Laboratory based correlative cryo-soft X-ray tomography and cryo-fluorescence microscopy.

Cryo-soft X-ray tomography is the unique technology that can image whole intact cells in 3D under normal and pathological conditions without labelling or fixation, at high throughput and spatial resolution. The sample preparation is relatively straightforward; requiring just fast freezing of the specimen before transfer to the microscope for imaging. It is also possible to image chemically fixed samples where necessary. The technique can be correlated with cryo fluorescence microscopy to localize fluorescent proteins to organelles within the whole cell volume. Cryo-correlated light and soft X-ray tomography is particularly useful for the study of gross morphological changes brought about by disease or drugs. For example, viral fluorescent tags can be co-localized to sites of viral replication in the soft X-ray volume. In general this approach is extremely useful in the study of complex 3D organelle structure, nanoparticle uptake or in the detection of rare events in the context of whole cell structure. The main challenge of soft X-ray tomography is that the soft X-ray illumination required for imaging has heretofore only been available at a small number of synchrotron labs worldwide. Recently, a compact device with a footprint small enough to fit in a standard laboratory setting has been deployed ("the SXT-100") and is routinely imaging cryo prepared samples addressing a variety of disease and drug research applications. The SXT-100 facilitates greater access to this powerful technique and greatly increases the scope and throughput of potential research projects. Furthermore, the availability of cryo-soft X-ray tomography in the laboratory will accelerate the development of novel correlative and multimodal workflows by integration with light and electron microscope based approaches. It also allows for co-location of this powerful imaging modality at BSL3 labs or other facilities where safety or intellectual property considerations are paramount. Here we describe the compact SXT-100 microscope along with its novel integrated cryo-fluorescence imaging capability.

Microstructural neural correlates of maximal grip strength in autistic children: the role of the cortico-cerebellar network and attention-deficit/hyperactivity disorder features.

Introduction: Maximal grip strength, a measure of how much force a person's hand can generate when squeezing an object, may be an effective method for understanding potential neurobiological differences during motor tasks. Grip strength in autistic individuals may be of particular interest due to its unique developmental trajectory. While autism-specific differences in grip-brain relationships have been found in adult populations, it is possible that such differences in grip-brain relationships may be present at earlier ages when grip strength is behaviorally similar in autistic and non-autistic groups. Further, such neural differences may lead to the later emergence of diagnostic-group grip differences in adolescence. The present study sought to examine this possibility, while also examining if grip strength could elucidate the neuro-motor sources of phenotypic heterogeneity commonly observed within autism. Methods: Using high resolution, multi-shell diffusion, and quantitative R1 relaxometry imaging, this study examined how variations in key sensorimotor-related white matter pathways of the proprioception input, lateral grasping, cortico-cerebellar, and corticospinal networks were associated with individual variations in grip strength in 68 autistic children and 70 non-autistic (neurotypical) children (6-11 years-old). Results: In both groups, results indicated that stronger grip strength was associated with higher proprioceptive input, lateral grasping, and corticospinal (but not cortico-cerebellar modification) fractional anisotropy and R1, indirect measures concordant with stronger microstructural coherence and increased myelination. Diagnostic group differences in these grip-brain relationships were not observed, but the autistic group exhibited more variability particularly in the cortico-cerebellar modification indices. An examination into the variability within the autistic group revealed that attention-deficit/hyperactivity disorder (ADHD) features moderated the relationships between grip strength and both fractional anisotropy and R1 relaxometry in the premotor-primary motor tract of the lateral grasping network and the cortico-cerebellar network tracts. Specifically, in autistic children with elevated ADHD features (60% of the autistic group) stronger grip strength was related to higher fractional anisotropy and R1 of the cerebellar modification network (stronger microstructural coherence and more myelin), whereas the opposite relationship was observed in autistic children with reduced ADHD features. Discussion: Together, this work suggests that while the foundational elements of grip strength are similar across school-aged autistic and non-autistic children, neural mechanisms of grip strength within autistic children may additionally depend on the presence of ADHD features. Specifically, stronger, more coherent connections of the cerebellar modification network, which is thought to play a role in refining and optimizing motor commands, may lead to stronger grip in children with more ADHD features, weaker grip in children with fewer ADHD features, and no difference in grip in non-autistic children. While future research is needed to understand if these findings extend to other motor tasks beyond grip strength, these results have implications for understanding the biological basis of neuromotor control in autistic children and emphasize the importance of assessing co-occurring conditions when evaluating brain-behavior relationships in autism.

