The structural and functional connectivity of the posterior cingulate cortex : comparison between deterministic and probabilistic tractography for the investigation of structure–function relationships

The default mode network (DMN) is one of the most studied resting-state networks, and is thought to be involved in the maintenance of consciousness within the alert human brain. Although many studies have examined the functional connectivity (FC) of the DMN, few have investigated its underlying structural connectivity (SC), or the relationship between the two. We investigated this question in fifteen healthy subjects, concentrating on connections to the precuneus/posterior cingulate cortex (PCC), commonly considered as the central node of the DMN. We used group independent component analysis (GICA) and seed-based correlation analysis of fMRI data to quantify FC, and streamline and probabilistic tractography to identify structural tracts from diffusion tensor imaging (DTI) data. We first assessed the presence of structural connections between the DMN regions identified with GICA. Of the 15 subjects, when using the probabilistic approach 15 (15) demonstrated connections between the PCC and mesial prefrontal cortex (mPFC), 11 (15) showed connections from the PCC to the right inferior parietal cortex (rIPC) and 8 (15) to the left IPC. Next, we assessed the strength of FC (magnitude of temporal correlation) and SC (mean fractional anisotropy of reconstructed tracts (streamline), number of super-threshold voxels within the mask region (probabilistic)). The lIPC had significantly reduced FC to the PCC compared to the mPFC and rIPC. No difference in SC strength between connections was found using the streamline approach. For the probabilistic approach, mPFC had significantly lower SC than both IPCs. The two measures of SC strength were significantly correlated, but not for all paired connections. Finally, we observed a significant correlation between SC and FC for both tractography approaches when data were pooled across PCC-lIPL, PCC-rIPL and PCC-mPFC connections, and for some individual paired connections. Our results suggest that the streamline approach is advantageous for characterising the connectivity of long white matter tracts (PCC-mPFC), whilst the probabilistic approach was more reliable at identifying PCC-IPC connections. The direct comparison of FC and SC indicated that pairs of nodes with stronger structural connections also had stronger functional connectivity, and that this was maintained with both tractography approaches. Whilst the definition of SC strength remains controversial, our results could be considered to provide some degree of validation for the measures of SC strength that we have used. Direct comparisons of SC and FC are necessary in order to understand the structural basis of functional connectivity, and to characterise and quantify the changes in the brain's functional architecture that occur as a result of normal physiology or pathology

Habitual sleep durations and subjective sleep quality predict white matter differences in the human brain

Self-imposed short sleep durations are increasingly commonplace in society, and have considerable health and performance implications for individuals. Reduced sleep duration over multiple nights has similar behavioural effects to those observed following acute total sleep deprivation, suggesting that lack of sleep affects brain function cumulatively. A link between habitual sleep patterns and functional connectivity has previously been observed, and the effect of sleep duration on the brain's intrinsic functional architecture may provide a link between sleep status and cognition. However, it is currently not known whether differences in habitual sleep patterns across individuals are related to changes in the brain's white matter, which underlies structural connectivity. In the present study we use diffusion–weighted imaging and a group comparison application of tract based spatial statistics (TBSS) to investigate changes to fractional anisotropy (FA) and mean diffusivity (MD) in relation to sleep duration and quality, hypothesising that white matter metrics would be positively associated with sleep duration and quality. Diffusion weighted imaging data was acquired from a final cohort of 33 (23–29 years, 10 female, mean 25.4 years) participants. Sleep patterns were assessed for a 14 day period using wrist actigraphs and sleep diaries, and subjective sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Median splits based on total sleep time and PSQI were used to create groups of shorter/longer and poorer/better sleepers, whose imaging data was compared using TBSS followed by post-hoc correlation analysis in regions identified as significantly different between the groups. There were significant positive correlations between sleep duration and FA in the left orbito-frontal region and the right superior corona radiata, and significant negative correlations between sleep duration and MD in right orbito-frontal white matter and the right inferior longitudinal fasciculus. Improved sleep quality was positively correlated with FA in left caudate nucleus, white matter tracts to the left orbito-frontal region, the left anterior cingulum bundle and the white matter tracts associated with the right operculum and insula, and negatively correlated with MD in left orbito-frontal white matter and the left anterior cingulum bundle. Our findings suggest that reduced cumulative total sleep time (cTST) and poorer subjective sleep quality are associated with subtle white matter micro-architectural changes. The regions we identified as being related to habitual sleep patterns were restricted to the frontal and temporal lobes, and the functions they support are consistent with those which have previously been demonstrated as being affected by short sleep durations (e.g., attention, cognitive control, memory). Examining how inter-individual differences in brain structure are related to habitual sleep patterns could help to shed light on the mechanisms by which sleep habits are associated with brain function, behaviour and cognition, as well as potentially the networks and systems responsible for variations in sleep patterns themselves

