Midline Regions Research Articles

Model selection to achieve reproducible associations between resting state EEG features and autism

A concern in the field of autism electroencephalography (EEG) biomarker discovery is their lack of reproducibility. In the present study, we considered the problem of learning reproducible associations between multiple features of resting state (RS) neural activity and autism, using EEG data collected during a RS paradigm from 36 to 96 month-old children diagnosed with autism (N = 224) and neurotypical children (N = 69). Specifically, EEG spectral power and functional connectivity features were used as inputs to a regularized generalized linear model trained to predict diagnostic group (autism versus neurotypical). To evaluate our model, we proposed a procedure that quantified both the predictive generalization and reproducibility of learned associations produced by the model. When prioritizing both model predictive performance and reproducibility of associations, a highly reproducible profile of associations emerged. This profile revealed a distinct pattern of increased gamma power and connectivity in occipital and posterior midline regions associated with an autism diagnosis. Conversely, model selection based on predictive performance alone resulted in non-robust associations. Finally, we built a custom machine learning model that further empirically improved robustness of learned associations. Our results highlight the need for model selection criteria that maximize the scientific utility provided by reproducibility instead of predictive performance.

Ventral Striatum is Preferentially Correlated with the Salience Network Including Regions in Dorsolateral Prefrontal Cortex.

The ventral striatum (VS) receives input from the cerebral cortex and is modulated by midbrain dopaminergic projections in support of processing reward and motivation. Here we explored the organization of cortical regions linked to the human VS using within-individual functional connectivity MRI in intensively scanned participants. In two initial participants (scanned 31 sessions each), seed regions in the VS were preferentially correlated with distributed cortical regions that are part of the Salience (SAL) network. The VS seed region recapitulated SAL network topography in each individual including anterior and posterior midline regions, anterior insula, and dorsolateral prefrontal cortex (DLPFC) - a topography that was distinct from a nearby striatal seed region. The region of DLPFC linked to the VS is positioned adjacent to regions associated with domain-flexible cognitive control. The full pattern was replicated in independent data from the same two individuals and generalized to 15 novel participants (scanned 8 or more sessions each). These results suggest that the VS forms a cortico-basal ganglia loop as part of the SAL network. The DLPFC is a neuromodulatory target to treat major depressive disorder. The present results raise the possibility that the DLPFC may be an effective neuromodulatory target because of its preferential coupling to the VS and suggests a path toward further personalization.

Characteristics of lymphoedema, in particular midline lymphoedema, after treatment for prostate cancer: a retrospective study

BackgroundPatients undergoing treatment for prostate cancer may develop lymphoedema of the midline region. This has a substantial impact on a patient’s quality of life and its diagnosis is often delayed or missed. Therefore, the purpose of this study is to compare the characteristics of patients with leg and midline lymphoedema to patients with only leg lymphoedema.MethodsWe retrospectively collected patient-, cancer-, lymphoedema- and lymphoedema treatment-related data of 109 men with lymphoedema after treatment for prostate cancer. First, 42 characteristics were compared between both groups. Second, factors predicting presence of midline lymphoedema were explored by multivariable analyses.ResultsThe mean age of the patients with lymphoedema was 68 ( ±7) years and mean BMI is 28 (±4) kg/m2. Median duration of lymphoedema before the first consultation was 27 (9;55) months. Based on univariable analyses, patients with leg and midline lymphoedema had more frequently upper leg lymphoedema (89% (31/35) vs. 69% (51/74), p = 0.026), skin fibrosis (34% (12/35) vs. 16% (12/74), p = 0.034) and lymphatic reconstructive surgery (9% (3/35) vs. 0% (0/71), p = 0.020) than patients with only leg lymphoedema. Additionally, patients with leg and midline lymphoedema reported less frequently lower leg lymphoedema (77% (27/35) vs. 95% (70/74), p = 0.007). Based on the multivariable analysis, not having lower leg lymphoedema, skin fibrosis, performing self-bandaging and self-manual lymphatic drainage appear to be predictors for having midline lymphoedema.ConclusionsIf patients with lymphoedema after prostate cancer do not have lower leg lymphoedema, have skin fibrosis, perform self-bandaging or self-manual lymphatic drainage, they possibly have midline lymphoedema.

The ion channel Anoctamin 10/TMEM16K coordinates organ morphogenesis across scales in the urochordate notochord.

