The Feeling of Time Passing Is Associated with Recurrent Sustained Activity and Theta Rhythms Across the Cortex.

Introduction: We are constantly estimating how much time has passed, and yet know little about the brain mechanisms through which this process occurs. In this pilot study, we evaluated so-called subjective time estimation with the temporal bisection task, while recording brain activity from electroencephalography (EEG). Methods: Nine adult participants were trained to distinguish between two durations of visual stimuli as either "short" (400 msec) or "long" (1600 msec). They were then presented with stimulus durations in between the long and short stimuli. EEG data from 128 electrodes were examined with a novel analytical method that identifies segments of sustained cortical activity during the task. Results: Participants tended to categorize intermediate durations as "long" more frequently than "short" and were thus experiencing time as moving faster while overestimating the amount of time passing. Their mean bisection point (during which frequency of selecting short vs. long is equal) was closer to the geometric mean of task stimuli (800 msec) rather than the arithmetic mean (1000 msec). In contrast, sustained brain activity occurred closer to the arithmetic mean. The recurrence rate of this activity was highly related to the bisection point, especially when analyzed within naturally occurring theta oscillations (4-8 Hz) (r = -0.90). Discussion: Sustained activity across the cortex within the theta range may reflect temporal durations, whereas its repeated appearance relates to the subjective feeling of time passing.

Mental and physical training with meditation and aerobic exercise improved mental health and well-being in teachers during the COVID-19 pandemic.

Teachers face significant stressors in relation to their work, placing them at increased risk for burnout and attrition. The COVID-19 pandemic has brought about additional challenges, resulting in an even greater burden. Thus, strategies for reducing stress that can be delivered virtually are likely to benefit this population. Mental and Physical (MAP) Training combines meditation with aerobic exercise and has resulted in positive mental and physical health outcomes in both clinical and subclinical populations. The aim of this pilot study was to evaluate the feasibility and potential effectiveness of virtual MAP Training on reducing stress and improving mood and well-being in teachers. Participants (n = 104) were from recruited online from kindergarten to grade twelve (K-12) schools in the Northeastern region of the United States and randomly assigned to a 6-week program of virtual MAP Training (n = 58) or no training (n = 13). Primary outcomes included pre-intervention and post-intervention ratings on self-report measures of social and emotional health. Changes in cognitive functioning and physical health were also examined in secondary analyses. By intervention end, participants in the MAP Training group reported less anxiety and work-related stress compared to those who received no training (ds = -0.75 to -0.78). Additionally, MAP Training participants reported improvements in depressive symptoms, rumination, work-related quality of life, perceived stress, and self-compassion (ds = 0.38 to -0.82), whereas no changes were observed in the no training group. Participants also reported increased subjective ratings of executive functioning, working memory, cognitive flexibility, and fewer sleep disturbances (ds = -0.41 to -0.74). Together, these results suggest that the combination of meditation and aerobic exercise is an effective virtual intervention for improving mental health and well-being among K-12 teachers and may enhance resilience to stressful life events such as occurred during the coronavirus pandemic.

Meditation and Aerobic Exercise Enhance Mental Health Outcomes and Pattern Separation Learning Without Changing Heart Rate Variability in Women with HIV.

Mental and physical (MAP) training targets the brain and the body through a combination of focused-attention meditation and aerobic exercise. The following feasibility pilot study tested whether 6 weeks of MAP training improves mental health outcomes, while enhancing discrimination learning and heart rate variability (HRV) in a group of women living with human immunodeficiency virus (HIV) and other stress-related conditions. Participants were assigned to training (n = 18) or no-training control (n = 8) groups depending on their ability and willingness to participate, and if their schedule allowed. Training sessions were held once a week for 6 weeks with 30 min of meditation followed by 30 min of aerobic exercise. Before and after 6 weeks of training, participants completed the Behavioral Pattern Separation Task as a measure of discrimination learning, self-report questionnaires of ruminative and trauma-related thoughts, depression, anxiety, and perceived stress, and an assessment of HRV at rest. After training, participants reported fewer ruminative and trauma-related thoughts, fewer depressive and anxiety symptoms, and less perceived stress (p's < 0.05). The positive impact on ruminative thoughts and depressive symptoms persisted 6 months after training. They also demonstrated enhanced discrimination of similar patterns of information (p < 0.05). HRV did not change after training (p > 0.05). Combining mental and physical training is an effective program for enhancing mental health and aspects of cognition in women living with HIV, although not necessarily through variance in heart rate.