Variability in Cumulative Habitual Sleep Duration Predicts Waking Functional Connectivity

STUDY OBJECTIVES: We examined whether interindividual differences in habitual sleep patterns, quantified as the cumulative habitual total sleep time (cTST) over a 2-w period, were reflected in waking measurements of intranetwork and internetwork functional connectivity (FC) between major nodes of three intrinsically connected networks (ICNs): default mode network (DMN), salience network (SN), and central executive network (CEN). METHODS: Resting state functional magnetic resonance imaging (fMRI) study using seed-based FC analysis combined with 14-d wrist actigraphy, sleep diaries, and subjective questionnaires (N = 33 healthy adults, mean age 34.3, standard deviation ± 11.6 y). Data were statistically analyzed using multiple linear regression. Fourteen consecutive days of wrist actigraphy in participant's home environment and fMRI scanning on day 14 at the Birmingham University Imaging Centre. Seed-based FC analysis on ICNs from resting-state fMRI data and multiple linear regression analysis performed for each ICN seed and target. cTST was used to predict FC (controlling for age). RESULTS: cTST was specific predictor of intranetwork FC when the mesial prefrontal cortex (MPFC) region of the DMN was used as a seed for FC, with a positive correlation between FC and cTST observed. No significant relationship between FC and cTST was seen for any pair of nodes not including the MPFC. Internetwork FC between the DMN (MPFC) and SN (right anterior insula) was also predicted by cTST, with a negative correlation observed between FC and cTST. CONCLUSIONS: This study improves understanding of the relationship between intranetwork and internetwork functional connectivity of intrinsically connected networks (ICNs) in relation to habitual sleep quality and duration. The cumulative amount of sleep that participants achieved over a 14-d period was significantly predictive of intranetwork and inter-network functional connectivity of ICNs, an observation that may underlie the link between sleep status and cognitive performance. CITATION: Khalsa S, Mayhew SD, Przezdzik I, Wilson R, Hale J, Goldstone A, Bagary M, Bagshaw AP. Variability in cumulative habitual sleep duration predicts waking functional connectivity. SLEEP 2016;39(1):87–95

Early haemodynamic changes observed in patients with epilepsy, in a visual experiment and in simulations

Objective: The objective of this study was to investigate whether previously reported early blood oxygen level dependent (BOLD) changes in epilepsy could occur as a result of the modelling techniques rather than physiological changes. Methods: EEG-fMRI data were analysed from seven patients with focal epilepsy, six control subjects undergoing a visual experiment, in addition to simulations. In six separate analyses the event timing was shifted by either -9,-6,-3,+3,+6 or +9 s relative to the onset of the interictal epileptiform discharge (IED) or stimulus. Results: The visual dataset and simulations demonstrated an overlap between modelled haemodynamic response function (HRF) at event onset and at \ub13 s relative to onset, which diminished at \ub16 s. Pre-spike analysis at -6 s improved concordance with the assumed IED generating lobe relative to the standard HRF in 43% of patients. Conclusion: The visual and simulated dataset findings indicate a form of "temporal bleeding", an overlap between the modelled HRF at time 0 and at \ub13 s which attenuated at \ub16 s. Pre-spike analysis at -6 s may improve concordance. Significance: This form of analysis should be performed at 6 s prior to onset of IED to minimise temporal bleeding effect. The results support the presence of relevant BOLD responses occurring prior to IEDs

