Cognitive Fatigue Research Articles

White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis

Multiple sclerosis (MS) is a prevalent neurological disorder marked by inflammation and demyelination, with fatigue being one of the most reported and debilitating symptoms. While fatigue occurs across various neurological conditions and even in healthy individuals, the specific mechanisms contributing to fatigue in each context remain unclear. In this study, we conducted a cross-sectional analysis involving 32 people with relapsing MS (PwRMS) and 29 healthy controls who reported fatigue. Participants underwent MRI scans, including T1-weighted and diffusion-weighted imaging. Additionally, the Modified Fatigue Impact Scale was utilized. We employed Bayesian LASSO and Spike-and-Slab LASSO regression models to investigate the hypothesis that fatigue correlates differently with brain structures in PwRMS. Our findings revealed brain regions associated with general and cognitive fatigue. In particular, reduced white matter volume and compromised microstructural integrity in specific areas—such as the cingulate gyrus, inferior frontal gyrus, and the banks of the superior temporal sulcus—showed significant associations with fatigue scores in PwRMS. These results suggest that alterations in specific brain regions may play a critical role in the clinical manifestation of fatigue in MS. Understanding these insights could help differentiate general mechanisms of fatigue from those affecting people with relapsing MS, which may guide future therapeutic strategies.

The Neurobiology of Cognitive Fatigue and Its Influence on Effort-Based Choice.

Feelings of cognitive fatigue emerge through repeated mental exertion and are ubiquitous in our daily lives. However, there is a limited understanding of the neurobiological mechanisms underlying the influence of cognitive fatigue on decisions to exert. We use functional magnetic resonance imaging while participants (18 female, 10 male) choose to exert effort for reward, before and after bouts of fatiguing cognitive exertion. We found that when participants became cognitively fatigued, they were more likely to choose to forgo higher levels of reward for more effort. We describe a mechanism by which signals related to cognitive exertion in dlPFC influence effort value computations, instantiated by the insula, thereby influencing an individual's decisions to exert while fatigued. Our results suggest that cognitive fatigue plays a critical role in decisions to exert effort and provides a mechanistic link through which information about cognitive state shapes effort-based choice.Significance statement Cognitive fatigue influences decisions to exert effort throughout our daily lives. However, it is unclear how the brain integrates information about cognitive fatigue to influence effort-based decision-making. We found that when individuals engage in repeated cognitive exertion, exertion-related signals in dlPFC influence effort value computations in insular cortex, thereby influencing an individual's decisions to exert while fatigued. These results provide a mechanistic account of how information about cognitive state impacts choice.

Cognitive function and fatigue before and after transsphenoidal surgery in patients with pituitary adenoma: a prospective study

PurposeThe aim of this prospective longitudinal study was to evaluate cognitive function and fatigue before and 12 months after transsphenoidal surgery (TSS) for a pituitary adenoma.MethodsThis study was part of the Gothenburg Pituitary Tumour Study, which consecutively includes patients undergoing TSS at Sahlgrenska University Hospital. Adult patients with a pituitary adenoma were recruited between October 2016 and May 2021. Cognitive function and fatigue were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Multidimensional Fatigue Inventory (MFI-20). Paired comparisons were made for total and subscale scores before and after TSS. Based on normative data, individual scores were classified into one of three categories for symptom severity (normal, moderate, or severe) before and after TSS.ResultsFifty-nine patients (31 females) were included. Among them, 42 had non-functioning pituitary adenomas (NFPA) and 17 had a functioning pituitary adenoma. There were no differences in RBANS total or domain indices before and 12 months after surgery except for the attention index which improved. Total MFI-20 and all subscale scores improved. The improvement was more pronounced in patients with functioning pituitary adenoma, who reported worse fatigue before surgery compared to patients with NFPA. Individual differences between pre- and postoperative scores that also changed category of symptom severity were seen for 37% of all patients regarding cognition and for 35% regarding fatigue. Improvements accounted for the majority of these changes.ConclusionCognitive function remained largely unchanged from before to 12 months after TSS, while self-reported fatigue improved.

Subjective cognitive, psychiatric, and fatigue symptoms two years after COVID-19: A prospective longitudinal cohort study.

