RESEARCH
Overview
Dr. Kuhn’s research integrates neuroimaging, neuropsychological assessment and neuromodulation to investigate functional neuroanatomy - that is, what brain networks and brain functions give rise to each aspect of cognition, emotion, and behavior. This is also called the brain-behavior relationship. Neuroimaging allows the brain’s structure, activity, and connectivity to be viewed, directly measured and quantified. Neuropsychological assessment allows for cognition (e.g. attention, memory, problem solving), emotion (e.g. anxiety, depression), and behavior (e.g. motor skills, real world function) to be quantified. Brain and neuropsychological changes caused by healthy development, healthy aging, neurologic and psychiatric diseases are used to test theories about the brain-behavior relationship. Neuromodulation, such as with focused ultrasound or transcranial magnetic or electrical stimulation, also allows for specific regions of the brain to be changed. Then, neuroimaging and neuropsychological assessment can assess how those changes affect the structure and function of the brain, cognition, emotion and behavior. In this way, Dr. Kuhn’s research seeks to further our understanding of the brain-behavior relationships and help develop and validate clinical tools for improving cognition and emotion across a host of neurological and psychiatric conditions.
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Systems and methods for imaging of neurovascular-coupling 2025
Apparatus, systems, and methods for comparative analysis of tissue and organ scans between patients or groups of patients without sensitivity to patient-specific or scanner specific characteristics, including prediction, diagnosis, prognosis, tracking, and treatment guidance are disclosed. Blood oxygen level dependent (BOLD) fMRI is performed on a patient, and the resulting structural and functional data is preprocessed to remove artifacts and correct motion defects.
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Investigating low intensity focused ultrasound pulsation in anhedonic depression—A randomized controlled trial 2025
Anhedonic depression is a subtype of depression characterized by deficits in reward processing. This subtype of depression is associated with higher suicide risk and longer depressive episodes, underscoring the importance of effective treatments. Anhedonia has also been found to correlate with alterations in activity in several subcortical regions, including the caudate head and nucleus accumbens.
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Contrasting cognitive, behavioral, and physiological responses to breathwork vs. naturalistic stimuli in reflective chamber and VR headset environments 2025
This study examined whether therapeutic experiences originally created in the MindGym could maintain their efficacy when delivered via 360-degree recordings through virtual reality (VR) headsets.
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The ENIGMA-Neuromodulation working group – A mission statement 2025
Founded in 2009, the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)[1] consortium brings together 2000+ researchers from over 47 countries with the shared mission of pooling brain imaging and other relevant data to advance scientific understanding of major brain diseases, disorders, and conditions, covering influential genetic, environmental and interventional factors.
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Your brain on art, nature, and meditation: a pilot neuroimaging study 2025
Exposure to art, nature, or meditation, all transcending human experiences, has beneficial effects on health and wellbeing. Focusing inward or watching art and nature videos elicits positive emotions that can help heal stress-related conditions. In a pilot functional magnetic resonance (fMRI) study, we explored the effect of watching digital art or nature videos compared to contemplating the universal connectedness (also known as transcendental meditation).
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Contrasting cognitive, behavioral, and physiological responses to breathwork vs. naturalistic stimuli in reflective chamber and VR headset environments 2025
The MindGym, a novel immersive technology utilizing a reflective chamber environment, was developed to create standardized experiential content, including anxiolytic experiences. This study examined whether therapeutic experiences originally created in the MindGym could maintain their efficacy when delivered via 360-degree recordings through virtual reality (VR) headsets.
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Development and Implementation of a Transcranial Focused Ultrasound Device 2025
Transcranial focused ultrasound (tFUS) is an emerging technology in brain research and clinical sciences, enabling non-invasive neuromodulation. Unlike High-Intensity Focused Ultrasound, which ablates brain tissue, Low-Intensity tFUS can modulate neuronal activity without causing permanent damage. Preclinical studies have demonstrated that ultrasonic pulses can selectively activate or inhibit neurons, and clinical pilots have shown preliminary efficacy for new therapeutic applications.
