The brain network for the recognition of biological motion includes visual areas and structures o... more The brain network for the recognition of biological motion includes visual areas and structures of the mirror-neuron system. The latter respond during action execution as well as during action recog- nition. Since motor and somatosensory areas predominantly represent the contralateral body-side, and visual areas predominantly process stimuli from the contralateral hemifield, we were interested in in- teractions between visual hemifield
Working memory (WM) processes depend on our momentary mental state and therefore exhibit consider... more Working memory (WM) processes depend on our momentary mental state and therefore exhibit considerable fluctuations. Here, we investigate the interplay of task-preparatory and task-related brain activity as represented by pre-stimulus BOLD-fluctuations and spectral EEG from the retention periods of a visual WM task. Visual WM is used to maintain sensory information in the brain enabling the performance of cognitive operations and is associated with mental health. We tested 22 subjects simultaneously with EEG and fMRI while performing a visuo-verbal Sternberg task with two different loads, allowing for the temporal separation of preparation, encoding, retention and retrieval periods. Four temporally coherent networks (TCNs)-the default mode network (DMN), the dorsal attention, the right and the left WM network-were extracted from the continuous BOLD data by means of a group ICA. Subsequently, the modulatory effect of these networks' pre-stimulus activation upon retention-related EEG activity in the theta, alpha, and beta frequencies was analyzed. The obtained results are informative in the context of state-dependent information processing. We were able to replicate two wellknown load-dependent effects: the frontal-midline theta increase during the task and the decrease of pre-stimulus DMN activity. As our main finding, these two measures seem to depend on each other as the significant negative correlations at frontal-midline channels suggested. Thus, suppressed pre-stimulus DMN levels facilitated later task related frontal midline theta increases. In general, based on previous findings that neuronal coupling in different frequency bands may underlie distinct functions in WM retention, our results suggest that processes reflected by spectral oscillations during retention seem not only to be "online" synchronized with activity in different attention-related networks but are also modulated by activity in these networks during preparation intervals.
Cerebral cortex (New York, N.Y. : 1991), Jan 26, 2014
Despite the crucial role of the brain in the control of the human lower urinary tract, little is ... more Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showe...
13 14 a b s t r a c t a r t i c l e i n f o 15 Available online xxxx 20 21 22 23 Keywords: 24 Vis... more 13 14 a b s t r a c t a r t i c l e i n f o 15 Available online xxxx 20 21 22 23 Keywords: 24 Visual system 25 Ventral stream 26 Dorsal stream 27 fMRI 28 International Affective Picture System 29 Sensory perception 30
Despite the crucial role of the brain in the control of the human lower urinary tract, little is ... more Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showe...
AimsUsing functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortic... more AimsUsing functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures.
Introduction: Lower urinary tract symptoms (LUTS) are highly prevalent, cause an enormous economi... more Introduction: Lower urinary tract symptoms (LUTS) are highly prevalent, cause an enormous economic burden on healthcare systems and significantly impair the quality of life (QoL) of affected patients. The dependence of the LUT on complex central neuronal circuits makes it unique in comparison to other visceral functions, such as the gastrointestinal tract, but also more vulnerable to neurological diseases.
Background: The control of the lower urinary tract is a complex, multilevel process involving bot... more Background: The control of the lower urinary tract is a complex, multilevel process involving both the peripheral and central nervous system. Due to lesions of the neuraxis, most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction, which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life. However, the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood.
The biomarker potential of the inhibitory neurotransmitter g-aminobutyric acid (GABA) for the in ... more The biomarker potential of the inhibitory neurotransmitter g-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimer's disease has not yet been explored. We measured GABA, glutamate þ glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound Bpositive subjects and APOE ε4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid b deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimer's disease.
