UNASSIGNED: An existing model suggests that some brain features of relatives of people affected by psychosis can be distinguished from both the probands and a control group.  Such findings can be interpreted as representing a compensating mechanism.
UNASSIGNED: We studied white matter features using diffusion tensor imaging in a cohort of 82 people affected by psychosis, 122 of their first-degree relatives, and 89 control subjects that were scanned between two to three times with an interval of approximately 3 years between consecutive scans. We measured both fractional anisotropy and other standard diffusivity measures such as axial diffusivity. Additionally, we calculated standard connectivity measures such as path length based on probabilistic or deterministic tractography. Finally, by averaging the values of the different measures over the two or three consecutive scans, we studied epoch-averagely the difference between these three groups.
UNASSIGNED: For several tracts and several connectivity measures, the relatives showed distinct features from both the probands and the control groups. In those cases, the relatives did not necessarily score between the probands and the control group. An aggregate analysis in the form of a group-dependent score for the different modes of the analysis (e.g., for fractional anisotropy) supported this observation.
UNASSIGNED: We interpret these results as evidence supporting a compensation mechanism in the brain of relatives that may be related to resilience that some of them exhibit in the face of the genetic risk they have for being affected by psychosis.

Objective biomarkers have been a critical challenge for the field of psychiatry, where diagnostic, prognostic, and theranostic assessments are still based on subjective narratives. Psychopathology operates with idiographic knowledge and subjective evaluations incorporated into clinical assessment inventories, but is considered to be a medical discipline and, as such, uses medical intervention methods (e.g., pharmacological, ECT; rTMS; tDCS) and, therefore, is supposed to operate with the language and methods of nomothetic networks. The idiographic assessments are provisionally \"quantified\" into \"structured clinical scales\" to in some way resemble nomothetic measures. Instead of fostering data merging and integration, this approach further encapsulates the clinical psychiatric methods, as all other biological tests (molecular, neuroimaging) are performed separately, only after the clinical assessment has provided diagnosis. Translational cross-validation of clinical assessment instruments and fMRI is an attempt to address the gap. The aim of this approach is to investigate whether there exist common and specific neural circuits, which underpin differential item responses to clinical self-rating scales during fMRI sessions in patients suffering from the two main spectra of mental disorders: schizophrenia and major depression. The current status of this research program and future implications to promote the development of psychiatry as a medical discipline are discussed.

Dispersal is a complex series of movements before an individual establishes a home range. Animals must travel and forage in unfamiliar landscapes that include anthropogenic risks such as road crossings, harvest, and urban landscapes. We compare dispersal behavior of juvenile mountain lions (Puma concolor) from two geographically distinct populations in California and Nevada, USA. These two sites are ecologically similar but have different management practices; hunting is permitted in Nevada, whereas mountain lions are protected in California. We used GPS-collar data and net-squared displacement analysis to identify three dispersal states: exploratory, departure, and transient home range. We then compared each dispersal state of the two mountain lion populations using an integrated step selection analysis (iSSA). The model included explanatory variables hypothesized to influence one or more dispersal states, including distance to forest, shrub, water, hay and crop, developed lands, and four-wheel drive roads, as well as elevation and terrain ruggedness. Results revealed consistent habitat selection between sites across most landscape variables, with one notable exception: anthropogenic covariates, including distance to developed land, distance to hay and crop, and distance to four-wheeled drive roads, were only statistically significant on modeled habitat selection during dispersal in the population subject to hunting (i.e., Nevada). Results suggest that hunting (pursuit with hounds resulting in harvest) and non-lethal pursuit (pursuit with hounds but no harvest allowed) increase avoidance of anthropogenic landscapes during dispersal for juvenile mountain lions. By comparing populations, we provided valuable insights into the role of management in shaping dispersal behavior.

