An ERP measure of non-conscious memory reveals dissociable implicit processes in human recognition using an open-source automated analytic pipeline.

Non-conscious processing of human memory has traditionally been difficult to objectively measure and thus understand. A prior study on a group of hippocampal amnesia (N = 3) patients and healthy controls (N = 6) used a novel procedure for capturing neural correlates of implicit memory using event-related potentials (ERPs): old and new items were equated for varying levels of memory awareness, with ERP differences observed from 400 to 800 ms in bilateral parietal regions that were hippocampal-dependent. The current investigation sought to address the limitations of that study by increasing the sample of healthy subjects (N = 54), applying new controls for construct validity, and developing an improved, open-source tool for automated analysis of the procedure used for equating levels of memory awareness. Results faithfully reproduced prior ERP findings of parietal effects that a series of systematic control analyses validated were not contributed to nor contaminated by explicit memory. Implicit memory effects extended from 600 to 1000 ms, localized to right parietal sites. These ERP effects were found to be behaviorally relevant and specific in predicting implicit memory response times, and were topographically dissociable from other traditional ERP measures of implicit memory (miss vs. correct rejections) that instead occurred in left parietal regions. Results suggest first that equating for reported awareness of memory strength is a valid, powerful new method for revealing neural correlates of non-conscious human memory, and second, behavioral correlations suggest that these implicit effects reflect a pure form of priming, whereas misses represent fluency leading to the subjective experience of familiarity.

Neural correlates of the Dunning-Kruger effect.

The Dunning-Kruger effect (DKE) is a metacognitive phenomenon of illusory superiority in which individuals who perform poorly on a task believe they performed better than others, yet individuals who performed very well believe they under-performed compared to others. This phenomenon has yet to be directly explored in episodic memory, nor explored for physiological correlates or reaction times. We designed a novel method to elicit the DKE via a test of item recognition while electroencephalography (EEG) was recorded. Throughout the task, participants were asked to estimate the percentile in which they performed compared to others. Results revealed participants in the bottom 25th percentile over-estimated their percentile, while participants in the top 75th percentile under-estimated their percentile, exhibiting the classic DKE. Reaction time measures revealed a condition-by-group interaction whereby over-estimators responded faster than under-estimators when estimating being in the top percentile and responded slower when estimating being in the bottom percentile. Between-group EEG differences were evident between over-estimators and under-estimators during Dunning-Kruger responses, which revealed FN400-like effects of familiarity supporting differences for over-estimators, whereas "old-new" memory event-related potential effects revealed a late parietal component associated with recollection-based processing for under-estimators that was not evident for over-estimators. Findings suggest over- and under-estimators use differing cognitive processes when assessing their performance, such that under-estimators may rely on recollection during memory while over-estimators may draw upon excess familiarity when over-estimating their performance. Episodic memory thus appears to play a contributory role in metacognitive judgements of illusory superiority.

Evidence for subtypes of freezing of gait in Parkinson's disease.

BACKGROUND: The purpose of this study is to identify and characterize subtypes of freezing of gait by using a novel questionnaire designed to delineate freezing patterns based on self-reported and behavioral gait assessment. METHODS: A total of 41 Parkinson's patients with freezing completed the Characterizing Freezing of Gait questionnaire that identifies situations that exacerbate freezing. This instrument underwent examination for construct validity and internal consistency, after which a data-driven clustering approach was employed to identify distinct patterns amongst individual responses. Behavioral freezing assessments in both dopaminergic states were compared across 3 identified subgroups. RESULTS: This novel questionnaire demonstrated construct validity (severity scores correlated with percentage of time frozen; r = 0.54) and internal consistency (Cronbach's α = .937), and thus demonstrated promising utility for identifying patterns of freezing that are independently related to motor, anxiety, and attentional impairments. CONCLUSIONS: Patients with freezing may be dissociable based on underlying neurobiological underpinnings that would have significant implications for targeting future treatments. © 2018 International Parkinson and Movement Disorder Society.

Retrospective Neuropsychological Profile of Patients With Parkinson Disease Prior to Developing Visual Hallucinations.

Visual hallucinations (VH) are a common feature of Parkinson disease (PD); however, the cognitive profile preceding the onset of VH has not yet been established. The present study investigated longitudinal neuropsychological performance of patients with PD who developed VH during follow-up compared to a group who did not develop VH. The patient groups were matched for demographic and disease severity variables at their baseline assessments. Patients who developed VH displayed impaired performance at baseline on measures of psychomotor speed, executive functioning, reaction time, and attention compared to patients who did not develop VH. These results demonstrate a profile of cognitive deficits specific to patients with PD at risk of developing VH and implicate attentional dysfunction in the early pathogenesis of VH.

