Navigating uncertainty: exploring parents' knowledge of concussion management and neuropsychological baseline testing.

Introduction: Parents play an important role in preventing and managing sport-related concussions among youth sport participants. Research indicates that parents understand the severity and consequences associated with the injury but gaps exist in their knowledge of its management. Neuropsychological baseline testing (NBT) is a modality that has gained interest in youth sport to purportedly better manage concussion injuries. Little is known about parents' perspectives on the use of NBT in the management process. Methods: The present qualitative study used Protection Motivation Theory as a guiding framework and employed focus groups (N = 2) with parents (N = 11) to gain insight into parents' perceptions and experiences with concussion management, specifically focusing on NBT. Results: Inductive Content Analysis developed a core theme of navigating uncertainty. Participants expressed uncertainty about the nature of concussion and its management process, where concussion was not always easy to identify, youth were not always reliable reporters, and there was no prescribed or proscribed path for recovery. Personal experience and concussion management policy provided participants with a degree of certainty in managing concussions. Participants gave NBT mixed reviews in potentially promoting greater certainty but also held reservations about its usefulness in concussion management. Discussion: We discuss findings relative to existing knowledge and theory in youth sport concussion and identify implications for practice.

Hippocampal damage causes retrograde amnesia for objects' visual, but not odour, properties in male rats.

Damage to the hippocampus produces profound retrograde amnesia, but odour and object discrimination memories can be spared in the retrograde direction. Prior lesion studies testing retrograde amnesia for object/odour discriminations are problematic due to sparing of large parts of the hippocampus, which may support memory recall, and/or the presence of uncontrolled, distinctive odours that may support object discrimination. To address these issues, we used a simple object discrimination test to assess memory in male rats. Two visually distinct objects, paired with distinct odour cues, were presented. One object was associated with a reward. Following training, neurotoxic hippocampal lesions were made using N-methyl-D-aspartate (NMDA). The rats were then tested on the preoperatively learned object discrimination problem, with and without the availability of odour or visual cues during testing. The rats were also postoperatively trained on a new object discrimination problem. Lesion sizes ranged from 67% to 97% of the hippocampus (average of 87%). On the preoperatively learned discrimination problem, the rats with hippocampal lesions showed preserved object discrimination memory when tested in the dark (i.e., without visual cues) but not when the explicit odour cues were removed from the objects. Hippocampal lesions increased the number of trials required to reach criterion but did not prevent rats from solving the postoperatively learned discrimination problem. Our results support the idea that long-term memories for odours, unlike recall of visual properties of objects, do not depend on the hippocampus in rats, consistent with previous observations that hippocampal damage does not cause retrograde amnesia for odour memories.

Effect of repeated seizures on spatial exploration and immediate early gene expression in the hippocampus and dentate gyrus.

Immediate early genes (IEGs) are coordinately activated in response to neuronal activity and can cause activation of secondary response genes that modulate synaptic plasticity and mediate long-lasting changes in behaviour. Excessive neuronal stimulation induced by epileptic seizures induce rapid and dramatic changes in IEG expression. Although the impact of acute seizure activity on IEG expression has been well studied, less is known about the long-term effects of chronic seizures on IEG induction during seizure free periods where behavioural and cognitive impairments are frequently observed in people with epilepsy and in animal models of epilepsy. The present study sought out to examine the impact of chronic pentylenetetrazole evoked seizures (PTZ kindling) on spatial exploration induced in IEG expression (c-Fos, ΔFosB, Homer1a, Egr1, Npas4, Nr4a1) in the hippocampus (CA1 and CA3 subfields) and dentate gyrus of rats. Male rats underwent two weeks of PTZ kindling (every 2 days) or received vehicle injections and were placed into a novel open field arena for 30 min either 24 hrs or 4 weeks after the last treatment. Although exploratory activity was similar between PTZ kindled and vehicle controls when examined 24 hrs after the last treatment, we observed a significant reduction in spatial exploration induced expression of c-Fos, Egr1, and ΔFosB in the hippocampus and dentate gyrus, and reduced expression of Nr4a1 in the dentate gyrus and Homer1a in the hippocampus only. When testing was conducted after a 4-week recovery period, only c-Fos continued to show reduced expression after exposure a novel environment in previously PTZ kindled animals. Interestingly, these animals also showed reduced activity in the center region of the open field suggestive of heightened anxiety-like behaviour. Collectively, these results suggest that repeated seizures may lead to longterm downregulation in hippocampal IEG expression that can extend into seizure free periods thereby providing a critical mechanism for the development of cognitive and behavioural deficits that arise during chronic epilepsy.

