Perturbation-based balance training of older adults and effects on physiological, cognitive and sociopsychological factors: a secondary analysis from a randomised controlled trial with 12-month follow-up.

BACKGROUND: Perturbation-based balance training (PBT) has shown promising, although diverging, fall-preventive effects; however, the effects on important physical, cognitive and sociopsychological factors are currently unknown. The study aimed to evaluate these effects on PBT at three different time points (post-training, 6-months and 12-months) in community-dwelling older adults compared with regular treadmill walking. METHODS: This was a preplanned secondary analysis from a randomised, controlled trial performed in Aalborg, Denmark, between March 2021 and November 2022. Community-dwelling older adults aged ≥65 were randomly assigned to participate in four sessions (lasting 20 min each) of either PBT (intervention) or regular treadmill walking (control). All participants were assigned to four testing sessions: pretraining, post-training, 6-month follow-up and 12-month follow-up. At these sessions, physical, cognitive and sociopsychological measures were assessed. RESULTS: In total, 140 participants were randomly allocated to either the PBT or control group. Short-term (pretraining to post-training) between-group differences were seen for choice stepping reaction time (-49 ms, 95% CI -80 to -18), dual-task gait speed (0.05 m/s, 95% CI 0.01 to 0.09) favouring the PBT group. However, these improvements were not sustained at the 6-month and 12-month follow-up. No significant between-group differences were found in other physical, cognitive or sociopsychological factors. CONCLUSIONS: This study showed that PBT, in the short term, improved choice stepping reaction time and dual-task gait speed among community-dwelling older adults. Yet, these improvements were not retained for 6- or 12-months. The healthy state of the study's population may have imposed a ceiling effect limiting the ability to show any clinically relevant effects of PBT. TRIAL REGISTRATION NUMBER: NCT04733222.

Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer's disease.

Protein aggregation in brainstem nuclei is thought to occur in the early stages of Alzheimer's disease (AD), but its specific role in driving prodromal symptoms and disease progression is largely unknown. The dorsal raphe nucleus (DRN) contains a large population of serotonin (5-hydroxytryptamine; 5-HT) neurons that regulate mood, reward-related behavior, and sleep, which are all disrupted in AD. We report here that tau pathology is present in the DRN of individuals 25-80 years old without a known history of dementia, and its prevalence was comparable to the locus coeruleus (LC). By comparison, fewer cases were positive for other pathological proteins including α-synuclein, ß-amyloid, and TDP-43. To evaluate how early tau pathology impacts behavior, we overexpressed human P301L-tau in the DRN of mice and observed depressive-like behaviors and hyperactivity without deficits in spatial memory. Tau pathology was predominantly found in neurons relative to glia and colocalized with a significant proportion of Tph2-expressing neurons in the DRN. 5-HT neurons were also hyperexcitable in P301L-tauDRN mice, and there was an increase in the amplitude of excitatory post-synaptic currents (EPSCs). Moreover, astrocytic density was elevated in the DRN and accompanied by an increase in IL-1α and Frk expression, which suggests increased inflammatory signaling. Additionally, tau pathology was detected in axonal processes in the thalamus, hypothalamus, amygdala, and caudate putamen. A significant proportion of this tau pathology colocalized with the serotonin reuptake transporter (SERT), suggesting that tau may spread in an anterograde manner to regions outside the DRN. Together these results indicate that tau pathology accumulates in the DRN in a subset of individuals over 50 years and may lead to behavioral dysregulation, 5-HT neuronal dysfunction, and activation of local astrocytes which may be prodromal indicators of AD.

Reducing Delays in MRIs Under Sedation and General Anesthesia Using Quality Improvement Tools.

