The feasibility of using robotic technology to quantify sensory, motor, and cognitive impairments associated with ALS

Figures & data

Figure 1 The KINARM exoskeleton robot and robotic assessment tasks. (a) The KINARM exoskeleton robot allows patients to sit and perform behavioral tasks as weight support is provided to their arms. Tasks are displayed on a horizontal virtual reality display aligned with the horizontal workspace of the arm. (b) Tasks are arranged in cognitive, motor, and sensory groups. Motor tasks: clockwise from Ball on Bar to Elbow Stretch (ND). Sensory task: Arm Position Matching. Cognitive tasks: clockwise from Spatial Span to Reverse Visually-Guided Reaching (inter-limb). Small markers: Task Scores above 1.96 indicate impairment as they are outside the 95th percentile of performance of healthy subjects. Large markers: performance within the 95th percentile of healthy controls.

Table 1 Task descriptions.

Task	Description
Visually guided reaching (VGR)	VGR required participants to reach quickly and accurately from a central target to a sequence of 4 peripheral targets [8,13]. This task tests the ability to make smooth and accurate reaches.
Object hit (OH)	Participants had to hit as many virtual balls away from them as possible. Balls fell more quickly as the task progressed and the task lasted for a fixed amount of time [9]. This task tests bimanual motor skill.
Object hit and avoid (OHA)	Participants had to hit two specific shapes (e.g. a vertical ellipse and a small square) and avoid 6 other distractors [10]. This task tests rapid decision-making processes.
Ball on bar (BOB)	Participants were required to move a ball balanced on a bar to a sequence of 4 targets as quickly as possible. In level 1 the ball was fixed to the bar but in subsequent levels the ball was able to move and fall off of the bar [12]. This task tests bimanual coordination.
Elbow stretch test (EST)	Participants were required to relax their arm as the robot moved the arm at one of two speeds [11]. This task tests the passive resistance of the arm to flexion and extension movements.
Arm position matching (APM)	In this task, the robot moved one of the participant’s arms (the “active” arm) and the participant was required to mirror-match the position of their active arm with their other arm. The goal of the task was to match position as accurately as possible and was not timed [7].
Reverse visually guided reaching (RVGR)	Similar to VGR except the white cursor representing the participant’s hand moved in the opposite direction of their hand [26]. This task tests the ability to inhibit an automatic motor response.
Trail making (TMT)	Participants must navigate between targets labeled with numbers (1..2..etc; variant A) or numbers and letters (1..2..etc; variant B) in order and as quickly as possible. The number of targets was the same in both variants [15,25,28,37]. This task tests processing speed (A) and set-switching (B).
Spatial span (SPS)	A random sequence of square targets was displayed on a 3x4 grid which participants were to recall in the same order as shown to them. Sequence length was increased 1 after a successful trial and reduced by 1 after an unsuccessful trial [27]. This task tests working memory capacity.

Table 2 Individual-specific clinical and demographic data.

Participant #	Age	Sex	ALS diagnosis	Etiology	ALSFRS-R bulbar	ALSFRS-R fine motor	ALSFRS-R gross motor	ALSFRS-R respiratory	ALSFRS-R total	FAB	MoCA	Purdue L	Purdue R	Dyn. L (kg)	Dyn. R (kg)	Strength L (sum)	Strength R (sum)
P1	73	M	CD	LMN	16	12	13	13	39	18	28	6	5.5	–	–	13	11
P2	51	M	CD	BUL	15	4	8	15	28	18	30	–	–	1.7	2	8	7
P3	70	F	CD	LMN	12	12	15	14	37	18	30	13.5	14.5	15	15	13	9
P4	56	M	CD	LMN	15	4	8	12	28	15	24	–	–	1	0	9	7
P5	67	M	CP	UMN	15	13	12	14	38	16	21	8.5	11	26	36	15	12
P6	60	M	CD	UMN	6	7	11	11	25	10	23	–	–	2	1	10	9
P7	61	M	CD	LMN	14	5	13	15	33	12	23	1.5	0.5	2	2	9	10
P8	72	F	CP	UMN	16	8	14	16	37	18	28	8.5	–	14	0.5	14	13
P9	72	M	CP	LMN	14	8	8	15	31	9	17	7.5	8	60	45	15	15
P10	59	F	CD	LMN	12	11	12	9	31	18	27	13.5	8	15.5	2	14	13
P11	69	F	CD	LMN	16	14	13	16	41	17	28	11.5	17	18	16	14	13
P12	63	M	CD	LMN	15	11	14	16	39	18	27	4	5	21	16	12	10
P13	64	M	PLS	UMN	11	10	14	13	33	18	27	3.5	4	20	23	15	13
P14	64	M	CD-FTD	LMN	11	8	17	13	35	17	24	4.5	–	8	2	15	11
P15	79	M	CD	LMN	15	8	9	15	32	15	22	3.5	3	13	1	10	7
P16	51	M	CP	LMN	15	13	16	15	42	17	25	11	11.5	24	27	11	9
P17	63	M	CD	LMN	15	13	17	16	42	13	25	–	5.5	2	5	6	1

