• A systematic review of resting state functional MRI connectivity changes and cognitive impairment in multiple sclerosis.

      Jandric, Danka; email: danka.jandric@manchester.ac.uk; Doshi, Anisha; email: anisha.doshi@ucl.ac.uk; Scott, Richelle; email: richelle.scott@student.manchester.ac.uk; Paling, David; email: david.paling@nhs.net; Rog, David; email: david.rog@srft.nhs.uk; Chataway, Jeremy; email: j.chataway@ucl.ac.uk; Schoonheim, Menno; email: m.schoonheim@amsterdamumc.nl; Parker, Geoff; email: geoff.parker@ucl.ac.uk; Muhlert, Nils; email: nils.muhlert@manchester.ac.uk (2021-08-12)
      Cognitive impairment in multiple sclerosis (MS) is increasingly being investigated with resting state functional MRI (rs-fMRI) functional connectivity (FC) . However, results remain difficult to interpret, showing both high and low FC associated with cognitive impairment. We conducted a systematic review of rs-fMRI studies in MS to understand whether the direction of FC change relates to cognitive dysfunction, and how this may be influenced by the choice of methodology. Embase, Medline and PsycINFO were searched for studies assessing cognitive function and rs-fMRI FC in adults with MS. Fifty-seven studies were included in a narrative synthesis. Of these, 50 found an association between cognitive impairment and FC abnormalities. Worse cognition was linked to high FC in 18 studies, and to low FC in 17 studies. Nine studies found patterns of both high and low FC related to poor cognitive performance, in different regions or for different MR metrics. There was no clear link to increased FC during early stages of MS and reduced FC in later stages, as predicted by common models of MS pathology. Throughout, we found substantial heterogeneity in study methodology, and carefully consider how this may impact on the observed findings. These results indicate an urgent need for greater standardisation in the field - in terms of the choice of MRI analysis and the definition of cognitive impairment. This will allow us to use rs-fMRI FC as a biomarker in future clinical studies, and as a tool to understand mechanisms underpinning cognitive symptoms in MS.
    • The effects of psychosocial stress on item, cued‐pair and emotional memory

      McManus, Elizabeth; orcid: 0000-0002-8508-2054; Talmi, Deborah; Haroon, Hamied; Muhlert, Nils; email: nils.muhlert@manchester.ac.uk (2021-06-14)
      Abstract: Physical stress, such as from the cold‐pressor test, has been robustly associated with altered memory retrieval, but it is less clear whether the same happens following psychosocial stress. Studies using psychosocial stressors report mixed effects on memory, leading to uncertainty about the common cognitive impact of both forms of stress. The current study uses a series of four carefully designed experiments, each differing by only a single critical factor to determine the effects of psychosocial stress on specific aspects of episodic memory. In three experiments, we induced psychosocial stress after participants encoded words, then assessed retrieval of those words after a prolonged delay. These experiments found no effect of post‐encoding stress on recognition of neutral words or cued recall of word‐pairs, but a small effect on recollection of semantically related words. There were, however, positive relationships within the stress group between measures of stress (cortisol in experiment 1 and self‐reported‐anxiety in experiment 3) and recollection of single word stimuli. In the fourth experiment, we found that psychosocial stress immediately before retrieval did not influence word recognition. Recollection, particularly for semantically related stimuli, may therefore be more susceptible to the effects of psychosocial stress, and future studies can assess how this relates to other forms of stress. Overall, our findings suggest that the effects of psychosocial stress on episodic memory may be more subtle than expected, warranting further exploration in larger studies.