A retrospective comparison of cognitive performance in individuals with advanced Parkinson's Disease in Hong Kong and Canada.

A deeper understanding of the cross-cultural applicability of cognitive tests across countries and cultures is needed to better equip neuropsychologists for the assessment of patients from diverse backgrounds. Our study compared cognitive test scores in patients with advanced Parkinson's disease (PD) at the Prince of Wales Hospital (n = 63; Hong Kong) and the Foothills Medical Center (n = 20; Calgary, Canada). The groups did not differ in age or sex (p > .05), but Western patients had significantly more years of education (M = 14.2, SD = 2.7) than Asian patients (M = 10.33, SD = 4.4). Cognitive tests administered to both groups included: digit span, verbal fluency (animals), the Boston Naming Test, and verbal memory (California Verbal Learning Test or Chinese Auditory Verbal Learning Test). Testing was completed before and 12 months after deep brain stimulation surgery. Results showed cognitive performance was similar across time, but significant group differences were found on digit span forward (longer among patients from Hong Kong; F(1, 75) = 44.155, p < .001) and the Boston Naming Test (higher percent spontaneous correct among patients from Canada; F(1, 62) = 7.218, p = .009, η2 = 0.104), after controlling for age, sex, and years of education. In conclusion, our findings provide preliminary support for the similarity of Chinese versions of tests originally developed for Western populations. Also, we caution that some aspects of testing may be susceptible to cultural bias and therefore warrant attention in clinical practice and refinement in future test development for Asian patients.

Action fluency identifies different sex, age, global cognition, executive function and brain activation profile in non-demented patients with Parkinson's disease.

Patients with Parkinson's disease (PD) have difficulties processing action words, which could be related to early cognitive decline. The action fluency test can be used to quickly and easily assess the processing of action words in PD. The goal of this study was to characterize how the action fluency test relates to personal characteristics, disease factors, cognition, and neural activity in PD. Forty-eight participants with PD (34 male, 14 female) and 35 control participants (16 male, 19 female) completed functional neuroimaging using a set-shifting task and a neuropsychological assessment including the action fluency test. PD participants with a score one standard deviation below the norm or lower on the action fluency test were identified. All PD participants with poor performance (PD-P, n = 15) were male. They were compared to male PD participants with scores within the normal range (PD-N, n = 19) and male healthy controls (HC, n = 16). PD-P were older, had lower global cognition scores, lower executive functions scores, and decreased activity in fronto-temporal regions compared with PD-N. There was no difference between the two PD groups in terms of the duration of the disease, dose of dopaminergic medication, and severity of motor symptoms. PD-N were younger than HC, but there was no other significant difference between these groups. The action fluency test identified a subgroup of PD patients with distinct sex, age, global cognition, executive functions, and brain activity characteristics. Implications for the evaluation of cognition are discussed.

Long versus short pulse width subcallosal cingulate stimulation for treatment-resistant depression: a randomised, double-blind, crossover trial.