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Evaluating Transcranial Focused Ultrasound Stimulation (tFUS) for Targeted Neuromodulation in Generalized Anxiety Disorder: A Double-Blind Feasibility Study 2025
Generalized Anxiety Disorder (GAD) is a prevalent mental health condition characterized by excessive worry. Current therapies often fail, necessitating new treatment modalities. Transcranial Focused Ultrasound Stimulation (tFUS) offers high spatial precision and non-invasive modulation of the amygdala, crucial for anxiety.
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Update on Ongoing Open Label Trial of Focused Ultrasound for Essential Tremor 2025
Essential Tremor (ET) is the most common movement disorder, characterized by involuntary, rhythmic tremors, primarily affecting the hands and arms. Current treatments, including medications and deep brain stimulation, often have limited efficacy and significant side effects, highlighting the need for alternative therapeutic options. Transcranial Focused Ultrasound (tFUS) offers a non-invasive method to modulate brain activity with high spatial precision, targeting thalamic nuclei associated with tremor control.
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Alterations in large-scale resting-state network nodes following transcranial focused ultrasound of deep brain structures 2024
Low-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds promise for the treatment of brain-based disorders. Studies in humans have shown that tFUS can successfully modulate perfusion in focal sonication targets, including the amygdala; however, limited research has explored how tFUS impacts large-scale neural networks.
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Preliminary Examination of the Effects of Focused Ultrasound on Living Skin and Temperature at the Skin–Transducer Interface 2024
Transcranial Focused Ultrasound Stimulation (tFUS) is a new, rapidly growing field related to the study and treatment of brain circuits. Establishing safety cutoffs for focused ultrasound is crucial for non-ablative neurological ultrasound experiments. In addition to potential focal heating, there is concern about temperature elevation at the skin surface. Much work has been performed at or near the FDA guideline of ISPTA.3 = 720 mW/cm2, which technically only applies to diagnostic, not therapeutic, ultrasound. Furthermore, evidence of brain tissue damage on histology in the focal region has been shown not to occur until ISPTA.3 > 14 W/cm2…
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Transcranial focused ultrasound targeting the amygdala may increase psychophysiological and subjective negative emotional reactivity in healthy older adults 2024
The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively.
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A phase 2, open-label study of anti-inflammatory NE3107 in patients with dementias 2024
Alzheimer’s disease (AD) is a progressive, multifactorial, neurodegenerative disorder affecting> 6 million Americans. Chronic, low-grade neuroinflammation, and insulin resistance may drive AD pathogenesis. We explored the neurophysiological and neuropsychological effects of NE3107, an oral, anti-inflammatory, insulin-sensitizing molecule, in AD.
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Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis 2024
This study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals.
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Corrigendum: A structural connectivity atlas of limbic brainstem nuclei 2024
Monoaminergic and other modulatory nuclei in the brainstem project widely to cortical limbic regions. We describe the structural connectivity across the several key brainstem nuclei theorized to influence emotion, reward, and cognitive functions. An increased understanding of the anatomic basis of the brainstem's role in emotion and other reward-related processing will support targeted neuromodulatary therapies aimed at alleviating the symptoms of neuropsychiatric disorders.
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The ENIGMA Neuromodulation Working Group: Goals, Challenges, and Opportunities for the Field 2024
Since 2009, the ENIGMA Consortium has brought together neuroimaging researchers from over 45 countries to perform some of the largest international studies of over 30 major brain disorders. The ENIGMA working groups tackle the growing challenge of data harmonization and standardization in analytic workflows, and address the need for well-powered, multi-center studies by providing a community-driven structure and platform for collaborations. The recently-formed ENIGMA Neuromodulation Working Group (ENIGMA-NeMo) includes subgroups representing individual neuromodulation modalities, supported by a machine learning/artificial intelligence core providing advanced analytic techniques within and across modulation modalities.
