Psychological/behavioral interventions for emerging adults with chronic pain.

Background: Emerging adults, of whom significant numbers report chronic pain, are characterized as having unique needs and challenges. Psychological/behavioral treatments found to be beneficial for reducing pain outcomes in children and adults are understudied in emerging adults. Following a systematic review of the literature, our objective is to report on quantitative studies of psychological/behavioral interventions for chronic pain in emerging adults. Method: We conducted a search of six databases (Cochrane Central Register of Controlled Trials, Google Scholar, ProQuest, PsycINFO, PubMed, and Web of Science) and reference sections in dissertations and systematic reviews to 4/29/2023. Keywords and phrases were search term combinations of "chronic/persistent pain", "emerging/young adults," and "intervention/treatment" using Boolean logic. Results: Our review resulted in identifying 37 articles, of which 2 duplicates were removed, and 31 were further excluded by a screening process based on various inclusionary and exclusionary criteria. The search yielded four studies on psychological/behavioral interventions (yoga, acceptance and commitment therapy and relaxation), all of which positively affected the pain experience and/or pain-related outcomes. These studies presented issues in design such as not being blinded or randomized, having a small sample size, and potential confounds that were not reported or examined. Discussion: The low number of studies reveals a large gap in the literature and is a call-to-action to further expand our understanding of effective and safer psychological/behavioral therapies for chronic pain in emerging adults. Successful pain management during this developmental phase may help young adults achieve positive trajectories for personal, occupational, relational, and health aspects of their lives.

Effect of nailing technique on length of stay in isolated ballistic femoral shaft fractures.

PURPOSE: The purpose of this study was to investigate length of stay, postoperative mobilization and discharge disposition following intramedullary nailing of ballistic femoral shaft fractures stratified by nailing technique. METHODS: All adult patients with isolated ballistic femoral shaft fractures between May 1, 2018, and September 1, 2021, were reviewed. The final cohort included 69 ballistic femur fractures in 69 patients. Of the 69 patients included, 29 were treated with retrograde nailing while 40 were treated with antegrade nailing. RESULTS: The average length of stay of patients treated with antegrade nailing was 2.55 days (SD 1.3 days) compared with 3.45 days (SD 2.3 days) for patients treated with retrograde nailing; this was statistically significant (P = 0.04). Median steps on POD1 for antegrade nailing were 20 and 8 for retrograde. There was no significant difference in VAS pain scores between the two cohorts. All patients were discharged home. CONCLUSION: The average length of stay for patients who underwent antegrade nailing was significantly shorter when compared with the retrograde nailing. Patients in the antegrade cohort mobilized further than the retrograde cohort in the immediate postoperative setting. We found no significant difference in VAS pain scores between the two cohorts.

Epidemiology of high-energy blunt pelvic ring injuries: A three-year retrospective case series in a level-I trauma center.

BACKGROUND: High-energy pelvic ring injuries (PRI) represent a heavy burden for institutions treating severely injured patients. Epidemiological data knowledge may help to provide them appropriate management. Only two epidemiologic studies about high-energy PRI were published during last decade. This study aimed to determine the gender-specific and global incidences of high-energy blunt AO/OTA type B or C PRI and their frequency among high-energy blunt trauma. It further reports the spectrum of these injuries and compares their characteristics and outcomes to high-energy blunt trauma without type B or C PRI. HYPOTHESIS: Type B or C PRI incidence isn't gender specific and approximates 5/100,000/year. PATIENTS AND METHODS: A prospective database of a level-I trauma center serving approximately 500,000 inhabitants was retrospectively queried for all high-energy trauma patients injured between 01.01.2014 and 12.31.2016. Inclusion criteria were: alive emergency department delivery; entire acute treatment at the authors' institution; age >16. Exclusion criteria were: penetrating, blast, burn and electrical injuries; drownings; low-energy trauma; patients living outside the institution's catchment area. Three authors performed PRI classifications. Clinical data were extracted from the database. RESULTS: We analyzed 434 patients. High-energy blunt type B or C PRI incidence was 3.8/100,000/year without gender disparity (p=0.6697). High-energy blunt trauma incidence was lower in women than in men (20.5 vs. 51.6/100,000/year, p<0.001). Type B or C PRI frequency during high-energy blunt trauma was higher in women than in men (17.6% vs. 7.9%, p=0.003). Type B or C PRI patients were more severely injured and needed more treatment resources than other high-energy blunt trauma patients but didn't present higher complication or death rates. DISCUSSION: The incidence of high-energy blunt type B or C PRI was comparable to previously published data. Women were less likely to sustain a high-energy blunt trauma, but when they sustained one, they were more likely to have a type B or C PRI. Despite higher injury severity score and resource requirements, complication and death rates weren't different between type B or C PRI patients and other high-energy blunt trauma patients. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Unplanned intubation after total hip and total knee arthroplasty: Assessing preoperative risk factors.

