Quadriceps and Hamstrings Activation Peaks Earlier as Athletes Repeatedly Hop, but There are Differences Depending on ACL Reconstruction Technique.

Background: After Anterior Cruciate Ligament Reconstruction (ACLR) athletes face the challenge of regaining their previous competitive level while avoiding re-injury and early knee joint cartilage degeneration. Quadriceps and hamstrings strength reductions and neuromuscular alterations potentially related to risk of re-injury are present after ACLR and relate to deficits in muscle activation. Design: Cross-sectional laboratory study. Purpose: To examine quadriceps and hamstrings muscle activation during repeated hops in healthy pivoting-sport athletes and those who had undergone ACLR (bone-tendon-bone and semitendinosus graft) who had met functional criteria allowing return to training. Methods: Surface electromyography (SEMG) was recorded from vastus medialis and lateralis and medial and lateral hamstrings bilaterally during 30 seconds' repeated hopping in male athletes on average eight months after ACLR surgery (5-12 months). All patients underwent hamstring (HS) (n=24) or bone-tendon-bone (BTB) reconstruction (n=20) and were compared to healthy controls (n=31). The SEMG signals were normalized to those obtained during maximal voluntary isometric contraction. Results: A significant time shift in peak muscle activation (earlier) was seen for: vastus medialis and vastus lateralis activation in the control group, in the BTB group's healthy (but not injured) leg and both legs of the HS group. A significant time shift in peak muscle activation was seen for lateral hamstrings (earlier) in all but the BTB group's injured leg and the medial hamstrings in the control group only. Lower peak activation levels of the vastus lateralis (p\<0.001) and vastus medialis (p\<0.001) were observed in the injured compared to healthy legs and lower peak lateral hamstrings activity (p\<0.009) in the injured leg compared to control leg. Decline in medial hamstring peak activation (p\<0.022) was observed between 1st and 3rd phase of the hop cycle in all groups. Conclusion: Repeated hop testing revealed quadriceps and hamstring activation differences within ACLR athletes, and compared to healthy controls, that would be missed with single hop tests. Level of evidence: 3.

Lower medial hamstring activity after ACL reconstruction during running: a cross-sectional study.

OBJECTIVE: Anterior cruciate ligament reconstruction (ACLR) predisposes footballers for subsequent ACL and hamstring (HS) injury. This case series examines HS muscle activation patterns during the running in ACLR patients (bone-patellar tendon-bone (BTB) and (HS) graft) after completion of functional criteria allowing return to training. METHODS: Electromyography (EMG) recorded from medial and lateral HS bilaterally during treadmill running (12, 14 and 16 km/hour) from 21 male ACLR patients on average 7 months from surgery (5-9) that underwent (HS) (n=12) or BTB reconstruction (n=9) were compared with 19 healthy runners. Main outcome measures: EMG signal was normalised to peak during the running. Pairwise comparisons were made for each muscle group examining stance and swing activation for mean and peak EMG for each patient group and leg. RESULTS: Significantly lower relative peak activation in stance (not swing) phase for medial HS was seen for all conditions with effect sizes ranging from -0.63 (controls, BTB non-injured leg) to -1.09 (HS injured). For lateral HS only BTB injured were significantly lower in stance phase (-1.05). CONCLUSION: ACLR patients show neuromuscular alterations during different phases of running. The finding of reduced medial HS activity in stance phase might have implications for knee instability and HS muscle injury on resumption of sport.

Marked asymmetry in vertical force (but not contact times) during running in ACL reconstructed athletes <9 months post-surgery despite meeting functional criteria for return to sport.

OBJECTIVES: Compare maximum plantar force (Fmax) during running in soccer players following anterior cruciate ligament reconstruction (ACLR) as they pass return to sport (RTS) criteria. DESIGN: Case control study. METHODS: Soccer players after ACLR (n=16) and matched healthy controls (n=16) ran on a treadmill at 12, 14 and 16km/h while plantar loading data was measured using an in-shoe pressure system (Pedar-X, Novel). Fmax and contact time of the injured and uninjured limbs in athletes <9months post-ACLR and those ≥9months ACLR were compared to healthy players (no ACLR). RESULTS: Significant differences with large effect sizes in Fmax asymmetry were seen at all running speeds for the athletes <9months ACLR compared to those ≥9months, and the healthy subjects. Fmax difference peaked at 16km/h; 32±11%BW in <9months ACLR group compared to 6±5%BW in ≥9months group; ES=1.67, p<0.01. There was a non-significant trend for increasing asymmetry with increasing speed for subjects who were <9months after ACLR while the reverse was true for those ≥9 months and the healthy subjects. CONCLUSIONS: Relatively large unloading of the ACLR limb (but not differences in contact times) are seen during running for athletes <9months post-ACLR despite having completed functional criteria required to permit RTS training. These asymmetries appear to slightly increase with increasing speed, and the reverse is true for healthy controls and those ≥9months after ACLR surgery.