COVID-19 survivors may present with cognitive and psychiatric symptoms long after the acute phase of SARS-CoV-2 infection. To determine subjective cognitive, psychiatric, and fatigue symptoms two years after COVID-19, and their change from six months to two years. We assessed three COVID-19 patient groups of different acute disease severity (ICU-treated, ward-treated, home-isolated) concerning subjective cognitive functioning (AB Neuropsychological Assessment Schedule), anxiety (Generalised Anxiety Disorder 7), depression (Patient Health Questionnaire 9), post-traumatic stress (Impact of Event Scale 6), and fatigue (Multidimensional Fatigue Inventory) with a mailed questionnaire approximately two years after acute COVID-19. We compared the results with those obtained six months after the acute disease. We studied whether any change emerged in the scores of symptomatic patients between six- and 24-month follow-ups. Two years post-COVID-19, 58 ICU-treated, 35 ward-treated, and 28 home-isolated patients responded to the questionnaire. Subjective cognitive symptoms and fatigue emerged as the most common problems occurring in 30.6 and 35.5% of patients, respectively. In patients with clinically significant symptoms at six months, symptom scores for depression, anxiety, and post-traumatic stress decreased at two years. Two years after COVID-19, particularly self-reported cognitive symptoms and fatigue remained clinically significant, but also some recovery was evident in depression, anxiety, and post-traumatic stress.

Music boosts the recovery of attention after mental fatigue in healthy young male subjects: A human auditory event-related potential study.

Music boosts the recovery of attention after mental fatigue in healthy young male subjects: A human auditory event-related potential study.

Distinct clinical, imaging, and cerebrospinal fluid profiles in people with late-onset multiple sclerosis.

Late-onset multiple sclerosis (LOMS), defined as onset after age 50, poses unique diagnostic challenges due to clinical and radiological differences from early-onset multiple sclerosis (EOMS), which typically manifests in adults between 20 and 40 years of age. Limited research on these differences hampers accurate diagnosis of LOMS. This study aims to bridge this gap by comparing clinical presentation, imaging, and cerebrospinal fluid (CSF) findings in LOMS and EOMS patients. We retrospectively analyzed clinical, MRI, and CSF data from 148 LOMS patients treated in the neuroimmunology outpatient clinic of a Swiss tertiary referral center between 2013 and 2023. A control group of 148 EOMS patients, matched by year of diagnosis, was included for comparison. LOMS patients, with a median onset age of 53 years (interquartile range (IQR) 51-58 years), more commonly presented with motor or multiple symptoms and a primary progressive multiple sclerosis subtype (p < 0.001). They were also more likely than EOMS patients (median onset age 28 years, IQR 24-33 years) to report cognitive impairment and fatigue at disease onset (p < 0.001). MRI analysis showed that LOMS patients had a significantly higher T2-lesion load (p = 0.026) but fewer Gadolinium-enhancing lesions at diagnosis (p < 0.001). The percentage of patients with CSF-specific oligoclonal bands was comparable between groups, whereas CSF pleocytosis was more common in EOMS patients (p < 0.001). Importantly, we noticed a significant delay in diagnosing multiple sclerosis in older adults likely due to misdiagnosis or difficulties in timely recognition. LOMS represents a subgroup of multiple sclerosis with unique clinical and radiological characteristics compared to EOMS. The higher T2-lesion burden and fewer Gadolinium-enhancing lesions in LOMS can pose diagnostic challenges. Recognizing these differences may enhance diagnostic accuracy and guide more effective management strategies for LOMS.

Identifying neuropsychological phenotypes in multiple sclerosis using latent profile analysis.

