Effective connectivity in the default mode network is distinctively disrupted in Alzheimer's disease-A simultaneous resting-state FDG-PET/fMRI study.

A prominent finding of postmortem and molecular imaging studies on Alzheimer's disease (AD) is the accumulation of neuropathological proteins in brain regions of the default mode network (DMN). Molecular models suggest that the progression of disease proteins depends on the directionality of signaling pathways. At network level, effective connectivity (EC) reflects directionality of signaling pathways. We hypothesized a specific pattern of EC in the DMN of patients with AD, related to cognitive impairment. Metabolic connectivity mapping is a novel measure of EC identifying regions of signaling input based on neuroenergetics. We simultaneously acquired resting-state functional MRI and FDG-PET data from patients with early AD (n = 35) and healthy subjects (n = 18) on an integrated PET/MR scanner. We identified two distinct subnetworks of EC in the DMN of healthy subjects: an anterior part with bidirectional EC between hippocampus and medial prefrontal cortex and a posterior part with predominant input into medial parietal cortex. Patients had reduced input into the medial parietal system and absent input from hippocampus into medial prefrontal cortex (p < 0.05, corrected). In a multiple linear regression with unimodal imaging and EC measures (F4,25 = 5.63, p = 0.002, r2 = 0.47), we found that EC (ß = 0.45, p = 0.012) was stronger associated with cognitive deficits in patients than any of the PET and fMRI measures alone. Our approach indicates specific disruptions of EC in the DMN of patients with AD and might be suitable to test molecular theories about downstream and upstream spreading of neuropathology in AD.

Aberrant striatal dopamine links topographically with cortico-thalamic dysconnectivity in schizophrenia.

Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal dopamine's topographic modulation of cortico-thalamic connectivity within cortico-basal-ganglia-thalamic circuits. We hypothesized that aberrant striatal dopamine links topographically with aberrant cortico-thalamic iFC, i.e. aberrant associative striatum dopamine is associated with aberrant iFC between the salience network and thalamus, and aberrant sensorimotor striatum dopamine with aberrant iFC between the auditory-sensorimotor network and thalamus. Nineteen patients with schizophrenia during remission of psychotic symptoms and 19 age- and sex-comparable control subjects underwent simultaneous fluorodihydroxyphenyl-l-alanine PET (18F-DOPA-PET) and resting state functional MRI (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure striatal dopamine synthesis capacity; correlation coefficients between rs-fMRI time series of cortical networks and thalamic regions of interest were used to measure iFC. In the salience network-centred system, patients had reduced associative striatum dopamine synthesis capacity, which correlated positively with decreased salience network-mediodorsal-thalamus iFC. This correlation was present in both patients and healthy controls. In the auditory-sensorimotor network-centred system, patients had reduced sensorimotor striatum dopamine synthesis capacity, which correlated positively with increased auditory-sensorimotor network-ventrolateral-thalamus iFC. This correlation was present in patients only. Results demonstrate that reduced striatal dopamine synthesis capacity links topographically with cortico-thalamic intrinsic dysconnectivity in schizophrenia. Data suggest that aberrant striatal dopamine and cortico-thalamic dysconnectivity are pathophysiologically related within dopamine-modulated cortico-basal ganglia-thalamic circuits in schizophrenia.

Reduced striatal dopamine synthesis capacity in patients with schizophrenia during remission of positive symptoms.

