Papers by Arkan Al-Zubaidi
The hypothalamus and insular cortex play an essential role in the integration of endocrine and ho... more The hypothalamus and insular cortex play an essential role in the integration of endocrine and homeostatic signals and their impact on food intake. Resting-state functional connectivity alterations of the hypothalamus, posterior insula (PINS) and anterior insula (AINS) are modulated by metabolic states and caloric intake. Nevertheless, a deeper understanding of how these factors affect the strength of connectivity between hypothalamus, PINS and AINS is missing. This study investigated whether effective (directed) connectivity within this network varies as a function of prandial states (hunger vs. satiety) and energy availability (glucose levels and/or hormonal modulation). To address this question, we measured twenty healthy male participants of normal weight twice: once after 36 h of fasting (except water consumption) and once under satiated conditions. During each session, resting-state functional MRI (rs-fMRI) and hormone concentrations were recorded before and after glucose administration. Spectral dynamic causal modeling (spDCM) was used to assess the effective connectivity between the hy-pothalamus and anterior and posterior insula. Using Bayesian model selection, we observed that the same model was identified as the most likely model for each rs-fMRI recording. Compared to satiety, the hunger condition enhanced the strength of the forward connections from PINS to AINS and reduced the strength of backward connections from AINS to PINS. Furthermore, the strength of connectivity from PINS to AINS was positively related to plasma cortisol levels in the hunger condition, mainly before glucose administration. However, there was no direct relationship between glucose treatment and effective connectivity. Our findings suggest that prandial states modulate connectivity between PINS and AINS and relate to theories of interoception and ho-meostatic regulation that invoke hierarchical relations between posterior and anterior insula.
Bookmarks Related papers MentionsView impact
Parkinsonism & Related Disorders, 2019
Background
In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effectiv... more Background
In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) go beyond DRT effects including highly beneficial tremor suppression.
Objectives
Here, we aimed to determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN DBS.
Methods
In a repeated-measurement design, 26 medicated PD patients (60.9 years (SD 8.9)) were investigated using resting state fMRI while bipolar STN stimulation was (i) active or (ii) switched off, and dynamic causal modelling was subsequently performed.
Results
DBS improved the MDS-UPDRS-III score by 26.4% (DBS ON/Med ON vs. DBS OFF/Med ON). Active stimulation resulted in an increased effective connectivity from cerebellum to putamen (p = 0.00118). In addition, there was a stronger coupling from PFC to cerebellum (p = 0.021), as well as from cerebellum to SMA (p = 0.043) on an uncorrected level. Coupling strength from PFC to cerebellum correlated with the DBS-related change of the resting tremor subscore (r = 0.54, p = 0.031). Self-connections increased as a function of DBS in the right PFC, PMC, SMA, M1, thalamus and left cerebellum.
Conclusions
DBS-related improvement of Parkinsonian signs appears to be driven by an interaction between the cerebellum and the putamen. Resting tremor suppression may be related to an enhanced prefronto-cerebellar network. Activation of the mesial premotor loop (PFC-SMA) as seen in DRT may thus be secondary due to the primary modulation of cerebellar networks.
Bookmarks Related papers MentionsView impact
Metabolism Clinical and Experimental, 2019
Introduction: Metabolic and hormonal signals have been shown to be associated with brain activity... more Introduction: Metabolic and hormonal signals have been shown to be associated with brain activity in the context
of ingestive behaviour. However, this has mostly been seen in studies using external administration of hormones
or glucose. We therefore studied endocrine-brain interaction in a physiological setting with hormone levels determined
by metabolic conditions such as normal food intake vs. prolonged fasting.
Methods: 24 healthy, normalweightmen participated in two sessions, one involving a 38-hour fasting period and
one a non-fasting control condition with standardized meals. Functional magnetic resonance imaging was performed
at the end of the experiment with participants being required to rate pictures of food. Brain activation
was compared between conditions in predefined regions of interest (ROIs). Multiple blood samples were
taken to determine levels of insulin, C-peptide, cortisol, ACTH, glucose and adiponectin. Thesewere used as a predictor
variable in a regression analysis on brain activations in the different ROIs.
Results: Food pictureswere rated asmore desirable in the fasting condition. Univariate analysis of ROI activations
revealedmainly effects of food rating and no significant effects of the metabolic state.Multiple regression analysis
revealed associations between orbitofrontal cortex activation and blood glucose in the non-fasting condition. In
the fasting condition adiponectin was associated with the signal from the caudate nucleus and insulin and Cpeptide
were associated with functional activity of orbitofrontal regions.
Discussion: Associations of endocrine signals and functional neural regions could be demonstrated in a realistic
setting without external administration of hormones. As the current approach was correlational, further studies
need to address the causal role of hormonal signals.
