Into the future with little past: exploring mental time travel in a patient with damage to the mammillary bodies/fornix

Objective: Remembering the past and imaging the future are both manifestations of ‘mental time travel’. These processes have been found to be impaired in patients with bilateral hippocampal lesions. Here, we examined the question of whether future thinking is affected by other Papez circuit lesions, namely: damage to the mammillary bodies/fornix. Method: Case (SL) was a 43-year-old woman who developed dense anterograde and retrograde amnesia suddenly, as a result of Wernicke–Korsakoff’s syndrome. A region of interest volumetric Magnetic resonance imaging (MRI) analysis was performed. We assessed past and future thinking in SL and 11 control subjects of similar age and education with the adapted Autobiographical Interview (AI). Participants also completed a battery of neuropsychological tests. Results: Volumetric MRI analyses revealed severely reduced fornix and mammillary body volumes, but intact hippocampi. SL showed substantial, albeit temporally graded retrograde memory deficits on the adapted AI. Strikingly, whilst SL could not provide any specific details of events from the past two weeks or past two years and had impaired recall of events from her late 30s, her descriptions of potential future events were normal in number of event details and plausibility. Conclusions: This dissociation of past and future events’ performance after mammillary body and fornix damage is at odds with the findings of the majority of patients with adult onset hippocampal amnesia. It suggests that these non-hippocampal regions of the Papez circuit are only critical for past event retrieval and not for the generation of possible future events

Investigation of the Chemical Changes from Crude and Processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma Herbal Pair Extracts by Using Q Exactive High-Performance Benchtop Quadrupole-Orbitrap LC-MS/MS

The Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pair is mainly used for regulating the functions of liver and spleen, benefiting qi, and nourishing blood. However, the bioactive compounds for the pharmacological activities of the crude and processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pair extracts are still unclear to date. In the present study, Q Exactive high-performance benchtop quadrupole-Orbitrap LC-MS/MS was applied to identify the complicated components from crude and processed Paeoniae Radix Alba, crude and processed Atractylodis Macrocephalae Rhizoma, and their crude and processed herbal pair extracts. 123 and 101 compounds were identified in crude and processed Paeoniae Radix Alba samples, respectively. Meanwhile, 32 and 26 compounds were identified in crude and processed Atractylodis Macrocephalae Rhizoma samples, respectively. In the crude and processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pair extracts, co-decoction could significantly change the chemical composition of Paeoniae Radix Alba and Atractylodis Macrocephalae Rhizoma in solution. The developed method may provide a scientific foundation for deeply elucidating the processing and compatibility mechanism of Paeoniae Radix Alba and Atractylodis Macrocephalae Rhizoma

Investigation of the Effect of Rice Wine on the Metabolites of the Main Components of Herbal Medicine in Rat Urine by Ultrahigh-Performance Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry: A Case Study on Cornus officinalis

Ultrahigh-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF/MS) was developed for rapid and sensitive analysis of the effect of rice wine on the metabolites of the main components of herbal medicine in rat urine. Using Cornus officinalis as a model of herbal medicine, the metabolite profiles of crude and processed (steaming the crude drug presteeped in rice wine) Cornus officinalis extracts in rat urine were investigated. The metabolites of Cornus officinalis were identified by using dynamic adjustment of the fragmentor voltage to produce structure-relevant fragment ions. In this work, we identified the parent compounds and metabolites of crude and processed Cornus officinalis in rats. In total, three parent compounds and seventeen new metabolites of Cornus officinalis were found in rats. The contents of the parent compounds and metabolites in vivo varied significantly after intragastric (i.g.) administration of aqueous extracts of crude and processed Cornus officinalis. Data from this study suggests that UPLC-QTOF/MS could be used as a potential tool for uncovering the effects of excipients found in the metabolites of the main components of herbal medicine, in vivo, to predict and discover the processing mechanisms of herbal medicine

Investigation of the Effect of Rice Wine on the Metabolites of the Main Components of Herbal Medicine in Rat Urine by Ultrahigh-Performance Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry: A Case Study on Cornus officinalis