Overtraining Strengthens the Visual Discrimination Memory Trace Outside the Hippocampus in Male Rats.

The hippocampus (HPC) may compete with other memory systems when establishing a representation, a process termed overshadowing. However, this overshadowing may be mitigated by repeated learning episodes, making a memory resistant to post-training hippocampal damage. In the current study, we examined this overshadowing process for a hippocampal-dependent visual discrimination memory in rats. In Experiment 1, male rats were trained to criterion (80% accuracy on two consecutive days) on a visual discrimination and then given 50 additional trials distributed over 5 days or 10 weeks. Regardless of this additional learning, extensive damage to the HPC caused retrograde amnesia for the visual discrimination, suggesting that the memory remained hippocampal-dependent. In Experiment 2, rats received hippocampal damage before learning and required approximately twice as many trials to acquire the visual discrimination as control rats, suggesting that, when the overshadowing or competition is removed, the non-hippocampal memory systems only slowly acquires the discrimination. In Experiment 3, increasing the additional learning beyond criterion by 230 trials, the amount needed in Experiment 2 to train the non-hippocampal systems in absence of competition, successfully prevented the retrograde amnesic effects of post-training hippocampal damage. Combined, the findings suggest that a visual discrimination memory trace can be strengthened in non-hippocampal systems with overtraining and become independent of the HPC.

Distributed learning episodes create a context fear memory outside the hippocampus that depends on perirhinal and anterior cingulate cortices.

Damage to the hippocampus (HPC) typically causes retrograde amnesia for contextual fear conditioning. Repeating the conditioning over several sessions, however, can eliminate the retrograde amnesic effects. This form of reinstatement thus permits modifications to networks that can support context memory retrieval in the absence of the HPC. The present study aims to identify cortical regions that support the nonHPC context memory. Specifically, the contribution of the perirhinal cortex (PRH) and the anterior cingulate cortex (ACC) were examined because of their established importance to context memory. The findings show that context memories established through distributed reinstatement survive damage limited only to the HPC, PRH, or ACC. Combined lesions of the HPC and PRH, as well as the HPC and ACC, caused retrograde amnesia, suggesting that network modifications in the PRH and ACC enable context fear memories to become resistant to HPC damage.

Has multiple trace theory been refuted?

Multiple trace theory (Nadel & Moscovitch, Current Opinion in Neurobiology, 1997, 7, 217-227) has proven to be one of the most novel and influential recent memory theories, and played an essential role in shifting perspective on systems-level memory consolidation. Here, we briefly review its impact and testable predictions and focus our discussion primarily on nonhuman animal experiments. Perhaps, the most often supported claim is that episodic memory tasks should exhibit comparable severity of retrograde amnesia (RA) for recent and remote memories after extensive damage to the hippocampus (HPC). By contrast, there appears to be little or no experimental support for other core predictions, such as temporally limited RA after extensive HPC damage in semantic memory tasks, temporally limited RA for episodic memories after partial HPC damage, or the existence of storage of multiple HPC traces with repeated reactivations. Despite these shortcomings, it continues to be a highly cited HPC memory theory.

Spatial exploration induced expression of immediate early genes Fos and Zif268 in adult-born neurons Is reduced after pentylenetetrazole kindling.

Seizure activity stimulates adult neurogenesis, the birth of new neurons, in the hippocampus. Many new neurons that develop in the presence of repeatedly induced seizures acquire abnormal morphological and functional characteristics that can promote network hyperexcitability and hippocampal dysfunction. However, the impact of seizure induced neurogenesis on behaviour remains poorly understood. In this study, we investigated whether adult-born neurons generated immediately before and during chronic seizures were capable of integration into behaviorally relevant hippocampal networks. Adult rats underwent pentylenetetrazole (PTZ) kindling for either 1 or 2 weeks. Proliferating cells were labelled with BrdU immediately before kindling commenced. Twenty-four hours after receiving their last kindling treatment, rats were placed in a novel environment and allowed to freely explore for 30 min. The rats were euthanized 90 min later to examine for behaviourally-induced immediate early gene expression (c-fos, Zif268). Using this approach, we found that PTZ kindled rats did not differ from control rats in regards to exploratory behaviour, but there was a marked attenuation in behaviour-induced expression of Fos and Zif268 for rats that received 2 weeks of PTZ kindling. Further examination revealed that PTZ kindled rats showed reduced colocalization of Fos and Zif268 in 2.5 week old BrdU + cells. The proportion of immature granule cells (doublecortin-positive) expressing behaviorally induced Zif268 was also significantly lower for PTZ kindled rats than control rats. These results suggest that chronic seizures can potentially disrupt the ability of adult-born cells to functionally integrate into hippocampal circuits important for the processing of spatial information.

