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.     

Possible selves in patients with right- versus left-onset Parkinson’s disease

Possible selves can be used to self-regulate and guide behavior towards what is desired to be achieved or avoided in life. Previous work suggests laterality effects exist within the brain regarding approach and avoidance systems to achieve self-regulation. A modified version of the possible selves task was administered to 45 patients with PD (22 right-onset and 23 left-onset) and 25 community dwelling control subjects (CS). Only 11.1% of patients exhibited balance among their hoped-for and feared possible selves versus 28% of CS. More right-onset patients used a promotion strategy whereas more left-onset patients used a prevention strategy. Patients with left-onset PD thought more about their feared selves, exhibiting reduced goal-directed behavior. Findings among the left-onset group indicate relative dependence of self-regulation on right-sided avoidance brain systems. This may point to an inability to move away from negative outcomes and to work towards rewarding outcomes, which could affect psychological health.     

Self-unawareness of levodopa induced dyskinesias in patients with Parkinson’s disease

The study analyzes the presence of dyskinesias-reduced-self-awareness in forty-eight patients suffering from Parkinson’s disease (PD). As the association with executive dysfunction is a matter of debate and we hypothesize it plays an important role in dyskinesias self-unawareness, we analyzed the role of dopaminergic treatment on the medial-prefrontal-ventral-striatal circuitry using a neurocognitive approach. Special attention was given to metacognitive abilities related to action-monitoring that represent a novel explanation of the phenomenon.PD patients were assessed using different rating scales that we devised to measure movement awareness disorders. In order to ascertain whether each variable measured at a cognitive-clinical level contributes to predicting the scores of the movement-disorder-awareness-scales, we conducted multiple logistic regression models using the latter as binary dependent variables. We used the Wisconsin Card Sorting Test-metacognitive-version to assess the executive functions of the prefrontal-ventral-striatal circuitry.Data showed that a reduction of self-awareness using the Dyskinesia rating scale was associated with global monitoring (p = .04), monitoring resolution (p = .04) and control sensitivity (p = .04). Patients failed to perceive their performance, distinguish between correct and incorrect sorts, be confident in their choice and consequently decide to gamble during the task.We did not find any association with executive functions using the hypo-bradykinesia rating scale.Our findings indicate that when the comparator mechanism for monitoring attentive performance is compromised at a prefrontal striatal level, patients lose the ability to recognize their motor disturbances that do not achieve conscious awareness.     

Subjective states associated with retrieval failures in Parkinson’s disease

Instances in which we cannot retrieve information immediately but know that the information might be retrieved later are subjective states that accompany retrieval failure. These are expressed in feeling-of-knowing (FOK) and Tip-of-the-tongue (TOT) experiences. In Experiment 1, participants with Parkinson’s disease (PD) and older adult controls were given general questions and asked to report when they experienced a TOT state and to give related information about the missing word. The PD group experienced similar levels of TOTs but provided less correct peripheral information related to the target when in a TOT state. In Experiment 2, participants were given a Semantic (general knowledge questions) and an Episodic (word pairs) FOK task. PD patients failed to accurately predict their future memory performance (FOK) in response to both episodic and semantic cues. Results are interpreted in the context of recent frameworks of memory and metacognition.     

Emotional state affects gait initiation in individuals with Parkinson’s disease

The purpose of the present study was to determine the impact of manipulating emotional state on gait initiation in persons with Parkinson’s disease (PD) and healthy older adults. Following the presentation of pictures that are known to elicit specific emotional responses, participants initiated gait and continued to walk for several steps at their normal pace. Reaction time, the displacement and velocity of the center of pressure (COP) trajectory during the preparatory postural adjustments, and length and velocity of the first two steps were measured. Analysis of the gait initiation measures revealed that exposure to (1) threatening pictures, relative to all other pictures, speeded the initiation of gait for PD patients and healthy older adults; (2) approach-oriented emotional pictures (erotic and happy people), relative to withdrawal-oriented pictures, facilitated the anticipatory postural adjustments of gait initiation for PD patients and healthy older adults, as evidenced by greater displacement and velocity of the COP movement; and (3) emotional pictures modulated gait initiation parameters in PD patients to the same degree as in healthy older adults. Collectively, these findings hold significant implications for understanding the circuitry underlying the manner by which emotions modulate movement and for the development of emotion-based interventions designed to maximize improvements in gait initiation for individuals with PD.     