Elevated visual dependency in young adults after chemotherapy in childhood.

Chemotherapy in childhood can result in long-term neurophysiological side-effects, which could extend to visual processing, specifically the degree to which a person relies on vision to determine vertical and horizontal (visual dependency). We investigated whether adults treated with chemotherapy in childhood experience elevated visual dependency compared to controls and whether any difference is associated with the age at which subjects were treated. Visual dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified CTS into two groups: those treated before 12 years of age and those treated from 12 years of age and older. Results were compared to 25 healthy, age-matched controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations was recorded by having subjects position an illuminated rod to their perceived horizontal and vertical with and without a surrounding frame tilted clockwise and counter-clockwise 20° from vertical. There was no significant difference in rod accuracy between any CTS groups and controls without a frame. However, when assessing visual dependency using a frame, CTS in general (p = 0.006) and especially CTS treated before 12 years of age (p = 0.001) tilted the rod significantly further in the direction of the frame compared to controls. Our findings suggest that chemotherapy treatment before 12 years of age is associated with elevated visual dependency compared to controls, implying a visual bias during spatial activities. Clinicians should be aware of symptoms such as visual vertigo in adults treated with chemotherapy in childhood.

Running speed increases plantar load more than per cent body weight on an AlterG® treadmill.

AlterG® treadmills allow for running at different speeds as well as at reduced bodyweight (BW), and are used during rehabilitation to reduce the impact load. The aim of this study was to quantify plantar loads borne by the athlete during rehabilitation. Twenty trained male participants ran on the AlterG® treadmill in 36 conditions: all combinations of indicated BW (50-100%) paired with different walking and running speeds (range 6-16 km · hr-1) in a random order. In-shoe maximum plantar force (Fmax) was recorded using the Pedar-X system. Fmax was lowest at the 6 km · hr-1 at 50% indicated BW condition at 1.02 ± 0.21BW and peaked at 2.31 ± 0.22BW for the 16 km · hr-1 at 100% BW condition. Greater increases in Fmax were seen when increasing running speed while holding per cent BW constant than the reverse (0.74BW-0.91BW increase compared to 0.19-0.31BW). A table is presented with each of the 36 combinations of BW and running speed to allow a more objective progression of plantar loading during rehabilitation. Increasing running speed rather than increasing indicated per cent BW was shown to have the strongest effect on the magnitude of Fmax across the ranges of speeds and indicated per cent BWs examined.

Decreased postural control in adult survivors of childhood cancer treated with chemotherapy.

The objective of cancer treatment is to secure survival. However, as chemotherapeutic agents can affect the central and peripheral nervous systems, patients must undergo a process of central compensation. We explored the effectiveness of this compensation process by measuring postural behaviour in adult survivors of childhood cancer treated with chemotherapy (CTS). We recruited sixteen adults treated with chemotherapy in childhood for malignant solid (non-CNS) tumours and 25 healthy age-matched controls. Subjects performed posturography with eyes open and closed during quiet and perturbed standing. Repeated balance perturbations through calf vibrations were used to study postural adaptation. Subjects were stratified into two groups (treatment before or from 12 years of age) to determine age at treatment effects. Both quiet (p = 0.040) and perturbed standing (p ≤ 0.009) were significantly poorer in CTS compared to controls, particularly with eyes open and among those treated younger. Moreover, CTS had reduced levels of adaptation compared to controls, both with eyes closed and open. Hence, adults treated with chemotherapy for childhood cancer may suffer late effects of poorer postural control manifested as reduced contribution of vision and as reduced adaptation skills. These findings advocate development of chemotherapeutic agents that cause fewer long-term side effects when used for treating children.

Blocking Synaptic Removal of GluA2-Containing AMPA Receptors Prevents the Natural Forgetting of Long-Term Memories.