Epilepsy, consciousness and neurostimulation

Abstract. Consciousness is often disrupted in epilepsy. This may involve altered responsiveness or changes in awareness of self and subjective experiences. Subcortical arousal systems and paralimbic fronto-parietal association cortices are thought to underpin current concepts of consciousness. The Network Inhibition Hypothesis proposes a common neuroanatomical substrate for impaired consciousness during absence, complex partial and tonic-clonic seizures. Neurostimulation in epilepsy remains in its infancy with vagal nerve stimulation (VNS) as the only firmly established technique and a series of other methods under investigation including deep brain stimulation (DBS), intracranial cortical stimulation and repetitive transcranial magnetic stimulation (rTMS). Many of these systems impact on the neural systems thought to be involved in consciousness as a continuous duty cycle although some adaptive (seizure triggered) techniques have been developed. Theoretically, fixed duty cycle neurostimulation could have profound effects on responsiveness, awareness of self and subjective experience. Animal studies suggest vagal nerve stimulation positively influences hippocampal long term potentiation. In humans, a chronic effect of increased alertness in VNS implanted subjects and acute effect on memory consolidation have been reported but convincing data on either improvements or deterioration in attention and memory is lacking. Thalamic deep brain stimulation (DBS) is perhaps the most interesting neurostimulation technique in the context of consciousness. Neither bilateral anterior or centromedian thalamic nucleus DBS seem to affect cognition. Unilateral globus pallidus internus DBS caused transient wakefulness in an anaesthetised individual. As intracranial neurostimulation, particularly thalamic DBS, becomes more established as a clinical intervention, the effects on consciousness and cognition with variations in stimulus parameters will need to be studied to understand whether these secondary effects of neurostimulation make a significant positive (or adverse) contribution to quality of life. Concepts of consciousness In the absence of a universally accepted definition, those of us working in clinical medicine tend to adopt a pragmatic meaning to the term consciousness to include the degree of wakefulness, the ability to perceive and to interpret sensory information enabling appropriate responses. These concepts concentrate on the responsiveness of an individual to the environment, much of which we can attempt to assess objectively with a range of observations including standardised scales with some prognostic value such as the Glasgow Coma Scale. Less attention is directed to the related concept of consciousness that involves awareness of self to * Address for correspondence: Department of Neuropsychiatry, The Barberry Building, UK Centre for Mental Health, 25, Vincent Drive, Edgbaston, Birmingham, UK, B15 2FG. Tel.: +44 (0)121 301 2294; E-mail: [email protected]. include subjective experiences and the recollection of those subjective experiences. Consciousness seems to be dependent on the association cortex and subcortical arousal systems in the thalamus, upper brainstem, and basal forebrai

Current practice and recommendations in UK epilepsy monitoring units. Report of a national survey and workshop

Purpose Inpatient video-EEG monitoring (VEM) is an important investigation in patients with seizures or blackouts, and in the pre-surgical workup of patients with epilepsy. There has been an expansion in the number of Epilepsy Monitoring Units (EMU) in the UK offering VEM with a necessary increase in attention on quality and safety. Previous surveys have shown variation across centres on issues including consent and patient monitoring. Method In an effort to bring together healthcare professionals in the UK managing patients on EMU, we conducted an online survey of current VEM practice and held a one-day workshop convened under the auspices of the British Chapter of the ILAE. The survey and workshop aimed to cover all aspects of VEM, including pre-admission, consent procedures, patient safety, drug reduction and reinstatement, seizure management, staffing levels, ictal testing and good data recording practice. Results This paper reports on the findings of the survey, the workshop presentations and workshop discussions. 32 centres took part in the survey and there were representatives from 22 centres at the workshop. There was variation in protocols, procedures and consent processes between units, and levels of observation of monitored patients. Nevertheless, the workshop discussion found broad areas of agreement on points. Conclusion A survey and workshop of UK epilepsy monitoring units found that some variability in practice is inevitable due to different local arrangements and patient groups under investigation. However, there were areas of clear consensus particularly in relation to consent and patient safety that can be applied to most units and form a basis for setting minimum standards

The management of Convulsive Refractory Status Epilepticus in adults in the UK: No consistency in practice and little access to continuous EEG monitoring.

PURPOSE Convulsive Status Epilepticus (CSE) is a common neurological emergency with patients presenting with prolonged epileptic activity. Sub-optimal management is coupled with high morbidity and mortality. Continuous electroencephalogram (EEG) monitoring is considered essential by the National Institute for Health and Care Excellence (NICE) in the management of Convulsive Refractory Status Epilepticus (CRSE). The aim of this research was to determine current clinical practice in the management of CRSE amongst adults in intensive care units (ICU) in the UK and establish if the use of a standardised protocol requires re-enforcement within trusts. METHODS 75 randomly selected UK NHS Trusts were contacted and asked to complete a questionnaire in addition to providing their protocol for CRSE management in ICU. RESULTS 55 (73%) trusts responded. While 31 (56% of responders) had a protocol available in ICU for early stages of CSE, just 21 (38%) trusts had specific guidelines if CRSE occurred. Only 23 (42%) trusts involved neurologists at any stage of management and just 18 (33%) have access to continuous EEG monitoring. CONCLUSION This study identifies significant inconsistency in the management of CSE in ICU's across the UK. A minority of ICU units have a protocol for CRSE or access to continuous EEG monitoring despite it being considered fundamental for management and supported by NICE guidance