Dr Philip Dean

There is significant overlap between the neuropathology of mild traumatic brain injury (mTBI) and the cellular role of creatine, as well as evidence of neural creatine alterations after mTBI. Creatine supplementation has not been researched in mTBI, but shows some potential as a neuroprotective when administered prior to or after TBI. Consistent with creatine’s cellular role, supplementation reduced neuronal damage, protected against the effects of cellular energy crisis and improved cognitive and somatic symptoms. A variety of factors influencing the efficacy of creatine supplementation are highlighted, as well as avenues for future research into the potential of supplementation as an intervention for mTBI. In particular, the slow neural uptake of creatine may mean that greater effects are achieved by pre-emptive supplementation in at-risk groups.

Motor disorders increase dramatically with age; however, little is known about non-clinical ageing of motor control mechanisms and their respective neural correlates. With the present experiment we aimed to study age effects on advance movement preparation, a key characteristic of motor behaviour that is known to involve premotor and primary motor circuits. The respective brain regions are subject to age-related brain atrophy of grey and white matter, and we therefore hypothesized that motor preparation mechanisms may be altered in older persons.Using a motor priming paradigm, performance data and event-related potentials were recorded in older (68–83 years) and younger (21–25 years) participants. The effect pattern observed for the younger group fully replicated previous findings, showing significant reaction time benefits and greater foreperiod activity for valid trials, as well as lateralized activation over motor regions. In older participants, the validity effect was insignificant, which corresponded to markedly reduced foreperiod amplitudes and the absence of lateralized activity. At the same time, the event-related potential showed a frontocentrally distributed positive component peaking in the P300 latency range after presentation of the prime. The amplitude of this potential was enhanced in elderly compared with young participants.The data suggest that the information processing related to the anticipation and preparation of an upcoming response changes substantially with age. In contrast to younger participants, older participants show no indication of effector-specific activation and recruit frontal areas in anticipation of a response signal. It is therefore not only movement execution that changes with age but also motor cognition. Keywords: ageing, contingent negative variation, electroencephalography, event-related laterality, lateralised readiness potential, movement preparation

Background. Initial evidence suggests that the integrity of the ipsilesional corticospinal tract (CST) after stroke is strongly related to motor function in the chronic state but not the treatment gain induced by motor rehabilitation. Objective. We examined the association of motor status and treatment benefit by testing patients with a wide range of severity of hemiparesis of the left and right upper extremity. Method. Diffusion tensor imaging was performed in 22 patients beyond 12 months after onset of stroke with severe to moderate hemiparesis. Motor function was tested before and after 2 weeks of modified constraint-induced movement therapy. Results. CST integrity, but not lesion volume, correlated with the motor ability measures of the Wolf Motor Function Test and the Motor Activity Log. No differences were found between left and right hemiparesis. Motor performance improved significantly with the treatment regime, and did so equally for patients with left and right arm paresis. However, treatment benefit was not associated with either CST integrity or lesion volume. Conclusion. CST integrity correlated best in this small trial with chronic long-term status but not treatment-induced improvements. The CST may play a different role in the mechanisms mediating long-term outcome compared to those underlying practice-induced gains after a chronic plateau in motor function.

Background: Persistent postconcussion syndrome (PCS) occurs in around 5– 10% of individuals after mild traumatic brain injury (mTBI), but research into the underlying biology of these ongoing symptoms is limited and inconsistent. One reason for this could be the heterogeneity inherent to mTBI, with individualized injury mechanisms and psychological factors. A multimodal imaging study may be able to characterize the injury better. Aim: To look at the relationship between functional (fMRI), structural (diffusion tensor imaging), and metabolic (magnetic resonance spectroscopy) data in the same participants in the long term (>1 year) after injury. It was hypothesized that only those mTBI participants with persistent PCS would show functional changes, and that these changes would be related to reduced structural integrity and altered metabolite concentrations. Methods: Functional changes associated with persistent PCS after mTBI (>1 year postinjury) were investigated in participants with and without PCS (both n = 8) and non-head injured participants (n = 9) during performance of working memory and attention/processing speed tasks. Correlation analyses were performed to look at the relationship between the functional data and structural and metabolic alterations in the same participants. Results: There were no behavioral differences between the groups, but participants with greater PCS symptoms exhibited greater activation in attention-related areas (anterior cingulate), along with reduced activation in temporal, default mode network, and working memory areas (left prefrontal) as cognitive load was increased from the easiest to the most difficult task. Functional changes in these areas correlated with reduced structural integrity in corpus callosum and anterior white matter, and reduced creatine concentration in right dorsolateral prefrontal cortex. Conclusion: These data suggest that the top-down attentional regulation and deactivation of task-irrelevant areas may be compensating for the reduction in working memory capacity and variation in white matter transmission caused by the structural and metabolic changes after injury. This may in turn be contributing to secondary PCS symptoms such as fatigue and headache. Further research is required using multimodal data to investigate the mechanisms of injury after mTBI, but also to aid individualized diagnosis and prognosis.

