Manuscript ID: BRB3-2024-05-0705
Journal Brain and Behavior
Title: "Apathy and impulsivity co-occur in Huntington’s disease"

Dear Editor and Authors:
Thank you for the opportunity to review this article. I enjoyed the review process and I hope you find my comments constructive. Firstly, I think this paper is suitable for the journal. I believe other researchers/practitioners around movement disorders, particularly HD, will benefit from this contribution. The paper is generally well-written and organised. I have provided a list of comments below for the editor and authors’ consideration. The references I provide as examples are not authored by me to avoid any conflict of interest.
Note: I will refer to Huntington’s Disease as HD in this review.
Abstract: provide keywords.
Key points: The authors state “Apathetic people with HD…”, This claim suggests that apathy is a personality trait that precedes HD. Although it is noted in the manuscript that apathy can be understood as a personality trait, it is my understanding that apathy is one of the core non-motor symptoms of many movement disorders affecting the basal ganglia. Therefore, it would be more accurate to say that people with HD and apathy are more likely to be impulsive.
Apathy is a core non-motor symptom in HD and one of the most investigated. According to a recent review, more research on this construct is needed because of the contention on the multidimensionality of this construct (see Matmati, J., Verny, C., & Allain, P. (2022). Apathy and Huntington’s disease: A literature review based on PRISMA. The Journal of Neuropsychiatry and Clinical Neurosciences, 34(2), 100-112.). The paper defines apathy using the multidimensional approach provided by Levy and Dubois (2006) but highlights that this model has been criticised by Dickson and Husain (2022). I think it is important for the authors to develop this critique and clearly state what kind of theoretical approach has been adopted in this paper, particularly because it has implications for the assessment tools, the analysis, and the discussion, where the authors argue for the multidimensionality of impulsivity and apathy, which is not the way they analysed these variables.
The authors recognise in the discussion that anosognosia in HD represents a limitation when using self-reported measurements. This should be briefly noted in the introduction because it feels like “the elephant in the room”. A recent paper (Isaacs, D., Gibson, J. S., Stovall, J., & Claassen, D. O. (2020). The impact of anosognosia on clinical and patient-reported assessments of psychiatric symptoms in Huntington’s disease. Journal of Huntington's Disease, 9(3), 291-302.) notes that anosognosia does not have the same impact on all behavioural assessments, so it would be important to argue/explain how all these scores were used and why this is appropriate for the aim of the paper. I understand that this is the authors' decision, but I thought it would be helpful to have the data described in all these subdomains.

In the ’measures’ section, the authors should specify the version and subdomains for all instruments because they are given for some but not others. For example, it is not clear what version was used for the AES and who are the original authors of this scale (I don’t think are Mason & Barker, 2015). All these scales are multidimensional, therefore, I assumed that the authors would analyse these data using the subdomains separately. Given that this is not the case as composite scores were created, I think it would be helpful to argue in the discussion the limitations of this (and the reasons behind this decision were clearly explained). Specifically, the claim “that the overlap between these two behavioural phenotypes may occur between particular dimensions of each construct” is particularly important for this paper and needs to be unpacked.
Clarify what “a mechanistic understanding of apathy and impulsivity” means (page 17).
I would recommend including in Table 2 data for the subdomains of each instrument. These data are important for comparison with other clinical and research data.
On page 17, the authors note: “At a clinical level, the results…. Screening for features of each”. I think this is an important issue and I wonder if the authors can suggest, based on the empirical evidence of their study, the best instruments to use.
The statement on page 19: “…it is clear that not all dimensions of apathy and impulsivity necessarily co-occur” should be referenced.
The statement on page 20: “… it remains vital for treating clinicians…” should be referenced.
The statement on page 20: “… although this is less likely an issue at the premanifest… should be referenced. This would be a good point to discuss the potential impact of anosognosia for this specific sample and the implications of not measuring it/including it in the design.