19 results found
Li L, Violante I, Zimmerman K, et al., 2019, Traumatic axonal injury influences the cognitive effect of non-invasive brain stimulation, Brain, Vol: 142, Pages: 3280-3293, ISSN: 1460-2156
Non-invasive brain stimulation has been widely investigated for as a potentialtreatment for a range of neurological and psychiatric conditions, including braininjury. However, the behavioural effects of brain stimulation are very variable, forreasons that are poorly understood. This is a particular challenge for traumatic braininjury, where patterns of damage and their clinical effects are heterogenous. Here wetest the hypothesis that the response to transcranial direct current stimulationfollowing traumatic brain injury is dependent on white matter damage within thestimulated network. We used a novel simultaneous stimulation-MRI protocolapplying anodal, cathodal and sham stimulation to 24 healthy and 35 moderate/severetraumatic brain injury patients. Stimulation was applied to the right inferior frontalgyrus/anterior insula node of the Salience Network, which was targeted because ourprevious work had shown its importance to executive function. Stimulation wasapplied during performance of the Stop Signal Task, which assesses responseinhibition, a key component of executive function. Structural MRI was used to assessthe extent of brain injury, including diffusion MRI assessment of post-traumaticaxonal injury. Functional MRI, which was simultaneously acquired to delivery ofstimulation, assessed the effects of stimulation on cognitive network function. Anodalstimulation improved response inhibition in control participants, an effect that was notobserved in the patient group. The extent of traumatic axonal injury within theSalience Network strongly influenced the behavioural response to stimulation.Increasing damage to the tract connecting the stimulated right inferior frontalgyrus/anterior insula to the rest of the SN was associated with reduced beneficialeffects of stimulation. In addition, anodal stimulation normalised Default ModeNetwork activation in patients with poor response inhibition, suggesting thatstimulation modulates communication between the networks invo
Li L, Ribeiro Violante I, Leech R, et al., 2019, Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation, Human Brain Mapping, Vol: 40, Pages: 904-915, ISSN: 1065-9471
Despite its widespread use in cognitive studies, there is still limited understanding of whether and how transcranial direct current stimulation (tDCS) modulates brain network function. To clarify its physiological effects, we assessed brain network function using functional magnetic resonance imaging (fMRI) simultaneously acquired during tDCS stimulation. Cognitive state was manipulated by having subjects perform a Choice Reaction Task or being at “rest.” A novel factorial design was used to assess the effects of brain state and polarity. Anodal and cathodal tDCS were applied to the right inferior frontal gyrus (rIFG), a region involved in controlling activity large‐scale intrinsic connectivity networks during switches of cognitive state. tDCS produced widespread modulation of brain activity in a polarity and brain state dependent manner. In the absence of task, the main effect of tDCS was to accentuate default mode network (DMN) activation and salience network (SN) deactivation. In contrast, during task performance, tDCS increased SN activation. In the absence of task, the main effect of anodal tDCS was more pronounced, whereas cathodal tDCS had a greater effect during task performance. Cathodal tDCS also accentuated the within‐DMN connectivity associated with task performance. There were minimal main effects of stimulation on network connectivity. These results demonstrate that rIFG tDCS can modulate the activity and functional connectivity of large‐scale brain networks involved in cognitive function, in a brain state and polarity dependent manner. This study provides an important insight into mechanisms by which tDCS may modulate cognitive function, and also has implications for the design of future stimulation studies.
