Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC).

Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a 'reservoir'. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.

Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

Complications of Implanted Vagus Nerve Stimulation: A Systematic Review and Meta-analysis.

INTRODUCTION: Vagus Nerve Stimulation (VNS) has emerged as a promising tool in ischemic stroke rehabilitation. However, there has been no systematic review summarizing its adverse effects, critical information for patients and providers when obtaining informed consent for this novel treatment. This systematic review and meta-analysis reports the adverse effects of VNS. METHODS: A systematic review was performed in accordance with PRISMA guidelines to identify common complications after VNS therapy. The search was executed in: Cochrane Central Register of Controlled Trials, Embase, and Ovid MEDLINE. All prospective, randomized controlled trials using implanted VNS therapy in adult patients were eligible for inclusion. Case studies and studies lacking complete complication reports were excluded. Extracted data included technology name, location of implantation, follow-up duration, purpose of VNS, and adverse event rates. RESULTS: After title-and-abstract screening of 4933 studies, 21 were selected for final inclusion. Across these studies, 1474 patients received VNS implantation. VNS was used as a potential therapy for epilepsy (9), depression (8), anxiety (1), ischemic stroke (1), chronic heart failure (1), and fibromyalgia (1). The 5 most common post-implant adverse events were voice alteration/hoarseness (n=671, 45.5%), paresthesia (n = 233, 15.8%), cough (n = 221, 15.0%), dyspnea (n = 211, 14.3%), and pain (n = 170, 11.5%). CONCLUSIONS: Complications from VNS are mild and transient, with reduction in severity and number of adverse events with increasing follow-up time. In prior studies, VNS has served as treatment option in several instances of treatment-resistant conditions, such as epilepsy and psychiatric conditions, and its use in stroke recovery and rehabilitation should continue to be explored.

Vagal Nerve Stimulation: A Bibliometric Analysis of Current Research Trends.

BACKGROUND: Vagal nerve stimulation (VNS) has become established as an effective tool for the management of various neurologic disorders. Consequently, a growing number of VNS studies have been published over the past four decades. This study presents a bibliometric analysis investigating the current trends in VNS literature. MATERIALS AND METHODS: Using the Web of Science collection data base, a search was performed to identify literature that discussed applications of VNS from 2000 to 2021. Analysis and visualization of the included literature were completed with VOSviewer. RESULTS: A total of 2895 publications were identified. The number of articles published in this area has increased over the past two decades, with the most citations (7098) occurring in 2021 and the most publications (270) in 2020. The h-index, i-10, and i-100 were 97, 994, and 91, respectively, with 17.0 citations per publication on average. The highest-producing country and institution of VNS literature were the United States and the University of Texas, respectively. The most productive journal was Epilepsia. Epilepsy was the predominant focus of VNS research, with the keyword "epilepsy" having the greatest total link strength (749) in the keyword analysis. The keyword analysis also revealed two major avenues of VNS research: 1) the mechanisms by which VNS modulates neural circuitry, and 2) therapeutic applications of VNS in a variety of diseases beyond neurology. It also showed a significant prevalence of noninvasive VNS research. Although epilepsy research appears more linked to implanted VNS, headache and depression specialists were more closely associated with noninvasive VNS. CONCLUSION: VNS may serve as a promising intervention for rehabilitation beyond neurologic applications, with an expanding base of literature over the past two decades. Although epilepsy researchers have produced most current literature, other fields have begun to explore VNS as a potential treatment, likely owing to the rise of noninvasive forms of VNS.

Neural representation in M1 and S1 cortex of bilateral hand actions during prehension.