During embryonic development, tissues and organs are gradually shaped into their functional morphologies through a series of spatiotemporally tightly orchestrated cell behaviors. A highly conserved organ shape across metazoans is the epithelial tube. Tube morphogenesis is a complex multistep process of carefully choreographed cell behaviors such as convergent extension, cell elongation, and lumen formation. The identity of the signaling molecules that coordinate these intricate morphogenetic steps remains elusive. The notochord is an essential tubular organ present in the embryonic midline region of all members of the chordate phylum. Here, using genome editing, pharmacology and quantitative imaging in the early chordate Ciona intestinalis we show that Ano10/Tmem16k, a member of the evolutionarily ancient family of transmembrane proteins called Anoctamin/TMEM16 is essential for convergent extension, lumen expansion, and connection during notochord morphogenesis. We find that Ano10/Tmem16k works in concert with the plasma membrane (PM) localized Na+/Ca2+ exchanger (NCX) and the endoplasmic reticulum (ER) residing SERCA, RyR, and IP3R proteins to establish developmental stage specific Ca2+ signaling molecular modules that regulate notochord morphogenesis and Ca2+ dynamics. In addition, we find that the highly conserved Ca2+ sensors calmodulin (CaM) and Ca2+/calmodulin-dependent protein kinase (CaMK) show an Ano10/Tmem16k-dependent subcellular localization. Their pharmacological inhibition leads to convergent extension, tubulogenesis defects, and deranged Ca2+ dynamics, suggesting that Ano10/Tmem16k is involved in both the "encoding" and "decoding" of developmental Ca2+ signals. Furthermore, Ano10/Tmem16k mediates cytoskeletal reorganization during notochord morphogenesis, likely by altering the localization of 2 important cytoskeletal regulators, the small GTPase Ras homolog family member A (RhoA) and the actin binding protein Cofilin. Finally, we use electrophysiological recordings and a scramblase assay in tissue culture to demonstrate that Ano10/Tmem16k likely acts as an ion channel but not as a phospholipid scramblase. Our results establish Ano10/Tmem16k as a novel player in the prevertebrate molecular toolkit that controls organ morphogenesis across scales.

Unveiling a novel memory center in human brain: neurochemical identification of the nucleus incertus, a key pontine locus implicated in stress and neuropathology

BackgroundThe nucleus incertus (NI) was originally described by Streeter in 1903, as a midline region in the floor of the fourth ventricle of the human brain with an ‘unknown’ function. More than a century later, the neuroanatomy of the NI has been described in lower vertebrates, but not in humans. Therefore, we examined the neurochemical anatomy of the human NI using markers, including the neuropeptide, relaxin-3 (RLN3), and began to explore the distribution of the NI-related RLN3 innervation of the hippocampus.MethodsHistochemical staining of serial, coronal sections of control human postmortem pons was conducted to reveal the presence of the NI by detection of immunoreactivity (IR) for the neuronal markers, microtubule-associated protein-2 (MAP2), glutamic acid dehydrogenase (GAD)-65/67 and corticotrophin-releasing hormone receptor 1 (CRHR1), and RLN3, which is highly expressed in NI neurons in diverse species. RLN3 and vesicular GABA transporter 1 (vGAT1) mRNA were detected by fluorescent in situ hybridization. Pons sections containing the NI from an AD case were immunostained for phosphorylated-tau, to explore potential relevance to neurodegenerative diseases. Lastly, sections of the human hippocampus were stained to detect RLN3-IR and somatostatin (SST)-IR.ResultsIn the dorsal, anterior-medial region of the human pons, neurons containing RLN3- and MAP2-IR, and RLN3/vGAT1 mRNA-positive neurons were observed in an anatomical pattern consistent with that of the NI in other species. GAD65/67- and CRHR1-immunopositive neurons were also detected within this area. Furthermore, RLN3- and AT8-IR were co-localized within NI neurons of an AD subject. Lastly, RLN3-IR was detected in neurons within the CA1, CA2, CA3 and DG areas of the hippocampus, in the absence of RLN3 mRNA. In the DG, RLN3- and SST-IR were co-localized in a small population of neurons.ConclusionsAspects of the anatomy of the human NI are shared across species, including a population of stress-responsive, RLN3-expressing neurons and a RLN3 innervation of the hippocampus. Accumulation of phosphorylated-tau in the NI suggests its possible involvement in AD pathology. Further characterization of the neurochemistry of the human NI will increase our understanding of its functional role in health and disease.Graphical

Neurophysiological Oscillatory Mechanisms Underlying the Effect of Mirror Visual Feedback-Induced Illusion of Hand Movements on Nociception and Cortical Activation.

