Risky monetary behavior in chronic back pain is associated with altered modular connectivity of the nucleus accumbens

Abstract

BackgroundThe nucleus accumbens (NAc) has a well established role in reward processing. Yet, there is growing evidence showing that NAc function, and its connections to other parts of the brain, is also critically involved in the emergence of chronic back pain (CBP). Pain patients are known to perform abnormally in reward-related tasks, which suggests an intriguing link between pain, NAc connectivity, and reward behavior. In the present study, we compared performance on a gambling task (indicating willingness to risk losing money) between healthy pain-free controls (CON) and individuals with CBP. We then measured modular connectivity of each participants’ NAc with resting state functional MRI to investigate how connectivity accounts for reward behavior in the presence and absence of pain.ResultsWe found gain sensitivity was significantly higher in CBP patients. These scores were significantly correlated to connectivity within the NAc module defined by CON subjects ( which had strong connections to the frontal cortex), but not within that defined by CBP patients ( which was more strongly connected to subcortical areas). An important part of our study was based on the precedence that a range of behaviors, from simple to complex, can be predicted from brain activity during rest. Thus, to corroborate our results we compared them closely to an independent study correlating the same connectivity metric to impulsive behaviors in healthy participants. We found that our CBP patients were highly similarin connectivity to this study’s highly-impulsive healthy subjects, strengthening the notion that there is an important link between the brain systems that support chronic pain and reward processing.ConclusionsOur results support previous findings that chronic back pain is accompanied by altered connectivity of the NAc. This lends itself to riskier behavior in these patients, a finding which establishes a potential cognitive consequence or co-morbidity of long-term pain and provides a behavioral link to growing research showing that chronic pain is related to abnormal changes in the dopaminergic system.

Functional and Structural Signatures of the Anterior Insula are associated with Risk-taking Tendency of Analgesic Decision-making

“…In accordance with our results, evidence from financial decision-making tasks has revealed that the NAc activation was associated with the anticipation preceding the selection of a risky option, which would receive more gains, compared to a riskless option1415. Notably, the patients with chronic pain, compared to healthy controls, showed a higher impulsivity to gain in a gambling task, and this impulsivity was associated with the changes in NAc connectivity36. As part of the mesolimbic dopaminergic system, the NAc plays a key role in processing of the pleasure from a reward17.…”

An epigenetic hypothesis for the genomic memory of pain

“…Studies in rodent models of chronic pain have demonstrated pain-related modifications in areas including the hippocampus, amygdala, perirhinal cortex, and prefrontal cortex (PFC; Seminowicz et al, 2009 ; Mutso et al, 2012 ; Alvarado et al, 2013 ; Tajerian et al, 2013 , 2014 ). These findings extend to humans—multiple studies have reported decreased gray matter, reduced cortical thickness, abnormal cortical function, and altered connectivity in various brain regions in a wide range of chronic pain conditions including low back pain (Giesecke et al, 2004 ; Apkarian et al, 2005 ; Schmidt-Wilcke et al, 2006 ; Tagliazucchi et al, 2010 ; Berger et al, 2014 ), headache (Schmidt-Wilcke et al, 2005 ), fibromyalgia (Kuchinad et al, 2007 ; Schmidt-Wilcke et al, 2007 ), post-stroke pain (Krause et al, 2014 ), complex regional pain syndrome (Pleger et al, 2014 ), burning mouth syndrome (Khan et al, 2014 ), and irritable bowel syndrome (Davis et al, 2008 ). The magnitude of these changes has been related to the duration and the intensity of chronic pain (Apkarian et al, 2004 ).…”

Sodium channels in pain disorders: pathophysiology and prospects for treatment

“…These findings also challenged the concept of the pain matrix [7]. Behavioral studies describing deficits in hedonic perception in CBP [54] and emotional decision making tasks [9; 16; 115] in CBP and fibromyalgia patients are consistent with the idea that chronic pain taxes the limbic brain.…”