OBJECTIVE: Develop structured, quality improvement interventions to achieve a 15%-point reduction in MRIs performed under sedation or general anesthesia (GA) delayed more than 15 min within a 6-month period. METHODS: A prospective audit of MRIs under sedation or GA from January 2022 to June 2023 was conducted. A multidisciplinary team performed process mapping and root cause analysis for delays. Interventions were developed and implemented over four Plan, Do, Study, Act (PDSA) cycles, targeting workflow standardization, preadmission patient counseling, reinforcing adherence to scheduled scan times and written consent respectively. Delay times (compared with Kruskal-Wallis and Dunn's tests), delays more than 15 min and delays of 60 min or more at baseline and after each PDSA cycle were recorded. RESULTS: In all, 627 MRIs under sedation or GA were analyzed, comprising 443 at baseline and 184 postimplementation. Of the 627, 556 (88.7%) scans were performed under sedation, 22 (3.5%) under monitored anesthesia care, and 49 (7.8%) under GA. At baseline, 71.6% (317 of 443) scans were delayed over 15 min and 28.2% (125 of 443) scans by 60 min or more, with a median delay of 30 min. Postimplementation, there was a 34.7%-point reduction in scans delayed more than 15 min, a 17.5%-point reduction in scans delayed by 60 min or more, and a reduction in median delay time by 15 min (P < .001). DISCUSSION: Structured interventions significantly reduced delays in MRIs under sedation and GA, potentially improving outcomes for both patients and providers. Key factors included a diversity of perspectives in the study team, continued stakeholder engagement and structured quality improvement tools including PDSA cycles.

Association of head and neck CT-derived sarcopenia with mortality and adverse outcomes: A systematic review.

BACKGROUND: There is growing interest in the association of CT-assessed sarcopenia with adverse outcomes in non-oncological settings. PURPOSE: The aim of this systematic review is to summarize existing literature on the prognostic implications of CT-assessed sarcopenia in non-oncological patients. MATERIALS AND METHODS: Three independent authors searched Medline/PubMed, Embase and Cochrane Library up to 30 December 2023 for observational studies that reported the presence of sarcopenia defined on CT head and neck in association with mortality estimates and other adverse outcomes, in non-oncological patients. The quality of included studies were assessed using the Quality of Prognostic Studies tool. RESULTS: Overall, 15 studies (3829 participants) were included. Nine studies were at low risk of bias, and six were at moderate risk of bias. Patient populations included those admitted for trauma or treatment of intracranial aneurysms, ischemic stroke, transient ischemic attack, and intracranial stenosis. Sarcopenia was associated with increased 30-day to 2-year mortality in inpatients and patients undergoing carotid endarterectomy or mechanical thrombectomy for acute ischemic stroke. Sarcopenia was also associated with poorer neurological and functional outcomes, increased likelihood of admission to long-term care facilities, and longer duration of hospital stays. The observed associations of sarcopenia with adverse outcomes remained similar across different imaging modalities and methods for quantifying sarcopenia. CONCLUSION: CT-assessed sarcopenia was associated with increased mortality and poorer outcomes across diverse patient populations. Measurement and early identification of sarcopenia in vulnerable patients allows for enhanced prognostication, and focused allocation of resources to mitigate adverse outcomes.

Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol-1; aged 64.2 ± 9.4 years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [ F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ] = 0.155; ∼2500 m simulated altitude) or normoxic conditions ( F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$  = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

Application of Artificial Intelligence Methods on Osteoporosis Classification with Radiographs-A Systematic Review.

Osteoporosis is a complex endocrine disease characterized by a decline in bone mass and microstructural integrity. It constitutes a major global health problem. Recent progress in the field of artificial intelligence (AI) has opened new avenues for the effective diagnosis of osteoporosis via radiographs. This review investigates the application of AI classification of osteoporosis in radiographs. A comprehensive exploration of electronic repositories (ClinicalTrials.gov, Web of Science, PubMed, MEDLINE) was carried out in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement (PRISMA). A collection of 31 articles was extracted from these repositories and their significant outcomes were consolidated and outlined. This encompassed insights into anatomical regions, the specific machine learning methods employed, the effectiveness in predicting BMD, and categorizing osteoporosis. Through analyzing the respective studies, we evaluated the effectiveness and limitations of AI osteoporosis classification in radiographs. The pooled reported accuracy, sensitivity, and specificity of osteoporosis classification ranges from 66.1% to 97.9%, 67.4% to 100.0%, and 60.0% to 97.5% respectively. This review underscores the potential of AI osteoporosis classification and offers valuable insights for future research endeavors, which should focus on addressing the challenges in technical and clinical integration to facilitate practical implementation of this technology.

Serotonergic dysfunction may mediate the relationship between alcohol consumption and Alzheimer's disease.