Major depressive disorder (MDD) is prevalent with a high subjective and socio-economic burden. Despite the effectiveness of classical treatment methods, 20-30% of patients stay treatment-resistant. Deep Brain Stimulation of the superolateral branch of the medial forebrain bundle is emerging as a clinical treatment. The stimulation region (ventral tegmental area, VTA), supported by experimental data, points to the role of dopaminergic (DA) transmission in disease pathology. This work sets out to develop a workflow that will allow the performance of analyses on midbrain DA-ergic neurons and projections in subjects who have committed suicide. Human midbrains were retrieved during autopsy, formalin-fixed, and scanned in a Bruker MRI scanner (7T). Sections were sliced, stained for tyrosine hydroxylase (TH), digitized, and integrated into the Montreal Neurological Institute (MNI) brain space together with a high-resolution fiber tract atlas. Subnuclei of the VTA region were identified. TH-positive neurons and fibers were semi-quantitatively evaluated. The study established a rigorous protocol allowing for parallel histological assessments and fiber tractographic analysis in a common space. Semi-quantitative readings are feasible and allow the detection of cell loss in VTA subnuclei. This work describes the intricate workflow and first results of an investigation of DA anatomy in VTA subnuclei in a growing naturalistic database.

Cross-species research has advanced human understanding of brain regions, with cross-species comparisons using magnetic resonance imaging technology becoming increasingly common. Currently, cross-species research on human language regions has primarily focused on traditional brain areas such as the Broca region. While some studies have indicated that human language function also involves other language regions, the corresponding relationships between these brain regions in humans and macaques remain unclear. This study calculated the strength of the connections between the high-level language processing regions in human and macaque brains, identified homologous target areas based on the structural connections of white-matter fiber bundles, and compared the connectivity profiles of both species. The results of the experiment demonstrated that macaques possess brain regions which exhibit connectivity patterns resembling those found in human high-level language processing regions. This discovery suggests that while the function of a human brain region is specialized, it still maintains a structural connectivity similar to that seen in macaques.

UNASSIGNED: Complex neuronal interactions underlie cortical information processing that can be compromised in altered states of consciousness. Here intracortical microstimulation was applied to investigate anesthetic state-dependent effective connectivity of neurons in rat visual cortex in vivo.
UNASSIGNED: Extracellular activity was recorded at 32 sites in layers 5/6 while stimulating with charge-balanced discrete pulses at each electrode in random order. The same stimulation pattern was applied at three levels of anesthesia with desflurane and in wakefulness. Spikes were sorted and classified by their waveform features as putative excitatory and inhibitory neurons. Network motifs were identified in graphs of effective connectivity constructed from monosynaptic cross-correlograms.
UNASSIGNED: Microstimulation caused early (<10 ms) increase followed by prolonged (11-100 ms) decrease in spiking of all neurons throughout the electrode array. The early response of excitatory but not inhibitory neurons decayed rapidly with distance from the stimulation site over 1 mm. Effective connectivity of neurons with significant stimulus response was dense in wakefulness and sparse under anesthesia. The number of network motifs, especially those of higher order, increased rapidly as the anesthesia was withdrawn indicating a substantial increase in network connectivity as the animals woke up.
UNASSIGNED: The results illuminate the impact of anesthesia on functional integrity of local cortical circuits affecting the state of consciousness.

UNASSIGNED: Multiple studies point to the role of neuroinflammation in the pathophysiology of schizophrenia (SCZ), however, there have been few in vivo tools for imaging brain inflammation. Diffusion basis spectrum imaging (DBSI) is an advanced diffusion-based MRI method developed to quantitatively assess microstructural alternations relating to neuroinflammation, axonal fiber, and other white matter (WM) pathologies.
UNASSIGNED: We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n = 27), schizophrenia (SCZ, n = 21), and bipolar disorder (BPD, n = 21) participants aged 18-30. We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain WM analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between groups. Clinical relationships of DBSI metrics with clinical symptoms were assessed across SCZ and control participants.
UNASSIGNED: In SCZ participants, we found a generalized increase in DBSI-derived cellularity (a putative marker of neuroinflammation), a decrease in restricted fiber fraction (a putative marker of apparent axonal density), and an increase in extra-axonal water (a putative marker of vasogenic edema) across several WM tracts. There were only minimal WM abnormalities noted in BPD, mainly in regions of the corpus callosum (increase in DTI-derived RD and extra-axonal water). DBSI metrics showed significant partial correlations with psychosis and mood symptoms across groups.
UNASSIGNED: Our findings suggest that SCZ involves generalized white matter neuroinflammation, decreased fiber density, and demyelination, which is not seen in bipolar disorder. Larger studies are needed to identify medication-related effects. DBSI metrics could help identify high-risk groups requiring early interventions to prevent the onset of psychosis and improve outcomes.