Structural neuroimaging markers of normal pressure hydrocephalus versus Alzheimer's dementia and Parkinson's disease, and hydrocephalus versus atrophy in chronic TBI-a narrative review.

Introduction: Normal Pressure Hydrocephalus (NPH) is a prominent type of reversible dementia that may be treated with shunt surgery, and it is crucial to differentiate it from irreversible degeneration caused by its symptomatic mimics like Alzheimer's Dementia (AD) and Parkinson's Disease (PD). Similarly, it is important to distinguish between (normal pressure) hydrocephalus and irreversible atrophy/degeneration which are among the chronic effects of Traumatic Brain Injury (cTBI), as the former may be reversed through shunt placement. The purpose of this review is to elucidate the structural imaging markers which may be foundational to the development of accurate, noninvasive, and accessible solutions to this problem. Methods: By searching the PubMed database for keywords related to NPH, AD, PD, and cTBI, we reviewed studies that examined the (1) distinct neuroanatomical markers of degeneration in NPH versus AD and PD, and atrophy versus hydrocephalus in cTBI and (2) computational methods for their (semi-) automatic assessment on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans. Results: Structural markers of NPH and those that can distinguish it from AD have been well studied, but only a few studies have explored its structural distinction between PD. The structural implications of cTBI over time have been studied. But neuroanatomical markers that can predict shunt response in patients with either symptomatic idiopathic NPH or post-traumatic hydrocephalus have not been reliably established. MRI-based markers dominate this field of investigation as compared to CT, which is also reflected in the disproportionate number of MRI-based computational methods for their automatic assessment. Conclusion: Along with an up-to-date literature review on the structural neurodegeneration due to NPH versus AD/PD, and hydrocephalus versus atrophy in cTBI, this article sheds light on the potential of structural imaging markers as (differential) diagnostic aids for the timely recognition of patients with reversible (normal pressure) hydrocephalus, and opportunities to develop computational tools for their objective assessment.

Behavioral and dysexecutive variant of Alzheimer's disease: Insights from structural and molecular imaging studies.

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aß deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.

Robust thalamic nuclei segmentation from T1-weighted MRI using polynomial intensity transformation.

Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation. HIPS was incorporated into THalamus Optimized Multi-Atlas Segmentation (THOMAS) pipeline, a method developed and optimized for WMn MRI. HIPS-THOMAS was compared to a convolutional neural network (CNN)-based segmentation method and THOMAS modified for the use of T1w images (T1w-THOMAS). The robustness and accuracy of the three methods were tested across different image contrasts (MPRAGE, SPGR, and MP2RAGE), scanner manufacturers (PHILIPS, GE, and Siemens), and field strengths (3 T and 7 T). HIPS-transformed images improved intra-thalamic contrast and thalamic boundaries, and HIPS-THOMAS yielded significantly higher mean Dice coefficients and reduced volume errors compared to both the CNN method and T1w-THOMAS. Finally, all three methods were compared using the frequently travelling human phantom MRI dataset for inter- and intra-scanner variability, with HIPS displaying the least inter-scanner variability and performing comparably with T1w-THOMAS for intra-scanner variability. In conclusion, our findings highlight the efficacy and robustness of HIPS in enhancing thalamic nuclei segmentation from standard T1w MRI.

Structural brain morphometry differences and similarities between young patients with Crohn's disease in remission and healthy young and old controls.

