The clock gene Per1 may exert diurnal control over hippocampal memory consolidation.

The circadian system influences many different biological processes, including memory performance. While the suprachiasmatic nucleus (SCN) functions as the brain's central pacemaker, downstream "satellite clocks" may also regulate local functions based on the time of day. Within the dorsal hippocampus (DH), for example, local molecular oscillations may contribute to time-of-day effects on memory. Here, we used the hippocampus-dependent Object Location Memory task to determine how memory is regulated across the day/night cycle in mice. First, we systematically determined which phase of memory (acquisition, consolidation, or retrieval) is modulated across the 24 h day. We found that mice show better long-term memory performance during the day than at night, an effect that was specifically attributed to diurnal changes in memory consolidation, as neither memory acquisition nor memory retrieval fluctuated across the day/night cycle. Using RNA-sequencing we identified the circadian clock gene Period1 (Per1) as a key mechanism capable of supporting this diurnal fluctuation in memory consolidation, as learning-induced Per1 oscillates in tandem with memory performance in the hippocampus. We then show that local knockdown of Per1 within the DH impairs spatial memory without affecting either the circadian rhythm or sleep behavior. Thus, Per1 may independently function within the DH to regulate memory in addition to its known role in regulating the circadian system within the SCN. Per1 may therefore exert local diurnal control over memory consolidation within the DH.

The clock gene Per1 is necessary in the retrosplenial cortex-but not in the suprachiasmatic nucleus-for incidental learning in young and aging male mice.

Aging impairs both circadian rhythms and memory, though the relationship between these impairments is not fully understood. Circadian rhythms are largely dictated by clock genes within the body's central pacemaker, the suprachiasmatic nucleus (SCN), though these genes are also expressed in local clocks throughout the body. As circadian rhythms can directly affect memory performance, one possibility is that memory deficits observed with age are downstream of global circadian rhythm disruptions stemming from the SCN. Here, we demonstrate that expression of clock gene Period1 within a memory-relevant cortical structure, the retrosplenial cortex (RSC), is necessary for incidental learning, and that age-related disruption of Period1 within the RSC-but not necessarily the SCN-contributes to cognitive decline. These data expand the known functions of clock genes beyond maintaining circadian rhythms and suggests that age-associated changes in clock gene expression modulates circadian rhythms and memory performance in a brain region-dependent manner.

Anxiety, Depression, and Trauma Among Immigrant Mexican Women up to Two-Years Post-partum.

Anxiety has significant consequences for maternal and infant health, and Mexican immigrant mothers are at significantly high-risk. This study examined whether maternal depressive symptoms and trauma are related to anxiety symptoms in perinatal Mexican immigrants. Data were collected from 103 Mexican women residing in the Midwestern United States who were pregnant or up to two years postpartum. Half were aged 30-34. The majority had two or more children and low socio-economic status. Linear regression analyses predicted current anxiety symptoms from current maternal depression symptoms, trauma history, and socio-demographics. Anxiety symptoms were significantly related to depressive symptoms (B = 0.87, 95% CI 0.73, 1.01) and trauma. Compared to women with no trauma history, women who experienced more than ten traumas had increased anxiety symptoms (B = 7.15, 95% CI 0.34, 13.96). Perinatal Mexican women with higher depression symptoms and trauma have increased anxiety symptoms, increasing the need for more comprehensive screening.

Rats with ventral hippocampal damage are impaired at various forms of learning including conditioned inhibition, spatial navigation, and discriminative fear conditioning to similar contexts.

The ventral hippocampus (vHPC) has been implicated in learning and memory functions that seem to differ from its dorsal counterpart. The goal of this series of experiments was to provide further insight into the functional contributions of the vHPC. Our previous work implicated the vHPC in spatial learning, inhibitory learning, and fear conditioning to context. However, the specific role of vHPC on these different forms of learning are not clear. Accordingly, we assessed the effects of neurotoxic lesions of the ventral hippocampus on retention of a conditioned inhibitory association, early versus late spatial navigation in the water task, and discriminative fear conditioning to context under high ambiguity conditions. The results showed that the vHPC was necessary for the expression of conditioned inhibition, early spatial learning, and discriminative fear conditioning to context when the paired and unpaired contexts have high cue overlap. We argue that this pattern of effects, combined with previous work, suggests a key role for vHPC in the utilization of broad contextual representations for inhibition and discriminative memory in high ambiguity conditions.

Gradual Cerebral Hypoperfusion Impairs Fear Conditioning and Object Recognition Learning and Memory in Mice: Potential Roles of Neurodegeneration and Cholinergic Dysfunction.

