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Background Progressive supranuclear palsy (PSP) with a frontal presentation, characterized by cognitive deficits and behavioral changes, has been recognized as an early clinical picture, distinct from the classical so-called Richardson and parkinsonism presentations. The midcingulate cortex is associated with executive and attention tasks and has consistently been found to be impaired in imaging studies of patients with PSP. The aim of the present study was to determine alterations in neurotransmission underlying the pathophysiology of PSP, as well as their significance for clinically identifiable PSP subgroups. Methods In vitro receptor autoradiography was used to quantify densities of 20 different receptors in the caudate nucleus and midcingulate area 24' of patients with PSP ( n  = 16) and age- and sex-matched control subjects ( n  = 14). Results Densities of γ-aminobutyric acid type B, peripheral benzodiazepine, serotonin receptor type 2, and N -methyl- d -aspartate receptors were significantly higher in area 24′ of patients with PSP, where tau impairment was stronger than in the caudate nucleus. Kainate and nicotinic cholinergic receptor densities were significantly lower, and adenosine receptor type 1 (A 1 ) receptors significantly higher, in the caudate nucleus of patients with PSP. Receptor fingerprints also segregated PSP subgroups when clinical parameters such as occurrence of frontal presentation and tau pathology severity were taken into consideration. Conclusions We demonstrate, for the first time to our knowledge, that kainate and A 1 receptors are altered in PSP and that clinically identifiable PSP subgroups differ at the neurochemical level. Numerous receptors were altered in the midcingulate cortex, further suggesting that it may prove to be a key region in PSP. Finally, we add to the evidence that nondopaminergic systems play a role in the pathophysiology of PSP, thus highlighting potential novel treatment strategies.

In mouse frontal cortex, fear conditioning and extinction cause dendritic spine elimination and, respectively, formation to occur on the same dendritic branches in a cue- and location-specific manner. Rewiring the memory circuits Learning and memory are thought to involve physical and functional changes to neuronal connections, but relatively little is known about structural changes to behaviour-relevant circuits. Two new studies highlight some of the physical alterations and mechanisms that may underlie learning and neural plasticity. Lai et al . analysed neurons participating in fear circuits: they found that fear learning induced a loss of dendritic spines, and that extinction of the fear caused a regrowth of spines in the same areas. Fu et al . reveal that repetitive activation of specific circuitry during motor learning can induce formation of new clusters of dendritic spines, which remain throughout prolonged learning sessions. It is generally believed that fear extinction is a form of new learning that inhibits rather than erases previously acquired fear memories 1 , 2 , 3 . Although this view has gained much support from behavioural and electrophysiological studies 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , the hypothesis that extinction causes the partial erasure of fear memories remains viable. Using transcranial two-photon microscopy 11 , 12 , we investigated how neural circuits are modified by fear learning and extinction by examining the formation and elimination of postsynaptic dendritic spines of layer-V pyramidal neurons in the mouse frontal association cortex. Here we show that fear conditioning by pairing an auditory cue with a footshock increases the rate of spine elimination. By contrast, fear extinction by repeated presentation of the same auditory cue without a footshock increases the rate of spine formation. The degrees of spine remodelling induced by fear conditioning and extinction strongly correlate with the expression and extinction of conditioned fear responses, respectively. Notably, spine elimination and formation induced by fear conditioning and extinction occur on the same dendritic branches in a cue- and location-specific manner: cue-specific extinction causes formation of dendritic spines within a distance of two micrometres from spines that were eliminated after fear conditioning. Furthermore, reconditioning preferentially induces elimination of dendritic spines that were formed after extinction. Thus, within vastly complex neuronal networks, fear conditioning, extinction and reconditioning lead to opposing changes at the level of individual synapses. These findings also suggest that fear memory traces are partially erased after extinction.

