Neurobiology of osteoarthritis: a systematic review and activation likelihood estimation meta-analysis.

Osteoarthritis (OA) affects 240 million people worldwide. Neuroimaging has been increasingly used to investigate brain changes in OA, however, there is considerable heterogeneity in reported results. The goal of this systematic review and meta-analysis was to synthesise existing literature and identify consistent brain alterations in OA. Six databases were searched from inception up to June, 2022. Full-texts of original human studies were included if they had: (i) neuroimaging data by site of OA (e.g. hand, knee, hip); (ii) data in healthy controls (HC); (iii) > 10 participants. Activation likelihood estimation (ALE) was conducted using GingerALE software on studies that reported peak activation coordinates and sample size. Our search strategy identified 6250 articles. Twenty-eight studies fulfilled the eligibility criteria, of which 18 were included in the meta-analysis. There were no significant differences in brain structure or function between OA and healthy control contrasts. In exploratory analysis, the right insula was associated with OA vs healthy controls, with less activity, connectivity and brain volume in OA. This region was implicated in both knee and hip OA, with an additional cluster in the medial prefrontal cortex observed only in the contrast between healthy controls and the hip OA subgroup, suggesting a possible distinction between the neural correlates of OA subtypes. Despite the limitations associated with heterogeneity and poor study quality, this synthesis identified neurobiological outcomes associated with OA, providing insight for future research. PROSPERO registration number: CRD42021238735.

Neural correlates of co-occurring pain and depression: an activation-likelihood estimation (ALE) meta-analysis and systematic review.

The relationship between pain and depression is thought to be bidirectional and the underlying neurobiology 'shared' between the two conditions. However, these claims are often based on qualitative comparisons of brain regions implicated in pain or depression, while focused quantitative studies of the neurobiology of pain-depression comorbidity are lacking. Particularly, the direction of comorbidity, i.e., pain with depression vs. depression with pain, is rarely addressed. In this systematic review (PROSPERO registration CRD42020219876), we aimed to delineate brain correlates associated with primary pain with concomitant depression, primary depression with concurrent pain, and equal pain and depression comorbidity, using activation likelihood estimation (ALE) meta-analysis. Neuroimaging studies published in English until the 28th of September 2021 were evaluated using PRISMA guidelines. A total of 70 studies were included, of which 26 reported stereotactic coordinates and were analysed with ALE. All studies were assessed for quality by two authors, using the National Institute of Health Quality Assessment Tool. Our results revealed paucity of studies that directly investigated the neurobiology of pain-depression comorbidity. The ALE analysis indicated that pain with concomitant depression was associated with the right amygdala, while depression with concomitant pain was related primarily to the left dorsolateral prefrontal cortex (DLPFC). We provide evidence that pain and depression have a cumulative negative effect on a specific set of brain regions, distinct for primary diagnosis of depression vs. pain.