MAP Train My Brain: Meditation Combined with Aerobic Exercise Reduces Stress and Rumination While Enhancing Quality of Life in Medical Students.

Medical students must commit a great deal of concentration and energy during their first 2 years of study, leaving minimal time for self-care. However, once they become physicians, they are in the position of instructing their patients to engage in self-care. Objectives: In this study, first- and second-year medical students participated in a combined mental and physical (MAP) training program with meditation and aerobic exercise that targeted brain health.* Design: Each weekly session began with 30 min of instructional training that emphasized the benefit of the program for brain and body health, followed by 30 min of silent meditation, and ending with 30 min of aerobic exercise. Participants monitored their heart rate to achieve 60%-80% of their personal maximum. Participants engaged in one additional session of MAP training each week on their own. Location and Subjects: First- and second-year medical students were recruited to be participants from the Robert Wood Johnson Medical School (RWJMS) in Piscataway, NJ. Outcome measures: Participants completed questionnaires of depressive symptoms, perceived stress, ruminative thoughts, and quality of life, before and after the training approximately 8-9 weeks apart. Results: After 8 weeks of training and in contrast to students who did not participate (n = 30), the medical students who completed at least 14 sessions out of 16 (n = 17) reported significantly fewer ruminations (-17%), including depressive (-16%) and brooding ruminations (-24%). Ruminations are repetitive thoughts that are typically negative in nature and associated with symptoms of depression. The medical students also reported greater quality of life at the end of training and less perceived stress. The majority (84%) would recommend these types of practices and this one in particular to their future patients. Conclusions: Previous studies have demonstrated that MAP training can reduce symptoms of depression as well as trauma-related cognitions, while increasing oxygen consumption and synchronized brain activity during cognitive control procedures. Overall, MAP training offers a time-efficient and evidence-based means of maintaining mental and physical wellness for students during medical school and into their future, as well as their patients alike.

Taking neurogenesis out of the lab and into the world with MAP Train My Brain™.

Neurogenesis in the adult hippocampus was rediscovered in the 1990's after being reported in the 1960's. Since then, thousands upon thousands of laboratories have reported on the characteristics and presumed functional significance of new neurons in the adult brain. In 1999, we reported that mental training with effortful learning could extend the survival of these new cells and in the same year, others reported that physical training with exercise could increase their proliferation. Based on these studies and others, we developed MAP Train My Brain™, which is a brain fitness program for humans. The program combines mental and physical (MAP) training through 30-min of effortful meditation followed by 30-min of aerobic exercise. This program, when practiced twice a week for eight weeks reduced depressive symptoms and ruminative thoughts in men and women with major depressive disorder (MDD) while increasing synchronized brain activity during cognitive control. It also reduced anxiety and depression and increased oxygen consumption in young mothers who had been homeless. Moreover, engaging in the program reduced trauma-related cognitions and ruminative thoughts while increasing self-worth in adult women with a history of sexual trauma. And finally, the combination of mental and physical training together was more effective than either activity alone. Albeit effortful, this program does not require inordinate amounts of time or money to practice and can be easily adopted into everyday life. MAP Training exemplifies how we as neuroscientists can take discoveries made in the laboratory out into the world for the benefit of others.

Stressful Life Memories Relate to Ruminative Thoughts in Women With Sexual Violence History, Irrespective of PTSD.