The impact of Alzheimer's disease (AD) and its related dementias is rapidly expanding, and its mitigation remains an urgent social and technical challenge. To date there are no effective treatments or interventions for AD, but recent studies suggest that alcohol consumption is correlated with the risk of developing dementia. In this review, we synthesize data from preclinical, clinical, and epidemiological models to evaluate the combined role of alcohol consumption and serotonergic dysfunction in AD, underscoring the need for further research on this topic. We first discuss the limitations inherent to current data-collection methods, and how neuropsychiatric symptoms common among AD, alcohol use disorder, and serotonergic dysfunction may mask their co-occurrence. We additionally describe how excess alcohol consumption may accelerate the development of AD via direct effects on serotonergic function, and we explore the roles of neuroinflammation and proteostasis in mediating the relationship between serotonin, alcohol consumption, and AD. Lastly, we argue for a shift in current research to disentangle the pathogenic effects of alcohol on early-affected brainstem structures in AD.

Dynamic threat-reward neural processing under semi-naturalistic ecologically relevant scenarios.

Studies of affective neuroscience have typically employed highly controlled, static experimental paradigms to investigate the neural underpinnings of threat and reward processing in the brain. Yet our knowledge of affective processing in more naturalistic settings remains limited. Specifically, affective studies generally examine threat and reward features separately and under brief time periods, despite the fact that in nature organisms are often exposed to the simultaneous presence of threat and reward features for extended periods. To study the neural mechanisms of threat and reward processing under distinct temporal profiles, we created a modified version of the PACMAN game that included these environmental features. We also conducted two automated meta-analyses to compare the findings from our semi-naturalistic paradigm to those from more constrained experiments. Overall, our results revealed a distributed system of regions sensitive to threat imminence and a less distributed system related to reward imminence, both of which exhibited overlap yet neither of which involved the amygdala. Additionally, these systems broadly overlapped with corresponding meta-analyses, with the notable absence of the amygdala in our findings. Together, these findings suggest a shared system for salience processing that reveals a heightened sensitivity toward environmental threats compared to rewards when both are simultaneously present in an environment. The broad correspondence of our findings to meta-analyses, consisting of more tightly controlled paradigms, illustrates how semi-naturalistic studies can corroborate previous findings in the literature while also potentially uncovering novel mechanisms resulting from the nuances and contexts that manifest in such dynamic environments.

Increased Segregation in Functional Connectivity Networks When Watching Unpleasant Arousing Videos: A Generalized Psychophysiological Interaction Analysis.

Background: Properties of functional connectivity (FC), such as network integration and segregation, are shown to be associated with various human behaviors. For example, Godwin et al. and Sun et al. found increased integration with attention allocation, whereas Cohen and D'Esposito and Shine et al. observed increased segregation with simple motor tasks. The current study investigated how viewing video clips with different valence and arousal influenced integration-segregation properties in task-based FC networks. Methods: We analyzed an open dataset collected by Kim et al. We performed a generalized psychophysiological interaction (gPPI) analysis paired with network analysis and community detection to investigate changes in brain network dynamics when people watched four types of videos that differed by affective valence (unpleasant or pleasant) and arousal (arousing or calm). Results: Results showed that unpleasant arousing videos produced greater FC deviation from the baseline (task-induced FC deviation [tiFCd]) and perturbed the brain into a more segregated state than other kinds of video. Increased segregation was only observed in association systems, not sensorimotor systems. Discussion: Unpleasant arousing content perturbed the brain to a functionally distinct state from the other three types of affective videos. We suggest that the change in brain state was related to people disengaging from the unpleasant arousing content or, alternatively, staying alert while exposed to unpleasant arousing stimuli. The study also added to our understanding of how combining task-based gPPI analysis with community detection methods and network segregation measures can advance our knowledge of the links between behavior and brain state changes. Impact statement Network integration and segregation is an important property of the human brain. We address the question of how affective stimuli influence brain dynamics from a functional connectivity (FC) network integration-segregation perspective. By conducting a whole-brain generalized psychophysiological interaction (gPPI) analysis paired with community detection methods, we found that highly aversive video content induced significant FC changes and perturbed the brain to a more segregated state.

Pedicle Screw Pseudofracture on Computed Tomography Secondary to Metal Artifact Reduction.