13 14 a b s t r a c t a r t i c l e i n f o 15 Available online xxxx 20 21 22 23 Keywords: 24 Vis... more 13 14 a b s t r a c t a r t i c l e i n f o 15 Available online xxxx 20 21 22 23 Keywords: 24 Visual system 25 Ventral stream 26 Dorsal stream 27 fMRI 28 International Affective Picture System 29 Sensory perception 30
There is growing evidence that reward processing is disturbed in schizophrenia. However, it is un... more There is growing evidence that reward processing is disturbed in schizophrenia. However, it is uncertain whether this dysfunction predates or is secondary to the onset of psychosis. Studying 21 unmedicated persons at risk for psychosis plus 24 healthy controls (HCs) we used a incentive delay paradigm with monetary rewards during functional magnetic resonance imaging. During processing of reward information, at-risk individuals performed similarly well to controls and recruited the same brain areas. However, while anticipating rewards, the high-risk sample exhibited additional activation in the posterior cingulate cortex, and the medio-and superior frontal gyrus, whereas no significant group differences were found after rewards were administered. Importantly, symptom dimensions were differentially associated with anticipation and outcome of the reward. Positive symptoms were correlated with the anticipation signal in the ventral striatum (VS) and the right anterior insula (rAI). Negative symptoms were inversely linked to outcome-related signal within the VS, and depressive symptoms to outcome-related signal within the medial orbitofrontal cortex (mOFC). Our findings provide evidence for a reward-associated dysregulation that can be compensated by recruitment of additional prefrontal areas. We propose that stronger activations within VS and rAI when anticipating a reward reflect abnormal processing of potential future rewards. Moreover, according to the aberrant salience theory of psychosis, this may predispose a person to positive symptoms. Additionally, we report evidence that negative and depressive symptoms are differentially associated with the receipt of a reward, which might demonstrate a broader vulnerability to motivational and affective symptoms in persons at-risk for psychosis.
Background: The physiopathological mechanism underlying the tinnitus phenomenon is still the subj... more Background: The physiopathological mechanism underlying the tinnitus phenomenon is still the subject of an ongoing debate. Since oscillatory EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions, this study investigates deviations from the norm of different resting EEG parameters in patients suffering from chronic tinnitus. Results: Spectral parameters of resting EEG of male tinnitus patients (n = 8, mean age 54 years) were compared to those of age-matched healthy males (n = 15, mean age 58.8 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz. Using LORETA source analysis, the generators of delta, theta, alpha and beta power increases were localized dominantly to left auditory (Brodmann Areas (BA) 41,42, 22), temporo-parietal, insular posterior, cingulate anterior and parahippocampal cortical areas.
The task-positive network (TPN) is anticorrelated with activity in the default mode network (DMN)... more The task-positive network (TPN) is anticorrelated with activity in the default mode network (DMN), and possibly reflects competition between the processing of external and internal information, while the salience network (SN) is pivotal in regulating TPN and DMN activity. Because abnormal functional connectivity in these networks has been related to schizophrenia, we tested whether alterations are also evident in subjects at risk for psychosis. Resting-state functional magnetic resonance imaging was tested in 28 subjects with basic symptoms reporting subjective cognitive-perceptive symptoms; 19 with attenuated or brief, limited psychotic symptoms; and 29 matched healthy controls. We characterized spatial differences in connectivity patterns, as well as internetwork connectivity. Right anterior insula (rAI) was selected as seed region for identifying the SN; medioprefrontal cortex (MPFC) for the DMN and TPN. The 3 groups differed in connectivity patterns between the MPFC and right dorsolateral prefrontal cortex (rDLPFC), and between the rAI and posterior cingulate cortex (PCC). In particular, the typically observed antagonistic relationship in MPFC-rDLPFC, rAI-PCC, and internetwork connectivity of DMN-TPN was absent in both at-risk groups. Notably, those connectivity patterns were associated with symptoms related to reality distortions, whereas enhanced connectivity strengths of MPFC-rDLPFC and TPN-DMN were related to poor performance in cognitive functions. We propose that the loss of a TPN-DMN anticorrelation, accompanied by an aberrant spatial extent in the DMN, TPN, and SN in the psychosis risk state, reflects the confusion of internally and externally focused states and disturbance of cognition, as seen in psychotic disorders.