Bimanual movements that require coordinated actions of the two hands may be coordinated by synchronous bilateral activation of somatosensory and motor cortical areas in both hemispheres, by enhanced activation of individual neurons specialized for bimanual actions, or by both mechanisms. To investigate cortical neural mechanisms that mediate unimanual and bimanual prehension, we compared actions of the left and right hands in a reach to grasp-and-pull instructed-delay task. Spike trains were recorded with multiple electrode arrays placed in the hand area of primary motor (M1) and somatosensory (S1) cortex of the right hemisphere in macaques, allowing us to measure and compare the relative timing, amplitude, and synchronization of cortical activity in these areas as animals grasped and manipulated objects that differed in shape and location. We report that neurons in the right hemisphere show common task-related firing patterns for the two hands but actions of the ipsilateral hand elicited weaker and shorter-duration responses than those of the contralateral hand. We report significant bimanual activation of neurons in M1 but not in S1 cortex when animals have free choice of hand use in prehension tasks. Population ensemble responses in M1 thereby provide an accurate depiction of hand actions during skilled manual tasks. These studies also demonstrate that somatosensory cortical areas serve important cognitive and motor functions in skilled hand actions. Bilateral representation of hand actions may serve an important role in "motor equivalence" when the same movements are performed by either hand and in transfer of skill learning between the hands.NEW & NOTEWORTHY Humans can manipulate small objects with the right or left hand but typically select the dominant hand to handle them. We trained monkeys to grasp and manipulate objects with either hand, while recording neural activity in primary motor (M1) and somatosensory (S1) cortex. Actions of both hands activate M1 neurons, but S1 neurons respond only to the contralateral hand. Bilateral sensitivity in M1 may aid skill transfer between hands after stroke or head injury.

An Emotion Regulation Tablet App for Middle-Aged and Older Adults at High Suicide Risk: Feasibility, Acceptability, and Two Case Studies.

OBJECTIVE: The unique features of technological applications may improve the treatment of people at risk of suicide. In this article, we present feasibility and acceptability data as well as two case studies demonstrating the use of WellPATH, a tablet app that aims to help suicidal patients during emotionally-charged situations outside of therapy sessions. The WellPATH app was part of a 12-week psychotherapy intervention (CRISP - Cognitive Reappraisal Intervention for Suicide Prevention) for middle-aged and older adults after their discharge from a suicide-related hospitalization. DESIGN: The use of WellPATH includes three stages: preparation and practice, incorporation, and actual use. MEASUREMENTS: Feasibility was measured by the overall use of WellPATH during 12 weeks, and acceptability was measured with the three items of the Client Satisfaction Questionnaire. RESULTS: Twelve study participants were administered WellPATH as part of CRISP. The results provide preliminary evidence of feasibility and acceptability of WellPATH. Study participants and therapists reported high satisfaction with WellPATH and provided feedback for future research and development. The patients in the case studies reported a reduction in negative emotions and an increase in emotion regulation (i.e., cognitive reappraisal ability) after using techniques on the WellPATH app. CONCLUSION: Our preliminary findings suggest that use of technology applications such as the WellPATH app is feasible and accepted among middle-aged and older adults at high suicide risk. Further research with an adequately powered sample is needed to further evaluate WellPATH's feasibility and accessibility, and test its efficacy with this high-risk population.

Gamified Neurorehabilitation Strategies for Post-stroke Motor Recovery: Challenges and Advantages.

PURPOSE OF REVIEW: Stroke is the leading cause of permanent motor disability in the United States (US), but there has been little progress in developing novel, effective strategies for treating post-stroke motor deficits. The past decade has seen the rapid development of many promising, gamified neurorehabilitation technologies; however, clinical adoption remains limited. The purpose of this review is to evaluate the recent literature surrounding the adoption and use of gamification in neurorehabilitation after stroke. RECENT FINDINGS: Gamification of neurorehabilitation protocols is both feasible and effective. Deployment strategies and scalability need to be addressed with more rigor. Relationship between engaged time on task and rehabilitation outcomes should be explored further as it may create benefits beyond repetitive movement. As gamification becomes a more common and feasible way of delivering exercise-based therapies, additional benefits of gamification are emerging. In spite of this, questions still exist about scalability and widespread clinical adoption.

Remote Patient Monitoring Identifies the Need for Triage in Patients with Acute COVID-19 Infection.