Bold text indicates that a score was below the impairment threshold. A dash indicates that the item was not completed. Strength score was the sum of scores for triceps, biceps, and deltoids (scale of 1–5; 5 indicates normal strength).

CD: Clinically definite; CP: Clinically probable; PLS: Primary lateral sclerosis; FTD: Frontotemporal dementia; UMN: upper motor neuron; LMN: lower motor neuron; BUL: bulbar.

Table 3 Individual task scores for all participants in the study.

	C					S		M
	RVGR: Dom	RVGR: Non dom	RVGR: Inter-limb	TMT	SPS	APM: Dom	APM: Non dom	EST: Dom	EST: Non dom	VGR: Dom	VGR: Non dom	VGR: Inter-limb	OH	OHA	BOB	Total
P1	2.87	2.47	1.92	1.30	0.86	0.34	1.83	0.41	3.51	3.61	1.93	2.30	2.49	1.97	-	7/14
P2	3.64	-	-	0.54	0.20	2.08	0.68	1.88	1.55	4.05	-	-	7.08	4.46	-	5/10
P3	1.81	0.77	1.89	0.12	0.76	0.32	1.46	0.76	0.81	0.88	0.35	0.55	1.98	0.25	1.05	1/15
P4	2.57	2.82	1.35	2.16	0.34	1.00	1.28	0.21	1.31	2.94	2.25	1.24	1.70	1.26	1.98	6/15
P5	2.87	2.21	2.78	1.09	1.23	0.52	0.81	3.53	1.46	2.55	1.18	2.09	1.16	0.43	1.61	6/15
P6	1.93	1.53	0.81	1.53	5.40	0.39	0.80	1.17	1.52	2.60	1.88	1.32	1.98	2.29	2.47	5/15
P7	3.36	2.79	4.29	3.18	2.50	3.18	1.25	3.48	3.41	2.62	2.21	1.64	2.34	2.07	-	12/14
P8	-	-	-	0.31	0.13	5.79	1.41	0.36	4.54	3.04	-	-	9.41	5.98	-	5/9
P9	3.05	1.96	4.46	2.83	7.85	0.68	2.28	3.90	3.48	1.01	1.38	0.59	0.55	1.29	0.70	7/15
P10	1.46	1.19	1.98	0.38	0.70	0.16	0.69	3.44	2.65	0.70	0.08	0.92	1.06	0.26	1.01	3/15
P11	2.22	3.68	4.62	0.77	2.54	1.04	0.04	2.78	2.44	0.40	0.83	1.00	0.22	0.06	0.40	6/15
P12	2.90	1.62	3.26	1.10	0.25	0.26	0.39	2.61	3.94	1.42	0.75	0.89	1.49	1.37	2.49	5/15
P13	1.61	1.30	0.34	1.56	0.54	0.08	0.97	3.88	4.07	2.41	1.74	1.85	3.17	2.90	-	5/14
P14	3.88	2.57	4.66	0.83	0.51	1.42	0.68	3.14	3.45	1.48	1.91	1.12	0.44	0.71	1.96	5/15
P15	4.32	3.79	5.06	-	-	-	-	-	-	2.85	2.61	2.01	-	-	-	6/6
P16	1.46	1.30	1.11	1.47	0.88	0.81	0.25	-	-	2.86	2.01	1.13	2.53	2.40	1.28	4/13
P17	3.93	3.59	4.50	1.53	1.76	1.92	0.94	-	-	1.79	1.74	0.07	3.33	2.50	2.15	6/13
Total	69%	53%	60%	19%	25%	19%	6%	57%	64%	59%	27%	20%	56%	50%	36%	41%