Presenting information in a coherent fashion has been shown to increase processing fluency, which in turn influences affective responses. The pattern of responses have been explained by two apparently competing accounts: hedonic marking (response to fluency is positive) and fluency amplification (response to fluency can be positive or negative, depending on stimuli valence). This paper proposes that these accounts are not competing explanations, but separate mechanisms, serving different purposes. Therefore, their individual contributions to overall affective responses should be observable. In three experiments, participants were presented with businesses scenarios, with riskiness (valence) and coherence (fluency) manipulated, and affective responses recorded. Results suggested that increasing the fluency of stimuli increases positive affect. If the stimulus is negative, then increasing fluency simultaneously increases negative affect. These affective responses appeared to cancel each other out (Experiment 1) when measured using self-report bipolar scales. However, separate measurement of positive and negative affect, either using unipolar scales (Experiment 2) or using facial electromyography (Experiment 3), provided evidence for co-occurring positive and negative affective responses, and therefore the co-existence of hedonic marking and fluency amplification mechanisms.

This pilot study explores the metabolic changes associated with persistent postconcussion syndrome (PCS) after mild traumatic brain injury (mTBI; >12 months after injury) using magnetic resonance spectroscopy. We hypothesized that those mTBI participants with PCS will have larger metabolic differences than those without. Data were collected from mTBI participants with PCS, mTBI participants without PCS and non-head-injured participants (all groups: n=8). Magnetic resonance spectroscopy metabolite profiles within the dorsolateral prefrontal cortex showed a reduced creatine/choline ratio in mTBI patients compared with control participants. This data provides initial evidence for residual metabolic changes in chronic mTBI patients, but there was no conclusive relationship between these metabolic changes and PCS symptom report. Creatine is involved in maintaining energy levels in cells with high or fluctuating energy demand, suggesting that there may be some residual energy impairment in chronic mTBI.

Although a proportion of individuals report chronic cognitive difficulties after mild traumatic brain injury (mTBI), results from behavioral testing have been inconsistent. In fact, the variability inherent to the mTBI population may be masking subtle cognitive deficits. We hypothesized that this variability could be reduced by accounting for post-concussion syndrome (PCS) in the sample. Thirty-six participants with mTBI (>1 year post-injury) and 36 non-head injured controls performed information processing speed (Paced Visual Serial Addition Task, PVSAT) and working memory (n-Back) tasks. Both groups were split by PCS diagnosis (4 groups, all n = 18), with categorization of controls based on symptom report. Participants with mTBI and persistent PCS had significantly greater error rates on both the n-Back and PVSAT, at every difficulty level except 0-Back (used as a test of performance validity). There was no difference between any of the other groups. Therefore, a cognitive deficit can be observed in mTBI participants, even 1 year after injury. Correlations between cognitive performance and symptoms were only observed for mTBI participants, with worse performance correlating with lower sleep quality, in addition to a medium effect size association (falling short of statistical significance) with higher PCS symptoms, post-traumatic stress disorder (PTSD), and anxiety. These results suggest that the reduction in cognitive performance is not due to greater symptom report itself, but is associated to some extent with the initial injury. Furthermore, the results validate the utility of our participant grouping, and demonstrate its potential to reduce the variability observed in previous studies.

The lateralization index (LI) as determined from functional transcranial Doppler sonography (fTCD) can be used to determine the hemispheric organization of neural activation during a behavioral task. Previous studies have proposed different methods to determine this index, but to our knowledge no studies have compared the performance of these methods. In this study, we compare two established methods with a simpler method proposed here. The aim was to see whether similar results could be achieved with a simpler method and to give an indication of the analysis steps required to determine the LI. A simple unimanual motor task was performed while fTCD was acquired, and the LI determined by each of these methods was compared. In addition, LI determined by each method was related to behavioural output in the form of degree of handedness. The results suggest that although the methods differed in complexity, they yielded similar results when determining the lateralization of motor functions, and its correlation with behavior. Further investigation is needed to expand the conclusions of this preliminary study, however the new method proposed in the paper has great potential as it is much simpler than the more established methods yet yields similar results.

