Parkinson's disease dementia: a neural networks perspective.

In the long-term, with progression of the illness, Parkinson's disease dementia affects up to 90% of patients with Parkinson's disease. With increasing life expectancy in western countries, Parkinson's disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson's disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson's disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson's disease dementia, and discuss how this may offer new therapeutic opportunities

The cognitive neuroscience of visual working memory

Visual working memory allows us to temporarily maintain and manipulate visual information in order to solve a task. The study of the brain mechanisms underlying this function began more than half a century ago, with Scoville and Milner’s (1957) seminal discoveries with amnesic patients. This timely collection of papers brings together diverse perspectives on the cognitive neuroscience of visual working memory from multiple fields that have traditionally been fairly disjointed: human neuroimaging, electrophysiological, behavioural and animal lesion studies, investigating both the developing and the adult brain

Attention network dysfunction underlies memory impairment in posterior cortical atrophy

Accumulating evidence suggests that memory is impaired in posterior cortical atrophy (PCA), alongside the early and defining visual disorder. The posterior parietal cortex is a key region of pathology in PCA and memory impairment may be the result of dysfunction of parietally dependent network function rather than the medial temporal lobe dependent dysfunction that defines the storage deficits in typical Alzheimer's disease. We assessed episodic memory performance and network function in16 PCA patients and 19 healthy controls who underwent structural and resting-state functional MRI and neuropsychological testing. Memory was assessed using the Free and Cued Selective Reminding Test (FCSRT), a sensitive test of episodic memory storage and retrieval. We examined correlations between memory performance and functional connectivity in the dorsal attention (DAN) and default mode network (DMN). Immediate recall on the FCSRT was relatively preserved in PCA patients. Total recall performance was impaired in patients relative to healthy controls and performance benefitted from retrieval cues. In patients only, disrupted connectivity in the DAN, but not the DMN, was associated with total recall. Memory impairment may arise from disruption to the dorsal attention network, subserved by the dorsal posterior parietal cortex, a key region of pathology in PCA, rather than classic medial temporal lobe memory circuitry.We propose that functional dysconnectivity in attentional circuits underpins memory impairment in PCA

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Hippocampus dependent and independent theta-networks of working memory maintenance

Working memory is the ability to briefly maintain and manipulate information beyond its transient availability to our senses. This process of short-term stimulus retention has often been proposed to be anatomically distinct from long-term forms of memory. Although it’s been well established that the medial temporal lobe (MTL) is critical to long-term declarative memory, recent evidence has suggested that MTL regions, such as the hippocampus, may also be involved in the working memory maintenance of configural visual relationships. I investigate this possibility in a series of experiments using Magnetoencephalography to record the cortical oscillatory activity within the theta frequency band of patients with bilateral hippocampal sclerosis and normal controls. The results demonstrate that working memory maintenance of configural-relational information is supported by a theta synchronous network coupling frontal, temporal and occipital visual areas, and furthermore that this theta synchrony is critically dependent on the integrity of the hippocampus. Alternate forms of working memory maintenance, that do not require the relational binding of visual configurations, engage dissociable theta synchronous networks functioning independently of the hippocampus. In closing, I will explore the interactions between long-term and short-term forms of memory and demonstrate that through these interactions, memory performance can effectively be improved