IntroductionMeta-analyses suggest that patients with schizophrenia show deficit in working memory – both verbal and visual – and are more distractible. Working memory disturbances are even regarded as the central deficit in schizophrenia by some researchers. Theta synchronization (especially over fronto-central areas) is related to cognitive control and executive functioning during working memory encoding and retention.ObjectivesThe main goal of the study was to gain more understanding of the nature of working memory deficit and attentional distractibility in schizophrenia.Methods35 patients with schizophrenia and 39 matched controls were enrolled in our study. Participants performed a modified Sternberg working memory task that contained salient and non-salient distractor items in the retention period. A high-density 128 channel EEG was recorded during the task. Event-related theta (4-7 Hz) synchronization was analyzed during working memory encoding (learning) and retention (distractor filtering) in a later time window (350-550 ms).ResultsPatients with schizophrenia showed weaker working memory performance and increased attentional distractibility compared to the control group: patients had significantly lower hit rates (p < 0.0001) and higher distractor-related commission error rates (p < 0.0001). Theta synchronization was modulated by condition (learning < distractor) in both groups but it was modulated by salience only in controls (salient distractor > non-salient distractor, p[patients] = 0.95, p[controls] < 0.001).ConclusionsOur results suggest that patients with schizophrenia show diminished cognitive control compared to controls in response to salient distractors. Difficulties in cognitive control allocation may contribute to the behavioral results observed in this study.DisclosureNo significant relationships.

Objectives To validate a visual rating scale of frontal atrophy with quantitative imaging and study its association with clinical status, APOE ε4, CSF biomarkers, and cognition. Methods The AddNeuroMed and ADNI cohorts were combined giving a total of 329 healthy controls, 421 mild cognitive impairment patients, and 286 Alzheimer’s disease (AD) patients. Thirty-four patients with frontotemporal dementia (FTD) were also included. Frontal atrophy was assessed with the frontal sub-scale of the global cortical atrophy scale (GCA-F) on T1-weighted images. Automated imaging markers of cortical volume, thickness, and surface area were evaluated. Manual tracing was also performed. Results The GCA-F scale reliably reflects frontal atrophy, with orbitofrontal, dorsolateral, and motor cortices being the regions contributing most to the GCA-F ratings. GCA-F primarily reflects reductions in cortical volume and thickness, although it was able to detect reductions in surface area too. The scale showed significant associations with clinical status and cognition. Conclusion The GCA-F scale may have implications for clinical practice as supportive diagnostic tool for disorders demonstrating predominant frontal atrophy such as FTD and the executive presentation of AD. We believe that GCA-F is feasible for use in clinical routine for the radiological assessment of dementia and other disorders. Key points • The GCA - F visual rating scale reliably reflects frontal brain atrophy . • Orbitofrontal , dorsolateral , and motor cortices are the most contributing regions . • GCA - F shows significant associations with clinical status and cognition . • GCA - F may be supportive diagnostic tool for disorders demonstrating predominant frontal atrophy . • GCA - F may be feasible for use in radiological routine .