Introduction: Telehealth was frequently used in the provision of care and remote patient monitoring (RPM) during the COVID-19 pandemic. The Precision Recovery Program (PRP) remotely monitored and supported patients with COVID-19 in their home environment. Materials and Methods: This was a single-center retrospective cohort study reviewing data acquired from the PRP clinical initiative. Results: Of the 679 patients enrolled in the PRP, 156 patients were screened by a clinician following a deterioration in symptoms and vital signs on a total of 240 occasions, and included in the analyses. Of these 240 occasions, 162 (67%) were escalated to the PRP physician. Thirty-six patients were referred to emergency department, with 12 (7%) admitted to the hospital. The most common risk factors coinciding with hospital admissions were cardiac (67%), age >65 (42%), obesity (25%), and pulmonary (17%). The most common symptoms reported that triggered a screening event were dyspnea/tachypnea (27%), chest pain (14%), and gastrointestinal issues (8%). Vital signs that commonly triggered a screening event were pulse oximetry (15%), heart rate (11%), and temperature (9%). Discussion: Common factors (risk factors, vital signs, and symptoms) among patients requiring screening, triage, and hospitalization were identified, providing clinicians with further information to support decision making when utilizing RPM in this cohort. Conclusion: A clinician-led RPM program for patients with acute COVID-19 infection provided supportive care and screening for deterioration. Similar models should be considered for implementation in COVID-19 cohorts and other conditions at risk of rapid clinical deterioration in the home setting.

Remote Patient Monitoring for Home Management of Coronavirus Disease 2019 in New York: A Cross-Sectional Observational Study.

Background: Coronavirus disease 2019 (COVID-19) poses a global public health emergency, overwhelming health systems worldwide and forcing rapid adoption of telemedicine strategies. Introduction: The COVID-19 Precision Recovery Program (PRP) is a remote patient monitoring (RPM) clinical program that was deployed by a New York health system to perform physiologic and symptomatic monitoring for patients with confirmed or suspected COVID-19 diagnoses. Methods: The present cross-sectional descriptive study reports retrospective data collected from the PRP during the COVID-19 crisis in New York. Results: One hundred twelve patients were included; mean (standard deviation) age was 49 (17.6) years and 60.7% were female. Most prevalent reported comorbidities were hypertension (36.3%), hypercholesterolemia (26.5%), and diabetes (17.7%). Less than half (44.6%) had a positive polymerase chain reaction COVID test (PCR-test), 33% had an unknown COVID status, and 17.9% had a negative test result. The most commonly reported symptoms included dyspnea (55.4%) and anxiety (55.4%). Anxiety was ranked as the most severe symptom (9.8%), followed by difficulty concentrating (4.5%). Symptom presentation did not significantly differ based on PCR-test status. Discussion: RPM can be a valuable tool for delivering care to patients with confirmed or suspected COVID-19 diagnoses. Considering similarities in symptom presentation between PCR-test statuses, access to COVID-related clinical care should not be based on PCR-test results. Conclusions: RPM has strong potential to assist in the effective management of suspected COVID-19 patients.

Use of Fitbit Technology Does Not Impact Health Biometrics in a Community of Older Adults.

Introduction: To evaluate if the offering of Fitbit technology led to changes in cardiovascular health metrics in a cohort of older adults. Methods: A retrospective cohort study was developed in two community-embedded health monitoring sites, located in aggregate housing communities for older adults in Westchester County, NY. Participants included older adults (55 years or older) enrolled in the Telehealth Intervention Programs for Seniors (TIPS) initiative, a community-embedded remote patient monitoring initiative. Weekly blood pressure, heart rate, weight, and blood oxygenation were taken on all participants. For participants who accepted a Fitbit Zip device, a weekly step count was also collected. Results: Ninety-four TIPS participants were offered Fitbit technology. Thirty participants accepted the technology and used it for a minimum of 6 months. No significant differences in any of the regularly acquired biometrics were noted between Fitbit users and non-Fitbit users. Across all participants, regardless of Fitbit use, there was a significant decrease in systolic blood pressure (SBP) over time. Conclusions: Neither Fitbit Zip ownership or compliance to Fitbit Zip usage influenced any of the biometrics taken as part of the TIPS. However, participation in the TIPS initiative may have an overall positive effect on SBP in older adults.

Telehealth Intervention Programs for Seniors: An Observational Study of a Community-Embedded Health Monitoring Initiative.