Mirror Visual Feedback (MVF)-induced illusion of hand movements produces beneficial effects in patients with chronic pain. However, neurophysiological mechanisms underlying these effects are poorly known. In this preliminary study, we test the novel hypothesis that such an MVF-induced movement illusion may exert its effects by changing the activity in midline cortical areas associated with pain processing. Electrical stimuli with individually fixed intensity were applied to the left hand of healthy adults to produce painful and non-painful sensations during unilateral right-hand movements with such an MVF illusion and right and bilateral hand movements without MVF. During these events, electroencephalographic (EEG) activity was recorded from 64 scalp electrodes. Event-related desynchronization (ERD) of EEG alpha rhythms (8-12 Hz) indexed the neurophysiological oscillatory mechanisms inducing cortical activation. Compared to the painful sensations, the non-painful sensations were specifically characterized by (1) lower alpha ERD estimated in the cortical midline, angular gyrus, and lateral parietal regions during the experimental condition with MVF and (2) higher alpha ERD estimated in the lateral prefrontal and parietal regions during the control conditions without MVF. These preliminary results suggest that the MVF-induced movement illusion may affect nociception and neurophysiological oscillatory mechanisms, reducing the activation in cortical limbic and default mode regions.

Integrating brain function and structure in the study of the human attentional networks: a functionnectome study

Attention is a heterogeneous function theoretically divided into different systems. While functional magnetic resonance imaging (fMRI) has extensively characterized their functioning, the role of white matter in cognitive function has gained recent interest due to diffusion-weighted imaging advancements. However, most evidence relies on correlations between white matter properties and behavioral or cognitive measures. This study used a new method that combines the signal from distant voxels of fMRI images using the probability of structural connection given by high-resolution normative tractography. We analyzed three fMRI datasets with a visual perceptual task and three attentional manipulations: phasic alerting, spatial orienting, and executive attention. The phasic alerting network engaged temporal areas and their communication with frontal and parietal regions, with left hemisphere dominance. The orienting network involved bilateral fronto-parietal and midline regions communicating by association tracts and interhemispheric fibers. The executive attention network engaged a broad set of brain regions and white matter tracts connecting them, with a particular involvement of frontal areas and their connections with the rest of the brain. These results partially confirm and extend previous knowledge on the neural substrates of the attentional system, offering a more comprehensive understanding through the integration of structure and function.

Reliability, concurrent validity, and clinical feasibility of measurement methods determining volume in patients with lower limb lymphedema and healthy controls

Purpose To investigate reliability, concurrent validity, and clinical feasibility of measurements assessing volume in patients with lower limb lymphedema (LLL) and healthy controls. Materials and methods To investigate intra- and interrater reliability, 47 patients with LLL and 30 healthy controls were assessed three times by two assessors. To investigate between session reliability, 50 participants were reassessed two weeks later. Each assessment included measurements of the midline region (hip circumference; suprapubic volume), leg volume (perimeter every 4 cm; Perometer®), and foot volume (water displacement; figure-of-eight method). Concurrent validity was assessed with correlation coefficients. Measurements were timed and practical limitations were reviewed. Clinical trial registration number: NCT: 05269264. Results Measurements of the total volume of different regions showed weak to very high intraclass correlation coefficients (ICCs) (0.131–998). Absolute and relative volume differences had lower ICC values (0.360–0.976). A strong correlation was found between the total volumes of the same region. The Perometer® and figure-of-eight method were the fastest method for leg and foot volume, respectively. Conclusions The assessed total volumes might be more valuable in assessing the evolution of volume in bilateral LLL than the calculated absolute and relative differences between both limbs. The Perometer® and figure-of-eight method were the most time efficient for leg and foot volume, respectively. Implications for rehabilitation Lymphedema is a chronic condition for which a reliable and clinically feasible assessment of volume is essential for the diagnosis, treatment decisions, and the evaluation of the treatment. This study shows that the total leg/foot volumes were more reliable than the calculated absolute and relative differences between both limbs and could therefore more valuable to evaluate bilateral lower limb lymphedema. For the assessment of leg volume, the Perometer® was the most reliable and fastest method. For the evaluation of the foot volume, the figure-of-eight method was overall the best method.