Background In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinson's disease incidence. Although not exhaustively studied in this devastating disease, the impact of sex represents a critical variable in Parkinson’s disease as epidemiological and clinical features differ between males and females. Methods To study sex bias in Parkinson’s disease, we conducted a systematic review to select sex-labeled transcriptomic data from three relevant brain tissues: the frontal cortex, the striatum, and the substantia nigra. We performed differential expression analysis on each study chosen. Then we summarized the individual differential expression results with three tissue-specific meta-analyses and a global all-tissues meta-analysis. Finally, results from the meta-analysis were functionally characterized using different functional profiling approaches. Results The tissue-specific meta-analyses linked Parkinson’s disease to the enhanced expression of MED31 in the female frontal cortex and the dysregulation of 237 genes in the substantia nigra. The global meta-analysis detected 15 genes with sex-differential patterns in Parkinson’s disease, which participate in mitochondrial function, oxidative stress, neuronal degeneration, and cell death. Furthermore, functional analyses identified pathways, protein–protein interaction networks, and transcription factors that differed by sex. While male patients exhibited changes in oxidative stress based on metal ions, inflammation, and angiogenesis, female patients exhibited dysfunctions in mitochondrial and lysosomal activity, antigen processing and presentation functions, and glutamic and purine metabolism. All results generated during this study are readily available by accessing an open web resource ( http://bioinfo.cipf.es/metafun-pd/ ) for consultation and reuse in further studies. Conclusions Our in silico approach has highlighted sex-based differential mechanisms in typical Parkinson Disease hallmarks (inflammation, mitochondrial dysfunction, and oxidative stress). Additionally, we have identified specific genes and transcription factors for male and female Parkinson Disease patients that represent potential candidates as biomarkers to diagnosis. Highlights Females show a significant increase in the expression of MED31 in the frontal cortex. This gene is involved in lipid metabolism and neural diseases. We found 237 genes having sex-based significantly differential expression in substantia nigra. Functional profiling of these genes reveals a differential sex-related behavior in PD regarding their biological functions, protein-protein interaction networks, and transcription factors activation. There are remarkable sex based differential mechanisms in typical PD hallmarks: inflammation, mitochondrial dysfunction, and oxidative stress. Studies on sex differences in PD are needed to improve more targeted interventions.

In today’s competitive e-commerce markets, it is crucial to promote product satisfaction and to quickly identify purchase intention in decision-making consumers. The present investigation examined the relationship between perceived garment fit and purchase intention, together with how product presentation methods (mannequin versus self-model) contribute to decision-making processes of clothing. Thirty-nine female volunteers were scanned using fMRI while performing an online shopping task. In Part 1, univariate analysis was conducted between garment fit and product presentation factors to assess their effects on purchase deliberation. In Part 2, univariate, multivariate pattern, and psychophysiological interaction analyses were carried out to examine the predictive ability of fit evaluation and product presentation on purchase intention. First, garment fit × product presentation interaction effects on purchase deliberation were observed in the frontopolar cortex, superior frontal gyrus, anterior cingulate cortex, and posterior cingulate cortex. Part 2 demonstrated neural signals of the dorsomedial prefrontal cortex, premotor cortex, supplementary motor area, superior parietal lobule, supramarginal gyrus, superior temporal sulcus, fusiform gyrus, and insula to distinguish subsequent purchase intentions. Overall, the findings denote directed exploration, visual and action processing as key neural processes in decision-making that uniquely reflect garment fit and product presentation type during purchase deliberation. Additionally, with respect to the effects of purchase intention on product evaluation, the evidence conveys that mental interactions with products and social cognition are fundamental processes that capture subsequent purchase intention at the product evaluation stage.

Abstract Alexithymia is characterized by impairments in emotion processing, frequently linked to facial expressions of emotion. The eye-region conveys information necessary for emotion processing. It has been demonstrated that alexithymia is associated with reduced attention to the eyes, but little is known regarding the cognitive and electrophysiological mechanisms underlying emotive eye-region processing in alexithymia. Here, we recorded behavioral and electrophysiological responses of individuals with alexithymia (ALEX; n = 25) and individuals without alexithymia (NonALEX; n = 23) while they viewed intact and eyeless faces with angry and sad expressions during a dual-target rapid serial visual presentation task. Results showed different eye-region focuses and differentiating N1 responses between intact and eyeless faces to anger and sadness in NonALEX, but not in ALEX, suggesting deficient perceptual processing of the eye-region in alexithymia. Reduced eye-region focus and smaller differences in frontal alpha asymmetry in response to sadness between intact and eyeless faces were observed in ALEX than NonALEX, indicative of impaired affective processing of the eye-region in alexithymia. These findings highlight perceptual and affective abnormalities of emotive eye-region processing in alexithymia. Our results contribute to understanding the neuropsychopathology of alexithymia and alexithymia-related disorders.