Dysfunction in attentional processing in patients with Parkinson's disease and visual hallucinations.

Mechanistic insights into visual hallucinations (VH) in Parkinson's disease (PD) have suggested a role for impaired attentional processes. The current study tested 25 PD patients with and 28 PD patients without VH on the attentional network test. Hallucinators had significantly lower accuracy rates compared to non-hallucinators, but no differences were found in reaction times. This suggests that hallucinators show deficits in attentional processes and conflict monitoring. Our findings provide novel behavioural insights that dovetail with current neurobiological frameworks of VH.

Imagine that: elevated sensory strength of mental imagery in individuals with Parkinson's disease and visual hallucinations.

Visual hallucinations occur when our conscious experience does not accurately reflect external reality. However, these dissociations also regularly occur when we imagine the world around us in the absence of visual stimulation. We used two novel behavioural paradigms to objectively measure visual hallucinations and voluntary mental imagery in 19 individuals with Parkinson's disease (ten with visual hallucinations; nine without) and ten healthy, age-matched controls. We then used this behavioural overlap to interrogate the connectivity both within and between the major attentional control networks using resting-state functional magnetic resonance imaging. Patients with visual hallucinations had elevated mental imagery strength compared with patients without hallucinations and controls. Specifically, the sensory strength of imagery predicted the frequency of visual hallucinations. Together, hallucinations and mental imagery predicted multiple abnormalities in functional connectivity both within and between the attentional control networks, as measured with resting-state functional magnetic resonance imaging. However, the two phenomena were also dissociable at the neural level, with both mental imagery and visual misperceptions associated with specific abnormalities in attentional network connectivity. Our results provide the first evidence of both the shared and unique neural correlates of these two similar, yet distinct phenomena.

Visual hallucinations in Parkinson's disease: theoretical models.

One of the most challenging tasks in neuroscience is to be able to meaningfully connect information across the different levels of investigation, from molecular or structural biology to the resulting behavior and cognition. Visual hallucinations are a frequent occurrence in Parkinson's disease and significantly contribute to the burden of the disease. Because of the widespread pathological processes implicated in visual hallucinations in Parkinson's disease, a final common mechanism that explains their manifestation will require an integrative approach, in which consideration is taken across all complementary levels of analysis. This review considers the leading hypothetical frameworks for visual hallucinations in Parkinson's disease, summarizing the key aspects of each in an attempt to highlight the aspects of the condition that such a unifying hypothesis must explain. These competing hypotheses include implications of dream imagery intrusion, deficits in reality monitoring, and impairments in visual perception and attention.

Understanding the encoding of object locations in small-scale spaces during free exploration using eye tracking.

Navigation is instrumental to daily life and is often used to encode and locate objects, such as keys in one's house. Yet, little is known about how navigation works in more ecologically valid situations such as finding objects within a room. Specifically, it is not clear how vision vs. body movements contribute differentially to spatial memory in such small-scale spaces. In the current study, participants encoded object locations by viewing them while standing (stationary condition) or by additionally being guided by the experimenter while blindfolded (walking condition) after viewing the objects. They then retrieved the objects from the same or different viewpoint, creating a 2 × 2 within subject design. We simultaneously recorded participant eye movements throughout the experiment using mobile eye tracking. The results showed no statistically significant differences among our four conditions (stationary, same viewpoint as encoding; stationary, different viewpoint; walking, same viewpoint; walking, different viewpoint), suggesting that in a small real-world space, vision may be sufficient to remember object locations. Eye tracking analyses revealed that object locations were better remembered next to landmarks and that participants encoded items on one wall together, suggesting the use of local wall coordinates rather than global room coordinates. A multivariate regression analysis revealed that the only significant predictor of object placement accuracy was average looking time. These results suggest that vision may be sufficient for encoding object locations in a small-scale environment and that such memories may be formed largely locally rather than globally.

Mind-wandering in Parkinson's disease hallucinations reflects primary visual and default network coupling.