Chronic Jet Lag Simulation Decreases Hippocampal Neurogenesis and Enhances Depressive Behaviors and Cognitive Deficits in Adult Male Rats.

There is a long history that protracted periods of circadian disruption, such as through frequent transmeridian travel or rotating shift work, can have a significant impact on brain function and health. In addition, several studies have shown that chronic periods of circadian misalignment can be a significant risk factor for the development of depression and anxiety in some individuals with a history of psychiatric illness. In animal models, circadian disruption can be introduced through either phase advances or delays in the light-dark cycle. However, the impact of chronic phase shifts on affective behavior in rats has not been well-studied. In the present study, male rats were subjected to either weekly 6 h phase advances (e.g., traveling eastbound from New York to Paris) or 6 h phase delays (e.g., traveling westbound from New York to Hawaii) in their light/dark cycle for 8 weeks. The effect of chronic phase shifts was then examined on a range of emotional and cognitive behaviors. We found that rats exposed to frequent phase advances, which mirror conditions of chronic jet lag in humans, exhibited impairments in object recognition memory and showed signature symptoms of depression, including anhedonia, increased anxiety behavior, and higher levels of immobility in the forced swim test. In addition, rats housed on the phase advance schedule also had lower levels of hippocampal neurogenesis and immature neurons showed reduced dendritic complexity compared to controls. These behavioral and neurogenic changes were direction-specific and were not observed after frequent phase delays. Taken together, these findings support the view that circadian disruption through chronic jet lag exposure can suppress hippocampal neurogenesis, which can have a significant impact on memory and mood-related behaviors.

The mitigating effect of repeated memory reactivations on forgetting.

Memory reactivation is a process whereby cueing or recalling a long-term memory makes it enter a new active and labile state. Substantial evidence suggests that during this state the memory can be updated (e.g., adding information) and can become more vulnerable to disruption (e.g., brain insult). Memory reactivations can also prevent memory decay or forgetting. However, it is unclear whether cueing recall of a feature or component of the memory can benefit retention similarly to promoting recall of the entire memory. We examined this possibility by having participants view a series of neutral images and then randomly assigning them to one of four reactivation groups: control (no reactivation), distractor (reactivation of experimental procedures), component (image category reactivation), and descriptive (effortful description of the images). The experiment also included three retention intervals: 1 h, 9 days, and 28 days. Importantly, the participants received three reactivations equally spaced within their respective retention interval. At the end of the interval, all the participants were given an in-lab free-recall test in which they were asked to write down each image they remembered with as many details as possible. The data revealed that both the participants in the descriptive reactivation and component reactivation groups remembered significantly more than the participants in the control groups, with the effect being most pronounced in the 28-day retention interval condition. These findings suggest that memory reactivation, even component reactivation of a memory, makes memories more resistant to decay.

Increased task demand during spatial memory testing recruits the anterior cingulate cortex.

We examined whether increasing retrieval difficulty in a spatial memory task would promote the recruitment of the anterior cingulate cortex (ACC) similar to what is typically observed during remote memory retrieval. Rats were trained on the hidden platform version of the Morris Water Task and tested three or 30 d later. Retrieval difficulty was manipulated by removing several prominent extra-pool cues from the testing room. Immediate early gene expression (c-Fos) in the ACC was greater following the cue removal and comparable to remote memory retrieval (30-d retention interval) levels, supporting the view of increased ACC contribution during high cognitive-demand memory processes.

Time averaged transmitter power and exposure to electromagnetic fields from mobile phone base stations.

Models for exposure assessment of high frequency electromagnetic fields from mobile phone base stations need the technical data of the base stations as input. One of these parameters, the Equivalent Radiated Power (ERP), is a time-varying quantity, depending on communication traffic. In order to determine temporal averages of the exposure, corresponding averages of the ERP have to be available. These can be determined as duty factors, the ratios of the time-averaged power to the maximum output power according to the transmitter setting. We determine duty factors for UMTS from the data of 37 base stations in the Swisscom network. The UMTS base stations sample contains sites from different regions of Switzerland and also different site types (rural/suburban/urban/hotspot). Averaged over all regions and site types, a UMTS duty factor for the 24 h-average is obtained, i.e., the average output power corresponds to about a third of the maximum power. We also give duty factors for GSM based on simple approximations and a lower limit for LTE estimated from the base load on the signalling channels.

