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THE CLINICAL CLARITY BLOG
Knees, Spines and the Bayesian Brain
Part 3
July 18, 2022 by DR MATTHEW D. LONG
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THE CLINICAL CLARITY BLOG
Knees, Spines and the Bayesian Brain
Part 3
July 18, 2022 by DR MATTHEW D. LONG
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THE CLINICAL CLARITY BLOG
July 18, 2022 by DR MATTHEW D. LONG
In the first two parts of this series (here and here) we examined the idea that the brain is a 'Bayesian probability machine' that constantly generates hypotheses about the body, and then uses them to determine whether we should be 'in pain' or not. As Brenner described it in an article on Medium.com, "Cognitive Science is realizing that the brain is not just a detector that passively takes in information about the world and reacts to it. It constantly shapes its vision of the world by making assumptions about how the world is and how the world will be, doing so in a top-down manner" (1). As such, we should not think of pain as an input to the brain - it is an output. In other words, it is a behavioural response. Interestingly, pain is not the only sensory experience that the brain might generate in response to perceived injury. About 30% of those with knee osteoarthritis report that their knee feels swollen, in spite of no objective markers of enlargement (2). Most experienced clinicians would have faced a patient that is convinced their knee is swollen, despite evidence to the contrary. Tanaka et al (2) suggests that,
"The tentative conclusion from these findings is that people who perceive their knees to be swollen in the absence of measurable effusion may be experiencing changes in how their knees are represented within the central nervous system (based on two-point discrimination findings) and have less confidence in using the knee and more maladaptive beliefs about the knee in pain."
Intriguingly, such patients typically 'see' their knee as enlarged, and find it hard to reconcile your counter-claim when proven with a simple tape-measure. However, we should understand that our experience of the world is highly integrated, and that each of our senses informs the others. What we hear is influenced by what we see (as shown in the video of the McGurk effect in part 2 of this series). And what we see is influenced by what we feel. Thus, patients who feel that their knee is swollen will see it as enlarged, an artefact of perception that arises from the brain's erroneous prediction.
Within the spine, movement-related prediction error often results in feelings of stiffness. This makes sense, if we appreciate that the brain is attempting to limit trunk motor variability and rein in the amount of allowable movement. But if we examine what's occurring within our patients, the waters get murkier. Indeed, in the acute phase, the literature suggests that the experience of 'feeling stiff' does not reflect the objective state of the biomechanical structures. Stanton et al (14) examined patients with back pain and tried to correlate their subjective description of stiffness with objective measurements. They found none. In other words, the patient's sensation of back stiffness did not mirror the anatomical reality of their spinal structures, and may simply be a mechanism to limit movement. They write that the stiffness patients describe may not be a 'resistance to movement', rather, it "may be a learned concept for what is actually a feeling of a lack of movement velocity." They also described stiffness as "protective perceptual inference that may serve to reduce movement and re-injury." So these feelings of stiffness may actually reflect an enforced slowing of movement, rather than an objective rigidity.
However, this strategy of reducing movement may cause significant consequences in the long term, as habits form and plasticity ensues. Meier et al (10) state that, "This might provide an explanation for cortical sensorimotor reorganization associated with a stable and more rigid but unfavorable motor control pattern, potentially leading to sustained increases in spinal loading, degeneration of spinal tissues, and muscle fatigue." These adverse anatomical changes have been documented by various researchers. For example, Wesselink and colleagues (11) looked at how the loss of fine, individual motor control of the back musculature is accompanied by a loss of individual cortical drive to the paraspinal muscles. This, in turn, seems to be associated with reduced muscular metabolic activity, and thence a greater fatty infiltration of the erector spinae. This change in the tissue composition of the spinal musculature also comes at a cost to the brain. Reduced muscle mass and tone, and the incorporation of greater fat content, will also diminish the sensory capacity of the spine and lead to greater proprioceptive error. And so the cycle persists.
