Postdoctoral researcher at the Biobehavioral Pediatric Pain (BPP) Lab, Department of Anesthesiology, Perioperative, and Pain Medicine since October 2017, under supervision of Laura Simons. My PhD research focused on Cognitive Neuroscience and Metabolic Pediatrics (Jan 2011-April 2014, Maastricht University, Netherlands, under supervision of Bernadette Jansma and Estela Rubio-Gozalbo). After my PhD, I started my first postdoc at Maastricht University, at the Department of Cognitive Neuroscience and the Department of Rehabilitation Medicine, under supervision of Amanda Kaas and Jeroen de Jong. My main research interests include (pediatric) chronic pain, psychosocial and sensory aspects of (chronic) pain, and pain rehabilitation.

Honors & Awards

  • Scanning Circles of Pain Engagement (SCOPE), Maternal and Child Health Research Institute (MCHRI) Postdoctoral Support Grant (1-1-2019)

Professional Education

  • Bachelor of Science, Maastricht University (2008)
  • Master of Science, Maastricht University (2010)
  • Doctor of Philosophy, Maastricht University (2014)

Stanford Advisors

Research & Scholarship

Current Research and Scholarly Interests

My main research interests include (pediatric) chronic pain, psychosocial and sensory aspects of (chronic) pain, and pain rehabilitation. My main focus is on using neuroimaging techniques -both functional and structural MRI- combined with self-reports and sensory testing to unravel underlying mechanisms of pain rehabilitation treatment. I am interested both in adult chronic pain, as well as pediatric chronic pain and parental influences on treatment responses.


All Publications

  • Parent Responses to Their Child's Pain: Systematic Review and Meta-Analysis of Measures. Journal of pediatric psychology Harrison, L. E., Timmers, I., Heathcote, L. C., Fisher, E., Tanna, V., Duarte Silva Bans, T., Simons, L. E. 2020


    OBJECTIVE: Parent responses can have a major impact on their child's pain. The purpose of this systematic review is to (a) identify and describe measures assessing pain-related cognitive, affective, and behavioral responses in parents of children with chronic pain and (b) meta-analyze reported correlations between parent constructs and child outcomes (i.e., pain intensity, functional disability, and school functioning). Prospero protocol registration ID: CRD42019125496.METHODS: We conducted a systematic search of studies including a measure of parent/caregiver responses to their child's chronic pain. Study characteristics and correlations between parent measures and child outcomes were extracted. Data were summarized and meta-analyzed.RESULTS: Seventy-nine met inclusion criteria using 18 different measures of cognitive/affective (n=3), behavioral (n=5), and multidimensional responses (n=10). Measures were used a median of three times (range 1-48), predominantly completed by mothers (88%), and primarily in mixed pain samples. Psychometrics of measures were generally adequate. Meta-analyses were based on 42 papers across five measures. Results showed that each of the cognitive, affective, and behavioral parent constructs we examined was significantly associated with pain-related functional disability. A small number of measures assessing parent cognitions and affective functioning were associated with higher child pain intensity; however, the majority were not.CONCLUSION: Findings demonstrate that there is a wealth of measures available, with adequate reliability overall but a lack of psychometrics on temporal stability. Synthesizing data across studies revealed small effects between parent responses and child functioning, and even smaller and/or absent effects on child pain intensity.

    View details for DOI 10.1093/jpepsy/jsaa005

    View details for PubMedID 32150254

  • Rapid identification and clinical indices of fear-avoidance in youth with chronic pain. Pain Heathcote, L. C., Bhandari, R. P., Timmers, I., Harrison, L. E., Simons, L. E. 2019


