Liliana Ramona Demenescu | RWTH Aachen University (original) (raw)

Papers by Liliana Ramona Demenescu

Neurobiology of stress, Mar 1, 2024

European Neuropsychopharmacology, Sep 30, 2011

European Neuropsychopharmacology, Sep 30, 2011

Neuro Imaging Researc

Neurobiology of Stress, Jul 1, 2023

Magnetic Resonance Materials in Physics Biology and Medicine, Feb 9, 2016

More than 50 % of individuals experienced vertigo and metallic taste while working with 7 T MRI s... more More than 50 % of individuals experienced vertigo and metallic taste while working with 7 T MRI scanners. However, participants' perceptions of safety were not affected by the prevalence of MR-related symptoms. Conclusions The overall data indicated an average perception of a moderately safe work environment. To our knowledge, this study delineates the first attempt to assess the subjective safety perception among 7 T MRI workers and suggests further investigations are indicated. Keywords Ultra-high field magnetic resonance imaging • Occupational exposure • Perception • Safety Abbreviations UHF MRI Ultra-high field magnetic resonance imaging SMF Static magnetic field GMF Gradient magnetic field RF Radiofrequency field EMF Electromagnetic field Abstract Objective To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla (T) magnetic resonance imaging (MRI) scanners. Materials and methods A total of 66 healthy individuals with a mean age of 31 ± 7 years participated in this retrospective multicentre survey study. Nonparametric correlation analysis was conducted to evaluate the relation between self-reported perception of safety and prevalence of sensory effects while working with 7 T MRI scanners for an average 47 months. Results The results indicated that 98.5 % of the study participants had a neutral or positive feeling about safety aspects at 7 T MRI scanners. 45.5 % reported that they feel very safe and none of the participants stated that they feel moderately or very unsafe while working with 7 T MRI scanners. Perception of safety was not affected by the Electronic supplementary material The online version of this article (

Neuropsychopharmacology, Sep 8, 2016

The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major d... more The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major depressive disorder. Subanesthetic doses of ketamine were repeatedly shown to improve depressive symptoms within 24 h after infusion and this antidepressant effect was attributed to increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) throughput. To elucidate ketamine's mechanism of action, we tested whether the clinical time course of the improvement is mirrored by the change of glutamine/glutamate ratio and if such effects show a regional and temporal specificity in two distinct subdivisions of ACC with different AMPA/N-methyl-D-aspartate receptor profiles. In a double-blind, placebo-controlled intravenous infusion study of ketamine, we measured glutamate and glutamine in the pregenual ACC (pgACC) and the anterior midcingulate cortex at 1 and 24 h post infusion with magnetic resonance spectroscopy at 7 T. A significant interaction of time, region, and treatment was found for the glutamine/glutamate ratios (placebo, n = 14; ketamine, n = 12). Posthoc analyses revealed that the glutamine/glutamate ratio increased significantly in the ketamine group, compared with placebo, specifically in the pgACC after 24 h. The glutamine/glutamate increase in the pgACC caused by ketamine at 24 h post infusion was reproduced in an enlarged sample (placebo, n = 24; ketamine, n = 20). Our results support a significant temporal and regional response in glutamine/ glutamate ratios to a single subanesthetic dose of ketamine, which mirrors the time course of the antidepressant response and reversal of the molecular deficits in patients and which may be associated with the histoarchitectonical receptor fingerprints of the ACC subregions.

European Psychiatry, Mar 1, 2016

In that survey, we ask residents if they ever have been physically assaulted, for how many times,... more In that survey, we ask residents if they ever have been physically assaulted, for how many times, the year of residence when it occurred, if they have in their hospital an aggression protocol, and if it included a specific topic for trainees. We also asked them about their feelings after they have been assaulted. Results We collected 282 answers from the survey. We could observe that 12.9% of respondent trainees had been assaulted as least once. Fifty-one percent of times, it occurs during the first year of residency. Among assaulted residents, 25.5% were psychiatric trainees, and 44.4% were medical trainees, but no psychiatrist. Twenty-three percent were psychiatric trainees, and the 35% of them had been assaulted once. Only 25.2% of the residents knew the aggression protocol of their work center, but the majority (65.5%) did not know it. About how do they feel after being assaulted, most of them responded that they felt anxiety, helplessness, fear and they had even thought of leaving de residency or change it. Conclusions Aggressions during the trainee period seems to be prevalent (12,9%). Most trainees don't even know if there is a aggression protocol in their hospitals, we think that a prevention and supporting guideline should be design for improve this prevalent situation. Disclosure of interest The authors have not supplied their declaration of competing interest.