When faced with uncertainty, and ongoing prediction error, the brain has two choices to resolve the situation. It can:
Within the spine, movement-related prediction error often results in feelings of stiffness. This makes sense, if we appreciate that the brain is attempting to limit trunk motor variability and rein in the amount of allowable movement. But if we examine what's occurring within our patients, the waters get murkier. Indeed, in the acute phase, the literature suggests that the experience of 'feeling stiff' does not reflect the objective state of the biomechanical structures. Stanton et al (14) examined patients with back pain and tried to correlate their subjective description of stiffness with objective measurements. They found none. In other words, the patient's sensation of back stiffness did not mirror the anatomical reality of their spinal structures, and may simply be a mechanism to limit movement. They write that the stiffness patients describe may not be a 'resistance to movement', rather, it "may be a learned concept for what is actually a feeling of a lack of movement velocity." They also described stiffness as "protective perceptual inference that may serve to reduce movement and re-injury." So these feelings of stiffness may actually reflect an enforced slowing of movement, rather than an objective rigidity.
However, this strategy of reducing movement may cause significant consequences in the long term, as habits form and plasticity ensues. Meier et al (10) state that, "This might provide an explanation for cortical sensorimotor reorganization associated with a stable and more rigid but unfavorable motor control pattern, potentially leading to sustained increases in spinal loading, degeneration of spinal tissues, and muscle fatigue." These adverse anatomical changes have been documented by various researchers. For example, Wesselink and colleagues (11) looked at how the loss of fine, individual motor control of the back musculature is accompanied by a loss of individual cortical drive to the paraspinal muscles. This, in turn, seems to be associated with reduced muscular metabolic activity, and thence a greater fatty infiltration of the erector spinae. This change in the tissue composition of the spinal musculature also comes at a cost to the brain. Reduced muscle mass and tone, and the incorporation of greater fat content, will also diminish the sensory capacity of the spine and lead to greater proprioceptive error. And so the cycle persists.
When faced with uncertainty, and ongoing prediction error, the brain has two choices to resolve the situation. It can:
1. Change the sensory input
2. Change what we believe about the sensory input
2. Change what we believe about the sensory input
In other words, we can use a 'bottom-up' approach to improve the quality of incoming data to the brain, or a 'top-down' approach to change the brain's meaning perspective on the inputs that it is receiving. As chiropractors, we have an ability to do both - through our manual interventions and through education. This dualistic approach to management is critical when faced with a patient suffering from chronic pain. According to Silfies et al (3),
"Historically, interventions that address only the predominant model of peripheral drivers such as specific muscle strengthening exercise and locally applied pain reduction modalities have had limited success in the rehabilitation of people with persistent musculoskeletal pain. Traditionally, the targeting of the peripheral system has focused on the motor system (muscles), with less consideration to the somatosensory aspects (e.g., proprioceptive exercises, postural control challenges, recovery from perturbations). In addition, there is often failure to move beyond 'exercises' to focus on retraining both simple and complex functional movement patterns to restore appropriate and flexible movement strategies. Perhaps this approach has been less successful given potential sensorimotor conflict that can contribute to a patient’s difficulty in learning exercises and new movement patterns without direct intervention and intensive sensorimotor retraining. As previously mentioned, practice of a motor task has been associated with expansion of S1 regions activated during the task and, importantly, may assist in improving the appropriate weighting of proprioceptive information in the region of the musculoskeletal injury. Thus, rehabilitation for painful musculoskeletal disorders may require specific intervention to address the sensory-motor conflict that hinders retraining of functional movement patterns. Suggested interventions include explicit training of sensory discrimination, practicing movement and muscle activation patterns while providing adequate feedback (e.g., visual or auditory cuing, sensory cuing) and reward (must occur simultaneously) with the execution of correct patterns."
Fortunately, the anatomical changes that we see in chronic pain patients appear to be reversible (20,21). Seminowicz and colleagues (12) found "strong evidence that pain-related neuroanatomical and functional changes are reversible with effective treatment." In their study they noted that the left dorsolateral prefrontal cortex was thinner and activated 'abnormally' in chronic low back pain sufferers prior to treatment. However, after treatment, "the same region became thicker and also functioned more similarly to controls on a cognitive task." Ceko et al (13) similarly found that successful treatment (either facet joint injections or surgery) also improved functional connectivity between the dorsolateral prefrontal cortex and the insula (a central structure in the pain neuromatrix).
