Validation of a Behavioral Approach for Measuring Saccades in Parkinson's Disease

Speed and control of saccades are related to disease progression and cognitive functioning in Parkinson's disease (PD). Traditional eye-tracking complexities encumber application for individual evaluations and clinical trials. The authors examined psychometric properties of standalone tasks for reflexive prosaccade latency, volitional saccade initiation, and saccade inhibition (antisaccade) in a heterogeneous sample of 65 PD patients. Demographics had minimal impact on task performance. Thirty-day test–retest reliability estimates for behavioral tasks were acceptable and similar to traditional eye tracking. Behavioral tasks demonstrated concurrent validity with traditional eye-tracking measures; discriminant validity was less clear. Saccade initiation and inhibition discriminated PD patients with cognitive impairment. The present findings support further development and use of the behavioral tasks for assessing latency and control of saccades in PD.     

Subtypes of Psychopathology in Children Referred for Neuropsychological Assessment

The validity of a Personality Inventory for Children-Revised edition (PIC-R) typology was examined in a sample of 323 children aged 6–16 years. These children had been referred to a children's mental health centre for neuropsychological assessment. In study 1, K-means cluster analysis (k = 12) was applied to the PIC clinical scales in an attempt to replicate the 12 clusters identified by Gdowski, Lachar, and Kline (1985). Partial cluster replication was achieved. Examination of the obtained clusters revealed significant overlap, suggesting that fewer clusters would represent an optimal solution. In study 2, a two-stage cluster analysis yielded a seven-cluster solution consistent with several key forms of psychopathology previously reported in the literature using specific neuropsychological populations. Identified subtypes included profiles characterized as: normal, cognitive deficit, cognitive deficit with internalized psychopathology, cognitive deficit with social impairment, cognitive deficit with hyperactivity, cognitive deficit with both internalized and externalized psychopathology, and combined internalized and externalized psychopathology without a cognitive deficit component.     

Subtypes of psychopathology in children referred for neuropsychological assessment.

The validity of a Personality Inventory for Children-Revised edition (PIC-R) typology was examined in a sample of 323 children aged 6-16 years. These children had been referred to a children's mental health centre for neuropsychological assessment. In study 1, K-means cluster analysis (k = 12) was applied to the PIC clinical scales in an attempt to replicate the 12 clusters identified by Gdowski, Lachar, and Kline (1985). Partial cluster replication was achieved. Examination of the obtained clusters revealed significant overlap, suggesting that fewer clusters would represent an optimal solution. In study 2, a two-stage cluster analysis yielded a seven-cluster solution consistent with several key forms of psychopathology previously reported in the literature using specific neuropsychological populations. Identified subtypes included profiles characterized as: normal, cognitive deficit, cognitive deficit with internalized psychopathology, cognitive deficit with social impairment, cognitive deficit with hyperactivity, cognitive deficit with both internalized and externalized psychopathology, and combined internalized and externalized psychopathology without a cognitive deficit component.     

Neuropsychological assessment could distinguish among different clinical phenotypes of progressive supranuclear palsy: A Machine Learning approach

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive neurodegenerative disease. Richardson’s syndrome (PSP-RS) and predominant parkinsonism (PSP-P) are characterized by wide range of cognitive and behavioural disturbances, but these variants show similar cognitive pattern of alterations, leading difficult differential diagnosis. For this reason, we explored with an Artificial Intelligence approach, whether cognitive impairment could differentiate the phenotypes. Forty Parkinson's disease (PD) patients, 25 PSP-P, 40 PSP-RS, and 34 controls were enrolled following the consensus criteria diagnosis. Participants were evaluated with neuropsychological battery for cognitive domains. Random Forest models were used for exploring the discriminant power of the cognitive tests in distinguishing among the four groups. The classifiers for distinguishing diseases from controls reached high accuracies (86% for PD, 95% for PSP-P, 99% for PSP-RS). Regarding the differential diagnosis, PD was discriminated from PSP-P with 91% (important variables: HAMA, MMSE, JLO, RAVLT_I, BDI-II) and from PSP-RS with 92% (important variables: COWAT, JLO, FAB). PSP-P was distinguished from PSP-RS with 84% (important variables: JLO, WCFST, RAVLT_I, Digit span_F). This study revealed that PSP-P, PSP-RS and PD had peculiar cognitive deficits compared with healthy subjects, from which they were discriminated with optimal accuracies. Moreover, high accuracies were reached also in differential diagnosis. Most importantly, Machine Learning resulted to be useful to the clinical neuropsychologist in choosing the most appropriate neuropsychological tests for the cognitive evaluation of PSP patients.     