Background Chronic hemiplegia is a common long-term consequence of stroke, and subsequent motor recovery is often incomplete. Neurophysiological studies have focused on motor execution deficits in relatively high functioning patients. Much less is known about the influence exerted by processes related to motor preparation, particularly in patients with poor motor recovery. Methodology/Principal Findings The current study investigates motor preparation using a modified response-priming experiment in a large sample of patients (n = 50) with moderate-to-severe chronic hemiparesis. The behavioural results revealed that hemiparetic patients had an increased response-priming effect compared to controls, but that their response times were markedly slower for both hands. Patients also demonstrated significantly enhanced midline late contingent negative variation (CNV) during paretic hand preparation, despite the absence of overall group differences when compared to controls. Furthermore, increased amplitude of the midline CNV correlated with a greater response-priming effect. We propose that these changes might reflect greater anticipated effort to respond in patients, and consequently that advance cueing of motor responses may be of benefit in these individuals. We further observed significantly reduced CNV amplitudes over the lesioned hemisphere in hemiparetic patients compared to controls during non-paretic hand preparation, preparation of both hands and no hand preparation. Two potential explanations for these CNV reductions are discussed: alterations in anticipatory attention or state changes in motor processing, for example an imbalance in inter-hemispheric inhibition. Conclusions/Significance Overall, this study provides evidence that movement preparation could play a crucial role in hemiparetic motor deficits, and that advance motor cueing may be of benefit in future therapeutic interventions. In addition, it demonstrates the importance of monitoring both the non-paretic and paretic hand after stroke and during therapeutic intervention.

Primary objective: To compare the prevalence of persistent post-concussion syndrome (PCS; >1 year post-injury) in participants with mild traumatic brain injury (mTBI) and those without head injury. Research design: A cross-sectional sample of 119 participants with mTBI and 246 without previous head injury. Methods: Online questionnaires collected data about post-concussion symptoms, cognitive failures, anxiety, depression, sleep behaviour and post-traumatic stress disorder. Variability within the sample was addressed by splitting by PCS diagnosis to create four groups: mTBI + PCS, mTBI-PCS, Control + PCS and Control-PCS. PCS was diagnosed using ICD-10 criteria in all groups, with controls not requiring previous head injury. Main outcomes and results: PCS was present to a similar extent in participants with no head injury (34%) compared to those with mTBI (31%). Only report of headaches, which could be caused by expectation bias, distinguished between mTBI + PCS and Control + PCS groups. In addition, significantly higher cognitive problems were observed in participants with mTBI compared with the control group. Conclusions: Persistent PCS, as currently defined, is not specific to mTBI. These data suggest that somatic and cognitive symptoms are most likely to be able to distinguish PCS after mTBI from that present in the general population. Further research is necessary into these factors in order to create more specific PCS diagnostic criteria.

In principle, information for 3-D motion perception is provided by the differences in position and motion between left- and right-eye images of the world. It is known that observers can precisely judge between different 3-D motion trajectories, but the accuracy of binocular 3-D motion perception has not been studied. The authors measured the accuracy of 3-D motion perception. In 4 different tasks, observers were inaccurate, overestimating trajectory angle, despite consistently choosing similar angles (high precision). Errors did not vary consistently with target distance, as would be expected had inaccuracy been due to misestimates of viewing distance. Observers appeared to rely strongly on the lateral position of the target, almost to the exclusion of the use of depth information. For the present tasks, these data suggest that neither an accurate estimate of 3-D motion direction nor one of passing distance can be obtained using only binocular cues to motion in depth.

To investigate sustained structural changes in the long-term (>1 year) after mild traumatic brain injury (mTBI) and their relationship to ongoing post-concussion syndrome (PCS).

CI therapy is effective in patients with relatively good levels of residual arm function but its applicability to patients with low-functioning hemiparesis is not entirely clear. In the present study, we examined the feasibility and efficacy of the CI therapy concept in patients with very limited upper arm function prior to treatment, and further tested how the length of daily shaping training and constraining the good arm affects treatment outcome. In a baseline-controlled design, 65 chronic patients were treated with 2weeks of modified CI therapy. Patients were randomly allocated to four treatment groups receiving 90 or 180 min of daily shaping training applied with or without constraint, respectively. Outcome was measured through the Reliable Change Index, which was calculated for parameters of motor function, health, and psychological wellbeing. Follow-up data were collected at 6 and 12 months.Two analyses were conducted, a whole-group analysis across all 65 participants and a sub-group analysis contrasting the four treatment variants. The whole-group analysis showed a significant treatment effect, which was largely sustained after 1 year. The sub-group analysis revealed a mixed picture; while improvements against the baseline period were observed in all four subgroups, 180 min of daily shaping training coupled with the constraint yielded better outcome on the MAL but not the WMFT, while for 90 min of training the level of improvement was similar for those who wore the constraint and those who did not. Together these results suggest that, at least in those patients available for follow-up measures, modified CI therapy induces sustained improvements in motor function in patients with chronic low-functioning hemiparesis. The absence of clear differences between the four treatment variants points to a complex relationship between the length of daily shaping training and the constraint in this patient group, which is likely to be mediated by fatigue and/or compliance with the constraint.

