A question of scale Irish, Muireann; Ramanan, Siddharth
eLife,
09/2019, Volume:
8
Journal Article
Peer reviewed
Open access
An fMRI experiment reveals distinct brain regions that respond in a graded manner as humans process distance information across increasing spatial scales.
Logopenic progressive aphasia (LPA) is a neurodegenerative disorder characterised by profound naming and sentence repetition disturbances, attributable to disproportionately left-sided ...temporo-parietal atrophy. Accumulating evidence suggests, in addition to language impairments, the presence of stark verbal and nonverbal episodic memory dysfunction in LPA. The neurocognitive bases of such impairments, however, remain to be clarified. Here, we characterised episodic memory disruption and its corresponding grey and white matter correlates in the LPA syndrome. Nineteen LPA patients were contrasted with 23 matched typical Alzheimer's disease (AD) patients and 31 healthy Controls on standardized verbal and nonverbal episodic delayed recall measures. Participants further underwent structural magnetic resonance and diffusion-weighted imaging. Significant verbal memory deficits were evident in both patient groups, with LPA patients performing at an intermediate level to AD and Controls. For nonverbal memory, however, LPA performance was indistinguishable from that of AD, with both groups displaying marked impairments relative to Controls. Whole-brain voxel-based morphometry analyses revealed significant left temporo-parietal and left hippocampal atrophy in the LPA group. Covariate analyses showed that verbal and nonverbal amnesia in LPA correlated with grey matter integrity of bilateral frontoparietal and left medial temporal lobe regions. Notably, the common regions underpinning verbal and nonverbal memory dysfunction in LPA were the left orbitofrontal cortex and bilateral angular gyri in the inferior parietal cortex. The bilateral angular gyri, along with prefrontal and hippocampal regions further emerged as disease-general correlates of verbal and nonverbal memory performance. Alterations in mean diffusivity in structural connections between the left angular gyrus and medial temporal lobes were further associated with verbal memory performance in all participants. Our findings reveal, for the first time, the presence of pervasive memory impairments in LPA mediated by degeneration of a distributed prefrontal-hippocampal-parietal network, and disrupted parieto-hippocampal structural connectivity.
Purpose
Arteriovenous fistula(AVF) is preferred vascular access for hemodialysis but has primary failure in 20–60%. Studying predictors of AVF failure would help plan appropriate management.We ...studied AVF outcomes, clinical and vascular factors predicting their failure in patients requiring hemodialysis.
Methods
Retrospective study of patients with AVF creation from January 2017 to December 2018. Outcomes studied were immediate (< 72 h), primary (3 months) AVF failure, six-month/one-year patency, analyzed for predictive clinical, vascular factors as assessed using Pre-operative Doppler Ultrasound(DUS).
Results
Of 530 AVFs in 460 patients, DUS was done in 426/530 (80.4%), 349/460 (75.8%) were males, mean age was 53.10 ± 14.54 (18–91), 215/460(46.7%) had Diabetes mellitus(DM), 423/460(92%) hypertension. AVFs were radiocephalic in 79/530 (14.9%), brachiocephalic 418/530 (78.9%), brachiobasilic 33/530 (6.2%). AVF Immediate/Primary failure was seen in 64/530 (12.1%), 90/352 (25.6%); Patency at six months/one year in 253/352(71.8%),191/305 (62.6%), respectively. Older age had less immediate failures (AOR 0.97, CI 0.95–0.99,
p
0.03). Feeding arterial diameter predicted immediate and primary failure on univariate analysis OR 0.64 (95% CI 0.49–0.83), 0.62 (95% CI 0.47–0.89), respectively, but not multivariate. Artery diameter of > 4.0 mm had less failures immediate (
p
0.01), primary (
p
0.02), < 2.0 mm had specificity 95.9% and 95.4% for immediate, primary failure respectively.
Conclusion
AVF failure is 12.1%, immediately; 25.6% three months after construction, Patency at 6 months is 71.8%, one year 62.6%. Immediate failures decrease with age. Artery diameters > 4.0 mm had less, < 2.0 mm had more failures.