Exploring the association of the Comprehensive Trail Making Test with driving indexes in patients with Parkinson’s disease

The Trail Making test (TMT) has been identified as predictor of driving ability in patients with Parkinson’s disease (PD). However, previous research has not explored the effectiveness of an alternative version of the TMT, namely of the Comprehensive Trail Making Test (CTMT; Reynolds, 2002) to show associations with measures related to driving fitness. Main objective of the current work was to evaluate the capacity of the CTMT to detect associations with fitness to drive related measures in patients with PD. Inclusion criteria were the presence of a valid driver’s license, regular car driving, a CDR score ≤ 0.5, and a Hoehn & Yahr score between 1 and 3. Twelve individuals with PD (Age: Mean = 63.75, SD = 10.50) and 12 cognitively intact individuals (Age: Mean = 63.50, SD = 10.43) were introduced in the study. Collection of data included a comprehensive neurological/neuropsychological assessment and a driving simulation experiment. Certain subtests of the CTMT were more strongly associated with a variety of driving indexes in individuals with PD as compared to the original TMT. In addition, according to the stepwise regression models that were applied, the CTMT was recognized as a more effective predictor of driving behavior than the TMT. The pattern of findings that was observed supports the usefulness of CTMT on detecting associations with fitness to drive related-measures in patients with PD. Underlying factors that may explain the effectiveness of the CTMT could be related to the greater variety of set shifting and inhibition processes that this alternative option integrates as compared to the original TMT.     

Separating the effect of reward from corrective feedback during learning in patients with Parkinson’s disease

Parkinson’s disease (PD) is associated with procedural learning deficits. Nonetheless, studies have demonstrated that reward-related learning is comparable between patients with PD and controls (Bódi et al., Brain, 132(9), 2385–2395, 2009; Frank, Seeberger, & O’Reilly, Science, 306(5703), 1940–1943, 2004; Palminteri et al., Proceedings of the National Academy of Sciences of the United States of America, 106(45), 19179–19184, 2009). However, because these studies do not separate the effect of reward from the effect of practice, it is difficult to determine whether the effect of reward on learning is distinct from the effect of corrective feedback on learning. Thus, it is unknown whether these group differences in learning are due to reward processing or learning in general. Here, we compared the performance of medicated PD patients to demographically matched healthy controls (HCs) on a task where the effect of reward can be examined separately from the effect of practice. We found that patients with PD showed significantly less reward-related learning improvements compared to HCs. In addition, stronger learning of rewarded associations over unrewarded associations was significantly correlated with smaller skin-conductance responses for HCs but not PD patients. These results demonstrate that when separating the effect of reward from the effect of corrective feedback, PD patients do not benefit from reward.     

Horizontal and vertical attentional orienting in Parkinson’s disease

Patients with Parkinson’s disease (PD) typically suffer from an asymmetric degeneration of dopaminergic cells in the substantia nigra, resulting in right-sided (RPD) or left-sided (LPD) predominance of motor symptomatology. As the dopaminergic system is also involved in attention, we examined horizontal and vertical orienting of attention in LPD (N = 10), RPD (N = 9) and controls (N = 10). Four LPD patients demonstrated left neglect and three LPD patients demonstrated neglect for the upper visual field. LPD patients demonstrated a slower performance in detecting targets in the left hemifield and did not demonstrate a validity effect, unlike RPD patients and controls. RPD patients performed similar to controls, with the exception of one patient showing left and another showing right neglect, and two RPD patients demonstrated lower neglect. In sum, horizontal and vertical orienting of attention can be affected in Parkinson’s disease – particularly in LPD – from very subtle slowing to clinically detectable horizontal and/or vertical neglect.     

