Castelnovo Veronica, Canu Elisa, Basaia Silvia, Spinelli Edoardo Gioele, Freri Fabiola, Schito Paride, Russo Tommaso, Falzone Yuri, Verde Federico, Torre Silvia, Poletti Barbara, Tremolizzo Lucio, Appollonio Ildebrando, Ticozzi Nicola, Silani Vincenzo, Filippi Massimo, Agosta Federica
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Neurol. 2025 Jul 14;272(8):509. doi: 10.1007/s00415-025-13247-1.
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.
冷漠和抑郁是肌萎缩侧索硬化症（ALS）中最常见的神经精神症状。尽管对其研究不足，但区分它们对于准确诊断伴有行为障碍的ALS以及患者的预后和管理具有重要的临床意义。在本研究中，我们旨在评估ALS患者的冷漠和抑郁症状，以及它们是否具有相似或不同的功能性神经关联。
使用图谱分析和连接组学，对无冷漠/抑郁的ALS患者（ALSn，n = 42）、有冷漠无抑郁的患者（ALSa，n = 14）、有抑郁症状无冷漠的患者（ALSd，n = 20）、有冷漠和抑郁症状的患者（ALSad，n = 6）以及46名健康对照者进行全脑和脑叶节点属性以及区域脑功能连接性评估。对所有患者的脑功能属性、冷漠和抑郁症状之间的相关性进行分析。
抑郁症状与双侧基底神经节（BG）网络内路径长度缩短有关，而冷漠与左BG网络内路径长度增加、节点强度降低和局部效率降低有关。与ALSn和ALSd相比，ALSa患者的BG网络内功能性节点属性发生改变。与健康对照者和所有无冷漠的患者（ALSn和ALSd）相比，所有有冷漠的患者（ALSa和ALSad）在顶叶、枕叶和额叶网络内的功能性节点属性均发生改变。与有冷漠的患者相比，无冷漠的患者在BG网络中表现出相对保留的功能性节点属性。
我们的研究结果表明，与冷漠和抑郁相关的脑功能神经组织存在差异，强调了在ALS中区分这些症状的重要性，并突出了针对性干预的必要性。