Li L, Ribeiro Violante I, Leech R, et al., 2019, Cognitive enhancement with Salience Network electrical stimulation is influenced by network structural connectivity, NeuroImage, Vol: 185, Pages: 425-433, ISSN: 1053-8119
The Salience Network (SN) and its interactions are important for cognitive control. We have previously shown that structural damage to the SN is associated with abnormal functional connectivity between the SN and Default Mode Network (DMN), abnormal DMN deactivation, and impaired response inhibition, which is an important aspect of cognitive control. This suggests that stimulating the SN might enhance cognitive control. Here, we tested whether non-invasive transcranial direct current stimulation (TDCS) could be used to modulate activity within the SN and enhance cognitive control. TDCS was applied to the right inferior frontal gyrus/anterior insula cortex during performance of the Stop Signal Task (SST) and concurrent functional (f)MRI. Anodal TDCS improved response inhibition. Furthermore, stratification of participants based on SN structural connectivity showed that it was an important influence on both behavioural and physiological responses to anodal TDCS. Participants with high fractional anisotropy within the SN showed improved SST performance and increased activation of the SN with anodal TDCS, whilst those with low fractional anisotropy within the SN did not. Cathodal stimulation of the SN produced activation of the right caudate, an effect which was not modulated by SN structural connectivity. Our results show that stimulation targeted to the SN can improve response inhibition, supporting the causal influence of this network on cognitive control and confirming it as a target to produce cognitive enhancement. Our results also highlight the importance of structural connectivity as a modulator of network to TDCS, which should guide the design and interpretation of future stimulation studies.
Deb S, Leeson V, Aimola L, et al., 2018, Aggression following traumatic brain injury: effectiveness of Risperidone (AFTER): study protocol for a feasibility randomised controlled trial, Trials, Vol: 19, ISSN: 1745-6215
BackgroundTraumatic brain injury (TBI) is a major public health concern and many people develop long-lasting physical and neuropsychiatric consequences following a TBI. Despite the emphasis on physical rehabilitation, it is the emotional and behavioural consequences that have greater impact on people with TBI and their families. One such problem behaviour is aggression which can be directed towards others, towards property or towards the self. Aggression is reported to be common after TBI (37–71%) and causes major stress for patients and their families. Both drug and non-drug interventions are used to manage this challenging behaviour, but the evidence-base for these interventions is poor and no drugs are currently licensed for the treatment of aggression following TBI. The most commonly used drugs for this purpose are antipsychotics, particularly second-generation drugs such as risperidone. Despite this widespread use, randomised controlled trials (RCTs) of antipsychotic drugs, including risperidone, have not been conducted. We have, therefore, set out to test the feasibility of conducting an RCT of this drug for people who have aggressive behaviour following TBI.Methods/designWe will examine the feasibility of conducting a placebo-controlled, double-blind RCT of risperidone for the management of aggression in adults with TBI and also assess participants’ views about their experience of taking part in the study.We will randomise 50 TBI patients from secondary care services in four centres in London and Kent to up to 4 mg of risperidone orally or an inert placebo and follow them up 12 weeks later. Participants will be randomised to active or control treatment in a 1:1 ratio via an external and remote web-based randomisation service. Participants will be assessed at baseline and 12-week follow-up using a battery of assessment scales to measure changes in aggressive behaviour (MOAS, IRQ) as well as global functioning (GOS-E, CGI), quality of life (EQ-5D-5L
Feeney C, Sharp DJ, Hellyer PJ, et al., 2017, Serum IGF-I levels are associated with improved white matter recovery after TBI., Annals of Neurology, Vol: 82, Pages: 30-43, ISSN: 0364-5134
OBJECTIVE: Traumatic brain injury (TBI) is a common disabling condition with limited treatment options. Diffusion tensor imaging (DTI) measures recovery of axonal injury in white matter (WM) tracts after TBI. Growth hormone deficiency (GHD) after TBI may impair axonal and neuropsychological recovery, and serum IGF-I may mediate this effect. We conducted a longitudinal study to determine the effects of baseline serum IGF-I concentrations on WM tract and neuropsychological recovery after TBI. METHODS: Thirty-nine adults after TBI (84.6% male; age median 30.5y; 87.2% moderate-severe; time since TBI median 16.3 months, n=4 with GHD) were scanned twice, 13.3 months (12.1-14.9) apart, and 35 healthy controls scanned once. Symptom and quality of life questionnaires and cognitive assessments were completed at both visits (n=33). Our main outcome measure was fractional anisotropy (FA), a measure of WM tract integrity, in a priori regions of interest: splenium of corpus callosum (SPCC), and posterior limb of internal capsule (PLIC). RESULTS: At baseline, FA was reduced in many WM tracts including SPCC and PLIC following TBI compared to controls, indicating axonal injury, with longitudinal increases indicating axonal recovery. There was a significantly greater increase in SPCC FA over time in patients with serum IGF-I above vs. below the median-for-age. Only the higher IGF-I group had significant improvements in immediate verbal memory recall over time. INTERPRETATION: WM recovery and memory improvements after TBI were greater in patients with higher serum IGF-I at baseline. These findings suggest that GH/IGF-I system may be a potential therapeutic target following TBI. This article is protected by copyright. All rights reserved.
