E Appendix 2. Neuropsychological examination

Psychomotor speed, motor function and attention.

The Trail Making Test A (TMT-A) and Tracing are tasks involving visual, conceptual, and visuo-motor tracking. TMT-A requires primarily perceptual-motor speed, visual scanning, attention, and numeric sequencing (1). The test consisted of two parts, TMT-A and tracing A. The criterion variable was the number of seconds needed to complete each part.

The Dots task is sensitive to psychomotor speed (proportion of correctly passed stimuli) and accuracy (defect proportion). The task consists of three one minute sections, with each of nine lines covered by groups of three, four, or five dots (2). Participants were required to draw a line through the groups of four dots. Time was limited in each section to one minute. Because this is a paced task, the scores may reflect the effects of psychomotor slowing per se, as well as the response slowing which results from motor performance defects.

The Finger Tapping Test assesses motor speed, co-ordination, attention, alertness, slowing of responses as well as motor control (3). Criterion variables were tapping speed, which was measured with left and right index fingers, five times each, alternating hands, for a period of 10 seconds.

The Grooved Pegboard test requires manipulative dexterity, speed in a fine motor task, and complex visual-motor coordination (1). Criterion variables were the number of pegs placed into the holes of the board and the time needed to complete each task.

The Dual Task Condition Test required the participants to tap with one hand and insert pegs with the other and vice versa (4). Subjects were instructed to perform both tasks at the same time as fast as possible, and not to concentrate on one to the exclusion of the other.

Executive functions

The Trail Making Test B (TMT-B) is a task of visual, conceptual, and visuo-motor tracking which requires primarily perceptual-motor speed, visual scanning, attention, working memory and secondarily the ability to shift conceptually between numerical and alphabetical order (1). TMT-B is a well-established test of executive functions and psycho-motor speed, sensitive to impairment in multiple cognitive domains, and proved to detect specific subcortical dysfunctions (1), as well as reduced working memory capacity (1). TMT-B was administered according to standard procedures (5).

Digit Symbol is a multidimensional task requiring sustained attention, motor persistence, response speed, visuo-motor coordination, and dexterity (1). It also measures performance speed and the ability to learn a ne(6)w task. The tasks were administered and scored according to standard procedures (7).

Episodic, primary, and working memory

Immediate and delayed recall of words (episodic memory) was measured by The Claeson-Dahl Verbal Learning and Retention Test (8, 9). It is a standardized auditory, verbal learning and retention task consisting of a list of ten common Swedish words of two syllables. The number of CDSS (Scaled Scores; cumulative memory loss score) was used as the criterion variable.

Digits Span Forward is primarily a measure of attention and auditory memory span, whereas Digits Span Backward measures both attention and working memory. These tasks were administered and scored according to standard procedures (Wechsler Adult Intelligence Scale-Revised [WAIS-R]).

Verbal and visuo-spatial working memory was assessed with a computerized program (Cogmed Cognitive Medical Systems AB, Stockholm, Sweden). The verbal WM tests were sequences of numbers and syllables (presented orally with a recorded voice). The stimuli in the visuo-spatial WM tests were cubes and circles. One test involved the presentation of an array of ten cubes, with a series of individual cubes highlighted sequentially. Another test involved the sequential presentation of circles in a 4 x 4 grid.

There were two conditions for each stimulus category, requiring subjects to repeat the sequence in the same and the reverse order. Subjects remembered the string of items and responded by clicking on the locations in which the stimuli appeared, in the required order, with the computer mouse. For each task subjects responded after a delay of 1 second. When subjects responded correctly to two consecutive sequences they were rewarded with a point, as indicated by a panel on the left side of the screen, and the number of items in the sequence was increased by one. The tasks ended when the working memory capacity of the subject was exceeded and they gave incorrect responses to two consecutive sequences. Prior to the examination the subjects were instructed to respond as fast and as accurately as possible.

Reaction time, total number of trials and the level (maximum number of items in a sequence) were automatically recorded for each task.

1. Lezak MD. Neuropsychological assessment. 4th ed. London ; New York: Oxford University Press, 2004.

2. Ekberg K, Hane M. Test battery for investigating functional disorders--the TUFF battery. Scand J Work Environ Health 1984;10 Suppl 1:14-17.

3. Dodrill CB. A neuropsychological battery for epilepsy. Epilepsia 1978;19(6):611-623.

4. Brown RG, Jahanshahi M, Marsden CD. The execution of bimanual movements in patients with Parkinson's, Huntington's and cerebellar disease. J Neurol Neurosurg Psychiatry 1993;56(3):295-297.

5. Reitan RM. Manual for Administration of Neuropsychological Test Batteries for Adults and Children. Indianapolis, Indiana, 1959.

6. Devinsky O, Gershengorn J, Brown E, Perrine K, Vazquez B, Luciano D. Frontal functions in juvenile myoclonic epilepsy. Neuropsychiatry Neuropsychol Behav Neurol 1997;10(4):243-246.

7. Wechsler D. Wechsler Adult Intelligence Scale-Revised (WAIS-R). New York: Harcourt, Brace, Jovanovich, 1981.

8. Claeson L-E, Dahl E. Claeson-Dahls inlärningstest för klinisk bruk. Stockholm: Psykologiförlaget, 1971.

9. Bergman H, Bergman I, Engelbrektsson. K., Holm L, Johannesson K, Lindberg S. Psykologhandbok vid Magnus Huss kliniken [Handbook for psychologists at the Magnus Huss Clinic]. Stockholm: Karolinska Sjukhuset, 1985.