More than one in every four women in the world experience sexual violence (SV) in their lifetime, most often as teenagers and young adults. These traumatic experiences leave memories in the brain, which are difficult if not impossible to forget. We asked whether women with SV history experience stronger memories of their most stressful life event than women without SV history and if so, whether strength relates to ruminative and trauma-related thoughts. Using the Autobiographical Memory Questionnaire (AMQ), women with SV history (n = 64) reported this memory as especially strong (p < 0.001), remembering more sensory and contextual details, compared to women without SV history (n = 119). They further considered the event a significant part of their personal life story. The strength of the memory was highly correlated with posttraumatic cognitions and ruminative thoughts, as well as symptoms of depression and anxiety (p's < 0.001, n = 183). A third (33%) of the women with SV history were diagnosed with posttraumatic stress disorder (PTSD), but PTSD alone did not account for the increase in memory strength (p's < 0.001). These data suggest that the experience of SV increases the strength of stressful autobiographical memories, which are then reexperienced in everyday life during posttraumatic and ruminative thoughts. We propose that the repeated rehearsal of vivid stressful life memories generates more trauma memories in the brain, making the experience of SV even more difficult to forget.

MAP Training My Brain™: Meditation Plus Aerobic Exercise Lessens Trauma of Sexual Violence More Than Either Activity Alone.

Sexual violence against women often leads to post-traumatic stress disorder (PTSD), a mental illness characterized by intrusive thoughts and memories about the traumatic event (Shors and Millon, 2016). These mental processes are obviously generated by the brain but often felt in the body. MAP Training My Brain™ is a novel clinical intervention that combines mental training of the brain with physical training of the body (Curlik and Shors, 2013; Shors et al., 2014). Each training session begins with 20-min of sitting meditation, followed by 10-min of slow-walking meditation, and ending with 30-min of aerobic exercise at 60-80% of the maximum heart rate (see maptrainmybrain.com). In previous studies, the combination of mental and physical (MAP) training together significantly reduced symptoms of depression and ruminative thoughts, while reducing anxiety (Shors et al., 2014, 2017; Alderman et al., 2016). We also documented positive changes in brain activity during cognitive control and whole-body oxygen consumption in various populations. In the present pilot study, we asked whether the combination of meditation and aerobic exercise during MAP Training would reduce trauma-related thoughts, ruminations, and memories in women and if so, whether the combination would be more effective than either activity alone. To test this hypothesis, interventions were provided to a group of women (n = 105), many of whom had a history of sexual violence (n = 32). Groups were trained with (1) MAP Training, (2) meditation alone, (3) aerobic exercise alone, or (4) not trained. Individuals in training groups completed two sessions a week for at least 6 weeks. MAP Training My Brain™ significantly reduced post-traumatic cognitions and ruminative thoughts in women with a history of sexual violence, whereas meditation alone, and exercise alone did not. MAP Training significantly enhanced a measure of self-worth, whereas meditation and exercise alone did not. Similar positive effects were observed for all participants, although meditation alone was also effective in reducing trauma-related thoughts. Overall, these data indicate the combination of meditation and exercise is synergistic. As a consequence, MAP Training is preferable and especially so for women who have experienced sexual violence in their past. Simply put, the whole is greater than the sum of its parts.

Mental and physical skill training increases neurogenesis via cell survival in the adolescent hippocampus.

The adolescent hippocampus produces thousands more new neurons daily than the adult, yet many die within weeks of their generation (Cameron and McCay, 2001; Curlik, DiFeo & Shors, 2014; Shors et al., 2016). Learning new skills can increase their survival. The present study tested the effects of physical skill training on the survival of these newly generated cells in males and female rodents during puberty. Newly generated cells were labeled with BrdU, a marker of cell mitosis, and training began one week later, just as the new cells begin to die. Significantly more BrdU-labeled cells were present in the hippocampus of both sexes after engaging in the physical training experiences. The young animals were able to maintain their balance on a modified rotarod task throughout most trials of training and as a consequence expended considerable energy and endurance during each training trial. These data suggest that a combination of both exercise and skill training can increase brain plasticity through increases in neurogenesis in the adolescent hippocampus. This finding supports the premise behind a clinical intervention known as MAP Training, which combines mental and physical training to enhance brain health in humans (Shors et al., 2014; Alderman et al., 2016). Although theoretical at this stage, the positive consequences of MAP Training for brain function may be mediated through neurogenesis. This article is part of a Special Issue entitled SI: Adolescent plasticity.

Do sex differences in rumination explain sex differences in depression?

