David Seminowicz

Robarts Scientist, CFMM
Professor, Department of Medical Biophysics and Medical Imaging, Western University

David Seminowicz
Degree: Ph.D. Neuroscience (University of Toronto), B.Sc.H  Psychology (University of Guelph)
Email: dseminow@uwo.ca
Phone: 519.661.2111
X 24398
Office: RRI 1232D
Wesite https://www.daslab.org/

  

Dr. Seminowicz earned a BSc from the University of Guelph, a PhD at the University of Toronto and completed postdoctoral training at McGill University. He was faculty at University of Maryland, Baltimore, 2010-2022, Principal Research Scientist at Neuroscience Research Australia, in Sydney, 2019-2022, and joined Western in 2022. 

Research Summary

Dr. Seminowicz's work focuses on the cognitive aspects of pain, individual differences in the response to pain, and the consequence of chronic pain on brain structure and function. His studies have clarified how pain-related and cognitive-related brain activity interact and how passive and active pain coping strategies affect these types of activity. His work further suggested a brain mechanism through which chronic pain might affect cognitive ability and continues testing this hypothesis in intervention studies in people with chronic pain. The clinical populations in these studies include chronic low back pain, chronic and episodic migraine, and burning mouth syndrome. Dr. Seminowicz has also used rodent MRI to ask a question that could not easily be addressed in humans, such as how the brain changes over time from before the onset of an injury that leads to chronic pain to the time when the disease affects cognitive and affective behaviors. Ongoing studies in Dr. Seminowicz’s lab employ longitudinal designs to assess how interventions affect brain function and whether pain biomarkers can be developed. Another line of work examines the role of the claustrum in cognitive control and pain. The main techniques in his lab include quantitative sensory testing, EEG, structural and functional MRI, and simultaneous EEG-fMRI. His main funding has been from the NIH, intercampus initiatives, private foundations, and industry.

Research Questions

A novel pain biomarker

We have identified a reliable and simple to measure cortical biomarker of pain sensitivity. Peak alpha frequency, recorded from resting state, eyes closed EEG, was capable of predicting future pain sensitivity on the scales of minutes, hours, days, and months. We have replicated our initial findings in several different pain models. Further work has shown that peak alpha frequency is reliable and could be useful in various clinical settings. Ongoing work is validating this biomarker and including other cortical measures of sensorimotor cortex function for more precise prediction.

  • Chowdhury NS*, Bi C, Furman AJ*, Chiang AKI*, Skippen P*, Si E, Millard SK*, Margerison SM*, Spies D, Keaser ML, Da Silva JT, Chen S, Schabrun SM, Seminowicz DA. Predicting Individual Pain Sensitivity Using a Novel Cortical Biomarker Signature. JAMA Neurol. 2025 1:237-246 PMID: 39869323
  • Furman AJ*, Prokhorenko M, Keaser ML, Zhang J, Chen S, Mazaheri A, Seminowicz DA. Sensorimotor peak alpha frequency is a reliable biomarker of prolonged pain sensitivity. Cereb Cortex. 2020 30:6069-6082. PMID: 32591813
  • Furman AJ*, Meeker TJ*, Rietschel JC, Yoo S*, Muthulingam J*, Prokhorenko M, Keaser ML, Goodman RN, Mazaheri A, Seminowicz DA. Cerebral peak alpha frequency predicts individual differences in pain sensitivity. Neuroimage. 2018 167:203-210. PMID: 29175204

 

Neuroimaging of the claustrum

My group was the first to publish a neuroimaging study specifically focused on resolving claustrum-related connectivity and cognitive-related activation and we have since performed neuroimaging studies of the claustrum in mice, rats, marmosets, and humans. This work catalyzed a new research domain being spearheaded by my lab and our collaborators, particularly Brian Mathur, who is the first president of the International Claustrum Society and recognized as a world leader in claustrum research. We are leading the field in fundamental discoveries about claustrum structure, function, connectivity, and its role in cognitive control. We are currently using 7T functional MRI to better understand the role of the claustrum in pain and cognition.