OBJECTIVE: The purpose of this study is to assess preoperative patient attributes as risk factors for unplanned intubation after primary total knee and total hip arthroplasty. METHODS: This was a retrospective analysis of data collected from the National Surgical Quality Improvement Program (NSQIP) database. Patients undergoing Total Hip Arthroplasty (THA) or Total Knee Arthroplasty (TKA) who experienced postoperative intubation were included in the study. A multivariate regression was used to assess preoperative characteristics as risk factors for postoperative intubation. RESULTS: Multivariate regression determined that perioperative transfusion of packed RBC's, cardiac comorbidities, patients older than 73, dyspnea with moderate exertion, dyspnea while at rest, diabetes mellitus requiring medical therapy, pulmonary comorbidities, current dialysis usage, body mass index greater than 29.9, and current smoker within the last year were variables associated with an increased risk of unplanned intubation after THA. Additionally, multivariate regression determined that anemia, perioperative transfusion of packed RBC's, cardiac comorbidities, patients older than 73, dyspnea with moderate exertion, diabetes mellitus requiring medical therapy, pulmonary comorbidities, and current dialysis usage were associated with unplanned intubation after TKA. CONCLUSION: This study identifies numerous risk factors for intubation after THA or TKA.

Risk Factors for Wound Complication following Primary Total Hip Arthroplasty.

This study assessed the National Surgical Quality Improvement Program (NSQIP), which provides data on 30-day post-operative complications from 500+ institutions, to identify risk factors for wound complications in patients undergoing primary total hip arthroplasty (THA). Patients undergoing primary THA between 2010-2017 were retrospectively reviewed. Patients experiencing post-operative wound complications were stratified based on pre-operative characteristics. Multivariate regression model was used to assess these characteristics as independent risk factors for post-operative complications. Of 119,096 patients undergoing primary THA, 1,264 (1.06%), 280 (0.2%), 622 (0.52%) and 139 (0.12%) experienced wound complications, deep surgical site infection, superficial surgical site infection, and wound dehiscence, respectively. Pre-operative transfusion (p < 0.0001), steroid use (p = 0.01), and obesity (p < 0.0001) were risk factors for wound dehiscence. Pre-operative transfusion (p < 0.0001), cardiac comorbidities (p = 0.02), and steroid use (p = 0.01) were risk factors for superficial surgical site infection. Assessment of the NSQIP identified modifiable risk factors for wound complications following primary THA, including pre-operative transfusion, steroid use, and obesity. (Journal of Surgical Orthopaedic Advances 31(4):242-247, 2022).

Autonomous lumbar spine pedicle screw planning using machine learning: A validation study.