But how do we achieve this?
But how do we achieve this?
THE 'BOTTOM-UP' APPROACH
Let's first consider how we might alter the sensory input to the brain, so that it might update its flawed model and distorted understanding of the body (which leads to pain). In the case of our patient with prolonged pain after a total knee replacement, we need to find ways of improving proprioceptive feedback so as to facilitate re-mapping of the joint within the somatosensory system. Interestingly, we could begin with something as simple as a soft knee brace.
There have been many theories put forward about why the humble soft brace might be helpful. But the current hypothesis is that it assists sensorimotor integration by stimulating cutaneous (skin) receptors (4,5,6), and not by simply 'supporting' the knee mechanically or reducing synovial irritation (6). Furthermore, it has been suggested that a slightly looser fit is preferable to a tight support. Cudejko et al (4) wrote that,
There have been many theories put forward about why the humble soft brace might be helpful. But the current hypothesis is that it assists sensorimotor integration by stimulating cutaneous (skin) receptors (4,5,6), and not by simply 'supporting' the knee mechanically or reducing synovial irritation (6). Furthermore, it has been suggested that a slightly looser fit is preferable to a tight support. Cudejko et al (4) wrote that,
"...a non-tight brace provides more recurrent stimuli by allowing movement between the brace and the skin and thus elicits continuous response from cutaneous mechanical receptors. In contrast, a tight brace might provide constant pressure to which skin mechanoreceptors may adapt. We observed that a non-tight brace significantly reduced the amount of deviation in varus/valgus angles, while a tight brace did not. These reports suggest the potential role of the somatosensory system in the processing of proprioceptive input and highlight the importance of sensorimotor mechanisms in providing joint stability."
Other novel forms of sensory training can also be employed - all with the goal of enhancing sensory representation of the knee within the brain. After all, the brain can only regulate what it can sense, and chronic pain suffers often demonstrate a reduction in sensory acuity within the affected area. According to Moseley (8), this disruption of cortical representation leads to imprecision in movement, but this lost function can be regained. He suggests that 'sensory discrimination training' is a useful strategy, and describes it thus,
"Sensory discrimination training was first developed for the treatment of phantom limb pain in amputees, on the basis of a very strong relationship between phantom limb pain (but not nonpainful phantom limb feelings) and reorganization of the primary sensory cortex (S1). Sensory discrimination training involved a range of different stimuli being delivered to the stump and the patient discriminating between them on the basis of location and quality of the tactile input. Patients showed correlated improvement in pain and normalization of cortical responses to tactile stimuli delivered to the face — an area adjacent in primary sensory cortex to the hand. Discovery of cortical reorganization in people with complex regional pain syndrome — although for critical clarifications of the initial data — led to an initial investigation of tactile discrimination training in that group, with preliminary data appearing promising. S1 reorganization is also present in people with back pain. Tactile discrimination training has been attempted as a stand-alone treatment for back pain. A recent systematic review showed that most trials show reductions of pain that are statistically significant, suggesting it might be useful as part of multimodal intervention in appropriate patients."
Such techniques have also been applied to the rehabilitation of chronic lower back pain, with Moseley (8) stating that, "We have now learnt that specific contraction of particular muscles, most often the lumbar multifidus or the transversus abdominis, partially normalizes primary motor cortex (M1) disorganization in people with back pain, as well as the abnormal activation of these muscles during postural tasks." But what else might we do? How might manipulation play a role in a patient's recovery? Can we use manipulation as a tool to change sensory input from the spinal tissues back to the brain?
Every time that we interact with a patient's tissues (muscles, joint structures etc), we create a complex discharge of neural firing that encodes the characteristics of our touch, to help the brain understand what is happening. Different types of input create their own unique 'sensory signature', depending upon the blend of mechanosensitive afferents that are stimulated. It is easy to appreciate that a high-velocity, low amplitude manipulation will create a different 'signature' to a low-velocity mobilisation, or deep-tissue massage, or even dry-needling. But all of these inputs can be useful when we seek to help the brain make greater sense of a deconditioned area of the body. The application of a novel sensory stimulus will usually result in the brain paying greater attention to it, as it strives to make sense of the new input. It has been theorised that this will, over time, allow the brain to update its model of the spine and enhance its ability to control movement. In turn, this decrease in ambiguity means that less pain is required to protect the area.