Neuropsychological impairment in Parkinson's disease without dementia

Cognitive dysfunction in Parkinson's Disease (PD) has been consistently reported, but little is known about cognitive impairment in PD patients without dementia, and its association with clinical characteristics, neuropsychiatric disturbance and functional activities. Therefore, we evaluated 52 non-demented PD patients, 22 of them with mild cognitive impairment (PD-MCI) who were matched with 52 healthy controls. Our results confirm the existence of dysfunction in information processing speed, executive function, verbal memory and visuo-perceptual processing in PD. On the other hand, PD-MCI was associated with advanced age at the onset of PD, more neuropsychiatric symptoms, caregiver stress and functional problems. The study supports the hypothesis that specific neuropsychological impairments may act as modulators of functional impairment in PD, for instance slowness of information processing.     

Investigating behavior inhibition in obsessive-compulsive disorder: Evidence from eye movements

We investigated the role of inhibition failure in Obsessive Compulsive Disorder (OCD) through an eye tracking experiment. Twenty-five subjects with OCD were recruited, as well as 25 with Generalized Anxiety Disorder (GAD) and 25 healthy controls. A 3 (group: OCD group, GAD group and control group) × 2 (target eccentricity: far and near) × 2 (saccade task: prosaccade and antisaccade) mixed design was used, with all participants completing two sets of tasks involving both prosaccade (eye movement towards a target) and antisaccade (eye movement away from a target). The main outcome was the eye movement index, including the saccade latency (the time interval from the onset of the target screen to the first saccade) and the error rate of saccade direction. The antisaccade latency and antisaccade error rates for OCDs were much higher than those for GADs and healthy controls. OCDs had longer latency and error rates for antisaccades than for prosaccades, and for far-eccentricity rather than near-eccentricity stimuli. These results suggest that OCDs experience difficulty with behavior inhibition, and that they have higher visual sensitivity to peripheral stimuli. In particular, they show greatest difficulty in inhibiting behavior directed towards peripheral stimuli.     

Neuropsychological functioning in hemiparkinsonism

A standardized neuropsychological battery including measures of intellectual cognitive, memory, attention-concentration, language, abstraction and mental flexibility, and sensory and motor functions was administered to 21 hemiparkinsonian patients (14 with right side and 7 with left side symptoms) and 17 controls matched for age and education. Patients were impaired in all functions except sensory. For motor functions, impairment was ipsilateral to the side of symptoms. For cognitive functions, right side symptoms were associated with verbal deficits whereas left side symptoms were associated with spatial deficits. Thus, a pattern of neuropsychological deficits consistent with the lateralization of motor symptoms may appear in the early stages of the disease.     

Oculomotor atypicalities in Developmental Coordination Disorder

Children with Developmental Coordination Disorder (DCD) fail to acquire adequate motor skill, yet surprisingly little is known about the oculomotor system in DCD. Successful completion of motor tasks is supported by accurate visual feedback. The purpose of this study was to determine whether any oculomotor differences can distinguish between children with and without a motor impairment. Using eye tracking technology, visual fixation, smooth pursuit, and pro‐ and anti‐saccade performance were assessed in 77 children that formed three groups: children with DCD (aged 7–10), chronologically age (CA) matched peers, and a motor‐match (MM) group (aged 4–7). Pursuit gain and response preparation in the pro‐ and anti‐saccade tasks were comparable across groups. Compared to age controls, children with DCD had deficits in maintaining engagement in the fixation and pursuit tasks, and made more anti‐saccade errors. The two typically developing groups performed similarly, except on the fast speed smooth pursuit and antisaccade tasks, where the CA group outperformed the younger MM group. The findings suggest that children with DCD have problems with saccadic inhibition and maintaining attention on a visual target. Developmental patterns were evident in the typically developing groups, suggesting that the pursuit system and cognitive control develop with age. This study adds to the literature by being the first to systematically identify specific oculomotor differences between children with and without a motor impairment. Further examination of oculomotor control may help to identify underlying processes contributing to DCD. A video abstract of this article can be viewed at: https://youtu.be/NinXa2KlB4M . [Correction added on 27 January 2017, after first online publication: The video abstract link was added.]     

The impact of Parkinson's disease on sequence learning: perceptual pattern learning and executive function

The current study examined the contribution of brain areas affected by Parkinson's disease (PD) to sequence learning, with a specific focus on response-related processes, spatial attentional control, and executive functioning. Patients with mild PD, patients with moderate PD, and healthy age-matched participants performed three tasks-a sequence learning task with a spatial pattern that was incidental to response selection, a spatial cuing task, and neuropsychological tests of executive function. Whereas moderate PD patients failed to show significant sequence learning, mild PD patients performed comparably with controls. Neither group of PD patients was impaired in the control of spatial attention. Sequence learning was correlated with neuropsychological measures of executive function but not with the ability to control spatial attention. These results suggest that the contribution of the brain areas affected by PD to sequence learning extends beyond motor learning to include the learning of perceptual patterns and involves executive function, including cognitive flexibility and set shifting.     

