Biology subjects

Johnsen, E.

Publications and source records attributed to Johnsen, E..

6 recordsLinked to original sources

bioRxiv2024

GABA, Glutamate dynamics and BOLD observed during cognitive processing in psychosis patients with hallucinatory traits

The perception of a voice in the absence of an external auditory source - an auditory verbal hallucination - is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate+Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task. HighlightsO_LIIn-vivo, GABA-edited functional 1H-MRS data were collected from 51 patients with hallucinations and a similar number of matched healthy controls C_LIO_LIReduced Glutamate+Glutamine (Glx) levels were observed in the patient group. C_LIO_LIBOLD association to baseline Glutamate+Glutamine (Glx) differed between patients and controls C_LIO_LIRobust task-related increases in measured Glx were observed in the Anterior Cingulate Cortex (ACC) C_LIO_LITask-related changes in measured Glx did not differ between patients and controls C_LI

neuroscience↗

bioRxiv2023

GABA, glutamatergic dynamics and BOLD contrast concurrently assessed using functional MR spectroscopy during a cognitive task

A recurring issue in functional neuroimaging is how to link task-driven hemodynamic BOLD-fMRI responses to underlying neurochemistry at the synaptic level. Glutamate and GABA, the major excitatory and inhibitory neurotransmitters respectively, are typically measured with MR spectroscopy (MRS) sequences in a resting state, in the absence of a task. We propose to resolve this disconnect by applying a novel method to concurrently acquire BOLD, Glx and GABA measurements from a single voxel, using a locally adapted MEGA-PRESS sequence implementation which incorporates unsuppressed water reference signals at a regular interval, allowing continuous assessment of BOLD-related linewidth variation for fMRS applications. Healthy subjects (N = 81) performed a cognitive task (Eriksen Flanker) which was presented visually in a task-OFF, task-ON block design, with individual event stimulus timing varied with respect to the MRS readout. BOLD data acquired with the adapted MEGA-PRESS sequence were correlated with data acquired using a standard fMRI EPI sequence as a means of validating the concurrent approach: a significant (although moderate) correlation was observed, specific to the fMRS-targeted region of interest. We additionally present a novel linear model for extracting modelled spectra associated with discrete functional stimuli, building on well-established processing and quantification tools. Behavioural outcomes from the Flanker task, and activation patterns from the BOLD-fMRI sequence, were as expected from the literature. fMRS-assessed BOLD response correlated strongly with slowing of response time in the incongruent Flanker condition. Moreover, there was a significant increase in measured Glx levels (~8.8%), between task-OFF and task-ON periods. These findings verify the efficacy of our functional task and analysis pipelines for the simultaneous assessment of BOLD and metabolite fluctuations in a single voxel. As well as providing a robust basis for further work using these techniques, we also identify a number of clear directions for further refinement in future studies. HighlightsO_LIConcurrent measurement of temporally resolved metabolite estimates and local BOLD-related signal changes is demonstrated C_LIO_LIIn-vivo, GABA-edited functional 1H-MRS data were collected from 81 healthy subjects whilst they performed a cognitive task C_LIO_LIRobust task-related increases in measured Glutamate+Glutamine were observed in the Anterior Cingulate Cortex C_LIO_LIModerate correlation was observed between BOLD contrast strength as assessed by fMRS and fMRI techniques, specific to the prescribed region C_LIO_LIA novel technique for extraction of block- or event-related sub-spectra is demonstrated C_LI Graphical AbstractA novel sequence adaption for concurrent measurement of GABA-edited spectroscopy and functional BOLD changes is demonstrated on N=81 healthy subjects. Significant changes in measured Glutamate+Glutamine concentration are found, along with the expected behavioural and BOLD effects in response to a Flanker task. O_FIG O_LINKSMALLFIG WIDTH=170 HEIGHT=200 SRC="FIGDIR/small/539017v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@e06295org.highwire.dtl.DTLVardef@1683a30org.highwire.dtl.DTLVardef@1c45f7aorg.highwire.dtl.DTLVardef@1587cf0_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Dopamine dysregulation in Parkinson's disease flattens the pleasurable urge to move to musical rhythms

