publications

2025

1. Front. Psychiatry

   Functional Movement Disorder Is Associated with Abnormal Interoceptive Brain Activity: A Task-Based Functional MRI Study

   Primavera A. Spagnolo, Jacob A. Parker, Mark Hallett, and Silvina G. Horovitz

   Frontiers in Psychiatry, Feb 2025

   DOI

2023

1. Brain Connect.

   Classification of Functional Movement Disorders with Resting-State Functional Magnetic Resonance Imaging

   Rebecca E. Waugh, Jacob A. Parker, Mark Hallett, and Silvina G. Horovitz

   Brain Connectivity, Feb 2023

   Abs DOI

   Introduction: Functional movement disorder (FMD) is a type of functional neurological disorder characterized by abnormal movements that patients do not perceive as self-generated. Prior imaging studies show a complex pattern of altered activity, linking regions of the brain involved in emotional responses, motor control, and agency. This study aimed to better characterize these relationships by building a classifier using a support vector machine to accurately distinguish between 61 FMD patients and 59 healthy controls using features derived from resting-state functional magnetic resonance imaging. Materials and Methods: First, we selected 66 seed regions based on prior related studies, then we calculated the full correlation matrix between them before performing recursive feature elimination to winnow the feature set to the most predictive features and building the classifier. Results: We identified 29 features of interest that were highly predictive of the FMD condition, classifying patients and controls with 80% accuracy. Several key features included regions in the right sensorimotor cortex, left dorsolateral prefrontal cortex, left cerebellum, and left posterior insula. Conclusions: The features selected by the model highlight the importance of the interconnected relationship between areas associated with emotion, reward, and sensorimotor integration, potentially mediating communication between regions associated with motor function, attention, and executive function. Exploratory machine learning was able to identify this distinctive abnormal pattern, suggesting that alterations in functional linkages between these regions may be a consistent feature of the condition in many FMD patients. Clinical-Trials.gov ID: NCT00500994 Impact statement Our research presents novel results that further elucidate the pathophysiology of functional movement disorder (FMD) with a machine learning model that classifies FMD and healthy controls correctly 80% of the time. Herein, we demonstrate how known differences in resting-state functional magnetic resonance imaging connectivity in FMD patients can be leveraged to better understand the complex pattern of neural changes in these patients. Knowing that there are measurable predictable differences in brain activity in patients with FMD may help both clinicians and patients conceptualize and better understand the illness at the point of diagnosis and during treatment. Our methods demonstrate how an effective combination of machine learning and qualitative approaches to analyzing functional brain connectivity can enhance our understanding of abnormal patterns of brain activity in FMD patients.

2021

1. Brain Sci.

   Corticolimbic Modulation via Intermittent Theta Burst Stimulation as a Novel Treatment for Functional Movement Disorder: A Proof-of-Concept Study

   Primavera A. Spagnolo, Jacob Parker, Silvina Horovitz, and Mark Hallett

   Brain Sciences, Jun 2021

   Abs DOI

   Neuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD). Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, the objective of this proof-of-concept study was to investigate the safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD. Six subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. The FMD symptom severity was assessed at baseline, during treatment and 24 h after the last iTBS session. Multiple doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a marked reduction in FMD symptom severity. Corticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research.

2. Neuroimage Clin.

   In Vivo Assessment of Neurodegeneration in Spinocerebellar Ataxia Type 7

   Jacob A. Parker, Shabbir H. Merchant, Sanaz Attaripour-Isfahani, Hyun Joo Cho, Patrick McGurrin, Brian P. Brooks, Albert R. La Spada, Mark Hallett, Laryssa A. Huryn, and Silvina G. Horovitz