Visual hallucinations are an underappreciated symptom affecting the majority of patients during the natural history of Parkinson's disease. Little is known about other forms of abstract and internally generated cognition - such as mind-wandering - in this population, but emerging evidence suggests that an interplay between the brain's primary visual and default networks might play a crucial role in both internally generated imagery and hallucinations. Here, we explored the association between mind-wandering and visual hallucinations in Parkinson's disease, and their relationship with brain network coupling. We administered a validated thought-sampling task to 38 Parkinson's disease patients (18 with hallucinations; 20 without) and 40 controls, to test the hypothesis that individuals with hallucinations experience an increased frequency of mind-wandering. Group differences in the association between mind-wandering frequency and brain network coupling were also examined using resting state functional magnetic resonance imaging. Our results showed that patients with hallucinations exhibited significantly higher mind-wandering frequencies compared to non-hallucinators, who in turn had reduced levels of mind-wandering relative to controls. At the level of brain networks, inter-network connectivity and seed-to-voxel analyses identified that increased mind-wandering in the hallucinating versus non-hallucinating group was associated with greater coupling between the primary visual cortex and dorsal default network. Taken together, our results suggest a relative preservation of mind-wandering in Parkinson's disease patients who experience visual hallucinations, which is associated with increased visual cortex-default network coupling. We propose that the preservation of florid abstract and internally generated cognition in the context of the Parkinson's disease can contribute to visual hallucinations, whereas healthy individuals experience only the vivid images of the mind's eye. These findings refine current models of visual hallucinations by identifying a specific cognitive phenomenon and neural substrate consistent with the top-down influences over perception that have been implicated in hallucinations across neuropsychiatric disorders.

Changes in structural network topology correlate with severity of hallucinatory behavior in Parkinson's disease.

Inefficient integration between bottom-up visual input and higher order visual processing regions is implicated in visual hallucinations in Parkinson's disease (PD). Here, we investigated white matter contributions to this perceptual imbalance hypothesis. Twenty-nine PD patients were assessed for hallucinatory behavior. Hallucination severity was correlated to connectivity strength of the network using the network-based statistic approach. The results showed that hallucination severity was associated with reduced connectivity within a subnetwork that included the majority of the diverse club. This network showed overall greater between-module scores compared with nodes not associated with hallucination severity. Reduced between-module connectivity in the lateral occipital cortex, insula, and pars orbitalis and decreased within-module connectivity in the prefrontal, somatosensory, and primary visual cortices were associated with hallucination severity. Conversely, hallucination severity was associated with increased between- and within-module connectivity in the orbitofrontal and temporal cortex, as well as regions comprising the dorsal attentional and default mode network. These results suggest that hallucination severity is associated with marked alterations in structural network topology with changes in participation along the perceptual hierarchy. This may result in the inefficient transfer of information that gives rise to hallucinations in PD.

Informant- and Self-Appraisals on the Psychosis and Hallucinations Questionnaire (PsycH-Q) Enhances Detection of Visual Hallucinations in Parkinson's Disease.

BACKGROUND: Clinicians vary in their ability to elicit and interpret hallucinatory symptoms in patients with Parkinson's disease (PD). There is limited evidence for informant-report measures of PD hallucinations as adjuncts to clinician-rated scales. OBJECTIVES: To determine the utility of an informant version of the validated Psychosis and Hallucinations Questionnaire (PsycH-Q) for assessing the presence and severity of hallucinations in PD; and, to evaluate accuracy of clinician judgements by comparison with informant report and self-report. METHODS: One hundred sixty-three PD patient-informant dyads completed self- and informant-report versions of PsycH-Q and three common questionnaire measures: Neuropsychiatric Inventory Questionnaire; Parkinson's Psychosis Questionnaire; and Scales for Outcomes in Parkinson's disease-Psychiatric Complications. We compared self-ratings and informant ratings across analogous subscales for the presence of hallucinations with clinician interview ratings on MDS-UPDRS as a diagnostic standard. RESULTS: There was a low level of agreement between dyads (average κ = 0.39; κ range = 0.32-0.47; P < 0.001), and patients indicated the highest prevalence of hallucinations compared to informant or clinician estimates. Clinician interview missed 32% of PsycH-Q hallucinators identified by dyads. Relative to the sample, 22 patients with exclusively clinician-appraised hallucinations had poorer overall quality of life measured by the Parkinson's Disease Questionnaire. CONCLUSIONS: The sole use of clinician-rated scales may underestimate prevalence of PD hallucinations, and there is room for introducing self- and informant-report tools. Nonetheless, clinician appraisals are critical in cases when informant and patient insight might be affected by the impact of illness on quality of life.

Cognitive training for freezing of gait in Parkinson's disease: a randomized controlled trial.