Advanced neuroimaging techniques have been quite helpful in understanding how the brain reacts to a manipulation. Isenburg et al (9) used functional MRI to compare the effects of manipulation and mobilisation, to determine the brain regions that are most strongly influenced by these inputs. In particular, they found that manipulation (but not mobilisation) increased the integration of the salience network (an area of the brain that is associated with pain severity in chronic pain patients) with the thalamus and the motor cortex (M1). The authors described the role of the salience network as "essential in the processing of sensory stimuli, as the salience network plays a key role in the assessment of the inherent danger of such stimuli and how one should respond to them."
Ellingsen and colleagues (15) showed that spinal manipulation can reduce the limbic response to potentially painful movements, in a fashion that is similar to 'desensitising' programs for the treatment of anxiety/phobias. The application of a forceful, but not harmful, thrust to the sensitive spinal tissues seems to help the brain learn that it can tolerate greater movement without additional injury. Following successful treatment a patient's brain is less likely to generate a pain/fear response during movements that were previously painful.
Every time that we interact with a patient's tissues (muscles, joint structures etc), we create a complex discharge of neural firing that encodes the characteristics of our touch, to help the brain understand what is happening. Different types of input create their own unique 'sensory signature', depending upon the blend of mechanosensitive afferents that are stimulated. It is easy to appreciate that a high-velocity, low amplitude manipulation will create a different 'signature' to a low-velocity mobilisation, or deep-tissue massage, or even dry-needling. But all of these inputs can be useful when we seek to help the brain make greater sense of a deconditioned area of the body. The application of a novel sensory stimulus will usually result in the brain paying greater attention to it, as it strives to make sense of the new input. It has been theorised that this will, over time, allow the brain to update its model of the spine and enhance its ability to control movement. In turn, this decrease in ambiguity means that less pain is required to protect the area.
Advanced neuroimaging techniques have been quite helpful in understanding how the brain reacts to a manipulation. Isenburg et al (9) used functional MRI to compare the effects of manipulation and mobilisation, to determine the brain regions that are most strongly influenced by these inputs. In particular, they found that manipulation (but not mobilisation) increased the integration of the salience network (an area of the brain that is associated with pain severity in chronic pain patients) with the thalamus and the motor cortex (M1). The authors described the role of the salience network as "essential in the processing of sensory stimuli, as the salience network plays a key role in the assessment of the inherent danger of such stimuli and how one should respond to them."
Ellingsen and colleagues (15) showed that spinal manipulation can reduce the limbic response to potentially painful movements, in a fashion that is similar to 'desensitising' programs for the treatment of anxiety/phobias. The application of a forceful, but not harmful, thrust to the sensitive spinal tissues seems to help the brain learn that it can tolerate greater movement without additional injury. Following successful treatment a patient's brain is less likely to generate a pain/fear response during movements that were previously painful.
'TOP-DOWN' TECHNIQUES
We can also help our chronic pain patients using a 'top-down' approach, in which we directly influence the brain's belief about what a sensory input might mean. One of the techniques available is motor imagery, which has been used successfully in treated patients with knee osteoarthritis, lower back pain (16), and also following total knee replacement. According to Briones-Cantero et al (17),
"In the early postsurgical phase of total knee arthroplasty, patients’ mobility is severely limited due to pain and high irritability. One intervention that might effectively allow working with no movement and, thus, no pain, is motor imagery (MI). MI is a type of movement representation technique where a patient mentally simulates a movement/action without real execution. Interestingly, MI leads to activation of the same neuronal networks as those activated by real movement, contributing to improvement of motor performance and learning of new motor skills. The underlying neural substrate of MI is the mirror neurons system, which is activated when imaging movements but also when observing others performing movement. The application of MI may allow to patients feel themselves performing the movement with no pain when movement is actually not possible or is difficult due to irritability or pain, thus resulting in positive outcomes."
