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Developing a Neuromodulation Approach for Treating Working Memory Deficits in Severe Mental Illness
- Paul M Briley, Tiffany Smith, Rebekah Pole, Peter F Liddle, Giovanni d'Avossa, Mohammad ZUH Katshu
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- Journal:
- BJPsych Open / Volume 9 / Issue S1 / July 2023
- Published online by Cambridge University Press:
- 07 July 2023, pp. S46-S47
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Aims
We report electroencephalography (EEG) results from a non-patient pilot study conducted whilst developing a neuromodulation approach for improving visual spatial working memory (vSWM) in people with schizophrenia. Working memory impairments are common in people with schizophrenia yet respond poorly to current drug treatments. Transcranial magnetic stimulation (TMS), a minimally-invasive, well-tolerated, brain stimulation technique that is performed whilst a person is awake and alert, may improve working memory performance. However, results have been inconsistent, possibly because TMS was delivered during the heterogenous “resting-state”. We delivered TMS to left dorsolateral prefrontal cortex time-locked to specific events in a vSWM task, aiming to modulate functional networks involved in encoding spatial data into working memory.
MethodsEach trial in the vSWM task started with a 2-second-long sample display containing either three or four coloured circles positioned at random locations. This was followed by a 2-second delay period. At the end of the delay period, a visual cue appeared, indicating the target colour. Participants moved a crosshair to the screen location where the target had appeared. We recorded 64-channel EEG throughout. In Experiment 1, twelve participants completed three- and four-item task versions. In Experiment 2, eighteen participants completed the four-item task in three separate blocks within a single session. Between blocks, they completed a short task version alongside TMS. TMS (intermittent theta burst stimulation, 600 pulses, 3.3 minutes) was delivered over the F3 electrode position. Each stimulation on-phase was synchronised to coincide with the onset of sample display. In a random order, one TMS block was active, and one was sham (90° coil rotation).
ResultsIn Experiment 1, EEG showed decreases (“desynchronisation”) in beta (13–30 Hz) power during sample display and increases (“synchronisation”) during the delay period. Both effects were greater in the four-item condition, and in posterior electrodes. In Experiment 2, posterior beta desynchronisation during sample display was greater following either active or sham stimulation. However, synchronisation during the delay period reduced following sham and increased only following active stimulation. Likewise, performance declined following sham but remained stable or improved following active stimulation.
ConclusionWe examined the effects of TMS on electrophysiological signals evoked during a spatial working memory task. We found that beta-band oscillatory activity, thought to safeguard stored information during memory delays, was increased by memory load and maintained or restored in blocks following active TMS. These effects were greatest over parietal/occipital areas. It is suggested that this beta activity serves to protect memory traces from distractors (in the current case, internal distractors). Notably, if TMS enhances delay activity within areas of the brain involved in stimulus representation that are distal from the stimulation site, then its effects are best understood as network level modulations of brain activity.
Beta-frequency electrophysiological bursts: BOLD correlates and relationships with psychotic illness
- Paul M Briley, Elizabeth B Liddle, Karen J Mullinger, Molly Simmonite, Lena Palaniyappan, Richard W Bowtell, Tom White, Marije Jansen, Vijender Balain
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- Journal:
- BJPsych Open / Volume 7 / Issue S1 / June 2021
- Published online by Cambridge University Press:
- 18 June 2021, pp. S37-S38
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Aims
To identify the BOLD (blood oxygenation level dependent) correlates of bursts of beta frequency band electrophysiological activity, and to compare BOLD responses between healthy controls and patients with psychotic illness.
The post movement beta rebound (PMBR) is a transient increase in power in the beta frequency band (13-30 Hz), recorded with methods such as electroencephalography (EEG), following the completion of a movement. PMBR size is reduced in patients with schizophrenia and inversely correlated with severity of illness. PMBR size is inversely correlated with measures of schizotypy in non-clinical groups. Therefore, beta-band activity may reflect a fundamental neural process whose disruption plays an important role in the pathophysiology of schizophrenia. Recent work has found that changes in beta power reflect changes in the probability-of-occurrence of transient bursts of beta-frequency activity. Understanding the generators of beta bursts could help unravel the pathophysiology of psychotic illness and thus identify novel treatment targets.
MethodEEG data were recorded simultaneously with BOLD data measured with 3T functional magnetic resonance imaging (fMRI), whilst participants performed an n-back working memory task. We included seventy-eight participants – 32 patients with schizophrenia, 16 with bipolar disorder and 30 healthy controls. Beta bursts were identified in the EEG data using a thresholding method and burst timings were used as markers in an event-related fMRI design convolved with a conventional haemodynamic response function. A region of interest analysis compared beta-event-related BOLD activity between patients and controls.
