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1.  Experimental Placebo Analgesia Changes Resting-State Alpha Oscillations  
PLoS ONE  2013;8(10):e78278.
The lack of clear understanding of the pathophysiology of chronic pain could explain why we currently have only a few effective treatments. Understanding how pain relief is realised during placebo analgesia could help develop improved treatments for chronic pain. Here, we tested whether experimental placebo analgesia was associated with altered resting-state cortical activity in the alpha frequency band of the electroencephalogram (EEG). Alpha oscillations have been shown to be influenced by top-down processes, which are thought to underpin the placebo response.
Seventy-three healthy volunteers, split into placebo or control groups, took part in a well-established experimental placebo procedure involving treatment with a sham analgesic cream. We recorded ongoing (resting) EEG activity before, during, and after the sham treatment.
We show that resting alpha activity is modified by placebo analgesia. Post-treatment, alpha activity increased significantly in the placebo group only (p < 0.001). Source analysis suggested that this alpha activity might have been generated in medial components of the pain network, including dorsal anterior cingulate cortex, medial prefrontal cortex, and left insula.
These changes are consistent with a cognitive state of pain expectancy, a key driver of the placebo analgesic response. The manipulation of alpha activity may therefore present an exciting avenue for the development of treatments that directly alter endogenous processes to better control pain.
doi:10.1371/journal.pone.0078278
PMCID: PMC3795660  PMID: 24147129
2.  Placebo analgesia: cognitive influences on therapeutic outcome 
The therapeutic response to a drug treatment is a mixture of direct pharmacological action and placebo effect. Therefore, harnessing the positive aspects of the placebo effect and reducing the negative ones could potentially benefit the patient. This article is aimed at providing an overview for clinicians of the importance of contextual psychosocial variables in determining treatment response, and the specific focus is on determinants of the placebo response. A better understanding of the physiological, psychological, and social mechanisms of placebo may aid in predicting which contexts have the greatest potential for inducing positive treatment responses. We examine the evidence for the role of psychological traits, including optimism, pessimism, and the effect of patient expectations on therapeutic outcome. We discuss the importance of the patient-practitioner relationship and how this can be used to enhance the placebo effect, and we consider the ethical challenges of using placebos in clinical practice.
doi:10.1186/ar3783
PMCID: PMC3446435  PMID: 22494482
3.  Comparative Effectiveness of Cognitive Therapies Delivered Face-to-Face or over the Telephone: An Observational Study Using Propensity Methods 
PLoS ONE  2012;7(9):e42916.
Objectives
To compare the clinical and cost-effectiveness of face-to-face (FTF) with over-the-telephone (OTT) delivery of low intensity cognitive behavioural therapy.
Design
Observational study following SROBE guidelines. Selection effects were controlled using propensity scores. Non-inferiority comparisons assessed effectiveness.
Setting
IAPT (improving access to psychological therapies) services in the East of England.
Participants
39,227 adults referred to IAPT services. Propensity score strata included 4,106 individuals; 147 pairs participated in 1∶1 matching.
Intervention
Two or more sessions of computerised cognitive behavioural therapy (CBT).
Main outcome measures
Patient-reported outcomes: Patient Health Questionnaire (PHQ-9) for depression; Generalised Anxiety Disorder questionnaire (GAD-7); Work and Social Adjustment Scale (WSAS). Differences between groups were summarised as standardised effect sizes (ES), adjusted mean differences and minimally important difference for PHQ-9. Cost per session for OTT was compared with FTF.
Results
Analysis of covariance controlling for number of assessments, provider site, and baseline PHQ-9, GAD-7 and WSAS indicated statistically significantly greater reductions in scores for OTT treatment with moderate (PHQ-9: ES: 0.14; GAD-7: ES: 0.10) or small (WSAS: ES: 0.03) effect sizes. Non-inferiority in favour of OTT treatment for symptom severity persisted as small to moderate effects for all but individuals with the highest symptom severity. In the most stringent comparison, the one-to-one propensity matching, adjusted mean differences in treatment outcomes indicated non-inferiority between OTT versus FTF treatments for PHQ-9 and GAD-7, whereas the evidence was moderate for WSAS. The per-session cost for OTT was 36.2% lower than FTF.
Conclusions
The clinical effectiveness of low intensity CBT-based interventions delivered OTT was not inferior to those delivered FTF except for people with more severe illness where FTF was superior. This provides evidence for better targeting of therapy, efficiencies for patients, cost savings for services and greater access to psychological therapies for people with common mental disorders.
doi:10.1371/journal.pone.0042916
PMCID: PMC3460939  PMID: 23028436
4.  The placebo effect: Advances from different methodological approaches 
There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.
doi:10.1523/JNEUROSCI.4099-11.2011
PMCID: PMC3242469  PMID: 22072664
5.  Placebo conditioning and placebo analgesia modulate a common brain network during pain anticipation and perception 
Pain  2009;145(1-2):24-30.
The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. In the control session participants were explicitly told that the treatment was inactive. The sham treatment group reported a significant reduction in pain rating (p = 0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia.
doi:10.1016/j.pain.2009.04.003
PMCID: PMC2743811  PMID: 19523766
Placebo analgesia; Placebo; fMRI; Laser; Conditioning

Results 1-6 (6)