CLBP and the brain - emotional, cognitive and psychological considerations

Various studies provide evidence of specific emotional, psychological and cognitive abnormalities in patients with CLBP that may result from or directly represent correlates of cortical abnormalities.

Apkarian et al. (2004b) found that compared to healthy controls CLBP patients performed poorly in a task designed to specifically assess emotional decision making. Using a gambling task in which participants are asked to choose between a deck of cards that yields immediate large rewards but subsequent larger losses (the bad deck) and one that yields lower but more consistent gains and fewer losses (the good deck) they found that CLBP patients were more likely to choose the bad deck for longer and over repeated trials they

took longer to learn to choose the good deck. Performance in this task was negatively related to pain intensity in CLBP patients. It appears that this deficit is not one of general attention or cognitive ability as a battery of other cognitive tasks was unaffected. Equally pain intensity was not enough to fully explain the finding as another group with CRPS and similar levels of pain demonstrated greater impairments. Deficits in performing this task have previously been associated with lesions of the orbito-frontal region of the prefrontal cortex (Bechara 2004) and the authors speculate that the deficit indicates abnormal involvement of this area in patients with chronic pain.

Using a different battery of cognitive tasks (Weiner et al. 2006) demonstrated in an elderly population that subjects with CLBP demonstrated significant deficits in neuropsychological (NP) performance compared to those without and that NP performance scores demonstrated a significant but weak negative correlation with pain severity, a positive moderate correlation with physical performance and mediated the relationship between the two. There is also evidence of memory dysfunction on CLBP, though this was correlated with catastrophizing but not pain levels (Jorge et al. 2009) Buckalew et al. (2008) found impairments in attention and mental flexibility in a group of elderly CLBP sufferers compared to those without pain. These findings appear at odds with those of Apkarian et al. (2004b) who found no evidence of a generalised deficit in cognitive performance in CLBP. Given that the correlations in this cohort (n=323) were not strong it seems reasonable that the study by Apkarian et al. (2004b) may have been underpowered to detect them (n=52 excluding CRPS patients). Alternative explanations might be that CLBP has a more global impact on general cognitive performance in elderly sufferers or that the deficits were specific to the tests employed. In a large (n=1400) population based study Gijsen et al. (2011) found that after controlling for a range of variables, subjects with recurrent pain were specifically impaired on the Stroop interference task (which seeks to measure speed of information processing interference control, Stroop 1935) but not a task that measured attentional skills or verbal memory. These results suggest that attentional deficit may be age dependent and speak to a degree of specificity in the cognitive impairments associated with chronic pain. Conversely Ling et al. (2007) found an impairment of short term prospective memory in CLBP patients after controlling for age.

Impairment of attentional processes does appear to be a phenomenon related to chronic pain generally, including chronic low back pain. It has been proposed that chronic pain patients may be unable to exercise voluntary cortical control over nociceptive interference

and be impaired at switching attention away from pain and pain-relevant stimuli (Legrain et al. 2009) and there is direct evidence to support this.

Using a dot-probe task Roelofs et al. (2005) found that both normal subjects and those with CLBP take longer to disengage from pictures of physical activities that they associated with the threat of back injury than from those without threat association. This difficulty in disengaging was significantly increased in the CLBP subjects, although the same was not found for threatening words. In contrast, using a similar task with similar group sizes Haggman et al. (2010) found a significant attentional bias towards words related to sensory aspects of pain, but not affective, disability or threat related words, in both acute and chronic back pain. The reason for these conflicting results is unclear, the participants in the study by Roelofs et al. had higher pain levels on average than those in the Haggman study which suggests against disease severity being a factor. While technical problems in the study by Roelofs et al. did reduce the size of the group considerably, it should be noted that no trend towards a bias to threatening words was observed. In a review of the wider chronic pain literature Pincus & Morley (2001) conclude that there is evidence for attentional biases towards sensory but not affective pain words and Dehghani et al. (2003) found similar results to Haggman et al. in a broader chronic pain group.

It is plausible that DLPFC dysfunction may contribute to attentional problems. The DLPFC is broadly accepted as playing a key role in selective attention and attention switching (Funahashi 2001; Milham et al. 2003; MacDonald III et al. 2000; Smith and Jonides 1999;

Wager, Jonides, and Smith 2006; Sylvester et al. 2003). Indeed disengagement from pain and pain related information has been suggested as a role of the DLPFC and unsurprisingly this role appears to be mediated by psychological factors. Seminowicz & Davis (2006) found that during moderately intense painful experimental stimulation in healthy subjects DLPFC activity bilaterally demonstrated a strong negative correlation with the level of pain related catastrophising, a psychological response characterised in part by difficulty disengaging with pain (Van Damme et al. 2004).

Given the prognostic role that psychological factors, notably depression and distress, have been shown to play in the development and maintenance of CLBP (see chapter 1), it is reasonable to suggest that these phenomena should be related to and reflected in the brain changes observed in this patient group. Grachev (2003) identified significant overlap in the neural regions involved in both depression and CLBP, particularly with regards the DLPFC. Imaging studies implicate prefrontal dysfunction in the pathogenesis of depression

(George et al. 1994; Liotti & Mayberg 2001) including grey matter reductions in this brain region (Brooks et al. 2009) although the precise role of the DLPFC in depression far from fully established. Recent meta-analyses of imaging studies found that while the DLPFC is commonly implicated by studies and is often found to demonstrate reduced activity at rest there is some inconsistency in the changes reported by different studies in terms of the direction of changes and their hemispheric laterality (Fitzgerald et al. 2006; Fitzgerald et al.

2008) and studies combining imaging of the DLPFC during neuropsychological tasks produce inconsistent results (Rogers et al. 2004). However Fitzgerald et al. (2008) did find consistent evidence of a failure to activate the DLPFC in response to negative emotional stimuli and suggest that dysfunction of this region might contribute to abnormal appraisal and response to negative emotional stimuli (such as pain). This conclusion is echoed by Koenigs & Grafman (2009) who emphasise the role of the DLPFC in appraisal and suppression of negative affect. If DLPFC dysfunction retards the ability to effectively appraise and suppress negative emotional stimuli, it is plausible that this might include painful stimuli. However abnormal DLPFC activity may not be specific to the processing of emotional stimuli. In their longitudinal study using fMRI Seminowicz et al. (2011) found that in CLBP patients left DLPFC activation was increased relative to healthy controls during performance a simple cognitive task with no specific emotional context. This had normalised after treatment, although this was not correlated with improvements in clinical signs and symptoms.

Together these data identify common circuitry that may underpin aspects of the CLBP experience and its associated psychological features and suggest a possible biological substrate for the clinical relationship between emotional and psychological phenomena and CLBP.