Driven by considerations arising from studies in hemiplegic patients, we examined how the insertion of rare n-response trials affects motor preparation studied in S1-S2 paradigms. Results for the motor priming task (experiment 1) showed that for response-requiring conditions the 'validity effect' was conserved for behavioural and ERP indices. For the no-response condition, foreperiod activities were similar to neutral trials suggesting motor preparation in both conditions and hence preparation for the unlikely event. A second experiment with fully predictive primes showed no evidence for movement preparation processes in no-response trials. These findings suggest different strategies for the anticipation of likely responses compared to likely events that don't require a response.

The present study explores the link between brain metabolites, PCS symptoms and cognitive ability in participants who have experienced an mTBI. Lactate has been previously been shown to be elevated in acute mTBI (Son, Park et al. 2000), however, 2 month post-incidence lactate levels had returned to normal. The present study suggests that PCS symptoms as well as metabolite abnormalities may persist. More specifically the data provides initial evidence for a link between the elevation of lactate and with severity of long-term PCS following mTBI. Poster presented in Session: Other Spectroscopy Methodology Proceedings of the International Society for Magnetic Resonance in Medicine, 18 (2010); p. 937. ISSN 1545-4428. Available at: http://www.ismrm.org/meetings-workshops/2010-annual-meeting-3/

Behavioural studies suggest that elevated blood glucose concentrations accelerate response times in complex tasks (Owens and Benton, 2004, Neuropsychobiology). With the present study we aimed to explore the mechanisms subserving elevated blood glucose effects (7 mmol/litre versus fasting levels of 5 mmol/litre) by studying EEG-derived indices of sensorimotor processing. More specifically, the Eriksen flanker task was used to examine glucose-dependent modulations of the P300, the stimulus lateralized readiness potentials (LRPs), and response-locked LRP, to see whether enhanced blood glucose levels affect stimulus evaluation, response planning, and response selection respectively. 10 participants took part in a within-participant double-blind 2-session experiment where either glucose (25 g) or placebo drinks were administered. Initial data suggests slower reaction times, higher error rates and delayed stimulus-locked LRP onset in incongruent compared to congruent and neutral trials. With placebo administration error rates were increased for the non-dominant hand but not the dominant hand; no effects were found for the EEG parameters. This suggests that hyperglycaemia does not affect senorimotor processing in the flanker task. However, the placebo-related increase in error rates together with the findings of (Donohoe and Benton, 2000) support the proposition that beneficial effects of increased blood glucose levels on cognition might only occur when cognitive demands are high.

Objective: This study employed EEG source localisation procedures to study the contribution of motor preparatory and attentional 10 processing to foreperiod activity in an S1–S2 motor priming task. Methods: Behavioural and high-density event-related potential (ERP) data were recorded in an S1–S2 priming task where participants 12 responded to S2 with a left or right-hand button press. S1 either provided information about response hand (informative) or ambiguous information (uninformative). Results: Responses were significantly faster in informative trials compared with uninformative trials. Dipole source analysis of fore-period lateralized ERPs revealed sources of motor preparatory activity in the dorsolateral premotor cortex (PMd) in line with previous work. In addition, two spatial attention components (ADAN, LDAP) were identified with generators in the PMd and occipitotemporal visual areas in the middle temporal (MT) region, respectively. Separation of motor-related and attentional PMd source locations was reliable along the rostral–caudal axis. Conclusions: The presence of attentional components in a motor priming paradigm supports the premotor theory of attention which suggests a close link between attention and motor preparatory processes. Separation of components in the premotor cortex is in accord with a functional division of PMd into rostral (higher-order processing) and caudal (motor-related processing) areas as suggested by imaging work. Significance: A prime for response preparation is a trigger for separate, but closely linked, attention-related activity in premotor areas. copyright: Mathews2006 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology.

