Browsing by Author "Howells, Fleur"
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- ItemOpen AccessInvestigating neuroinflammation in schizophrenia: a proton magnetic resonance spectroscopy (1H-MRS) and cytokine study(2022) Burger, Antoinette; Stein, Dan; Howells, FleurIntroduction: There are similarities in the phenomenology and psychobiology of schizophrenia and methamphetamine psychosis, with evidence of alterations in glutamatergic function in both conditions, and of involvement of inflammatory pathways in schizophrenia and methamphetamine abuse. Few studies have directly compared glutamatergic and inflammatory metabolites in thalamo-cortical circuitry across schizophrenia and methamphetamine-induced psychosis or assessed the relationship between such metabolites and inflammatory markers in either disorder. This study aimed to 1) compare glutamatergic and neuroinflammatory metabolites in thalamo-cortical circuitry in schizophrenia and methamphetamine-induced psychosis, and 2) to investigate associations between glutamatergic metabolites, neuroinflammatory metabolites, and peripheral cytokine levels in both disorders. Methods: One hundred and sixteen participants were recruited – 44 with schizophrenia, 34 with methamphetamine-induced psychosis, and 38 healthy controls. All participants underwent a magnetic resonance imaging scan, which included magnetic resonance spectroscopy with voxels located in the anterior cingulate cortex (ACC) and left thalamus as well as a chemical-shift imaging 2-dimensional slice. Neurometabolites obtained included glutamatergic metabolites (glutamate (Glu), glutamine (Gln) and glutamate plus glutamine (Glx)) and neuroinflammatory metabolites (myo-inositol (mI), n-acetyl-aspartate (NAA), and n-acetyl aspartate plus n-acetyl-aspartyl glutamate (NAA+NAAG)). Absolute metabolite concentrations are reported. Serum cytokine concentrations were measured. For group differences, parametric data were analysed with one-way analysis of variance and nonparametric data analysed with Kruskal Wallis tests, followed by relevant post-hoc tests. Associations were determined using Spearman's rank-order coefficient. Significant associations were followed by comparison of correlations of independent samples. Results: There were no differences between neurometabolites in schizophrenia and healthy controls. The methamphetamine-induced psychotic disorder group had lower relative nacetyl-aspartate plus n-acetyl-aspartyl glutamate in left dorsolateral prefrontal cortex and left frontal white matter, compared to healthy controls. In schizophrenia, positive associations were found between absolute glutamatergic metabolites and absolute inflammatory metabolites in the anterior cingulate cortex (n-acetyl-aspartate with glutamate, lower n-acetylaspartate with n-acetyl-aspartyl glutamate plus glutamate, myo-inositol with glutamate, myoinositol with glutamate plush glutamine). Several positive relationships were found in mI between different brain areas of the thalamo-cortical circuitry in the methamphetamineinduced psychosis group. Conclusion: In schizophrenia, the associations between lower glutamatergic and lower neuroinflammatory metabolites suggest dysfunction in neuronal tissues in the glutamateglutamine cycle within the thalamo-cortical circuit. In methamphetamine-induced psychosis, lower NAA+NAAG/Cr+PCr in the left dorsolateral prefrontal cortex and left frontal white mattersuggest compromised neuronal integrity associated with chronic disease progression. Furthermore, in this group the associations of mI between brain areas in the thalamo-cortical 6 circuit suggest that neuroinflammatory pathways in this circuit are dysfunctional. Taken together, there may be important differences in the neurobiology of schizophrenia and methamphetamine-induced psychosis.
- ItemOpen AccessMindfulness based cognitive therapy improves frontal control in bipolar disorder: a pilot EEG study(BioMed Central Ltd, 2012) Howells, Fleur; Ives-Deliperi, Victoria; Horn, Neil; Stein, DanBACKGROUND: Cognitive processing in Bipolar Disorder is characterized by a number of attentional abnormalities. Mindfulness Based Cognitive Therapy combines mindfulness meditation, a form of attentional training, along with aspects of cognitive therapy, and may improve attentional dysfunction in bipolar disorder patients. METHODS: 12 euthymic BD patients and 9 control participants underwent record of electroencephalography (EEG, band frequency analysis) during resting states (eyes open, eyes closed) and during the completion of a continuous performance task (A-X version, EEG event-related potential (ERP) wave component analysis). The individuals with BD completed an 8-week MBCT intervention and record of EEG was repeated. RESULTS: (1) Brain activity, individuals with BD showed significantly decreased theta band power, increased beta band power, and decreased theta/beta ratios during the resting state, eyes closed, for frontal and cingulate cortices. Post MBCT intervention improvement over the right frontal cortex was seen in the individuals with BD, as beta band power decreased. (2) Brain activation, individuals with BD showed a significant P300-like wave form over the frontal cortex during the cue. Post MBCT intervention the P300-like waveform was significantly attenuated over the frontal cortex. CONCLUSIONS: Individuals with BD show decreased attentional readiness and activation of non-relevant information processing during attentional processes. These data are the first that show, MBCT in BD improved attentional readiness, and attenuated activation of non-relevant information processing during attentional processes.
