Online Resource 1. Neurocognitive Tests Performed in the Participants.

A battery of neurocognitive tests were administered on the day of scanning that were selected initially based on their sensitivity in detecting differences between groups from previous large scale multi-site studies (Stout et al. 2011; Tabrizi et al. 2009). The tests assessed visuomotor speed and attention [Symbol Digit Modalities Test, SDMT; (Smith 1982)], speeded reading [STROOP word test; (Stroop 1935)], odour recognition [University of Pennsylvania Smell Identification Test, UPSIT; (Doty et al. 1984)], and motor performance [speeded tapping and self-timed finger tapping tasks; (Hinton et al. 2007; Paulsen et al. 2004)]. Participants also completed assessments of behaviours associated with frontal-striatal brain dysfunction, including executive function, apathy and disinhibition [Frontal Systems Behaviour Scale, FrSBe; (Grace and Mallory 2001)] and psychiatric disturbances [Schedule of Obsessions, Compulsions and Psychological Impulses, SCOPI; Watson (Watson and Wu 2005); Hospital Anxiety and Depression Scale, HADS; (Zigmond and Snaith 1983); Beck Depression Inventory Version II, BDI-II; (Beck et al. 1996)]. Neurocognitive data for both testing sessions are provided for descriptive purposes in Supplementary Table S1.

Table S1: Summary neurocognitive data for participants included in all longitudinal analyses for N-BACK for all groups: Means±Standard Deviations (SD).

Baseline
18m(18 months)
30m(30 months) / Controls
(N=20) / Pre-HD
(N=22) / Symp-HD
(N=11)
SDMT / Baseline / 58.30+10.27 / 54.23+9.89 / 43.64+11.66**+
18m / 57.65+8.25 / 55.23+10.29 / 42.55+8.77**+
30m / 60.20+10.84 / 54.50+9.62 / 42.00+11.57**+
STROOP word test / Baseline / 113.20+18.20 / 105.05+19.13 / 95.73+15.73*
18m / 103.60+15.41 / 101.18+14.59 / 89.18+14.32*
30m / 109.00+17.07 / 103.18+19.08 / 92.45+18.21
FrSBe / Baseline / 83.80+21.27 / 88.77+21.10 / 91.36+17.66
18m / 76.75+17.08 / 85.55+18.55 / 86.73+18.03
30m / 79.45+16.69 / 83.91+20.71 / 87.91+21.31
UPSIT / Baseline / 34.40+3.17 / 33.91+3.31 / 28.73+8.22*+
18m / 33.95+2.82 / 33.45+4.67 / 27.18+7.01**+
30m / 34.53+3.15 / 32.59+4.48 / 24.18+6.29**++
Speeded tapping task (msec) / Baseline / 208.31+25.82 / 242.12+46.55 / 310.30+72.06**++
18m / 211.10+33.83 / 232.07+41.98 / 312.41+81.06**++
30m / 208.23+27.94 / 233.08+46.75 / 320.85+95.78**++
Self- timed finger tapping task:
(1/SD ITI) 333ms / Baseline / 24.19+7.47 / 20.16+6.94 / 11.88+4.04**+
18m / 28.70+8.55 / 22.34+6.94^ / 13.90+6.28**+
30m / 25.60+8.37 / 22.31+6.75 / 12.48+5.97**+
Self-timed finger tapping task :
(1/SD ITI) 550ms / Baseline / 29.98+7.88 / 24.60+9.42 / 14.32+7.46**+
18m / 32.81+7.22 / 27.46+9.60 / 16.66+10.12**+
30m / 32.47+8.20 / 28.25+10.08 / 15.08+9.56**+
SCOPI / Baseline / 84.15+23.23 / 79.95+24.27 / 85.18+16.67
18m / 76.30+14.51 / 73.55+16.94 / 84.36+21.95
30m / 79.80+17.22 / 79.00+24.90 / 86.91+20.21
HADS A / Baseline / 5.70+2.68 / 5.95+2.52 / 4.36+1.69
18m / 4.45+2.21 / 5.09+3.69 / 3.00+2.15
30m / 4.05+3.07 / 5.23+2.98 / 3.00+2.65
HADS D / Baseline / 2.30+2.39 / 2.05+1.84 / 2.18+1.89
18m / 2.55+1.91 / 2.50+1.97 / 2.91+2.77
30m / 2.15+1.95 / 2.18+1.84 / 3.00+3.10
BDI II / Baseline / 4.50+4.06 / 5.68+6.88 / 5.00+5.57
18m / 3.75+3.73 / 5.45+4.74 / 4.64+4.59
30m / 4.75+5.07 / 5.00+4.16 / 5.09+5.45

SDMT, Symbol Digit Modalities Test; STROOP, STROOP word test (number of correct words); FrSBe, Frontal Systems Behaviour Scale (Total score); SCOPI, Schedule of Compulsions, Obsessions, and Pathological Impulses (Total OCD score); HADS Hospital Anxiety and Depression scale (A: Anxiety subscale; D: Depression subscale); BDI-II, Beck Depression Inventory score Version II; UPSIT: University of Pennsylvania Smell Identification Test (score out of 40); Self-timed finger tapping task: (1/SD, ITI, inter-tap interval ) 333ms; Self-timed finger tapping task:(1/SD, ITI) 550ms. One way Anova, (Boferroni, post-hoc analyses for between groups differences) : ΔControls vs Symp-HD *p<0.05; **p<0.001; ΔControls vs Pre-HD ^p<0.05; ^^p<0.001; ΔPre-HD vs Symp-HD + p<0.05; ++p<0.001

References

Beck AT, Steer RA, Brown GK (1996) Manual for the beck depression inventory-II. Psychological Corporation, San Antonio.

Doty RL, Shaman P, Kimmelman CP, Dann MS (1984) University of pennsylvania smell identification test: A rapid quantitative olfactory function test for the clinic. Laryngoscope 94:176-178.

Grace J, Mallory PF (2001) Frontal systems behavior scale: Professional manual. Psychological Assessment Resources, Lutz.

Hinton SC, Paulsen JS, Hoffmann RG, Reynolds NC, Zimbelman JL, Rao SM (2007) Motor timing variability increases in preclinical Huntington's disease patients as estimated onset of motor symptoms approaches. J Int Neuropsychol Soc 13:539-543.

Paulsen JS, Zimbelman JL, Hinton SC, Langbehn DR, Leveroni CL, Benjamin ML, Reynolds NC, Rao SM (2004) fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's disease. Am J Neuroradiol 25:1715-1721.

Smith A (1982) Symbol digit modality test (SDMT): Manual (revised). Psychological Services, Los Angeles.

Stout JC, Paulsen JS, Queller S, Solomon AC, Whitlock KB, Campbell JC, Carlozzi N, Duff K, Beglinger LJ, et al. (2011) Neurocognitive Signs in Prodromal Huntington Disease. Neuropsychology 25:1-14.

Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18:643-662.

Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D, Kennard C, Hicks SL, Fox NC, et al. (2009) Biological and clinical manifestations of huntington's disease in the longitudinal TRACK-HD study: Cross-sectional analysis of baseline data. Lancet Neurol 8:791-801.

Watson D, Wu KD (2005) Development and validation of the schedule of compulsions, obsessions, and pathological impulses (SCOPI). Assessment 12:50-65.

Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361-370.