Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations ...correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.
Traumatic brain injury is one of the leading causes of morbidity and mortality throughout the world. Its increasing incidence, in addition to its fundamental role in the development of ...neurodegenerative disease, proves especially concerning. Despite extensive preclinical and clinical studies, researchers have yet to identify a safe and effective neuroprotective strategy. Following brain trauma, secondary injury from molecular, metabolic, and cellular changes causes progressive cerebral tissue damage. Chronic neuroinflammation following traumatic brain injuries is a key player in the development of secondary injury. Targeting this phenomenon for development of effective neuroprotective therapies holds promise. This strategy warrants a concrete understanding of complex neuroinflammatory mechanisms. In this review, we discuss pathophysiological mechanisms such as the innate immune response, glial activation, blood-brain barrier disruption, activation of immune mediators, as well as biological markers of traumatic brain injury. We then review existing and emerging pharmacological therapies that target neuroinflammation to improve functional outcome.
Temporomandibular disorders (TMD) are characterised by chronic pain and dysfunction in the jaw joint and masticatory muscles. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a ...potential non-invasive treatment for chronic pain; however, its effectiveness in individuals with TMD has not been thoroughly investigated. This study aimed to evaluate the immediate and sustained (over seven consecutive days) effects of a single session of active rTMS compared to sham stimulation on pain intensity and pain unpleasantness in individuals with TMD.
A randomised, double-blind, sham-controlled trial enrolled 41 female participants with chronic TMD. Pain intensity and pain unpleasantness were assessed immediately pre- and post-intervention, as well as twice daily for 21 days using electronic diaries. Secondary outcomes included pain interference, sleep quality, positive and negative affect and pain catastrophizing. Adverse effects were monitored. Repeated measures ANOVA and multilevel modelling regression analyses were employed for data analysis.
Active rTMS demonstrated a significant immediate mild reduction in pain intensity and pain unpleasantness compared to sham stimulation. However, these effects were not sustained over the 7-day post-intervention period. No significant differences were observed between interventions for pain interference, sleep quality and negative affect. A minority of participants reported minor and transient side effects, including headaches and fatigue.
A single session of active rTMS was safe and led to immediate mild analgesic effects in individuals with TMD compared to sham stimulation. However, no significant differences were observed between interventions over the 7-day post-intervention period. Based on this study, rTMS stimulation appears to be a promising safe approach to be tested in TMD patients with longer stimulation protocols.
The aim of this study was to determine the neuropsychological consequences of a middle interhemispheric approach for the removal of tumors of the third or lateral ventricles. A retrospective analysis ...of eight callosotomized patients for ventricular tumors (three males/five females; mean age: 48.7 ± 11.2 years; education level: 11.9 ± 2.9 years) and eight healthy subjects was performed. An extensive neuropsychological test battery was used to evaluate global intellectual efficiency, memory capacities, executive functions, and interhemispheric transfer of a procedural learning task (serial reaction time task/SRTT). Neuropsychological results showed that: (1) five of eight patients operated through a middle transcallosal approach had disturbances of verbal or visual memory; (2) three of eight patients displayed a dysexecutive cognitive syndrome (two of eight of whom presenting with a deficit of verbal fluency); (3) two of eight patients presented a dysexecutive behavior syndrome; and (4) with regard to the SRTT, although all participants learned the task, in contrast to controls, the callosotomized patients showed an increase in reaction times and an absence of interhemispheric transfer of learning from one hand to the other. The transcallosal approach transects a large number of callosal fibers. This damage accounts for the deficits of memory, the dysexecutive cognitive and behavioral syndrome, and disturbances in interhemispheric transfer of learning.
While most studies have been interested in the distinct, predisposing roles of the common BDNF Val66Met variant and extraversion personality traits on episodic memory, very few studies have looked at ...the synergistic effects of genetic and personality factors to account for cognitive variance. This is surprising considering recent reports challenging the long-held belief that the BDNFMet variant negatively impacts cognitive function. A total of 75 young healthy adults (26 of them carried at least one copy of the BDNFMet allele) took part in this study consisting of genetic profiling from saliva, personality assessment using the Revised NEO Personality Inventory (NEO PI-R) and a short battery of neuropsychological tests. An ANOVA revealed that BDNFMet carriers were significantly less extraverted than BDNFVal carriers (F1,73 = 9.54; p < 0.01; ηp2 = 0.126). Moreover, extraversion was found to significantly moderate the relationship between the BDNF genotype and episodic memory performance (p = 0.03). Subsequent correlational analyses yielded a strong and significant correlation (r = 0.542; p < 0.005) between introversion and delayed episodic memory specific to BDNFMet individuals. The present study suggests that introversion and the BDNFMet variant synergistically interact to reduce episodic memory performance in healthy, young adults. These findings reaffirm that a more accurate explanation of cognitive variance can be achieved by looking at the synergistic effects of genotype and phenotype factors.
Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation techniques that are being explored as therapeutic alternatives for the ...management of various chronic pain conditions.
The primary objective of this systematic review is to assess the efficacy of TMS and tDCS in reducing clinical pain intensity in chronic orofacial pain (OFP) disorders. The secondary objectives are to describe adverse effects, duration of relief, and TMS/tDCS methodologies used in chronic OFP disorders.
A search was performed in MEDLINE, Embase, Web of Science, Scopus, and Google Scholar. Inclusion criteria were 1) population: adults diagnosed with chronic OFP including neuropathic and non-neuropathic disorders; 2) intervention: active TMS or tDCS stimulation regardless of the used protocol; 3) comparison: sham TMS or tDCS stimulation; and 4) outcome: primary outcome was patient reported pain intensity. Secondary outcomes were duration of pain relief, adverse effects, and methodological parameters. Risk of bias and quality of study reporting were also assessed.
