disease progression. METHOD: We applied algebraic-topology to explore the CN and UN using individualised resting-state fMRI data from 31 patients with nfvPPA, 32 with svPPA, and 38 age- and sex-matched controls (scanned at first visit). Using persistent homology, we identified the networks that differentiated (p < 0.01) each patient group from healthy controls. Since the subset of these subjects was scanned at the 6th and 12th months, the longitudinal changes in the rsfMRI networks were evaluated at each interval. Network features were correlated with clinical behaviours, and the longitudinal impact of the changes in these networks on behaviours was evaluated over the 12-month period. To validate the rsfMRI networks and the longitudinal changes, we evaluated the grey matter (GM) volume, GM atrophy and the rate-of-atrophy of the brain areas. To corroborate the findings, we applied persistent homology on the structural networks derived from diffusion tensor images. RESULT: We found the existence of a left lateralised functional network identical in both PPA groups. This CN, comprising regions associated with language and cognition, remained stable over time (12 months period) and was associated with the severity of dementia. Conversely, the right-dominant UN in both variants showed progressive disintegration annually. In svPPA, cerebellar disassociation led to a decline in daily life activities, while parietal lobe degradation in nfvPPA impaired naming abilities. The CN and UN with similar regions were also found in the structural connectivity and the longitudinal changes in UN aligned with accelerated GM atrophy in the affected regions. DISCUSSION: Given the limited availability of pharmacological treatments, rehabilitation in PPA has primarily focused on modulating the left hemisphere using brain stimulation techniques. However, our findings indicate that while the disintegrated left hemispheric CN remained relatively stable, dysconnectivity progressed in the right hemisphere. These observations, along with the phylogenetic organization of brain networks and the variant-specific patterns of progression, highlight the need to incorporate right hemispheric rehabilitation strategies alongside the conventional left-hemispheric approaches in PPA.

  PublisherOA PDFDOI

• 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.

  PublisherOA PDFDOI

• Dynamic inferior olive activation in a cognitive task: an fMRI study

  Brain Structure and Function · 2025-05-21 · 3 citations

  articleOpen accessSenior author

  The inferior olive provides powerful inputs to the cerebellum hypothesized to support cerebellar learning and error detection. Given cerebellar involvement in verbal working memory and the close interplay with the inferior olive, the inferior olive is likely also involved in verbal working memory. In order to elucidate the inferior olive's role in verbal working memory, we utilized an MRI-based Sternberg verbal working memory task which involved learning novel vs repeated sequences. As hypothesized, inferior olive activation was stronger during encoding and retrieval compared to maintenance, especially for novel compared to repeated sequences, indicative of diminished inferior olive activity with stimulus repetition. Results also revealed differential inferior olive activation during retrieval, with increased activation on matching probes for novel and on non-matching probes for repeated sequences. This underlines the crucial role of the inferior olive in novel information encoding and error feedback, and that conditions triggering strong inferior olive responses can change as a function of novelty.

  PublisherOA PDFDOI

• Identifying target regions for non-invasive brain stimulation of the language network in primary progressive aphasia: A narrative review

  Brain Disorders · 2025-07-01

  reviewOpen access

  • The language network in PPA is organised into dorsal (involved in amalgamation) and ventral (involved in concatenation) pathways. • There are prominent anatomical clusters of regions specific to PPA patients' phonetic, semantic, and motor functions. • Selective NIBS stimulation of the hubs in the dorsal and ventral pathways of language networks is suggested according to the patient's specific deficits. Primary progressive aphasia (PPA) is a heterogeneous neurodegenerative condition characterized by loss of language function. The present review discusses that Non-invasive brain stimulation (NIBS) holds the potential to benefit these patients by inducing neuroplasticity in language networks. Studies have also shown that neuroplasticity in the language networks is accompanied by behavioural gains irrespective of the degree of regional atrophy in PPA patients. However, the generalizability of NIBS in remediating speech deficits is currently restricted by inter-individual variability, lack of consistency, and understanding of the underlying improvement mechanism. Here, we highlight the organization of language networks in PPA patients by consolidating anatomical, functional, and tractography-based imaging studies. These imaging and brain-computer interface studies point out functional segregation of language processing in dorsal and ventral pathways that brace with the regional atrophy pattern seen in PPA patients. The dorsal pathway involved in the sequential processing of phonetics and syntax encompasses the neuronal network around the left posterior temporal-parietal region and inferior frontal gyrus. The ventral pathway is involved in the amalgamation of sensory input into semantics around the left middle and inferior temporal lobes, including the polar cortices. A separate speech production network is identified around the left inferior frontal gyrus and motor cortices dedicated to integrated motor articulation. Thus, the present review suggests selectively stimulating brain regions within these different speech processing networks to address specific speech deficits seen in PPA patients to maximize the benefits of functionality-specific NIBS.

  PublisherDOI

• 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.

  PublisherOA PDFDOI

• Early adversity affects cerebellar structure and function – A systematic review of human and animal studies

  2024-03-07

  reviewOpen access

  Recent research has highlighted cerebellar involvement in cognition and several psychiatric conditions such as mood and anxiety disorders and schizophrenia. Attention-deficit/hyperactivity disorder and autism spectrum disorder have been linked to reduced cerebellar volume as well. Cerebellar alterations are frequently present after early adversity in humans and animals, but a systematic integration of results is lacking. To this end, a systematic literature search was conducted in PubMed, Web of Science, and EBSCO databases using the keywords “early adversity OR early life stress” AND “cerebellum OR cerebellar.” A total of 45 publications met the inclusion criteria: 25 studies investigated human subjects and 20 reported results from animal models. Findings in healthy subjects show bilateral volume reduction and decreased functional connectivity within the cerebellum and between the cerebellum and frontal regions after adversity throughout life, especially when adversity was assessed with the Childhood Trauma Questionnaire. In clinical populations, adults demonstrate increased cerebellar volume and functional connectivity after adversity, whereas pediatric patients show reduced cerebellar volume. Animal findings reveal cerebellar alterations without necessarily co-occurring pathological behavior, highlighting alterations in stress hormone receptor levels, cell density, and neuroinflammation markers. Cerebellar alterations after early adversity are robust findings across human and animal studies and occur independent of clinical symptoms.

  PublisherOA PDFDOI

Recent grants

• Investigation of cerebellar involvement in AUD

  NIH · $2.9M · 2022–2027

• Investigation of Cerebellar Involvement in Cognitive Function

  NIH · $2.7M · 2015–2021

• fMRI Investigations of Cognition in Alcoholics

  NIH · $2.9M · 2010–2017

• NIH Grant F32NS009628

  NIH · $71k

• NIH Grant R01AG021501

  NIH · $1.6M · 2010

Frequent coauthors

• Edith V. Sullivan

  Stanford University

  54 shared

• Dominic T. Cheng

  Johns Hopkins University

  50 shared

• Adolf Pfefferbaum

  SRI International

  50 shared

• Argye E. Hillis

  Johns Hopkins University

  48 shared

• Kyrana Tsapkini

  Johns Hopkins University

  47 shared

• Kelvin O. Lim

  University of Minnesota

  43 shared

• Bronte Ficek

  Neurology, Inc

  42 shared

• Kenichi Oishi

  42 shared