The pathophysiological mechanism of freezing of gait (FoG) has been linked to executive dysfunction. Cognitive training (CT) is a non-pharmacological intervention which has been shown to improve executive functioning in Parkinson's disease (PD). This study aimed to explore whether targeted CT can reduce the severity of FoG in PD. Patients with PD who self-reported FoG and were free from dementia were randomly allocated to receive either a CT intervention or an active control. Both groups were clinician-facilitated and conducted twice-weekly for seven weeks. The primary outcome was percentage of time spent frozen during a Timed Up and Go task, assessed both on and off dopaminergic medications. Secondary outcomes included multiple neuropsychological and psychosocial measures. A full analysis was first conducted on all participants randomized, followed by a sample of interest including only those who had objective FoG at baseline, and completed the intervention. Sixty-five patients were randomized into the study. The sample of interest included 20 in the CT group and 18 in the active control group. The primary outcome of percentage time spent frozen during a gait task was significantly improved in the CT group compared to active controls in the on-state. There were no differences in the off-state. Patients who received CT also demonstrated improved processing speed and reduced daytime sleepiness compared to those in the active control. The findings suggest that CT can reduce the severity of FoG in the on-state, however replication in a larger sample is required.

Visual Hallucinations Are Characterized by Impaired Sensory Evidence Accumulation: Insights From Hierarchical Drift Diffusion Modeling in Parkinson's Disease.

BACKGROUND: Models of hallucinations emphasize imbalance between sensory input and top-down influences over perception, as false perceptual inference can arise when top-down predictions are afforded too much precision (certainty) relative to sensory evidence. Visual hallucinations in Parkinson's disease (PD) are associated with lower-level visual and attentional impairments, accompanied by overactivity in higher-order association brain networks. PD therefore provides an attractive framework to explore contributions of bottom-up versus top-down disturbances in hallucinations. METHODS: We characterized sensory processing during perceptual decision making in patients with PD with (n = 20) and without (n = 25) visual hallucinations and control subjects (n = 12), by fitting a hierarchical drift diffusion model to an attentional task. The hierarchical drift diffusion model uses Bayesian estimates to decompose task performance into parameters reflecting drift rates of evidence accumulation, decision thresholds, and nondecision time. RESULTS: We observed slower drift rates in patients with hallucinations, which were less sensitive to changes in task demand. In contrast, wider decision boundaries and shorter nondecision times relative to control subjects were found in patients with PD regardless of hallucinator status. Inefficient and less flexible sensory evidence accumulation emerges as a unique feature of PD hallucinators. CONCLUSIONS: We integrate these results with evidence accumulation and predictive coding models of hallucinations, suggesting that in PD sensory evidence is less informative and may therefore be down-weighted, resulting in overreliance on top-down influences. Considering impaired drift rates as an approximation of reduced sensory precision, our findings provide a novel computational framework to specify impairments in sensory processing that contribute to development of visual hallucinations.

Abnormal connectivity between the default mode and the visual system underlies the manifestation of visual hallucinations in Parkinson's disease: a task-based fMRI study.

BACKGROUND: The neural substrates of visual hallucinations remain an enigma, due primarily to the difficulties associated with directly interrogating the brain during hallucinatory episodes. AIMS: To delineate the functional patterns of brain network activity and connectivity underlying visual hallucinations in Parkinson's disease. METHODS: In this study, we combined functional magnetic resonance imaging (MRI) with a behavioral task capable of eliciting visual misperceptions, a confirmed surrogate for visual hallucinations, in 35 patients with idiopathic Parkinson's disease. We then applied an independent component analysis to extract time series information for large-scale neuronal networks that have been previously implicated in the pathophysiology of visual hallucinations. These data were subjected to a task-based functional connectivity analysis, thus providing the first objective description of the neural activity and connectivity during visual hallucinations in patients with Parkinson's disease. RESULTS: Correct performance of the task was associated with increased activity in primary visual regions; however, during visual misperceptions, this same visual network became actively coupled with the default mode network (DMN). Further, the frequency of misperception errors on the task was positively correlated with the strength of connectivity between these two systems, as well as with decreased activity in the dorsal attention network (DAN), and with impaired connectivity between the DAN and the DMNs, and ventral attention networks. Finally, each of the network abnormalities identified in our analysis were significantly correlated with two independent clinical measures of hallucination severity. CONCLUSIONS: Together, these results provide evidence that visual hallucinations are due to increased engagement of the DMN with the primary visual system, and emphasize the role of dysfunctional engagement of attentional networks in the pathophysiology of hallucinations.