Brain Structure and Function of Chronic Low Back Pain Patients on Long-Term Opioid Analgesic Treatment: A Preliminary Study.

Chronic low back pain (CLBP) is often treated with opioid analgesics (OA), a class of medications associated with a significant risk of misuse. However, little is known about how treatment with OA affect the brain in chronic pain patients. Gaining this knowledge is a necessary first step towards understanding OA associated analgesia and elucidating long-term risk of OA misuse. Here we study CLBP patients chronically medicated with opioids without any evidence of misuse and compare them to CLBP patients not on opioids and to healthy controls using structural and functional brain imaging. CLBP patients medicated with OA showed loss of volume in the nucleus accumbens and thalamus, and an overall significant decrease in signal to noise ratio in their sub-cortical areas. Power spectral density analysis (PSD) of frequency content in the accumbens' resting state activity revealed that both medicated and unmedicated patients showed loss of PSD within the slow-5 frequency band (0.01-0.027 Hz) while only CLBP patients on OA showed additional density loss within the slow-4 frequency band (0.027-0.073 Hz). We conclude that chronic treatment with OA is associated with altered brain structure and function within sensory limbic areas.

Phantom Acupuncture Induces Placebo Credibility and Vicarious Sensations: A Parallel fMRI Study of Low Back Pain Patients.

Although acupuncture is an effective therapeutic intervention for pain reduction, the exact difference between real and sham acupuncture has not been clearly understood because a somatosensory tactile component is commonly included in the existing sham acupuncture protocols. In an event-related fMRI experiment, we implemented a novel form of sham acupuncture, phantom acupuncture, that reproduces the acupuncture needling procedure without somatosensory tactile stimulation while maintaining the credibility of the acupuncture treatment context. Fifty-six non-specific low back pain patients received either real (REAL) or phantom (PHNT) acupuncture stimulation in a parallel group study. The REAL group exhibited greater activation in the posterior insula and anterior cingulate cortex, reflecting the needling-specific components of acupuncture. We demonstrated that PHNT could be delivered credibly. Interestingly, the PHNT-credible group exhibited bilateral activation in SI/SII and also reported vicarious acupuncture sensations without needling stimulation. The PHNT group showed greater activation in the bilateral dorsolateral/ventrolateral prefrontal cortex (dlPFC/vlPFC). Moreover, the PHNT group exhibited significant pain reduction, with a significant correlation between the subjective fMRI signal in the right dlPFC/vlPFC and a score assessing belief in acupuncture effectiveness. These results support an expectation-related placebo analgesic effect on subjective pain intensity ratings, possibly mediated by right prefrontal cortex activity.

Self-regulation of primary motor cortex activity with motor imagery induces functional connectivity modulation: A real-time fMRI neurofeedback study.

Recent developments in data acquisition of functional magnetic resonance imaging (fMRI) have led to rapid preprocessing and analysis of brain activity in a quasireal-time basis, what so called real-time fMRI neurofeedback (rtfMRI-NFB). This information is fed back to subjects allowing them to gain a voluntary control over their own region-specific brain activity. Forty-one healthy participants were randomized into an experimental (NFB) group, who received a feedback directly proportional to their brain activity from the primary motor cortex (M1), and a control (CTRL) group who received a sham feedback. The M1 ROI was functionally localized during motor execution and imagery tasks. A resting-state functional run was performed before and after the neurofeedback training to investigate the default mode network (DMN) modulation after training. The NFB group revealed increased DMN functional connectivity after training to the cortical and subcortical sensory/motor areas (M1/S1 and caudate nucleus, respectively), which may be associated with sensorimotor processing of learning in the resting state. These results show that motor imagery training through rtfMRI-NFB could modulate the DMN functional connectivity to motor-related areas, suggesting that this modulation potentially subserved the establishment of motor learning in the NFB group.

Functional topography of the primary motor cortex during motor execution and motor imagery as revealed by functional MRI.