In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding wo... more In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was -in contrast to EEG power-positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that these opposite correlations with different distributions undergo similar and significant neuronal developments with brain maturation.
Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but chan... more Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.
Background: EEG studies of working memory (WM) have demonstrated load dependent frequency band mo... more Background: EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown.
Oscillatory and coherent EEG activity is increasingly recognized as a fundamental hallmark of cor... more Oscillatory and coherent EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions. We aimed to study deviations from the norm of different resting EEG parameters in Parkinson's disease (PD) patients.
Several studies demonstrated that resting-state EEG power differs tremendously between school-age... more Several studies demonstrated that resting-state EEG power differs tremendously between school-aged children and adults. Low-frequency oscillations (delta and theta, <7 Hz) are dominant in children but become less prominent in the adult brain, where higher-frequency alpha oscillations (8-12 Hz) dominate the mature brain rhythm. However, this assessment of developmental effects with EEG power mapping is restricted to the scalp level and blind to the information flow between brain regions, thus limiting insights about brain development. In contrast dynamic source synchronization provides a tool to study inter-regional directionality on the cortical and sub-cortical source level. In this study we investigated functional and directed connectivities (information flow) with renormalized partial directed coherence during resting state EEG (eyes open and eyes closed) recordings in 17 school-aged children and 17 young adults. First, we found higher spectral mean source power in children relative to adults, irrespective of the examined frequency band and resting state. We further found that coherence values were stronger in adults compared to children in all frequency bands. The directed within-group coherence analysis indicated information flow from frontal to parietal sources in children, while information flow from parietal to frontal was observed in adults. In addition, significant thalamocortical connectivity was unidirectional (i.e., outflow to cortical regions) in adults, but bidirectional in children. Group comparison confirmed the results of the single subject analyses for both functional and directed connectivities. Our results suggest that both functional and directed connectivities are sensitive to brain maturation as the distribution and directionality of functional connections differ between the developing and adult brains.
The brain network for the recognition of biological motion includes visual areas and structures o... more The brain network for the recognition of biological motion includes visual areas and structures of the mirror-neuron system. The latter respond during action execution as well as during action recog- nition. Since motor and somatosensory areas predominantly represent the contralateral body-side, and visual areas predominantly process stimuli from the contralateral hemifield, we were interested in in- teractions between visual hemifield
Working memory (WM) processes depend on our momentary mental state and therefore exhibit consider... more Working memory (WM) processes depend on our momentary mental state and therefore exhibit considerable fluctuations. Here, we investigate the interplay of task-preparatory and task-related brain activity as represented by pre-stimulus BOLD-fluctuations and spectral EEG from the retention periods of a visual WM task. Visual WM is used to maintain sensory information in the brain enabling the performance of cognitive operations and is associated with mental health. We tested 22 subjects simultaneously with EEG and fMRI while performing a visuo-verbal Sternberg task with two different loads, allowing for the temporal separation of preparation, encoding, retention and retrieval periods. Four temporally coherent networks (TCNs)-the default mode network (DMN), the dorsal attention, the right and the left WM network-were extracted from the continuous BOLD data by means of a group ICA. Subsequently, the modulatory effect of these networks' pre-stimulus activation upon retention-related EEG activity in the theta, alpha, and beta frequencies was analyzed. The obtained results are informative in the context of state-dependent information processing. We were able to replicate two wellknown load-dependent effects: the frontal-midline theta increase during the task and the decrease of pre-stimulus DMN activity. As our main finding, these two measures seem to depend on each other as the significant negative correlations at frontal-midline channels suggested. Thus, suppressed pre-stimulus DMN levels facilitated later task related frontal midline theta increases. In general, based on previous findings that neuronal coupling in different frequency bands may underlie distinct functions in WM retention, our results suggest that processes reflected by spectral oscillations during retention seem not only to be "online" synchronized with activity in different attention-related networks but are also modulated by activity in these networks during preparation intervals.
