# Brain functional connectivity changes in amyotrophic lateral sclerosis with apathy and depression

## TL;DR

This study explores how brain connectivity differs in ALS patients with apathy, depression, or both, highlighting the importance of distinguishing these symptoms for better diagnosis and treatment.

## Contribution

The study identifies distinct neural correlates of apathy and depression in ALS using brain functional connectivity analysis.

## Key findings

- Depressive symptoms correlate with reduced path length in the bilateral basal ganglia network.
- Apathy is associated with increased path length and decreased efficiency in the left basal ganglia network.
- Apathetic ALS patients show altered functional properties in parietal, occipital, and frontal networks compared to non-apathetic patients.

## Abstract

Apathy and depression are the most prevalent neuropsychiatric symptoms in amyotrophic lateral sclerosis (ALS). Although insufficiently investigated, their distinction holds important clinical relevance for accurate diagnosis of ALS with behavioural impairment and for patients’ prognosis and management. In the present study, we aimed to assess both apathy and depressive symptoms in patients with ALS and whether they have similar or different functional neural correlates.

Using graph analysis and connectomics, global and lobar nodal properties and regional functional brain connectivity were assessed in ALS patients without apathy/depression (ALSn, n = 42), with apathy without depression (ALSa, n = 14), with depressive symptoms without apathy (ALSd, n = 20), and with apathy and depressive symptoms (ALSad, n = 6), and 46 healthy controls. Correlations between brain functional properties, apathy and depressive symptoms were performed in all patients.

Depressive symptoms were related with reduced path length within bilateral basal ganglia (BG) network, and apathy was related with increased path length, decreased nodal strength and local efficiency within left BG network. ALSa patients showed altered functional nodal properties within BG network compared to ALSn and ALSd. Compared to healthy controls and all non-apathetic patients (ALSn and ALSd), all apathetic patients (ALSa and ALSad) exhibited altered functional nodal properties within parietal, occipital and frontal networks. Non-apathetic patients, compared to apathetic patients, showed relatively preserved functional nodal properties in the BG network.

Our findings indicate differences in brain functional neural organization associated with apathy and depression, underscoring the importance of distinguishing these symptoms in ALS and highlighting the need for targeted interventions.

The online version contains supplementary material available at 10.1007/s00415-025-13247-1.