Updating predictions in a complex repertoire of actions and its neural representation

Even though actions we observe in everyday life seem to unfold in a continuous manner, they are automatically divided into meaningful chunks, that are single actions or segments, which provide information for the formation and updating of internal predictive models. Specifically, boundaries between actions constitute a hub for predictive processing since the prediction of the current action comes to an end and calls for updating of predictions for the next action. In the current study, we investigated neural processes which characterize such boundaries using a repertoire of complex action sequences with a predefined probabilistic structure. Action sequences consisted of actions that started with the hand touching an object (T) and ended with the hand releasing the object (U). These action boundaries were determined using an automatic computer vision algorithm. Participants trained all action sequences by imitating demo videos. Subsequently, they returned for an fMRI session during which the original action sequences were presented in addition to slightly modified versions thereof. Participants completed a post-fMRI memory test to assess the retention of original action sequences. The exchange of individual actions, and thus a violation of action prediction, resulted in increased activation of the action observation network and the anterior insula. At U events, marking the end of an action, increased brain activation in supplementary motor area, striatum, and lingual gyrus was indicative of the retrieval of the previously encoded action repertoire. As expected, brain activation at U events also reflected the predefined probabilistic branching structure of the action repertoire. At T events, marking the beginning of the next action, midline and hippocampal regions were recruited, reflecting the selected prediction of the unfolding action segment. In conclusion, our findings contribute to a better understanding of the various cerebral processes characterizing prediction during the observation of complex action repertoires.

EEG markers of successful allocentric spatial working memory maintenance in humans.

Several brain regions in the frontal, occipital and medial temporal lobes are known to contribute to spatial information processing. In contrast, the oscillatory patterns contributing to allocentric spatial working memory maintenance are poorly understood, especially in humans. Here, we tested twenty-three 21- to 32-year-old and twenty-two 64- to 76-year-old healthy right-handed adults in a real-world, spatial working memory task and recorded electroencephalographic (EEG) activity during the maintenance period. We established criteria for designating recall trials as perfect (no errors) or failed (errors and random search) and identified 8 young and 13 older adults who had at least 1 perfect and 1 failed trial amongst 10 recall trials. Individual alpha frequency-based analyses were used to identify oscillatory patterns during the maintenance period of perfect and failed trials. Spectral scalp topographies showed that individual theta frequency band relative power was stronger in perfect than in failed trials in the frontal midline and posterior regions. Similarly, gamma band (30-40 Hz) relative power was stronger in perfect than in failed trials over the right motor cortex. Exact low-resolution brain electromagnetic tomography in the frequency domain identified greater theta power in perfect than in failed trials in the secondary visual area (BA19) and greater gamma power in perfect than in failed trials in the right supplementary motor area. The findings of this exploratory study suggest that theta oscillations in the occipital lobe and gamma oscillations in the secondary motor cortex (BA6) play a particular role in successful allocentric spatial working memory maintenance.

Neural Tracking of Perceived Parent, but Not Peer, Norms Is Associated with Longitudinal Changes in Adolescent Attitudes about Externalizing Behaviors.

Adolescents' perceptions of parent and peer norms about externalizing behaviors influence the extent to which they adopt similar attitudes, yet little is known about how the trajectories of perceived parent and peer norms are related to trajectories of personal attitudes across adolescence. Neural development of midline regions implicated in self-other processing may underlie developmental changes in parent and peer influence. Here, we examined whether neural processing of perceived parent and peer norms in midline regions during self-evaluations would be associated with trajectories of personal attitudes about externalizing behaviors. Trajectories of adolescents' perceived parent and peer norms were examined longitudinally with functional neuroimaging (n = 165; ages 11-16 years across three waves; 86 girls, 79 boys; 29.7% White, 21.8% Black, 35.8% Latinx, 12.7% other/multiracial). Behavioral results showed perceived parent norms were less permissive than adolescents' own attitudes about externalizing behaviors, whereas perceived peer norms were more permissive than adolescents' own attitudes, effects that increased from early to middle adolescence. Although younger adolescents reported less permissive attitudes when they spontaneously tracked perceived parent norms in the ventromedial and medial pFCs during self-evaluations, this effect weakened as they aged. No brain-behavior effects were found when tracking perceived peer norms. These findings elucidate how perceived parent and peer norms change in parallel with personal attitudes about externalizing behaviors from early to middle adolescence and underscore the importance of spontaneous neural tracking of perceived parent norms during self-evaluations for buffering permissive personal attitudes, particularly in early adolescence.