Memory precision across space and time in Alzheimer's disease

This thesis aimed to deepen current understanding of the mechanisms underlying visual short-term memory (VSTM) impairments in Alzheimer’s Disease (AD). The mixture model of working memory (WM) was deployed to dissect the differential contributions of distinct VSTM processes: ability to detect a target, swapping an item with another item in memory (misbinding), random guessing and precision of item representation (memory precision). Proficiency in filtering an unwanted item out (filtering ability), whether presented simultaneously with the to-be-remembered stimuli (encoding) or during the retention phase (maintenance) was also studied. In addition, measures of overall task performance, spatial localisation errors and reaction times were analysed. Chapter 2 showed that healthy ageing was associated with a decline in VSTM memory precision, while in AD patients higher guessing and lower target detection were the main sources of memory errors. AD patients were also particularly affected when a distractor was presented during maintenance (filtering at maintenance), but not at encoding. As a comparator, patients with Parkinson’s Disease (PD) showed higher guessing rates, but preserved filtering abilities. In Chapter 3 the “What was where” Oxford Memory Task (OMT), was used to assess VSTM performance in people at risk of developing AD dementia, i.e., patients with subjective cognitive impairment (SCI) and mild cognitive impairment (MCI), compared to patients with established AD dementia. Apart from reaction time measures, most metrics derived from the OMT task were able to discriminate between healthy controls and patients with MCI, and between MCI and AD dementia. Mixture model metrics and spatial localization error also differed significantly between people with SCI and MCI. All metrics were correlated with hippocampal atrophy. Chapter 4 showed that OMT metrics clustered into four specific spatial patterns of atrophy in the grey matter across a cohort of healthy controls and AD patients, with the Precuneus being associated only with metrics that carried spatial information. In Chapter 5 a key white matter region encompassing three tracts (Optic radiation, Forceps Major and Middle Longitudinal Fasciculus) was identified to be associated with VSTM performance on OMT in the left hemisphere in AD patients, but in the right hemisphere in healthy controls. Finally, In Chapter 6 OMT metrics and several other cognitive measures derived from an online battery testing VSTM, executive functions, processing speed, long-term memory and visuospatial abilities, were related to plasma biomarkers of AD; phospotau (pTau)181, Glial fibrillary acidic protein (GFAP), Neurofilament Light Chain (NfL), and amyloid β 42/40 ratio (Aβ42/40 ratio). The results showed that of these biomarkers, pTau181 was most closely correlated to cognitive performance. However, cognitive measures and plasma biomarkers had different degrees of test-retest reliability, with pTau181 showing the highest degree of variability among plasma biomarkers in this sample

The very same thing: Extending the object token concept to incorporate causal constraints on individual identity

The contributions of feature recognition, object categorization, and recollection of episodic memories to the re-identification of a perceived object as the very same thing encountered in a previous perceptual episode are well understood in terms of both cognitive-behavioral phenomenology and neurofunctional implementation. Human beings do not, however, rely solely on features and context to re-identify individuals; in the presence of featural change and similarly-featured distractors, people routinely employ causal constraints to establish object identities. Based on available cognitive and neurofunctional data, the standard object-token based model of individual re-identification is extended to incorporate the construction of unobserved and hence fictive causal histories (FCHs) of observed objects by the pre-motor action planning system. Cognitive-behavioral and implementation-level predictions of this extended model and methods for testing them are outlined. It is suggested that functional deficits in the construction of FCHs are associated with clinical outcomes in both Autism Spectrum Disorders and later-stage stage Alzheimer's disease.\u

Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat

Working memory (WM) is the cognitive capacity for short-term maintenance and manipulation of stimuli and goals for the purpose of guiding behaviour. Research in primates has indicated that WM relies on a large network including the prefrontal cortex, various posterior cortical areas, and subcortical nuclei. However, the circuit mapping of WM in rodents is incomplete as it pertains to the specific involvement of thalamocortical and frontoparietal circuitry across WM tasks. In this dissertation, I present the findings of three sets of experiments using two different rodent WM tasks: The odour span task (OST), an incrementing delayed non-matching-to-sample task using odours, and; the Trial-Unique Non-matching-to-Location (TUNL) task, a touchscreen-based visuospatial delayed non-matching-to-sample task. 1) I found evidence that the OST relies on a thalamocortical circuit connecting the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (mdThal). Moreover, the mPFC and mdThal played dissociable roles in the foraging element of the OST, with mdThal inactivation causing a dramatic reduction in exploratory motor activity. 2) I examined the role of the PPC in the OST and found that it is not necessary for OST performance. 3) I found that the PPC is critical for TUNL, confirming that the rodent PPC plays an essential role in visuospatial WM. Additionally, I found that TUNL is independent of NMDA signalling in the PPC and instead depends only on AMPA/Kainate receptors in contrast to previous research showing an important role for NMDA receptors in WM. Overall, the results indicate that thalamocortical and frontoparietal pathways are differentially involved across WM tasks, with frontoparietal circuitry being more sensory modality-specific than thalamocortical circuitry