Background:Chronic disease in older adults is estimated to account for 84% of annual health care spending in the United States, with many preventable costs expected to rise as the population continues to age.Introduction:Telehealth Intervention Programs for Seniors (TIPS) is a community-embedded program targeting low-income older adults, providing weekly assessment of vital signs and subjective wellness, and wrap-around aging services.Materials and Methods:TIPS recruited 765 volunteers over 55 years, who were Medicaid and/or Medicare eligible. Data were collected from 2014 to 2016 [median enrollment 343 days (105-435)] using 12 TIPS sites. This observational study evaluated the efficacy of TIPS by measuring within-subject changes in self-reported hospital visits and <30-day readmissions, before and during TIPS participation. Data of 617 participants (median age 74.3; interquartile range 16) were analyzed.Results:Self-reported hospital visits were reduced by 28.9% (p = 0.0013). Medicare participants benefited the most, with a 50% (p < 0.0001) reduction in hospital visits, and a 75.5% (p = 0.017) reduction in <30-day readmissions. Multivariate analysis revealed that participants (1) Medicaid-registered (odds ratio [OR] = 2.72, 95% confidence interval [CI] 0.392-1.611), (2) reporting feeling unwell (OR = 1.33, 95% CI 0.118-0.459), and (3) living alone (OR = 2.34, 95% CI 0.115-1.592) were significantly more likely than other participants to experience a hospital visit.Discussion:TIPS demonstrates that community-embedded health services can reduce rates of hospital visits in older adults.Conclusion:The success of TIPS highlights the potential of successfully deployed remote patient-monitoring initiatives in reducing the utilization of costly health services.

Lesion Localization of Poststroke Lateropulsion.

Background and Purpose- Hemispheric stroke studies associating lateropulsion (pusher syndrome) with the location of brain lesions have had mixed results from small, unmatched samples. This study was designed to determine whether lateropulsion localizes to specific brain regions across patients with stroke using a case-control design. Methods- Fifty patients with lateropulsion after stroke were matched with 50 stroke patients without lateropulsion using age, time since onset of stroke, admission motor Functional Independence Measure score, lesion side, and gender. The primary analysis included multivariate lesion symptom mapping using sparse canonical correlations to identify regions most associated with lateropulsion as assessed with the Burke Lateropulsion Scale. Secondary analyses included evaluating paired comparisons for lesion volume, degree of motor impairment, motor and cognitive Functional Independence Measure scores. Results- The lesion symptom mapping analysis of all lesions mapped onto a common hemisphere produced an overall significant model ( P<5×10-5) with a regional peak at the inferior parietal lobe at the junction of the post-central gyrus (Brodmann Area 2) and Brodmann Area 40 as the lesion location most associated with lateropulsion. Lesion volume was larger for patients with lateropulsion. Despite adequate matching, motor performance and total Functional Independence Measure scores differed at a group level between patients with and without lateropulsion. Conclusions- This analysis implicated lesion involvement of the inferior parietal lobe as a key neuroanatomical determinant of developing lateropulsion. A better understanding of the anatomic underpinnings of lateropulsion may improve rehabilitation efforts, including the potential for informing noninvasive neuromodulation approaches.

Developing a neurobehavioral animal model of poverty: Drawing cross-species connections between environments of scarcity-adversity, parenting quality, and infant outcome.

Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social-emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional-translational research to inform interventions for at-risk families.

Cognitive Reappraisal Intervention for Suicide Prevention (CRISP) for Middle-Aged and Older Adults Hospitalized for Suicidality.

Middle-aged and older adults constitute a high suicide-risk group. Among adults aged 50 years old and older, suicide rates increased and suicide deaths almost doubled during the period from 2000 to 2015. Suicide rates are elevated for patients hospitalized for suicidality (i.e., active suicidal ideation or suicide attempt) and the 3 months post-hospitalization is the time of the highest suicide risk. Psychosocial interventions for middle-aged and older adults hospitalized for suicidality are sparse. In this article, we present the main aspects, stages, techniques and a clinical case study of Cognitive Reappraisal Intervention for Suicide Prevention (CRISP), a psychosocial intervention targeting cognitive reappraisal to reduce suicide risk in middle-aged and older adults who have been recently hospitalized for suicidal ideation or a suicide attempt. CRISP is based on the theory that hospitalization for suicidality is preceded by an emotional crisis ("perfect storm"); this emotional crisis is related to personalized (patient- and situation-specific) triggers; and identifying these personalized triggers and the associated negative emotions and providing strategies for an adaptive response to these triggers and negative emotions will reduce suicidal ideation and improve suicide prevention. CRISP therapists identify these triggers of negative emotions and use cognitive reappraisal techniques to reduce these negative emotions. The cognitive reappraisal techniques have been selected from different psychosocial interventions and the affective neuroscience literature and have been simplified for use with middle-aged and older adults. CRISP may fill a treatment need for the post-discharge high-risk period for middle-aged and older adults hospitalized for suicidality.