A machine-learning approach for differentiating borderline personality disorder from community participants with brain-wide functional connectivity

BackgroundFunctional connectivity has garnered interest as a potential biomarker of psychiatric disorders including borderline personality disorder (BPD). However, small sample sizes and lack of within-study replications have led to divergent findings with no clear spatial foci. AimsEvaluate discriminative performance and generalizability of functional connectivity markers for BPD. MethodWhole-brain fMRI resting state functional connectivity in matched subsamples of 116 BPD and 72 control individuals defined by three grouping strategies. We predicted BPD status using classifiers with repeated cross-validation based on multiscale functional connectivity within and between regions of interest (ROIs) covering the whole brain—global ROI-based network, seed-based ROI-connectivity, functional consistency, and voxel-to-voxel connectivity—and evaluated the generalizability of the classification in the left-out portion of non-matched data. ResultsFull-brain connectivity allowed classification (∼70 %) of BPD patients vs. controls in matched inner cross-validation. The classification remained significant when applied to unmatched out-of-sample data (∼61–70 %). Highest seed-based accuracies were in a similar range to global accuracies (∼70–75 %), but spatially more specific. The most discriminative seed regions included midline, temporal and somatomotor regions. Univariate connectivity values were not predictive of BPD after multiple comparison corrections, but weak local effects coincided with the most discriminative seed-ROIs. Highest accuracies were achieved with a full clinical interview while self-report results remained at chance level. LimitationsThe accuracies vary considerably between random sub-samples of the population, global signal and covariates limiting the practical applicability. ConclusionsSpatially distributed functional connectivity patterns are moderately predictive of BPD despite heterogeneity of the patient population.

The neuroanatomical correlates of daily habitual tendencies and mediating effect on the association between daily habitual tendencies and symptoms of behavioral addictions

Habitual behaviors significantly shape our daily actions. Furthermore, habit formation is proposed as a key mechanism contributing to the development and maintenance of addiction. However, the neural substrates underlying daily habitual tendencies and their contribution to behavioral addiction symptoms in everyday life remain poorly understood. To explore these questions, we conducted a comprehensive analysis of data from 219 individuals who underwent neuroimaging (structural MRI) assessments alongside evaluations of their daily habitual tendencies and symptoms of Internet Gaming Disorder (IGD) and Problematic Smartphone Use (PSU). Using voxel-based morphometry, meta-analytic decoding, and mediation analysis, we found that daily habitual tendencies were positively correlated with larger gray matter volumes in the ventromedial prefrontal cortex (vmPFC), precuneus, superior frontal gyrus (SFG), inferior temporal gyrus (ITG), and supplementary motor area (SMA). Notably, the midline regions, including the vmPFC and precuneus, play a crucial role in value-based computation, emotional regulation, social cognition, and self-referential thinking. Individual variations in gray matter volumes within these regions served as mediators, influencing the bidirectional relationship between daily habitual tendencies and IGD symptoms. However, vmPFC variations were specifically found to mediate the pathway from PSU to daily habitual tendencies. Our findings suggest that the morphological architecture of the vmPFC and precuneus is associated with habitual tendencies in daily life and may mediate the development of addictive behaviors. This study contributes to a more nuanced understanding of the neuroanatomical basis of daily habitual tendencies and their role in addictive behaviors.

The importance of the palatine bone for endoscopic endonasal skull base surgery.