The neurobiological processes underpinning the natural forgetting of long-term memories are poorly understood. Based on the critical role of GluA2-containing AMPA receptors (GluA2/AMPARs) in long-term memory persistence, we tested in rats whether their synaptic removal underpins time-dependent memory loss. We found that blocking GluA2/AMPAR removal with the interference peptides GluA23Y or G2CT in the dorsal hippocampus during a memory retention interval prevented the normal forgetting of established, long-term object location memories, but did not affect their acquisition. The same intervention also preserved associative memories of food-reward conditioned place preference that would otherwise be lost over time. We then explored whether this forgetting process could play a part in behavioral phenomena involving time-dependent memory change. We found that infusing GluA23Y into the dorsal hippocampus during a 2 week retention interval blocked generalization of contextual fear expression, whereas infusing it into the infralimbic cortex after extinction of auditory fear prevented spontaneous recovery of the conditioned response. Exploring possible physiological mechanisms that could be involved in this form of memory decay, we found that bath application of GluA23Y prevented depotentiation, but not induction of long-term potentiation, in a hippocampal slice preparation. Together, these findings suggest that a decay-like forgetting process that involves the synaptic removal of GluA2/AMPARs erases consolidated long-term memories in the hippocampus and other brain structures over time. This well regulated forgetting process may critically contribute to establishing adaptive behavior, whereas its dysregulation could promote the decline of memory and cognition in neuropathological disorders. SIGNIFICANCE STATEMENT: The neurobiological mechanisms involved in the natural forgetting of long-term memory and its possible functions are not fully understood. Based on our previous work describing the role of GluA2-containing AMPA receptors in memory maintenance, here, we tested their role in forgetting of long-term memory. We found that blocking their synaptic removal after long-term memory formation extended the natural lifetime of several forms of memory. In the hippocampus, it preserved spatial memories and inhibited contextual fear generalization; in the infralimbic cortex, it blocked the spontaneous recovery of extinguished fear. These findings suggest that a constitutive decay-like forgetting process erases long-term memories over time, which, depending on the memory removed, may critically contribute to developing adaptive behavioral responses.

Oculomotor Deficits after Chemotherapy in Childhood.

Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy.

Decreased postural control in adolescents born with extremely low birth weight.

The survival rates of infants born preterm with extremely low birth weight (ELBW ≤ 1000 g) have gradually improved over the last decades. However, these infants risk to sustain long-term disorders related to poor neurodevelopment. The objective was to determine whether adolescents born with ELBW have decreased postural control and stability adaptation. Twenty-nine ELBW subjects performed posturography with eyes open and closed under unperturbed and perturbed standing by repeated calf vibration. Their results were compared with twenty-one age- and gender-matched controls born after full-term pregnancy. The ELBW group had significantly decreased stability compared with controls in anteroposterior direction, both during the easier quiet stance posturography (p = 0.007) and during balance perturbations (p = 0.007). The ELBW group had similar stability decrease in lateral direction during balance perturbations (p = 0.013). Statistically, the stability decreases were similar with eyes closed and open, but proportionally larger with eyes open in both directions. Both groups manifested significant adaptation (p ≤ 0.023) to the balance perturbations in anteroposterior direction, though this adaptation process could not compensate for the general stability deficits caused by ELBW on postural control. Hence, adolescent survivors of ELBW commonly suffer long-term deficits in postural control, manifested as use of substantially more recorded energy on performing stability regulating high-frequency movements and declined stability with closed and open eyes both in anteroposterior and lateral direction. The determined relationship between premature birth and long-term functional deficits advocates that interventions should be developed to provide preventive care in neonatal care units and later on in life.

Systems reconsolidation reveals a selective role for the anterior cingulate cortex in generalized contextual fear memory expression.

After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory.

Long-term effects from bacterial meningitis in childhood and adolescence on postural control.

Bacterial meningitis in childhood is associated with cognitive deficiencies, sensorimotor impairments and motor dysfunction later in life. However, the long-term effects on postural control is largely unknown, e.g., whether meningitis subjects as adults fully can utilize visual information and adaptation to enhance stability. Thirty-six subjects (20 women, mean age 19.3 years) treated in childhood or adolescence for bacterial meningitis, and 25 controls (13 women, mean age 25.1 years) performed posturography with eyes open and closed under unperturbed and perturbed standing. The meningitis subjects were screened for subjective vertigo symptoms using a questionnaire, clinically tested with headshake and head thrust test, as well as their hearing was evaluated. Meningitis subjects were significantly more unstable than controls during unperturbed (p≤0.014) and perturbed standing, though while perturbed only with eyes open in anteroposterior direction (p = 0.034) whereas in lateral direction both with eyes open and closed (p<0.001). Meningitis subjects had poorer adaption ability to balance perturbations especially with eyes open, and they frequently reported symptoms of unsteadiness (88% of the subjects) and dizziness (81%), which was found significantly correlated to objectively decreased stability. Out of the 36 subjects only 3 had unilateral hearing impairment. Hence, survivors of childhood bacterial meningitis may suffer long-term disorders affecting postural control, and would greatly benefit if these common late effects became generally known so treatments can be developed and applied.

Involvement of the anterior cingulate cortex in formation, consolidation, and reconsolidation of recent and remote contextual fear memory.

It has been suggested that memories become more stable and less susceptible to the disruption of reconsolidation over weeks after learning. Here, we test this by targeting the anterior cingulate cortex (ACC) and test its involvement in the formation, consolidation, and reconsolidation of recent and remote contextual fear memory. We found that inhibiting NMDAR-NR2B activity disrupts memory formation, and that infusion of the protein-synthesis inhibitor anisomycin impairs memory consolidation and reconsolidation of recent and remote memory. Our findings demonstrate for the first time that the ACC plays an important role in reconsolidation of contextual fear memory at recent and remote time points.