People with Multiple Sclerosis (MS) frequently experience cognitive impairment and neurobehavioral issues including depression and fatigue. We aim to define neuropsychological phenotypes in MS based on cognitive function, depression and fatigue. In this cross-sectional study, we collected clinical and neuropsychological data for 600 MS patients. Neuropsychological assessments included Brief International Cognitive Assessment for MS (BICAMS), Beck Depression Inventory (BDI-II) and Modified Fatigue Impact Scale (MFIS). We employed a latent profile analysis (LPA) to unveil latent neuropsychological profiles in MS patients, clustering individuals in unobserved groups, and we compared clinical and MRI features between groups. LPA identified five neuropsychological phenotypes: Normal neuropsychological phenotype, with normal cognitive and neurobehavioral scores; Isolated cognitive impairment, showing mild reduction in BICAMS scores; Isolated neurobehavioral impairment, showing increased BDI-II and MFIS scores; Mild neuropsychological impairment, showing mildly reduced BICAMS scores, and mildly increased BDI-II and MFIS scores; Severe neuropsychological impairment, showing severely reduced BICAMS scores, and great increase in BDI-II and MFIS scores vs patients with normal neuropsychological phenotype. Relapsing-onset and paediatric-onset patients are more likely in the normal neuropsychological phenotype and isolated cognitive impairment class. Patients with severe neuropsychological impairment showed lower cortical grey matter, thalamic, amygdala, pallidum and putamen volume compared with those with isolated neurobehavioral impairment. We identified five neuropsychological phenotypes in patients with MS that showed distinct clinical and radiologic features, as from different stages of the disease pathology accrual. Clinical and MRI features may help distinguishing patients requiring closer monitoring of cognitive or neurobehavioral symptoms. Antonio Luca Spiezia, Fabrizia Falco, Federica Lamagna, Martina Eliano, Valerio Nicolella, Antonio Esposito and Cristina Di Monaco have nothing to disclose. Marcello Moccia has received financial support by the MUR PNRR Extended Partnership (MNESYS no. PE00000006, and DHEAL-COM no. PNC-E3-2022-23,683,267); research grants from the ECTRIMS-MAGNIMS, the UK MS Society, and Merck; salary as Assistant Editor of Neurology; and honoraria from Abbvie, Biogen, BMS Celgene, Ipsen, Jansenn, Merck, Novartis, Roche, and Sanofi-Genzyme. Sirio Cocozza has served on scientific advisory board for Amicus Therapeutics, has received speaker honoraria from Sanofi and research grants from Fondazione Italiana Sclerosi Multipla and Telethon. Giuseppe Pontillo was supported by the MAGNIMS/ECTRIMS (2020), ESNR (2021), and ECTRIMS (2022) research fellowship programs. Roberta Lanzillo has received honoraria from Biogen, Merck, Novartis, Roche and Teva. VBM has received research grants from the Italian MS Society, and Roche, and honoraria from Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi- Genzyme and Teva. Vincenzo Brescia Morra has received research grants from Italian MS Federation and Roche; and honoraria from Almirall, Biogen, BMS Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Viatris. Maria Petracca discloses travel/meeting expenses from Novartis, Janssen, Roche and Merck; speaking honoraria from HEALTH&LIFE S.r.l., AIM Education S.r.l., Biogen, Novartis and FARECOMUNICAZIONE E20; honoraria for consulting services and advisory board participation from Biogen; research grants from Baroni Foundation and the Italian Ministry of University and Research. Antonio Carotenuto disclosed research grants from ECTRIMS-MAGNIMS and Almirall, travel/meeting expenses from Novartis, Janssen, Roche and Merck and speaking honoraria from Merk, BMS, Biogen, Novartis, Roche and Almirall.

Association of reperfusion therapy in acute ischemic stroke on PROMs after one year; a registry-based case-control study.

Association of reperfusion therapy in acute ischemic stroke on PROMs after one year; a registry-based case-control study.

Moral Judgments Are (Most Probably) Robust to Physical Fatigue.

Across two experiments (N = 303), we examined the effect of physical fatigue on moral decision-making. Participants were subjected to acute physical exercise. Half of the participants were presented with moral dilemmas before the physical exercise and the other half after the exercise. We measured moral judgement using a shortened version of the Process Dissociation procedure, allowing us to investigate (1) decisions in the traditional sacrificial dilemmas and (2) deontological and utilitarian moral inclinations. The results showed no significant differences in moral judgments between fatigued and nonfatigued participants in nine out of 10 statistical tests. This suggests a unique resilience of moral judgments to physical fatigue, in contrast to what is known about cognitive fatigue.

Association of Virtual Nurses' Workflow and Cognitive Fatigue During Inpatient Encounters: Cross-Sectional Study.

The virtual nursing delivery model enables the provision of expert nursing care from a remote location, using technology such as audio and video communication, remote monitoring devices, and access to electronic health records. Virtual nurses spend an extensive amount of time on computers to provide care, and little is known about how this workflow may affect and contribute to cognitive fatigue. This study aimed to use eye tracking technology and pupil size variation to determine instances of virtual nurse cognitive fatigue during their typical workflow. This study examined the virtual nursing workflow by recording and analyzing virtual nurse encounters using eye tracking. This cross-sectional study was conducted during regular 12-hour shifts at a major Southeastern health center in the United States. The study found that 75% (22/29) of virtual nursing encounters demonstrated a first fatigue instance at 9.8 minutes during patient discharges and at 11.9 minutes during patient admissions. This study provides valuable insights into virtual nursing workflow design and how it may impact the cognitive fatigue levels of nurses providing inpatient virtual care.