INTRODUCTION: Several techniques for pedicle screw placement have been described including freehand techniques, fluoroscopy assisted, computed tomography (CT) guidance, and robotics. Image-guided surgery offers the potential to combine the benefits of CT guidance without the added radiation. This study investigated the ability of a neural network to place lumbar pedicle screws with the correct length, diameter, and angulation autonomously within radiographs without the need for human involvement. MATERIALS AND METHODS: The neural network was trained using a machine learning process. The method combines the previously reported autonomous spine segmentation solution with a landmark localization solution. The pedicle screw placement was evaluated using the Zdichavsky, Ravi, and Gertzbein grading systems. RESULTS: In total, the program placed 208 pedicle screws between the L1 and S1 spinal levels. Of the 208 placed pedicle screws, 208 (100%) had a Zdichavsky Score 1A, 206 (99.0%) of all screws were Ravi Grade 1, and Gertzbein Grade A indicating no breech. The final two screws (1.0%) had a Ravi score of 2 (<2 mm breech) and a Gertzbein grade of B (<2 mm breech). CONCLUSION: The results of this experiment can be combined with an image-guided platform to provide an efficient and highly effective method of placing pedicle screws during spinal stabilization surgery.

Preoperative risk factors for postoperative pneumonia following primary Total Hip and Knee Arthroplasty.

BACKGROUND: The purpose of this study is to evaluate risk factors for pneumonia following THA and TKA. METHODS: Patients were identified from the American College of Surgeons National Quality Improvement Database (NSQIP) who experienced postoperative pneumonia after undergoing primary THA and TKA. RESULTS: Many characteristics including old age, anemia, diabetes, cardiac comorbidities, dialysis, and smoking were independent risk factors for postoperative pneumonia after THA or TKA. CONCLUSION: This analysis offers new evidence on risk factors associated with the development of pneumonia after THA and TKA. These risk factors can help guide clinicians in preventing postoperative pneumonia after THA and TKA.

Inter- and intraobserver reliability assessment of the 2018 AO/OTA classification for high-energy pelvic ring injuries: A retrospective study.

BACKGROUND: A fracture classification system should be a reliable and reproducible means of communication between different observers. It should be logical, comprehensible, and shouldn't contain an unmanageable number of categories. The aim of this study was to assess the intra- and interobserver agreement and reliability of the revised 2018 AO/OTA classification for high-energy pelvic ring injuries (PRI), at the level of the types, groups, subgroups and qualifications. HYPOTHESIS: Agreement and reliability of the revised 2018 AO/OTA classification for high-energy PRI are improved when compared to previous versions of the classification. PATIENTS AND METHODS: Plain radiographs and computed tomography images of a consecutive series of 86 adult patients admitted at a level I trauma center with a high-energy PRI between 01.01.2014 and 31.12.2016 were retrospectively analyzed. Three orthopedic surgeons independently classified these PRI using the 2018 AO/OTA and the Young and Burgess classifications. The senior surgeon analyzed all injuries twice, at 6 months interval, to determine intraobserver reliability. Classification agreement was assessed using percent agreement and classification reliability was assessed using kappa coefficients. RESULTS: For the intraobserver analysis, injury classifications with the 2018 AO/OTA classification were concordant in 88% of cases (type), 74% (group), 66% (subgroup) and 49% (qualification). Respective kappa coefficients were 0.79, 0.68, 0.62 and 0.47. Interobserver agreement declined from 77% (type) to 42% (group), 36% (subgroup) and 24% (qualification). Respective kappa coefficients were 0.72, 0.48, 0.48 and 0.37. Intraobserver (respectively interobserver) percent agreement with the Young and Burgess classification was 76% (50%) and kappa coefficient was 0.69 (0.51). DISCUSSION: The 2018 AO/OTA classification is a reliable tool for daily clinical use and for research purpose at the fracture type level but not at the group, subgroup and qualification levels. These results compare favorably with previously published data for older versions of the classification and may represent an improvement of the AO/OTA classification system in terms of reliability. LEVEL OF EVIDENCE: III; retrospective diagnostic study.

Incidence rate and topography of intra-pelvic arterial lesions associated with high-energy blunt pelvic ring injuries: a retrospective cohort study.

