ORCID Profile
0000-0002-0008-4326
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Publisher: Wiley
Date: 09-10-2013
DOI: 10.1111/SJOP.12080
Abstract: Schizophrenia is characterized by cognitive impairment, especially in relation to executive functions. Brain structural abnormalities are also often seen in schizophrenia although little is known of the relationship between cognitive impairment and structural brain changes. Our aim was therefore to investigate this relationship further using MRI and a dichotic listening (DL) task with simple speech sounds and with instructions to focus attention and report only from the left or right ear stimulus. When instructed to focus attention on the left ear syllable a cognitive conflict is induced requiring the allocation of executive resources to be resolved. Grey matter (GM) volume was measured with MRI from four volumes of interests (VOIs), left and right frontal and temporal cortex, respectively, and correlated with DL performance. The results showed significant differences between the groups in their ability to focus attention on and report the left ear stimulus, which was accompanied by reduced GM volume in the left frontal and right temporal lobe VOIs. There was also a significant positive correlation between left frontal GM volume and performance on the DL task, for the groups combined. The results did not support a conclusion that an impairment in cognitive function in schizophrenia was driven by an corresponding impairment in brain structure, since there were no significant correlations when the groups were analyzed separately. It is however concluded that patients with schizophrenia are impaired in executive functions and that they also show reduced GM volumes in left frontal and right temporal lobe areas, compared to healthy controls.
Publisher: Frontiers Media SA
Date: 22-06-2015
Publisher: Oxford University Press (OUP)
Date: 22-06-2018
Publisher: Springer Science and Business Media LLC
Date: 30-10-2023
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2018
DOI: 10.1158/0008-5472.CAN-17-3034
Abstract: Neuroblastoma is a pediatric cancer of the sympathetic nervous system where MYCN lification is a key indicator of poor prognosis. However, mechanisms by which MYCN promotes neuroblastoma tumorigenesis are not fully understood. In this study, we analyzed global miRNA and mRNA expression profiles of tissues at different stages of tumorigenesis from TH-MYCN transgenic mice, a model of MYCN-driven neuroblastoma. On the basis of a Bayesian learning network model in which we compared pretumor ganglia from TH-MYCN+/+ mice to age-matched wild-type controls, we devised a predicted miRNA–mRNA interaction network. Among the miRNA–mRNA interactions operating during human neuroblastoma tumorigenesis, we identified miR-204 as a tumor suppressor miRNA that inhibited a subnetwork of oncogenes strongly associated with MYCN- lified neuroblastoma and poor patient outcome. MYCN bound to the miR-204 promoter and repressed miR-204 transcription. Conversely, miR-204 directly bound MYCN mRNA and repressed MYCN expression. miR-204 overexpression significantly inhibited neuroblastoma cell proliferation in vitro and tumorigenesis in vivo. Together, these findings identify novel tumorigenic miRNA gene networks and miR-204 as a tumor suppressor that regulates MYCN expression in neuroblastoma tumorigenesis. Significance: Network modeling of miRNA–mRNA regulatory interactions in a mouse model of neuroblastoma identifies miR-204 as a tumor suppressor and negative regulator of MYCN. Cancer Res 78(12) 3122–34. ©2018 AACR.
Publisher: Wiley
Date: 09-07-2014
DOI: 10.1111/SJOP.12145
Abstract: The purpose of the study was to investigate a possible association between brain activation in functional magnetic resonance imaging scans, cognition and school performance in extremely preterm children and term born controls. Twenty eight preterm and 28 term born children were scanned while performing a working memory/selective attention task, and school results from national standardized tests were collected. Brain activation maps reflected difference in cognitive skills but not in school performance. Differences in brain activation were found between children born preterm and at term, and between high and low performers in cognitive tests. However, the differences were located in different brain areas. The implication may be that lack of cognitive skills does not alone explain low performance due to prematurity.
Publisher: Proceedings of the National Academy of Sciences
Date: 15-05-2018
Abstract: Left–right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population and how biological factors such as age, sex, and genetic variation affect these asymmetries. Here, we describe by far the largest-ever study of cerebral cortical asymmetry, based on data from 17,141 participants. We found a global anterior–posterior “torque” pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an online resource that will serve future studies of human brain anatomy in health and disease.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.SCHRES.2014.11.015
Abstract: This is a (1)H MR spectroscopy (MRS) study of glutamate (Glu), measured as Glx, levels in temporal and frontal lobe regions in patients with schizophrenia compared with a healthy control group with the objective of revealing aspects of the underlying neurochemistry of auditory hallucinations. We further compared and correlated Glu(Glx) levels for the patients-only against frequency and severity of auditory hallucinations and the sum of Positive symptoms, and also for frequency and severity of emotional withdrawal, and sum of Negative symptoms. The s le included 23 patients with an ICD-10 and DSM-IV diagnosis of schizophrenia, and 26 healthy control subjects without any known psychiatric or neurological disorders. Symptom scores were obtained from the Positive and Negative Syndrome Scale (PANSS). (1)H MRS data were acquired on a 3T MR scanner from two temporal and two frontal voxels, using standard sequences and analysis parameters. The results showed that schizophrenia patients as a group had reduced Glu(Glx) levels in the voxels of interest compared to the healthy control subjects, while increased levels were found for patients with frequent and severe auditory hallucinations, relative to patients with less frequent and severe hallucination. We further found significant positive correlations between frequency and severity of auditory hallucinations, and for sum Positive symptoms, and Glu(Glx) levels in all regions, not seen when the analysis was done for negative symptoms. It is concluded that the results show for the first time that glutamate may be a mediating factor in auditory hallucinations in schizophrenia.