Antisaccades in Parkinson’s Disease: A Meta-Analysis

Neuropsychology Review - The usefulness of eye-tracking tasks as potential biomarkers for motor or cognitive disease burden in Parkinson’s disease (PD) has been subject of debate for many...     

Control of saccades in Parkinson's disease

Parkinson's patients (PD) made pro- and antisaccades: In the no-delay condition, the target appeared concurrent with the GO signal. In the delay condition, the target appeared before the signal for movement. Second, we probed spatial working memory in PD. Subjects looked to the remembered locations of sequential targets. In the no-delay prosaccade condition, PD had faster reaction times, made more express saccades, and exhibited hypometria. In the no-delay antisaccade condition, PD had longer reaction times and made more direction errors. In the delay tasks, PD made more direction errors and had more difficulty withholding a movement. PD made more sequencing errors in the spatial working memory task. These findings are consistent with a basal ganglia pathophysiology influencing eye movement processing in the frontal cortex.     

Structural brain abnormalities in patients with Parkinson’s disease with visual hallucinations: A comparative voxel-based analysis

The objective is to evaluate clinical characteristics and cerebral alterations in Parkinson’s disease (PD) patients with diurnal visual hallucinations (VHs). Assessment was performed using magnetic resonance image (MRI) and voxel-based morphometry (VBM). Thirty-nine patients with PD (53.8%) and ten controls were studied. Voxel based morphology analysis was performed. Eleven patients presented diurnal VHs and among these, six had cognitive dysfunction. Patients with VHs performed worse in the mentation-related UPDRS I (p = 0.005) and motor-related UPDRS III (p = 0.02). Patients with VHs showed significant clusters of reduced grey matter volume compared to controls in the left opercula frontal gyrus and left superior frontal gyrus. PD without hallucinations demonstrated reduced grey matter volume in the left superior frontal gyrus compared to controls. Comparisons between patients with VHs regarding the presence of cognitive dysfunction showed that cases with cognitive dysfunction as compared to those without cognitive dysfunction showed significant clusters of reduced grey matter volume in the left opercular frontal gyrus. Cases without cognitive dysfunction had reduced grey matter substance in the left insula and left trigonal frontal gyrus. Judging from our findings, an abnormal frontal cortex, particularly left sided insula, frontal opercular, trigonal frontal gyrus and orbital frontal would make PD patients vulnerable to hallucinations. Compromise of the left operculum distinguished cases with VHs and cognitive dysfunction. Our findings reinforce the theoretical concept of a top-down visual processing in the genesis of VHs in PD.     

Saccadic Eye Movements in Parkinson's Disease: II. Remembered Saccades— Towards a Unified Hypothesis?

Ten patients with mild to moderate Parkinson's disease were compared with ten age-matched normal controls in a series of saccadic paradigms in order to test various hypotheses relating to the origin of the Parkinsonian saccadic defect. The paradigms comprised a reflex saccade paradigm, a standard remembered saccade paradigm, a remembered saccade paradigm with delayed centre-offset, and a remembered saccade paradigm with a second target flash immediately prior to saccade execution. Finally, subjects executed both reflex and remembered saccades in a standard remembered paradigm (the “two-saccade” paradigm). As has been reported previously, Parkinsonian subjects demonstrated hypometria on all remembered saccade paradigms, particularly the “two-saccade” paradigm. There was, however, no significant difference between the first three remembered saccade paradigms. These studies serve to refute a simple attentional capture hypothesis, and a hypothesis that suggests that the abnormality of remembered saccades is due to concurrent reflex saccade suppression. On the basis of the results, further hypotheses are advanced in an attempt to explain all published work on Parkinsonian saccades.     

Positive affect increases cognitive control in the antisaccade task

To delineate the modulatory effects of induced positive affect on cognitive control, the current study investigated whether positive affect increases the ability to suppress a reflexive saccade in the antisaccade task. Results of the antisaccade task showed that participants made fewer erroneous prosaccades in the condition in which a positive mood was induced compared to the neutral condition (i.e. in which no emotional mood was induced). This improvement of oculomotor inhibition was restricted to saccades with an express latency. These results are in line with the idea that enhanced performance in the positive affect condition could be caused by increased dopaminergic neurotransmission the brain.     