Introduction: Crohn's disease (CD), one of the main phenotypes of inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. It can impact the function of gastrointestinal secretions, as well as increasing the intestinal permeability leading to an aberrant immunological response and subsequent intestinal inflammation. Studies have reported anatomical and functional brain changes in Crohn's Disease patients (CDs), possibly due to increased inflammatory markers and microglial cells that play key roles in communicating between the brain, gut, and systemic immune system. To date, no studies have demonstrated similarities between morphological brain changes seen in IBD and brain morphometry observed in older healthy controls.. Methods: For the present study, twelve young CDs in remission (M = 26.08 years, SD = 4.9 years, 7 male) were recruited from an IBD Clinic. Data from 12 young age-matched healthy controls (HCs) (24.5 years, SD = 3.6 years, 8 male) and 12 older HCs (59 years, SD = 8 years, 8 male), previously collected for a different study under a similar MR protocol, were analyzed as controls. T1 weighted images and structural image processing techniques were used to extract surface-based brain measures, to test our hypothesis that young CDs have different brain surface morphometry than their age-matched young HCs and furthermore, appear more similar to older HCs. The phonemic verbal fluency (VF) task (the Controlled Oral Word Association Test, COWAT) (Benton, 1976) was administered to test verbal cognitive ability and executive control. Results/Discussion: On the whole, CDs had more brain regions with differences in brain morphometry measures when compared to the young HCs as compared to the old HCs, suggesting that CD has an effect on the brain that makes it appear more similar to old HCs. Additionally, our study demonstrates this atypical brain morphometry is associated with function on a cognitive task. These results suggest that even younger CDs may be showing some evidence of structural brain changes that demonstrate increased resemblance to older HC brains rather than their similarly aged healthy counterparts.

Relationship between neuroimaging and emotion recognition in mild cognitive impairment patients.

OBJECTIVE: Dementia is a major public health problem with high needs for early detection, efficient treatment, and prognosis evaluation. Social cognition impairment could be an early dementia indicator and can be assessed with emotion recognition evaluation tests. The purpose of this study is to investigate the link between different brain imaging modalities and cognitive status in Mild Cognitive Impairment (MCI) patients, with the goal of uncovering potential physiopathological mechanisms based on social cognition performance. METHODS: The relationship between the Reading the Mind in the Eyes Test (RMET) and some clinical and biochemical variables ([18 F]FDG PET-CT and anatomical MR parameters, neuropsychological evaluation, and CSF biomarkers) was studied in 166 patients with MCI by using a correlational approach. RESULTS: The RMET correlated with neuropsychological variables, as well as with structural and functional brain parameters obtained from the MR and FDG-PET imaging evaluation. However, significant correlations between the RMET and CSF biomarkers were not found. DISCUSSION: Different neuroimaging parameters were found to be related to an emotion recognition task in MCI. This analysis identified potential minimally-invasive biomarkers providing some knowledge about the physiopathological mechanisms in MCI.

Brain volumetric changes in menopausal women and its association with cognitive function: a structured review.

The menopausal transition has been proposed to put women at risk for undesirable neurological symptoms, including cognitive decline. Previous studies suggest that alterations in the hormonal milieu modulate brain structures associated with cognitive function. This structured review provides an overview of the relevant studies that have utilized MRI to report volumetric differences in the brain following menopause, and its correlations with the evaluated cognitive functions. We performed an electronic literature search using Medline (Ovid) and Scopus to identify studies that assessed the influence of menopause on brain structure with MRI. Fourteen studies met the inclusion criteria. Brain volumetric differences have been reported most frequently in the frontal and temporal cortices as well as the hippocampus. These regions are important for higher cognitive tasks and memory. Additionally, the deficit in verbal and visuospatial memory in postmenopausal women has been associated with smaller regional brain volumes. Nevertheless, the limited number of eligible studies and cross-sectional study designs warrant further research to draw more robust conclusions.

A cross-comparative analysis of in vivo versus ex vivo MRI indices in a mouse model of concussion.

BACKGROUND: We present a cross-sectional, case-matched, and pair-wise comparison of structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) measures in vivo and ex vivo in a mouse model of concussion, thus aiming to establish the concordance of structural and diffusion imaging findings in living brain and after fixation. METHODS: We allocated 28 male mice aged 3-4 months to sham injury and concussion (CON) groups. CON mice had received a single concussive impact on day 0 and underwent MRI at day 2 (n = 9) or 7 (n = 10) post-impact, and sham control mice likewise underwent imaging at day 2 (n = 5) or 7 (n = 4). Immediately after the final scanning, we collected the perfusion-fixed brains, which were stored for imaging ex vivo 6-12 months later. We then compared the structural imaging, DTI, and NODDI results between different methods. RESULTS: In vivo to ex vivo structural and DTI/NODDI findings were in notably poor agreement regarding the effects of concussion on structural integrity of the brain. COMPARISON WITH EXISTING METHODS: ex vivo imaging was frequently done to study the effects of diseases and treatments, but our results showed that ex vivo and in vivo imaging can detect completely opposite and contradictory results. This is also the first study that compares in vivo and ex vivo NODDI. CONCLUSION: Our findings call for caution in extrapolating translational capabilities obtained ex vivo to physiological measurements in vivo. The divergent findings may reflect fixation artefacts and the contribution of the glymphatic system changes.