Negative Emotions and Suicidal Ideation during Psychosocial Treatments in Older Adults with Major Depression and Cognitive Impairment.

OBJECTIVE: To examine the relationship of negative emotions with suicidal ideation during 12 weeks of Problem Adaptation Therapy (PATH) versus Supportive Therapy of Cognitively Impaired Older Adults (ST-CI), hypothesizing that improved negative emotions are associated with reduced suicidal ideation, PATH improves negative emotions more than ST-CI, and improved negative emotions, rather than other depression symptoms, predict reduction in suicidal ideation. METHODS: In a randomized controlled trial of two home-delivered psychosocial interventions, 74 older participants (65-95 years old) with major depressive disorder and cognitive impairment were recruited in collaboration with community agencies. The sample reported less intense feelings than suicidal intention. Interventions and assessments were conducted in participants' homes. PATH focuses on improving emotion regulation, whereas ST-CI focuses on nonspecific therapeutic factors, such as understanding and empathy. Improved negative emotions were measured as improvement in Montgomery Asberg's Depression Rating Scales' (MADRS) observer ratings of sadness, anxiety, guilt, hopelessness, and anhedonia. Suicidal ideation was assessed with the MADRS Suicide Item. RESULTS: MADRS Negative Emotions scores were significantly associated with suicidal ideation during the course of treatment (F[1,165] = 12.73, p = 0.0005). PATH participants had significantly greater improvement in MADRS emotions than ST-CI participants (treatment group by time: F[1,63.2] = 7.02, p = 0.0102). Finally, improved negative emotions, between lagged and follow-up interview, significantly predicted reduction in suicidal ideation at follow-up interview (F[1, 96] = 9.95, p = 0.0022). CONCLUSION: Findings thatimprovement in negative emotions mediates reduction in suicidal ideation may guide the development of psychosocial interventions for reduction of suicidal ideation (clinicaltrials.gov; NCT00368940).

Quantifying Poststroke Apathy With Actimeters.

The authors tested the hypothesis that wrist-worn actimeters can quantify the severity of poststroke apathy. The authors studied 57 patients admitted to an acute rehabilitation unit for ischemic or hemorrhagic stroke. After accounting for motor deficit of the affected arm and accounting for age, each increment of the Apathy Inventory score correlated with 5.6 fewer minutes of moving per hour. The overall statistical model had an R(2) of only 0.34, suggesting unexplained factors for total movement time. Wrist-worn actimeters may serve as an objective, quantifiable measure of poststroke apathy in patients with an intact upper extremity but cannot be used alone to diagnose apathy.

Dynamic cortical lateralization during olfactory discrimination learning.

Bilateral cortical circuits are not necessarily symmetrical. Asymmetry, or cerebral lateralization, allows functional specialization of bilateral brain regions and has been described in humans for such diverse functions as perception, memory and emotion. There is also evidence for asymmetry in the human olfactory system, although evidence in non-human animal models is lacking. In the present study, we took advantage of the known changes in olfactory cortical local field potentials that occur over the course of odour discrimination training to test for functional asymmetry in piriform cortical activity during learning. Both right and left piriform cortex local field potential activities were recorded. The results obtained demonstrate a robust interhemispheric asymmetry in anterior piriform cortex activity that emerges during specific stages of odour discrimination learning, with a transient bias toward the left hemisphere. This asymmetry is not apparent during error trials. Furthermore, functional connectivity (coherence) between the bilateral anterior piriform cortices is learning- and context-dependent. Steady-state interhemispheric anterior piriform cortex coherence is reduced during the initial stages of learning and then recovers as animals acquire competent performance. The decrease in coherence is seen relative to bilateral coherence expressed in the home cage, which remains stable across conditioning days. Similarly, transient, trial-related interhemispheric coherence increases with task competence. Taken together, the results demonstrate transient asymmetry in piriform cortical function during odour discrimination learning until mastery, suggesting that each piriform cortex may contribute something unique to odour memory.