Neuropsychological performance in patients with fibromyalgia syndrome: relation to pain and anxiety

Previous studies have revealed the presence of cognitive impairment in patients with fibromyalgia syndrome (FMS). However, they have not determined the possible influence of the diverse clinical variables in these disturbances. The first aim of the current study is to compare the cognitive function of 81 patients with FMS and 35 healthy controls by means of a neuropsychological battery. The second aim is to determine the influence of anxiety and pain in the cognitive impairment of patients with FMS. The results of our study show that patients with FMS display a significantly lower cognitive performance and a significantly higher anxiety level than the healthy controls in all the parameters assessed. The neuropsychological performance in patients with FMS is associated with pain, and this relation was independent of the anxiety level. The relationship between cognitive performance and anxiety level was also significant. Therefore, we conclude that cognitive performance is primarily affected by pain. The level of anxiety explains part of the variability in neuropsychological tests that is not explained by pain.     

Revisiting the suitability of antisaccade performance as an endophenotype in schizophrenia

Poor performance on the antisaccade task has been proposed as a candidate endophenotype in schizophrenia. Caveats to this proposal, however, include inconsistent findings in first-degree relatives of individuals with schizophrenia, and substantial heterogeneity in individuals with the disorder. In this study, we examined antisaccade performance in patients and relatives, and sought to establish whether antisaccade measures could differentiate between two patients clusters identified in the Western Australian Family Study of Schizophrenia with either pervasive cognitive deficits (CD) or cognitively spared (CS). Ninety-three patients (CD = 47, CS = 46), 99 relatives and 62 healthy controls carried out a standard antisaccade task. Results showed: (i) significantly greater error rate, and prolonged latencies to correct responses and self-correction saccades in patients compared with controls; (ii) high error rates in relatives of poorly performing patients; (iii) longer latencies of self-correction saccades in relatives compared to controls; and (iv) higher error rate and longer latencies of self-correction saccades in the CD subgroup compared with CS. Unaffected relatives as a group were unimpaired in error rate as compared to healthy controls. These findings suggest that the antisaccade error rate and latency of self-correction saccades are useful measures in specific applications of genetic research in schizophrenia, without fully meeting endophenotype co-familiality requirements.     

Saccadic eye movements as indicators of cognitive function in older adults

Older adults appear to have greater difficulty ignoring distractions during day-to-day activities than younger adults. To assess these effects of age, the ability of adults aged between 50 and 80 years to ignore distracting stimuli was measured using the antisaccade and oculomotor capture tasks. In the antisaccade task, observers are instructed to look away from a visual cue, whereas in the oculomotor capture task, observers are instructed to look toward a colored singleton in the presence of a concurrent onset distractor. Index scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were compared with capture errors, and with prosaccade errors on the antisaccade task. A higher percentage of capture errors were made on the oculomotor capture tasks by the older members of the cohort compared to the younger members. There was a weak relationship between the attention index and capture errors, but the visuospatial/constructional index was the strongest predictor of prosaccade error rate in the antisaccade task. The saccade reaction times (SRTs) of correct initial saccades in the oculomotor capture task were poorly correlated with age, and with the neurospsychological tests, but prosaccade SRTs in both tasks moderately correlated with antisaccade error rate. These results were interpreted in terms of a competitive integration (or race) model. Any variable that reduces the strength of the top-down neural signal to produce a voluntary saccade, or that increases saccade speed, will enhance the likelihood that a reflexive saccade to a stimulus with an abrupt onset will occur.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Subjective organization in the episodic memory of individuals with Parkinson’s disease associated with mild cognitive impairment

Word clustering (i.e., the ability to reproduce the same word pairs in consecutive recall trials of an unrelated word list) has been extensively investigated as a proxy of subjective organization (SO) of memorandum. In healthy subjects and in groups of brain-damaged patients, the rate of SO generally predicts accuracy of word list recall. This study aimed at evaluating SO in the performance of patients with Parkinson’s disease (PD) on a word list recall task in order to investigate the basic mechanisms of episodic memory impairment that are frequently observed in these patients. For this purpose, 56 PD patients, who were stratified according to the presence and quality of mild cognitive impairment (MCI), and a group of healthy controls (HCs) were administered a word list task and an extensive battery of neuropsychological tests. Results showed that recall accuracy on the word list task progressively decreased passing from HC to PD patients without cognitive impairment, to patients with single-domain dysexecutive MCI and to patients with multiple-domain dysexecutive and amnesic MCI. Conversely, only the latter PD group showed a lower SO score than that achieved by the other groups. In the overall PD group, correlational and regression analyses demonstrated that SO scores and a composite score of executive functions were not reciprocally related, but both provided an independent and significant contribution to the prediction of word list recall accuracy. These data are discussed in terms of the contribution of executive functions and hippocampal storage processes to the onset of memory impairment in PD.