Bookmarks Related papers MentionsView impact
Frontiers in human neuroscience, 2019
Objective: Resting-state functional magnetic resonance imaging (rs-fMRI) has become an essential ... more Objective: Resting-state functional magnetic resonance imaging (rs-fMRI) has become an essential measure to investigate the human brain's spontaneous activity and intrinsic functional connectivity. Several studies including our own previous work have shown that the brain controls the regulation of energy expenditure and food intake behavior. Accordingly, we expected different metabolic states to influence connectivity and activity patterns in neuronal networks. Methods: The influence of hunger and satiety on rs-fMRI was investigated using three connectivity models (local connectivity, global connectivity and amplitude rs-fMRI signals). After extracting the connectivity parameters of 90 brain regions for each model, we used sequential forward floating selection strategy in conjunction with a linear support vector machine classifier and permutation tests to reveal which connectivity model differentiates best between metabolic states (hunger vs. satiety). Results: We found that the amplitude of rs-fMRI signals is slightly more precise than local and global connectivity models in order to detect resting brain changes during hunger and satiety with a classification accuracy of 81%. Conclusion: The amplitude of rs-fMRI signals serves as a suitable basis for machine learning based classification of brain activity. This opens up the possibility to apply this combination of algorithms to similar research questions, such as the characterization of brain states (e.g., sleep stages) or disease conditions (e.g., Alzheimer's disease, minimal cognitive impairment). Keywords: brain functional activity and connectivity, feature selection, resting-state fMRI, hunger, satiety, support vector machine HIGHLIGHTS-We compare fALFF, DC, and ReHo for classifying human metabolic states within an rs-fMRI scan based on SVM.-We combine an rs-fMRI based voxel-wise frequency-domain approach with sequential forward floating selection method to identify brain areas modulated as a function of hunger/satiety.-It turns out that fALFF is a reliable and stable index of spontaneous brain activity.
Bookmarks Related papers MentionsView impact
Frontiers in Human Neuroscience, 2019
To study the interplay of metabolic state (hungry vs. satiated) and glucose administration (inclu... more To study the interplay of metabolic state (hungry vs. satiated) and glucose administration (including hormonal modulation) on brain function, resting-state functional magnetic resonance imaging (rs-fMRI) and blood samples were obtained in 24 healthy normal-weight men in a repeated measurement design. Participants were measured twice: once after a 36 h fast (except water) and once under satiation (three meals/day for 36 h). During each session, rs-fMRI and hormone concentrations were recorded before and after a 75 g oral dose of glucose. We calculated the amplitude map from blood-oxygen-level-dependent (BOLD) signals by using the fractional amplitude of low-frequency fluctuation (fALFF) approach for each volunteer per condition. Using multiple linear regression analysis (MLRA) the interdependence of brain activity, plasma insulin and blood glucose was investigated. We observed a modulatory impact of fasting state on intrinsic brain activity in the posterior cingulate cortex (PCC). Strikingly, differences in plasma insulin levels between hunger and satiety states after glucose administration at the time of the scan were negatively related to brain activity in the posterior insula and superior frontal gyrus (SFG), while plasma glucose levels were positively associated with activity changes in the fusiform gyrus. Furthermore, we could show that changes in plasma insulin enhanced the connectivity between the posterior insula and SFG. Our results indicate that hormonal signals like insulin alleviate an acute hemostatic energy deficit by modifying the homeostatic and frontal circuitry of the human brain.
Bookmarks Related papers MentionsView impact
Bildverarbeitung für die Medizin. Springer, Berlin, Heidelberg. , 2013
Transcranial sonography is a new tool for the diagnosis of Parkinson's disease according to a dis... more Transcranial sonography is a new tool for the diagnosis of Parkinson's disease according to a distinct hyperechogenic pattern in the substantia nigra region. In order to reduce the influence of the image properties from different settings of ultrasound machine, we propose a robust feature extraction method using rotation-invariant Gabor filter bank. Except the general Gabor features, such as mean and standard deviation, we suggest to use the entropy of the filtered images for the TCS images classification. The performance of the Gabor features is evaluated by a feature selection method with the objective function of support vector machine classifier. The results show that the rotation-invariant Gabor filter is better than the conventional one, and the entropy is invariant to the intensity and the contrast changes.