Kongress der Deutschen Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde e. V. (DGPPN 2018), Nov 1, 2018

Increasing evidence suggests a hypoglutamatergic state in major depressive disorder (MDD), howeve... more Increasing evidence suggests a hypoglutamatergic state in major depressive disorder (MDD), however spatial- and metabolite specific abnormalities have not been fully characterized. Using short TE/TM STEAM MRS, we evaluated Glu, Gln, Gln/Glu and GABA metabolism in two histoarchitectonically distinct subdivisions of the anterior cingulate cortex (ACC). The pregenual ACC, involved in emotion processing, showed altered glutamine-glutamine cycling but not altered GABAergic metabolism in MDD, whereas no differences between patients and controls were found in the anteromedial ACC. Increased Gln/Glu in MDD in pgACC but not aMCC confirms a regionally specific role of altered glutamatergic metabolism and neuronal-glial interaction

BioMedical Engineering OnLine, 2019

Background: Avoidance to look others in the eye is a characteristic symptom of Autism Spectrum Di... more Background: Avoidance to look others in the eye is a characteristic symptom of Autism Spectrum Disorders (ASD), and it has been hypothesised that quantitative monitoring of gaze patterns could be useful to objectively evaluate treatments. However, tools to measure gaze behaviour on a regular basis at a manageable cost are missing. In this paper, we investigated whether a smartphone-based tool could address this problem. Specifically, we assessed the accuracy with which the phone-based, state-ofthe-art eye-tracking algorithm iTracker can distinguish between gaze towards the eyes and the mouth of a face displayed on the smartphone screen. This might allow mobile, longitudinal monitoring of gaze aversion behaviour in ASD patients in the future. Results: We simulated a smartphone application in which subjects were shown an image on the screen and their gaze was analysed using iTracker. We evaluated the accuracy of our setup across three tasks in a cohort of 17 healthy volunteers. In the first two tasks, subjects were shown different-sized images of a face and asked to alternate their gaze focus between the eyes and the mouth. In the last task, participants were asked to trace out a circle on the screen with their eyes. We confirm that iTracker can recapitulate the true gaze patterns, and capture relative position of gaze correctly, even on a different phone system to what it was trained on. Subject-specific bias can be corrected using an error model informed from the calibration data. We compare two calibration methods and observe that a linear model performs better than a previously proposed support vector regression-based method. Conclusions: Under controlled conditions it is possible to reliably distinguish between gaze towards the eyes and the mouth with a smartphone-based setup. However, future research will be required to improve the robustness of the system to roll angle of the phone and distance between the user and the screen to allow deployment in a home setting. We conclude that a smartphone-based gaze-monitoring tool provides promising opportunities for more quantitative monitoring of ASD.

Neuropsychologia, Jan 21, 2017

In "Two heads are better than one," "head" stands for people and focuses the ... more In "Two heads are better than one," "head" stands for people and focuses the message on the intelligence of people. This is an example of figurative language through metonymy, where substituting a whole entity by one of its parts focuses attention on a specific aspect of the entity. Whereas metaphors, another figurative language device, are substitutions based on similarity, metonymy involves substitutions based on associations. Both are figures of speech but are also expressed in coverbal gestures during multimodal communication. The closest neuropsychological studies of metonymy in gestures has been nonlinguistic tool-use, illustrated by the classic apraxic problem of body-part-as-object (BPO, equivalent to an internal metonymy representation of the tool) vs. pantomimed action (external metonymy representation of the absent object/tool). Combining these research domains with concepts in cognitive linguistic research on gestures, we conducted an fMRI study to in...

Biological Psychiatry, 2017

European archives of psychiatry and clinical neuroscience, Jan 25, 2016

Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depres... more Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest...