Mild traumatic brain injury (mTBI) can induce persistent somatic, affective and cognitive symptoms, collectively known as post-concussion syndrome (PCS). It is debated whether this syndrome is due to biological or psychological factors. Standard structural imaging only detects lesions in a small proportion of those with mTBI, and these lesions are not associated with PCS in the acute (< 3 months) or chronic (> 3 months) stage. However, microlesions and diffuse axonal injury (DAI) have been observed using novel imaging techniques such as diffusion tensor imaging (DTI). White matter damage examined in acute and post-acute/chronic mTBI has been correlated with cognitive and behavioural measures, as well as outcome from injury. Increased damage within the white matter tracts of the corpus callosum and thalamic radiations is observed in those with poorer outcome at 3 months, whereas grey matter damage is independent of outcome. This present study aims to investigate the relation of structural changes and long-term consequences in more detail by assessing the correlation between DTI-based indices and persistent PCS symptomatology. Structural changes were investigated in participants with chronic (>1 year) mTBI and persistent PCS (n¼10), participants with mTBI and no on-going PCS (n¼8) and non-head injured controls (n¼10). Fractional Anisotropy (FA) and cortical thickness were compared between groups to assess white matter integrity and focal damage respectively. In addition, the association between neural structure and level of PCS symptom report was evaluated. We hypothesised that long fibre white matter bundles, such as the corpus callosum, would be damaged in participants with chronic mTBI, with cortical thinning around these areas. Furthermore, we hypothesised that this damage would be related to the persistent PCS symptoms seen after mTBI. If PCS has a biological basis, then participants with mTBI and persistent PCS may have sustained greater damage to these areas at the time of injury than participants without ongoing symptoms. Preliminary analysis demonstrates a reduction in cortical thickness and white matter integrity in participants with chronic (>1 year) mTBI, independent of PCS, compared to controls. Diminished cortical thickness and white matter integrity were seen for cingulate cortex and corpus callosum. In addition, similar reductions were observed when comparing mTBI participants without PCS to those with PCS. This suggests that persistent PCS may have a biological element, with those reporting greater symptoms in the chronic state sustaining greater damage at the time of injury. Future research will investigate the correlation between the constituent symptoms of PCS (cognitive, affective, somatic) and structural damage in order to allow more definitive brain-behaviour associations.

The last-in first-out theory suggests that late-maturing brain regions are affected earlier in the life span than those maturing early. Maturation of the motor system and the frontal executive control system continues into early adulthood. Evidence further suggests that motor preparation, index by the contingent negative variation (CNV), matures relatively late in adolescence and is compromised in persons aged 68–83 years. With the present study we explored the progression of age-related changes in motor preparation control by contrasting behavioral and CNV effects in young (18–23), middle-aged (33–44) and older (61–72) persons using a modified response priming paradigm. All three groups showed the typical motor priming effect pattern with faster RTs in valid trials compared to invalid trials. RTs were significantly slower in the older than the middle-aged and young groups, with no significant difference in error rates. A significantly larger CNV validity effect was found for the young group compared to the older group. CNV topography shifted from parietal to more frontal regions with age. These data provide initial evidence for early changes in motor preparation control mechanisms and lend support for the last-in first-out hypothesis.

Descriptors: motor preparation, hemiparesis, CNV Movement preparation in patients with left hand hemiparesis (n 5 26) was investigated using a response priming paradigm, and in addition compared to age-matched controls (n 5 26). In this experiment, trials with valid, neutral and no response cues were presented 1300 ms before the imperative stimulus. Behavioral results showed validity effects for the control and the patient group’s affected and unaffected hand. In addition, patients responded slower with both the affected and the unaffected hand compared to the control group. Analysis of CNV amplitude within the patient group revealed validity effects over the contralateral left hemisphere for the unaffected hand. Interestingly, similar validity effects where found for both hemispheres for the affected hand. This additional usage of the ipsilateral left hemisphere might reflect a greater effort required for movement preparation. A comparison between conditions of patient and control groups showed reduced CNV amplitude over central and centro-parietal right hemisphere for validly prepared trials of the unaffected hand compared to the control group’s right hand. This might suggest a reduced usage of the lesioned ipsilateral cortex side possibly reflecting reduced innervation after the acute phase of the stroke. The competition for resources in the left hemisphere between the affected and unaffected hand and the reduced usage of the right ipsilateral hemisphere for the unaffected hand might explain why patients are generally slower than controls in the task.

Descriptors: glucose, LRP, flanker task Behavioural studies suggest that elevated blood glucose concentrations accelerate response times in complex tasks (Owens and Benton, 2004, Neuropsychobiology). With the present study we aimed to explore the mechanisms subserving elevated blood glucose effects (7 mmol/litre versus fasting levels of 5 mmol/litre) by studying EEG-derived indices of sensorimotor processing. More specifically, the Eriksen flanker task was used to examine glucose-dependent modulations of the P300, the stimulus lateralized readiness potentials (LRPs), and response-locked LRP, to see whether enhanced blood glucose levels affect stimulus evaluation, response planning, and response selection respectively. 10 participants took part in a within-participant double-blind 2-session experiment where either glucose (25 g) or placebo drinks were administered. Initial data suggests slower reaction times, higher error rates and delayed stimulus-locked LRP onset in incongruent compared to congruent and neutral trials. With placebo administration error rates were increased for the non-dominant hand but not the dominant hand; no effects were found for the EEG parameters. This suggests that hyperglycaemia does not affect senorimotor processing in the flanker task. However, the placebo-related increase in error rates together with the findings of (Donohoe and Benton, 2000) support the proposition that beneficial effects of increased blood glucose levels on cognition might only occur when cognitive demands are high.