    Pain-related fear and avoidance are increasingly demonstrated to play an important role in adult and childhood chronic pain. The Fear of Pain Questionnaire for Children (FOPQC) is a 24-item measure of pain-related fear-avoidance in youth that has demonstrated good indices of reliability and validity, treatment responsiveness, and associations with brain circuitry alterations. This study describes the development and psychometric examination of the FOPQC-SF, a short form of the original measure. We selected 10 items for the short form that best represented the content and two-factor (Fear and Avoidance) structure of the original measure from a cohort of 613 youth (Mage = 14.7 years) with chronic pain. Next, confirmatory factor analyses from a second sample of 526 youth (Mage = 14.7 years) with chronic pain who completed the FOPQC-SF supported the original two-factor model but indicated that one item should be moved to the avoidance subscale. The FOPQC-SF demonstrates strong internal consistency and moderate-to-strong construct and criterion validity. Three-month test-retest reliability estimates (N=94) were strong and there was preliminary evidence of responsivity to change. To aid integration into intervention trials and clinical practice, we provide clinical reference points and a criterion to assess reliable change. The short form could be used for rapid identification of pain-related fear and avoidance in youth during clinic evaluations, and is optimized for clinical registries.

    View details for DOI 10.1097/j.pain.0000000000001742

    View details for PubMedID 31688496

  • Exposure in vivo Induced Changes in Neural Circuitry for Pain-Related Fear: A Longitudinal fMRI Study in Chronic Low Back Pain FRONTIERS IN NEUROSCIENCE Timmers, I., de Jong, J. R., Goossens, M., Verbunt, J. A., Smeets, R. J., Kaas, A. L. 2019; 13
  • Parent psychological flexibility in the context of pediatric pain: Brief assessment and associations with parent behaviour and child functioning EUROPEAN JOURNAL OF PAIN Timmers, I., Simons, L. E., Hernandez, J. M., McCracken, L. M., Wallace, D. P. 2019; 23 (7): 1340?50

    View details for DOI 10.1002/ejp.1403

    View details for Web of Science ID 000475495900010

  • Pain neuroscience education on YouTube PEERJ Heathcote, L. C., Pate, J. W., Park, A. L., Leake, H. B., Moseley, G., Kronman, C. A., Fischer, M., Timmers, I., Simons, L. E. 2019; 7: e6603


    The Internet in general, and YouTube in particular, is now one of the most popular sources of health-related information. Pain neuroscience education has become a primary tool for managing persistent pain, based in part on the discovery that information about pain can change pain. Our objective was to examine the availability, characteristics, and content of YouTube videos that address the neuroscience of pain.We conducted a systematic review of videos on YouTube using the search terms "pain education", "what is pain", and "pain brain" in January 2018. Videos were included if they were in English, were under 10 minutes long, and included information on the neuroscience of pain. Videos were coded for (i) descriptive characteristics (e.g., number of views, duration on YouTube), (ii) source and style, (iii) whether or not they addressed seven pre-determined target concepts of pain neuroscience education (e.g., 'Pain is not an accurate marker of tissue state'), and (iv) how engaging they were.We found 106 unique videos that met the inclusion criteria. The videos ranged from having four views to over five million views (Mdn = 1,163 views), with the three most highly viewed videos accounting for 75% of the total views. Animated videos were much more highly viewed than non-animated videos. Only a small number of videos had been posted by a clearly-identifiable reputable source such as an academic or medical institution (10%), although a number of videos were posted by healthcare professionals and professional medical societies. For a small number of videos (7%), the source was unclear. We found 17 videos that addressed at least one target concept of pain neuroscience science education, only nine of which were considered to be at least somewhat engaging. The target concept 'Pain is a brain output' was considered to be well addressed by the most videos (N†=†11), followed by 'Pain is a protector' (N†=†10). We found only one video that adequately addressed all seven target concepts of pain neuroscience education.YouTube contains a variety of videos that practitioners, patients, and families may view to access pain neuroscience education information. A small portion of these videos addressed one or more target concepts of pain neuroscience education in an engaging manner. It is yet to be determined to what extent patients are able to learn information from these videos, to what extent the videos promote behavior change, and thus to what extent the videos may be useful for clinical practice.