In the present study, male C57BL/6J mice were subjected to gradual cerebral hypoperfusion by implanting an ameroid constrictor (AC) on the left common carotid artery (CCA) and a stenosis on the right CCA. In the sham group, all surgical procedures were kept the same except no AC was implanted and stenosis was not performed. One month following the surgical procedures, fear conditioning and object recognition tests were conducted to evaluate learning and memory functions and motor functions were assessed using a balance beam test. At the experimental endpoint, mice were perfused and brains were collected for immunostaining and histology. Learning and memory as well as motor functions were significantly impaired in the hypoperfusion group. The immunoreactivity to choline acetyltransferase was decreased in dorsal striatum and basal forebrain of the hypoperfusion group indicating that cholinergic tone in these brain regions was compromised. In addition, an increased number of Fluoro-Jade positive neurons was also found in cerebral cortex, dorsal striatum and hippocampus indicating neurodegeneration in these brain regions. Based on this pattern of data, we argued that this mouse model would be a useful tool to investigate the therapeutic interventions for the treatment of vascular dementia. Additionally, this model could be employed to exploit the effect of microvascular occlusions on cognitive impairment in the absence and presence of Alzheimer's disease pathology.

Returning Adolescents to Driving after Sports-Related Concussions: What Influences Physician Decision-Making.

OBJECTIVE: To determine which data collected on an initial patient clinic visit for a sports-related concussion (SRC) might influence physicians to clear an adolescent to return to drive (RTD) after injury. STUDY DESIGN: Retrospective cohort study of 189 adolescents with a SRC referred to a hospital-based concussion clinic between June 1, 2015, and May 31, 2016. Subjects were ≥16 years with a valid driver's license (median age = 16, IQR [16, 17]). Concussion evaluations included Post-Concussion Symptom Scale, modified Balance Error Scoring System, and postinjury computerized neurocognitive testing (CNT). Clearance for RTD was the main outcome. Statistical comparisons were conducted with Mann-Whitney U and χ2 tests and logistic regression. RESULTS: In multivariable analysis, odds of being fully cleared to drive were 5.9-fold greater among patients who were administered CNT. Stated symptoms of "headache" and "sensitivity to light" were statistically significantly associated with RTD clearance. For a subset of 113 individuals undergoing CNT, each additional 10-millisecond decrease in simple reaction time was associated with 9% greater odds of being cleared to drive. Each additional 10-millisecond decrease in choice reaction time was associated with 4% greater odds of being cleared to drive. CONCLUSIONS: CNT and associated reaction time measures may facilitate a physician's objective decision-making. Making a RTD determination for adolescents recovering from an SRC should be a core component of a physician's assessment.

Musculoskeletal Low Back Pain in School-aged Children: A Review.

Importance: Low back pain (LBP) in children and adolescents is a common problem. The differential diagnosis of LBP in this population is broad and different from that seen in the adult population. Most causes of LBP are musculoskeletal and benign in their clinical course. Clinicians should have an understanding of the relevant anatomy and the most commonly encountered etiologic factors of LBP in children and adolescents to provide effective care. Observations: Low back pain is rarely seen in youth before they reach school age. Subsequently, rates of LBP rise until age 18 years, at which age the prevalence of LBP is similar to that in adults. The differential diagnosis of LBP in this population is broad, and individual etiologic factors are most often associated with musculoskeletal overuse or trauma. Sinister etiologic factors are rare. The patient's history and physical examination are the foundation of evaluating a child with LBP. The indication for and timing of specific imaging or other studies will vary depending on the etiologic factor of concern. Most treatment of LBP in this population is centered on relative rest, rehabilitation, and identification of predisposing risk factors. Pharmacologic treatment may be used but is typically a brief course. Orthopedic, rheumatologic, and other subspecialty referrals may be considered when indicated, but most of these patients can be managed by a general pediatrician with a good understanding of the principles described in this article. Conclusions and Relevance: Low back pain in children and adolescents is a common problem. It is most often nonspecific, musculoskeletal, and self-limiting. Pediatricians should recognize the importance of a proper history, physical examination, and general knowledge of the lumbar spine and pelvic anatomy relevant to the child in their evaluation with this presenting symptom.

Return to Drive Counseling After Sports-Related Concussion: A Quality Improvement Project.

INTRODUCTION: Concussion is a common injury in adolescent athletes, many of whom also drive. Counseling athletes and their families about driving risks post concussion is a potentially significant intervention. The aim of this quality improvement project was to increase driving recommendations for concussed athletes in a pediatric sports medicine clinic. METHODS: Patients in this quality improvement project were seen in the sports medicine concussion clinic between February 2014 and August 2015. We determined how often driving recommendations were documented through a retrospective chart review. Once the "return to drive" project was introduced to the sports medicine staff, multiple interventions were completed including handing out flyers to remind families about driving and creating changes to the electronic medical record. RESULTS: At baseline, 9.3% of visits had driving recommendations documented. After an intervention requiring clinical documentation in the electronic medical record, 97% of patients received driving recommendations. CONCLUSIONS: The quality improvement effort was successful at increasing the frequency of delivery of appropriate driving recommendations provided to concussed athletes.

Electroconvulsive therapy for patients with major depression and probable Lewy body dementia.

Patients with dementia and depression are commonly encountered in ECT practice. A large body of case reports and case series in demented patients attests to the utility of ECT in treating concomitant depression in this population. However, there are no reported cases of patients with suspected Lewy Body dementia and depression treated with ECT. We describe our experience in treating seven such patients. All of them enjoyed substantial relief from depression with ECT, which they tolerated well. It is concluded that ECT can be effective in treating depression associated with probable Lewy Body dementia.