Violante IR, Li LM, Carmichael DW, et al., 2017, Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance., Elife, Vol: 6, ISSN: 2050-084X
Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.
Violante IR, Li LM, Carmichael DW, et al., 2017, Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance, ELIFE, Vol: 6, ISSN: 2050-084X
Jamall O, Feeney C, Zaw-Linn J, et al., 2016, Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury, Clinical Endocrinology, Vol: 85, Pages: 636-644, ISSN: 1365-2265
Objectives: Traumatic brain injury (TBI) is a major cause of long-term disability with variable recovery. Preclinicalstudies suggest that vitamin D status influences recovery after TBI. However, there is no publishedclinical data on links between vitamin D status and TBI outcomes. To determine the: (i) prevalence ofvitamin D deficiency/insufficiency, and associations of vitamin D status with (ii) demographic factors andTBI severity, and with (iii) cognitive function, symptoms and quality of life, in adults after TBI.Design: Retrospective audit of patients seen between July 2009 and March 2015. Serum vitamin D (25-hydroxy-cholecalciferol) was categorised as deficient (<40nmol/L), insufficient (40-70nmol/L) or replete(>70nmol/L).Patients: 353 adults seen in tertiary hospital clinic (75.4% lighter-skinned, 74.8% male, age median 35.1y,range 26.6-48.3y), 0.3-56.5 months after TBI (74.5% moderate-severe).Measurements: Serum vitamin D concentrations; Addenbrooke’s Cognitive Examination (ACE-R), BeckDepression Inventory II (BDI-II), SF-36 Quality of Life, Pittsburgh Sleep Quality Index.Results: 46.5% of patients after TBI had vitamin D deficiency and 80.2% insufficiency/deficiency. Patientswith vitamin D deficiency had lower ACE-R scores than those vitamin D replete (mean effect size ± SEM 4.5± 2.1, P=0.034), and higher BDI-II scores than those vitamin D insufficient (4.5 ± 1.6, P=0.003), correcting forage, gender, time since TBI, TBI severity. There was no association between vitamin D status and markers ofTBI severity, sleep or quality of life.Conclusion: Vitamin D deficiency is common in patients after TBI and associated with impaired cognitivefunction and more severe depressive symptoms.
Li LM, Leech R, Scott GT, et al., 2015, The effect of oppositional parietal transcranial direct current stimulation on lateralized brain functions, European Journal of Neuroscience, Vol: 42, Pages: 2904-2914, ISSN: 1460-9568
Cognitive functions such as numerical processing and spatial attention show varying degrees of lateralization. Transcranial direct current stimulation (tDCS) can be used to investigate how modulating cortical excitability affects performance of these tasks. This study investigated the effect of bi-parietal tDCS on numerical processing, spatial and sustained attention. It was hypothesized that tDCS would have distinct effects on these tasks because of varying lateralization (numerical processing left, spatial attention right) and that these effects are partly mediated by modulation of sustained attention. A single-blinded, crossover, sham-controlled study was performed. Eighteen healthy right-handed participants performed cognitive tasks during three sessions of oppositional parietal tDCS stimulation: sham; right anodal with left cathodal (RA/LC); and right cathodal with left anodal (RC/LA). Participants performed a number comparison task, a modified Posner task, a choice reaction task (CRT) and the rapid visual processing task (RVP). RA/LC tDCS impaired number comparison performance compared with sham, with slower responses to numerically close numbers pairs. RA/LC and RC/LA tDCS had distinct effects on CRT performance, specifically affecting vigilance level during the final block of the task. No effect of stimulation on the Posner task or RVP was found. It was demonstrated that oppositional parietal tDCS affected both numerical performance and vigilance level in a polarity-dependent manner. The effect of tDCS on numerical processing may partly be due to attentional effects. The behavioural effects of tDCS were specifically observed under high task demands, demonstrating the consequences of an interaction between stimulation type and cognitive load.