Presurgical planning prior to brain tumor resection is critical for the preservation of neurologic function post-operatively. Neurosurgeons increasingly use advanced brain mapping techniques pre- and intra-operatively to delineate brain regions which are \"eloquent\" and should be spared during resection. Functional MRI (fMRI) has emerged as a commonly used non-invasive modality for individual patient mapping of critical cortical regions such as motor, language, and visual cortices. To map motor function, patients are scanned using fMRI while they perform various motor tasks to identify brain networks critical for motor performance, but it may be difficult for some patients to perform tasks in the scanner due to pre-existing deficits. Connectome fingerprinting (CF) is a machine-learning approach that learns associations between resting-state functional networks of a brain region and the activations in the region for specific tasks; once a CF model is constructed, individualized predictions of task activation can be generated from resting-state data. Here we utilized CF to train models on high-quality data from 208 subjects in the Human Connectome Project (HCP) and used this to predict task activations in our cohort of healthy control subjects (n = 15) and presurgical patients (n = 16) using resting-state fMRI (rs-fMRI) data. The prediction quality was validated with task fMRI data in the healthy controls and patients. We found that the task predictions for motor areas are on par with actual task activations in most healthy subjects (model accuracy around 90%-100% of task stability) and some patients suggesting the CF models can be reliably substituted where task data is either not possible to collect or hard for subjects to perform. We were also able to make robust predictions in cases in which there were no task-related activations elicited. The findings demonstrate the utility of the CF approach for predicting activations in out-of-sample subjects, across sites and scanners, and in patient populations. This work supports the feasibility of the application of CF models to presurgical planning, while also revealing challenges to be addressed in future developments. PRACTITIONER POINTS: Precision motor network prediction using connectome fingerprinting. Carefully trained models\' performance limited by stability of task-fMRI data. Successful cross-scanner predictions and motor network mapping in patients with tumor.

Functional magnetic resonance imaging (fMRI) studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here, we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.

Alzheimer\'s disease may be conceptualized as a \'disconnection syndrome\', characterized by the breakdown of neural connectivity within the brain as a result of amyloid-beta plaques, tau neurofibrillary tangles and other factors leading to progressive degeneration and shrinkage of neurons, along with synaptic dysfunction. It has been suggested that misfolded tau proteins spread through functional connections (known as \'prion-like\' properties of tau). However, the local effect of tau spreading on the synaptic function and communication between regions is not well understood. I aimed to investigate how the spreading of tau aggregates through connections can locally influence functional connectivity. In total, the imaging data of 211 participants including 117 amyloid-beta-negative non-demented and 94 amyloid-beta-positive non-demented participants were recruited from the Alzheimer\'s Disease Neuroimaging Initiative. Furthermore, normative resting-state functional MRI connectomes were used to model tau spreading through functional connections, and functional MRI of the included participants was used to determine the effect of tau spreading on functional connectivity. I found that lower functional connectivity to tau epicentres is associated with tau spreading through functional connections in both amyloid-beta-negative and amyloid-beta-positive participants. Also, amyloid-beta-PET in tau epicentres mediated the association of tau spreading and functional connectivity to epicentres suggesting a partial mediating effect of amyloid-beta deposition in tau epicentres on the local effect of tau spreading on functional connectivity. My findings provide strong support for the notion that tau spreading through connection is locally associated with disrupted functional connectivity between tau epicentre and non-epicentre regions independent of amyloid-beta pathology. Also, I defined several groups based on the relationship between tau spreading and functional disconnection, which provides quantitative assessment to investigate susceptibility or resilience to functional disconnection related to tau spreading. I showed that amyloid-beta, other copathologies and the apolipoprotein E epsilon 4 allele can be a leading factor towards vulnerability to tau relative functional disconnection.