European Psychiatry, 2015

The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major d... more The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major depressive disorder. Subanesthetic doses of ketamine were repeatedly shown to improve depressive symptoms within 24 h after infusion and this antidepressant effect was attributed to increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) throughput. To elucidate ketamine's mechanism of action, we tested whether the clinical time course of the improvement is mirrored by the change of glutamine/glutamate ratio and if such effects show a regional and temporal specificity in two distinct subdivisions of ACC with different AMPA/N-methyl-D-aspartate receptor profiles. In a double-blind, placebo-controlled intravenous infusion study of ketamine, we measured glutamate and glutamine in the pregenual ACC (pgACC) and the anterior midcingulate cortex at 1 and 24 h post infusion with magnetic resonance spectroscopy at 7 T. A significant interaction of time, region, and treatment was found for the glutamine/glutamate ratios (placebo, n = 14; ketamine, n = 12). Posthoc analyses revealed that the glutamine/glutamate ratio increased significantly in the ketamine group, compared with placebo, specifically in the pgACC after 24 h. The glutamine/glutamate increase in the pgACC caused by ketamine at 24 h post infusion was reproduced in an enlarged sample (placebo, n = 24; ketamine, n = 20). Our results support a significant temporal and regional response in glutamine/ glutamate ratios to a single subanesthetic dose of ketamine, which mirrors the time course of the antidepressant response and reversal of the molecular deficits in patients and which may be associated with the histoarchitectonical receptor fingerprints of the ACC subregions.

Magma (New York, N.Y.), Jan 9, 2016

To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla ... more To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla (T) magnetic resonance imaging (MRI) scanners. A total of 66 healthy individuals with a mean age of 31 ± 7 years participated in this retrospective multicentre survey study. Nonparametric correlation analysis was conducted to evaluate the relation between self-reported perception of safety and prevalence of sensory effects while working with 7 T MRI scanners for an average 47 months. The results indicated that 98.5 % of the study participants had a neutral or positive feeling about safety aspects at 7 T MRI scanners. 45.5 % reported that they feel very safe and none of the participants stated that they feel moderately or very unsafe while working with 7 T MRI scanners. Perception of safety was not affected by the number of hours per week spent in the vicinity of the 7 T MRI scanner or the duration of experience with 7 T MRI. More than 50 % of individuals experienced vertigo and metallic ...

European Neuropsychopharmacology, 2019

European Neuropsychopharmacology, Mar 1, 2013

ABSTRACT The neurobiology of social anxiety disorder (SAD) is not yet fully understood. Structura... more ABSTRACT The neurobiology of social anxiety disorder (SAD) is not yet fully understood. Structural and functional neuroimaging studies in SAD have identified abnormalities in various brain areas, particularly the amygdala and elements of the salience network. This study is the first to examine resting-state functional brain connectivity in a drug-naive sample of SAD patients without psychiatric comorbidity and healthy controls, using seed regions of interest in bilateral amygdala, in bilateral dorsal anterior cingulate cortex for the salience network, and in bilateral posterior cingulate cortex for the default mode network. Twelve drug-naive SAD patients and pair-wise matched healthy controls, all drawn from the Netherlands Study of Depression and Anxiety sample, underwent resting-state fMRI. Group differences were assessed with voxel-wise gray matter density as nuisance regressor. All results were cluster corrected for multiple comparisons (Z>2.3, p<.05). Relative to control subjects, drug-naive SAD patients demonstrated increased negative right amygdala connectivity with the left middle temporal gyrus, left supramarginal gyrus and left lateral occipital cortex. In the salience network patients showed increased positive bilateral dorsal anterior cingulate connectivity with the left precuneus and left lateral occipital cortex. Default mode network connectivity was not different between groups. These data demonstrate that drug-naive SAD patients without comorbidity show differences in functional connectivity of the amygdala, and of areas involved in self-awareness, some of which have not been implicated in SAD before.