The pleasurable urge to move to music (PLUMM) elicits activity in motor and reward areas of the brain and is thought to be driven by predictive processes. Dopamine within motor and limbic cortico-striatal networks is implicated in the predictive processes underlying beat-based timing and music-induced pleasure, respectively. This suggests a central role of cortico-striatal dopamine in PLUMM. This study tested this hypothesis by comparing PLUMM in Parkinsons disease patients, healthy age-matched, and young controls. Participants listened to musical sequences with varying rhythmic and harmonic complexity (low, medium, high), and rated their experienced pleasure and urge to move to the rhythm. In line with previous results, healthy younger participants showed an inverted U-shaped relation between rhythmic complexity and ratings, with a preference for medium complexity rhythms, while age-matched controls showed a similar, but weaker, inverted U-shaped response. Conversely, PD patients showed a significantly flattened response for both the urge to move and pleasure. Crucially, this flattened response could not be attributed to differences in rhythm discrimination and did not reflect an overall decrease in ratings. Together, these results support the role of dopamine within cortico-striatal networks in the predictive processes that form the link between the perceptual processing of rhythmic patterns, and the affective and motor responses to rhythmic music.

neuroscience↗

bioRxiv2020

Neural activity precedes conscious awareness of being in or out of a transient hallucinatory state

Auditory verbal hallucinations, or "hearing voices", is a remarkable state of the mind, occurring in psychiatric and neurological patients, and in a significant minority of the general population. An unexplained characteristic of this phenomenon is that it transiently fluctuates, with coming and going of episodes with time. We monitored neural activity with BOLD-fMRI second-by-second before and after participants indicated the start and end of a transient hallucinatory episode during the scanning session by pressing a response-button. We show that a region in the ventro-medial frontal cortex is activated in advance of conscious awareness of going in or out of a transient hallucinatory state. There was an increase in activity initiated a few seconds before the button-press for onsets, and a corresponding decrease in activity initiated a few seconds before the button-press for offsets. We identified the time between onset and offset button-presses, extracted the corresponding BOLD time-courses from nominated regions-of-interest, and analyzed changes in the signal from 10 seconds before to 15 seconds after the response-button was pressed, which identified onset and offset events. We suggest that this brain region act as a switch to turn on and off a hallucinatory episode. The results may have implications for new interventions for intractable hallucinations.

neuroscience↗

bioRxiv2019

Positive relation between arcuate fasciculus white matter fiber structure and severity of auditory hallucinations: A DTI tractography study

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conflicting. Studying the underlying white matter structure of the AF could shed light on functional connectivity between temporal and frontal language areas in AVHs. The participants were 66 patients with a schizophrenia diagnosis, where AVHs were defined from the Positive and Negative Syndrome Scale (PANSS), and compared with a healthy control group. DTI was performed on a 3T MR scanner, and tensor estimation was done using deterministic streamline tractography. Statistical analysis of the data showed significantly longer tracts along the AF in patients with severe and frequent AVHs, as well as an overall significant asymmetry with longer fibers on the left side. In addition, there were significant positive correlations between PANSS scores and tract length, tract volume, and number of streamlines for the posterior AF segment on the left side. It is concluded that the present structural results complement previous functional findings of fronto-temporal connectivity in AVH patients.

neuroscience↗

bioRxiv2019

Brain age prediction reveals aberrant brain white matter in schizophrenia and bipolar disorder: A multi-sample diffusion tensor imaging study

BackgroundSchizophrenia (SZ) and bipolar disorders (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, BD, and healthy controls across 10 cohorts. MethodsWe trained six cross-validated models using different combinations of DTI data from 927 healthy controls (HC, 18-94 years), and applied the models to the test sets including 648 SZ (18-66 years) patients, 185 BD patients (18-64 years), and 990 HC (17-68 years), estimating brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results. Results10-fold cross-validation revealed high accuracy for all models. Compared to controls, the model including all feature sets significantly over-estimated the age of patients with SZ (d=-.29) and BD (d=.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy (FA) based models showed larger group differences than the models based on other DTI-derived metrics. ConclusionsBrain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.

neuroscience↗