    View details for PubMedID 30923652

  • Exposure in vivo Induced Changes in Neural Circuitry for Pain-Related Fear: A Longitudinal fMRI Study in Chronic Low Back Pain. Frontiers in neuroscience Timmers, I., de Jong, J. R., Goossens, M., Verbunt, J. A., Smeets, R. J., Kaas, A. L. 2019; 13: 970


    Exposure in vivo (EXP) is a cognitive-behavioral treatment aimed at reducing pain-related fear in chronic pain, and has proven successful in reducing pain-related disability in patients with chronic low back pain (cLBP). The current longitudinal study aimed to reveal the neural correlates of changes in pain-related fear as a result of EXP. Twenty-three patients with cLBP were included in this study. Patients with cLBP underwent MRI scanning pre-treatment (pre-EXP), post-treatment (post-EXP), and 6 months after end of treatment (FU-EXP). Pain-free controls were scanned at two time points. In the scanner, participants were presented with pictures involving back-related movements, evoking pain-related fear in patients. Pre-treatment, functional MRI revealed increased activation in right posterior insula and increased deactivation in medial prefrontal cortex (mPFC) in patients compared to controls. Post-treatment, patients reported reduced fear and pre-EXP group differences were no longer present. Contrasting pre- to post- and FU-EXP in patients revealed that stimulus-evoked neural responses changed in sensorimotor as well as cognitive/affective brain regions. Lastly, exploratory analyses revealed a tendency toward an association between changes in neural activation and changes in fear ratings, including the hippocampus and temporal lobe (pre- to post-EXP changes), and mPFC and posterior cingulate cortex (pre- to FU-EXP changes). Taken together, we show evidence that neural circuitry for pain-related fear is modulated by EXP, and that changes are associated with self-reported decreases in pain-related fear.

    View details for DOI 10.3389/fnins.2019.00970

    View details for PubMedID 31607840

    View details for PubMedCentralID PMC6758595

  • Brain signatures of threat-safety discrimination in adolescent chronic pain. Pain Heathcote, L. C., Timmers, I., Kronman, C. A., Mahmud, F., Hernandez, J. M., Bentley, J., Youssef, A. M., Pine, D. S., Borsook, D., Simons, L. E. 2019


    Approximately 1.7 million youth suffer from debilitating chronic pain in the US alone, conferring risk for continued pain in adulthood. Abberations in threat-safety (T-S) discrimination are proposed to contribute to pain chronicity in adults and youth by interacting with pain-related distress. Yet, few studies have examined the neural circuitry underlying T-S discrimination in patients with chronic pain or how T-S discrimination relates to pain-related distress. In this study, 91 adolescents (10-24 years; 78 females) including 30 chronic pain patients with high pain-related distress, 29 chronic pain patients with low pain-related distress, and 32 healthy peers without chronic pain completed a developmentally-appropriate T-S learning paradigm. We measured self-reported fear, psychophysiology (skin conductance response), and functional MRI responses (N = 72 after fMRI exclusions). After controlling for age and anxiety symptoms, patients with high pain-related distress showed altered self-reported fear and fronto-limbic activity in response to learned threat and safety cues compared to both patients with low pain-related distress and healthy controls. Specifically, adolescent patients with high pain-related distress reported elevated fear and showed elevated limbic (hippocampus, amygdala) activation in response to a learned threat cue (CS+). In addition, they showed decreased frontal (vmPFC) activation and aberrant fronto-limbic connectivity in response to a learned safety cue (CS-). Patients with low pain-related distress and healthy controls appeared strikingly similar across brain and behavior. These findings indicate that altered T-S discrimination, mediated by fronto-limbic activation and connectivity, may be one mechanism maintaining pain chronicity in adolescents with high levels of pain-related distress.

    View details for DOI 10.1097/j.pain.0000000000001753

    View details for PubMedID 31764389

  • The interaction between stress and chronic pain through the lens of threat learning. Neuroscience and biobehavioral reviews Timmers, I., Quaedflieg, C. W., Hsu, C., Heathcote, L. C., Rovnaghi, C. R., Simons, L. E. 2019


    Stress and pain are interleaved at multiple levels - interacting and influencing each other. Both are modulated by psychosocial factors including fears, beliefs, and goals, and are served by overlapping neural substrates. One major contributing factor in the development and maintenance of chronic pain is threat learning, with pain as an emotionally-salient threat - or stressor. Here, we argue that threat learning is a central mechanism and contributor, mediating the relationship between stress and chronic pain. We review the state of the art on (mal)adaptive learning in chronic pain, and on effects of stress and particularly cortisol on learning. We then provide a theoretical integration of how stress may affect chronic pain through its effect on threat learning. Prolonged stress, as may be experienced by patients with chronic pain, and its resulting changes in key brain networks modulating stress responses and threat learning, may further exacerbate these impairing effects on threat learning. We provide testable hypotheses and suggestions for how this integration may guide future research and clinical approaches in chronic pain.