Ultrahigh-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF/MS) was developed for rapid and sensitive analysis of the effect of rice wine on the metabolites of the main components of herbal medicine in rat urine. Using Cornus officinalis as a model of herbal medicine, the metabolite profiles of crude and processed (steaming the crude drug presteeped in rice wine) Cornus officinalis extracts in rat urine were investigated. The metabolites of Cornus officinalis were identified by using dynamic adjustment of the fragmentor voltage to produce structure-relevant fragment ions. In this work, we identified the parent compounds and metabolites of crude and processed Cornus officinalis in rats. In total, three parent compounds and seventeen new metabolites of Cornus officinalis were found in rats. The contents of the parent compounds and metabolites in vivo varied significantly after intragastric (i.g.) administration of aqueous extracts of crude and processed Cornus officinalis. Data from this study suggests that UPLC-QTOF/MS could be used as a potential tool for uncovering the effects of excipients found in the metabolites of the main components of herbal medicine, in vivo, to predict and discover the processing mechanisms of herbal medicine

Association of triglyceride-glucose index with the prevalence of cardiovascular disease in malnourished/non-malnourished patients: a large cross-sectional study

BackgroundNumerous investigations have demonstrated a strong association between the TyG (triglyceride-glucose) index, which is derived from lipid and glucose levels in the bloodstream, and the onset and progression of cardiovascular diseases (CVD). Blood glucose and blood lipids are affected by nutritional status, and few studies have explored whether the correlation between TyG index and the risk of CVD is affected by nutritional status.AimsTo investigate the connection between TyG index and the risk of CVD among individuals with varying nutritional statuses.MethodA total of 19,847 were included in the analysis, of which 15,955 participants were non-malnourished and 3,892 patients were malnourished. According to the TyG index quartile, the patients were categorized into four groups. Logistic regression analysis and restricted cubic spline was used to study the relationship between TyG index and the risk of CVD in normal and malnourished populations.ResultsThe results of the restricted cubic spline showed that the TyG index was positively associated with the risk of CVD in the non-malnourished population. The TyG index showed a U-shaped association with the risk of CVD in malnourished people. The result is consistent with that of logistic regression (Malnutrition: Group 2: OR: 1.14; 95% CI: 0.85–1.53; Group 3: OR: 1.36; 95% CI: 1.03–1.79; Group 4: OR: 1.72; 95% CI:1.31–2.25, P for trend <0.001; Non-malnutrition: Group 2: OR: 0.82; 95% CI: 0.46–1.48; Group 3: OR: 0.88; 95% CI: 0.49–1.57; Group 4: OR: 1.45; 95% CI:0.83–2.52, P for trend =0.067).ConclusionsThe association between the TyG index and the risk of CVD varied depending on the nutritional states. When using TyG index to assess the risk of CVD, stratification combined with nutritional status helps to more accurately screen patients at high risk of CVD

Lost in spatial translation - A novel tool to objectively assess spatial disorientation in Alzheimer's disease and frontotemporal dementia

Spatial disorientation is a prominent feature of early Alzheimer's disease (AD) attributed to degeneration of medial temporal and parietal brain regions, including the retrosplenial cortex (RSC). By contrast, frontotemporal dementia (FTD) syndromes show generally intact spatial orientation at presentation. However, currently no clinical tasks are routinely administered to objectively assess spatial orientation in these neurodegenerative conditions. In this study we investigated spatial orientation in 58 dementia patients and 23 healthy controls using a novel virtual supermarket task as well as voxel-based morphometry (VBM). We compared performance on this task with visual and verbal memory function, which has traditionally been used to discriminate between AD and FTD. Participants viewed a series of videos from a first person perspective travelling through a virtual supermarket and were required to maintain orientation to a starting location. Analyses revealed significantly impaired spatial orientation in AD, compared to FTD patient groups. Spatial orientation performance was found to discriminate AD and FTD patient groups to a very high degree at presentation. More importantly, integrity of the RSC was identified as a key neural correlate of orientation performance. These findings confirm the notion that i) it is feasible to assess spatial orientation objectively via our novel Supermarket task; ii) impaired orientation is a prominent feature that can be applied clinically to discriminate between AD and FTD and iii) the RSC emerges as a critical biomarker to assess spatial orientation deficits in these neurodegenerative conditions

Preservation of episodic memory in semantic dementia:The importance of regions beyond the medial temporal lobes

