TABLE 1.

Highlights of the findings.

Gray matter damage	• The majority of studies demonstrated an involvement of BG in ALS, particularly in patients with cognitive/behavioral impairment. • Measures of iron deposition, metabolism and atrophy of BG are able to distinguish ALS cases from controls with relatively high accuracy. • Longitudinal studies considering 6–9 months of follow-up evidenced a progressive reduction of the striatum volume, mainly in ALS patients with a fast progression. • Longitudinal studies considering 24 months of follow-up evidenced a widespread progressive reduction of BG volume, including caudate, pallidum, putamen, and thalamus in ALS patients. • ALS patients with C9orf72 expansion show more extensive involvement of BG structures than those who do not carry a C9orf72 mutation.
Microstructural changes	• DTI studies revealed lower microstructural integrity of the striatum in ALS when compared to controls, mainly in cases with cognitive/behavioral involvement and/or fast progression. • The structural connectivity is reduced between the head of caudate, the dorsomedial frontal and the lateral orbitofrontal cortices in ALSci and ALS-FTD patients. • Longitudinal studies considering 6–24 months of follow-up evidenced progressive microstructural changes in the bilateral thalamus of ALS patients.
Functional MRI studies	• Compared with ALScn, ALSci, and ALS-FTD patients show hypoconnectivity in the ventral attentional network. • At the 0.03–0.06 frequency bands ALS patients exhibit increased BG connectivity. • Altered RS-FC between BG and orbitofrontal and temporal regions is associated with worse cognitive performances in ALS. • Altered RS-FC between striatum and SMA and cerebellum is related with greater disease severity and shorter disease duration. • Most fMRI studies reported an increased activation of caudate and putamen when ALS patients performed a motor task. • The altered functional connectivity between GP and frontal and temporal cortices is related with worse emotional processing in ALScn.
Graph analysis and connectome	• So far, few studies investigated structural and functional connectivity in ALS using graph analysis and connectomics. • Compared to controls, ALS showed reduced mean structural local efficiency and longer path length in BG, as well as reduced microstructural integrity within the BG structural network. • Distruction of the structural connectome, which includes BG, occurs also in ALScn and precedes functional alterations. • Nodal efficiency of the left caudate is decreased in ALSci.

ALS, amyotrophic lateral sclerosis; ALSci, ALS with cognitive impairment; ALScn, ALS cognitively normal; ALS-FTD, ALS-frontotemporal dementia; BG, basal ganglia; DTI, diffusion tensor imaging; fMRI, functional magnetic resonance imaging; GP, globus pallidus; RS-FC, resting state-functional connectivity; SMA, supplementary motor area.