Metal artifact reduction (MAR) algorithms are commonly used in computed tomography (CT) scans where metal implants are involved. However, MAR algorithms also have the potential to create new artifacts in reconstructed images. We present a case of a screw pseudofracture due to MAR on CT.

Trends in surgical management of spinal metastases in a Singaporean tertiary referral center: a 17-year retrospective review.

Introduction: Surgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore. Methods: This is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 - 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups. Results: There was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p<0.001) and Separation surgery (p<0.001). There was also a significant decrease in mean blood loss (1061ml vs 664 ml vs 594ml) (p<0.001) and total transfusion (562ml vs 349ml vs 239ml) (p<0.001). Group 3 patients were more likely to have improved or normal neurology (p=<0.001) and independent ambulatory status(p=0.012). There was no significant change in overall survival. Conclusion: There has been a significant change in our surgical practice with decreased blood loss, transfusion and improved neurological and functional outcomes. Patients should be managed in a multidisciplinary manner and surgical treatment should be recommended when indicated.

Artificial Intelligence Applications for Osteoporosis Classification Using Computed Tomography.

Osteoporosis, marked by low bone mineral density (BMD) and a high fracture risk, is a major health issue. Recent progress in medical imaging, especially CT scans, offers new ways of diagnosing and assessing osteoporosis. This review examines the use of AI analysis of CT scans to stratify BMD and diagnose osteoporosis. By summarizing the relevant studies, we aimed to assess the effectiveness, constraints, and potential impact of AI-based osteoporosis classification (severity) via CT. A systematic search of electronic databases (PubMed, MEDLINE, Web of Science, ClinicalTrials.gov) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 39 articles were retrieved from the databases, and the key findings were compiled and summarized, including the regions analyzed, the type of CT imaging, and their efficacy in predicting BMD compared with conventional DXA studies. Important considerations and limitations are also discussed. The overall reported accuracy, sensitivity, and specificity of AI in classifying osteoporosis using CT images ranged from 61.8% to 99.4%, 41.0% to 100.0%, and 31.0% to 100.0% respectively, with areas under the curve (AUCs) ranging from 0.582 to 0.994. While additional research is necessary to validate the clinical efficacy and reproducibility of these AI tools before incorporating them into routine clinical practice, these studies demonstrate the promising potential of using CT to opportunistically predict and classify osteoporosis without the need for DEXA.

The effect of repeated hot water immersion on insulin sensitivity, heat shock protein 70, and inflammation in individuals with type 2 diabetes mellitus.

Repeated hot water immersion (HWI) can improve glycemic control in healthy individuals but data are limited for individuals with type 2 diabetes mellitus (T2DM). The present study investigated whether repeated HWI improves insulin sensitivity and inflammatory status and reduces plasma ([extracellular heat shock protein 70]) [eHSP70] and resting metabolic rate (RMR). Fourteen individuals with T2DM participated in this pre- versus postintervention study, with outcome measures assessed in fasted (≥12 h) and postprandial (2-h post-75 g glucose ingestion) states. HWI consisted of 1 h in 40°C water (target rectal temperature 38.5°C-39°C) repeated 8-10 times within a 14-day period. Outcome measures included insulin sensitivity, plasma [glucose], [insulin], [eHSP70], inflammatory markers, RMR, and substrate utilization. The HWI intervention increased fasted insulin sensitivity (QUICKI; P = 0.03) and lowered fasted plasma [insulin] (P = 0.04), but fasting plasma [glucose] (P = 0.83), [eHSP70] (P = 0.08), [IL-6] (P = 0.55), [IL-10] (P = 0.59), postprandial insulin sensitivity (P = 0.19), plasma [glucose] (P = 0.40), and [insulin] (P = 0.47) were not different. RMR was reduced by 6.63% (P < 0.05), although carbohydrate (P = 0.43) and fat oxidation (P = 0.99) rates were unchanged. This study shows that 8-10 HWIs within a 14-day period improved fasting insulin sensitivity and plasma [insulin] in individuals with T2DM, but not when glucose tolerance is challenged. HWI also improves metabolic efficiency (i.e., reduced RMR). Together these results could be clinically important and have implications for metabolic health outcomes and well-being in individuals with T2DM.NEW & NOTEWORTHY This is the first study to investigate repeated HWI to raise deep body temperature on insulin sensitivity, inflammation, eHSP70, and substrate utilization in individuals with T2DM. The principal novel findings were improvements in fasting insulin sensitivity and fasting plasma [insulin] but no change in fasting plasma [glucose], postprandial insulin sensitivity, plasma [insulin], or [glucose]. There was also no change in eHSP70, inflammatory status, or substrate utilization but there were reductions in RMR and oxygen consumption.

