Objective:

To assess resting-state functional connectivity (RS-FC) of the hypothalamus in patients with amyotrophic lateral sclerosis (ALS) as compared to healthy controls (HC), and to evaluate its relationship with clinical measures.

Background:

Hypermetabolism is a newly identified clinical feature of ALS, associated with shorter survival. Hypothalamic volume reduction and white matter structural connectivity alterations between hypothalamus, orbitofrontal and insular regions have been recently reported as a possible underlying cause. However, changes in functional connectivity of hypothalamus and its relationship with patients’ clinical severity have not been thoroughly investigated yet.

Design/Methods:

Seventy-one ALS patients and 39 age- and sex- matched HC underwent brain structural and resting state functional MRI (rs-fMRI) on a 3 Tesla scanner. In each subject, the bilateral hypothalamus was manually segmented and a seed-based RS-FC analysis was performed between this region and the rest of the brain. Hypothalamic RS-FC was then compared among groups, and the relationship between RS-FC significant changes and ALS Functional Rating Scarle – revised (ALSFRS-r) scores was investigated.

Results:

The seed-based analysis showed that, compared to HC, ALS patients exhibited increased hypothalamic RS-FC with the caudate nuclei bilaterally. Additionally, greater disease severity in terms of ALSFRS-r scores in patients correlated with an increase of RS-FC between hypothalamus and both the bilateral caudate nucleus and orbitofrontal cortex.

Conclusions:

These findings support the presence of hypothalamic alterations in ALS. These RS-FC changes may be related to the hypermetabolic clinical feature in these patients. The early detection of the hypothalamic changes in ALS could be useful for prognostic stratification and for monitoring the effect of specific interventions.