Life After Mild Traumatic Brain Injury: Widespread Structural Brain Changes Associated With Psychological Distress Revealed With Multimodal Magnetic Resonance Imaging.

Background: Traumatic brain injury (TBI) can alter brain structure and lead to onset of persistent neuropsychological symptoms. This study investigates the relationship between brain injury and psychological distress after mild TBI using multimodal magnetic resonance imaging. Methods: A total of 89 patients with mild TBI from the TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury) pilot study were included. Subscales of the Brief Symptoms Inventory 18 for depression, anxiety, and somatization were used as outcome measures of psychological distress approximately 6 months after the traumatic event. Glasgow Coma Scale scores were used to evaluate recovery. Magnetic resonance imaging data were acquired within 2 weeks after injury. Perivascular spaces (PVSs) were segmented using an enhanced PVS segmentation method, and the volume fraction was calculated for the whole brain and white matter regions. Cortical thickness and gray matter structures volumes were calculated in FreeSurfer; diffusion imaging indices and multifiber tracts were extracted using the Quantitative Imaging Toolkit. The analysis was performed considering age, sex, intracranial volume, educational attainment, and improvement level upon discharge as covariates. Results: PVS fractions in the posterior cingulate, fusiform, and postcentral areas were found to be associated with somatization symptoms. Depression, anxiety, and somatization symptoms were associated with the cortical thickness of the frontal-opercularis and occipital pole, putamen and amygdala volumes, and corticospinal tract and superior thalamic radiation. Analyses were also performed on the two hemispheres separately to explore lateralization. Conclusions: This study shows how PVS, cortical, and microstructural changes can predict the onset of depression, anxiety, and somatization symptoms in patients with mild TBI.

Investigations of the subarachnoid space as a potential link between aura and headache in migraine: A case-control MRI study.

BACKGROUND: The connection between migraine aura and headache is poorly understood. Some patients experience migraine aura without headache, and patients with migraine aura with headache commonly experience milder headaches with age. The distance between the cerebral cortex and the overlying dura mater has been hypothesized to influence development of headache following aura. We tested this hypothesis by comparing approximated distances between visual cortical areas and overlying dura mater between female patients with migraine aura without headache and female patients with migraine aura with headache. METHODS: Twelve cases with migraine aura without headache and 45 age-matched controls with migraine aura with headache underwent 3.0 T MRI. We calculated average distances between the occipital lobes, between the calcarine sulci, and between the skull and visual areas V1, V2 and V3a. We also measured volumes of corticospinal fluid between the occipital lobes, between the calcarine sulci, and overlying visual areas V2 and V3a. We investigated the relationship between headache status, distances and corticospinal fluid volumes using conditional logistic regression. RESULTS: Distances between the occipital lobes, calcarine sulci and between the skull and V1, V2 and V3a did not differ between patients with migraine aura with headache and patients with migraine aura without headache. We found no differences in corticospinal fluid volumes between groups. CONCLUSION: We found no indication for a connection between visual migraine aura and headache based on cortico-cortical, cortex-to-skull distances, or corticospinal fluid volumes overlying visual cortical areas. Longitudinal studies with imaging sequences optimized for measuring the cortico-dural distance and a larger sample of patients are needed to further investigate the hypothesis.

Longitudinal Gray Matter Development Associated With Psychotic Experiences in Young People.