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Dec 1, 2019

BACKGROUND Patients with major depressive disorder (MDD) show glutamatergic deficits in the ventr... more BACKGROUND Patients with major depressive disorder (MDD) show glutamatergic deficits in the ventral anterior cingulate cortex. The glutamine/glutamate (Gln/Glu) ratio was proposed to be connected to glutamatergic cycling, which is hypothesized to be dysregulated in MDD. As an indicator of regional metabolite status, this ratio might be a robust state marker sensitive to clinical heterogeneity. METHODS Thirty-two MDD patients (mean age 40.88 ± 13.66 years, 19 women) and control subjects (mean age 33.09 ± 8.24 years, 19 women) were compared for pregenual anterior cingulate cortex levels of Gln/Glu, Gln/total creatine (tCr), Glu/tCr, and gamma-aminobutyric acid/tCr as determined by high-field magnetic resonance spectroscopy. We tested if symptom severity (Hamilton Depression Rating Scale) and anhedonia (Snaith-Hamilton Pleasure Scale) influence the relation of metabolites to clinical symptoms. RESULTS MDD patients showed higher Gln/Glu. This was driven by marginally higher Gln/tCr and nonsignificantly lower Glu/tCr. Groups defined by severity moderated relationship between Gln/Glu and the Hamilton Depression Rating Scale. Moreover, severe cases differed from both control subjects and moderate cases. Groups defined by the Snaith-Hamilton Pleasure Scale also displayed differential relationship between Gln/Glu and levels of anhedonia, predominantly driven by Gln/tCr. CONCLUSIONS We elaborate previous accounts of metabolite deficits in the anterior cingulate cortex toward increased Gln/Glu. There is a moderated relationship between severity and the ratio, which suggests consideration of different mechanisms or disease state for the respective subgroups in future studies.

Biological Psychiatry, Apr 1, 2012

Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most p... more Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may be characterized by a common deficiency in processing of emotional information. We used functional magnetic resonance imaging during the performance of an emotional word encoding and recognition paradigm in patients with MDD (n = 51), comorbid MDD and anxiety (n = 59), panic disorder and/or social anxiety disorder without comorbid MDD (n = 56), and control subjects (n = 49). In addition, we studied effects of illness severity, regional brain volume, and antidepressant use. Patients with MDD, prevalent anxiety disorders, or both showed a common hyporesponse in the right hippocampus during positive (>neutral) word encoding compared with control subjects. During negative encoding, increased insular activation was observed in both depressed groups (MDD and MDD + anxiety), whereas increased amygdala and anterior cingulate cortex activation during positive word encoding were observed as depressive state-dependent effects in MDD only. During recognition, anxiety patients showed increased inferior frontal gyrus activation. Overall, effects were unaffected by medication use and regional brain volume. Hippocampal blunting during positive word encoding is a generic effect in depression and anxiety disorders, which may constitute a common vulnerability factor. Increased insular and amygdalar involvement during negative word encoding may underlie heightened experience of, and an inability to disengage from, negative emotions in depressive disorders. Our results emphasize a common neurobiological deficiency in both MDD and anxiety disorders, which may mark a general insensitiveness to positive information.

Social Cognitive and Affective Neuroscience, Sep 4, 2015

Alexithymia, a personality construct marked by difficulties in processing one's emotions, has bee... more Alexithymia, a personality construct marked by difficulties in processing one's emotions, has been linked to the altered activity in the anterior cingulate cortex (ACC). Although longitudinal studies reported sex differences in alexithymia, what mediates them is not known. To investigate sex-specific associations of alexithymia and neuronal markers, we mapped metabolites in four brain regions involved differentially in emotion processing using a point-resolved spectroscopy MRS sequence in 3 Tesla. Both sexes showed negative correlations between alexithymia and N-acetylaspartate (NAA) in pregenual ACC (pgACC). Women showed a robust negative correlation of the joint measure of glutamate and glutamine (Glx) to NAA in posterior cingulate cortex (PCC), whereas men showed a weak positive association of Glx to NAA in dorsal ACC (dACC). Our results suggest that lowered neuronal integrity in pgACC, a region of the default mode network (DMN), might primarily account for the general difficulties in emotional processing in alexithymia. Association of alexithymia in women extends to another region in the DMN-PCC, while in men a region in the salience network (SN) was involved. These observations could be representative of sex specific regulation strategies that include diminished internal evaluation of feelings in women and cognitive emotion suppression in men.