While there is consistent evidence for increased presynaptic dopamine synthesis capacity in the striatum of patients with schizophrenia during psychosis, it is unclear whether this also holds for patients during psychotic remission. This study investigates whether striatal dopamine synthesis capacity is altered in patients with schizophrenia during symptomatic remission of positive symptoms, and whether potential alterations relate to symptoms other than positive, such as cognitive difficulties. Twenty-three patients with schizophrenia in symptomatic remission of positive symptoms according to Andreasen, and 24 healthy controls underwent 18F-DOPA-PET and behavioural-cognitive assessment. Imaging data were analysed with voxel-wise Patlak modelling with cerebellum as reference region, resulting in the influx constant kicer reflecting dopamine synthesis capacity. For the whole striatum and its subdivisions (i.e. limbic, associative, and sensorimotor), averaged regional kicer values were calculated, compared across groups, and correlated with behavioural-cognitive scores, including a mediation analysis. Patients had negative symptoms (Positive and Negative Syndrome Scale-negative 14.13 ± 5.91) and cognitive difficulties, i.e. they performed worse than controls in Trail-Making-Test-B (TMT-B; P = 0.01). Furthermore, kicer was reduced in patients for whole striatum (P = 0.004) and associative (P = 0.002) and sensorimotor subdivisions (P = 0.007). In patients, whole striatum kicer was negatively correlated with TMT-B (rho = -0.42, P = 0.04; i.e. the lower striatal kicer, the worse the cognitive performance). Mediation analysis showed that striatal kicer mediated the group difference in TMT-B. Results demonstrate that patients with schizophrenia in symptomatic remission of positive symptoms have decreased striatal dopamine synthesis capacity, which mediates the disorder's impact on cognitive difficulties. Data suggest that striatal dopamine dysfunction contributes to cognitive difficulties in schizophrenia.

Long-wavelength infrared transmission filters via two-step subwavelength dielectric gratings.

We experimentally demonstrate a long-wavelength infrared narrowband transmission filter using an asymmetric subwavelength dielectric grating. A two-step grating geometry is used to define the asymmetry, which enables resonant narrowband transmission response at normal incidence. Computational modeling is used to show that varying the grating parameter dimensions can shift the transmission peak wavelength. Silicon/air gratings are experimentally demonstrated, with the peak transmission wavelength varying between 10 and 11.3 µm.

Changes in extra-striatal functional connectivity in patients with schizophrenia in a psychotic episode.

BACKGROUND: In patients with schizophrenia in a psychotic episode, intra-striatal intrinsic connectivity is increased in the putamen but not ventral striatum. Furthermore, multimodal changes have been observed in the anterior insula that interact extensively with the putamen. AIMS: We hypothesised that during psychosis, putamen extra-striatal functional connectivity is altered with both the anterior insula and areas normally connected with the ventral striatum (i.e. altered functional connectivity distinctiveness of putamen and ventral striatum). METHOD: We acquired resting-state functional magnetic resonance images from 21 patients with schizophrenia in a psychotic episode and 42 controls. RESULTS: Patients had decreased functional connectivity: the putamen with right anterior insula and dorsal prefrontal cortex, the ventral striatum with left anterior insula. Decreased functional connectivity between putamen and right anterior insula was specifically associated with patients' hallucinations. Functional connectivity distinctiveness was impaired only for the putamen. CONCLUSIONS: Results indicate aberrant extra-striatal connectivity during psychosis and a relationship between reduced putamen-right anterior insula connectivity and hallucinations. Data suggest that altered intrinsic connectivity links striatal and insular pathophysiology in psychosis.

Aberrant topology of striatum's connectivity is associated with the number of episodes in depression.

In major depressive disorder, depressive episodes reoccur in ∼60% of cases; however, neural mechanisms of depressive relapse are poorly understood. Depressive episodes are characterized by aberrant topology of the brain's intrinsic functional connectivity network, and the number of episodes is one of the most important predictors for depressive relapse. In this study we hypothesized that specific changes of the topology of intrinsic connectivity interact with the course of episodes in recurrent depressive disorder. To address this hypothesis, we investigated which changes of connectivity topology are associated with the number of episodes in patients, independently of current symptoms and disease duration. Fifty subjects were recruited including 25 depressive patients (two to 10 episodes) and 25 gender- and age-matched control subjects. Resting-state functional magnetic resonance imaging, Harvard-Oxford brain atlas, wavelet-transformation of atlas-shaped regional time-series, and their pairwise Pearson's correlation were used to define individual connectivity matrices. Matrices were analysed by graph-based methods, resulting in outcome measures that were used as surrogates of intrinsic network topology. Topological scores were subsequently compared across groups, and, for patients only, related with the number of depressive episodes and current symptoms by partial correlation analysis. Concerning the whole brain connectivity network of patients, small-world topology was preserved but global efficiency was reduced and global betweenness-centrality increased. Aberrant nodal efficiency and centrality of regional connectivity was found in the dorsal striatum, inferior frontal and orbitofrontal cortex as well as in the occipital and somatosensory cortex. Inferior frontal changes were associated with current symptoms, whereas aberrant right putamen network topology was associated with the number of episodes. Results were controlled for effects of total grey matter volume, medication, and total disease duration. This finding provides first evidence that in major depressive disorder aberrant topology of the right putamen's intrinsic connectivity pattern is associated with the course of depressive episodes, independently of current symptoms, medication status and disease duration. Data suggest that the reorganization of striatal connectivity may interact with the course of episodes in depression thereby contributing to depressive relapse risk.