  • Holzscherer EJ*, Zanini A, Liu CY*, Everling S, Seminowicz DA. Resting-state functional connectivity of the marmoset claustrum. Imaging Neurosci (Camb). 2025 3:IMAG.a.109. PMID: 40808791/  
  • Stewart BW*, Cormie MA*, Keaser ML, Moayedi M, Mathur BN, Seminowicz DA. The human claustrum initiates networks for externally and internally driven task demands. bioRxiv [Preprint]. 2025 PMID: 40666884
  • Stewart BW*, Keaser ML, Lee H, Margerison SM*, Cormie MA*, Moayedi M, Lindquist MA, Chen S, Mathur BN, Seminowicz DA. Pathological claustrum activity drives aberrant cognitive network processing in human chronic pain. Curr Biol. 2024 34:1953-1966.e6. PMID: 38614082
  • Madden MB*, Stewart BW*, White MG*, Krimmel SR*, Qadir H*, Barrett FS, Seminowicz DA, Mathur BN. A role for the claustrum in cognitive control. Trends Cogn Sci. 2022 26:1133-1152. PMID: 36192309

 

Affective and cognitive consequences of acute and chronic pain

Pain has sensory, cognitive, and emotional components, and people suffering from chronic pain often have cognitive impairment and emotional disruption (including mood, stress, and anxiety). Our lab studies the effects of acute and chronic pain on cognitive and affective function and brain circuitry. Our previous work has indicated that acute pain enhances cognitive-related brain network activity and suggested that people in chronic pain would have ongoing engagement of brain systems that could explain cognitive impairment. We further tested this in models of ongoing pain in healthy subjects and in clinical populations, and found that altered engagement of cognitive networks occurred in migraine, burning mouth syndrome, chronic low back pain, and fibromyalgia. In addition, we have shown brain functional and structural changes associated with affective components of pain, including increased recruitment of emotional neural circuitry related to pain catastrophizing and mood.

  • Čeko M, Gracely JL, Fitzcharles MA, Seminowicz DA, Schweinhardt P, Bushnell MC. Is a responsive default mode network required for successful working memory task performance? J Neurosci. 2015 35:11595-605. PMID: 26290236.
  • Khan SA, Keaser ML, Meiller TF, Seminowicz DA. Altered structure and function in the hippocampus and medial prefrontal cortex in patients with burning mouth syndrome. Pain. 2014 155:1472-80. PMID: 24769366 .
  •   Seminowicz DA, Davis KD. Cortical responses to pain in healthy individuals depends on pain catastrophizing. Pain. 2006 120:297-306. PMID: 16427738 .

 

Effects of chronic pain treatment on brain function and structure

Many studies have reported altered brain structure and function across most types of chronic pain conditions. We investigated whether these brain changes were reversible with treatment. We showed that treatment of chronic low back pain could result in a reversal of cortical thinning, particularly in the left dorsolateral prefrontal cortex (DLPFC), and similarly a reversal of impaired deactivation of this same brain area during cognitive task performance. The extent of recovery in the left DLPFC correlated with the effectiveness of the treatment in terms of reducing disability and pain. Furthermore, we showed that complex alteration of resting state cognitive networks – particularly involving the bilateral insula and the left DLPFC – was altered in chronic back pain and could be partially normalized with treatment. Later work on other nonpharmacological interventions for pain demonstrated the left DLPFC gray matter increased in association with a reduction of pain catastrophizing. Ongoing work examines treatment effects in larger clinical samples, including chronic and episodic migraine patients.

  • Čeko M, Shir Y, Ouellet JA, Ware MA, Stone LS, Seminowicz DA. Partial recovery of abnormal insula and dorsolateral prefrontal connectivity to cognitive networks in chronic low back pain after treatment. Hum Brain Mapp. 2015 36:2075-92. PMID: 25648842 .
  • Seminowicz DA, Shpaner M, Keaser ML, Krauthamer GM, Mantegna J, Dumas JA, Newhouse PA, Filippi CG, Keefe FJ, Naylor MR. Cognitive-behavioral therapy increases prefrontal cortex gray matter in patients with chronic pain. J Pain. 2013 14:1573-84. PMID: 24135432.
  • Seminowicz DA, Wideman TH, Naso L, Hatami-Khoroushahi Z, Fallatah S, Ware MA, Jarzem P, Bushnell MC, Shir Y, Ouellet JA, Stone LS. Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J Neurosci. 2011 31:7540-50. PMID: 21593339 .