Induction versus Concurrent Chemotherapy for Advanced Nasopharyngeal Carcinoma

BackgroundCisplatin-based concurrent chemoradiotherapy (CCRT) is the mainstay treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), which usually leads to intolerable toxicities. We investigated whether or not induction chemotherapy (IC) plus intensity-modulated radiation therapy (IMRT) could replace CCRT.MethodsThis is an open-label, phase 3, noninferiority trial. Patients with stage T1-4N2-3 or T3-4N0-1 LA-NPC were randomly assigned (1:1) to receive gemcitabine (1000 mg/m2) and cisplatin (80 mg/m2) for two cycles followed by IMRT, or IMRT plus concomitant weekly cisplatin (40 mg/m2) for up to seven cycles. Two-year failure-free survival (FFS) was the primary end point, and noninferiority was confirmed by an upper limit of the 95% confidence interval (CI) for a hazard ratio of less than 2.12 (absolute margin of −10 percentage points). Secondary end points include overall survival, locoregional recurrence-free survival, distant metastasis-free survival, toxicity profile, and quality of life (QoL).ResultsWe enrolled 124 patients in the IC group and 125 patients in the CCRT group. The median follow-up was 60 months. Two-year FFS was 90.2% for IC versus 86.3% for CCRT, with a hazard ratio of 0.636 (95% CI, 0.267 to 1.514) and an absolute difference of 3.9 percentage points (95% CI, −5.2 to 13.0). Compared with the CCRT group, fewer grade ≥3 adverse events occurred in the IC group (47.5% vs. 61.5%; P=0.029), including leukopenia, anemia, mucositis, nausea, and dysphagia. IC was associated with better QoL, including global health status, social and cognitive functioning, fatigue, nausea and vomiting, pain, appetite loss, and constipation.ConclusionsFor 2-year FFS for LA-NPC, gemcitabine and cisplatin IC plus IMRT alone was noninferior to CCRT. (Funded by Key-Area Research and Development of Guangdong Province and others.)

Dynamic brain glymphatic changes and cognitive function in COVID-19 recovered patients: a DTI-ALPS prospective cohort study.

This study aimed to evaluate brain glymphatic function in COVID-19 recovered patients using the non-invasive Diffusion Tensor Imaging-Analysis Along the Perivascular Space (DTI-ALPS) technique. The DTI-ALPS technique was employed to investigate changes in brain glymphatic function in these patients and explore correlations with cognitive function and fatigue. Follow-up assessments were conducted at 1, 3, and 12 months post-recovery. A total of 31 patients completed follow-ups at all three time points, with 30 healthy controls (HCs) for comparison. Compared to HCs, COVID-19 recovered patients showed a significant decline in MoCA scores at 3 months post-recovery (p < 0.05), which returned to near-normal levels by 12 months. Mental fatigue, measured by the Fatigue Assessment Scale (FAS), was significantly higher in COVID-19 patients at all follow-up points compared to HCs (p < 0.05). The DTI-ALPS index in both hemispheres showed significant differences at 3 months post-recovery compared to HCs (p < 0.001), indicating increased glymphatic activity. Longitudinal analysis revealed a peak in the DTI-ALPS index at 3 months post-recovery, which then decreased by 12 months. Correlation analysis showed a significant negative correlation between the Bilateral brain hemisphere DTI-ALPS index and MoCA scores (right side: r = -0.373, p = 0.003; left side: r = -0.255, p = 0.047), and a positive correlation with mental fatigue (right side: r = 0.275, p = 0.032; left side: r = 0.317, p = 0.013). This study demonstrates dynamic changes in brain glymphatic function in COVID-19 recovered patients, with a peak in activity at 3 months post-recovery. These changes are associated with cognitive function and mental fatigue, suggesting potential targets for addressing neurological symptoms of long COVID. The non-invasive DTI-ALPS technique proves to be a valuable tool for assessing brain glymphatic function in this population.