    View details for DOI 10.1016/j.neubiorev.2019.10.007

    View details for PubMedID 31622630

  • Is Empathy for Pain Unique in Its Neural Correlates? A Meta-Analysis of Neuroimaging Studies of Empathy FRONTIERS IN BEHAVIORAL NEUROSCIENCE Timmers, I., Park, A. L., Fischer, M. D., Kronman, C. A., Heathcote, L. C., Hernandez, J., Simons, L. E. 2018; 12
  • Precipitating events in child and adolescent chronic musculoskeletal pain. Pain reports Becker, A. J., Heathcote, L. C., Timmers, I., Simons, L. E. 2018; 3 (Suppl 1): e665


    Introduction: The epidemiology of chronic pain in youth has been increasingly documented over the past decade. However, the precipitating events associated with the onset of pediatric chronic pain are not well studied.Objectives: Understanding the events that precede the onset of pain, and are reported by patients as germane to the early stages of their pain, may add one piece to the puzzle of the causal etiology of pediatric chronic pain disorders.Methods: We conducted a retrospective chart review of 320 young people attending a tertiary care chronic pain clinic with musculoskeletal chronic pain.Results: Approximately two-thirds of patients reported a precipitating event for their pain; injury was the most commonly reported event, followed by a chronic disease, then an infection or illness. Surgery was the least commonly reported event. About one-third of patients did not report any precipitating event for their pain. Patients with neuropathic pain were even more likely to report a precipitating event compared to those with localized and diffuse musculoskeletal pain. Patients with localized musculoskeletal pain and neuropathic pain were most likely to report an injury, whereas patients with diffuse musculoskeletal pain were most likely to report a chronic disease. We found little to no evidence that the presence or type of precipitating event was associated with patients' psychological or physical functioning.Conclusion: This study adds to the epidemiological evidence base for pediatric chronic pain disorders.

    View details for PubMedID 30324167

  • Fear of pain and cortisol reactivity predict the strength of stress-induced hypoalgesia EUROPEAN JOURNAL OF PAIN Timmers, I., Kaas, A. L., Quaedflieg, C. M., Biggs, E. E., Smeets, T., de Jong, J. R. 2018; 22 (7): 1291?1303


    Acute stress can have an effect on pain sensitivity, yet the direction of the effect - whether it is hypoalgesic or hyperalgesic - is mixed across studies. Moreover, which part of the stress response influences pain sensitivity is still unclear. In the current experimental study, we aim to examine the effect of acute stress on heat pain thresholds and pain tolerance levels in healthy participants, while taking into account individual differences in stress responses.Forty-two healthy participants were randomly assigned to either a well-validated stress paradigm: the Maastricht Acute Stress Task (MAST; combining physical and psychological stressors) or to a nonstressful version of the task. Heat pain thresholds and tolerance levels were assessed at three times: prior to the MAST, immediately after the MAST during the presumed sympatho-adrenal medullary (SAM) response, and 15†min after MAST to cover the presumed hypothalamus-pituitary-adrenal (HPA) axis response. Stress responses were assessed both subjectively and physiologically.We observed that the acute stress induction led to increased heat pain thresholds, an effect that was present only in participants showing a cortisol response following stress induction and only in the presumed HPA axis time window. The strength of this hypoalgesic effect was further predicted by the change in cortisol and by fear of pain levels.Our findings indicate that the HPA axis - and not the autonomic - stress response specifically underlies this stress-induced hypoalgesic effect, having important implications for clinical states with HPA axis dysfunctions.This experimental study shows that an acute stress induction - that combines physical and psychological stressors - increases heat pain thresholds, but not tolerance in healthy participants. Furthermore, the magnitude of this stress-induced hypoalgesic effect is predicted by cortisol reactivity and fear of pain, revealing specific involvement of the HPA axis stress system and interactions with pain-related psychosocial aspects.