BACKGROUND: The aim of this study was to determine the rate and topography of intra-pelvic arterial lesions associated with high-energy blunt pelvic ring injuries (PRI). METHODS: This retrospective cohort study was conducted in a level I trauma center serving 500,000 inhabitants. A total of 127 consecutive patients with high-energy blunt PRI were included between January 1st, 2014 and December 31st, 2017. Every patient had a total body or thoraco-abdominal computed tomography scan including contrast enhanced arterial sequences. A board-certified radiologist reviewed all the vascular images and precisely described every intra-pelvic arterial lesion in terms of localization. Complete pelvic series (standard radiographs and fine cut computed tomography images) were reviewed by three board-certified orthopedic surgeons experienced in PRI management, and Young and Burgess and AO/OTA classifications were determined. Demographic, clinical, therapeutic and outcome data were extracted from the institutional severely injured patients' registry. RESULTS: Patients' mean age was 45.3 years and 58.3% were males. Fifteen (11.8%) had a total of 21 intra-pelvic arterial lesions: seven lesions of the obturator artery, four of the superior gluteal artery, three of the inferior gluteal artery, two of the vesical artery, and one of each of the following arteries: internal iliac, internal pudendal, fifth lumbar, lateral sacral, ilio-lumbar. These lesions occurred in 8.6% of lateral compression injuries, 33.3% of anteroposterior compression injuries and 23.5% of vertical shear and combined mechanism injuries (Young and Burgess classification, p = 0.003); and in 0% of type A injuries, 9.9% of type B injuries and 35% of type C injuries (AO/OTA classification, p = 0.001). Patients with an intra-pelvic arterial lesion were more likely to present with pre-hospital hemodynamic instability (p = 0.046) and to need packed red blood cells transfusion within the first 24 h (p = 0.023; they needed a mean of 7.53 units vs. 1.88, p = 0.0016); however, they did not have a worst outcome in terms of complications or mortality. CONCLUSIONS: This systematic study found an 11.8% rate of intra-pelvic arterial lesion related to high-energy blunt PRI. The obturator, superior gluteal and inferior gluteal arteries were most often injured. These findings are important for the aggressive management of high-energy blunt PRI.

Changes in femoral offset is not associated with increased incidence of lateral hip pain following total hip arthroplasty.

PURPOSE: Increased femoral offset following total hip arthroplasty allows for greater stability of the hip joint. However, the increase in femoral offset can cause an impingement of local structures resulting in persistent lateral hip pain. There is conflicting evidence whether changes in femoral offset increases the rates of lateral hip pain following total hip arthroplasty. METHODS: This was a retrospective case control study that grouped patients based on the presence of persistent lateral hip pain following total hip arthroplasty. Patients were then stratified according to their change in femoral offset (<-5 mm, -5 mm < x < 5 mm, and 5 mm<). A chi squared analysis was then performed to see if there was a statistical difference in the rates of lateral hip pain amongst these groups. RESULTS: A change in femoral offset of the implanted hip relative to the native hip was not associated with increased rates of lateral hip pain following total hip arthroplasty (p = 0.35). A change in femoral offset of the implanted hip relative to the contralateral hip was not associated with increased rates of lateral hip pain following total hip arthroplasty (p = 0.40). CONCLUSION: This study found that there was no association between increased femoral offset and rates of postoperative lateral hip pain following total hip arthroplasty. Future investigations should look at a larger sample size with multiple institutions to further assess the impact on femoral offset changes on rates of persistent lateral hip pain.

Preoperative risk factors for postoperative cardiac arrest following primary total hip and knee arthroplasty: A large database study.