Impact of aversive affect on neural mechanisms of categorization decisions.

INTRODUCTION: Many theories contend that evidence accumulation is a critical component of decision-making. Cognitive accumulation models typically interpret two main parameters: a drift rate and decision threshold. The former is the rate of accumulation, based on the quality of evidence, and the latter is the amount of evidence required for a decision. Some studies have found neural signals that mimic evidence accumulators and can be described by the two parameters. However, few studies have related these neural parameters to experimental manipulations of sensory data or memory representations. Here, we investigated the influence of affective salience on neural accumulation parameters. High affective salience has been repeatedly shown to influence decision-making, yet its effect on neural evidence accumulation has been unexamined. METHODS: The current study used a two-choice object categorization task of body images (feet or hands). Half the images in each category were high in affective salience because they contained highly aversive features (gore and mutilation). To study such quick categorization decisions with a relatively slow technique like functional magnetic resonance imaging, we used a gradual reveal paradigm to lengthen cognitive processing time through the gradual "unmasking" of stimuli. RESULTS: Because the aversive features were task-irrelevant, high affective salience produced a distractor effect, slowing decision time. In visual accumulation regions of interest, high affective salience produced a longer time to peak activation. Unexpectedly, the later peak appeared to be the product of changes to both drift rate and decision threshold. The drift rate for high affective salience was shallower, and the decision threshold was greater. To our knowledge, this is the first demonstration of an experimental manipulation of sensory data or memory representations that changed the neural decision threshold. CONCLUSION: These findings advance our knowledge of the neural mechanisms underlying affective responses in general and the influence of high affective salience on object representations and categorization decisions.

Outcomes and Complications of Surgery for Symptomatic Spinal Metastases; a Comparison Between Patients Aged ≥ 70 and <70.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Physicians may be deterred from operating on elderly patients due to fears of poorer outcomes and complications. We aimed to compare the outcomes of surgical treatment of spinal metastases patients aged ≥70-yrs and <70-yrs. MATERIALS AND METHODS: This is a retrospective study of patients surgically treated for metastatic epidural spinal cord compression and spinal instability between January-2005 to December-2021. Follow-up was till death or minimum 1-year post-surgery. Outcomes included post-operative neurological status, ambulatory status, medical and surgical complications. Two Sample t-test/Mann Whitney U test were used for numerical variables and Pearson Chi-Squared or Fishers Exact test for categorical variables. Survival was presented with a Kaplan-Meier curve. P < .05 was significant. RESULTS: We identified 412 patients of which 29 (7.1%) patients were excluded due to loss to follow-up and previous surgical treatment. 79 (20.6%) were ≥70-yrs. Age ≥70-yrs patients had poorer ECOG scores (P = .0017) and Charlson Comorbidity Index (P < .001). No significant difference in modified Tokuhashi score (P = .393) was observed with significantly more ≥ prostate (P < .001) and liver (P = .029) cancer in ≥70-yrs. Improved or maintained normal neurological function (P = .934), independent ambulatory status (P = .171), and survival at 6 months (P = .119) and 12 months (P = .659) was not significantly different between both groups. Medical (P = .528) or surgical (P = .466) complication rates and readmission rates (P = .800) were similar. CONCLUSION: ≥70-yrs patients have comparable outcomes to <70-yr old patients with no significant increase in complication rates. Age should not be a determining factor in deciding surgical management of spinal metastases.

Neural segregation and integration of sensory, decision, and action processes during object categorization.