Link between hippocampus' raised local and eased global intrinsic connectivity in AD.

BACKGROUND: The hippocampus (HP) is part of the default mode network (DMN), and both are key targets of Alzheimer's disease (AD). Because of widespread network degeneration, it has been suggested that increasing HP disconnection from the DMN may lead to progressive disinhibition of intra-HP synchronized activity. METHODS: To analyze HP local (i.e., within HP) and global (i.e., within DMN) intrinsic functional connectivity (local/global intrinsic functional connectivity [iFC]), healthy controls and patients with mild cognitive impairment and AD dementia were assessed by spatial high and normal resolution resting-state functional magnetic resonance imaging. RESULTS: Although patients' parietal local-iFC was reduced and positively correlated with reduced global-iFC within the DMN, HP local connectivity was progressively increased and negatively correlated with HP decreased global connectivity. Increased intra-HP connectivity was associated with impaired memory. CONCLUSION: Our result demonstrates a link between increased local and reduced global hippocampal connectivity in AD. Increased intra-HP synchrony may contribute to distinct symptoms such as memory impairment or more speculatively epileptic seizure.

Patterns of cognitive performance in Subcortical Ischemic Vascular Disease (SIVD).

Subcortical ischemic vascular disease (SIVD) is characterized by extensive white-matter lesions and lacunar infarcts in deep gray matter. The aim of this study was to investigate patterns of cognitive impairment in patients with SIVD. In a retrospective analysis, the authors compared the cognitive performance of 58 patients meeting MRI-defined criteria for SIVD (26 women; 47.3%) with age- and gender-matched control subjects. SIVD patients showed impairments in measures of verbal fluency, verbal memory, speed of cognitive processing, and divided attention. There were no significant differences in constructional praxis, figurative memory, verbal recognition memory, or semantic processing.

Helper Syndrome and Pathological Altruism in nurses - a study in times of the COVID-19 pandemic.

Background: Pathological Altruism and the concept of Helper Syndrome are comparable. We focused on Schmidbauer's description because it provides a comprehensive and testable definition. Nevertheless, this concept of Helper Syndrome has not yet been empirically investigated in a sample of helping professionals. Aim: To investigate whether nurses working with covid-19 patients are more likely to have Helper Syndrome compared with individuals from non-helper professions. Methods: The online survey took place between April 2021 and February 2022, in urban and rural regions of Salzburg, during the time of the COVID-19 pandemic. Nurses (n = 447) and controls (n = 295) were compared regarding Helper Syndrome characteristics. To measure characteristics of Helper Syndrome the following questionnaires were used: WHO-Five (WHO-5), selected scales of the Personality, Style and Disorder Inventory (PSSI) and the Freiburg Personality Inventory-Revised (FPI-R), the Alcohol Use Disorders Identification Test (AUDIT). Insecure gender identity and self-assessment of having a Helper Syndrome was measured by a Likert scale. Results: In both groups, Helper Syndrome was detected (nurses 29.5%, controls 30.5%). Participants with Helper Syndrome showed significant differences in personality styles and traits, namely significantly higher scores for Foreboding-Schizotypical Personality Style, Spontaneous-Borderline Personality Style, Amiable-Histrionic Personality Style, Ambitious-Narcissistic Personality Style, Loyal-Dependent Personality Style, Helpful-Selfless Personality Style, Carefully-Obsessive Personality Style, Optimistic-Rhapsodic Personality Style, Social Orientation, Strain, Emotionality and lower well-being. The only difference between nurses and controls was that nurses were significantly less open aggressive. Conclusion: For the first time, we were able to demonstrate Schmidbauer's concept of Helper Syndrome. According to our data, we found a subgroup of individuals similar to Schmidbauer's description of Helper Syndrome, but this sample was independent of helping or non-helping profession. These individuals seem to be at higher risk for psychiatric disorders.