BACKGROUND: Cardiac arrest (CA) has been identified as a potential complication following Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA). This retrospective, case-controlled study aims to identify risk factors in order to improve the management of patients undergoing THA or TKA with known preoperative comorbidities. METHODS: CPT codes were used to investigate the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for patients who underwent THA or TKA from 2010 to 2017. Patients were classified as having cardiac arrest (CA) by the NSQIP guidelines. Patient samples with all possible covariates were included for the multivariate logistic regression analysis and assessed for independent association. RESULTS: Patients receiving perioperative transfusion, experiencing dyspnea with moderate exertion, dyspnea at rest, patients currently on dialysis, and patients aged ≥72 are all independently associated with increased rates of cardiac arrest (CA) following THA. Patients receiving perioperative transfusion, patients with anemia, bleeding disorders, dyspnea with moderate exertion, cardiac comorbidities, pulmonary comorbidities, and patients aged ≥73 are all associated with increased rates of cardiac arrest (CA) following TKA. CONCLUSION: Patients with the identified risk factors are at a greater risk of suffering cardiac arrest within 30 days following THA and TKA. It is imperative that we recognize which risk factors may precipitate CA in THA and TKA recipients so that prophylactic management can be employed. Furthermore, management guidelines should be updated for patients at high risk of CA following THA and TKA to prevent this complication.

Preoperative Risk Factors for Postoperative Urinary Tract Infection After Primary Total Hip and Knee Arthroplasties.

BACKGROUND: Establishing clear risk factors for complications such as urinary tract infection (UTI) after arthroplasty procedures helps guide clinical practice and provides more information to both surgeons and patients. This study aims to assess selected preoperative patient characteristics as risk factors for postoperative UTI after primary total hip and knee arthroplasties (THA and TKA). METHODS: This was a retrospective analysis using current procedural terminology codes to investigate the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database for patients who underwent THA or TKA from 2010 to 2017. Patients were classified for UTI by NSQIP guidelines. Patient samples with all possible covariates were included for multivariate logistic regression analysis and assessed for independent associations. RESULTS: In a cohort of 983 identified patients (983 of 119,096; 0.83%): ages 57+ years, preoperative red blood cell (RBC) transfusion, perioperative RBC transfusion, bleeding disorders, operative time 110+ minutes, preoperative steroid use, diabetes, pulmonary comorbidities, body mass index 30+ kg/m2 were independent risk factors for postoperative UTI after THA. In a cohort of 1503 identified patients (1503 of 189,327; 0.8%): ages 60+ years, preoperative RBC transfusion, perioperative RBC transfusion, anemia, platelets less than 150k, preoperative steroid use, diabetes, and body mass index 30+ kg/m2 were independent risk factors for postoperative UTI after TKA. Male sex was associated with a decreased risk of UTI in both THA and TKA. CONCLUSION: This study provides novel evidence on risk factors associated with the development of UTI after THA or TKA. Clinicians should be aware of risk factors in the manifestation of postoperative UTI after primary THA or TKA procedures.

Dynamic Changes in EEG Power Spectral Densities During NIH-Toolbox Flanker, Dimensional Change Card Sort Test and Episodic Memory Tests in Young Adults.

Much is known about electroencephalograph (EEG) patterns during sleep, but until recently, it was difficult to study EEG patterns during conscious, awake behavior. Technological advances such as powerful wireless EEG systems have led to a renewed interest in EEG as a clinical and research tool for studying real-time changes in the brain. We report here the first normative study of EEG activity while healthy young adults completed a series of cognitive tests recently published by the National Institutes of Health Toolbox Cognitive Battery (NIH-TCB), a commonly-used standardized measure of cognition primarily used in clinical populations. In this preliminary study using a wireless EEG system, we examined power spectral density (PSD) in four EEG frequency bands. During baseline and cognitive testing, PSD activity for the lower frequency bands (theta and alpha) was greater, relative to the higher frequency bands (beta and gamma), suggesting participants were relaxed and mentally alert. Alpha, beta and gamma activity was increased during a memory test compared to two other, less demanding executive function tests. Gamma activity was also inversely correlated with performance on the memory test, consistent with the neural efficiency hypothesis which proposes that better cognitive performance may link with lower cortical energy consumption. In summary, our study suggests that cognitive performance is related to the dynamics of EEG activity in a normative young adult population.

