
John A. Wolf
· Ph.D.VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1967–2024
Research topics
- Medicine
- Neuroscience
- Psychology
- Computer Science
- Artificial Intelligence
- Political Science
- Biology
- Medical emergency
- Computer vision
- Telecommunications
- Speech recognition
- Nanotechnology
- Cell biology
- Medical physics
- Pathology
- Internal medicine
- Psychiatry
Selected publications
Automatic High-Frequency Oscillations Detection Using Time-Frequency Analysis
2023 · 3 citations
Senior authorCorresponding- Computer Science
- Artificial Intelligence
- Computer Science
The role of high-frequency oscillations (HFO) has been established in a multitude of the brain functions such as retrieval and consolidation of memory. Moreover, HFOs have been identified as a biomarker for pathological brain conditions, including epileptogenicity. Therefore, there has been a continuous effort to reliably detect and characterize HFOs. Here, we present an unsupervised HFO detector using characteristics of signals in the time-frequency domain obtained by continuous wavelet transform. By using L1 normalization for continuous wavelet transform, we improved the detection of HFOs without the need to normalize time-frequency maps. The elimination of normalizing the time-frequency maps reduces the computational cost of the analysis. We used two different benchmark datasets available in the literature to validate our proposed automatic HFO detector. The results demonstrate that our detector outperforms other commonly available HFO detectors including those that use time-frequency maps. Our HFO detector shows superior performance especially when signal-to-noise ratio (SNR) is low. Moreover, our detector can simultaneously detect artifacts, physiological spikes, and provide useful information about the HFOs such as their dominant frequency of oscillation, their average amplitude and their duration. This information can later be utilized to stratify HFOs for further analysis. Changes in HFO characteristics may be utilized as biomarkers in pathological conditions such as post-traumatic epilepsy.
Hippocampal interneuronal dysfunction and hyperexcitability in a porcine model of concussion
Communications Biology · 2023 · 9 citations
Senior authorCorresponding- Neuroscience
- Psychology
- Medicine
Cognitive impairment is a common symptom following mild traumatic brain injury (mTBI or concussion) and can persist for years in some individuals. Hippocampal slice preparations following closed-head, rotational acceleration injury in swine have previously demonstrated reduced axonal function and hippocampal circuitry disruption. However, electrophysiological changes in hippocampal neurons and their subtypes in a large animal mTBI model have not been examined. Using in vivo electrophysiology techniques, we examined laminar oscillatory field potentials and single unit activity in the hippocampal network 7 days post-injury in anesthetized minipigs. Concussion altered the electrophysiological properties of pyramidal cells and interneurons differently in area CA1. While the firing rate, spike width and amplitude of CA1 interneurons were significantly decreased post-mTBI, these parameters were unchanged in CA1 pyramidal neurons. In addition, CA1 pyramidal neurons in TBI animals were less entrained to hippocampal gamma (40-80 Hz) oscillations. Stimulation of the Schaffer collaterals also revealed hyperexcitability across the CA1 lamina post-mTBI. Computational simulations suggest that reported changes in interneuronal physiology may be due to alterations in voltage-gated sodium channels. These data demonstrate that a single concussion can lead to significant neuronal and circuit level changes in the hippocampus, which may contribute to cognitive dysfunction following mTBI.
Epilepsia Open · 2021 · 40 citations
- Political Science
- Medicine
- Political Science
Epilepsy is one of the most common chronic brain diseases and is often associated with cognitive, behavioral, or other medical conditions. The need for therapies that would prevent, ameliorate, or cure epilepsy and the attendant comorbidities is a priority for both epilepsy research and public health. In 2018, the National Institute of Neurological Disease and Stroke (NINDS) convened a workshop titled "Accelerating the Development of Therapies for Antiepileptogenesis and Disease Modification" that brought together preclinical and clinical investigators and industry and regulatory bodies' representatives to discuss and propose a roadmap to accelerate the development of antiepileptogenic (AEG) and disease-modifying (DM) new therapies. This report provides a summary of the discussions and proposals of the Preclinical Science working group. Highlights of the progress of collaborative preclinical research projects on AEG/DM of ongoing research initiatives aiming to improve infrastructure and translation to clinical trials are presented. Opportunities and challenges of preclinical epilepsy research, vis-à-vis clinical research, were extensively discussed, as they pertain to modeling of specific epilepsy types across etiologies and ages, the utilization of preclinical models in AG/DM studies, and the strategies and study designs, as well as on matters pertaining to transparency, data sharing, and reporting research findings. A set of suggestions on research initiatives, infrastructure, workshops, advocacy, and opportunities for expanding the borders of epilepsy research were discussed and proposed as useful initiatives that could help create a roadmap to accelerate and optimize preclinical translational AEG/DM epilepsy research.
eNeuro · 2020 · 19 citations
Senior authorCorresponding- Neuroscience
- Psychology
- Medicine
While hippocampal-dependent learning and memory are particularly vulnerable to traumatic brain injury (TBI), the functional status of individual hippocampal neurons and their interactions with oscillations are unknown following injury. Using the most common rodent TBI model and laminar recordings in CA1, we found a significant reduction in oscillatory input into the radiatum layer of CA1 after TBI. Surprisingly, CA1 neurons maintained normal firing rates despite attenuated input, but did not maintain appropriate synchronization with this oscillatory input or with local high-frequency oscillations. Normal synchronization between these coordinating oscillations was also impaired. Simultaneous recordings of medial septal neurons known to participate in theta oscillations revealed increased GABAergic/glutamatergic firing rates postinjury under anesthesia, potentially because of a loss of modulating feedback from the hippocampus. These results suggest that TBI leads to a profound disruption of connectivity and oscillatory interactions, potentially disrupting the timing of CA1 neuronal ensembles that underlie aspects of learning and memory.
Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation
Cell stem cell · 2020 · 484 citations
- Biology
- Cell biology
- Nanotechnology
Recent grants
Neuromodulation as a Therapy for PTSD following Chronic TBI
NIH · 2018–2028
Network Dysfunction and Neuromodulation following TBI
NIH · $3.3M · 2017–2028
Mechanisms of Cortico-Limbic Network Dysfunction Underlying PTSD after TBI
NIH · 2015–2018
Frequent coauthors
- 81 shared
D. Kacy Cullen
- 55 shared
H. Isaac Chen
- 44 shared
Douglas H. Smith
University of Pennsylvania
- 39 shared
Kevin D. Browne
University of Pennsylvania
- 31 shared
James P. Harris
University of Pennsylvania
- 25 shared
Daniel P. Brown
University of Cambridge
- 24 shared
Victoria E. Johnson
Creighton University
- 24 shared
Christopher D. Adam
University of Pennsylvania
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