 

Migraine mechanisms and treatment

We completed the first, fully powered randomized control trial of a mindfulness intervention for episodic migraine and showed that enhanced mindfulness-based stress reduction is an effective preventive treatment. In addition, our neuroimaging outcomes pointed to changes in cognitive networks. Our other work in migraine patients has contributed to the current literature by showing brain structural and functional changes associated with clinical variables, including migraine frequency, duration, intensity, and pain catastrophizing. We found that migraine patients had altered cognitive-related neural activity, which were primarily blunted task-related activations and deactivations. Notably, during acute pain and concomitant task performance, cognitive-related brain activity was similar between patient and controls. It also appeared that cognitive resources were being diverted from task-related to pain-modulatory-related processes in migraine. We also showed widespread morphological and functional brain abnormalities in migraineurs in affective, cognitive, visual, and pain-related brain areas, which are associated with increased pain catastrophizing, disease chronicity, and severity of symptoms, suggesting that these structural and functional changes may be a consequence of repeated, long-term nociceptive signaling leading to increased pain sensitivity, mood disturbances, and maladaptive coping strategies to deal with unrelenting pain. These findings will have important implications for our understanding of altered brain circuitry associated with the development and progression of migraine and could lead to better treatment options.

  • Krimmel SR, DeSouza DD, Keaser ML, Sanjanwala BM, Cowan RP, Lindquist MA, Haythornthwaite JA, Seminowicz DA. Three Dimensions of Association Link Migraine Symptoms and Functional Connectivity. J Neurosci. 2022 42:6156-6166. PMID: 35768210 .
  • Burrowes SAB, Goloubeva O, Stafford K, McArdle PF, Goyal M, Peterlin BL, Haythornthwaite JA, Seminowicz DA. Enhanced mindfulness-based stress reduction in episodic migraine-effects on sleep quality, anxiety, stress, and depression: A secondary analysis of a randomized clinical trial. Pain. 2021 163:436-444. PMID: 34407032
  • Seminowicz DA , Burrowes SAB, Kearson A, Zhang J, Krimmel SR, Samawi L, Furman AJ, Keaser ML, Gould NF, Magyari T, White L, Goloubeva O, Goyal M, Peterlin BL, Haythornthwaite JA. Enhanced mindfulness-based stress reduction in episodic migraine: A randomized clinical trial with magnetic resonance imaging outcomes. Pain. 2020 161:1837-1846. PMID: 32701843.

 

Rodent neuroimaging studies in pain

In addition to our human neuroimaging studies, we turn to rodent models to address problems that require invasive techniques to understand the brain mechanisms of chronic pain development and maintenance. Our first study demonstrated structural changes associated with a rat model of neuropathic pain: early and sustained gray matter volume decreases in sensory processing regions (thalamus, S1) that were correlated with pain sensitivity, and later volume decreases in prefrontal cortex, which was concurrent with the onset of anxiety-like behavior. In a follow-up study using functional MRI, we showed early increases in nociceptive-related activity in sensory areas, and later changes in prefrontal areas. In a third study, we showed altered thalamocortical connectivity in a model of spinal cord injury. We are currently studying the effects of stress in a visceral pain model. These studies allow us to tease apart early and late mechanisms of chronic pain and will allow for testing interventions at various stages and targeting specific cortical networks.                   

  • Da Silva JT, Tricou C, Zhang Y, Tofighbakhsh A, Seminowicz DA, Ro JY. Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats. Aging Cell. 2021 20:e13292. PMID: 33400367.
  • Seminowicz DA, Jiang L, Ji Y, Xu S, Gullapalli RP, Masri R. Thalamocortical asynchrony in conditions of spinal cord injury pain in rats. J Neurosci. 2012 32:15843-8. PMID: 23136423 .
  • Seminowicz DA, Laferriere AL, Millecamps M, Yu JS, Coderre TJ, Bushnell MC. MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain. Neuroimage. 2009 47:1007-14. PMID: 19497372 .

Lab Photo