Biology subjects

Kazimierczak, K.

Publications and source records attributed to Kazimierczak, K..

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

Networks extracted from nonlinear fMRI connectivity exhibit unique spatial variation and enhanced sensitivity to differences between individuals with schizophrenia and controls

Functional magnetic resonance imaging (fMRI) studies often estimate brain intrinsic connectivity networks (ICNs) from temporal relationships between hemodynamic signals using approaches such as independent component analysis (ICA). While ICNs are thought to represent functional sources that play important roles in various psychological phenomena, current approaches have been tailored to identify ICNs that mainly reflect linear statistical relationships. However, the elements comprising neural systems often exhibit remarkably complex nonlinear interactions that may be involved in cognitive operations and altered in psychiatric conditions such as schizophrenia. Consequently, there is a need to develop methods capable of effectively capturing ICNs from measures that are sensitive to nonlinear relationships. Here, we advance a novel approach to estimate ICNs from explicitly nonlinear whole-brain functional connectivity (ENL-wFC) by transforming resting-state fMRI (rsfMRI) data into the connectivity domain, allowing us to capture unique information from distance correlation patterns that would be missed by linear whole-brain functional connectivity (LIN-wFC) analysis. Our findings provide evidence that ICNs commonly extracted from linear (LIN) relationships are also reflected in explicitly nonlinear (ENL) connectivity patterns. ENL ICN estimates exhibit higher reliability and stability, highlighting our approachs ability to effectively quantify ICNs from rsfMRI data. Additionally, we observed a consistent spatial gradient pattern between LIN and ENL ICNs with higher ENL weight in core ICN regions, suggesting that ICN function may be subserved by nonlinear processes concentrated within network centers. We also found that a uniquely identified ENL ICN distinguished individuals with schizophrenia from healthy controls while a uniquely identified LIN ICN did not, emphasizing the valuable complementary information that can be gained by incorporating measures that are sensitive to nonlinearity in future analyses. Moreover, the ENL estimates of ICNs associated with auditory, linguistic, sensorimotor, and self-referential processes exhibit heightened sensitivity towards differentiating between individuals with schizophrenia and controls compared to LIN counterparts, demonstrating the translational value of our approach and of the ENL estimates of ICNs that are frequently reported as disrupted in schizophrenia. In summary, our findings underscore the tremendous potential of connectivity domain ICA and nonlinear information in resolving complex brain phenomena and revolutionizing the landscape of clinical FC analysis.

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↗

bioRxiv2020

Dynamic switching between intrinsic and extrinsic mode networks as demands change from passive to active processing

We here report on the relationship between default and extrinsic mode networks across alternating brief periods of rest and active task processing. We used three different visual tasks: mental rotation, working memory and mental arithmetic in a classic fMRI ON-OFF block design where task (ON) blocks alternated with equal periods of rest (OFF) blocks. By analysing data in two ways, using an ON-OFF contrast, we showed the existence of a generalized task-positive network, labelled the extrinsic mode network (EMN) which was anti-correlated with the default mode network (DMN) as processing demands shifted from rest to active processing. We then identified two key regions of interest (ROIs) in the SMA and Precuneus/PCC regions as hubs for the extrinsic and intrinsic networks, and extracted the time-course from these ROIs. The results showed a close to perfect correlations for the SMA and Precuneus/PCC time-courses for ON-respective OFF-blocks. We suggest the existence of two large-scale networks, an extrinsic mode network and an intrinsic mode network, respectively, which are up- and down-regulated as environmental demands change from active to passive processing.

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

Dynamic up- and down-regulation of the default (DMN) and extrinsic (EMN) mode networks during alternating task-on and task-off periods

Using fMRI, Hugdahl et al. (2015) reported the existence of a general-domain cortical network during active task-processing which was non-specific to the cognitive task being processed. They labelled this network the extrinsic mode network (EMN). The EMN would be predicted to be negatively, or anti-correlated with the classic default mode network (DMN), typically observed during periods of rest, such that while the EMN should be down-regulated and the DMN up-regulated in the absence of demands for task-processing, the reverse should occur when demands change from resting to task-processing. This would require alternating periods of task-processing and resting, and analyzing data continuously when demands change from active to passive periods and vice versa. We were particularly interested in how the networks interact in the critical transition points between conditions. For this purpose we used an auditory task with multiple cognitive demands in a standard fMRI block-design. Task-present (ON) blocks were alternated with an equal number of task-absent, or rest (OFF) blocks to capture network dynamics across time and changing environmental demands. To achieve this, we specified the onset of each block, and used a finite-impulse response function (FIR) as basis function for estimation of the fMRI-BOLD response. During active (ON) blocks, the results showed an initial rapid onset of activity in the EMN network, which remained throughout the period, and faded away during the first scan of the OFF-block. During OFF blocks, activity in the DMN network showed an initial time-lag where neither the EMN nor the DMN was active, after which the DMN was up-regulated. Studying network dynamics in alternating passive and active periods may provide new insights into brain network interaction and regulation.

neuroscience↗