It is generally accepted that women tend to ruminate more than men do and these thought patterns are often associated with depressive symptoms (Nolen-Hoeksema et al., ). Based on these findings, we considered whether the relationship between rumination and depression is stronger in women than in men and if so, whether this might explain the higher prevalence of major depressive disorder (MDD) in women and finally, whether the association can be disrupted through a mind/body intervention. Adult men and women, most of whom were clinically depressed, participated in an intervention known as MAP Training, which combines "mental" training with silent meditation and "physical" training with aerobic exercise (Shors et al., ). After eight weeks of training, both men and women reported significantly fewer symptoms of depression and fewer ruminative thoughts (Alderman et al., ). Statistical correlations between depressive symptoms and ruminative thoughts were strong and significant (rho > 0.50; p < 0.05) for both men and women before and after MAP Training. However, only in women did depressive symptoms relate to "reflective" ruminations, which involve analyses of past events, feelings, and behaviors. This is also the only relationship that dissipated after the intervention. In general, these analyses suggest that the strength of the relationship between depressive symptoms and rumination does not necessarily explain sex differences in depression; but because the relationship is strong, targeting rumination through intervention can reduce the incidence of MDD, which is more prevalent among women. © 2016 Wiley Periodicals, Inc.

Sexual trauma and the female brain.

Sexual aggression and violence against women (VAM) are not only social problems; they are mental health problems. Women who experience sexual trauma often express disruptions in emotional and cognitive processes, some of which lead to depression and post-traumatic stress disorder (PTSD). Animal models of neurogenesis and learning suggest that social yet aggressive interactions between a pubescent female and an adult male can disrupt processes of learning related to maternal care, which in turn reduce survival of new neurons in the female hippocampus. Mental and Physical (MAP) Training is a novel clinical intervention that was translated from neurogenesis research. The intervention, which combines meditation and aerobic exercise, is currently being used to help women learn to recover from traumatic life experiences, especially those related to sexual violence and abuse.

A trip down memory lane about sex differences in the brain.

Scientific studies funded by the United States government must now include both males and females as experimental subjects. This is a welcomed change for those of us who have been reporting on sex differences for decades. That said, there are some issues to consider; I focus on one in this review: females used in animal models of mental illness and health are almost always virgins and yet most adult females around the world, irrespective of species, are not virgins. I am not advocating that all scientists include non-virgin females in laboratory studies, but rather to consider the dynamic nature of the female brain when drawing conclusions through discovery. Stressful life experiences, including those related to sexual aggression and trauma, can have a lasting impact on processes of learning related to mental health and plasticity in the female brain. Her response to stress can change rather dramatically as she emerges from puberty to become pregnant and produce offspring, as she must learn to care for those offspring. The inclusion of females in scientific research has been a long time coming but it comes with a history. Going forward, we should take advantage of that history to generate hypotheses that are both reasonable and meaningful.

Sexual Conspecific Aggressive Response (SCAR): A Model of Sexual Trauma that Disrupts Maternal Learning and Plasticity in the Female Brain.

Sexual aggression can disrupt processes related to learning as females emerge from puberty into young adulthood. To model these experiences in laboratory studies, we developed SCAR, which stands for Sexual Conspecific Aggressive Response. During puberty, a rodent female is paired daily for 30-min with a sexually-experienced adult male. During the SCAR experience, the male tracks the anogenital region of the female as she escapes from pins. Concentrations of the stress hormone corticosterone were significantly elevated during and after the experience. Moreover, females that were exposed to the adult male throughout puberty did not perform well during training with an associative learning task nor did they learn well to express maternal behaviors during maternal sensitization. Most females that were exposed to the adult male did not learn to care for offspring over the course of 17 days. Finally, females that did not express maternal behaviors retained fewer newly-generated cells in their hippocampus whereas those that did express maternal behaviors retained more cells, most of which would differentiate into neurons within weeks. Together these data support SCAR as a useful laboratory model for studying the potential consequences of sexual aggression and trauma for the female brain during puberty and young adulthood.

Rumination in major depressive disorder is associated with impaired neural activation during conflict monitoring.