Depressive symptoms are more influenced by personality traits and styles than working in nursing-a study during the COVID-19 pandemic.

Background: According to literature, the COVID-19 pandemic caused stressful working conditions for nurses, which may have a negative impact on their Well-Being and mental health. Aim: To investigate whether nurses and non-helping professionals differ in their Well-Being. Furthermore, we analyzed, for the first time, which personality traits and styles are a risk factor for nurses' wellbeing during COVID-19 pandemic. Methods: In an online survey, the following psychological tests were used on nursing staff (n = 518) and non-helping professionals (n = 335): WHO-Five (WHO-5), the Personality, Style and Disorder Inventory (PSSI), and the Freiburg Personality Inventory-Revised (FPI-R). Results: Nurses and non-helping professionals did not differ significantly in terms of Well-Being. The Well-Being of nurses was correlated with the following personality traits and styles, namely Spontaneous-Borderline Personality Style, Silent-Depressive Personality Style, Strain, Emotionality, and Life Satisfaction. According to our results, 33% of participants suffered from clinically significant depressive symptoms. Discussion: According to our results, nurses are not more at risk for depression. However, it was shown that Well-Being during the pandemic is highly dependent on personality. Conclusion: Specific personality traits and styles are a greater predictor of depressive symptoms than profession. The stressful occupational environment during COVID-19 pandemic is not the only cause for depressive symptoms in nurses. Psychotherapeutic interventions are especially important for particular individuals and are necessary to prevent depressive symptoms during COVID-19 pandemic.

Environmental risk factors and their impact on the age of onset of schizophrenia: Comparing familial to non-familial schizophrenia.

BACKGROUND AND AIMS: Several risk factors for schizophrenia have yet been identified. The aim of our study was to investigate how certain childhood and adolescent risk factors predict the age of onset of psychosis in patients with and without a familial component (i.e. a relative with schizophrenia or schizoaffective disorder). METHODS: Aside from the age of onset of psychosis, we examined the risk factors for schizophrenia including obstetric complications, birth during winter or spring, behavioral deviances or delayed motor and speech development, exposure to adverse life events and exposure to substance use within a group of 100 patients (45 female, 55 male) with a mean age (± standard deviation) of 35.15 ± 13.21. RESULTS: Birth complications and cannabis abuse are predictors for an earlier onset of schizophrenia in patients with non-familial schizophrenia. No environmental risk factors for an earlier age of onset in familial schizophrenia have been identified. CONCLUSIONS: Certain environmental risk factors for schizophrenia seem to have an impact on the age of onset of psychosis in non-familial schizophrenia, they do not seem to have an impact on familial schizophrenia.

Impact of non-uniform attenuation correction in a dynamic [18F]-FDOPA brain PET/MRI study.