Impaired cerebellar plasticity and eye-blink conditioning in calpain-1 knock-out mice.

Calpain-1 and calpain-2 are involved in the regulation of several signaling pathways and neuronal functions in the brain. Our recent studies indicate that calpain-1 is required for hippocampal synaptic plasticity, including long-term depression (LTD) and long-term potentiation (LTP) in field CA1. However, little is known regarding the contributions of calpain-1 to cerebellar synaptic plasticity. Low frequency stimulation (LFS, 5 Hz, 5 min)-induced LTP at parallel fibers to Purkinje cell synapses was markedly impaired in cerebellar slices from calpain-1 knock-out (KO) mice. Application of a selective calpain-2 inhibitor enhanced LFS-induced LTP in both wild-type (WT) and calpain-1 KO mice. Three protocols were used to induce LTD at these synapses: LFS (1 Hz, 15 min), perfusion with high potassium and glutamate (K-Glu) or dihydroxyphenylglycine (DHPG), a mGluR1 agonist. All three forms of LTD were impaired in calpain-1 KO mice. DHPG application stimulated calpain-1 but not calpain-2 in cerebellar slices, and DHPG-induced LTD impairment was reversed by application of a protein phosphatase 2A (PP2A) inhibitor, okadaic acid. As in hippocampus, BDNF induced calpain-1 activation and PH domain and Leucine-rich repeat Protein Phosphatase 1/suprachiasmatic nucleus oscillatory protein (PHLPP1/SCOP) degradation followed by extracellular signal-regulated kinase (ERK) activation, as well as calpain-2 activation leading to degradation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in cerebellar slices. The role of calpain-1 in associative learning was evaluated in the delay eyeblink conditioning (EBC). Calpain-1 KO mice exhibited significant learning impairment in EBC during the first 2 days of acquisition training. However, after 5 days of training, the percentage of conditioned responses (CRs) between calpain-1 KO and WT mice was identical. Both calpain-1 KO and WT mice exhibited typical extinction patterns. Our results indicate that calpain-1 plays critical roles in multiple forms of synaptic plasticity and associative learning in both hippocampus and cerebellum.

Tracking Lithium Ions via Widefield Fluorescence Microscopy for Battery Diagnostics.

Direct tracking of lithium ions with time and spatial resolution can provide an important diagnostic tool for understanding mechanisms in lithium ion batteries. A fluorescent indicator of lithium ions, 2-(2-hydroxyphenyl)naphthoxazole, was synthesized and used for real-time tracking of lithium ions via widefield fluorescence microscopy. The fluorophore can be excited with visible light and was shown to enable quantitative determination of the lithium ion diffusion constant in a microfluidic model system for a plasticized polymer electrolyte lithium battery. The use of widefield fluorescence microscopy for in situ tracking of lithium ions in batteries is discussed.

The search for the engram in eyeblink conditioning: A synopsis of past and present perspectives on the role of the cerebellum.

One of the most prolific behavioral neuroscientists of his generation, Richard F. Thompson published more than 450 research articles during his almost 60-year career before his death in 2014. The breadth and reach of his scholarship has extended to a large multidisciplinary audience of scientists. The focal point of this article is arguably his most influential paper on cerebellar classical conditioning entitled "The Neurobiology of Learning and Memory" that appeared in Science in 1986 and has been cited 700 times since its publication. Here, a summary of the initial Thompson laboratory research leading up to an understanding of the cerebellum and its critical role in memory traces will be discussed, along with conclusions from the Science article pertinent to cerebellar classical conditioning. The summary will also discuss how the original 1986 article continues to stimulate and influence new research and provide further insights into the role of the cerebellum in the neurobiology of learning and memory function relevant to studies of mammalian classical conditioning. (PsycINFO Database Record

Ovarian hormones, aging and stress on hippocampal synaptic plasticity.