Neurobiology of stress, Mar 1, 2024

European Neuropsychopharmacology, Sep 30, 2011

European Neuropsychopharmacology, Sep 30, 2011

Neuro Imaging Researc

Neurobiology of Stress, Jul 1, 2023

Magnetic Resonance Materials in Physics Biology and Medicine, Feb 9, 2016

More than 50 % of individuals experienced vertigo and metallic taste while working with 7 T MRI s... more More than 50 % of individuals experienced vertigo and metallic taste while working with 7 T MRI scanners. However, participants' perceptions of safety were not affected by the prevalence of MR-related symptoms. Conclusions The overall data indicated an average perception of a moderately safe work environment. To our knowledge, this study delineates the first attempt to assess the subjective safety perception among 7 T MRI workers and suggests further investigations are indicated. Keywords Ultra-high field magnetic resonance imaging • Occupational exposure • Perception • Safety Abbreviations UHF MRI Ultra-high field magnetic resonance imaging SMF Static magnetic field GMF Gradient magnetic field RF Radiofrequency field EMF Electromagnetic field Abstract Objective To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla (T) magnetic resonance imaging (MRI) scanners. Materials and methods A total of 66 healthy individuals with a mean age of 31 ± 7 years participated in this retrospective multicentre survey study. Nonparametric correlation analysis was conducted to evaluate the relation between self-reported perception of safety and prevalence of sensory effects while working with 7 T MRI scanners for an average 47 months. Results The results indicated that 98.5 % of the study participants had a neutral or positive feeling about safety aspects at 7 T MRI scanners. 45.5 % reported that they feel very safe and none of the participants stated that they feel moderately or very unsafe while working with 7 T MRI scanners. Perception of safety was not affected by the Electronic supplementary material The online version of this article (

Neuropsychopharmacology, Sep 8, 2016

The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major d... more The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major depressive disorder. Subanesthetic doses of ketamine were repeatedly shown to improve depressive symptoms within 24 h after infusion and this antidepressant effect was attributed to increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) throughput. To elucidate ketamine's mechanism of action, we tested whether the clinical time course of the improvement is mirrored by the change of glutamine/glutamate ratio and if such effects show a regional and temporal specificity in two distinct subdivisions of ACC with different AMPA/N-methyl-D-aspartate receptor profiles. In a double-blind, placebo-controlled intravenous infusion study of ketamine, we measured glutamate and glutamine in the pregenual ACC (pgACC) and the anterior midcingulate cortex at 1 and 24 h post infusion with magnetic resonance spectroscopy at 7 T. A significant interaction of time, region, and treatment was found for the glutamine/glutamate ratios (placebo, n = 14; ketamine, n = 12). Posthoc analyses revealed that the glutamine/glutamate ratio increased significantly in the ketamine group, compared with placebo, specifically in the pgACC after 24 h. The glutamine/glutamate increase in the pgACC caused by ketamine at 24 h post infusion was reproduced in an enlarged sample (placebo, n = 24; ketamine, n = 20). Our results support a significant temporal and regional response in glutamine/ glutamate ratios to a single subanesthetic dose of ketamine, which mirrors the time course of the antidepressant response and reversal of the molecular deficits in patients and which may be associated with the histoarchitectonical receptor fingerprints of the ACC subregions.

European Psychiatry, Mar 1, 2016

In that survey, we ask residents if they ever have been physically assaulted, for how many times,... more In that survey, we ask residents if they ever have been physically assaulted, for how many times, the year of residence when it occurred, if they have in their hospital an aggression protocol, and if it included a specific topic for trainees. We also asked them about their feelings after they have been assaulted. Results We collected 282 answers from the survey. We could observe that 12.9% of respondent trainees had been assaulted as least once. Fifty-one percent of times, it occurs during the first year of residency. Among assaulted residents, 25.5% were psychiatric trainees, and 44.4% were medical trainees, but no psychiatrist. Twenty-three percent were psychiatric trainees, and the 35% of them had been assaulted once. Only 25.2% of the residents knew the aggression protocol of their work center, but the majority (65.5%) did not know it. About how do they feel after being assaulted, most of them responded that they felt anxiety, helplessness, fear and they had even thought of leaving de residency or change it. Conclusions Aggressions during the trainee period seems to be prevalent (12,9%). Most trainees don't even know if there is a aggression protocol in their hospitals, we think that a prevention and supporting guideline should be design for improve this prevalent situation. Disclosure of interest The authors have not supplied their declaration of competing interest.