Stroke patients with motor deficits often report daytime sleepiness. While slowing of the EEG during wakefulness has been shown after stroke, it is unknown if and how this is linked to their perception of sleepiness. Using waking EEG and a motor task (associated with mild sleepiness), we examined: 1) differences in the frequency composition and lateralisation of the EEG between stroke patients and controls, and 2) the relationship between the EEG and subjective sleepiness ratings. EEG and Karolinska Sleepiness Scale (KSS) data were collected from 15 right hemispheric stroke patients and 15 matched controls before and after a motor priming task. Frequency analysis was performed on C3 and C4 channels. Prior to the task, the stroke group revealed increased power density below 10 Hz compared to controls for both hemispheres, with more pronounced effects within the lesioned hemisphere. The motor task significantly increased KSS scores in both groups. Increased beta and alpha activity was observed after the task in the control group. The stroke group showed post task increases in beta activity for the non-affected hemisphere and bilateral increases in alpha and theta activity. An association between KSS and the EEG was observed post task in the stroke patients within the theta and alpha bands. Therefore, slowing of the EEG is related to perception of daytime sleepiness in stroke patients. This effect may not have been observed in the controls due to the way in which the motor task manipulates sleepiness within each group, as it is more challenging for those with motor deficits.

OBJECTIVES: Previous research on the biological markers of sustained post-concussion syndrome (PCS) after mild traumatic brain injury (mTBI) has suggested that those with mTBI have a reduction in prefrontal creatine (Dean et al., 2013), which is associated with poorer performance and reduced prefrontal BOLD response in cognitive tasks (Dean et al., 2015). In addition, dietary supplementation of creatine can alleviate PCS symptoms in the acute stage after injury (Sakellaris et al., 2006) or protect from PCS symptoms (Sullivan et al., 2000). It is an intriguing possibility that creatine may also alleviate symptoms, even in the long-term after injury. This study represents a first step, whereby it is investigated whether dietary supplementation leads to increases of creatine in the brain in a non-brain injured population, and whether this is related to behavioural performance or symptom report. METHODS: MRS and behavioural (n-Back; 0-, 2-, 4-back) data was acquired from ten vegetarian participants at three time points, one week apart. Week 1 was baseline, week 2 after placebo (maltodextrin) and week 3 after intervention (creatine monohydrate). Single voxel MRS was acquired from right dorsolateral prefrontal cortex. Both placebo and intervention were taken as 5g of powder dissolved in 250ml of water/milk, two times a day (morning/evening). RESULTS: Behavioural results indicated an effect of condition (0-, 2-, 4-back, p

This study aimed to evaluate on-task electroencephalographic spectral measures and its correlation to performance during a motor imagery (MI) task. By investigating this aspect, we hope to understand what makes some individuals MI "illliterates". Eighteen healthy subjects performed an experimental task whereby a cursor was moved to one of two targets (left and right) using only MI of the left and right hands. To evaluate the effect of aptitude, performance was measured as percentage of correct movement to target, and Mahalanobis distances were calculated between whole-scalp spectral patterns during left and right motor imagery. Then the correlation between performance and Mahalanobis distance was investigated for central, and whole-head topographies using Spearman's correlations. In central topographies, distances on alpha band were positively correlated with performance (ρ=0.562, p=0.032), while distances on theta band were negatively correlated to performance (ρ--0.648, p=0.018) in whole-head maps. The investigation of on-task whole-scalp differences allows a holistic comprehension of the neural basis of motor imagery, as well as how this leads to performance variations.

When an object moves in three dimensions (3-D), a combination of binocular disparity and lateral motion (change in visual direction) can, in principle, be used to determine its direction. We know from previous research that observers can be very poor at judging 3-D direction (e.g. Harris, ECVP, 2000). However, we do not know whether the misperception is due to errors in the processing of visual direction or of binocular disparity. Here we tested how well observers can detect different trajectory angles when disparity, or visual direction, are varied separately. We compared two conditions. In the first, the distance moved in depth by a target (with respect to a stationary reference) was held constant at 27.3 min arc (13.2cm in depth). Trajectory angle was varied by changing the extent of lateral target motion (hence changing the final visual direction of the target), to produce trajectories ranging from straight ahead to 20deg to the left or right of the nose. In the second condition, the lateral distance moved was held constant at 1.2cm to the left or right of straight ahead, and the change in depth of the target was varied to create the same range of trajectory angles. Stimuli were presented stereoscopically using stereo shutter goggles running at 120Hz. When depth was held constant, observers were highly inaccurate at perceiving the trajectory angle, but there was a monotonic relationship between physical and perceived angle: wider physical angles were perceived as wider. However, when visual direction was held constant, many observers perceived the whole range of angles as being very similar. The results suggest that observers may be basing their responses primarily on the visual direction of the target, rather than on the relative extent laterally and in depth. Although in principle disparity and lateral position specify 3-D trajectory angle, in practise the human brain may use very much simpler strategies.