A total of 556 individual citations were identified by the search strategy, with 14 articles meeting selection criteria (TMS=11; tDCS=3). Data were obtained for a total of 228 patients. Included OFP disorders were trigeminal neuralgia, trigeminal neuropathy, burning mouth syndrome, atypical facial pain, and temporomandibular disorders. Significant pain reductions were obtained in both techniques. More number of sessions yielded to more durable effects. Overall, high risk of bias and poor study quality were found.
TMS and tDCS appear to be safe and promising alternatives to reduce pain intensity in different chronic OFP disorders. Additional research effort is needed to reduce bias, improve quality, and characterize optimal brain stimulation parameters to promote their efficacy.
Mild traumatic brain injury (MTBI), often referred to as concussion when it occurs in sports, produces persistent cognitive problems in at least 15% of patients. Unfortunately, conventional ...neuropsychological tests usually yield results within normal limits in this population. The main objective of this event-related potential (ERP) study was to understand brain functioning during the performance of a working memory (WM) task in patients who have sustained an MTBI, mostly due to motor vehicle accident or sports concussion. This study also aimed for a better understanding of the association between brain functioning as measured with ERP, behavioral performance on the WM task, postconcussion symptoms, type of injury (that is, sports concussion vs other types), and time since the injury.
Forty-four patients with MTBI (7.6 ± 8.4 months postinjury) were tested on a visual WM task with simultaneous recording of ERP, and were compared with 40 control volunteers who were their equivalent for age and sex. Amplitude and latency of frontal (N200 and N350) and parietal (P200 and P300) ERP waves were measured and were compared between groups. Correlation analyses were also performed between ERP characteristics, clinical variables, and behavioral performance.
A significant group difference was found for behavioral performance on the WM task, in which the MTBI group had a lower percentage of correct answers than the control group (p < 0.05). The patients with MTBI also had smaller amplitudes of both frontal N350 and parietal P300 ERP components when compared with control volunteers (p < 0.05). No changes were found for latency of ERP components. Smaller ERP amplitudes were associated with slower reaction times and worse accuracy on the WM task among patients with MTBI (p < 0.05). Types of injury (that is, sports concussion vs other mechanisms) were not associated with different ERP characteristics.
Abnormal ERP results are observed in patients after MTBI or sports concussion, even for those in the nonacute stage after their injury. Current standard clinical evaluations most often fail to detect cerebral dysfunction after MTBI, even when patients or athletes report symptoms. Clinicians should be aware that patients with MTBI, including sports concussion, probably have underlying mild but persistent cerebral dysfunctions that require further investigation.
In Parkinson's disease (PD), motor dysfunctions only become apparent after extensive loss of DA innervation. This resilience has been hypothesized to be due to the ability of many motor behaviors to ...be sustained through a diffuse basal tone of DA; but experimental evidence for this is limited. Here we show that conditional deletion of the calcium sensor synaptotagmin-1 (Syt1) in DA neurons (Syt1 cKO
mice) abrogates most activity-dependent axonal DA release in the striatum and mesencephalon, leaving somatodendritic (STD) DA release intact. Strikingly, Syt1 cKO
mice showed intact performance in multiple unconditioned DA-dependent motor tasks and even in a task evaluating conditioned motivation for food. Considering that basal extracellular DA levels in the striatum were unchanged, our findings suggest that activity-dependent DA release is dispensable for such tasks and that they can be sustained by a basal tone of extracellular DA. Taken together, our findings reveal the striking resilience of DA-dependent motor functions in the context of a near-abolition of phasic DA release, shedding new light on why extensive loss of DA innervation is required to reveal motor dysfunctions in PD.
Although there is a growing body of literature on the impact of multiple concussions on cognitive function with aging, less is known about the long-term impact of sustaining a single mild traumatic ...brain injury (mTBI). Additionally, very few interventions exist to treat mTBI patients and prevent a possible accelerated cognitive decline. This study aimed to: 1) examine the long-term effects of a single mTBI on cognition in patients aged between 55 and 70 years old; and 2) evaluate the cognitive effects of an aerobic exercise program for these patients.
Thirty-five participants (average age: 58.89, SD=4.14) were assessed using neuropsychological tests. Among them, 18 hadsustained a mTBI two to seven years earlier. Significant differences in information processing speed, executive function and visual memory were found between controls and mTBI patients. Sixteen of the mTBI patients then engaged in a 12-week physical exercise program. They were divided into equivalent groups: 1) aerobic training (cycle ergometers); or 2) stretching exercises. The participants' cardiopulmonary fitness (VO2max) was evaluated pre- and postintervention and neuropsychological tests were re-administered postintervention.
Participants from the aerobic group significantly improved their fitness compared to the stretching group. However, no between-group difference was found on neuropsychological measures postintervention.
In summary, this study shows long-term cognitive effects of mTBI in late adulthood patients. Moreover, the controlled, 12-week aerobic exercise program did not lead to cognitive improvements in our small mTBI sample. Lastly, future directions in optimizing mTBI intervention are discussed.
This study extracted the error-related negativity (ERN) waveform component recorded from a visual-spatial attention and a visual short-term memory task to assess rigorously the long-term and ...cumulative effects of concussions on evaluative processes of cognitive control related to performance monitoring. This study demonstrates that, relative to control athletes, multiply concussed athletes show significant ERN amplitude reduction elicited by error generation. These cumulative effects of concussions on ERN amplitude were found in two distinct experimental paradigms designed to solicit concussion-sensitive cognitive abilities such as attention and short-term memory. This suggests that the mechanisms that contribute to the evaluation of cognitive performance may be significantly affected following multiple concussions even in low-conflict situations.
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