Perhaps the most studied top-down approach is Pain Neuroscience Education. This is a technique that seeks to challenge a patient's beliefs about the nature of pain generally, and what might be causing their pain specifically (18). Importantly, such education is not simply the addition of new information on top of the patient's existing belief system. We must actually de-educate the patient, and their faulty beliefs, before re-educating them. Leake et al (18) have found that there are three important themes to tackle during this process:
1. Pain does not mean my body is damaged
2. Thoughts, emotions and experiences affect pain
3. I can retrain my overprotective pain system
2. Thoughts, emotions and experiences affect pain
3. I can retrain my overprotective pain system
But does this mean that we can simply talk our patients out of pain? Is it really that simple? Usually not, according to Shala et al (19),
"We need to provide the opportunities for patients to experience activity and exercise without any significant flare up of their pain. They need to be shown they can regain their daily life again. Therefore, it is important to combine pain neuroscience education (PNE) with other treatment modalities such as exercise and even manual therapy, and this has been termed, PNE+."
Indeed, there is a large accruing body of evidence that chronic pain patients do best when we combine re-education with treatment and exercise (22,23,24,25). In other words, we should use a 'top-down' and a 'bottom-up' approach for maximum effect. Over time, with better quality sensory input and a refined meaning perspective, the brain can enhance its understanding of the painful area and reduce prediction error accordingly.
Something to think about...
Dr Matthew D. Long
BSc (Syd), M.Chiro (Macq), DIANM
Dr Matthew D. Long
BSc (Syd), M.Chiro (Macq), DIANM
References:
1. Brenner, M. (2019). The Bayesian Brain Hypothesis - How our brain evolved to look into the future. https://towardsdatascience.com/the-bayesian-brain-hypothesis-35b98847d331
2. Tanaka, S. et al. “But it feels swollen!”: the frequency and clinical characteristics of people with knee osteoarthritis who report subjective knee swelling in the absence of objective swelling. Pain Reports 6, e971 (2021)
3. Silfies, S. P., Vendemia, J. M. C., Beattie, P. F., Stewart, J. C., & Jordon, M. (2017). Changes in Brain Structure and Activation May Augment Abnormal Movement Patterns: An Emerging Challenge in Musculoskeletal Rehabilitation. Pain Medicine (Malden, Mass), 18(11), 2051–2054. http://doi.org/10.1093/pm/pnx190
4. Cudejko, T., van der Esch, M., Schrijvers, J., Richards, R., van den Noort, J. C., Wrigley, T., et al. (2018). The immediate effect of a soft knee brace on dynamic knee instability in persons with knee osteoarthritis. Rheumatology (Oxford, England), 57(10), 1735–1742. http://doi.org/10.1093/rheumatology/key162
5. Cudejko, T., van der Esch, M., van der Leeden, M., Roorda, L. D., Pallari, J., Bennell, K. L., et al. (2018). Effect of Soft Braces on Pain and Physical Function in Patients With Knee Osteoarthritis: Systematic Review With Meta-Analyses. Archives of Physical Medicine and Rehabilitation, 99(1), 153–163. http://doi.org/10.1016/j.apmr.2017.04.029
6. Thijs, Y., Vingerhoets, G., Pattyn, E., Rombaut, L., & Witvrouw, E. (2010). Does bracing influence brain activity during knee movement: an fMRI study. Knee Surgery, Sports Traumatology, Arthroscopy, 18(8), 1145–1149. http://doi.org/10.1007/s00167-009-1012-9