   NeuroImage: Clinical, Jan 2021

   Abs DOI

   Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive cerebellar ataxia and retinal degeneration. Increasing loss of visual function complicates the use of clinical scales to track the progression of motor symptoms, hampering our ability to develop accurate biomarkers of disease progres\-sion, and thus test the efficacy of potential treatments. We aimed to identify imaging measures of neuro\-degeneration, which may more accurately reflect SCA7 severity and progression. While common structural MRI techniques have been previously used for this purpose, they can be biased by neurodegeneration-driven increases in extracellular CSF-like water. In a cross-sectional study, we analyzed diffusion tensor imaging (DTI) data collected from a cohort of 13 SCA7 patients and 14 healthy volunteers using: 1) a diffusion tensor-based image registration technique, and 2) a dual-compartment DTI model to control for the potential increase in extracellular CSF-like water. These methodologies allowed us to assess both volumetric and microstructural abnormalities in both white and gray matter brain-wide in SCA7 patients for the first time. To measure tissue volume, we per\-formed diffusion tensor-based morphometry (DTBM) using the tensor-based registration. To assess tissue microstructure, we computed the parenchymal mean diffusivity (pMD) and parenchymal fractional anisotropy (pFA) using the dual compartment model. This model also enabled us to estimate the parenchymal volume fraction (pVF), a measure of parenchymal tissue volume within a given voxel. While DTBM and pVF revealed tissue loss primarily in the brainstem, cerebellum, thalamus, and major motor white matter tracts in patients (p < 0.05, FWE corrected; Hedge’s g > 1), pMD and pFA detected microstructural abnormalities in virtually all tissues brain-wide (p < 0.05, FWE corrected; Hedge’s g > 1). The Scale for the Assessment and Rating of Ataxia trended towards correlation with cerebellar pVF (r = - 0.66, p = 0.104, FDR corrected) and global white matter pFA (r = - 0.64, p = 0.104, FDR corrected). These results advance our understanding of neurodegeneration in living SCA7 patients by providing the first voxel-wise characterization of white matter volume loss and gray matter microstructural abnormalities. Moving forward, this comprehensive approach could be applied to char\-acterize the full spatiotemporal pattern of neurodegeneration in SCA7, and potentially develop an accurate imaging biomarker of disease progression.

2020

1. Brain

   

   The Role of the Inferior Parietal Lobule in Writer’s Cramp

   Shabbir Hussain I. Merchant, Eleni Frangos, Jacob Parker, Megan Bradson, Tianxia Wu, Felipe Vial-Undurraga, Giorgio Leodori, M. C. Bushnell, Silvina G. Horovitz, Mark Hallett, and 1 more author

   Brain, Jun 2020

   Abs DOI

   Task-specific dystonia (TSD) can be viewed as a loss of motor control confined to a single motor skill. Merchant et al. use a novel multimodal approach to explo

2. Behav. Res.

   

   Modeling Pupil Responses to Rapid Sequential Events

   Rachel N. Denison^*, Jacob A. Parker^*, and Marisa Carrasco

   Behavior Research Methods, Mar 2020

   *equal contribution

   Abs DOI

   Pupil size is an easily accessible, noninvasive online indicator of various perceptual and cognitive processes. Pupil measurements have the potential to reveal continuous processing dynamics throughout an experimental trial, including anticipatory responses. However, the relatively sluggish (~2 s) response dynamics of pupil dilation make it challenging to connect changes in pupil size to events occurring close together in time. Researchers have used models to link changes in pupil size to specific trial events, but such methods have not been systematically evaluated. Here we developed and evaluated a general linear model (GLM) pipeline that estimates pupillary responses to multiple rapid events within an experimental trial. We evaluated the modeling approach using a sample dataset in which multiple sequential stimuli were presented within 2-s trials. We found: (1) Model fits improved when the pupil impulse response function (PuRF) was fit for each observer. PuRFs varied substantially across individuals but were consistent for each individual. (2) Model fits also improved when pupil responses were not assumed to occur simultaneously with their associated trial events, but could have non-zero latencies. For example, pupil responses could anticipate predictable trial events. (3) Parameter recovery confirmed the validity of the fitting procedures, and we quantified the reliability of the parameter estimates for our sample dataset. (4) A cognitive task manipulation modulated pupil response amplitude. We provide our pupil analysis pipeline as open-source software (Pupil Response Estimation Toolbox: PRET) to facilitate the estimation of pupil responses and the evaluation of the estimates in other datasets.

2025

1. Category learning drives neural repulsion initially but integration at a delay.

   M. C. Tandoc, S. H. Solomon, A. B. Williams, A. Gordienko, J. A. Parker, and A. C. Schapiro

   Cognitive Neuroscience Society Annual Meeting, Boston, MA, USA, Mar 2025

   [Poster]

2024

1. Suboptimal human decision-making can reflect an efficient information bottleneck.

   J. A. Parker, A. Filipowicz, V. Balasubramanian, J. W. Kable, and J. I. Gold

   Society for Industrial and Applied Mathematics Conference on the Life Sciences, Portland, OR, USA, Jun 2024

   [Invited Talk]
2. The representation and retrieval of general versus specific category knowledge.

   M. C. Tandoc, S. H. Solomon, J. A. Parker, A. Gordienko, and A. C. Schapiro

   Cognitive Neuroscience Society Annual Meeting, Toronto, Canada, Apr 2024

   [Poster]

2023

1. Suboptimal human decision-making can reflect an efficient information bottleneck.

   J. A. Parker, A. Filipowicz, V. Balasubramanian, J. W. Kable, and J. I. Gold

   Society for Neuroscience Annual Meeting, Washington, DC, USA, Nov 2023

   [Poster]

2020

1. Structural alterations in functional movement disorders: a diffusion weighted imaging study.

   S. G. Horovitz, J. A. Parker, P. Bedard, C. Maurer, and M Hallett

   28th Annual Meeting of the International Society for Magnetic Resonance in Medicine, Virtual, Aug 2020

   [Poster]

2019

1. Structural Magnetic Resonance Imaging Correlates of Neurodegeneration in a Spinocerebellar Ataxia Type 7 Cohort.

   J. A. Parker, Shabbir H. Merchant, Sanaz Attaripour-Isfahani, Patrick McGurrin, Laryssa A. Huryn, Mark Hallett, and Silvina G. Horovitz

   Society for Neuroscience Annual Meeting, Chicago, IL, USA, Nov 2019

   [Poster]
2. Interactions within Fine Motor Control Network in Task-specific Dystonia.