Neither time nor number of context-shock pairings affect long-term dependence of memory on hippocampus.

There are still basic uncertainties concerning the role of the hippocampus (HPC) in maintaining long-term context memories. All experiments examining the effects of extensive HPC damage on context memory for a single learning episode find that damage soon after learning results in robust retrograde amnesia. Some experiments find that if the learning-to-damage interval is extended, remote context memories are spared. In contrast, other experiments fail to find spared remote context memory. One possible explanation for inconsistency might be the potency of the context memory conditioning procedure, as the experiments showing spared remote memory used a greater number of context-shock pairings, likely creating a stronger context fear memory. We designed an experiment to directly test the question: does increasing the number of context-shock pairings result in sparing of remote context memory after HPC damage? Six independent groups of rats received either 3 or 12 context-shock pairings during a single conditioning session and then either received extensive HPC damage or Control surgery at 1-week, 2-months, or 4-months after conditioning. 10 days after surgery rats were tested for memory of the shock context. Consistent with all relevant studies, HPC damage at the shortest training-surgery interval produced robust retrograde amnesia for both 3- and 12-shock groups whereas the Control rats expressed significantly high levels of memory. At the longer training-surgery interval, HPC damage produced similarly robust retrograde amnesia in the rats in both the 3- and 12-shock groups. These results clearly demonstrate that increasing the number of context-shock pairings within a single learning session does not change the dependence of the memory on the HPC. Current evidence from our group on retrograde amnesia has now shown that partial damage, dorsal vs. ventral damage, discrete cue+context conditioning, time after training, and number of context-shock pairings do not affect HPC dependence of context fear memories. When taken together, the evidence strongly supports a permanent role of the HPC in context memory.

Novel odour recognition memory is independent of the hippocampus in rats.

We examined the effects of hippocampal (HPC) damage on odour recognition memory, using a novel odour recognition task that was adapted from the more common novel object recognition task. Three separate experiments were conducted. In Experiment 1, we tested rats in novel odour recognition across different retention intervals (i.e. 15 min, 24 h, 1 week, 5 weeks). Given a single acquisition session, rats' performance deteriorated after 24 h, but given multiple acquisition sessions (i.e. four sessions over 2 days), rats were able to perform well after retention intervals up to 5 weeks. In Experiment 2, we examined the possible anterograde amnesic effects of HPC damage on novel odour recognition, finding that pre-training damage to the entire HPC failed to cause amnesia for retention delays extending up to 5 weeks. In Experiment 3, we examined whether post-training HPC damage would cause retrograde amnesia, but failed to find any evidence of an impairment. The combined results suggest that the neural network supporting odour recognition is independent of the HPC.

Single session contextual fear conditioning remains dependent on the hippocampus despite an increase in the number of context-shock pairings during learning.

We examined if the strength of contextual fear learning determines whether remote memories become independent of the hippocampus. Rats received 3 or 10 shocks in a single contextual fear conditioning session and then received sham or complete neurotoxic lesions of the hippocampus 7, 50, or 100 days later. Following recovery from surgery, the rats were returned to the conditioning context for a 5-min retention test. During this test, freezing, complete immobility except for breathing, was used as an index of memory. Regardless of the learning-to-surgery interval, the rats with hippocampal damage from the 3-shock condition showed little and significantly less freezing than their respective control group, suggesting profound flat graded retrograde amnesia. Similarly, each group of hippocampal-damaged rats from the 10-shock condition froze significantly less than their respective control group. However, the rats that received hippocampal damage 50 days after learning froze significantly more than the rats that received the damage 7 days after learning. The latter gradient to the retrograde amnesia did not increase with more time as the freezing was not as high in the most remote memory group (100 days). Combined, these findings suggest that a contextual fear memory acquired in a single session under stronger learning parameters remains dependent on the hippocampus.

Head exposure system for a human provocation study to assess the possible influence of UMTS-like electromagnetic fields on cerebral blood circulation using near-infrared imaging.