Kongress der Deutschen Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde e. V. (DGPPN 2018), Nov 1, 2018

Increasing evidence suggests a hypoglutamatergic state in major depressive disorder (MDD), howeve... more Increasing evidence suggests a hypoglutamatergic state in major depressive disorder (MDD), however spatial- and metabolite specific abnormalities have not been fully characterized. Using short TE/TM STEAM MRS, we evaluated Glu, Gln, Gln/Glu and GABA metabolism in two histoarchitectonically distinct subdivisions of the anterior cingulate cortex (ACC). The pregenual ACC, involved in emotion processing, showed altered glutamine-glutamine cycling but not altered GABAergic metabolism in MDD, whereas no differences between patients and controls were found in the anteromedial ACC. Increased Gln/Glu in MDD in pgACC but not aMCC confirms a regionally specific role of altered glutamatergic metabolism and neuronal-glial interaction

BioMedical Engineering OnLine, 2019

Background: Avoidance to look others in the eye is a characteristic symptom of Autism Spectrum Di... more Background: Avoidance to look others in the eye is a characteristic symptom of Autism Spectrum Disorders (ASD), and it has been hypothesised that quantitative monitoring of gaze patterns could be useful to objectively evaluate treatments. However, tools to measure gaze behaviour on a regular basis at a manageable cost are missing. In this paper, we investigated whether a smartphone-based tool could address this problem. Specifically, we assessed the accuracy with which the phone-based, state-ofthe-art eye-tracking algorithm iTracker can distinguish between gaze towards the eyes and the mouth of a face displayed on the smartphone screen. This might allow mobile, longitudinal monitoring of gaze aversion behaviour in ASD patients in the future. Results: We simulated a smartphone application in which subjects were shown an image on the screen and their gaze was analysed using iTracker. We evaluated the accuracy of our setup across three tasks in a cohort of 17 healthy volunteers. In the first two tasks, subjects were shown different-sized images of a face and asked to alternate their gaze focus between the eyes and the mouth. In the last task, participants were asked to trace out a circle on the screen with their eyes. We confirm that iTracker can recapitulate the true gaze patterns, and capture relative position of gaze correctly, even on a different phone system to what it was trained on. Subject-specific bias can be corrected using an error model informed from the calibration data. We compare two calibration methods and observe that a linear model performs better than a previously proposed support vector regression-based method. Conclusions: Under controlled conditions it is possible to reliably distinguish between gaze towards the eyes and the mouth with a smartphone-based setup. However, future research will be required to improve the robustness of the system to roll angle of the phone and distance between the user and the screen to allow deployment in a home setting. We conclude that a smartphone-based gaze-monitoring tool provides promising opportunities for more quantitative monitoring of ASD.

Neuropsychologia, Jan 21, 2017

In "Two heads are better than one," "head" stands for people and focuses the ... more In "Two heads are better than one," "head" stands for people and focuses the message on the intelligence of people. This is an example of figurative language through metonymy, where substituting a whole entity by one of its parts focuses attention on a specific aspect of the entity. Whereas metaphors, another figurative language device, are substitutions based on similarity, metonymy involves substitutions based on associations. Both are figures of speech but are also expressed in coverbal gestures during multimodal communication. The closest neuropsychological studies of metonymy in gestures has been nonlinguistic tool-use, illustrated by the classic apraxic problem of body-part-as-object (BPO, equivalent to an internal metonymy representation of the tool) vs. pantomimed action (external metonymy representation of the absent object/tool). Combining these research domains with concepts in cognitive linguistic research on gestures, we conducted an fMRI study to in...

Biological Psychiatry, 2017

European archives of psychiatry and clinical neuroscience, Jan 25, 2016

Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depres... more Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest...