Whether theory of mind (ToM) is preserved in Alzheimer's disease (AD) remains a controversial subject. Recent studies have showed that performance on some ToM tests might be altered in AD, though to ...a lesser extent than in behavioural-variant Frontotemporal Dementia (bvFTD). It is however, unclear if this reflects a genuine impairment of ToM or a deficit secondary to the general cognitive decline observed in AD. Aiming to investigate the cognitive determinants of ToM performance in AD, a data-mining study was conducted in 29 AD patients then replicated in an independent age-matched group of 19 AD patients to perform an independent replication of the results. 44 bvFTD patients were included as a comparison group. All patients had an extensive neuropsychological examination. Hierarchical clustering analyses showed that ToM performance clustered with measures of executive functioning (EF) in AD. ToM performance was also specifically correlated with the executive component extracted from a principal component analysis. In a final step, automated linear modelling conducted to determine the predictors of ToM performance showed that 48.8% of ToM performance was significantly predicted by executive measures. Similar findings across analyses were observed in the independent group of AD patients, thereby replicating our results. Conversely, ToM impairments in bvFTD appeared independent of other cognitive impairments. These results suggest that difficulties of AD patients on ToM tests do not reflect a genuine ToM deficit, rather mediated by general (and particularly executive) cognitive decline. They also suggest that EF has a key role in mental state attribution, which support interacting models of ToM functioning. Finally, our study highlights the relevancy of data-mining statistical approaches in clinical and cognitive neurosciences.
Ramanan explores the distinct neural networks that support autobiographical and episodic remembering. He cites a study which sought to control for methodological differences between autobiographical ...and episodic remembering by using an elegant experimental design. In the study phase of their first experiment, young, healthy participants were asked to classify scenes as indoor or outdoor while in the scanner. In the episodic retrieval condition, participants had to remember whether they had seen the scene during the study phase and to recall specific details about the stimulus. In conclusion, the findings deepen the understanding of the underlying brain networks that mediate distinct aspects of human declarative memory.
Ramanan and Bellana explain a domain-general role for the angular gyrus in retrieving internal representations of the external world. Autobiographical memories for pergonal past experiences vary ...along multiple interrelated dimensions, such as sensory-perceptual, spatiotemporal and emotional information. The complex, highly relational nature of information within autobiographical memory .illown us not only to relive personal past experiences, but further confers a sense of subjective time, and shapes a sense of self. Understanding how tin· human brain stores and accesses the rich content ot our autobiographical memories has, there fore, been a longstanding goal of memory research.
Memory impairment in behavioral variant frontotemporal dementia (bvFTD) is traditionally considered to be mild and attributed to prefrontal cortex dysfunction. Recent studies, however, indicated that ...some patients can present with a memory impairment of the hippocampal type, showing storage and consolidation deficits in addition to the more executive/prefrontal related encoding and strategic difficulties.
This study aimed to study the relationship between executive functions (EF) and memory processes in bvFTD via a data-driven approach.
Participants consisted of 71 bvFTD (among which 60.6% had a lumbar puncture showing non-Alzheimer biomarker profile) and 60 controls (among which 45% had amyloid imaging showing a normal profile). EF were assessed by the Frontal Assessment Battery, semantic/lexical verbal fluency tests, and forward/backward digit spans. Patients were split into amnestic (n = 33) and non-amnestic (n = 38) subgroups based on normative data (total recall score) from the Free and Cued Selective Reminding Test (FCSRT). Relationships between FCSRT subscores and EF measures were explored through hierarchical clustering analysis, partial correlation analysis with an EF component, and automated linear modeling.
Convergent findings across the statistical approaches show that, overall, memory performance was independent from EF in bvFTD whereas the relationship was stronger in controls. Indeed, in bvFTD, memory performance did not cluster with EF, was not correlated with the EF component, and was only partially (4% - 12.7%) predicted by EF.
These findings show that executive dysfunctions cannot solely explain the memory deficits occurring in bvFTD. Indeed, some patients present with a genuine amnesia affecting storage and consolidation abilities, which are independent from executive dysfunctions. On the clinical level, this study highlights the importance of revising the neuropsychological diagnosis criteria for bvFTD.