7. Swaminathan, V., Parkes, M. J., Callaghan, M. J., O'Neill, T. W., Hodgson, R., Gait, A. D., & Felson, D. T. (2017). With a biomechanical treatment in knee osteoarthritis, less knee pain did not correlate with synovitis reduction. BMC Musculoskelet Disord, 18(1), 289–7. http://doi.org/10.1186/s12891-017-1691-1
8. Moseley, G. L. (2017). Innovative treatments for back pain. Pain, 158 Suppl 1, S2–S10. http://doi.org/10.1097/j.pain.0000000000000772
9. Isenburg, K. et al. Increased salience network connectivity following manual therapy is associated with reduced pain in chronic low back pain patients. J Pain 22, 545–555 (2020)
10. Meier, M. L., Vrana, A., & Schweinhardt, P. (2019). Low Back Pain: The Potential Contribution of Supraspinal Motor Control and Proprioception. The Neuroscientist, 25(6), 583–596. http://doi.org/10.1177/1073858418809074
11. Wesselink, E., de Raaij, E., Pevenage, P., van der Kaay, N., & Pool, J. (2019). Fear-avoidance beliefs are associated with a high fat content in the erector spinae: a 1.5 tesla magnetic resonance imaging study. Chiropractic & Manual Therapies, 27(1), 1714–8. http://doi.org/10.1186/s12998-019-0234-2
12. Seminowicz, D. A., Wideman, T. H., Naso, L., Hatami-Khoroushahi, Z., Fallatah, S., Ware, M. A., et al. (2011). Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. The Journal of Neuroscience, 31(20), 7540–7550. http://doi.org/10.1523/JNEUROSCI.5280-10.2011
13. Ceko, M. et al. Partial recovery of abnormal insula and dorsolateral prefrontal connectivity to cognitive networks in chronic low back pain after treatment. Human Brain Mapping 36, 2075–2092 (2015)
14. Stanton, T. R., Moseley, G. L., Wong, A. Y. L. & Kawchuk, G. N. Feeling stiffness in the back: a protective perceptual inference in chronic back pain. Scientific Reports 7, 9681 (2017)
15. Ellingsen, D.-M., Napadow, V., Protsenko, E., Mawla, I., Kowalski, M. H., Swensen, D., et al. (2018). Brain Mechanisms of Anticipated Painful Movements and Their Modulation by Manual Therapy in Chronic Low Back Pain. The Journal of Pain, 19(11), 1352–1365. http://doi.org/10.1016/j.jpain.2018.05.012
16. Goossens, N., Rummens, S., Janssens, L., Caeyenberghs, K. & Brumagne, S. Association Between Sensorimotor Impairments and Functional Brain Changes in Patients With Low Back Pain. Am J Phys Med Rehab 97, 200–211 (2018)
17. Briones-Cantero, M. et al. Effects of Adding Motor Imagery to Early Physical Therapy in Patients with Knee Osteoarthritis who Had Received Total Knee Arthroplasty: A Randomized Clinical Trial. Pain Med 21, 3548–3555 (2020)
18. Leake, H. B., Moseley, G. L., Stanton, T. R., O’Hagan, E. T. & Heathcote, L. C. What do patients value learning about pain? A mixed-methods survey on the relevance of target concepts after pain science education. Pain Publish Ahead of Print, 2558–2568 (2021)
19. Shala, R., Roussel, N., Moseley, G. L., Osinski, T. & Puentedura, E. J. Can we just talk our patients out of pain? Should pain neuroscience education be our only tool? The Journal of Manual & Manipulative Therapy 31, 1–3 (2021)
20. Gagnon, C. M. et al. Structural MRI Analysis of Chronic Pain Patients Following Interdisciplinary Treatment Shows Changes in Brain Volume and Opiate-Dependent Reorganization of the Amygdala and Hippocampus. Pain Med 21, 2765–2776 (2020)
21. Seminowicz, D. A., Shpaner, M., Keaser, M. L., Krauthamer, G. M., Mantegna, J., Dumas, J. A., et al. (2013). Cognitive-behavioral therapy increases prefrontal cortex gray matter in patients with chronic pain. The Journal of Pain, 14(12), 1573–1584. http://doi.org/10.1016/j.jpain.2013.07.020
22. Louw, A., Farrell, K., Landers, M., Barclay, M., Goodman, E., Gillund, J., et al. (2017). The effect of manual therapy and neuroplasticity education on chronic low back pain: a randomized clinical trial. The Journal of Manual & Manipulative Therapy, 25(5), 227–234. http://doi.org/10.1080/10669817.2016.1231860
