Purpose

In spite of the well-known importance of the thalamus in multiple sclerosis (MS), only limited data on whole and sub-regional thalamic functional connectivity (FC) are available [1]. Aim of this study was to investigate the sub-regional thalamic resting state (RS) FC and its relationship with clinical and cognitive measures in multiple sclerosis (MS) patients.

Methods

Diffusion tensor (DT), 3D T1-weighted and RS functional MRI data were acquired from 187 right–handed MS patients and 94 age- and sex-matched healthy controls (HC). MS patients underwent a clinical assessment, with rating of the EDSS score [2], and a cognitive evaluation [3]. Patients were considered cognitively impaired if they had abnormal scores in at least two cognitive tests [4]. DT MRI data were used to parcellate the thalamus into five sub-regions, according to their structural connectivity profile (frontal, motor, post-central, occipital and temporal, Figure 1), as described in details elsewhere [5]. For each sub-region, a seed-based RS FC analysis was performed. Multiple regression models were run to assess correlations between thalamic RS FC and clinical/cognitive variables.

Results

Compared to HC, MS patients had higher intra- and inter-thalamic RS FC in almost all thalamic sub-regions. Conversely, temporal thalamic sub-region showed reduced intra-thalamic RS FC and higher RS FC with the fronto-parietal somatomotor cortex (Figure 2). Compared to cognitively preserved, cognitively impaired MS patients had lower RS FC between thalamic sub-regions and caudate nucleus, anterior cingulate cortex, as well as higher RS FC between thalamic sub-regions and several temporal areas (Figure 3). This latter finding was correlated with poor motor and cognitive performance. Lower RS FC between thalamic sub-regions and caudate and cingulate cortex was correlated with worst motor/cognitive performance.

Conclusions

In MS, the different behavior of temporal thalamic sub-region, compared to other thalamic sub-regions, could contribute to explain the variability of thalamic RS FC findings in previous studies. The increased RS FC between temporal thalamic sub-region and temporal/frontal regions seen in MS patients compared to HC, as well as in cognitively impaired compared to cognitively preserved MS patients is likely to be a maladaptive mechanism, associated with clinical/cognitive impairment.

Acknowledgements

This study has been partially supported by a grant from FISM 2011/R/19 and Italian Ministry of Health (GR-2009-1529671).

References

[1] Schoonheim M., et al. Neurology 2015; 84:776-83. [2] Kurtzke J.F. Neurology 1983; 33:1444-52. [3] Rao S., et al., Neurology 1991. [4] Amato M.P., et al. Mult Scler 2006; 12:787-93. [5] Bisecco A., et al. Hum Brain Mapp 2015; 36:2809-25.