    View details for PubMedID 29577522

  • Atypical White Matter Connectivity in Dyslexic Readers of a Fairly Transparent Orthography FRONTIERS IN PSYCHOLOGY Zaric, G., Timmers, I., Gerretsen, P., Gonzalez, G., Tijms, J., van der Molen, M. W., Blomert, L., Bonte, M. 2018; 9
  • Is Empathy for Pain Unique in Its Neural Correlates? A Meta-Analysis of Neuroimaging Studies of Empathy. Frontiers in behavioral neuroscience Timmers, I., Park, A. L., Fischer, M. D., Kronman, C. A., Heathcote, L. C., Hernandez, J. M., Simons, L. E. 2018; 12: 289


    Empathy is an essential component of our social lives, allowing us to understand and share other people's affective and sensory states, including pain. Evidence suggests a core neural network-including anterior insula (AI) and mid-cingulate cortex (MCC)-is involved in empathy for pain. However, a similar network is associated to empathy for non-pain affective states, raising the question whether empathy for pain is unique in its neural correlates. Furthermore, it is yet unclear whether neural correlates converge across different stimuli and paradigms that evoke pain-empathy. We performed a coordinate-based activation likelihood estimation (ALE) meta-analysis to identify neural correlates of empathy, assess commonalities and differences between empathy for pain and for non-pain negative affective states, and differences between pain-empathy evoking stimuli (i.e., facial pain expressions vs. acute pain inflictions) and paradigms (i.e., perceptual/affective vs. cognitive/evaluative paradigms). Following a systematic search, data from 128 functional brain imaging studies presenting whole-brain results of an empathy condition vs. baseline/neutral condition were extracted. Synthesizing neural correlates of empathy confirmed a core network comprising AI, MCC, postcentral gyrus, inferior parietal lobe, thalamus, amygdala, and brainstem. There was considerable overlap in networks for empathy for pain and empathy for non-pain negative affective states. Important differences also arose: empathy for pain uniquely activated bilateral mid-insula and more extensive MCC. Regarding stimuli, painful faces and acute pain inflictions both evoked the core empathy regions, although acute pain inflictions activated additional regions including medial frontal and parietal cortex. Regarding paradigms, both perceptual/affective and cognitive/evaluative paradigms recruited similar neural circuitry, although cognitive/evaluative paradigms activated more left MCC regions while perceptual/affective paradigms activated more right AI. Taken together, our findings reveal that empathy for pain and empathy for non-pain negative affective states share considerable neural correlates, particularly in core empathy regions AI and MCC. Beyond these regions, important differences emerged, limiting generalizability of findings across different affective/sensory states. Within pain-empathy studies, the core regions were recruited robustly irrespective of stimuli or instructions, allowing one to tailor designs according to specific needs to some extent, while ensuring activation of core regions.

    View details for PubMedID 30542272

    View details for PubMedCentralID PMC6277791

  • Atypical White Matter Connectivity in Dyslexic Readers of a Fairly Transparent Orthography. Frontiers in psychology ?ari?, G., Timmers, I., Gerretsen, P., Fraga GonzŠlez, G., Tijms, J., van der Molen, M. W., Blomert, L., Bonte, M. 2018; 9: 1147


    Atypical structural properties of the brain's white matter bundles have been associated with failing reading acquisition in developmental dyslexia. Because these white matter properties may show dynamic changes with age and orthographic depth, we examined fractional anisotropy (FA) along 16 white matter tracts in 8- to 11-year-old dyslexic (DR) and typically reading (TR) children learning to read in a fairly transparent orthography (Dutch). Our results showed higher FA values in the bilateral anterior thalamic radiations of DRs and FA values of the left thalamic radiation scaled with behavioral reading-related scores. Furthermore, DRs tended to have atypical FA values in the bilateral arcuate fasciculi. Children's age additionally predicted FA values along the tracts. Together, our findings suggest differential contributions of cortical and thalamo-cortical pathways to the developing reading network in dyslexic and typical readers, possibly indicating prolonged letter-by-letter reading or increased attentional and/or working memory demands in dyslexic children during reading.

    View details for PubMedID 30042708

    View details for PubMedCentralID PMC6049043

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