Pott’s puffy tumour (PPT) is a known complication of frontal sinusitis. It is defined as subperiosteal abscess formation due to osteomyelitis of the frontal bone presenting as a forehead swelling. It is a life-threatening condition that can lead to intracranial and intraorbital complications. Gadolinium-enhanced MRI and contrast CT scan are the best modalities to localise and define the collection, in addition to confirming disease extension. Once confirmed by imaging and depending on disease extension, management of PPT requires a multidisciplinary team approach and depends on the local provision of surgical care. Following surgical drainage of the abscess cavity, a prolonged course of antibiotics is required postoperatively to treat the underlying osteomyelitis.

Objective:Higher levels of inflammation are associated with risk factors for Alzheimer’s disease and related dementias (ADRD) in older Black adults including psychosocial stressors (e.g., discrimination and early life adversity) and white matter alterations. Yet, limited work has investigated these risk factors together in a longitudinal neuroimaging study, despite the well-known ADRD disparity in older Black adults. Using data from the Minority Aging Research Study and African American Clinical Core of the Rush Alzheimer’s Disease Center, we examined interactions of psychosocial stressors and change in inflammation on changes in white matter integrity as measured via diffusion tensor imaging (DTI).Participants and Methods:Older Black adults (n=102) without known dementia at baseline (age=75.8±6.1 years; 87.3% female; education=15.4±2.7 years) completed blood draws at two time points (follow-up=2.4±0.7 years), neuroimaging at two or more time points (follow-up=3.7±1.8 years), and psychosocial questionnaires at one time point coinciding with the first blood draw/neuroimaging. Blood serum was assayed using highly-sensitive multiplexed sandwich ELISA for interleukin-6, c-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-a) and a change score was calculated for each inflammatory marker (T2 - T1). The Williams Everyday Discrimination Scale quantified experiences of discrimination in all participants and a 16-item questionnaire of emotional and physical trauma from age 0-18 assessed early life adversity in a participant subset (n=63). DTI-derived tract-based spatial statistics (TBSS) slope change measures for trace of the diffusion tensor, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were calculated, with the first two scans matched in time to blood assays. Linear regression models investigated interactions of each inflammatory marker change score (separately) and either discrimination or early life adversity (separately) on trace, FA, AD, and RD slopes as individual outcomes adjusting for age, sex, education, white matter hyperintensities (total volume and voxelwise), cardiovascular risk factors, statin and analgesic medications, thyroid conditions, and depression. Statistical significance was determined at p<0.05 using family wise error correction and threshold free cluster enhancement.Results:Discrimination moderated the relationship between TNF-a and AD whereby those with increasing TNF-a and higher levels of discrimination had increasing levels of AD over time in white matter tracts connecting the left and right cerebellum, the left pallidum and medulla, and the left superior frontal gyrus and left thalamus. Both discrimination and early life adversity moderated associations between CRP and AD, where increases in CRP and higher psychosocial stressors (of either type) resulted in decreasing AD over time in tracts involving cingulate, frontal, and parietal regions. Discrimination and early life adversity also moderated associations between CRP and RD, where increasing CRP combined with greater psychosocial stressors resulted in decreasing RD in right hemisphere association and projection tracts connecting frontal, parietal, central, and subcortical regions.Conclusions:TNF-a and CRP interacted with measures of psychosocial stress to associate with DTI-derived TBSS slope change measures of AD and RD in differential, and at times, paradoxical ways. Findings suggest that both risk and resilience as related to brain connectivity may be co-occurring in the presence of psychosocial stressors for older Black adults.

An 18-month-old boy presented with lytic lesion of skull and recurrent abscesses with Serratia marcescens. The extensive work up revealed a gene mutation confirming the diagnosis of chronic granulomatous disease (CGD). This case scenario underscores the importance of exploring the possibility of immunodeficiency if there is a history of recurrent abscesses with atypical organism. The case also demonstrates that CGD can present as lytic lesion of skull.