Neural and computational evidence suggests that perceptual decisions depend on an evidence accumulation process. The gradual reveal fMRI method, which prolongs a decision to match the slow temporal resolution of fMRI measurements, has classified dorsal visual stream regions as "Action" (alternatively, "Moment of Recognition" or "Commitment") and ventral visual stream regions as "Accumulator." Previous gradual reveal fMRI studies, however, only tested actions that were in response to decisions and, thus, related to evidence accumulation. To fully dissociate the contribution of sensory, decision, and motor components to Action and Accumulator regions in the dorsal and ventral visual streams, we extended the gradual reveal paradigm to also include responses made to cues where no decision was necessary. We found that the lateral occipital cortex in the ventral visual stream showed a highly selective Accumulator profile, whereas regions in the fusiform gyrus were influenced by action generation. Dorsal visual stream regions showed strikingly similar profiles as classical motor regions and also as regions of the salience network. These results suggest that the dorsal and ventral visual streams may appear highly segregated because they include a small number of regions that are highly selective for Accumulator or Action. However, the streams may be more integrated than previously thought and this integration may be accomplished by regions with graded responses that are less selective (i.e., more distributed).

Epithelioid Sarcoma of the Spine: A Review of Literature and Case Report.

Epithelioid sarcoma is a rare malignant mesenchymal tumor that represents less than 1% of soft-tissue sarcomas. Despite its slow growth, the overall prognosis is poor with a high rate of local recurrence, lymph-node spread, and hematogenous metastasis. Primary epithelioid sarcoma arising from the spine is extremely rare, with limited data in the literature. We review the existing literature regarding spinal epithelioid sarcoma and report a case of epithelioid sarcoma arising from the spinal cord. A 54 year old male presented with a 1-month history of progressive left upper-limb weakness and numbness. Magnetic resonance imaging (MRI) of the spine showed an enhancing intramedullary mass at the level of T1 also involving the left T1 nerve root. Systemic radiological examination revealed no other lesion at presentation. Surgical excision of the mass was performed, and histology was consistent with epithelioid sarcoma of the spine. Despite adjuvant radiotherapy, there was aggressive local recurrence and development of intracranial metastatic spread. The patient died of the disease within 5 months from presentation. To the best of our knowledge, spinal epithelioid sarcoma arising from the spinal cord has not yet been reported. We review the challenges in diagnosis, surgical treatment, and oncologic outcome of this case.

Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens.

Social interaction is a core component of motivational behavior that is perturbed across multiple neuropsychiatric disorders, including alcohol use disorder (AUD). Positive social bonds are neuroprotective and enhance recovery from stress, so reduced social interaction in AUD may delay recovery and lead to alcohol relapse. We report that chronic intermittent ethanol (CIE) induces social avoidance in a sex-dependent manner and is associated with hyperactivity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN). While 5-HT DRN neurons are generally thought to enhance social behavior, recent evidence suggests that specific 5-HT pathways can be aversive. Using chemogenetic iDISCO, the nucleus accumbens (NAcc) was identified as one of 5 regions that were activated by 5-HT DRN stimulation. We then employed an array of molecular genetic tools in transgenic mice to show that 5-HT DRN inputs to NAcc dynorphin neurons drive social avoidance in male mice after CIE by activating 5-HT 2C receptors. NAcc dynorphin neurons also inhibit dopamine release during social interaction, reducing the motivational drive to engage with social partners. This study reveals that excessive serotonergic drive after chronic alcohol can promote social aversion by inhibiting accumbal dopamine release. Drugs that boost brain serotonin levels may be contraindicated for individuals with AUD.

Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens.

Social interaction is a core component of motivational behavior that is perturbed across multiple neuropsychiatric disorders, including alcohol use disorder (AUD). Positive social bonds are neuroprotective and enhance recovery from stress, so reduced social interaction in AUD may delay recovery and lead to alcohol relapse. We report that chronic intermittent ethanol (CIE) induces social avoidance in a sex-dependent manner and is associated with hyperactivity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN). While 5-HTDRN neurons are generally thought to enhance social behavior, recent evidence suggests that specific 5-HT pathways can be aversive. Using chemogenetic iDISCO, the nucleus accumbens (NAcc) was identified as one of 5 regions that were activated by 5-HT DRN stimulation. We then employed an array of molecular genetic tools in transgenic mice to show that 5-HT DRN inputs to NAcc dynorphin neurons drive social avoidance in male mice after CIE by activating 5-HT2C receptors. NAcc dynorphin neurons also inhibit dopamine release during social interaction, reducing the motivational drive to engage with social partners. This study reveals that excessive serotonergic drive after chronic alcohol can promote social aversion by inhibiting accumbal dopamine release. Drugs that boost brain serotonin levels may be contraindicated for individuals with AUD.