Episodic memory impairment represents one of the hallmark clinical features of patients with Alzheimer's disease (AD) attributable to the degeneration of medial temporal and parietal regions of the brain. In contrast, a somewhat paradoxical profile of relatively intact episodic memory, particularly for non-verbal material, is observed in semantic dementia (SD), despite marked atrophy of the hippocampus. This retrospective study investigated the neural substrates of episodic memory retrieval in 20 patients with a diagnosis of SD and 21 disease-matched cases of AD and compared their performance to that of 35 age- and education-matched healthy older Controls. Participants completed the Rey Complex Figure and the memory subscale of the Addenbrooke's Cognitive Examination-Revised as indices of visual and verbal episodic recall, respectively. Relative to Controls, AD patients showed compromised memory performance on both visual and verbal memory tasks. In contrast, memory deficits in SD were modality-specific occurring exclusively on the verbal task. Controlling for semantic processing ameliorated these deficits in SD, while memory impairments persisted in AD. Voxel-based morphometry analyses revealed significant overlap in the neural correlates of verbal episodic memory in AD and SD with predominantly anteromedial regions, including the bilateral hippocampus, strongly implicated. Controlling for semantic processing negated this effect in SD, however, a distributed network of frontal, medial temporal, and parietal regions was implicated in AD. Our study corroborates the view that episodic memory deficits in SD arise very largely as a consequence of the conceptual loading of traditional tasks. We propose that the functional integrity of frontal and parietal regions enables new learning to occur in SD in the face of significant hippocampal and anteromedial temporal lobe pathology, underscoring the inherent complexity of the episodic memory circuitry

False recognition in behavioral variant frontotemporal dementia and Alzheimer's Disease - Disinhibition or amnesia?

Episodic memory recall processes in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39 bvFTD, 77 AD and 61 control participants from two centers (India, Australia), as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits—false-positives). Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients

Scene construction impairments in Alzheimer's disease – A unique role for the posterior cingulate cortex

Episodic memory dysfunction represents one of the most prominent and characteristic clinical features of patients with Alzheimer's disease (AD), attributable to the degeneration of medial temporal and posterior parietal regions of the brain. Recent studies have demonstrated marked impairments in the ability to envisage personally relevant events in the future in AD. It remains unclear, however, whether AD patients can imagine fictitious scenes free from temporal constraints, a process that is proposed to rely fundamentally upon the integrity of the hippocampus. The objective of the present study was to investigate the capacity for atemporal scene construction, and its associated neural substrates, in AD. Fourteen AD patients were tested on the scene construction task and their performance was contrasted with 14 age- and education-matched healthy older Control participants. Scene construction performance was strikingly compromised in the AD group, with significant impairments evident for provision of contextual details, spatial coherence, and the overall richness of the imagined experience. Voxel-based morphometry analyses based on structural MRI revealed significant associations between scene construction capacity and atrophy in posterior parietal and lateral temporal brain structures in AD. In contrast, scene construction performance in Controls was related to integrity of frontal, parietal, and medial temporal structures, including the parahippocampal gyrus and posterior hippocampus. The posterior cingulate cortex (PCC) emerged as the common region implicated for scene construction performance across participant groups. Our study highlights the importance of regions specialised for spatial and contextual processing for the construction of atemporal scenes. Damage to these regions in AD compromises the ability to construct novel scenes, leading to the recapitulation of content from previously experienced events

Linking Sketch Patches by Learning Synonymous Proximity for Graphic Sketch Representation

Graphic sketch representations are effective for representing sketches. Existing methods take the patches cropped from sketches as the graph nodes, and construct the edges based on sketch's drawing order or Euclidean distances on the canvas. However, the drawing order of a sketch may not be unique, while the patches from semantically related parts of a sketch may be far away from each other on the canvas. In this paper, we propose an order-invariant, semantics-aware method for graphic sketch representations. The cropped sketch patches are linked according to their global semantics or local geometric shapes, namely the synonymous proximity, by computing the cosine similarity between the captured patch embeddings. Such constructed edges are learnable to adapt to the variation of sketch drawings, which enable the message passing among synonymous patches. Aggregating the messages from synonymous patches by graph convolutional networks plays a role of denoising, which is beneficial to produce robust patch embeddings and accurate sketch representations. Furthermore, we enforce a clustering constraint over the embeddings jointly with the network learning. The synonymous patches are self-organized as compact clusters, and their embeddings are guided to move towards their assigned cluster centroids. It raises the accuracy of the computed synonymous proximity. Experimental results show that our method significantly improves the performance on both controllable sketch synthesis and sketch healing