The Role of the Cerebellum in Multiple Sclerosis-Related Fatigue and Disability

Background: Fatigue is a prevalent and debilitating symptom in people with multiple sclerosis (pwMS), significantly impairing quality of life. While the cerebellum is traditionally associated with motor control, emerging evidence suggests its involvement in cognitive, emotional, and integrative functions. This study aimed to explore the relationship between fatigue components (physical, cognitive, and psychosocial), clinical disability, and cerebellar structural changes in pwMS acquired via magnetic resonance imaging (MRI). Methods: Participants of this cross-sectional study underwent clinical assessments for fatigue (Modified Fatigue Impact Scale) and disability (Expanded Disability Status Scale). Cerebellar volumes were measured using high-resolution MRI and voxel-based morphometry (VBM) to identify correlations between fatigue subdomains and specific cerebellar subregions. Statistical analyses included group comparisons and correlation tests. Results: Forty-four pwMS were included. Fatigued MS patients exhibited reduced sensorimotor cerebellar volumes compared to non-fatigued counterparts. Physical fatigue correlated negatively with sensorimotor cerebellum volume, while cognitive fatigue showed an inverse relationship with limbic cerebellum regions. Interestingly, psychosocial fatigue was positively associated with limbic cerebellum volume, contrary to initial hypotheses. Higher disability scores were linked to atrophy in cognitive and limbic cerebellar regions. Conclusions: The findings highlight the cerebellum’s multifaceted role in MS-related fatigue, with distinct subregions contributing to physical, cognitive, and psychosocial fatigue components. These results underscore the cerebellum’s critical function as a hub for motor, cognitive, and emotional integration. Future longitudinal studies incorporating objective measures and advanced imaging are essential to elucidate these relationships further and inform targeted therapeutic strategies for pwMS.

Feels like being a hamster on a running wheel: an interpretative phenomenon analysis of online dating fatigue among Indian millennial women

ABSTRACT Objective This study aimed to explore online dating fatigue among millennial women living in India. Methods In-depth semi-structured interviews were undertaken with seven heterosexual women (age: 33.71 ± 1.98 years) engaged in online dating for at least one year. Interpretative Phenomenological Analysis (IPA) was utilized to analyse and illustrate individuals' experiences and fatigue. Result Participants’ experiences revealed three superordinate and nine sub-themes: (i) emotional exhaustion and fatigue (repetitive conversation fatigue, deceit, and misogyny), (ii) physical fatigue (wasting time,energy, and excessive screen time), and (iii) cognitive fatigue (decision overload, hopelessness, compulsive and mindless swiping, and self-doubt) Conclusion These findings offer an understanding of the experiences and fatigue of online dating in millennial women. The findings highlight socio-cultural and cognitive-emotive factors associated with online dating fatigue, offering a foundation for policymakers and mental health professionals to develop evidence-based interventions.

Long COVID in pediatric age: an observational, prospective, longitudinal, multicenter study in Italy.

This observational prospective longitudinal multicenter study examines the occurrence and characteristics of long COVID (LC) in the Italian pediatric population. Conducted across 12 Pediatric Units in Italy from January to March 2022, the study involved 1129 children diagnosed with SARS-CoV-2 infection. Data were collected via self-administered questionnaires at 1-3 months, 3-6 months, and 6-12 months post-infection, with LC defined as symptoms persisting for at least 2 months and occurring 3 months post-diagnosis. Results revealed that 68.6% of children reported at least one post-COVID symptom, with 16.2% experiencing LC. The most frequent symptoms included respiratory issues (43.4%), neurological and cognitive dysfunction (27.7%), gastrointestinal symptoms (22.1%), fatigue (21.6%), and sleep disturbances (18.8%). Age and gender differences were significant, with older children and females more prone to cardiovascular and neurological & cognitive dysfunction. The study highlights that LC in children presents similarly to adults, though less frequently. The occurrence of LC was lower compared to adult populations, likely due to the generally milder course of COVID-19 in children. The findings underscore the need for targeted follow-up and support for affected children, especially considering the long-term persistence of symptoms. Further research is necessary to explore the impact of COVID-19 vaccines on pediatric LC and the effects of different SARS-CoV-2 variants. These insights are crucial for developing strategies to manage and mitigate long-term impacts in children recovering from COVID-19.

Transcranial Direct Current Stimulation (tDCS) to Improve Cognitive Function and Reduce Cognitive Fatigue and Fatigability in Parkinson’s Disease (P2-5.031)

Transcranial Direct Current Stimulation (tDCS) to Improve Cognitive Function and Reduce Cognitive Fatigue and Fatigability in Parkinson’s Disease (P2-5.031)

The Role of Sleep Quality and Sleepiness in the Relationship Between Cognitive Flexibility and Fatigue