BACKGROUND: Stimulation adjustment is required to optimise outcomes of deep brain stimulation (DBS) for treatment-resistant depression, but controlled data for ideal stimulation parameters are poor or insufficient. We aimed to establish the efficacy and safety of short pulse width (SPW) and long pulse width (LPW) subcallosal cingulate DBS in depression. METHODS: We did a double-blind, randomised, crossover trial in an academic hospital in Calgary, AB, Canada. Patients had DSM IV-defined major depressive disorder and bipolar depression (20-70 years old, both sexes) and did not respond to treatment for more than 1 year, with a score of 20 or more on the 17-item Hamilton Depression Rating Scale (HDRS) at recruitment. Patients underwent bilateral DBS implantation into the subcallosal cingulate white matter using diffusion tensor imaging tractography. Patients were randomly assigned 1:1 without stratification using a computerised list generator to receive either SPW (90 µs) or LPW (210-450 µs) stimulation for 6 months. Patients and the clinician assessing outcomes were masked to the stimulation group. Keeping frequency constant (130 Hz), either pulse width or voltage was increased monthly, based on response using the HDRS. Patients who did not respond to treatment (<50% reduction in HDRS from baseline) at 6 months crossed over to the opposite stimulation for another 6 months. All patients received individualised cognitive behavioural therapy (CBT) for 12 weeks. The primary outcome was change in HDRS at 6 months and 12 months using intention-to-treat analysis. This study is registered with ClinicalTrials.gov, NCT01983904. FINDINGS: Between Dec 5, 2013, and Sept 30, 2016, of 225 patients screened for eligibility, 23 patients were selected for DBS surgery. After one patient withdrew, 22 (mean age 46·4 years, SEM 3·1; 10 [45%] female, 12 [55%] male) were randomly assigned, ten (45%) to LPW stimulation and 12 (55%) to SPW stimulation. Patients were followed up at 6 months and 12 months. There was a significant reduction in HDRS scores (p<0·0001) with no difference between SPW and LPW groups (p=0·54) in the randomisation phase at 6 months. Crossover groups did not show a significant decrease in HDRS within groups (p=0·15) and between groups (p=0·21) from 6-12 months. Adverse events were equal between groups. Worsening anxiety and depression were the most common psychological adverse events. One patient in the SPW group died by suicide. INTERPRETATION: Both LPW and SPW stimulation of subcallosal cingulate white matter tracts carried similar risks and were equally effective in reducing depressive symptoms, suggesting a role for both pulse width and amplitude titration in optimising clinical outcomes in patients with treatment-resistant depression. FUNDING: Alberta Innovates Health Solutions.

Cerebral Amyloid Angiopathy Is Associated With Executive Dysfunction and Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Autopsy studies suggest that cerebral amyloid angiopathy (CAA) is associated with cognitive impairment and risk for dementia. We analyzed neuropsychological test data from a prospective cohort study of patients with CAA to identify the prevalence of cognitive impairment and its associations with brain magnetic resonance imaging features and the apolipoprotein E genotype. METHODS: Data were analyzed from 34 CAA, 16 Alzheimer's disease, 69 mild cognitive impairment, and 27 ischemic stroke participants. Neuropsychological test results were expressed as z scores in relation to normative data provided by the test manuals and then grouped into domains of memory, executive function, and processing speed. RESULTS: Mean test scores in CAA participants were significantly lower than norms for memory (-0.44±1.03; P=0.02), executive function (-1.14±1.07; P<0.001), and processing speed (-1.06±1.12; P<0.001). Twenty-seven CAA participants (79%) had mild cognitive impairment based on low cognitive performance accompanied by cognitive concerns. CAA participants had similarly low executive function scores as Alzheimer's disease, but relatively preserved memory. CAA participants' scores were lower than those of ischemic stroke controls for executive function and processing speed. Lower processing speed scores in CAA were associated with higher magnetic resonance imaging white matter hyperintensity volume. There were no associations with the apolipoprotein E ε4 allele. CONCLUSIONS: Mild cognitive impairment is very prevalent in CAA. The overall cognitive profile of CAA is more similar to that seen in vascular cognitive impairment rather than Alzheimer's disease. White matter ischemic lesions may underlie some of the impaired processing speed in CAA.

Degradation of stored movement representations in the Parkinsonian brain and the impact of levodopa.

Parkinson's disease (PD) results from the depletion of dopamine and other neurotransmitters within the basal ganglia, and is typically characterized by motor impairment (e.g., bradykinesia) and difficulty initiating voluntary movements. Difficulty initiating a movement may result from a deficit in accessing or executing a stored representation of the movement, or having to create a new representation each time a movement is required. To date, it is unclear which may be responsible for movement initiation impairments observed in PD. In this study, we used functional magnetic resonance imaging and a task in which participants passively viewed familiar and unfamiliar graspable objects, with no confounding motor task component. Our results show that the brains of PD patients implicitly analyze familiar graspable objects as if the brain has little or no motor experience with the objects. This was observed as a lack of differential activity within brain regions associated with stored movement representations for familiar objects relative to unfamiliar objects, as well as significantly greater activity for familiar objects when off levodopa relative to on medication. Symptom severity modulated this activity difference within the basal ganglia. Levodopa appears to normalize brain activity, but its effect may be one of attenuation of brain hyperactivity within the basal ganglia network, which is responsible for controlling motor behavior and the integration of visuomotor information. Overall, this study demonstrates that difficulty initiating voluntary movements experienced by PD patients may be the result of degradation in stored representations responsible for the movement.

Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study.

BACKGROUND: Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is reported to be a safe and effective new treatment for treatment-resistant depression (TRD). However, the optimal electrical stimulation parameters are unknown and generally selected by trial and error. This pilot study investigated the relationship between stimulus parameters and clinical effects in SCC-DBS treatment for TRD. METHODS: Four patients with TRD underwent SCC-DBS surgery. In a double-blind stimulus optimization phase, frequency and pulse widths were randomly altered weekly, and corresponding changes in mood and depression were evaluated using a visual analogue scale (VAS) and the 17-item Hamilton Rating Scale for Depression (HAM-D-17). In the open-label postoptimization phase, depressive symptoms were evaluated biweekly for 6 months to determine long-term clinical outcomes. RESULTS: Longer pulse widths (270-450 µs) were associated with reductions in HAM-D-17 scores in 3 patients and maximal happy mood VAS responses in all 4 patients. Only 1 patient showed acute clinical or mood effects from changing the stimulation frequency. After 6 months of open-label therapy, 2 patients responded and 1 patient partially responded. LIMITATIONS: Limitations include small sample size, weekly changes in stimulus parameters, and fixed-order and carry-forward effects. CONCLUSION: Longer pulse width stimulation may have a role in stimulus optimization for SCC-DBS in TRD. Longer pulse durations produce larger apparent current spread, suggesting that we do not yet know the optimal target or stimulus parameters for this therapy. Investigations using different stimulus parameters are required before embarking on large-scale randomized sham-controlled trials.

Attention and reach-to-grasp movements in Parkinson's disease.

The role of attention in grasping movements directed at common objects has not been examined in Parkinson's disease (PD), though these movements are critical to activities of daily living. Our primary objective was to determine whether patients with PD demonstrate automaticity in grasping movements directed toward common objects. Automaticity is assumed when tasks can be performed with little or no interference from concurrent tasks. Grasping performance in three patient groups (newly diagnosed, moderate, and advanced/surgically treated PD) on and off of their medication or deep brain stimulation was compared to performance in an age-matched control group. Automaticity was demonstrated by the absence of a decrement in grasping performance when attention was consumed by a concurrent spatial-visualization task. Only the control group and newly diagnosed PD group demonstrated automaticity in their grasping movements. The moderate and advanced PD groups did not demonstrate automaticity. Furthermore, the well-known effects of pharmacotherapy and surgical intervention on movement speed and muscle activation patterns did not appear to reduce the impact of attention-demanding tasks on grasping movements in those with moderate to advanced PD. By the moderate stage of PD, grasping is an attention-demanding process; this change is not ameliorated by dopaminergic or surgical treatments. These findings have important implications for activities of daily living, as devoting attention to the simplest of daily tasks would interfere with complex activities and potentially exacerbate fatigue.

The Canadian multicentre study of deep brain stimulation for cervical dystonia.

Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective treatment for generalized dystonia. Its role in the management of other types of dystonia is uncertain. Therefore we performed a prospective, single-blind, multicentre study assessing the efficacy and safety of bilateral GPi-DBS in 10 patients with severe, chronic, medication-resistant cervical dystonia. Two blinded neurologists assessed patients before surgery and at 6 and 12 months post-operatively using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The primary outcome measure was the severity subscore (range 0-30, higher scores indicating greater impairment). Secondary outcomes included disability (0 to 30), pain (0 to 40) subscores and total scores of the TWSTRS, Short Form-36 and Beck depression inventory. Swallowing and neuropsychological assessment were also performed at baseline and 12 months. One-way repeated measures analysis of variance was used to analyse the data. The TWSTRS severity score improved from a mean (SD) of 14.7 (4.2) before surgery to 8.4 (4.4) at 12 months post-operatively (P = 0.003). The disability and pain scores improved from 14.9 (3.8) and 26.6 (3.6) before surgery, to 5.4 (7.0) and 9.2 (13.1) at 12 months, respectively (both P < 0.001). General health and physical functioning as well as depression scores improved significantly. Complications were mild and reversible in four patients. Some changes in neuropsychological tests were observed, although these did not impact daily life or employment. Our results support the efficacy and safety of GPi-DBS for the treatment of patients with severe and prolonged cervical dystonia who have failed medical management.