Cerebral cortex (New York, N.Y. : 1991), Jan 26, 2014
Despite the crucial role of the brain in the control of the human lower urinary tract, little is ... more Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showe...
13 14 a b s t r a c t a r t i c l e i n f o 15 Available online xxxx 20 21 22 23 Keywords: 24 Vis... more 13 14 a b s t r a c t a r t i c l e i n f o 15 Available online xxxx 20 21 22 23 Keywords: 24 Visual system 25 Ventral stream 26 Dorsal stream 27 fMRI 28 International Affective Picture System 29 Sensory perception 30
Despite the crucial role of the brain in the control of the human lower urinary tract, little is ... more Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showe...
AimsUsing functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortic... more AimsUsing functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures.
Introduction: Lower urinary tract symptoms (LUTS) are highly prevalent, cause an enormous economi... more Introduction: Lower urinary tract symptoms (LUTS) are highly prevalent, cause an enormous economic burden on healthcare systems and significantly impair the quality of life (QoL) of affected patients. The dependence of the LUT on complex central neuronal circuits makes it unique in comparison to other visceral functions, such as the gastrointestinal tract, but also more vulnerable to neurological diseases.
Background: The control of the lower urinary tract is a complex, multilevel process involving bot... more Background: The control of the lower urinary tract is a complex, multilevel process involving both the peripheral and central nervous system. Due to lesions of the neuraxis, most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction, which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life. However, the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood.
The biomarker potential of the inhibitory neurotransmitter g-aminobutyric acid (GABA) for the in ... more The biomarker potential of the inhibitory neurotransmitter g-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimer's disease has not yet been explored. We measured GABA, glutamate þ glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound Bpositive subjects and APOE ε4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid b deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimer's disease.
13 14 a b s t r a c t a r t i c l e i n f o 15 Available online xxxx 20 21 22 23 Keywords: 24 Vis... more 13 14 a b s t r a c t a r t i c l e i n f o 15 Available online xxxx 20 21 22 23 Keywords: 24 Visual system 25 Ventral stream 26 Dorsal stream 27 fMRI 28 International Affective Picture System 29 Sensory perception 30
There is growing evidence that reward processing is disturbed in schizophrenia. However, it is un... more There is growing evidence that reward processing is disturbed in schizophrenia. However, it is uncertain whether this dysfunction predates or is secondary to the onset of psychosis. Studying 21 unmedicated persons at risk for psychosis plus 24 healthy controls (HCs) we used a incentive delay paradigm with monetary rewards during functional magnetic resonance imaging. During processing of reward information, at-risk individuals performed similarly well to controls and recruited the same brain areas. However, while anticipating rewards, the high-risk sample exhibited additional activation in the posterior cingulate cortex, and the medio-and superior frontal gyrus, whereas no significant group differences were found after rewards were administered. Importantly, symptom dimensions were differentially associated with anticipation and outcome of the reward. Positive symptoms were correlated with the anticipation signal in the ventral striatum (VS) and the right anterior insula (rAI). Negative symptoms were inversely linked to outcome-related signal within the VS, and depressive symptoms to outcome-related signal within the medial orbitofrontal cortex (mOFC). Our findings provide evidence for a reward-associated dysregulation that can be compensated by recruitment of additional prefrontal areas. We propose that stronger activations within VS and rAI when anticipating a reward reflect abnormal processing of potential future rewards. Moreover, according to the aberrant salience theory of psychosis, this may predispose a person to positive symptoms. Additionally, we report evidence that negative and depressive symptoms are differentially associated with the receipt of a reward, which might demonstrate a broader vulnerability to motivational and affective symptoms in persons at-risk for psychosis.