Behavioural studies have indicated that response times on complex reaction time tasks are faster if blood glucose concentrations are slightly elevated above normal (Donohoe & Benton, 2000). Such tasks involve several cognitive processing stages but it is not clear which of these stages are speeded after glucose administration. In order to investigate this problem we have used a double blind repeated measures design for the administration of glucose and placebo drinks. Participants performed a Flanker task while EEG was recorded as a physiological measure. More specifically, we used a Flanker task that required participants to respond to either left or right pointing central arrows by pressing a left or a right button, respectively. In addition on each trial there are extra arrows surrounding the central arrow which all either pointed in the same (congruent condition) or opposite (incongruent condition) direction as the central arrow or they were lines without an arrow head (neutral condition) All condition were presented equiprobably. No significant differences between the glucose and placebo condition were observed in mean reaction times and errors rates. However the ERP data showed that the N1 amplitude was significantly increased after glucose administration. This could indicate that stimulus identification is influenced by glucose administration, as previous researchers have found an increased N1 amplitude during discriminative feature processing compared to simple detection tasks (Hopf et al., 2002). In addition, mean reaction times and error rates were analysed separately for each of the 8 blocks. Differences between drink types were only found for the reaction times of the first block. Participants who had received glucose during their 1st session and placebo during the 2nd session, had longer reaction times after glucose administration compared to placebo. However this effect was not found for participants who received placebo before glucose drinks. These findings might be linked to task difficulty effects. Previous research has shown that high task difficulty is necessary to find glucose enhancement effects on the Hick task (sensorimotor function; Donohoe & Benton, 2000), working memory (Kennedy & Scholey, 2001) and episodic memory (Sünram-Lea et al., 2002). Our results conflict directly with Donohoe and Benton’s (2000), potentially caused by methodological or task differences. It might be also possible that separate cognitive processes might be differently affected by glucose; which should be explored in future studies.

OBJECTIVES: Previous research on the biological markers of sustained post-concussion syndrome (PCS) after mild traumatic brain injury (mTBI) has suggested that those with mTBI have a reduction in prefrontal creatine (Dean et al., 2013), which is associated with poorer performance and reduced prefrontal BOLD response in cognitive tasks (Dean et al., 2015). In addition, dietary supplementation of creatine can alleviate PCS symptoms in the acute stage after injury (Sakellaris et al., 2006) or protect from PCS symptoms (Sullivan et al., 2000). It is an intriguing possibility that creatine may also alleviate symptoms, even in the long-term after injury. The previous study (Dean et al., 2015) demonstrated altered fMRI indices, correlated to reduced creatine, despite no difference in behavioural performance between those with mTBI and controls. This study therefore investigates the underlying functional changes brought about by creatine supplementation during a working memory task using combined fMRI and EEG in a non-brain injured population. METHODS: fMRI and EEG data was acquired during an n-back (0-, 2-, 4-back) task from ten vegetarian participants at three time points, one week apart. Week 1 was baseline, week 2 after placebo (maltodextrin) and week 3 after intervention (creatine monohydrate). Both placebo and intervention were taken as 5g of powder dissolved in 250ml of water/milk, two times a day (morning/evening). Analysis of the EEG and fMRI data is ongoing, and will be completed by the conference date. RESULTS: Behavioural results indicated an effect of condition (0-, 2-, 4-back, p

Mild traumatic brain injury (mTBI) can induce persistent somatic, affective and cognitive symptoms, collectively known as post-concussion syndrome (PCS). Standard structural imaging only detects lesions in a small proportion of those with mTBI, and these lesions are not associated with PCS. However, subtle changes in structure have been observed with imaging techniques such as diffusion tensor imaging (DTI). Furthermore, these changes have been shown to correlate with cognitive and behavioural outcome in mTBI participants. This study aims to further this research by investigating the relationship between changes in neural structure and function, cognitive outcome and PCS symptomatology in the long term (>1 year) after mTBI. DTI and functional magnetic resonance imaging (fMRI) data were acquired from participants with chronic (>1 year) mTBI and persistent PCS (n=10), participants with mTBI and no on-going PCS (n=8) and non-head injured controls (n=10). Fractional Anisotropy (FA) and cortical thickness were calculated from DTI and standard structural data acquisitions. Two cognitive tasks were presented to participants in the fMRI study, one assessing working memory (n-Back) and the other assessing information processing speed (paced visual serial addition task [PVSAT]). We hypothesised that participants with mTBI would show greater structural damage and larger BOLD response during the cognitive tasks. In addition, these changes should be related to the persistent PCS symptoms reported. Preliminary analysis demonstrates a reduction in cortical (cingulate, frontal and temporal cortex) and white matter (corpus callosum, internal capsule) integrity in participants with mTBI compared to controls. Reductions in similar areas were associated with higher PCS symptom report (figure A and B). The fMRI analysis revealed little difference between groups for the n-Back, but evidence of increased prefrontal activity (figure C) in participants with mTBI and persistent PCS during PVSAT performance. This early analysis supports the hypothesis that persistent PCS symptoms may have a biological element, with those reporting greater symptoms having greater structural damage and functional changes.