European Psychiatry, 2015

The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major d... more The anterior cingulate cortex (ACC) has shown decreased glutamate levels in patients with major depressive disorder. Subanesthetic doses of ketamine were repeatedly shown to improve depressive symptoms within 24 h after infusion and this antidepressant effect was attributed to increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) throughput. To elucidate ketamine's mechanism of action, we tested whether the clinical time course of the improvement is mirrored by the change of glutamine/glutamate ratio and if such effects show a regional and temporal specificity in two distinct subdivisions of ACC with different AMPA/N-methyl-D-aspartate receptor profiles. In a double-blind, placebo-controlled intravenous infusion study of ketamine, we measured glutamate and glutamine in the pregenual ACC (pgACC) and the anterior midcingulate cortex at 1 and 24 h post infusion with magnetic resonance spectroscopy at 7 T. A significant interaction of time, region, and treatment was found for the glutamine/glutamate ratios (placebo, n = 14; ketamine, n = 12). Posthoc analyses revealed that the glutamine/glutamate ratio increased significantly in the ketamine group, compared with placebo, specifically in the pgACC after 24 h. The glutamine/glutamate increase in the pgACC caused by ketamine at 24 h post infusion was reproduced in an enlarged sample (placebo, n = 24; ketamine, n = 20). Our results support a significant temporal and regional response in glutamine/ glutamate ratios to a single subanesthetic dose of ketamine, which mirrors the time course of the antidepressant response and reversal of the molecular deficits in patients and which may be associated with the histoarchitectonical receptor fingerprints of the ACC subregions.

Magma (New York, N.Y.), Jan 9, 2016

To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla ... more To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla (T) magnetic resonance imaging (MRI) scanners. A total of 66 healthy individuals with a mean age of 31 ± 7 years participated in this retrospective multicentre survey study. Nonparametric correlation analysis was conducted to evaluate the relation between self-reported perception of safety and prevalence of sensory effects while working with 7 T MRI scanners for an average 47 months. The results indicated that 98.5 % of the study participants had a neutral or positive feeling about safety aspects at 7 T MRI scanners. 45.5 % reported that they feel very safe and none of the participants stated that they feel moderately or very unsafe while working with 7 T MRI scanners. Perception of safety was not affected by the number of hours per week spent in the vicinity of the 7 T MRI scanner or the duration of experience with 7 T MRI. More than 50 % of individuals experienced vertigo and metallic ...

European Neuropsychopharmacology, 2019

European Neuropsychopharmacology, Mar 1, 2013

ABSTRACT The neurobiology of social anxiety disorder (SAD) is not yet fully understood. Structura... more ABSTRACT The neurobiology of social anxiety disorder (SAD) is not yet fully understood. Structural and functional neuroimaging studies in SAD have identified abnormalities in various brain areas, particularly the amygdala and elements of the salience network. This study is the first to examine resting-state functional brain connectivity in a drug-naive sample of SAD patients without psychiatric comorbidity and healthy controls, using seed regions of interest in bilateral amygdala, in bilateral dorsal anterior cingulate cortex for the salience network, and in bilateral posterior cingulate cortex for the default mode network. Twelve drug-naive SAD patients and pair-wise matched healthy controls, all drawn from the Netherlands Study of Depression and Anxiety sample, underwent resting-state fMRI. Group differences were assessed with voxel-wise gray matter density as nuisance regressor. All results were cluster corrected for multiple comparisons (Z>2.3, p<.05). Relative to control subjects, drug-naive SAD patients demonstrated increased negative right amygdala connectivity with the left middle temporal gyrus, left supramarginal gyrus and left lateral occipital cortex. In the salience network patients showed increased positive bilateral dorsal anterior cingulate connectivity with the left precuneus and left lateral occipital cortex. Default mode network connectivity was not different between groups. These data demonstrate that drug-naive SAD patients without comorbidity show differences in functional connectivity of the amygdala, and of areas involved in self-awareness, some of which have not been implicated in SAD before.