23. Hill, J. J., & Keating, J. L. (2015). Daily exercises and education for preventing low back pain in children: cluster randomized controlled trial. Physical Therapy, 95(4), 507–516. http://doi.org/10.2522/ptj.20140273
24. Louw, A., Farrell, K., Landers, M., Barclay, M., Goodman, E., Gillund, J., et al. (2017). The effect of manual therapy and neuroplasticity education on chronic low back pain: a randomized clinical trial. The Journal of Manual & Manipulative Therapy, 25(5), 227–234. http://doi.org/10.1080/10669817.2016.1231860
25. Malfliet, A., Kregel, J., Coppieters, I., De Pauw, R., Meeus, M., Roussel, N., et al. (2018). Effect of Pain Neuroscience Education Combined With Cognition-Targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial. JAMA Neurology, 75(7), 808–817. http://doi.org/10.1001/jamaneurol.2018.0492
1. Brenner, M. (2019). The Bayesian Brain Hypothesis - How our brain evolved to look into the future. https://towardsdatascience.com/the-bayesian-brain-hypothesis-35b98847d331
2. Tanaka, S. et al. “But it feels swollen!”: the frequency and clinical characteristics of people with knee osteoarthritis who report subjective knee swelling in the absence of objective swelling. Pain Reports 6, e971 (2021)
3. Silfies, S. P., Vendemia, J. M. C., Beattie, P. F., Stewart, J. C., & Jordon, M. (2017). Changes in Brain Structure and Activation May Augment Abnormal Movement Patterns: An Emerging Challenge in Musculoskeletal Rehabilitation. Pain Medicine (Malden, Mass), 18(11), 2051–2054. http://doi.org/10.1093/pm/pnx190
4. Cudejko, T., van der Esch, M., Schrijvers, J., Richards, R., van den Noort, J. C., Wrigley, T., et al. (2018). The immediate effect of a soft knee brace on dynamic knee instability in persons with knee osteoarthritis. Rheumatology (Oxford, England), 57(10), 1735–1742. http://doi.org/10.1093/rheumatology/key162
5. Cudejko, T., van der Esch, M., van der Leeden, M., Roorda, L. D., Pallari, J., Bennell, K. L., et al. (2018). Effect of Soft Braces on Pain and Physical Function in Patients With Knee Osteoarthritis: Systematic Review With Meta-Analyses. Archives of Physical Medicine and Rehabilitation, 99(1), 153–163. http://doi.org/10.1016/j.apmr.2017.04.029
6. Thijs, Y., Vingerhoets, G., Pattyn, E., Rombaut, L., & Witvrouw, E. (2010). Does bracing influence brain activity during knee movement: an fMRI study. Knee Surgery, Sports Traumatology, Arthroscopy, 18(8), 1145–1149. http://doi.org/10.1007/s00167-009-1012-9
7. Swaminathan, V., Parkes, M. J., Callaghan, M. J., O'Neill, T. W., Hodgson, R., Gait, A. D., & Felson, D. T. (2017). With a biomechanical treatment in knee osteoarthritis, less knee pain did not correlate with synovitis reduction. BMC Musculoskelet Disord, 18(1), 289–7. http://doi.org/10.1186/s12891-017-1691-1
8. Moseley, G. L. (2017). Innovative treatments for back pain. Pain, 158 Suppl 1, S2–S10. http://doi.org/10.1097/j.pain.0000000000000772
9. Isenburg, K. et al. Increased salience network connectivity following manual therapy is associated with reduced pain in chronic low back pain patients. J Pain 22, 545–555 (2020)
10. Meier, M. L., Vrana, A., & Schweinhardt, P. (2019). Low Back Pain: The Potential Contribution of Supraspinal Motor Control and Proprioception. The Neuroscientist, 25(6), 583–596. http://doi.org/10.1177/1073858418809074
11. Wesselink, E., de Raaij, E., Pevenage, P., van der Kaay, N., & Pool, J. (2019). Fear-avoidance beliefs are associated with a high fat content in the erector spinae: a 1.5 tesla magnetic resonance imaging study. Chiropractic & Manual Therapies, 27(1), 1714–8. http://doi.org/10.1186/s12998-019-0234-2