This study aimed to evaluate whether current electroencephalographic spectral measures can predict participant's performance during future sessions of a motor imagery task. By investigating this point, we hope to understand which spectral components are related to MI "literacy". Twelve healthy subjects performed a neurofeedback task whereby a cursor was moved to one of two targets (left and right) using only motor imagery of the corresponding hands. To evaluate the effect of aptitude, we measured the Mahalanobis' distances between whole-scalp spectral patterns in four frequency bands (theta, alpha, beta, and gamma) during the first session of left and right motor imagery. Later, we used these features as inputs in a Support Vector Regressor to predict performance during the following two sessions. The performance was measured as the percentage of trials where the cursor correctly reached the target. Since our sample was balanced, this approach predicted performance on sessions two and three with mean absolute errors of 15.07±12.94% and 11.98±11.40%, respectively. The most relevant feature in both cases was the Mahalanobis' distance in alpha. These results suggest that participants who can not evoke different patterns of alpha power during left- and right-hand motor imagery during the first session, also are less likely to improve during the following training sessions. The investigation of whole-scalp differences allows a holistic comprehension of the neural basis of motor imagery. This method also characterizes a potential predictor of performance for future applications of MI-based neurofeedback and brain-computer interfaces.

The study assessed a mobile electroencephalography system with water-based electrodes for its applicability in cognitive and behavioural neuroscience. It was compared to a standard gel-based wired system. Electroencephalography was recorded on two occasions (first with gel-based, then water-based system) as participants completed the flanker task. Technical and practical considerations for the application of the water-based system are reported based on participant and experimenter experiences. Empirical comparisons focused on electroencephalography data noise levels, frequency power across four bands (theta, alpha, low beta and high beta) and event-related components (P300 and ERN). The water-based system registered more noise compared to the gel-based system which resulted in increased loss of data during artefact rejection. Signal-to-noise ratio was significantly lower for the water-based system in the parietal channels which affected the observed parietal beta power. It also led to a shift in topography of the maximal P300 activity from parietal to frontal regions. The water-based system may be prone to slow drift noise which may affect the reliability and consistency of low-frequency band analyses. Practical considerations for the use of water-based electrode electroencephalography systems are provided.

OBJECTIVES: Mild traumatic brain injury (mTBI) is a heterogeneous injury, and it is difficult to predict those that will go on to experience sustained post-concussion syndrome (PCS, >3mths). As such, data from a wide variety of sources would be useful in investigating long term outcome, preferably within the same population. This study explored the interplay between functional, structural and metabolic changes after mTBI and their relationship with persistent PCS and cognitive performance. METHODS: fMRI, DTI and MRS data were acquired from participants with chronic (>1 year) mTBI and persistent PCS (n=8), participants with mTBI but no on-going PCS (n=8) and non-head injured controls (n=9). Functional data was acquired whilst participants undertook an n-Back and Paced Serial Visual Addition Task (PVSAT). Conventional analysis was undertaken to investigate areas of difference in BOLD response and fractional anisotropy (FA) between groups. These regions of interest were then used to extract individual BOLD contrast values or FA for each participant. MRS acquired from right DLPFC was analysed. Metabolites which differed between groups were used in further analysis. The relationship between functional, structural and metabolic indices was investigated using partial correlation, controlling the effect of age. RESULTS: Participants with mTBI and PCS displayed less of an increase in BOLD response in prefrontal (left inferior/middle frontal gyrus; PVSAT) and temporal (right medial/inferior temporal lobe; n-Back) areas when performing the most difficult task compared to controls, despite similar task performance in both groups. Greater post-concussion symptom report correlated with reduced temporal (right medial/inferior temporal; n-Back) and posterior cingulate/precuneus (PVSAT) BOLD response, as well as increased anterior cingulate (n-Back) BOLD response. Correlations revealed that reduced BOLD response in the left inferior/middle frontal gyrus also was associated with reduced FA in posterior corpus callosum (r=0.4, p