Bold: Task Scores outside of the 95% range of healthy controls (>1.96); Dash: task not completed; C: cognitive tasks; S: sensory tasks; M: motor tasks; Bottom row: proportion of participants outside of 95% range of healthy controls for each task.

Figure 2 Example patient performance on robotic assessment tasks. Each row displays Task Scores for four example participants and hand paths for three tasks. Task Scores are written underneath each task and are indicated as impaired (bold) when appropriate. ‘Dom’ denotes dominant hand and ‘Non-dom’ denotes non-dominant hand.

Table 4 Correlations between clinical scores and robotic tasks.

		C					S		M
		RVGR: Dom	RVGR: Non dom	RVGR: Inter	TMT	SPS	APM: Dom	APM: Non dom	EST: Dom	EST: Non dom	VGR: Dom	VGR: Non dom	VGR: Inter	OH	OHA	BOB
C	FAB	−0.24	−0.26	−0.26	−0.75*	−0.88*	0.03	−0.47	−0.18	0.10	0.10	−0.30	0.20	0.19	−0.09	−0.13
	MoCA	−0.30	−0.25	−0.35	−0.72*	−0.71*	0.14	−0.35	−0.44	−0.05	0.09	−0.37	−0.08	0.45	0.16	−0.05
S	R reflexes	−0.64	−0.45	−0.25	−0.36	0.24	0.09	−0.23	−0.18	−0.24	−0.36	−0.66	−0.60	−0.35	−0.44	−0.85
	L reflexes	−0.09	−0.11	0.04	0.31	0.51	0.48	0.34	0.15	0.52	0.07	0.06	−0.03	−0.01	0.26	−0.26
M	ALSFRS − R bulbar	0.36	0.48	0.41	0.00	−0.33	0.31	0.06	−0.11	0.21	0.18	−0.01	0.07	0.11	−0.02	−0.34
	ALSFRS − R fine motor	−0.33	−0.17	−0.01	−0.37	−0.11	−0.37	−0.43	0.19	0.05	−0.43	−0.51	−0.16	−0.35	−0.43	−0.37
	ALSFRS − R gross motor	−0.15	−0.14	0.00	−0.30	−0.38	0.11	−0.23	0.09	0.38	−0.29	−0.14	−0.28	−0.19	−0.18	0.17
	ALSFRS − R respiratory	0.46	0.44	0.58	0.08	0.00	0.44	0.05	0.03	0.30	0.05	0.13	−0.19	0.17	0.20	−0.10
	ALSFRS − R total	−0.01	0.14	0.25	−0.23	−0.31	0.05	−0.24	0.05	0.33	−0.23	−0.23	−0.17	−0.21	−0.26	−0.20
	Dynamometer L hand	−0.18	−0.31	0.12	0.20	0.52	−0.26	0.11	0.49	0.29	−0.38	−0.26	−0.10	−0.42	−0.29	−0.56
	Dynamometer R hand	−0.27	−0.34	−0.06	0.24	0.42	−0.40	0.02	0.54	0.07	−0.26	−0.19	0.00	−0.29	−0.19	−0.47
	Purdue R	−0.48	−0.25	−0.13	−0.62	0.02	−0.47	−0.55	−0.27	−0.75	−0.49	−0.60	−0.33	−0.53	−0.68	−0.72
	Purdue L	−0.62	−0.45	−0.31	−0.61	−0.03	−0.24	−0.42	−0.28	−0.65	−0.43	−0.74	−0.51	−0.29	−0.60	−0.72
	R arm strength	−0.42	−0.37	−0.08	−0.01	0.23	−0.02	0.14	0.57	0.63	−0.32	−0.31	0.29	−0.53	−0.44	−0.56
	L arm strength	−0.42	−0.45	−0.11	−0.24	0.05	−0.16	−0.04	0.40	0.38	−0.41	−0.40	0.22	−0.63	−0.62	−0.57