BACKGROUND: PET (positron emission tomography) biokinetic modelling relies on accurate quantitative data. One of the main corrections required in PET imaging to obtain high quantitative accuracy is tissue attenuation correction (AC). Incorrect non-uniform PET-AC may result in local bias in the emission images, and thus in relative activity distributions and time activity curves for different regions. MRI (magnetic resonance imaging)-based AC is an active area of research in PET/MRI neuroimaging, where several groups developed in the last few years different methods to calculate accurate attenuation (µ-)maps. Some AC methods have been evaluated for different PET radioisotopes and pathologies. However, AC in PET/MRI has scantly been investigated in dynamic PET studies where the aim is to get quantitative kinetic parameters, rather than semi-quantitative parameters from static PET studies. In this work, we investigated the impact of AC accuracy in PET image absolute quantification and, more importantly, in the slope of the Patlak analysis based on the simplified reference tissue model, from a dynamic [18F]-fluorodopa (FDOPA) PET/MRI study. In the study, we considered the two AC methods provided by the vendor and an in-house AC method based on the dual ultrashort time echo MRI sequence, using as reference a multi-atlas-based AC method based on a T1-weighted MRI sequence. RESULTS: Non-uniform bias in absolute PET quantification across the brain, from - 20% near the skull to - 10% in the central region, was observed using the two vendor's µ-maps. The AC method developed in-house showed a - 5% and 1% bias, respectively. Our study resulted in a 5-9% overestimation of the PET kinetic parameters with the vendor-provided µ-maps, while our in-house-developed AC method showed < 2% overestimation compared to the atlas-based AC method, using the cerebellar cortex as reference region. The overestimation obtained using the occipital pole as reference region resulted in a 7-10% with the vendor-provided µ-maps, while our in-house-developed AC method showed < 6% overestimation. CONCLUSIONS: PET kinetic analyses based on a reference region are especially sensitive to the non-uniform bias in PET quantification from AC inaccuracies in brain PET/MRI. Depending on the position of the reference region and the bias with respect to the analysed region, kinetic analyses suffer different levels of bias. Considering bone in the µ-map can potentially result in larger errors, compared to the absence of bone, when non-uniformities in PET quantification are introduced.

[Trichoma (Plica polonica) - a contemporary case with a historical disease]. / Der Weichselzopf (Plica polonica) - eine aktuelle Kasuistik zu einem historischen Krankheitskonzept.

We describe a 62-year-old patient with a chronic delusional disorder who presented with severely matted hair ("plica polonica"). Until the late 19th century such dreadlocks were considered as cause, consequence and treatment of mental disease. The historical development of "plica polonica" is briefly reviewed as an example of early and once popular psychiatric disease concepts.

Decoupling of Local Metabolic Activity and Functional Connectivity Links to Amyloid in Alzheimer's Disease.

BACKGROUND: Both ongoing local metabolic activity (LMA) and corresponding functional connectivity (FC) with remote brain regions are progressively impaired in Alzheimer's disease (AD), particularly in the posterior default mode network (pDMN); however, it is unknown how these impairments interact. It is well known that decreasing mean synaptic activity of a region, i.e., decreasing LMA, reduces the region's sensitivity to afferent input from other regions, i.e., FC. OBJECTIVE: We hypothesized progressive decoupling between LMA and FC in AD, which is linked to amyloid-ß pathology (Aß). METHODS: Healthy adults (n=20) and Aß+patients without memory impairment (n=9), early MCI (n=21), late MCI (n=18) and AD (n=22) were assessed by resting-state fMRI, FDG-PET, and AV-45-PET to measure FC, LMA, and Aß of the pDMN. Coupling between LMA and FC (rLA/FC) was estimated by voxelwise correlation. RESULTS: RLMA/FC decreased with disease severity (F=20.09, p<0.001). This decrease was specifically associated with pDMN Aß (r=-0.273, p=0.029) but not global Aß (r=-0.112, p=0.378) and with the impact of Aß on FC (i.e., rAß/FC,r=-0.339; p=0.006). In multiple regression models rLMA/FC was also associated with memory impairment, reduced cognitive speed and flexibility, outperforming global Aß, pDMN Aß, pDMN LMA, and pDMN FC, respectively. CONCLUSION: Results demonstrate increasing decoupling of LMA from its FC in AD. Data suggest that decoupling is driven by local Aß and contributes to memory decline.

Individual Correspondence of Amyloid-ß and Intrinsic Connectivity in the Posterior Default Mode Network Across Stages of Alzheimer's Disease.