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Dec 1, 2019

BACKGROUND Patients with major depressive disorder (MDD) show glutamatergic deficits in the ventr... more BACKGROUND Patients with major depressive disorder (MDD) show glutamatergic deficits in the ventral anterior cingulate cortex. The glutamine/glutamate (Gln/Glu) ratio was proposed to be connected to glutamatergic cycling, which is hypothesized to be dysregulated in MDD. As an indicator of regional metabolite status, this ratio might be a robust state marker sensitive to clinical heterogeneity. METHODS Thirty-two MDD patients (mean age 40.88 ± 13.66 years, 19 women) and control subjects (mean age 33.09 ± 8.24 years, 19 women) were compared for pregenual anterior cingulate cortex levels of Gln/Glu, Gln/total creatine (tCr), Glu/tCr, and gamma-aminobutyric acid/tCr as determined by high-field magnetic resonance spectroscopy. We tested if symptom severity (Hamilton Depression Rating Scale) and anhedonia (Snaith-Hamilton Pleasure Scale) influence the relation of metabolites to clinical symptoms. RESULTS MDD patients showed higher Gln/Glu. This was driven by marginally higher Gln/tCr and nonsignificantly lower Glu/tCr. Groups defined by severity moderated relationship between Gln/Glu and the Hamilton Depression Rating Scale. Moreover, severe cases differed from both control subjects and moderate cases. Groups defined by the Snaith-Hamilton Pleasure Scale also displayed differential relationship between Gln/Glu and levels of anhedonia, predominantly driven by Gln/tCr. CONCLUSIONS We elaborate previous accounts of metabolite deficits in the anterior cingulate cortex toward increased Gln/Glu. There is a moderated relationship between severity and the ratio, which suggests consideration of different mechanisms or disease state for the respective subgroups in future studies.

Biological Psychiatry, Apr 1, 2012

Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most p... more Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may be characterized by a common deficiency in processing of emotional information. We used functional magnetic resonance imaging during the performance of an emotional word encoding and recognition paradigm in patients with MDD (n = 51), comorbid MDD and anxiety (n = 59), panic disorder and/or social anxiety disorder without comorbid MDD (n = 56), and control subjects (n = 49). In addition, we studied effects of illness severity, regional brain volume, and antidepressant use. Patients with MDD, prevalent anxiety disorders, or both showed a common hyporesponse in the right hippocampus during positive (>neutral) word encoding compared with control subjects. During negative encoding, increased insular activation was observed in both depressed groups (MDD and MDD + anxiety), whereas increased amygdala and anterior cingulate cortex activation during positive word encoding were observed as depressive state-dependent effects in MDD only. During recognition, anxiety patients showed increased inferior frontal gyrus activation. Overall, effects were unaffected by medication use and regional brain volume. Hippocampal blunting during positive word encoding is a generic effect in depression and anxiety disorders, which may constitute a common vulnerability factor. Increased insular and amygdalar involvement during negative word encoding may underlie heightened experience of, and an inability to disengage from, negative emotions in depressive disorders. Our results emphasize a common neurobiological deficiency in both MDD and anxiety disorders, which may mark a general insensitiveness to positive information.

Social Cognitive and Affective Neuroscience, Sep 4, 2015

Alexithymia, a personality construct marked by difficulties in processing one's emotions, has bee... more Alexithymia, a personality construct marked by difficulties in processing one's emotions, has been linked to the altered activity in the anterior cingulate cortex (ACC). Although longitudinal studies reported sex differences in alexithymia, what mediates them is not known. To investigate sex-specific associations of alexithymia and neuronal markers, we mapped metabolites in four brain regions involved differentially in emotion processing using a point-resolved spectroscopy MRS sequence in 3 Tesla. Both sexes showed negative correlations between alexithymia and N-acetylaspartate (NAA) in pregenual ACC (pgACC). Women showed a robust negative correlation of the joint measure of glutamate and glutamine (Glx) to NAA in posterior cingulate cortex (PCC), whereas men showed a weak positive association of Glx to NAA in dorsal ACC (dACC). Our results suggest that lowered neuronal integrity in pgACC, a region of the default mode network (DMN), might primarily account for the general difficulties in emotional processing in alexithymia. Association of alexithymia in women extends to another region in the DMN-PCC, while in men a region in the salience network (SN) was involved. These observations could be representative of sex specific regulation strategies that include diminished internal evaluation of feelings in women and cognitive emotion suppression in men.