Bold: Correlation significant uncorrected for multiple comparisons, not significant after correction 0.0033<p < 0.05; Bold/asterisk: Correlation significant after multiple comparisons correction p < 0.0033. Dom: denotes dominant hand; Non dom: denotes non − dominant hand; Inter: denotes inter − limb comparison.

Coderre AM, Abou Zeid A, Dukelow SP, Demmer MJ, Moore KD, Demers MJ, et al. Assessment of upper-limb sensorimotor function of subacute stroke patients using visually guided reaching. Neurorehabil Neural Repair. 2010;24:528–41.

 PubMed Web of Science ®Google Scholar

Mostafavi SM, Dukelow SP, Glasgow JI, Scott SH, Mousavi P. Reduction of stroke assessment time for visually guided reaching task on KINARM exoskeleton robot. Conf Proc IEEE Eng Med Biol Soc. 2014;2014:5296–9.

 PubMedGoogle Scholar

Tyryshkin K, Coderre AM, Glasgow JI, Herter TM, Bagg SD, Dukelow SP, et al. A robotic object hitting task to quantify sensorimotor impairments in participants with stroke. J NeuroEngineering Rehabil. 2014;11:47.

 PubMed Web of Science ®Google Scholar

Bourke TC, Lowrey CR, Dukelow SP, Bagg SD, Norman KE, Scott SH. A robot-based behavioural task to quantify impairments in rapid motor decisions and actions after stroke. J Neuroeng Rehabil. 2016;13:91.

 PubMed Web of Science ®Google Scholar

Lowrey CR, Jackson CPT, Bagg SD, Dukelow SP, Scott SH. A novel robotic task for assessing impairments in bimanual coordination post-stroke. Int J Phys Med Rehabil. 2014;S3:1–10.

 Google Scholar

Centen A, Lowrey CR, Scott SH, Yeh TT, Mochizuki G. KAPS (kinematic assessment of passive stretch): a tool to assess elbow flexor and extensor spasticity after stroke using a robotic exoskeleton. J Neuroeng Rehab. 2017;14:1–13.

 PubMed Web of Science ®Google Scholar

Dukelow SP, Herter TM, Moore KD, Demers MJ, Glasgow JI, Bagg SD, et al. Quantitative assessment of limb postion sense following stroke. Neurorehabil Neural Repair. 2010;24:178–87.

 PubMed Web of Science ®Google Scholar

Hawkins KM, Sergio LE. Visuomotor impairments in older adults at increased Alzheimer’s disease risk. Jad. 2014;42:607–21.

 Google Scholar

Little CE, Emery C, Black A, Scott SH, Meeuwisse W, Nettel-Aguirre A, et al. Test-retest reliability of KINARM robot sensorimotor and cognitive assessment: in pediatric ice hockey players. J Neuroeng Rehab. 2015;12:78.

 PubMed Web of Science ®Google Scholar

Ahn SW, Kim SH, Kim JE, Kim SM, Kim SH, Sung JJ, et al. Frontal assessment battery to evaluate frontal lobe dysfunction in ALS patients. Can J Neurol Sci. 2011;38:242–6.

 PubMed Web of Science ®Google Scholar

Arbuthnott K, Frank J. Trail making test, part b as a measure of executive control: validation using a set-switching paradigm. J Clin Exp Neuropsychol. 2000;22:518–28.

 PubMed Web of Science ®Google Scholar

Tombaugh TN. Trail making Test A and B: normative data stratified by age and education. Arch Clin Neuropsychol. 2004;19(2):203–14.

 PubMed Web of Science ®Google Scholar

Corsi PM. Memory and the medial temporal region of the brain [dissertation]. Montreal (Quebec): McGill University; 1972.

 Google Scholar

Data availability

All relevant data are included in the manuscript, figures, and tables.