Physical Effort Exertion for Peer Feedback Reveals Evolving Social Motivations From Adolescence to Young Adulthood.

Peer relationships and social belonging are particularly important during adolescence. Using a willingness-to-work paradigm to quantify incentive motivation, we examined whether evaluative information holds unique value for adolescents. Participants (N = 102; 12-23 years old) rated peers, predicted how peers rated them, and exerted physical effort to view each peer's rating. We measured grip force, speed, and opt-out behavior to examine the motivational value of peer feedback, relative to money in a control condition, and to assess how peer desirability and participants' expectations modulated motivated effort across age. Overall, when compared with adolescents, adults were relatively less motivated for feedback than money. Whereas adults exerted less force and speed for feedback when expecting rejection, adolescents exerted greater force and speed when expecting to be more strongly liked or disliked. These findings suggest that the transition into adulthood is accompanied by a self-protective focus, whereas adolescents are motivated to consume highly informative feedback, even if negative.

Predictors of postoperative performance status after surgical management of infratemporal fossa malignancies.

Infratemporal fossa (ITF) tumors are difficult to access surgically due to anatomical constraints. Moreover, aggressive ITF carcinomas and sarcomas necessitate aggressive treatment strategies that, along with tumor-related symptoms, contribute to decreases in patient performance status. To assess factors that predict postoperative performance in patients undergoing surgery for ITF tumors. We reviewed medical records for all patients surgically treated for an ITF malignancy between January 1, 1999, and December 31, 2017, at our institution. We collected patient demographics, preoperative performance, tumor stage, tumor characteristics, treatment modalities, pathological data, and postoperative performance data. The 5-year survival rate was 62.2%. Higher preoperative Karnofsky Performance Status (KPS) score (n = 64; p < 0.001), short length of stay (p = 0.002), prior surgery at site (n = 61; p = 0.0164), and diagnosis of sarcoma (n = 62; p = 0.0398) were predictors of higher postoperative KPS scores. Percutaneous endoscopic gastrostomy (PEG) (n = 9; p = 0.0327), and tracheostomy tube placement (n = 20; p = 0.0436) were predictors of lower postoperative KPS scores, whereas age at presentation (p = 0.72), intracranial tumor spread (p = 0.8197), and perineural invasion (n = 40; p = 0.2195) were not. Male patients and patients with carcinomas showed the greatest decreases in KPS scores between pretreatment and posttreatment. Higher preoperative KPS score and short length of stay were the best predictors of higher postoperative KPS scores. This work provides treatment teams and patients with better information on outcomes for shared decision-making.

Commentary: Building the developmental foundations of developmental computational psychiatry: reflections on Hauser et al. (2019).

There is a growing interest in applying the conceptual and analytical frameworks of computational psychiatry to developmental populations. This is motivated by appreciation that psychiatric illness needs to be understood from a neurodevelopmental perspective. The target article by Hauser and colleagues highlights progress in applying the computational psychiatry perspectives to identifying the developmental mechanisms of mental illness. We share the enthusiasm and optimism for this venture, while recognizing the substantial theoretical and pragmatic challenges associated with applying computational frameworks to developing populations. In this commentary, we highlight the ways that taking a developmental perspective in this arena stretches beyond merely identifying age differences in a computational parameter of interest. These include the need for experimental and computational frameworks to recognize that developmental changes can be quantitative or qualitative in nature, the need to consider developmental stage beyond age groupings or even numerical age, and the need for large quantities of data to model age-related changes in a reproducible manner. In doing so, we hope to stimulate progress in uncovering the mechanisms of psychiatric illness in a way that is developmentally informed.

Cost-effectiveness and threshold analysis of deep brain stimulation vs. treatment-as-usual for treatment-resistant depression.

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare reimbursement rates and health economics data were used to approximate costs. We performed Monte Carlo (MC) simulations and probabilistic sensitivity analyses to estimate incremental cost-effectiveness ratios (ICER; USD/quality-adjusted life year [QALY]) at a 5-year time horizon. Cost-effectiveness was defined using willingness-to-pay (WTP) thresholds of $100,000/QALY and $50,000/QALY for moderate and definitive cost-effectiveness, respectively. We included 274 patients across 16 studies from 2009-2021 who underwent DBS for TRD and had ≥12 months follow-up in our model inputs. From a healthcare sector perspective, DBS using non-rechargeable devices (DBS-pc) would require 55% and 85% remission, while DBS using rechargeable devices (DBS-rc) would require 11% and 19% remission for moderate and definitive cost-effectiveness, respectively. From a societal perspective, DBS-pc would require 35% and 46% remission, while DBS-rc would require 8% and 10% remission for moderate and definitive cost-effectiveness, respectively. DBS-pc will unlikely be cost-effective at any time horizon without transformative improvements in battery longevity. If remission rates ≥8-19% are achieved, DBS-rc will likely be more cost-effective than TAU for TRD, with further increasing cost-effectiveness beyond 5 years.

Effective deep brain stimulation for obsessive-compulsive disorder after failed anterior capsulotomy: illustrative cases.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by recurrent, unwanted thoughts (obsessions) and repetitive behaviors (compulsions) performed to relieve distress related to the obsessions. For patients with severe illness refractory to first-line pharmacotherapy and psychotherapy, neurosurgical treatments such as deep brain stimulation (DBS) and stereotactic lesioning are an option. The choice between DBS and lesioning is often driven by patient preference, but these options are not mutually exclusive. Here, the authors highlight the success of one surgical therapy (DBS) after the failure of another (lesioning). OBSERVATIONS: Two patients with severe, treatment-refractory OCD underwent DBS lead implantation targeting the ventral capsule/ventral striatum after they did not attain any worthwhile benefit from a previous anterior capsulotomy. Both patients showed significant improvement (≥ 35% reduction in Yale-Brown Obsessive-Compulsive Scale [YBOCS] score) of their OCD symptoms at the long-term follow-up after DBS. One patient experienced a 37% reduction in symptom severity as measured by the YBOCS, and the other patient experienced a 47% reduction. LESSONS: DBS and lesioning procedures are both effective surgical options for patients with intractable OCD. In these cases, the authors demonstrate that DBS can be utilized even after a lesioning procedure in nominally the same target (ventral portion of the anterior limb of the internal capsule). https://thejns.org/doi/10.3171/CASE24289.

