Professor Paul Dockree

Title

Cognitive impairments in Traumatic Brain Injury: Novel biomarkers for new treatments

Summary

Traumatic Brain Injury (TBI) represents an urgent and growing mental health burden for which new treatments must be developed. Standardised assessment of cognitive problems in TBI patients provides the clinician with an accurate profile of key disabling behavioural problems of memory, attention, emotional regulation and insight that are present to a greater or lesser extent in different TBI patients. Basic brain science reveals that microscopic haemhorrages invisible to standard MRI, diffuse white matter (axonal) damage and widespread neurotransmitter disruption underlies TBI deficits and as such there is poor specificity and sensitivity linking discrete cognitive problems with associated functional neuroanatomy in TBI patients. However, we urgently require biomarkers for new treatments that target the different types of cognitive problems experienced by TBI patients. A highly successful technique for identifying biomarkers of cognitive function is the electroencephalogram (EEG). EEG provides a continuous recording of the brains electrical activity and discrete neural signals can be extracted called Event-Related-Potentials (ERPs). We propose that key EEG/ERP biomarkers can dissociate symptom-clusters in different TBI patients that reflect 1) inattention and related memory problems, 2) impulsivity/disinhibition and 3) reduced insight/self-awareness. Biomarkers for these three clusters will help elucidate the neuro-cognitive processes underlying a range of distressing problems frequently experienced by TBI patients that have thus far been largely untreatable. We will select 100 post-acute outpatients suffering from TBI. Patients' symptom rating scores will be divided into high, medium and low categories; therefore, the relative pervasiveness of each symptom clusters can be determined for each patient. EEG/ERP biomarker signals will be compared across each of the patients and controls for key cognitive probes (laboratory tasks) that measure cognitive deficits which map to each symptom cluster. Finally, structural equation modelling will be employed to test the predictive strength of biomarkers for symptom rating severity.

Funding Agency

Health Research Board

Date From

Oct 2007

Date To

Oct 2010

Title

INDIREA - Individualised Diagnostics and Rehabilitation for Attentional Disorders

Summary

This research is central to Work Package 4 (Rehabilitation of Attention) of the INDIREA project and has followed two key aims: 1) An investigation of non-invasive brain stimulation for the enhancement of attention in older adults and stroke patients (ESR 11) a) This study investigated the influence of right prefrontal transcranial direct current stimulation (tDCS) to enhance sustained attention and response inhibition in a healthy ageing sample. In this study mechanistic changes in electrophysiology during stimulation were assessed using simultaneous tDCS-EEG. b) A second intervention investigated whether right prefrontal or right parietal stimulation using tDCS could enhance different parameters dirived from Theory of Visual Attention (TVA) assessment (visual attention capacity [K] and processing speed [C]) c) Thirdly we investigated the temporal dynamics of sustained attention deficits following right hemisphere stroke, and the potential for right tDCS to ameliorate such deficits. 2) To investigate the electrophysiological correlates of mind-wandering for the purpose of identifying tractable signals for EEG biofeedback (ESR 12). a) First we investigated two classes of Mind-Wandering (MW) for prospective use in a neurofeedback based brain computer-interface (BCI) capable of increasing deliberate MW (dMW), associated with positive aspects of cognition such as creative incubation and planning, and decreasing spontaneous MW (sMW), correlated with depression and other mental health issues. b) The second study provided an examination of whether subjective and objective markers of attention exhibit similar behavioural and electrophysiological correlates c) Thirdly we applied classification algorithms commonly used in the field of brain-computer interfaces to classify on-task and off-task MW activity by their EEG.

Funding Agency

Marie Curie Sklodowska

Date From

2014

Date To

2017

Title

Investigating Cortical and Subcortical Interactions during Sustained Attention

Summary

Sustained attention describes our ability to modulate the intensity of our alertness in the service of key goals. Our capability to sustain attention is essential for error-free human performance and provides a vital gateway to the working efficiency of all other higher-cognitive mechanisms. In the last two decades, significant advances have been made in understanding the functional neuroarchitecture of sustained attention. However, there is a limited knowledge of the time-scale over which sustained attention and its neural signatures evolve. The roles of specific brain regions within a broad cortico-subcortical network are also unresolved with respect to these neural dynamics. We have developed a set of innovative state-of-the-art paradigms with unique ability to isolate discrete brain signals as they unfold in time with precise millisecond resolution using human electroencephalography (EEG). These paradigms pave the way for a timely series of experiments that will employ lesion-based and neuromodulatory approaches to investigate how changes to cortical or subcortical networks influence sustained attention. First, we will compare patients with lesions to the right prefrontal cortex and lesions to brainstem disrupting the Locus Coeruleus/Noradrenergic system. Psychophysiological markers will be tracked at both shorter time-scales (milliseconds to seconds) and longer-term timescales (tens-of-seconds to minutes) and MRI lesion maps will be derived to elucidate the neural mechanisms that support sustained attention at these different time-scales. Second, we will examine the nature of attentional disengagement during episodes of intentional and unintentional task-unrelated thought or 'mind wandering' (MW). For the first time, we will track neural signatures of both types of MW state as they fluctuate over time and perturb these states with non-invasive brain stimulation to reveal their underlying neural mechanisms.

Funding Agency

Irish Research Council

Date From

Sept 2018

Date To

Sept 2022