Despite consistent activation on tasks of episodic memory, the precise contribution of the left angular gyrus (AG) to mnemonic functions remains vigorously debated. Mounting evidence suggests that AG ...activity scales with subjective ratings of vividness and confidence in recollection, with further evidence pointing to its involvement during construction of detailed and coherent future simulations. Lesion studies, however, indicate that damage to the AG does not render patients amnesic on standard source and associative memory paradigms. To reconcile these findings, we present the Contextual Integration Model as a unifying framework that couches the mnemonic role of the AG in terms of multimodal integration and representation of contextual information across temporal contexts. Irrespective of whether one is remembering the past or constructing future or hypothetical scenarios, the Contextual Integration Model holds that the core elements of an event (i.e., the who, what, when, where) are bound within the medial temporal lobes while the multimodal details, which give rise to perceptually rich recollection, are integrated and represented in the AG. Building on previous work, the Contextual Integration Model therefore provides a comprehensive exposition of the mnemonic and constructive functions of the AG across temporal contexts, offering a novel test-bed for future work.
Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there ...is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear. Understanding the relationship between these variables would improve PPA clinical/research characterisation and strengthen clinical trial and symptomatic treatment design. We address these knowledge gaps using a data-driven transdiagnostic approach to chart cognitive-linguistic differences and their associations with grey/white matter degeneration across multiple PPA variants.
Forty-seven patients (13 semantic, 15 non-fluent, and 19 logopenic variant PPA) underwent assessment of general cognition, errors on language performance, and structural and diffusion magnetic resonance imaging to index whole-brain grey and white matter changes. Behavioural data were entered into varimax-rotated principal component analyses to derive orthogonal dimensions explaining the majority of cognitive variance. To uncover neural correlates of cognitive heterogeneity, derived components were used as covariates in neuroimaging analyses of grey matter (voxel-based morphometry) and white matter (network-based statistics of structural connectomes).
Four behavioural components emerged: general cognition, semantic memory, working memory, and motor speech/phonology. Performance patterns on the latter three principal components were in keeping with each variant's characteristic profile, but with a spectrum rather than categorical distribution across the cohort. General cognitive changes were most marked in logopenic variant PPA. Regardless of clinical diagnosis, general cognitive impairment was associated with inferior/posterior parietal grey/white matter involvement, semantic memory deficits with bilateral anterior temporal grey/white matter changes, working memory impairment with temporoparietal and frontostriatal grey/white matter involvement, and motor speech/phonology deficits with inferior/middle frontal grey matter alterations.
Cognitive-linguistic heterogeneity in PPA closely relates to individual-level variations on multiple behavioural dimensions and grey/white matter degeneration of regions within and beyond the language network. We further show that employment of transdiagnostic approaches may help to understand clinical symptom boundaries and reveal clinical and neural profiles that are shared across categorically defined variants of PPA.
Semantic dementia (SD) is a younger-onset neurodegenerative disease characterised by progressive deterioration of the semantic knowledge base in the context of predominantly left-lateralised anterior ...temporal lobe (ATL) atrophy. Mounting evidence indicates the emergence of florid socioemotional changes in SD as atrophy encroaches into right temporal regions. How lateralisation of temporal lobe pathology impacts the hedonic experience in SD remains largely unknown yet has important implications for understanding socioemotional and functional impairments in this syndrome. Here, we explored how lateralisation of temporal lobe atrophy impacts anhedonia severity on the Snaith–Hamilton Pleasure Scale in 28 SD patients presenting with variable right- (SD-R) and left-predominant (SD-L) profiles of temporal lobe atrophy compared to that of 30 participants with Alzheimer’s disease and 30 healthy older Control participants. Relative to Controls, SD-R but not SD-L or Alzheimer’s patients showed clinically significant anhedonia, representing a clear departure from premorbid levels. Overall, anhedonia was more strongly associated with functional impairment on the Frontotemporal Dementia Functional Rating Scale and motivational changes on the Cambridge Behavioural Inventory in SD than in Alzheimer’s disease patients. Voxel-based morphometry analyses revealed that anhedonia severity correlated with reduced grey matter intensity in a restricted set of regions centred on right orbitofrontal and temporopolar cortices, bilateral posterior temporal cortices, as well as the anterior cingulate gyrus and parahippocampal gyrus, bilaterally. Finally, regression and mediation analysis indicated a unique role for right temporal lobe structures in modulating anhedonia in SD. Our findings suggest that degeneration of predominantly right-hemisphere structures deleteriously impacts the capacity to experience pleasure in SD. These findings offer important insights into hemispheric lateralisation of motivational disturbances in dementia and suggest that anhedonia may emerge at different timescales in the SD disease trajectory depending on the integrity of the right hemisphere.
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