In Alzheimer's disease (AD), amyloid-ß (Aß) pathology and intrinsic functional connectivity (iFC) interact. Across stages of AD, we expected individual spatial correspondence of Aß and iFC to reveal both Aß accumulation and its detrimental effects on iFC. We used resting-state functional magnetic imaging and Aß imaging in a cross-sectional sample of 90 subjects across stages of AD and healthy older adults. Global and local correspondence of Aß and iFC were assessed within the posterior default mode network (pDMN) by within-subject voxel-wise correlations. Beginning at preclinical stages, global Aß-iFC correspondence was positive for the whole pDMN, showing that Aß accumulates in areas of high connectivity, and reached a plateau at prodromal stages. Starting at preclinical stages, local correspondence was negative in network centers, indicating that Aß reduces connectivity of the pDMN as a function of local plaque concentration, and peaked at prodromal stages. Positive global correspondence suggests that Aß accumulation progresses along iFC, with this effect starting in preclinical stages, and being constant along clinical periods. Negative local correspondence suggests detrimental effects of Aß on iFC in network centers, starting at preclinical stages, and peaking when first symptoms appear. Data reveal a complex trajectory of Aß and iFC correspondence, affecting both Aß accumulation and iFC impairments.

Degradation in intrinsic connectivity networks across the Alzheimer's disease spectrum.

INTRODUCTION: Changes in intrinsic functional connectivity (iFC) have been reported at various stages of the Alzheimer's disease (AD) spectrum. We aimed to investigate such alterations over a variety of large-scale intrinsic brain networks (iBNs) across the spectrum of amyloid ß positivity and uncover their relation to cognitive impairment. METHODS: Eight iBNs were defined from resting-state functional magnetic resonance imaging data. In amyloid ß-positive healthy subjects, prodromal, and AD patients (N = 70), within-network iFC (intra-iFC) and between-network iFC (inter-iFC) were correlated with scores of cognitive impairment. RESULTS: Across all iBNs, a general degradation in intra-iFC along the scale of cognitive impairment severity was found. Only subtle changes in inter-iFC were identified. DISCUSSION: Across the AD spectrum, changes in iFC that are strongly related to cognitive impairment occur within an extensive variety of networks.

More Consistently Altered Connectivity Patterns for Cerebellum and Medial Temporal Lobes than for Amygdala and Striatum in Schizophrenia.

BACKGROUND: Brain architecture can be divided into a cortico-thalamic system and modulatory "subcortical-cerebellar" systems containing key structures such as striatum, medial temporal lobes (MTLs), amygdala, and cerebellum. Subcortical-cerebellar systems are known to be altered in schizophrenia. In particular, intrinsic functional brain connectivity (iFC) between these systems has been consistently demonstrated in patients. While altered connectivity is known for each subcortical-cerebellar system separately, it is unknown whether subcortical-cerebellar systems' connectivity patterns with the cortico-thalamic system are comparably altered across systems, i.e., if separate subcortical-cerebellar systems' connectivity patterns are consistent across patients. METHODS: To investigate this question, 18 patients with schizophrenia (3 unmedicated, 15 medicated with atypical antipsychotics) and 18 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI). Independent component analysis of fMRI data revealed cortical intrinsic brain networks (NWs) with time courses representing proxies for cortico-thalamic system activity. Subcortical-cerebellar systems' activity was represented by fMRI-based time courses of selected regions-of-interest (ROIs; i.e., striatum, MTL, amygdala, cerebellum). Correlation analysis among ROI- and NWs-time courses yielded individual connectivity matrices [i.e., connectivity between NW and ROIs (allROIs-NW, separateROI-NW), only NWs (NWs-NWs), and only ROIs (allROIs-allROIs)] as main outcome measures, which were classified by support-vector-machine-based (SVM) leave-one-out cross-validation. Differences in classification accuracy were statistically evaluated for consistency across subjects and systems. RESULTS: Correlation matrices based on allROIs-NWs yielded 91% classification accuracy, which was significantly superior to allROIs-allROIs and NWs-NWs (56 and 74%, respectively). Considering separate subcortical-cerebellar systems, cerebellum-NWs and MTL-NWs reached highest accuracy values with 91 and 85%, respectively, while those of striatum-NW and amygdala-NW were significantly lower with about 65% classification accuracy. CONCLUSION: RESULTS provide initial evidence for differential consistency of altered intrinsic connectivity patterns between subcortical-cerebellar systems and the cortico-thalamic system. Data suggest that differential dysconnectivity patterns between subcortical-cerebellar and cortical systems might reflect different disease states or patient subgroups.