Publisher: Frontiers Media SA
Date: 08-01-2019
Publisher: S. Karger AG
Date: 24-05-2018
DOI: 10.1159/000488930
Abstract: We present a case of a young female with a slowly progressing visual impairment who was examined with multifocal visual evoked potentials and functional magnetic resonance imaging (fMRI) for underlying neuronal abnormality. The fMRI examination consisted of presenting black-and-white checkerboard stimuli, and her activation patterns were compared to the patterns from 4 normal-sighted subjects. The results showed clear differences in neuronal activation between the patient and the controls in the occipital and parietal lobes. Although we have shown neuronal correlates in a case of unexplained visual loss, it is still an open question as to whether this has an organic or functional cause, which should be the subject for future research.
Publisher: Wiley
Date: 03-02-2015
DOI: 10.1002/HBM.22753
Publisher: Cold Spring Harbor Laboratory
Date: 02-05-2023
DOI: 10.1101/2023.05.02.539017
Abstract: 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 in idual 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. Concurrent measurement of temporally resolved metabolite estimates and local BOLD-related signal changes is demonstrated In-vivo, GABA-edited functional 1 H-MRS data were collected from 81 healthy subjects whilst they performed a cognitive task Robust task-related increases in measured Glutamate+Glutamine were observed in the Anterior Cingulate Cortex Moderate correlation was observed between BOLD contrast strength as assessed by fMRS and fMRI techniques, specific to the prescribed region A novel technique for extraction of block- or event-related sub-spectra is demonstrated A 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.
Publisher: Wiley
Date: 27-04-2015
DOI: 10.1111/PSYP.12445
Abstract: Mismatch negativity (MMN), an ERP elicited by a deviant stimulus in a train of standard stimuli, has been suggested to be associated to glutamatergic neurotransmission, mediated by glutamatergic NMDA receptors. In this study, we examined the relationship between interin idual variation of (1)H-MRS-measured glutamate+glutamine (Glx) in the superior temporal gyrus and MMN for duration and frequency deviants in 19 healthy young adults (9 male). We found a significant relationship between the peak latency of the duration-MMN peak and creatine-scaled Glx (p = .0003, η(2) = .43), with increased Glx level being associated to earlier peak of the duration-MMN (r = -.63). In contrast, the litude of the duration-MMN was not related to Glx. There was no significant relationship between Glx and the frequency-MMN. The present study is the first to demonstrate that interin idual variation in the glutamatergic neurotransmission affects the MMN response in healthy in iduals.
Publisher: Springer Science and Business Media LLC
Date: 18-05-2015
Publisher: Bentham Science Publishers Ltd.
Date: 04-01-2019
DOI: 10.2174/1568026619666181130103559
Abstract: Magnetic Resonance Spectroscopy (MRS) has become a valuable tool for investigating the biochemical bases of both normal processes in the healthy brain and elucidating the pathophysiology of neuropsychiatric disorders. As a rapidly advancing field, new developments in pulse sequence design have seen new possibilities arise in terms of what can be done with in vivo spectroscopy. While the applications of MRS are numerous, this review has been confined to the use of single voxel spectroscopy in the assessment of five key metabolites and their roles in schizophrenia: N-acetylaspartate (NAA), glutamate (Glu) and glutamine (Gln), γ-aminobutyric acid (GABA) and glutathione (GSH). This article will briefly cover the roles they play in schizophrenia, review current methods being used in their assessment and highlight new approaches that may potentially overcome some of the limitations current methods pose.