Endoscopic endonasal skull base surgery is increasingly prevalent, with its scope expanding from pathogens in the midline region to those in the paramedian region. Maximizing anterior sphenoidectomy is important for the median approach, and lateralizing the pterygopalatine fossa is crucial for the paramedian approach. Maximizing the surgical corridor in the nasal cavity and minimizing damage to neurovascular structures are vital for establishing a surgical field with minimal bleeding, ensuring safe, precise, and gentle procedures. However, the relationship between the maxillofacial and skull base bones in endoscopic endonasal skull base surgery is difficult to understand because these bones are intricately articulated, making it challenging to visualize each bone's outline. Understanding important bones and their related neurovascular structures is essential for all skull base surgeons to maximize the surgical corridor and minimize iatrogenic injury to neurovascular structures. This study aimed to elucidate the role of the palatine bone from a microsurgical anatomical perspective. Three dry skulls were used to demonstrate the structure of the palatine bone and its relationship with surrounding bones. A formalin-perfused cadaveric head was dissected to show the related neurovascular structures. The arteries and veins of the cadaveric heads were injected with red- and blue-colored silicon. Dissection was performed using a surgical microscope and endoscope. In addition, the utilization of the palatine bone as a landmark to identify neurovascular structures, which aids in creating a wider surgical field with less bleeding, was shown in two representative cases. The palatine bone consists of unique complex structures, including the sphenoidal process, ethmoidal crest, pterygopalatine canal, and sphenopalatine notch, which are closely related to the sphenopalatine artery, maxillary nerve, and its branches. The ethmoidal crest of the palatine bone is a well-known structure that is useful for identifying the sphenopalatine foramen, controlling the sphenopalatine artery and nerve, and safely opening the pterygopalatine fossa. The sphenoidal process of the palatine bone is a valuable landmark for identifying the palatovaginal artery, which is a landmark used to safely and efficiently expose the vidian canal. The sphenoidal process is easily cracked with an osteotome and removed to expose the palatovaginal artery, which runs along the pharyngeal groove, just medial to the vidian canal. By opening the pterygopalatine canal (also known as the greater palatine canal), further lateralization of the periosteum-covered pterygopalatine fossa contents can be achieved. Overall, the sphenoidal process and ethmoidal crest can be used as important landmarks to maximize the surgical corridor and minimize unnecessary injury to neurovascular structures.

Auditory Steady-State Evoked Potentials in Post Traumatic Stress Disorder: Introduction of a Potential Biomarker.

Objective: The lack of steady-state evoked potential (SSEP) studies on post-traumatic stress disorder (PTSD) has led to undiscovered useful information about the pathophysiology of the disorder. Thus, we explored SSEP patterns in PTSD patients during a stop-signal task to disclose possible impairments in these informative brain potentials. Method : 25 adult patients with PTSD and 25 healthy adults participated in this research. Subjects were assessed with electroencephalography while the tone signal stimuli at 40 Hz were used to evoke SSEPs and subjects performed a stop-signal task. The amplitude and phase of SSEPs were then computed in different brain regions. The subjects were also evaluated using the Mississippi PTSD questionnaire. Appropriate statistical methods such as repeated measure ANOVA were used to compare the two groups, and the correlation between SSEPs and clinical symptoms was assessed using Pearson correlation analysis. Results: Patients showed considerably poorer performance in the cognitive task (P < 0.01), accompanied by raised SSEP phase and amplitude in the anterior and midline regions compared to healthy controls (P < 0.05). The Mississippi total score was positively correlated with the SSEP amplitude in the midline region (r = 0.62, P < 0.05). Furthermore, based on ROC analysis, the SSEP amplitude in the midline region provided an excellent AUC value (AUC = 0.850) for distinguishing patients with PTSD from normal subjects. Conclusion: Current findings suggest that abnormalities in the anterior and midline cortical neural networks are involved in the pathophysiology of PTSD. Importantly, midline abnormalities may provide a clinically-relevant measure for researchers wishing to assess the use of biomarkers for early diagnosis of PTSD as well as to evaluate new therapeutic and management approaches in the treatment of PTSD.

Distribution of neurovascular structures within the prostate gland and their relationship to complications after radical prostatectomy.