ResultBeta bursts phasically activated brain regions implicated in coding task-relevant content (specifically, regions involved in the phonological representation of letter stimuli, as well as areas representing motor responses). Further, bursts were associated with suppression of tonically-active regions. In the EEG, PMBR was greater in controls than patients, and, in patients, PMBR size was positively correlated with Global Assessment of Functioning scores, and negatively correlated with persisting symptoms of disorganisation and performance on a digit symbol substition test. Despite this, patients showed greater, more extensive, burst-related BOLD activation than controls.
ConclusionOur findings are consistent with a recent model in which beta bursts serve to reactivate latently-maintained, task-relevant, sensorimotor information. The increased BOLD response associated with bursts in patients, despite reduced PMBR, could reflect inefficiency of burst-mediated cortical synchrony, or it may suggest that the sensorimotor information reactivated by beta bursts is less precisely specified in psychosis. We propose that dysfunction of the mechanisms by which beta bursts reactivate task-relevant content can manifest as disorganisation and working memory deficits, and may contribute to persisting symptoms and impairment in psychosis.
Pilot study of the use of handheld 6-lead ECG for patients on acute general adult mental health wards who refuse traditional 12-lead ECG
- Paul M Briley, Sudheer Lankappa
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- Journal:
- BJPsych Open / Volume 7 / Issue S1 / June 2021
- Published online by Cambridge University Press:
- 18 June 2021, p. S11
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Aims
To assess patient and clinician acceptability of handheld 6-lead ECG, for obtaining information about cardiac rhythm and electrical intervals, in acute general adult mental health ward inpatients who refuse traditional 12-lead ECG.
BackgroundIn a previous audit of patients admitted to four acute general adult mental health wards, we found that 1 in 4 patients refused 12-lead ECG for at least two weeks, with 1 in 6 refusing throughout their entire stay. ECG refusers were significantly more likely to have a psychotic illness than non-refusers and were thus more likely to benefit from medications that carry a risk of prolonging the QT interval. Less invasive, handheld, 6-lead ECG, which includes measurement of lead II (the lead used to define traditional QT-interval cut-off values) is available on the NHS supply chain. Whilst not providing the full range of information that 12-lead ECG is able to provide, handheld 6-lead ECG might be an acceptable alternative in patients who would otherwise never have any form of ECG performed.
MethodWe developed a Standard Operating Procedure for use of handheld 6-lead ECG and provided training for junior doctors on the four wards that were the subject of our original audit. These doctors were then able to offer the device to patients on their wards who refused 12-lead ECG. Doctors completed a short feedback form each time a handheld ECG was offered.
ResultSo far, handheld 6-lead ECGs have been offered to 17 patients who refused 12-lead ECGs. Mean age (± SD) was 36.1 (± 12.6) years, and 4 of these patients were female. 13 patients (76%) accepted a handheld ECG. One of these attempts failed due to patient agitation. Attempts took a mean of 7 (± 5.4) minutes. 54% of recordings were described as “very easy” by clinicians, whereas 15%, 23% and 8% were described as “somewhat easy”, “intermediate”, and “somewhat difficult”, respectively. Clinician difficulties focussed on patient movement with impact on electrode contact and trace quality. Where answered (N = 10), 90% of patients stated they would recommend a handheld ECG to others. Patients liked the speed of the process, that it felt “less scary”, and that it was less invasive and did not involve removing clothing.
ConclusionOur initial findings from this pilot suggest that handheld 6-lead ECG may be acceptable, both to clinicians and patients, as a means of obtaining information on cardiac rhythm and electrical intervals for patients who refuse 12-lead ECGs.
Explaining why childhood abuse is a risk factor for poorer clinical course in bipolar disorder: a path analysis of 923 people with bipolar I disorder
- Steven Marwaha, Paul M. Briley, Amy Perry, Phillip Rankin, Arianna DiFlorio, Nick Craddock, Ian Jones, Matthew Broome, Katherine Gordon-Smith, Lisa Jones
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- Journal:
- Psychological Medicine / Volume 50 / Issue 14 / October 2020
- Published online by Cambridge University Press:
- 18 September 2019, pp. 2346-2354
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Background
Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity.
MethodsWe analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators.
ResultsAffective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data.
ConclusionsAffective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.