Learned perceptual associations influence visuomotor programming under limited conditions: cues as surface patterns.

The present set of three experiments was designed to extend the findings that visuomotor programming can make use of learned size information under some, but not all, conditions. An association was established between the size of square wooden blocks and a perceptual cue in all experiments. In Experiment 1 the perceptual cue to size was a small two-dimensional drawing of a shape affixed to the top of the blocks (e.g. triangle = large; circle = small, or vice versa). In Experiment 2 size and shape were again associated but this time a pattern of two-dimensional shapes covered the visible surface of the blocks. In Experiment 3 block size was associated with the colour of a small circle affixed to the top of the blocks (e.g. red = large; yellow = small, or vice versa). All of the subjects grasped the blocks, and on other trials estimated the size of the blocks by opening their thumb and finger a matching amount. Consistent with previous reports, in all experiments, the learned associations changed the perceived size of two test blocks halfway in size between the large and small blocks: estimations of the test block matched by shape or colour to the group of large objects were smaller than estimations of the test block matched to the group of small objects. The effect appears to result from relative-size comparisons being made between the medium-sized test blocks and the size category (large or small) associated with the matching shape or colour cue. Despite the significant effect of the learned perceptual associations on manual estimations, no effect on grip scaling was seen when the cues associated with size were single small elements centred on the top of the block (Experiment 1 and Experiment 3). Changes in grip scaling corresponded to the change in perceived size only when the cue to size covered the entire block (Experiment 2), forming a surface pattern. These findings suggest that visuomotor programming is more likely to use learned size information when the cue providing the size association covers the visible surface of the target objects, perhaps by acting as a texture that provides reliable information about the target's material and identity.

Learned perceptual associations influence visuomotor programming under limited conditions: kinematic consistency.

Previous findings have suggested that visuomotor programming can make use of learned size information in experimental paradigms where movement kinematics are quite consistent from trial to trial. The present experiment was designed to test whether or not this conclusion could be generalized to a different manipulation of kinematic variability. As in previous work, an association was established between the size and colour of square blocks (e.g. red = large; yellow = small, or vice versa). Associating size and colour in this fashion has been shown to reliably alter the perceived size of two test blocks halfway in size between the large and small blocks: estimations of the test block matched in colour to the group of large blocks are smaller than estimations of the test block matched to the group of small blocks. Subjects grasped the blocks, and on other trials estimated the size of the blocks. These changes in perceived block size were incorporated into grip scaling only when movement kinematics were highly consistent from trial to trial; that is, when the blocks were presented in the same location on each trial. When the blocks were presented in different locations grip scaling remained true to the metrics of the test blocks despite the changes in perceptual estimates of block size. These results support previous findings suggesting that kinematic consistency facilitates the incorporation of learned perceptual information into grip scaling.

A temporal analysis of grasping in the Ebbinghaus illusion: planning versus online control.

Recent work has shown that pictorial illusions have a greater effect on perceptual judgements than they do on the visual control of actions, such as object-directed grasping. This dissociation between vision for perception and vision for action is thought to reflect the operation of two separate streams of visual processing in the brain. Glover and Dixon claim, however, that perceptual illusions can influence the control of grasping but that these effects are evident only at early stages of the movement. By the time the action nears its completion any effect of illusions disappears. Glover and Dixon suggest that these results are consistent with what they call a 'planning and control' model of action, in which actions are planned using a context-dependent visual representation but are monitored and corrected online using a context-independent representation. We reanalysed data from an earlier experiment on grasping in the Ebbinghaus illusion in which we showed that maximum grip aperture was unaffected by this size-contrast illusion. When we looked at these data more closely, we found no evidence for an effect of the illusion even at the earliest stages of the movement. These findings support the suggestion that the initial planning of a simple object-directed grasping movement in this illusory context is indeed refractory to the effects of the illusion. This is not to suggest that more deliberate and/or complex movements could not be influenced by contextual information.