Background: Gray matter abnormalities are observed across the psychosis spectrum. The trajectory of these abnormalities in healthy adolescents reporting subthreshold psychotic experiences (PEs) may provide insight into the neural mechanisms underlying psychotic symptoms. The risk of psychosis and additional psychopathology is even higher among these individuals who also report childhood adversity/DSM-5 diagnoses. Thus, the aims of this longitudinal study were to investigate PE-related volumetric changes in young people, noting any effects of childhood adversity/DSM-5 diagnosis. Methods: A total of 211 young people 11 to 13 years of age participated in the initial Adolescent Brain Development study. PE classification was determined by expert consensus at each time point. Participants underwent neuroimaging at 3 time points over 6 years. A total of 76 participants with at least one scan were included in the final sample; 34 who met criteria for PEs at least once across all the time points (PE group) and 42 control subjects. Data from 20 bilateral regions of interest were extracted for linear mixed-effects analyses. Results: Right hippocampal volume increased over time in the control group, with no increase in the PE group (p = .00352). DSM-5 diagnosis and childhood adversity were not significantly associated with right hippocampal volume. There was no significant effect of group or interaction in any other region. Conclusions: These findings further implicate right hippocampal volumetric abnormalities in the pathophysiology underlying PEs. Furthermore, as suggested by previous studies in those at clinical high risk for psychosis and those with first-episode psychosis, it is possible that these deficits may be a marker for later clinical outcomes.

The Use of Diffusion Kurtosis Imaging for the Differential Diagnosis of Alzheimer's Disease Spectrum.

Structural and diffusion kurtosis imaging (DKI) can be used to assess hippocampal macrostructural and microstructural alterations respectively, in Alzheimer's disease (AD) spectrum, spanning from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and AD. In this study, we explored the diagnostic performance of structural imaging and DKI of the hippocampus in the AD spectrum. Eleven SCD, thirty-seven MCI, sixteen AD, and nineteen age- and sex-matched normal controls (NCs) were included. Bilateral hippocampal volume, mean diffusivity (MD), and mean kurtosis (MK) were obtained. We detected that in AD vs. NCs, the right hippocampal volume showed the most prominent AUC value (AUC = 0.977); in MCI vs. NCs, the right hippocampal MD was the most sensitive discriminator (AUC = 0.819); in SCD vs. NCs, the left hippocampal MK was the most sensitive biomarker (AUC = 0.775). These findings suggest that, in the predementia stage (SCD and MCI), hippocampal microstructural changes are predominant, and the best discriminators are microstructural measurements (left hippocampal MK for SCD and right hippocampal MD for MCI); while in the dementia stage (AD), hippocampal macrostructural alterations are superior, and the best indicator is the macrostructural index (right hippocampal volume).

Three-photon excited fluorescence imaging in neuroscience: From principles to applications.

The development of three-photon microscopy (3PM) has greatly expanded the capability of imaging deep within biological tissues, enabling neuroscientists to visualize the structure and activity of neuronal populations with greater depth than two-photon imaging. In this review, we outline the history and physical principles of 3PM technology. We cover the current techniques for improving the performance of 3PM. Furthermore, we summarize the imaging applications of 3PM for various brain regions and species. Finally, we discuss the future of 3PM applications for neuroscience.

Impact of an optimized epilepsy surgery imaging protocol for focal epilepsy: A monocentric prospective study.

OBJECTIVE: To evaluate in a real clinical scenario the impact of the ILAE-recommended "Harmonized neuroimaging of epilepsy structural sequences"- HARNESS protocol in patients affected by focal epilepsy. METHODS: We prospectively enrolled focal epilepsy patients who underwent a structural brain MRI between 2020 and 2021 at Modena University Hospital. For all patients, MRIs were: (a) acquired according to the HARNESS-MRI protocol (H-MRI); (b) reviewed by the same neuroradiology team. MRI outcomes measures were: the number of positive (diagnostic) and negative MRI; the type of radiological diagnosis classified in: (1) Hippocampal Sclerosis; (2) Malformations of cortical development (MCD); (3) Vascular malformations; (4) Glial scars; (5) Low-grade epilepsy-associated tumors; (6) Dual pathology. For each patient we verified for previous MRI (without HARNESS protocol, noH-MRI) and the presence of clinical information in the MRI request form. Then the measured outcomes were reviewed and compared as appropriate. RESULTS: A total of 131 patients with H-MRI were included in the study. 100 patients out from this cohort had at least one previous noH-MRI scan. Of those, 92/100 were acquired at the same Hospital than H-MRI and 71/92 on a 3T scanner. The HARNESS protocol revealed 81 (62%) positive and 50 (38%) negative MRI, and MCD was the most common diagnosis (60%). Among the entire pool of 100 noH-MRI, 36 resulted positive with a significant difference (p < .001) compared to H-MRI. Similar findings were observed when accounting for the expert radiologists (H-MRI = 57 positive; noH-MRI = 33, p < .001) and the scanner field strength (H-MRI 43 = positive, noH-MRI = 23, p < .001), while clinical information were more present in H-MRI (p < .002). SIGNIFICANCE: The adoption of a standardized and optimized MRI acquisition protocol together with adequate clinical information contribute to identify a higher number of potentially epileptogenic lesions (especially FCD) thus impacting concretely on the clinical management of patients with focal epilepsy.