Periodically reactivated context memory retains its precision and dependence on the hippocampus.

Hippocampus is hypothesized to play a temporary role in the retrieval of context memories. Similarly, previous studies have reported that the expression of context memories becomes more generalized as memory ages. We report, first, that contextual fear memory expression changes from being sensitive to dorsal hippocampus inactivation by muscimol at 2 days post-conditioning, to insensitive at 28 days, and second, that over the same period rats lose their ability to discriminate between a novel and conditioned context. Furthermore, we show that repeated brief memory reactivation sessions prevent memory from becoming both hippocampus-independent and generalized.

Severe difficulties with word recognition in noise after platinum chemotherapy in childhood, and improvements with open-fitting hearing-aids.

OBJECTIVE: To investigate word recognition in noise in subjects treated in childhood with chemotherapy, study benefits of open-fitting hearing-aids for word recognition, and investigate whether self-reported hearing-handicap corresponded to subjects' word recognition ability. DESIGN: Subjects diagnosed with cancer and treated with platinum-based chemotherapy in childhood underwent audiometric evaluations. STUDY SAMPLE: Fifteen subjects (eight females and seven males) fulfilled the criteria set for the study, and four of those received customized open-fitting hearing-aids. RESULTS: Subjects with cisplatin-induced ototoxicity had severe difficulties recognizing words in noise, and scored as low as 54% below reference scores standardized for age and degree of hearing loss. Hearing-impaired subjects' self-reported hearing-handicap correlated significantly with word recognition in a quiet environment but not in noise. Word recognition in noise improved markedly (up to 46%) with hearing-aids, and the self-reported hearing-handicap and disability score were reduced by more than 50%. CONCLUSIONS: This study demonstrates the importance of testing word recognition in noise in subjects treated with platinum-based chemotherapy in childhood, and to use specific custom-made questionnaires to evaluate the experienced hearing-handicap. Open-fitting hearing-aids are a good alternative for subjects suffering from poor word recognition in noise.

Long term hearing degeneration after platinum-based chemotherapy in childhood.

The aim of this study was to investigate long-term development of hearing in subjects who had received platinum-based chemotherapy in childhood or adolescence. Another aim was to assess the self-reported hearing loss handicap and compare it to audiometric measurements. Medical records from individuals diagnosed with childhood cancer and treated with platinum-based chemotherapy between 1985 and 2000 at the University Hospital in Lund Sweden were reviewed retrospectively. Fifteen subjects, who fulfilled the eligibility criteria set for the study, underwent a thorough audiometric evaluation. The results show that the hearing loss, in subjects with ototoxicity had increased after the end of treatment, to include also the lower frequencies. The largest deterioration in hearing thresholds, up to 55 dB HL, was found at frequencies above 2 kHz. The findings also reveal that the subjects have a considerably greater hearing loss handicap and disability than would be expected from the results of the audiometric evaluations. The conclusion of this study is that children and adolescence treated with platinum-based chemotherapy should have regular audiometric follow-up examinations, also many years after the end of treatment. Furthermore, assessments of self-reported hearing disability should be made during and after chemotherapy.

Memory reconsolidation: an update.

Memory consolidation refers to the stabilization that a new memory has to undergo in order to persist. Recently, this dominant view of memory has been challenged by renewed interest in reconsolidation, where consolidated memories return to a transient unstable state following their retrieval, from which they must again stabilize in order to persist. In this review, we discuss how reconsolidation is supported by the same line of evidence as consolidation and recent findings of boundary conditions of reconsolidation. Furthermore, we discuss how recent controversies on the nature of amnesia following challenges to reconsolidation are using the same paradigm that failed to resolve the nature of amnesia after challenges to consolidation; we also discuss a new paradigm that can lead to more fruitful ways of studying amnesia in general.

A bridge over troubled water: reconsolidation as a link between cognitive and neuroscientific memory research traditions.

There are two research traditions on dynamic memory processes. In cognitive psychology, the malleable nature of long-term memory has been extensively documented. Distortions, such as the misinformation effect or hindsight bias, illustrate that memories can be easily changed, often without their owner taking notice. On the other hand, effects like hypermnesia demonstrate that memory might be more reliable than these distortions suggest. In the neuroscience field, similar observations were obtained mostly from animal studies. Research on memory consolidation suggested that memories become progressively resistant to amnesic treatments over time, but the reconsolidation phenomenon showed that this stability can be transiently lifted when these memories are reactivated, i.e., retrieved. Surprisingly, both research traditions have not taken much notice of each others' advances in understanding memory dynamics. We apply concepts developed in neuroscience to phenomena revealed in cognitive psychology to illustrate how these twins separated at birth may be reunited again.