Efficacy of deep brain stimulation for treatment-resistant depression: systematic review and meta-analysis.

BACKGROUND: Treatment-resistant depression (TRD) affects about 30% of individuals with major depressive disorder. Deep brain stimulation (DBS) is an investigational intervention for TRD with varied results. We undertook this meta-analysis to synthesize outcome data across trial designs, anatomical targets, and institutions to better establish efficacy and side effect profiles. METHODS: We conducted a systematic PubMed review following PRISMA guidelines. Seven randomized-controlled trials (n=198) and eight open-label trials (n=77) were included, spanning 2009-2020. Outcome measures included Hamilton Depression Rating Scale or Montgomery-Åsberg Depression Rating Scale scores, as well as response and remission rates over time. Outcomes were tracked at last follow-up and quantified as a time course using model-based network meta-analysis. Linear mixed models were fit to individual patient data to identify covariates. RESULTS: DBS achieved 47% improvement in long-term depression scale scores, with an estimated time to reach 50% improvement around 23 months. There were no significant subgroup effects of stimulation target, time of last follow-up, sex, age of disease onset, or duration of disease, but open-label trials showed significantly greater treatment effects compared to randomized controlled trials. Long-term (12-60 month) response and remission rates were 48% and 35%, respectively. The time course of improvement with active stimulation could not be adequately distinguished from that with sham stimulation, when available. CONCLUSIONS: DBS produces significant chronic improvement in symptoms of TRD. The limited sham-controlled data, however, does not demonstrate significant improvement over placebo. Future advancements in stimulation optimization and careful blinding and placebo schemes are important next steps for this therapy.

Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder.

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.

Cerebral microdialysis and glucopenia in traumatic brain injury: A review.

Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such measurements of cellular metabolism can yield critical missing information about a patient's physiologic state and help limit secondary damage. Glucose management in traumatic brain injury is still an unresolved question. As cerebral glucose metabolism may be uncoupled from systemic glucose levels due to the metabolic dysfunction, measurement of cerebral extracellular glucose concentrations could provide more predictive information and prove to be a better biomarker to avoid secondary injury of at-risk brain tissue. Based on data obtained from cerebral microdialysis, specific interventions such as ICP-directed therapy, blood glucose increment, seizure control, and/or brain oxygen optimization can be instituted to minimize or prevent secondary insults. Thus, microdialysis measurements of parenchymal metabolic function provides clinically valuable information that cannot be obtained by other monitoring adjuncts in the standard ICU setting.

How adolescents and adults translate motivational value to action: Age-related shifts in strategic physical effort exertion for monetary rewards.

Adults titrate the degree of physical effort they are willing to expend according to the magnitude of reward they expect to obtain, a process guided by incentive motivation. However, it remains unclear whether adolescents, who are undergoing normative developmental changes in cognitive and reward processing, translate incentive motivation into action in a way that is similarly tuned to reward value and economical in effort utilization. The present study adapted a classic physical effort paradigm to quantify age-related changes in motivation-based and strategic markers of effort exertion for monetary rewards from adolescence to early adulthood. One hundred three participants aged 12-23 years completed a task that involved exerting low or high amounts of physical effort, in the form of a hand grip, to earn low or high amounts of money. Adolescents and young adults exhibited highly similar incentive-modulated effort for reward according to measures of peak grip force and speed, suggesting that motivation for monetary reward is consistent across age. However, young adults expended energy more economically and strategically: Whereas adolescents were prone to exert excess physical effort beyond what was required to earn reward, young adults were more likely to strategically prepare before each grip phase and conserve energy by opting out of low reward trials. This work extends theoretical models of development of incentive-driven behavior by demonstrating that layered on similarity in motivational value for monetary reward, there are important differences in the way behavior is flexibly adjusted in the presence of reward from adolescence to young adulthood. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Interrupting Neuron-Tumor Interactions to Overcome Treatment Resistance.

Neurons in the tumor microenvironment release neurotransmitters, neuroligins, chemokines, soluble growth factors, and membrane-bound growth factors that solid tumors leverage to drive their own survival and spread. Tumors express nerve-specific growth factors and microRNAs that support local neurons and guide neuronal growth into tumors. The development of feed-forward relationships between tumors and neurons allows tumors to use the perineural space as a sanctuary from therapy. Tumor denervation slows tumor growth in animal models, demonstrating the innervation dependence of growing tumors. Further in vitro and in vivo experiments have identified many of the secreted signaling molecules (e.g., acetylcholine, nerve growth factor) that are passed between neurons and cancer cells, as well as the major signaling pathways (e.g., MAPK/EGFR) involved in these trophic interactions. The molecules involved in these signaling pathways serve as potential biomarkers of disease. Additionally, new treatment strategies focus on using small molecules, receptor agonists, nerve-specific toxins, and surgical interventions to target tumors, neurons, and immune cells of the tumor microenvironment, thereby severing the interactions between tumors and surrounding neurons. This article discusses the mechanisms underlying the trophic relationships formed between neurons and tumors and explores the emerging therapies stemming from this work.