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Sublingual Ketamine for Depression and Anxiety: A Retrospective Study of Real-World Clinical Outcomes 2024
To evaluate the effectiveness of repeated at-home ketamine treatments for depression, generalized anxiety, and social anxiety and assess safety in terms of adverse effects and tendency towards long-term use.
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Transcranial focused ultrasound for the treatment of tremor: A preliminary case series 2024
Essential tremor (ET) can be debilitating. Treatments for ET include beta-blockers and surgical interventions. Low-intensity focused ultrasound (LIFU) may offer an office-based non-invasive alternative.
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Treatment‐Induced Epigenetic Modifications in MCI and Probable Alzheimer’s Disease 2023
NE3107 is an oral small molecule, blood‐brain permeable anti‐inflammatory insulin sensitizer that binds ERK, inhibits inflammatory NFkB and TNF signaling in macrophage lineage cells, and in clinical studies for AD (NCT04669028) and Parkinson’s disease (NCT05083260). NE3107 does not inhibit homeostatic activity of ERK or NFkB, and has a good safety profile in preclinical, non‐clinical and clinical studies. Safety, clinical, biomarker and neuroimaging results from a 3‐month open‐label phase 2 study of NE3107 treatment of mild dementia (NCT05007820) were reported at CTAD 2022.
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Bridging big data: Procedures for combining non-equivalent cognitive measures from the ENIGMA consortium 2023
Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individual’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our …
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Path Signature Representation of Patient-Clinician Interactions as a Predictor for Neuropsychological Tests Outcomes in Children: A Proof of Concept 2023
This research report presents a proof-of-concept study on the application of machine learning techniques to video and speech data collected during diagnostic cognitive assessments of children with a neurodevelopmental disorder. The study utilised a dataset of 39 video recordings, capturing extensive sessions where clinicians administered, among other things, four cognitive assessment tests. From the first 40 minutes of each clinical session, covering the administration of the Wechsler Intelligence Scale for Children (WISC-5), we extracted head positions and speech turns of both clinician and child. Despite the limited sample size and heterogeneous recording styles, the analysis successfully extracted path signatures as features from the recorded data, focusing on patient-clinician interactions. Importantly, these features quantify the interpersonal dynamics of the assessment process (dialogue and movement …
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A Systematic Approach to Neuropsychiatric Intervention: Functional Neuroanatomy Underlying Symptom Domains as Targets for Treatment
An ever-growing population experiences a wide range of psychopathologies, and there is now more than ever a need for clear differential diagnoses between disorders. Furthering this need is the fact that many psychological, psychiatric, and neurological disorders have overlapping features. Functional neuroimaging has been shown to differentiate not only between the function of different brain structures but also between the roles of these structures in functional networks. The aim of this article is to aid in the goal of parsing out disorders on the basis of specific symptom domains by utilizing the most recent literature on functional networks. Current literature on the role of brain networks in relation to different psychopathological symptom domains is examined and corresponding circuit-based therapies that have been or may be used to treat them are discussed. Research on depression, obsession and compulsions …
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Transcranial infrared laser stimulation for the treatment of traumatic brain injury: a case series
This study intended to evaluate the safety and possible therapeutic effect of transcranial infrared laser stimulation (TILS) based on photobiomodulation (PBM) among patients with traumatic brain injury (TBI).
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Neuroanatomical differences in the memory systems of intellectual giftedness and typical development
Studying neuro‐structural markers of intellectual giftedness (IG) will inform scientific understanding of the processes helping children excel academically.
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Treatment of dementia with bosutinib: an open-label study of a tyrosine kinase inhibitor
The pursuit of an effective therapeutic intervention for dementia has inspired interest in the class of medications known as tyrosine kinase inhibitors such as bosutinib.