12. Seminowicz, D. A., Wideman, T. H., Naso, L., Hatami-Khoroushahi, Z., Fallatah, S., Ware, M. A., et al. (2011). Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. The Journal of Neuroscience, 31(20), 7540–7550. http://doi.org/10.1523/JNEUROSCI.5280-10.2011
13. Ceko, M. et al. Partial recovery of abnormal insula and dorsolateral prefrontal connectivity to cognitive networks in chronic low back pain after treatment. Human Brain Mapping 36, 2075–2092 (2015)
14. Stanton, T. R., Moseley, G. L., Wong, A. Y. L. & Kawchuk, G. N. Feeling stiffness in the back: a protective perceptual inference in chronic back pain. Scientific Reports 7, 9681 (2017)
15. Ellingsen, D.-M., Napadow, V., Protsenko, E., Mawla, I., Kowalski, M. H., Swensen, D., et al. (2018). Brain Mechanisms of Anticipated Painful Movements and Their Modulation by Manual Therapy in Chronic Low Back Pain. The Journal of Pain, 19(11), 1352–1365. http://doi.org/10.1016/j.jpain.2018.05.012
16. Goossens, N., Rummens, S., Janssens, L., Caeyenberghs, K. & Brumagne, S. Association Between Sensorimotor Impairments and Functional Brain Changes in Patients With Low Back Pain. Am J Phys Med Rehab 97, 200–211 (2018)
17. Briones-Cantero, M. et al. Effects of Adding Motor Imagery to Early Physical Therapy in Patients with Knee Osteoarthritis who Had Received Total Knee Arthroplasty: A Randomized Clinical Trial. Pain Med 21, 3548–3555 (2020)
18. Leake, H. B., Moseley, G. L., Stanton, T. R., O’Hagan, E. T. & Heathcote, L. C. What do patients value learning about pain? A mixed-methods survey on the relevance of target concepts after pain science education. Pain Publish Ahead of Print, 2558–2568 (2021)
19. Shala, R., Roussel, N., Moseley, G. L., Osinski, T. & Puentedura, E. J. Can we just talk our patients out of pain? Should pain neuroscience education be our only tool? The Journal of Manual & Manipulative Therapy 31, 1–3 (2021)
20. Gagnon, C. M. et al. Structural MRI Analysis of Chronic Pain Patients Following Interdisciplinary Treatment Shows Changes in Brain Volume and Opiate-Dependent Reorganization of the Amygdala and Hippocampus. Pain Med 21, 2765–2776 (2020)
21. Seminowicz, D. A., Shpaner, M., Keaser, M. L., Krauthamer, G. M., Mantegna, J., Dumas, J. A., et al. (2013). Cognitive-behavioral therapy increases prefrontal cortex gray matter in patients with chronic pain. The Journal of Pain, 14(12), 1573–1584. http://doi.org/10.1016/j.jpain.2013.07.020
22. Louw, A., Farrell, K., Landers, M., Barclay, M., Goodman, E., Gillund, J., et al. (2017). The effect of manual therapy and neuroplasticity education on chronic low back pain: a randomized clinical trial. The Journal of Manual & Manipulative Therapy, 25(5), 227–234. http://doi.org/10.1080/10669817.2016.1231860
23. Hill, J. J., & Keating, J. L. (2015). Daily exercises and education for preventing low back pain in children: cluster randomized controlled trial. Physical Therapy, 95(4), 507–516. http://doi.org/10.2522/ptj.20140273
24. Louw, A., Farrell, K., Landers, M., Barclay, M., Goodman, E., Gillund, J., et al. (2017). The effect of manual therapy and neuroplasticity education on chronic low back pain: a randomized clinical trial. The Journal of Manual & Manipulative Therapy, 25(5), 227–234. http://doi.org/10.1080/10669817.2016.1231860
25. Malfliet, A., Kregel, J., Coppieters, I., De Pauw, R., Meeus, M., Roussel, N., et al. (2018). Effect of Pain Neuroscience Education Combined With Cognition-Targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial. JAMA Neurology, 75(7), 808–817. http://doi.org/10.1001/jamaneurol.2018.0492