Publisher: Cambridge University Press (CUP)
Date: 23-06-2017
DOI: 10.1017/S003329171700174X
Abstract: Disturbances in Pavlovian valuation systems are reported to follow traumatic stress exposure. However, motivated decisions are also guided by instrumental mechanisms, but to date the effect of traumatic stress on these instrumental systems remain poorly investigated. Here, we examine whether a single episode of severe traumatic stress influences flexible instrumental decisions through an impact on a Pavlovian system. Twenty-six survivors of the 2011 Norwegian terror attack and 30 matched control subjects performed an instrumental learning task in which Pavlovian and instrumental associations promoted congruent or conflicting responses. We used reinforcement learning models to infer how traumatic stress affected learning and decision-making. Based on the importance of dorsal anterior cingulate cortex (dACC) for cognitive control, we also investigated if in idual concentrations of Glx (=glutamate + glutamine) in dACC predicted the Pavlovian bias of choice. Survivors of traumatic stress expressed a greater Pavlovian interference with instrumental action selection and had significantly lower levels of Glx in the dACC. Across subjects, the degree of Pavlovian interference was negatively associated with dACC Glx concentrations. Experiencing traumatic stress appears to render instrumental decisions less flexible by increasing the susceptibility to Pavlovian influences. An observed association between prefrontal glutamatergic levels and this Pavlovian bias provides novel insight into the neurochemical basis of decision-making, and suggests a mechanism by which traumatic stress can impair flexible instrumental behaviours.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.NEUROIMAGE.2018.01.043
Abstract: Creatine is a key regulator of brain energy homeostasis, and well-balanced creatine metabolism is central in healthy brain functioning. Still, the variability of brain creatine metabolism is largely unattended in magnetic resonance spectroscopy (MRS) research. In the human brain, marginal sex differences in creatine levels have been found in the prefrontal cortex. It is however not known to what degree these sex differences are stable or change with varying gonadal hormone levels. The current study therefore investigated creatine in the prefrontal cortex across the menstrual cycle. In addition, we explored cerebral asymmetries. Creatine, Choline (Cho), N-acetylaspartate (NAA), Myo inositol (mI), and glutamate + glutamine (Glx) were assessed three times in 15 women and 14 men using MRS. Women were tested in cycle phases of varying hormone levels (menstrual, follicular, and luteal phase). Prefrontal creatine was found to change across the menstrual cycle, in a hemisphere-specific manner. Women in the follicular phase showed increased left prefrontal creatine accompanied with reduced right prefrontal creatine, while this asymmetry was not present in the luteal phase. In men, the creatine levels remained stable across three testing sessions. In general, both men and women were found to have higher creatine levels in the left as compared to the right prefrontal cortex. Exploratory analyses of other metabolites showed similar asymmetries in NAA, Cho, and mI, while Cho also showed a menstrual cycle effect. This is the first time that sex hormone-related changes in creatine metabolism have been demonstrated in the human brain. These findings may have important methodological implications for MRS research, as it supports previous concerns against uncritical usage of creatine as a reference measure for other metabolites, assumed to be invariant across in iduals and conditions.
Publisher: Frontiers Media SA
Date: 18-06-2018
Publisher: Elsevier BV
Date: 08-2015
Publisher: Cambridge University Press (CUP)
Date: 18-09-2018
DOI: 10.1017/S0033291718002519
Abstract: Neurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry. We combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy ( 1 H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects. Traumatized youths showed altered amygdala–anterior midcingulate cortex (aMCC) and amygdala–ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al ., 2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the in idual amygdala–aMCC and amygdala–vmPFC functional connectivity, and also mediated the observed group difference in amygdala–aMCC connectivity. Our findings suggest that traumatic stress may influence amygdala–prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness.
Publisher: Cold Spring Harbor Laboratory
Date: 10-2017
DOI: 10.1101/196634
Abstract: Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across in iduals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy in iduals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippoc al gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets ( N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders. Left-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.
Publisher: Cold Spring Harbor Laboratory
Date: 18-03-2020
DOI: 10.1101/2020.03.17.995282
Abstract: 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.
Publisher: Oxford University Press (OUP)
Date: 2019
Publisher: Wiley
Date: 15-02-2017
DOI: 10.1002/JMRI.25588
Abstract: The reproducibility of the MEGA-PRESS (MEshcher-GArwood Point RESolved Spectroscopy) MR spectroscopy sequence for the measurement of gamma- aminobutyric acid (GABA) is addressed, focusing on optimizing the number of repetitions at two voxel locations in the human brain and associated possibilities in analysis tools. Two 20-min MEGA-PRESS acquisitions were run (echo time = 68 ms, repetition time = 1800 ms, repetitions = 328): one from a 21 mL volume in the anterior cingulate cortex (ACC) and one from a 22 mL volume in the left Broca's area in 21 healthy male volunteers (age 32 years ± 6[SD]). Subjects were scanned twice with identical protocols, 1 week apart. Data were acquired on a 3 Tesla GE Discovery 750 scanner using a 32-channel head coil. Spectroscopy data were partitioned into shorter epochs, numerically equivalent to scans of progressively increasing duration, and compared both within and between sessions. Three different analysis schemes were applied: (1) Vendor prototype preprocessor, with quantification by LCModel. (2) Pure Gannet pipeline. (3) Preprocessing with Gannet, and quantification with LCModel. The coefficient of variation (CV) were calculated as a measure of reproducibility. Increasing the number of repetitions showed improvements for within- and between-session reproducibility up to around 218 repetitions. (CV ranging from 4 to 14%). Gannet combined with LCModel approach proved the best method. (CV = 4-5%). Measurements from the ACC area had higher CVs than the Broca area. (CV = 6-14% versus 4-7%). Measurement in the Broca area yields better reproducibility than the ACC. With appropriate acquisition times and preprocessing tools, measurements from the ACC area are also reliable. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017 :421-430.
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 17-08-2020
DOI: 10.1038/S41398-020-00974-4
Abstract: The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24–36 months post-trauma. PTSD symptoms were assessed 4–5, 14–15 and 24–36 months following the trauma. We found that increased PTSD symptom severity 24–36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4–5 months and 24–36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.
No related grants have been discovered for Kenneth Hugdahl.