Individuals with major depressive disorder (MDD) often ruminate about past experiences, especially those with negative content. These repetitive thoughts may interfere with cognitive processes related to attention and conflict monitoring. However, the temporal nature of these processes as reflected in event-related potentials (ERPs) has not been well-described. We examined behavioral and ERP indices of conflict monitoring during a modified flanker task and the allocation of attention during an attentional blink (AB) task in 33 individuals with MDD and 36 healthy controls, and whether their behavioral performance and ERPs varied with level of rumination. N2 amplitude elicited by the flanker task was significantly reduced in participants with MDD compared to healthy controls. Level of self-reported rumination was also correlated with N2 amplitude. In contrast, P3 amplitude during the AB task was not significantly different between groups, nor was it correlated with rumination. No significant differences were found in behavioral task performance measures between groups or by rumination levels. These findings suggest that rumination in MDD is associated with select deficits in cognitive control, particularly related to conflict monitoring.

The motirod: a novel physical skill task that enhances motivation to learn and thereby increases neurogenesis especially in the female hippocampus.

Males and females perform differently on a variety of training tasks. In the present study we examined performance of male and female rats while they were trained with a gross motor skill in which they learn to maintain their balance on an accelerating rotating rod (the accelerating rotarod). During training, many animals simply step off the rod, thus terminating the training. This problem was addressed by placing cold water below the rod. We termed the new training procedure "motirod" training because the trained animals were apparently motivated to remain on the rod for longer periods of time. Groups of male and female adult Sprague-Dawley rats were trained on either the standard accelerating rotarod or the motirod for four trials per day on four consecutive days. Latency to fall from the rod (in seconds) was recorded. The motivating feature increased performance especially in females (p=.001). As a consequence of enhanced performance, females retained significantly more new cells in the dentate gyrus of the hippocampus than those trained on the accelerating rotarod or those that received no training. In addition, individuals that learned well retained more new cells, irrespective of sex or task conditions. Previous studies have established that new cells rescued from death by learning remain in the hippocampus for months and mature into neurons (Leuner et al., 2004a; Shors, 2014). These data suggest that sex differences in physical skill learning can arise from sex differences in motivation, which thereby influence how many new neurons survive in the adult brain. This article is part of a Special Issue entitled SI: Brain and Memory.

Mental and Physical (MAP) Training: a neurogenesis-inspired intervention that enhances health in humans.

New neurons are generated in the hippocampus each day and their survival is greatly enhanced through effortful learning (Shors, 2014). The numbers of cells produced can be increased by physical exercise (van Praag, Kempermann, & Gage, 1999). These findings inspired us to develop a clinical intervention for humans known as Mental and Physical Training, or MAP Training. Each session consists of 30min of mental training with focused attention meditation (20min sitting and 10min walking). Meditation is an effortful training practice that involves learning about the transient nature of thoughts and thought patterns, and acquiring skills to recognize them without necessarily attaching meaning and/or emotions to them. The mental training component is followed by physical training with 30min of aerobic exercise performed at moderate intensity. During this component, participants learn choreographed dance routines while engaging in aerobic exercise. In a pilot "proof-of-concept" study, we provided supervised MAP Training (2 sessions per week for 8weeks) to a group of young mothers in the local community who were recently homeless, most of them having previously suffered from physical and sexual abuse, addiction, and depression. Preliminary data suggest that MAP Training improves dependent measures of aerobic fitness (as assessed by maximal rate of oxygen consumed) while decreasing symptoms of depression and anxiety. Similar changes were not observed in a group of recently homeless women who did not participate in MAP Training. It is not currently possible to determine whether new neurons in the human brain increase in number as a result of MAP Training. Rather these preliminary results of MAP Training illustrate how neuroscientific research can be translated into novel clinical interventions that benefit human health and wellness.

Preparing for adulthood: thousands upon thousands of new cells are born in the hippocampus during puberty, and most survive with effortful learning.