Abstract This study aimed to determine the pathways linking cognitive flexibility to fatigue through the serial mediation effect of sleep quality and sleepiness in 564 healthy adults using various scales, including the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Chalder Fatigue Scale, and Cognitive Flexibility Inventory. Analysis was performed using two mediating variables (sleep quality and sleepiness) with age and gender as covariates. The simple mediation effect was evaluated using the Causal Step. The indirect effect was examined using bootstrap method and Sobel test. The total and direct effects of cognitive flexibility on fatigue were both found to be statistically significant. The research model revealed three significant indirect effects: cognitive flexibility affecting fatigue through sleep quality, cognitive flexibility affecting fatigue through sleepiness and cognitive flexibility affecting fatigue through both sleep quality and sleepiness. Additionally, serial mediation analysis showed that the relationship between cognitive flexibility and fatigue is sequentially mediated by sleep quality and sleepiness (B = -0.064, SE = 0.013, 95% CI: -0.070 to -0.017). All effects were confirmed through the 95% confidence intervals, which did not include zero, and with significant p values. These findings highlight the role of sleep quality and sleepiness as serial mediators of the relationship between cognitive flexibility and fatigue. The study's major contribution is to provide insight on the independent and serial mediating role of sleep quality and sleepiness in the relationship between cognitive flexibility to fatigue.

Sleep quality and physical fitness as modifiable contributors of fatigue in childhood cancer survivors.

Advances in cancer treatment have increased childhood cancer patient's survival rates. However, many childhood cancer survivors (CCS) face long-term effects such as fatigue. This study assessed fatigue in CCS and healthy controls (HCs), its contributors, and associated outcomes. This cross-sectional study included 90 CCS and 55 age and sex-matched HCs. Fatigue was measured using the Pediatric Quality of Life Multidimensional Fatigue Scale, and modifiable contributors included sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and physical fitness (VO2 peak during a treadmill test). Quality of life (QoL) and emotional and cognitive functioning were evaluated using the Pediatric Quality of Life Inventory, Beck Depression Inventory II, Cognitive Failure Questionnaire, and the Impact of Event Scale-Revised. Stepwise linear regressions identified predictors of general, sleep/rest, cognitive, and total fatigue. General, cognitive, and total fatigue were significantly higher in CCS compared to HCs (44.7% vs. 23%, p < .001; cognitive: 64.7% vs. 29.3%, p < .001; total fatigue: 56.5% vs. 25%, p < .001). Sex, PSQI, PSQI × sex, and PSQI × VO₂ were significant predictors for general fatigue, PSQI and PSQI × VO₂ for cognitive fatigue, and PSQI for sleep/rest and total fatigue. Cognitive and total fatigue correlated most strongly with cognitive and work-related functioning, whereas general and sleep/rest fatigue were more related to psychosocial functioning. Fatigue is highly prevalent among CCS, with distinct factors influencing general, sleep/rest, cognitive, and total fatigue. Female survivors, those with poorer sleep quality and lower physical fitness, are at risk. This study underscores the need for tailored interventions for each type of fatigue. Improving sleep quality, physical fitness, and psychological well-being may contribute to reducing fatigue and enhancing overall quality of life in CCS.

A focused review of saliva biomarkers in cognitive fatigue: Current challenges and future directions.

A focused review of saliva biomarkers in cognitive fatigue: Current challenges and future directions.

The cingulate cortex facilitates auditory perception under challenging listening conditions

We often exert greater cognitive resources (i.e., listening effort) to understand speech under challenging acoustic conditions. This mechanism can be overwhelmed in those with hearing loss, resulting in cognitive fatigue in adults and potentially impeding language acquisition in children. However, the neural mechanisms that support listening effort are uncertain. Evidence from human studies suggests that the cingulate cortex is engaged under difficult listening conditions and may exert top-down modulation of the auditory cortex (AC). Here, we asked whether the gerbil cingulate cortex (Cg) sends anatomical projections to the AC that facilitate perceptual performance. To model challenging listening conditions, we used a sound discrimination task in which stimulus parameters were presented in either "Easy" or "Hard" blocks (i.e., long or short stimulus duration, respectively). Gerbils achieved statistically identical psychometric performance in Easy and Hard blocks. Anatomical tracing experiments revealed a strong, descending projection from layer 2/3 of the Cg1 subregion of the cingulate cortex to superficial and deep layers of the primary and dorsal AC. To determine whether Cg improves task performance under challenging conditions, we bilaterally infused muscimol to inactivate Cg1 and found that psychometric thresholds were degraded for only Hard blocks. To test whether the Cg-to-AC projection facilitates task performance, we chemogenetically inactivated these inputs and found that performance was only degraded during Hard blocks. Taken together, the results reveal a descending cortical pathway that facilitates perceptual performance during challenging listening conditions.