- ItemOpen AccessNeurocircuitry of attention in methamphetamine induced psychosis: a comparison against schizophrenia patients and healthy controls(2022) Hsieh, Jennifer Hsin-Wen; Stein, Dan; Howells, FleurBackground Methamphetamine induced psychosis (MAP) and schizophrenia present with similar positive symptoms of psychosis, are characterized by evidence of attentional impairment, and show symptomatic response to treatment with dopamine antagonists. At the same time, MAP is considered a transient condition, while schizophrenia can be conceptualized as a neurodevelopmental disorder. Despite advances in the neurobiology of these two conditions, the extent to which their underlying attentional neurocircuitry show overlaps or differences has not often been directly compared. This thesis compared MAP, schizophrenia and healthy controls, in order to examine overlap and differences in 1) subcortical regulation of cortical inhibition and excitability, 2) resting state cortical and subcortical connectivity, and the dynamics of rhythmic neural activity between states, and 3) cortical-cortical connectivity using event related potential (ERP) responses to stimuli with a continuous performance task (CPT). Methods Outpatients treated for MAP and schizophrenia were recruited through hospitals and psychiatric institutions in the Western Cape. A final cohort of 24 MAP and 28 schizophrenia and 32 healthy control participants were included in the analyses for this thesis. For the cortical silent period (CSP) paradigm, the participant was asked to maintain isometric contraction between the thumb and index finger while TMS pulses at 120% and 140% resting motor threshold (RMT) were delivered to the primary motor cortical area corresponding to the abductor pollicis brevis (APB). Parameters extracted from CSP data included the latency to motor evoked potential (MEP), MEP amplitude and CSP duration. Electroencephalographs (EEGs) were performed with bilateral prefrontal, frontal, frontal temporal, central and parietal electrode locations. Relative EEG frequency power data were extracted from 3 stages during the EEG session, including states of eyes open, eyes closed, and during performance of the CPT. The CPT consisted of a series of random consonant letters. Participants were asked to respond to the letter "S" with a finger press only if it was the 3rd consecutive occurrence. ERP data were extracted and averaged from consecutive cues (S1 and S2), target (S3) and distractor (individual "S") stimuli in the CPT task. ERP data were analysed for group differences in N100, P200, N200 and P300 amplitudes and latencies at each electrode location with sufficient signal quality. Results In the CSP protocol, MAP and schizophrenia groups showed smaller MEP amplitudes at both 120% and 140% RMT stimulation levels in comparison to controls. Both MAP and schizophrenia groups had lower alpha and higher delta relative frequency band power, with schizophrenia showing significant differences from controls at more electrode positions than MAP. While controls demonstrated a decrease in alpha power between the eyes closed and eyes open resting states, this did not occur in MAP or schizophrenia. During the CPT, both MAP and schizophrenia achieved fewer correct targets and showed slower reaction times than healthy controls. In addition, MAP responded more often than the other two groups to the S2 stimulus (which required response inhixii Abstract bition). ERP analysis found smaller N100, larger P200, larger N200 and larger P300 amplitudes in MAP in response to stimuli requiring inhibition than in schizophrenia and controls, whereas schizophrenia showed longer P300 latencies in response to the target and distractor stimuli than in MAP and controls. Conclusions MEP results suggest that MAP and schizophrenia may have similar subcortical dysregulation, suggestive of altered dopaminergic regulation in the basal ganglia-thalamus-cortex loop. EEG frequency power results suggest that MAP and schizophrenia both display an inflexibility of subcortical systems involved in adaptation to environmental changes, suggesting deficiencies in the CT-TRN-TC loop in both MAP and schizophrenia. CPT performance and the pattern of ERP alterations in MAP suggests greater cholinergic impairment during attentional performance in MAP than in schizophrenia. Taken together, while there is considerable overlap in cortical-subcortical inhibition and connectivity in MAP and schizophrenia, there are also important differences; findings that emphasize both the similarities and dissimilarities that are seen clinically.
- ItemOpen AccessResearch perceived mental effort correlates with changes in tonic arousal during attentional tasks(BioMed Central Ltd, 2010) Howells, Fleur; Stein, Dan; Russell, VivienneBACKGROUND: It has been suggested that perceived mental effort reflects changes in arousal during tasks of attention. Such changes in arousal may be tonic or phasic, and may be mediated by the locus-coeruleus norepinephrine (LC-NE) system. We hypothesized that perceived mental effort during attentional tasks would correlate with tonic changes in cortical arousal, as assessed by relative electroencephalogram (EEG) band power and theta/beta ratio, and not with phasic changes in cortical arousal, assessed by P300 amplitude and latency. METHODS: Forty-six healthy individuals completed tasks that engage the anterior and posterior attention networks (continuous performance task, go/no-go task, and cued target detection task). During completion of the three attentional tasks a continuous record of tonic and phasic arousal was taken. Cortical measures of arousal included frequency band power, theta/beta ratios over frontal and parietal cortices, and P300 amplitude and latency over parietal cortices. Peripheral measures of arousal included skin conductance responses, heart rate and heart rate variance. Participants reported their perceived mental effort during each of the three attentional tasks. RESULTS: First, changes in arousal were seen from rest to completion of the three attentional tasks and between the attentional tasks. Changes seen between the attentional tasks being related to the task design and the attentional network activated. Second, perceived mental effort increased when demands of the task increased and correlated with left parietal beta band power during the three tasks of attention. Third, increased mental effort during the go/no-go task and the cued target detection task was inversely related to theta/beta ratios. CONCLUSION: These results indicate that perceived mental effort reflects tonic rather than phasic changes in arousal during tasks of attention. We suggest that perceived mental effort may reflect in part tonic activity of the LC-NE system in healthy individuals.