Background: The physiopathological mechanism underlying the tinnitus phenomenon is still the subj... more Background: The physiopathological mechanism underlying the tinnitus phenomenon is still the subject of an ongoing debate. Since oscillatory EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions, this study investigates deviations from the norm of different resting EEG parameters in patients suffering from chronic tinnitus. Results: Spectral parameters of resting EEG of male tinnitus patients (n = 8, mean age 54 years) were compared to those of age-matched healthy males (n = 15, mean age 58.8 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz. Using LORETA source analysis, the generators of delta, theta, alpha and beta power increases were localized dominantly to left auditory (Brodmann Areas (BA) 41,42, 22), temporo-parietal, insular posterior, cingulate anterior and parahippocampal cortical areas.
The task-positive network (TPN) is anticorrelated with activity in the default mode network (DMN)... more The task-positive network (TPN) is anticorrelated with activity in the default mode network (DMN), and possibly reflects competition between the processing of external and internal information, while the salience network (SN) is pivotal in regulating TPN and DMN activity. Because abnormal functional connectivity in these networks has been related to schizophrenia, we tested whether alterations are also evident in subjects at risk for psychosis. Resting-state functional magnetic resonance imaging was tested in 28 subjects with basic symptoms reporting subjective cognitive-perceptive symptoms; 19 with attenuated or brief, limited psychotic symptoms; and 29 matched healthy controls. We characterized spatial differences in connectivity patterns, as well as internetwork connectivity. Right anterior insula (rAI) was selected as seed region for identifying the SN; medioprefrontal cortex (MPFC) for the DMN and TPN. The 3 groups differed in connectivity patterns between the MPFC and right dorsolateral prefrontal cortex (rDLPFC), and between the rAI and posterior cingulate cortex (PCC). In particular, the typically observed antagonistic relationship in MPFC-rDLPFC, rAI-PCC, and internetwork connectivity of DMN-TPN was absent in both at-risk groups. Notably, those connectivity patterns were associated with symptoms related to reality distortions, whereas enhanced connectivity strengths of MPFC-rDLPFC and TPN-DMN were related to poor performance in cognitive functions. We propose that the loss of a TPN-DMN anticorrelation, accompanied by an aberrant spatial extent in the DMN, TPN, and SN in the psychosis risk state, reflects the confusion of internally and externally focused states and disturbance of cognition, as seen in psychotic disorders.
In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding wo... more In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was -in contrast to EEG power-positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that these opposite correlations with different distributions undergo similar and significant neuronal developments with brain maturation.
Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but chan... more Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.
Background: EEG studies of working memory (WM) have demonstrated load dependent frequency band mo... more Background: EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown.
Oscillatory and coherent EEG activity is increasingly recognized as a fundamental hallmark of cor... more Oscillatory and coherent EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions. We aimed to study deviations from the norm of different resting EEG parameters in Parkinson's disease (PD) patients.
Several studies demonstrated that resting-state EEG power differs tremendously between school-age... more Several studies demonstrated that resting-state EEG power differs tremendously between school-aged children and adults. Low-frequency oscillations (delta and theta, <7 Hz) are dominant in children but become less prominent in the adult brain, where higher-frequency alpha oscillations (8-12 Hz) dominate the mature brain rhythm. However, this assessment of developmental effects with EEG power mapping is restricted to the scalp level and blind to the information flow between brain regions, thus limiting insights about brain development. In contrast dynamic source synchronization provides a tool to study inter-regional directionality on the cortical and sub-cortical source level. In this study we investigated functional and directed connectivities (information flow) with renormalized partial directed coherence during resting state EEG (eyes open and eyes closed) recordings in 17 school-aged children and 17 young adults. First, we found higher spectral mean source power in children relative to adults, irrespective of the examined frequency band and resting state. We further found that coherence values were stronger in adults compared to children in all frequency bands. The directed within-group coherence analysis indicated information flow from frontal to parietal sources in children, while information flow from parietal to frontal was observed in adults. In addition, significant thalamocortical connectivity was unidirectional (i.e., outflow to cortical regions) in adults, but bidirectional in children. Group comparison confirmed the results of the single subject analyses for both functional and directed connectivities. Our results suggest that both functional and directed connectivities are sensitive to brain maturation as the distribution and directionality of functional connections differ between the developing and adult brains.
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Papers by Lars Michels