Effort to reduce postural sway affects both cognitive and motor performances in individuals with Parkinson’s disease

ObjectivesTo assess the effects of voluntarily reducing postural sway on postural control and to determine the attention level needed to do so in healthy adults (n = 16, 65.9 ± 9.7) and persons with PD (n = 25, 65.8 ± 9.5 years). Tasks: quiet and still standing conditions with and without a category task. Cognitive performance, center of pressure (CoP) displacement variability (RMSCoP) and velocity (VCoP) were assessed in the anterior-posterior (AP) and medial-lateral (ML) directions.Controls showed larger RMSCoP (AP) and VCoP (AP and ML) during still versus quiet standing (p < 0.01), while the PD group demonstrated no changes. In the PD group, RMSCoP and VCoP (ML) increased in still standing when performed with the cognitive task (p < 0.05). In both groups, cognitive responses decreased in still standing (p < 0.05).In PD, attempting to reduce postural sway did not affect postural control under single task conditions, however ML CoP variability and velocity did increase as a dual task. In older adults, increased displacement and velocity in both AP and ML directions was observed during single, but not dual task conditions. Therefore standing still might not be an adequate postural strategy as it increases the attentional demand and affects motor performance, putting persons with PD at greater risk for falls.     

Rhythmic priming across effector systems: A randomized controlled trial with Parkinson’s disease patients

This study investigated the immediate effects of auditory-motor entrainment across effector systems by examining whether Rhythmic Auditory Stimulation training of arm or finger movements would modulate gait speed. Forty-one participants with idiopathic Parkinson’s Disease were randomly assigned to 3 groups. Participants in the finger-tapping group tapped in synchrony with a metronome set to 20% faster pace than the pre-training walking cadence, whereas participants in the other group were asked to swing both arms in an alternating motion in synchrony with the metronome. Participants in the control condition did not receive training. To assess gait parameters pre- and post-training, participants walked on a 14-meter flat walkway at his/her preferred walking cadence with no auditory cueing. Results indicated that there was a significant increase in gait velocity after the finger tapping training (p < .005), whereas no differences were observed in the arm swing (p = .802) and in the control conditions (p = .525). Similarly, there were significant changes in gait cadence post-training in the finger tapping group (p < .005), but not after arm swing training (p = .879) or control (p = .759). There were no significant changes in stride length post-training in none of the groups. These findings suggest that auditory-motor entrainment in one effector system may prime a second effector system. Interestingly, however, the priming effect on gait was only observed in the finger tapping condition and not with synchronized arm swing movements. These findings have significant implications for motor rehabilitation and open new avenues for further investigation of the mechanisms underlying cross-effector coupling.     

Dysexecutive syndrome in Parkinson’s disease: the GREFEX study

The objectives of this study were to characterize the frequencies and profiles of behavioral and cognitive dysexecutive syndromes in PD (based on validated battery and diagnostic criteria) and to develop a shortened diagnostic battery. Eighty-eight non-demented patients with a diagnosis of PD were examined with an executive validated battery. Using a validated framework, the patients’ test results were interpreted with respect to normative data from 780 controls. A dysexecutive syndrome was observed in 80.6% of the patients [95% confidence interval: 71.1–90.1]. The dysexecutive profile was characterized by prominent impairments in deduction, flexibility, inhibition and initiation in the cognitive domain, and by global hypoactivity with apathy and hyperactivity in the behavioral domain. This finding implies that patients with PD should be assessed with cognitive tests and a validated inventory for behavioral dysexecutive syndromes. A shortened battery (based on three cognitive tests and three behavioral domains) provided high diagnostic accuracy.     