Enhanced brain parcellation via abnormality inpainting for neuroimage-based consciousness evaluation of hydrocephalus patients by lumbar drainage.

Brain network analysis based on structural and functional magnetic resonance imaging (MRI) is considered as an effective method for consciousness evaluation of hydrocephalus patients, which can also be applied to facilitate the ameliorative effect of lumbar cerebrospinal fluid drainage (LCFD). Automatic brain parcellation is a prerequisite for brain network construction. However, hydrocephalus images usually have large deformations and lesion erosions, which becomes challenging for ensuring effective brain parcellation works. In this paper, we develop a novel and robust method for segmenting brain regions of hydrocephalus images. Our main contribution is to design an innovative inpainting method that can amend the large deformations and lesion erosions in hydrocephalus images, and synthesize the normal brain version without injury. The synthesized images can effectively support brain parcellation tasks and lay the foundation for the subsequent brain network construction work. Specifically, the novelty of the inpainting method is that it can utilize the symmetric properties of the brain structure to ensure the quality of the synthesized results. Experiments show that the proposed brain abnormality inpainting method can effectively aid the brain network construction, and improve the CRS-R score estimation which represents the patient's consciousness states. Furthermore, the brain network analysis based on our enhanced brain parcellation method has demonstrated potential imaging biomarkers for better interpreting and understanding the recovery of consciousness in patients with secondary hydrocephalus.

Neurocognitive markers of passive suicidal ideation in late-life depression.

OBJECTIVES: (1) To delineate whether cognitive flexibility and inhibitory ability are neurocognitive markers of passive suicidal ideation (PSI), an early stage of suicide risk in depression and (2) to determine whether PSI is associated with volumetric differences in regions of the prefrontal cortex (PFC) in middle-aged and older adults with depression. DESIGN: Cross-sectional study. SETTING: University medical school. PARTICIPANTS: Forty community-dwelling middle-aged and older adults with depression from a larger study of depression and anxiety (NIMH R01 MH091342-05 PI: O'Hara). MEASUREMENTS: Psychiatric measures were assessed for the presence of a DSM-5 depressive disorder and PSI. A neurocognitive battery assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains. RESULTS: The PSI group (n = 18) performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks, compared to the group without PSI (n = 22). The group with PSI had larger left mid-frontal gyri (MFG) than the no-PSI group. There was no association between cognitive flexibility/inhibitory ability and left MFG volume. CONCLUSIONS: Findings implicate a neurocognitive signature of PSI: poorer cognitive flexibility and poor inhibitory ability not better accounted for by other domains of cognitive dysfunction and not associated with volumetric differences in the left MFG. This suggests that there are two specific but independent risk factors of PSI in middle- and older-aged adults.

Rapid anatomical imaging of the neonatal brain using T2 -prepared 3D balanced steady-state free precession.

PURPOSE: To develop a new approach to 3D gradient echo-based anatomical imaging of the neonatal brain with a substantially shorter scan time than standard 3D fast spin echo (FSE) methods, while maintaining a high SNR. METHODS: T2 -prepration was employed immediately prior to image acquisition of 3D balanced steady-state free precession (bSSFP) with a single trajectory of center-out k-space view ordering, which requires no magnetization recovery time between imaging segments during the scan. This approach was compared with 3D FSE, 2D single-shot FSE, and product 3D bSSFP imaging in numerical simulations, plus phantom and in vivo experiments. RESULTS: T2 -prepared 3D bSSFP generated image contrast of gray matter, white matter, and CSF very similar to that of reference T2 -weighted imaging methods, without major image artifacts. Scan time of T2 -prepared 3D bSSFP was remarkably shorter compared to 3D FSE, whereas SNR was comparable to that of 3D FSE and higher than that of 2D single-shot FSE. Specific absorption rate of T2 -prepared 3D bSSFP remained within the safety limit. Determining an optimal imaging flip angle of T2 -prepared 3D bSSFP was critical to minimizing blurring of images. CONCLUSION: T2 -prepared 3D bSSFP offers an alternative method for anatomical imaging of the neonatal brain with dramatically reduced scan time compared to standard 3D FSE and higher SNR than 2D single-shot FSE.