Controversy exists regarding the involvement of the primary motor cortex (M1) during motor imagery (MI) and also regarding the differential somatotopic representation of motor execution (ME) and mental simulation of movement, that is, MI within M1. Although some research reported clear M1 involvement during MI without overt motor output, others did not. However, possible somatotopic representation between execution and imagery has not been clearly investigated to date. The aim of the present study was to aid in the resolution of this controversy by investigating the possible involvement of M1 during MI, and the differential, within M1, somatotopic representation between execution and imagery by quantitatively assessing different location markers such as activation peak and center of mass as well as intensity differences between the two tasks in case of with and without the overlap between the two representations. Forty-one healthy volunteers participated in two functional MRI runs of mouth-stretching ME and MI tasks. Our findings suggest the clear involvement of M1 (BA 4) during MI with lower signal intensity compared with ME, and further showed distinct centers for each representation along the y-axis (anteroposterior plane), with MI showing more involvement of the anterior sector of M1 (BA 4a), whereas ME recruited more of the posterior sector (BA 4p). These results parallel the pioneering findings of a functional distinction between BA 4a and BA 4p, where BA 4a is more involved in the cognitive aspects of MI, whereas BA 4p is more related to executive function, promoting the idea of distinctive somatotopic mapping between execution and imagery within M1 sectors.

Greater corticostriatal activation associated with facial motor imagery compared with motor execution: a functional MRI study.

Motor imagery (MI) relies on conscious mental simulation of a motor act without overt motor output and can promote motor skill acquisition and facilitate rehabilitation for patients with stroke or neurological conditions. Although a plethora of neuroimaging studies have investigated the neural network of MI regarding different body parts, exploration of the neural correlates to facial MI remains warranted. Here, we used functional MRI with a large cohort of 41 participants who underwent motor execution (ME) and MI runs of mouth-stretching tasks. Then, we carried out conjunction and contrast analyses to investigate the commonalities and differences between the two conditions. Conjunction analysis, representing the shared neural network between ME and MI, showed activation in the primary motor cortex, primary and secondary somatosensory cortices, premotor cortex, parietal lobe, anterior insula, supplementary motor area (SMA) and pre-SMA, thalamus, putamen, and caudate. Contrast analysis showed greater activation of primary motor cortex, primary and secondary somatosensory cortices, SMA, anterior insula, and the thalamus in response to ME than MI and greater activation of the premotor cortex, pre-SMA, putamen, and caudate in response to MI than ME. Interestingly, we found exclusive activation in the anterior cingulate cortex and left ventrolateral prefrontal cortex in response to MI, reflecting the motor inhibition network responsible for blocking the transmission of motor commands to peripheral effectors during mental rehearsal. Taken together, these findings show that, despite the neural overlap between ME and MI, there are different degrees of activation within this overlap, and that MI normally involves motor command inhibition possibly mediated by the anterior cingulate cortex and ventrolateral prefrontal cortex.

Evaluating validity of various acupuncture device types: a random sequence clinical trial.

BACKGROUND: Although various placebo acupuncture devices have been developed and used in acupuncture research, there is controversy concerning whether these devices really serve as appropriate placebos for control groups. METHODS/DESIGN: The proposed study is a single-center prospective random sequence participant- and assessor-blinded trial with two parallel arms. A total of 76 participants will be randomly assigned to Group 1 or Group 2 in a 1:1 ratio. Group 1 will consist of Sham Streitberger's needle, Real Streitberger's needle, and Phantom acupuncture session. Group 2 will consist of Park Sham device with real needle, Park Sham device with sham needle, and no treatment session. Participants will have a total of three acupuncture sessions in a day. The primary endpoint is blinding test questionnaire 1. Secondary endpoints are the Bang's blinding index, the Massachusetts General Hospital Acupuncture Sensation Scale index, and physiological data including heart rate, heart rate variability, and skin conductance response. DISCUSSION: This trial will evaluate the relevance of using placebo acupuncture devices as controls using a validation test procedure. TRIAL REGISTRATION: Clinical Research Information Service: KCT0001347 .