   S. H. Merchant, E. Frangos, S. G. Horovitz, T. Popa, J. A. Parker, and M. Hallett

   International Congress of Parkinson’s Disease and Movement Disorders, Nice, France, Sep 2019

   [Poster]
3. Estimation of pupillary responses to rapid events.

   R. N. Denison, J. A. Parker, and M. Carrasco

   9th Annual Meeting of the Vision Sciences Society, St. Pete Beach, FL, USA, May 2019

   [Poster]
4. Structural Magnetic Resonance Imaging Correlates of Neurodegeneration in a Spinocerebellar Ataxia Type 7 Cohort.

   J. A. Parker, S. H. Merchant, S. Attaripour-Isfahani, P. McGurrin, L. A. Huryn, M. Hallett, and S. G. Horovitz

   American Academy of Neurology Annual Meeting, Philadelphia, PA, USA, May 2019

   [Poster]
5. Deciding and Instructed to go and no-go.

   S. Attaripour-Isfahani, P. McGurrin, J. A. Parker, N. Dang, F. Vial, and M. Hallett

   Second International Conference on Neuroscience and Free Will, Orange, CA, USA, Mar 2019

   [Poster]

2018

1. Pathophysiologic insights into Spinocerebellar Ataxia Type 7 through Structural Imaging Analysis.

   J. A. Parker, S. H. Merchant, S. Attaripour-Isfahani, P. McGurrin, M. Hallett, and S. G. Horovitz

   Society for Neuroscience Annual Meeting, San Diego, CA, USA, Nov 2018

   [Poster]
2. Pathophysiologic insights into ataxia and spasticity through structural imaging of a Spinocerebellar Ataxia Type 7 cohort.

   J. A. Parker, S. H. Merchant, S. Attaripour-Isfahani, P. McGurrin, M. Hallett, and S. G. Horovitz

   International Congress of Parkinson’s Disease and Movement Disorders, Hong Kong, China, Oct 2018

   [Poster]

2017

1. Pupil dilation reveals the timecourse of voluntary temporal attention.

   R. N. Denison, J. A. Parker, and M. Carrasco

   40th European Conference on Visual Perception, Berlin, Germany, Aug 2017

   [Poster]
2. Pupil Size as an Index of Voluntary Temporal Attention.

   J. A. Parker, R. N. Denison, and M. Carrasco

   43rd Undergraduate Research Conference of the New York University College of Arts and Science, New York, NY, USA, May 2017

   [Talk]

2024

1. PennNeuroKnow

   Decide Quickly or Decide Accurately- How Your Brain Solves a Classic Decision-Making Problem

   Jacob A. Parker

   PennNeuroKnow, Jun 2024

   Abs URL

   It is often difficult to do tasks both quickly and well at the same time. While the same applies to decision making, the brain has found an effective way to make decisions that are reasonably accur…

2. PennNeuroKnow

   The Experiments That Opened the Brain’s Black Box

   Jacob A. Parker

   PennNeuroKnow, May 2024

   Abs URL

   Despite centuries of scientific advancements, the inner workings of much of the brain remained a complete mystery. A groundbreaking set of experiments changed this.

3. PennNeuroKnow

   Why Forgetting Might Actually Be a Good Thing

   Jacob A. Parker

   PennNeuroKnow, Jan 2024

   Abs URL

   Our tendency to forget names, passwords, and skills is a source of endless frustration. However, this forgetfulness might actually be crucial for optimal brain function.

2023

1. PennNeuroKnow

   ChatGPT versus the Brain: A Nerve-Wracking Matchup

   Jacob A. Parker

   PennNeuroKnow, Aug 2023

   Abs URL

   ChatGPT is able to write entire essays and explain rocket science while speaking in Shakespearean English. But does it have enough to take the world intelligence title from the human brain?

2022

1. SciTech Fore.

   Neutralizing the Algorithm: Approaches for Reducing the Spread of Disinformation Online

   Walker Gosrich, Jacob A. Parker, Hersh Sangvhi, Tuhina Srivastava, and Shannon L. Wolfman

   SciTech Forefront, Jul 2022

   Abs URL

   Online disinformation has increased political polarization and elongated the COVID-19 pandemic.