La depresión con ideas suicidas presenta disfunciones corticales prefrontales que favorecen significativamente el intento suicida / Depression with suicidal ideas presents prefrontal cortical dysfunctions that significantly favor suicidal intent

Se realiza una revisión de estudios de resonancia magnética integral y funcional, así como estudios bioquímicos en pacientes con y sin ideas suicidas. Estos estudios en pacientes con alto riesgo de suicidio presentan una disminución de volúmenes corticales en la corteza prefrontal dorso y ventrolateral. Lo importante de estos estudios es que resultan de la comparación con pacientes deprimidos con bajo riesgo de suicidio. Los estudios de resonancia magnética funcional mostraron una hipofuncionalidad del lóbulo prefrontal en los pacientes depresivos con ideas suicidas severas, que se observa como una disminución del flujo sanguíneo cerebral en las áreas lateral y ventral. Se observa una disminución del metabolismo de serotonina, en clara relación con la severidad de las ideas de muerte, también con un foco en la región lateroventral prefrontal. Dado que las funciones de la corteza prefrontal afirman al individuo en su perspectiva vital, disfunciones como las descritas debilitan la coordinación y organización del apego a la vida, quedando, por el contrario, la posibilidad de la búsqueda de la muerte. Se concluye que los pacientes depresivos con ideas suicidas tienen una alta vulnerabilidad para el intento de suicidio por la afectación de las zonas prefrontales.

A review of functional integral magnetic resonance and biochemical data from patients with and without suicidal ideation is presented. Patients with high suicidal risk show a decrease in cortical volume in ventrolateral and dorsal prefrontal cortex. These studies are compared to those of depressed patients with low suicidal risk. Functional magnetic resonance in depressed patients with severe suicidal ideation show an hypo functional prefrontal lobe, seen as a decrease in blood flow in lateral and ventral areas. There is a decrease in serotonin metabolism, clearly related to the severity of suicidal ideation, also in ventrolateral prefrontal cortex. As prefrontal cortex functions enhance vital perspectives, such dysfunctions weaken coordination and organization of attachment to life, making search for death a possibility. Authors conclude that depressed patients with suicidal ideation have a high vulnerability for suicidal intent due to changes in prefrontal areas.

Global and Regional Structural Differences and Prediction of Autistic Traits during Adolescence.

BACKGROUND: Autistic traits are commonly viewed as dimensional in nature, and as continuously distributed in the general population. In this respect, the identification of predictive values of markers such as subtle autism-related alterations in brain morphology for parameter values of autistic traits could increase our understanding of this dimensional occasion. However, currently, very little is known about how these traits correspond to alterations in brain morphology in typically developing individuals, particularly during a time period where changes due to brain development processes do not provide a bias. Therefore, in the present study, we analyzed brain volume, cortical thickness (CT) and surface area (SA) in a cohort of 14-15-year-old adolescents (N = 285, female: N = 162) and tested their predictive value for autistic traits, assessed with the social responsiveness scale (SRS) two years later at the age of 16-17 years, using a regression-based approach. We found that autistic traits were significantly predicted by volumetric changes in the amygdala (r = 0.181), cerebellum (r = 0.128) and hippocampus (r = -0.181, r = -0.203), both in boys and girls. Moreover, the CT of the superior frontal region was negatively correlated (r = -0.144) with SRS scores. Furthermore, we observed a significant association between the SRS total score and smaller left putamen volume, specifically in boys (r = -0.217), but not in girls. Our findings suggest that neural correlates of autistic traits also seem to lie on a continuum in the general population, are determined by limbic-striatal neuroanatomical brain areas, and are partly dependent on sex. As we imaged adolescents from a large population-based cohort within a small age range, these data may help to increase the understanding of autistic-like occasions in otherwise typically developing individuals.