Radical prostatectomy remains the main choice of treatment for prostate cancer. However, despite improvements in surgical techniques and neurovascular sparing procedures, rates of erectile dysfunction, and urinary incontinence remain variable. This is due, at least in part, to an incomplete understanding of neurovascular structures associated with the prostate. The objective of this study was to provide a comprehensive, detailed histological overview of the distribution of nerves and blood vessels within the prostate, facilitating subsequent correlation of prostatic neurovascular structures with patients' clinical outcomes after radical prostatectomy. Neurovascular structures within the prostate were investigated in a total of 309 slides obtained from 15 patients who underwent non-nerve-sparing radical prostatectomy. Immunohistochemical staining was performed to identify and distinguish between parasympathetic and sympathetic nerves, whereas hematoxylin and eosin staining was used to identify blood vessels. The total number, density, and relative position of nerves and blood vessels were established using quantitative morphometry and illustrated using visualization approaches. Patient-specific outcome data were then used to establish whether the internal distribution of nerves and blood vessels within the prostate correlated with the nature and extent of complications after surgery. One-way analysis of variance tests and unpaired ttests were applied to establish statistically significant differences across the measured variables. Nerves and blood vessels were present across all prostatic levels and regions. However, their number and density varied considerably between regions. Assessment of the precise positioning of neurovascular structures revealed that the majority of nerve fibers were located within the dorsal and peripheral aspects of the gland. In contrast, blood vessels were predominantly located within ventral and dorsal midline regions. The number of intraprostatic nerves was found to be significantly lower in patients who recovered their continence within 12 months of surgery, compared to those whose recovery took 12 months or longer. We report an unexpected disconnect between the localization and positioning of nerve fibers and blood vessels within the prostate. Moreover, individual variability in the density of intraprostatic neurovascular structures appears to correlate with the successful recovery of urinary continence after radical prostatectomy, suggesting that differences in intrinsic neurovascular arrangements of the prostate influence postoperative outcomes.

Comparative evaluation of masticatory efficiency, clinical performance, and patient satisfaction of single implant-retained mandibular overdenture versus conventional complete denture: A prospective in vivo study.

The aim of this within-subject prospective clinical study was to investigate the scope of single implant mandibular overdenture by assessing its masticatory efficiency, clinical performance, and patient satisfaction compared to conventional complete dentures. Prospective In Vivo Study. This prospective in vivo study was conducted in the Department of Prosthodontics and Crown and Bridge, Christian Dental College, Ludhiana. A total of 12 completely edentulous patients received a single implant in the mandibular anterior midline region. After the healing period, the conventional maxillary and mandibular dentures were fabricated. 15 days post insertion of the conventional dentures, patients were evaluated for masticatory efficiency, clinical performance including retention and stability, and patient satisfaction. To evaluate the masticatory efficiency blue raspberry and original pink "Hubba Bubba tape gum" were used as a test food. Colorimetric analysis was done to assess variance of hue. To assess clinical performance, retention, and stability of the mandibular denture was recorded using a digital force gauge and was tabulated as per CU-modified Kapur's criteria. OHIP-14 index was used to assess patient satisfaction. After evaluation of the parameters of conventional dentures, the denture was converted into an implant-retained mandibular denture by chairside conversion with locator attachments. 15 days post-implant loading, parameters of the implant retained mandibular overdenture were assessed again followed by statistical analysis. The masticatory efficiency was assessed using a paired t-test. The patient satisfaction was sequentially assessed with Wilcoxon signed rank test and thereafter paired t-test was used to compare between conventional complete denture and overdenture. Clinical performance was assessed using the Wilcoxon signed rank test. The masticatory efficiency of single implant mandibular overdenture was higher than that of conventional complete dentures. The clinical performance of the overdenture was higher than that of the conventional denture. Stability being a time-dependent parameter might need longer follow-ups for further conclusions. Patient satisfaction with single implant retained overdenture was significantly higher than conventional complete dentures. Single implant mandibular overdenture has improved masticatory efficiency, clinical performance, and patient satisfaction compared to conventional complete dentures.

Changes in Mental Health and EEG Biomarkers of Undergraduates Under Different Patterns of Mindfulness.

The effects of short-term mindfulness are associated with the different patterns (autonomic, audio guided, or experienced and certified mindfulness instructor guided mindfulness). However, robust evidence for reported the impacts of different patterns of mindfulness on mental health and EEG biomarkers of undergraduates is currently lacking. Therefore, we aimed to test the hypotheses that mindfulness training for undergraduates would improve mental health, and increase alpha power over frontal region and theta power over midline region at the single electrode level. We also describe the distinction among frequency bands patterns in different sites of frontal and midline regions. 70 participants were enrolled and assigned to either 5-day mindfulness or a waiting list group. Subjective questionnaires measured mental health and other psychological indicators, and brain activity was recorded during various EEG tasks before and after the intervention. The 5-day mindfulness training improved trait mindfulness, especially observing (p = 0.001, d = 0.96) and nonreactivity (p = 0.03, d = 0.56), sleep quality (p = 0.001, d = 0.91), and social support (p = 0.001, d = 0.95) while not in affect. Meanwhile, the expected increase in the alpha power of frontal sites (p < 0.017, d > 0.84) at the single electrode level was confirmed by the current data rather than the theta. Interestingly, the alteration of low-beta power over the single electrode of the midline (p < 0.05, d > 0.71) was difference between groups. Short-term mindfulness improves practitioners' mental health, and the potentially electrophysiological biomarkers of mindfulness on neuron oscillations were alpha activity over frontal sites and low-beta activity over midline sites.