Theory of mind and joint action in Parkinson’s disease

It has been suggested that the Theory of Mind (ToM) may rely on more basic processes of social cognition, such as action control (e.g., joint action), even if little is known about this relationship. The relationship between ToM and joint action can be studied in patients with Parkinson’s disease (PD), because they are characterized not only by a deficit in ToM (and in its cognitive and affective subcomponents) but also by a deficit in the inhibition of competing responses. Sixty PD patients and 60 matched healthy controls (HCs) performed a go/no-go Flanker task in both joint and individual conditions. Cognitive (Advanced Test or AT) and affective (Emotion Attribution Task or EAT) ToM also were measured. Thirty-five PD patients and matched HCs also performed the standard Flanker task, as a control measure. In patients, only individuals with high AT scores exhibited a joint Flanker effect, whereas in HCs the joint effect was found irrespectively of AT score. Patients with low EAT scores showed a greater interference effect than patients with high scores, whereas the opposite pattern was found for HCs. In regression analysis AT and EAT scores predicted the Flanker effect in the joint condition only. In the standard task, both groups showed a Flanker effect. The role of different fronto-striatal circuits, especially in PD patients, could explain the different involvement of cognitive and affective ToM in joint tasks. The Flanker effect is discussed considering the referential coding account and the attention-focus account as possible candidates to explain joint action effects.     

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.     

Differences in performance in CAMCOG-R domains between old and oldest old patients with Alzheimer’s disease

The purpose of this study is to evaluate the neuropsychological performance in a ≥90-year-old population with Alzheimer disease (AD) in comparison with younger elderly patients. We retrospectively studied all patients with AD attended in a specialized clinic between 1999 and 2011. Age, sex, educational level, and sensory loss data were collected. Neuropsychological evaluation included Mini-Mental State Examination and Global Deterioration Scale. We used the eight Cambridge Cognitive Assessment (CAMCOG-R) domains to evaluate and compare the neuropsychological performance in the younger than 90 years old (<90) and older than 90 years old (≥90) groups. We selected 2931 patients, 2897 <90 (98.83%) and 34 ≥90 years old (1.17%). The ≥90 group had significant lower punctuations in memory, praxis, and abstract thinking CAMOCG-R domains with 1.49, 0.75, and 0.58 less points, respectively, (p < 0.05). Neuropsychological characteristics of cognitive decline seem to be different in ≥90 compared to <90 years old patients. According to age, the biggest differences in the CAMCOG-R performance are in the memory, praxis, and abstract thinking domains.     

Cognitive and motor deficits in older adults with HIV infection: Comparison with normal ageing and Parkinson’s disease

Despite the life-extending success of antiretroviral pharmacotherapy in HIV infection (HIV), the prevalence of mild cognitive impairment in HIV remains high. Near-normal life expectancy invokes an emerging role for age–infection interaction and a potential synergy between immunosenescence and HIV-related health factors, increasing risk of cognitive and motor impairment associated with degradation in corticostriatal circuits. These neural systems are also compromised in Parkinson’s disease (PD), which could help model the cognitive deficit pattern in HIV. This cross-sectional study examined three groups, age 45–79 years: 42 HIV, 41 PD, and 37 control (CTRL) participants, tested at Stanford University Medical School and SRI International. Neuropsychological tests assessed executive function (EF), information processing speed (IPS), episodic memory (MEM), visuospatial processing (VSP), and upper motor (MOT) speed and dexterity. The HIV and PD deficit profiles were similar for EF, MEM, and VSP. Although only the PD group was impaired on MOT compared with CTRL, MOT scores were related to cognitive scores in HIV but not PD. Performance was not related to depressive symptoms, socioeconomic status, or CD4⁺ T-cell counts. The overlap of HIV-PD cognitive deficits implicates frontostriatal disruption in both conditions. The motor-cognitive score relation in HIV provides further support for the hypothesis that these processes share similar underlying mechanisms in HIV infection possibly expressed with or exacerbated by ageing.     

Understanding the role of configural processing in face emotion recognition in Parkinson’s disease

This investigation examined whether impairment in configural processing could explain deficits in face emotion recognition in people with Parkinson’s disease (PD). Stimuli from the Radboud Faces Database were used to compare recognition of four negative emotion expressions by older adults with PD (n = 16) and matched controls (n = 17). Participants were tasked with categorizing emotional expressions from upright and inverted whole faces and facial composites; it is difficult to derive configural information from these two types of stimuli so featural processing should play a larger than usual role in accurate recognition of emotional expressions. We found that the PD group were impaired relative to controls in recognizing anger, disgust and fearful expressions in upright faces. Then, consistent with a configural processing deficit, participants with PD showed no composite effect when attempting to identify facial expressions of anger, disgust and fear. A face inversion effect, however, was observed in the performance of all participants in both the whole faces and facial composites tasks. These findings can be explained in terms of a configural processing deficit if it is assumed that the disruption caused by facial composites was specific to configural processing, whereas inversion reduced performance by making it difficult to derive both featural and configural information from faces.     

