1. Transcranial direct current stimulation and
cognitive training for working memory
in Huntington’s disease
Clare M. Eddy1, Kimron Shapiro2, Andrew Clouter2, Peter C. Hansen2, Hugh E. Rickards1
1 Department of Neuropsychiatry, BSMHFT National Centre for Mental Health, Birmingham, UK
& College of Medical and Dental Sciences, University of Birmingham, UK
2 School of Psychology, College of Life and Environmental Sciences,
University of Birmingham, UK
BACKGROUND AND AIMS:
Transcranial direct current stimulation (tDCS: Figure 1) involves passing a gentle electrical current across the skull. This technique can enhance brain function when combined with a cognitive task. For example, tDCS can improve executive functions in Alzheimer’s disease [1] and Parkinson’s disease [2]. One aspect of cognition that is frequently impaired in Huntington’s disease (HD) is working memory (WM), a short-term memory system used to maintain, manipulate and update information [3]. WM is integral to everyday skills such as comprehension [4] and reasoning [5]. In HD, WM deficits can precede motor symptom onset [6] and are correlated with reduced functional capacity [7]. Previous studies have enhanced WM in healthy participants via tDCS over dorsolateral prefrontal cortex (DLPFC) [8]. We conducted a double-blind sham controlled trial of left DLPFC tDCS with WM training in HD.
Figure 1. Prof Rickards kindly showcases this season’s trend: the tDCS cap with designer electrodes
METHOD:
Participants were 20 HD gene carriers (9 females; Table 1). Visit one commenced with consent and demographic interview, followed by baseline clinical and cognitive assessments (executive functions, motor assessment [9]). Participants were then given instructions and practice on the computerised 1-back and 2-back tests in separate blocks. These tests showed a stream of letters appearing one by one on the computer screen and participants pressed a button if the letter on screen matched the letter immediately before (e.g. N,N) or 2 before (e.g. N,Y,N) tests. They completed pre-stimulation tests on these two measures, plus the Digit Ordering Test-Adapted (DOT-A [10]: recall a series of digits in ascending order e.g. 3,6,7,2,4 = 2,3,4,6,7) and Stroop colour word test (control task). They then received anodal or sham stimulation, while completing further blocks of 1-back and 2-back. Immediately after stimulation, participants completed post-stimulation tests on the above measures in the same order, and were asked about side-effects. At visit two (one week later) participants received the other stimulation condition, and were debriefed. Real stimulation proceeded with ramp up of 60 seconds, 1500mA anodal tDCS over left DLPFC for 15 minutes, then 60 seconds ramp down. For sham, participants received only ramp up and down to create a similar sensation. Both patient and assessor were blinded to condition order, which was randomised across participants. In case of stimulation termination due to skin resistance, the software was programmed to terminate during some sham sessions, maintaining blinding.
Table 1. Participant characteristics PP
Age
Disease burden
UHDRS motor score
Med
Baseline WAIS forward
Baseline WAIS back
Baseline verbal fluency
Baseline semantic fluency
HADS dep
HADS anx 1 54
513 62
MTZ 5
3.5 45 36 2 65
422.5 59
TBZ
5.5 3 12 24 4 50
425 49
CMZ 18 25
225 42
AMY/MZ
2.5 16 33 11 8
279 58
FLX
1.5 19 21 14 6
6.5 26 7 56
364 N 52
527 22 9
275 53 51 13 10
377 46 48
120 20
SRT 35 28 61
457.5 73
RP/SRT 15 43
279.5
AMY/CTL 57
375 30
4.5 68
374
CTL 72
396 27 17 55
OZ/VFX
216
319 23 38 41
202.5 39 44
Figure 2. Performance on the Digit Ordering Test-Adapted
Left axis: Mean score, pre-stimulation (Pre) and post-stimulation (Post) in the sham-stimulation (Sham) and real stimulation (tDCS) sessions. Right axis: The difference between the pre and post stimulation mean scores for the sham and tDCS sessions. Error bars represent 95% confidence intervals.
Figure 3. Correlation between change in working memory span on the DOT-A pre to post-test and UHDRS motor score at baseline
Change in working memory span is in number of digits on the Digit Ordering Test-Adapted; motor symptom severity is as measured using the Unified Huntington’s Disease Rating Scale.
AMY: amitryptiline; CMZ: carbamazepine; CTL: citalopram; FLX: fluoxetine; HADS: Hospital Anxiety and Depression Scale; Med: medication; MZ: mirtazapine; OZ: olanzapine; PP: participant; RP: risperidone; SRT: sertraline; TBZ: tetrabenazone; VFX: venlafaxine; WAIS: Wechsler Adult Intelligence Scale.
RESULTS:
Paired t-tests indicated differences from pre to post-test on specific measures. There was a significant improvement in patients’ WM span for tDCS (p=.018; Figure 2), but no significant difference for sham (p=.614). In addition, there was no difference for pre-test WM scores in the two conditions (p=.748) but there was for post-test (p<.05; greater WM span for tDCS). 2-back errors also reduced after tDCS (p=.029) but were not significantly less after sham (p=.882). However, neither pre- (p=.122) nor post-test scores (p=.254) differed for the two conditions. Time to complete the Stroop decreased after both tDCS (p=0.14) and sham (p=.015). This finding may reflect effort as it was the final task completed. No order effects were found. There was a positive correlation (p=.008) between motor symptoms and gains in WM span for tDCS (Figure 3), but not for sham. Patients with poorer baseline category fluency (p=.014) also showed greater improvement in WM after tDCS. A few mild side-effects (tingling, sleepiness, concentration effects) were reported, but with no difference between tDCS and sham.
CONCLUSIONS:
Dorsolateral prefrontal tDCS appears well tolerated in HD and could enhance working memory span.
Motor symptoms and verbal fluency scores may help identify patients who are most likely to benefit from this intervention.
Our findings encourage further trials of tDCS alone or in combination with cognitive tasks or therapy to treat other symptoms in HD.
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This research was funded by the Jacques and Gloria Gossweiler Foundation