The Human Brain Nucleus Incertus: A New Target in Dementia?

AbstractBackgroundThe brainstem nucleus incertus (NI) or ‘uncertain nucleus’, was originally described by Streeter in 1903 as a midline region in the floor of the fourth ventricle of the human brain with an ‘unknown’ function. A century later, the NI has been shown to play a key role in memory formation in rodents, through direct and indirect inhibition of the hippocampus; and the anatomy of the NI and its projections throughout the brain have been systematically mapped in rats, mice, and primates, but not in humans. In these novel studies, we mapped the human NI using the neuropeptide, relaxin‐3 (RLN3), as neurochemical marker. In rodents, RLN3 is produced mostly in NI neurons with some subsidiary positive cells in the periaqueductal gray and an area dorsal to the substantia nigra.MethodsSerial, free‐floating coronal sections of formalin‐fixed postmortem tissue were prepared from the pons of an adult female (aged 96 years) without a history of dementia or other neurological disorders, provided by the Banner Brain and Body Donation Program, Sun City, Arizona, USA. Using immunohistochemistry, we first identified the NI by mapping the distribution of microtubule‐associated protein‐2 (MAP2) and RLN3. The specificity of the RLN3 antibody used was verified in a dot‐blot using native RLN3 peptide. We also investigated the presence of markers detected in the NI of rats ‐ glutamic acid dehydrogenase‐65/67 (GAD65/67) and corticotropin‐releasing factor type 1 receptor (CRF1); and used a phosphorylated‐tau (AT8) to determine if the NI displayed tau accumulation.ResultsDetection of MAP2‐immunoreactivity revealed the neuronal distribution throughout the pons. RLN3‐immunoreactivity was detected in neurons in the dorsal, anterior‐medial region, revealing the broad anatomy of the human NI. Neurons within this same area were also positive for GAD65/67‐ and CRF1‐immunoreactivity, in line with previous studies; and AT8‐immunoreactivity was also detected.ConclusionsRLN3 is present in neurons of the human NI and aspects of its anatomy are shared across species, including the macaque. Accumulation of phosphorylated‐tau in the NI suggests its possible involvement in the pathology of Alzheimer’s disease and related dementias. Further comparative studies are required to better understand the neurochemical anatomy of the human NI.

Dynamic Functional Connectivity in Pediatric Mild Traumatic Brain Injury

Resting-state fMRI can be used to identify recurrent oscillatory patterns of functional connectivity within the human brain, also known as dynamic brain states. Alterations in dynamic brain states are highly likely to occur following pediatric mild traumatic brain injury (pmTBI) due to the active developmental changes. The current study used resting-state fMRI to investigate dynamic brain states in 200 patients with pmTBI (ages 8-18 years, median = 14 years) at the subacute (∼1-week post-injury) and early chronic (∼ 4 months post-injury) stages, and in 179 age- and sex-matched healthy controls (HC). A k-means clustering analysis was applied to the dominant time-varying phase coherence patterns to obtain dynamic brain states. In addition, correlations between brain signals were computed as measures of static functional connectivity. Dynamic connectivity analyses showed that patients with pmTBI spend less time in a frontotemporal default mode/limbic brain state, with no evidence of change as a function of recovery post-injury. Consistent with models showing traumatic strain convergence in deep grey matter and midline regions, static interhemispheric connectivity was affected between the left and right precuneus and thalamus, and between the right supplementary motor area and contralateral cerebellum. Changes in static or dynamic connectivity were not related to symptom burden or injury severity measures, such as loss of consciousness and post-traumatic amnesia. In aggregate, our study shows that brain dynamics are altered up to 4 months after pmTBI, in brain areas that are known to be vulnerable to TBI. Future longitudinal studies are warranted to examine the significance of our findings in terms of long-term neurodevelopment.