Executive function in Parkinson’s disease: contributions of the dorsal frontostriatal pathways to action and motivation

Disruption of the dorsal frontostriatal pathways in Parkinson’s disease (PD) is associated with impairments in motivation, as well as in executive function. The goal of this study was to investigate whether these impairments are related and, if so, whether the disruption of frontostriatal pathways compromises the ability to process the motivational aspects of feedback in such tasks. In Experiment 1, informative feedback improved the performance of young, healthy participants in a task-switching paradigm. This task-switching paradigm was then used in Experiment 2 to test whether feedback would improve the performance of 17 PD patients and age-matched controls. The PD group benefitted from feedback to the same degree as control participants; however, depression scores on the Beck Depression Inventory were significantly related to feedback usage, especially when response selection demands were high. Regardless of feedback, PD patients were more impaired when response demands were high than in an equally difficult condition with low action demands. These results suggest that response selection is a core impairment of insufficient dopamine to the dorsal frontal striatal pathways.     

Optimized cuttlefish algorithm for diagnosis of Parkinson’s disease

This paper presents an optimized cuttlefish algorithm for feature selection based on the traditional cuttlefish algorithm, which can be used for diagnosis of Parkinson’s disease at its early stage. Parkinson is a central nervous system disorder, caused due to the loss of brain cells. Parkinson's disease is incurable and could eventually lead to death but medications can help to control symptoms and elongate the patient's life to some extent. The proposed model uses the traditional cuttlefish algorithm as a search strategy to ascertain the optimal subset of features. The decision tree and k-nearest neighbor classifier as a judgment on the selected features. The Parkinson speech with multiple types of sound recordings and Parkinson Handwriting sample’s datasets are used to evaluate the proposed model. The proposed algorithm can be used in predicting the Parkinson’s disease with an accuracy of approximately 94% and help individual to have proper treatment at early stage. The experimental result reveals that the proposed bio-inspired algorithm finds an optimal subset of features, maximizing the accuracy, minimizing number of features selected and is more stable.     

Effects of disease severity and medication state on postural control asymmetry during challenging postural tasks in individuals with Parkinson’s disease

The aim of this study was to investigate the effects of disease severity and medication state on postural control asymmetry during challenging tasks in individuals with Parkinson’s disease (PD). Nineteen people with PD and 11 neurologically healthy individuals performed three standing task conditions: bipedal standing, tandem and unipedal adapted standing; the individuals with PD performed the tasks in ON and OFF medication state. The participants with PD were distributed into 2 groups according to disease severity: unilateral group (n = 8) and bilateral group (n = 11). The two PD groups performed the evaluations both under and without the medication. Two force plates were used to analyze the posture. The symmetric index was calculated for various of center of pressure. ANOVA one-way (groups) and two-way (PD groups × medication), with repeated measures for medication, were calculated. For main effects of group, the bilateral group was more asymmetric than CG. For main effects of medication, only unipedal adapted standing presented effects of PD medication. There was PD groups × medication interaction. Under the effects of medication, the unilateral group presented lower asymmetry of RMS in anterior–posterior direction and area than the bilateral group in unipedal adapted standing. In addition, the unilateral group presented lower asymmetry of mean velocity, RMS in anterior–posterior direction and area in unipedal standing and area in tandem adapted standing after a medication dose. Postural control asymmetry during challenging postural tasks was dependent on disease severity and medication state in people with PD. The bilateral group presented higher postural control asymmetry than the control and unilateral groups in challenging postural tasks. Finally, the medication dose was able to reduce postural control asymmetry in the unilateral group during challenging postural tasks.