Does hippocampal atrophy explain anterograde and retrograde amnesia following autoimmune limbic encephalitis?

Letter to the Edito

The cerebellum, internal models and prediction in 'non-motor' aspects of language: A critical review

The emergence of studies on cerebellar contributions in ‘non-motor’ aspects of predictive language processing has long been awaited by researchers investigating the neural foundations of language and cognition. Despite (i) progress in research implicating the cerebellum in language processing, (ii) the widely-accepted nature of the uniform, multi-modal computation that the cerebellum implements in the form of internal models, as well as (iii) the long tradition of psycholinguistic studies addressing prediction mechanisms, research directly addressing cerebellar contributions to ‘non-motor’ predictive language processing has only surfaced in the last five years. This paper provides the first review of this novel field, along with a critical assessment of the studies conducted so far. While encouraging, the evidence for cerebellar involvement in ‘non-motor’ aspects of predictive language processing remains inconclusive under further scrutiny. Future directions are finally discussed with respect to outstanding questions in this novel field of research

Editorial: The cerebellar role in psychiatric disorders: Emerging evidence and future perspectives

First paragraph: Over the past decades, clinical, neuroimaging, anatomical, and physiological studies have established the presence of a “cognitive” and a “limbic” cerebellum—the former being represented primarily in posterolateral regions and the dentate nuclei, and the latter in the vermis and the fastigial nuclei (Schmahmann et al., 2007). The “dysmetria of thought,” following damage to the cognitive cerebellum (Schmahmann, 1998) and the neuropsychiatric impairments, following damage to the limbic cerebellum (Schmahmann et al., 2007) comprise the so called “cerebellar cognitive affective syndrome” (Schmahmann and Sherman, 1998). These findings have recently renewed interest in a cerebellar pathophysiology of a broad range of neurodevelopmental and psychiatric disorders (e.g. Hoppenbrouwers et al., 2008; Lupo et al., 2019; Van Overwalle et al., 2020)

Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2

Bilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with a FOXP2 mutation in affected members of the ‘KE family’, who present with developmental orofacial and verbal dyspraxia in conjunction with pervasive language deficits. Despite the gene’s early and prominent expression in the cerebellum and the evidence for reciprocal cerebellum-basal ganglia connectivity, very little is known about cerebellar abnormalities in affected KE members. Using cerebellum-specific voxel-based morphometry (VBM) and volumetry, we provide converging evidence from subsets of affected KE members scanned at three time points for grey matter (GM) volume reduction bilaterally in neocerebellar lobule VIIa Crus I compared with unaffected members and unrelated controls. We also show that right Crus I volume correlates with left and total caudate nucleus volumes in affected KE members, and that right and total Crus I volumes predict the performance of affected members in non-word repetition and non-verbal orofacial praxis. Crus I also shows bilateral hypo-activation in functional MRI in the affected KE members relative to controls during non-word repetition. The association of Crus I with key aspects of the behavioural phenotype of this FOXP2 point mutation is consistent with recent evidence of cerebellar involvement in complex motor sequencing. For the first time, specific cerebello-basal ganglia loops are implicated in the execution of complex oromotor sequences needed for human speech

Network-wide abnormalities explain memory variability in hippocampal amnesia

Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n = 38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic and entorhinal cortical volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Network abnormalities may explain the variability across studies of amnesia and speak to debates in memory neuroscience

Pathologic tearfulness after limbic encephalitis: A novel disorder and its neural basis

Objective We investigated the nature and neural foundations of pathologic tearfulness in a uniquely large cohort of patients who had presented with autoimmune limbic encephalitis (aLE). Methods We recruited 38 patients (26 men, 12 women; median age 63.06 years; interquartile range [IQR] 16.06 years) in the postacute phase of aLE who completed questionnaires probing emotion regulation. All patients underwent structural/functional MRI postacutely, along with 67 age- and sex-matched healthy controls (40 men, 27 women; median age 64.70 years; IQR 19.87 years). We investigated correlations of questionnaire scores with demographic, clinical, neuropsychological, and brain imaging data across patients. We also compared patients diagnosed with pathologic tearfulness and those without, along with healthy controls, on gray matter volume, resting-state functional connectivity, and activity. Results Pathologic tearfulness was reported by 50% of the patients, while no patient reported pathologic laughing. It was not associated with depression, impulsiveness, memory impairment, executive dysfunction in the postacute phase, or amygdalar abnormalities in the acute phase. It correlated with changes in specific emotional brain networks: volume reduction in the right anterior hippocampus, left fusiform gyrus, and cerebellum, abnormal hippocampal resting-state functional connectivity with the posteromedial cortex and right middle frontal gyrus, and abnormal hemodynamic activity in the left fusiform gyrus, right inferior parietal lobule, and ventral pons. Conclusions Pathologic tearfulness is common following aLE, is not a manifestation of other neuropsychiatric features, and reflects abnormalities in networks of emotion regulation beyond the acute hippocampal focus. The condition, which may also be present in other neurologic disorders, provides novel insights into the neural basis of affective control and its dysfunction in disease

Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis

Objective Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment. Method A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined. Results Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531). Conclusion VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy

Permanent water swelling effect in low temperature thermally reduced graphene oxide

We demonstrate permanent water trapping in reduced graphene oxide after high relative humidity exposure. For this purpose, we grew graphene oxide films via spin-coating on glass substrates followed by thermal reduction. The electrical resistance of the planar device was then measured. We observed that resistance is significantly increased after water vapor exposure and remains stable even after 250 days in ambient conditions. Various techniques were applied to desorb the water and decrease (recover) the material's resistance, but it was achieved only with low temperature thermal annealing (180 °C) under forming gas (H2/N2 mixture). The permanent effect of water absorption was also detected by x-ray photoelectron spectroscopy.</p

Early prediction of COVID-19 outcome using artificial intelligence techniques and only five laboratory indices

We aimed to develop a prediction model for intensive care unit (ICU) hospitalization of Coronavirus disease-19 (COVID-19) patients using artificial neural networks (ANN). We assessed 25 laboratory parameters at first from 248 consecutive adult COVID-19 patients for database creation, training, and development of ANN models. We developed a new alpha-index to assess association of each parameter with outcome. We used 166 records for training of computational simulations (training), 41 for documentation of computational simulations (validation), and 41 for reliability check of computational simulations (testing). The first five laboratory indices ranked by importance were Neutrophil-to-lymphocyte ratio, Lactate Dehydrogenase, Fibrinogen, Albumin, and D-Dimers. The best ANN based on these indices achieved accuracy 95.97%, precision 90.63%, sensitivity 93.55%. and F1-score 92.06%, verified in the validation cohort. Our preliminary findings reveal for the first time an ANN to predict ICU hospitalization accurately and early, using only 5 easily accessible laboratory indices

Urinary MicroRNA Profiling in the Nephropathy of Type 1 Diabetes

Background: Patients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease. Methods and Findings: We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease. Conclusions: Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes. © 2013 Argyropoulos et al