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Treating dissociative post-traumatic stress disorder presenting as a functional movement disorder with transcranial magnetic stimulation targeting the cingulate gyrus
A 29-year-old woman presented with head and neck dystonia, as well as functional seizures. The patient was an active military service member with a history of combat-related trauma. Resting blood oxygen level dependent (BOLD) functional MRI (fMRI) scans of the brain demonstrated an increased anterior cingulate component of the salience network and hyper-connectivity between the insula and cingulate. Following neurological and psychiatric evaluation, she was diagnosed with dissociative post-traumatic stress disorder, partially presenting as a functional movement disorder. Inhibitory repetitive transcranial magnetic stimulation (rTMS) was prescribed with the anterior cingulate as the primary target, and supplementary motor and premotor cortices as secondary targets. The treatment was intended to suppress tremors both directly and indirectly. Thirty-six sessions later, her symptoms were in remission
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The lifespan human connectome project in aging: an overview
The original Human Connectome Project yielded a rich data set on structural and functional connectivity in a large sample of healthy young adults using improved methods of data acquisition, analysis, and sharing. More recent efforts are extending this approach to include infants, children, older adults, and brain disorders. This paper introduces and describes the Human Connectome Project in Aging (HCP-A), which is currently recruiting 1200 + healthy adults aged 36 to 100+, with a subset of 600 + participants returning for longitudinal assessment. Four acquisition sites using matched Siemens Prisma 3T MRI scanners with centralized quality control and data analysis are enrolling participants. Data are acquired across multimodal imaging and behavioral domains with a focus on factors known to be altered in advanced aging. MRI acquisitions include structural (whole brain and high resolution hippocampal) plus
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Temporal lobe epilepsy affects spatial organization of entorhinal cortex connectivity
Evidence for structural connectivity patterns within the medial temporal lobe derives primarily from postmortem histological studies. In humans and nonhuman primates, the parahippocampal gyrus (PHg) is subdivided into parahippocampal (PHc) and perirhinal (PRc) cortices, which receive input from distinct cortical networks. Likewise, their efferent projections to the entorhinal cortex (ERc) are distinct. The PHc projects primarily to the medial ERc (M-ERc). The PRc projects primarily to the lateral portion of the ERc (L-ERc). Both M-ERc and L-ERc, via the perforant pathway, project to the dentate gyrus and hippocampal (HC) subfields. Until recently, these neural circuits could not be visualized in vivo. Diffusion tensor imaging algorithms have been developed to segment gray matter structures based on probabilistic connectivity patterns. However, these algorithms have not yet been applied to investigate connectivity in
Effects of social adversity and HIV on subcortical shape and neurocognitive function
Thames, A. D., Kuhn, T. P., Mahmood, Z., Bilder, R. M., Williamson, T. J., Singer, E. J., & Arentoft, A. (2018). Brain imaging and behavior.
Effects of fMRI navigated TMS on treatment outcomes in major depressive disorder
Packham, H.R. & Nicodemus, N.E. & Jordan, S.E. & Whitney, M. & Pereles, F.S. & Duncan, J.C. & Becerra, S.B. & Bystritsky, A. & Kuhn, Taylor & Mamoun, Michael. (2018). Brain Stimulation.
Utilizing fMRI correlates of cognitive reappraisal to identify additional TMS targets for the treatment of GAD
Nicodemus, N.E. & Packham, H.R. & Jordan, S.E. & Whitney, M. & Pereles, S. & Duncan, J.C. & Becerra, S.A. & Bystritsky, A. & Kuhn, Taylor & Mamoun, Michael. (2018). Brain Stimulation.
Intraindividual variability in neuropsychological performance predicts cognitive decline and death in HIV
Anderson AE, Jones JD, Thaler NS, Kuhn TP, Singer EJ, Hinkin CH. (2018). Neuropsychology.
An Augmented Aging Process in Brain White Matter in HIV
Kuhn, T., Kaufmann, T., Doan, N.T., Westlye, L.T., Jones, J., Nunez, R.A., Bookheimer, S.Y., Singer, E.J., Hinkin, C.H., Thames, A.D. (2018). Human Brain Mapping.
Reverters from PD-MCI to cognitively intact are at risk for future cognitive impairment: Analysis of the PPMI cohort
Jones, J. D., Kuhn, T. P., & Szymkowicz, S. M. (2018). Parkinsonism & related disorders.