The ovarian steroid hormones estradiol and progesterone regulate a wide variety of non-reproductive functions in the central nervous system by interacting with molecular and cellular processes. A growing literature from studies using rodent models suggests that 17ß-estradiol, the most potent of the biologically relevant estrogens, enhances synaptic transmission and the magnitude of long-term potentiation recorded from in vitro hippocampal slices. In contrast, progesterone has been shown to decrease synaptic transmission and reduce hippocampal long-term potentiation in this model system. Hippocampal long-term depression, another form of synaptic plasticity, occurs more prominently in slices from aged rats. A decrease in long-term potentiation magnitude has been recorded in hippocampal slices from both adult and aged rats behaviorally stressed just prior to hippocampal slice tissue preparation and electrophysiological recording. 17ß-estradiol modifies synaptic plasticity in both adult and aged rats, whether behaviorally stressed or not by enhancing long-term potentiation and attenuating long-term depression. The studies discussed in this review provide an understanding of new approaches used to investigate the protective effects of ovarian hormones against aging and stress, and how these hormones impact age and stress-related learning and memory dysfunction.

Regulation of hippocampal synaptic plasticity by estrogen and progesterone.

Accumulating evidence indicates that the ovarian steroid hormones estrogen and progesterone regulate a wide variety of nonreproductive functions in the central nervous system by interacting with several molecular and cellular processes. A growing literature reporting results obtained in rodent models suggests that 17beta-estradiol, the most potent of the biologically relevant estrogens, facilitates some forms of learning and memory, and in particular, those involving hippocampus-dependent tasks. Hippocampal long-term potentiation and long-term depression of synaptic transmission are types of synaptic plasticity that have been extensively studied, as they are considered as cellular models of memory formation in the brain. In this chapter, we review the literature that analyzes and compares the effects of estrogen and progesterone on synaptic transmission and synaptic plasticity in rodents. Understanding the nonreproductive functions of estrogen and progesterone in the hippocampus has far-reaching implications not only for our basic understanding of neuroendocrinology and neurobiology, but also for developing better treatment of age-related diseases such as Alzheimer's disease.

Differential effects and rates of normal aging in cerebellum and hippocampus.

Cognitive functions show many alternative outcomes and great individual variation during normal aging. We examined learning over the adult life span in CBA mice, along with morphological and electrophysiological substrates. Our aim was to compare cerebellum-dependent delay eyeblink classical conditioning and hippocampus-dependent contextual fear conditioning in the same animals using the same conditioned and unconditioned stimuli for eyeblink and fear conditioning. In a subset of the behaviorally tested mice, we used unbiased stereology to estimate the total number of Purkinje neurons in cerebellar cortex and pyramidal neurons in the hippocampus. Several forms of synaptic plasticity were assessed at different ages in CBA mice: long-term depression (LTD) in both cerebellum and hippocampus and NMDA-mediated long-term potentiation (LTP) and voltage-dependent calcium channel LTP in hippocampus. Forty-four CBA mice tested at one of five ages (4, 8, 12, 18, or 24 months) demonstrated statistically significant age differences in cerebellum-dependent delay eyeblink conditioning, with 24-month mice showing impairment in comparison with younger mice. These same CBA mice showed no significant differences in contextual or cued fear conditioning. Stereology indicated significant loss of Purkinje neurons in the 18- and 24-month groups, whereas pyramidal neuron numbers were stable across age. Slice electrophysiology recorded from an additional 48 CBA mice indicated significant deficits in LTD appearing in cerebellum between 4 and 8 months, whereas 4- to 12-month mice demonstrated similar hippocampal LTD and LTP values. Our results demonstrate that processes of aging impact brain structures and associated behaviors differentially, with cerebellum showing earlier senescence than hippocampus.