The dentate gyrus of the hippocampal formation generates new granule neurons throughout life. The number of neurons produced each day is inversely related to age, with thousands more produced during puberty than during adulthood, and many fewer produced during senescence. In adulthood, approximately half of these cells undergo apoptosis shortly after they are generated. Most of these cells can be rescued from death by effortful and successful learning experiences (Gould et al., 1999; Waddell and Shors, 2008; Curlik and Shors, 2011). Once rescued, the newly-generated cells differentiate into neurons, and remain in the hippocampus for at least several months (Leuner et al., 2004). Here, we report that many new hippocampal cells also undergo cell death during puberty. Because the juvenile brain is more plastic than during adulthood, and because many experiences are new, we hypothesized that a great number of cells would be rescued by learning during puberty. Indeed, adolescent rats that successfully acquired the trace eyeblink response retained thousands more cells than animals that were not trained, and those that failed to learn. Because the hippocampus generates thousands more cells during puberty than during adulthood, these results support the idea that the adolescent brain is especially responsive to learning. This enhanced response can have significant consequences for the functional integrity of the hippocampus. Such a massive increase in cell proliferation is likely an adaptive response as the young animal must emerge from the care of its mother to face the dangers, challenges, and opportunities of adulthood.

Physical skill training increases the number of surviving new cells in the adult hippocampus.

The dentate gyrus is a major site of plasticity in the adult brain, giving rise to thousands of new neurons every day, through the process of adult neurogenesis. Although the majority of these cells die within two weeks of their birth, they can be rescued from death by various forms of learning. Successful acquisition of select types of associative and spatial memories increases the number of these cells that survive. Here, we investigated the possibility that an entirely different form of learning, physical skill learning, could rescue new hippocampal cells from death. To test this possibility, rats were trained with a physically-demanding and technically-difficult version of a rotarod procedure. Acquisition of the physical skill greatly increased the number of new hippocampal cells that survived. The number of surviving cells positively correlated with performance on the task. Only animals that successfully mastered the task retained the cells that would have otherwise died. Animals that failed to learn, and those that did not learn well did not retain any more cells than those that were untrained. Importantly, acute voluntary exercise in activity wheels did not increase the number of surviving cells. These data suggest that acquisition of a physical skill can increase the number of surviving hippocampal cells. Moreover, learning an easier version of the task did not increase cell survival. These results are consistent with previous reports revealing that learning only rescues new neurons from death when acquisition is sufficiently difficult to achieve. Finally, complete hippocampal lesions did not disrupt acquisition of this physical skill. Therefore, physical skill training that does not depend on the hippocampus can effectively increase the number of surviving cells in the adult hippocampus, the vast majority of which become mature neurons.

The stressed female brain: neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress.

Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD), indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA) is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC) during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL) and infralimbic (IL) subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. About 24 h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similarly to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful life events.

Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain.

Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood-brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3-12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague-Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta-band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'.

Learning to learn: theta oscillations predict new learning, which enhances related learning and neurogenesis.

Animals in the natural world continuously encounter learning experiences of varying degrees of novelty. New neurons in the hippocampus are especially responsive to learning associations between novel events and more cells survive if a novel and challenging task is learned. One might wonder whether new neurons would be rescued from death upon each new learning experience or whether there is an internal control system that limits the number of cells that are retained as a function of learning. In this experiment, it was hypothesized that learning a task that was similar in content to one already learned previously would not increase cell survival. We further hypothesized that in situations in which the cells are rescued hippocampal theta oscillations (3-12 Hz) would be involved and perhaps necessary for increasing cell survival. Both hypotheses were disproved. Adult male Sprague-Dawley rats were trained on two similar hippocampus-dependent tasks, trace and very-long delay eyeblink conditioning, while recording hippocampal local-field potentials. Cells that were generated after training on the first task were labeled with bromodeoxyuridine and quantified after training on both tasks had ceased. Spontaneous theta activity predicted performance on the first task and the conditioned stimulus induced a theta-band response early in learning the first task. As expected, performance on the first task correlated with performance on the second task. However, theta activity did not increase during training on the second task, even though more cells were present in animals that had learned. Therefore, as long as learning occurs, relatively small changes in the environment are sufficient to increase the number of surviving neurons in the adult hippocampus and they can do so in the absence of an increase in theta activity. In conclusion, these data argue against an upper limit on the number of neurons that can be rescued from death by learning.