A head exposure setup for efficient and precisely defined exposure of human subjects equipped with a near-infrared imaging (NIRI) sensor is presented. In a partially shielded anechoic chamber the subjects were exposed to Universal Mobile Telecommunications System (UMTS)-like electromagnetic fields (EMF) by using a patch antenna at a distance of 4 cm from the head. The non-contact design of the exposure setup enabled NIRI sensors to easily attach to the head. Moreover, different regions of the head were chosen for localised exposure and simultaneous NIRI investigation. The control software enabled the simple adaptation of the test parameters during exploratory testing as well as the performance of controlled, randomised, crossover and double-blind provocation studies. Four different signals with a carrier frequency of 1900 MHz were chosen for the exposure: a simple continuous wave signal and three different UMTS signals. Furthermore, three exposure doses were available: sham, low (spatial peak specific absorption rate (SAR) = 0.18 W/kg averaged over 10 g) and high (spatial peak SAR = 1.8 W/kg averaged over 10 g). The SAR assessment was performed by measurement and simulation. Direct comparison of measurement and numerical results showed good agreement in terms of spatial peak SAR and SAR distribution. The variability analysis of the spatial peak SAR over 10 g was assessed by numerical simulations. Maximal deviations of -22% and +32% from the nominal situation were observed. Compared to other exposure setups, the present setup allows for low exposure uncertainty, combined with high SAR efficiency, easy access for the NIRI sensor and minimal impairment of test subjects.

Assessment of intermittent UMTS electromagnetic field effects on blood circulation in the human auditory region using a near-infrared system.

The aim of the present study was to assess the potential effects of intermittent Universal Mobile Telecommunications System electromagnetic fields (UMTS-EMF) on blood circulation in the human head (auditory region) using near-infrared spectroscopy (NIRS) on two different timescales: short-term (effects occurring within 80 s) and medium-term (effects occurring within 80 s to 30 min). For the first time, we measured potential immediate effects of UMTS-EMF in real-time without any interference during exposure. Three different exposures (sham, 0.18 W/kg, and 1.8 W/kg) were applied in a controlled, randomized, crossover, and double-blind paradigm on 16 healthy volunteers. In addition to oxy-, deoxy-, and total haemoglobin concentrations ([O(2) Hb], [HHb], and [tHb], respectively), the heart rate (HR), subjective well-being, tiredness, and counting speed were recorded. During exposure to 0.18 W/kg, we found a significant short-term increase in Δ[O(2) Hb] and Δ[tHb], which is small (≈17%) compared to a functional brain activation. A significant decrease in the medium-term response of Δ[HHb] at 0.18 and 1.8 W/kg exposures was detected, which is in the range of physiological fluctuations. The medium-term ΔHR was significantly higher (+1.84 bpm) at 1.8 W/kg than for sham exposure. The other parameters showed no significant effects. Our results suggest that intermittent exposure to UMTS-EMF has small short- and medium-term effects on cerebral blood circulation and HR.

Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory.

Damage to the hippocampus (HPC) using the excitotoxin N-methyl-D-aspartate (NMDA) can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity) during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA-induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX), a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA-induced, or no damage to the HPC at a recent (24 hours) or remote (5 weeks) time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories.

Between-systems memory interference during retrieval.

Context memories normally depend on the hippocampus (HPC) but, in the absence of the HPC, other memory systems are capable of acquiring and supporting these memories. This suggests that the HPC can interfere with other systems during memory acquisition. Here we ask whether the HPC can also interfere with the retrieval of a context memory that was independently acquired by a non-HPC system. Specifically, we assess whether the HPC can impair the retrieval of a contextual fear-conditioning memory that was acquired while the HPC was temporarily inactive. Rats were infused with the γ-aminobutyric acid (GABA)(A) receptor agonist muscimol in the dorsal and ventral HPC either before acquisition, retrieval, or prior to both acquisition and retrieval, consistent with the effects of permanent HPC lesions on contextual fear conditioning, if the HPC was inactive at the time of acquisition and retention memory was intact. Thus, non-HPC systems acquired and supported this memory in absence of the HPC. However, if the HPC was inactive during acquisition but active thereafter, rats displayed severe deficits during the retention test. Moreover, when the same rats received a second retention test but with the HPC inactive at this time, the memory was recovered, suggesting that removal of a form of interference allowed the memory to be expressed. Combined, these findings imply that the HPC competes and/or interferes with retrieval of a long-term memory that was established in non-HPC systems.

A novel animal model of hippocampal cognitive deficits, slow neurodegeneration, and neuroregeneration.

Long-term adrenalectomy (ADX) results in an extensive and specific loss of dentate gyrus granule cells in the hippocampus of adult rats. This loss of granule cells extends over a period of weeks to months and ultimately results in cognitive deficits revealed in a number of tasks that depend on intact hippocampal function. The gradual nature of ADX-induced cell death and the ensuing deficits in cognition resemble in some important respects a variety of pathological conditions in humans. Here, we characterize behavioural and cellular processes, including adult neurogenesis, in the rat ADX model. We also provide experimental evidence for a neurogenic treatment strategy by which the lost hippocampal cells may be replaced, with the goal of functional recovery in mind.