Li LM, Uehara K, Hanakawa T, 2015, The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies, Frontiers in Cellular Neuroscience, Vol: 9, ISSN: 1662-5102
There has been an explosion of research using transcranial direct current stimulation (tDCS) for investigating and modulating human cognitive and motor function in healthy populations. It has also been used in many studies seeking to improve deficits in disease populations. With the slew of studies reporting “promising results” for everything from motor recovery after stroke to boosting memory function, one could be easily seduced by the idea of tDCS being the next panacea for all neurological ills. However, huge variability exists in the reported effects of tDCS, with great variability in the effect sizes and even contradictory results reported. In this review, we consider the interindividual factors that may contribute to this variability. In particular, we discuss the importance of baseline neuronal state and features, anatomy, age and the inherent variability in the injured brain. We additionally consider how interindividual variability affects the results of motor-evoked potential (MEP) testing with transcranial magnetic stimulation (TMS), which, in turn, can lead to apparent variability in response to tDCS in motor studies.
Li LM, Menon DK, Janowitz T, 2014, Cross-Sectional Analysis of Data from the U.S. Clinical Trials Database Reveals Poor Translational Clinical Trial Effort for Traumatic Brain Injury, Compared with Stroke, PLoS ONE, Vol: 9, Pages: e84336-e84336
Kolias AG, Li LM, Guilfoyle MR, et al., 2013, Decompressive craniectomy for acute subdural hematomas: time for a randomized trial, Acta Neurochirurgica, Vol: 155, Pages: 187-188, ISSN: 0001-6268
Li LM, Guilfoyle MR, Hutchinson PJA, 2012, Prediction of outcome and prognosis after head injury, Practical management of head and neck injury, Editors: Rosenfeld, ISBN: 978-0729539562
Kolias AG, Belli A, Li LM, et al., 2012, Primary decompressive craniectomy for acute subdural haematomas: results of an international survey, Acta Neurochirurgica, Vol: 154, Pages: 1563-1565, ISSN: 0001-6268
Li LM, Kolias AG, Guilfoyle MR, et al., 2012, Outcome following evacuation of acute subdural haematomas: a comparison of craniotomy with decompressive craniectomy, Acta Neurochirurgica, Vol: 154, Pages: 1555-1561, ISSN: 0001-6268
Li LM, Bulters DO, Kirollos RW, 2012, A mathematical model of utility for single screening of asymptomatic unruptured intracranial aneurysms at the age of 50 years, Acta Neurochirurgica, Vol: 154, Pages: 1145-1152, ISSN: 0001-6268
Li LM, Timofeev I, Czosnyka M, et al., 2010, The Surgical Approach to the Management of Increased Intracranial Pressure After Traumatic Brain Injury, Anesthesia & Analgesia, Vol: 111, Pages: 736-748, ISSN: 0003-2999
Sabir IN, Li LM, Jones VJ, et al., 2007, Criteria for arrhythmogenicity in genetically-modified Langendorff-perfused murine hearts modelling the congenital long QT syndrome type 3 and the Brugada syndrome, Pflügers Archiv - European Journal of Physiology, Vol: 455, Pages: 637-651, ISSN: 0031-6768
Sabir IN, Li LM, Grace AA, et al., 2007, Restitution analysis of alternans and its relationship to arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts, Pflügers Archiv - European Journal of Physiology, Vol: 455, Pages: 653-666, ISSN: 0031-6768
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