Ignoring floor and ceiling effects may underestimate the effect of carotid artery stenting on cognitive performance.

INTRODUCTION: Data on neuropsychological outcome after carotid artery stenting (CAS) remain inconsistent, furthermore cognitive outcome seems to be unpredictable in the individual case. Previous studies reporting improvement or decline might be due to ceiling and floor effects of the applied cognitive tests. We applied cognitive testing before and after CAS, avoiding the pitfall of ceiling and floor effects. METHODS: In our prospective database, we identified 72 patients free of clinical stroke with ≥70% carotid artery stenosis, who were treated with CAS. They were administered a neurocognitive test battery before and 3 months after CAS to compare cognitive performance before and after CAS. To avoid ceiling and floor effects of test performances, we additionally analysed subgroups of patients without baseline floor and ceiling cognitive performance. RESULTS: Pre-interventional to post-interventional cognitive performance improved significantly in the subtests measuring verbal episodic memory; deterioration was observed in spatial memory. The subgroups of patients without baseline floor and ceiling cognitive performance improved in measures of global cognition, verbal episodic memory (patients with left-sided CAS) and divided attention (patients with right-sided CAS); we observed no significant effects in the other domains. CONCLUSIONS: Ignoring floor and ceiling effects may underestimate the impact of CAS on cognitive performance.

Increased Intrinsic Activity of Medial-Temporal Lobe Subregions is Associated with Decreased Cortical Thickness of Medial-Parietal Areas in Patients with Alzheimer's Disease Dementia.

In Alzheimer's disease (AD), disrupted connectivity between medial-parietal cortices and medial-temporal lobes (MTL) is linked with increased MTL local functional connectivity, and parietal atrophy is associated with increased MTL memory activation. We hypothesized that intrinsic activity in MTL subregions is increased and associated with medial-parietal degeneration and impaired memory in AD. To test this hypothesis, resting-state-functional and structural-MRI was assessed in 22 healthy controls, 22 mild cognitive impairment patients, and 21 AD-dementia patients. Intrinsic activity was measured by power-spectrum density of blood-oxygenation-level-dependent signal, medial-parietal degeneration by cortical thinning. In AD-dementia patients, intrinsic activity was increased for several right MTL subregions. Raised intrinsic activity in dentate gyrus and cornu ammonis 1 was associated with cortical thinning in posterior cingulate cortices, and at-trend with impaired delayed recall. Critically, increased intrinsic activity in the right entorhinal cortex was associated with ipsilateral posterior cingulate degeneration. Our results provide evidence that in AD, intrinsic activity in MTL subregions is increased and associated with medial-parietal atrophy. Results fit a model in which medial-parietal degeneration contributes to MTL dysconnectivity from medial-parietal cortices, potentially underpinning disinhibition-like changes in MTL activity.

Ultrashort Channel Length Black Phosphorus Field-Effect Transistors.

This paper reports high-performance top-gated black phosphorus (BP) field-effect transistors with channel lengths down to 20 nm fabricated using a facile angle evaporation process. By controlling the evaporation angle, the channel length of the transistors can be reproducibly controlled to be anywhere between 20 and 70 nm. The as-fabricated 20 nm top-gated BP transistors exhibit respectable on-state current (174 µA/µm) and transconductance (70 µS/µm) at a VDS of 0.1 V. Due to the use of two-dimensional BP as the channel material, the transistors exhibit relatively small short channel effects, preserving a decent on-off current ratio of 10(2) even at an extremely small channel length of 20 nm. Additionally, unlike the unencapsulated BP devices, which are known to be chemically unstable in ambient conditions, the top-gated BP transistors passivated by the Al2O3 gate dielectric layer remain stable without noticeable degradation in device performance after being stored in ambient conditions for more than 1 week. This work demonstrates the great promise of atomically thin BP for applications in ultimately scaled transistors.