Bookmarks Related papers MentionsView impact
Neuroscience, 2018
A major regulatory task of the organism is to keep brain functions relatively constant in spite o... more A major regulatory task of the organism is to keep brain functions relatively constant in spite of metabolic changes (e.g., hunger vs. satiety) or availability of energy (e.g., glucose administration). Resting-state functional magnetic resonance imaging (rs-fMRI) can reveal resulting changes in brain function but previous studies have focused mostly on the hypothalamus. Therefore, we took a whole brain approach and examined 24 healthy normal-weight men once after 36 hours of fasting and once in a satiated state (six meals over the course of 36 hours). At the end of each treatment, rs-fMRI was recorded before and after the oral administration of 75 g of glucose. We calculated local connectivity (regional homogeneity [ReHo]), global connectivity (degree of centrality [DC]), and amplitude (fractional amplitude of low-frequency fluctuation [fALFF]) maps from the rs-fMRI data. We found that glucose administration reduced all measures selectively in the left supplementary motor area and increased ReHo and fALFF in the right middle and superior frontal gyri. For fALFF, we observed a significant interaction between metabolic states and glucose in the left thalamus. This interaction was driven by a fALFF increase after glucose treatment in the hunger relative to the satiety condition. Our results indicate that fALFF analysis is the most sensitive measure to detect effects of metabolic states on resting state brain activity. Moreover, we show that multimethod rs-fMRI provides an unbiased approach to identify spontaneous brain activity associated with changes in homeostasis and caloric intake.
Bookmarks Related papers MentionsView impact
PloS One, 2019
Introduction
Different metabolic conditions can affect what and how much we eat. Hormones of glu... more Introduction
Different metabolic conditions can affect what and how much we eat. Hormones of glucose metabolism and adipokines such as adiponectin take part in the control of these decisions and energy balance of the body. However, a comprehensive understanding of how these endocrine and metabolic factors influence food intake has not been reached. We hypothesised that the amount of food a person consumes differs substantially after a fasting period even after the energy deficit was partially removed by glucose ingestion and endocrine signals like insulin and C-peptide indicated a high glucose metabolic status. Furthermore, the macronutrient composition of the consumed food and a possible association with adiponectin under the influence of glucose ingestion was assessed.
Methods
In a within-subject design, 24 healthy males participated in both a fasting (42 h) and control (non-fasting) condition. A total of 20 blood samples from each subject were collected during each condition to assess serum levels of adiponectin, insulin, C-peptide, cortisol and ACTH. At the end of each condition food intake was measured with an ad libitum buffet after the acute energy deficit was compensated using a carbohydrate-rich drink.
Results
The total amount of caloric intake and single macronutrients was higher after the fasting intervention after replenishment with glucose. All recorded hormone levels, except for adiponectin, were significantly different for at least one of the study intervals. The relative proportions of the macronutrient composition of the consumed food were stable in both conditions under the influence of glucose ingestion. In the non-fasting condition, the relative amount of protein intake correlated with adiponectin levels during the experiment.
Discussion and conclusion
An anabolic glucose metabolism after glucose ingestion following a fasting intervention did not even out energy ingestion compared to a control group with regular food intake and glucose ingestion. Anorexigenic hormones like insulin in this context were not able despite higher levels than in the control condition to ameliorate the drive for food intake to normal or near normal levels. Relative macronutrient intake remains stable under these varying metabolic conditions and glucose influence. Serum adiponectin levels showed a positive association with the relative protein intake in the non-fasting condition under the influence of glucose although adiponectin levels overall did not differ in between the conditions.
Bookmarks Related papers MentionsView impact
Conference Presentations by Arkan Al-Zubaidi
Bildverarbeitung für die Medizin. Springer Vieweg, Berlin, Heidelberg., 2018
Resting-state fMRI (rs-fMRI) is a method of functional brain imaging that allows the task-free ex... more Resting-state fMRI (rs-fMRI) is a method of functional brain imaging that allows the task-free exploration of the intrinsic functional connectivity in humans. Since central nervous pathways regulate food intake and eating behavior, it is assumed that changes in the homeostatic state have an impact on the connec-tivity patterns of rs-fMRI. Here, we compare the accuracy of three data-driven approaches in classifying two metabolic states (hunger vs. satiety) depending on the observed rs-fMRI fluctuations. These methods assess local and global functional connectivity as well as amplitude (intensity) fluctuations of neural signals: First, regional homogeneity (ReHo), which describes the synchronization of time series of a given voxel and its nearest neighbors. Second, the degree of centrality (DC), which measures the number of connections of a voxel to all the other vox-els above a certain threshold. Third, the fractional amplitude of low-frequency fluctuation (fALFF), which measures voxel-wise signal amplitude. After extracting the associated connectivity parameters of 90 brain regions for each method, we use features selection algorithms with the objective function of linear support vector machine classifier and permutation tests to investigate which method and which brain regions differentiate best between hungry and satiety. Our results indicate that the fALFF method is more accurate than ReHo and DC in capturing the changes of the resting brain during states of hunger and satiety. This opens up the possibility to use this measure to characterize certain states (e.g., sleep stages) or disease conditions (e.g., mitochondrial encephalopathy).
Bookmarks Related papers MentionsView impact
Uploads
Papers by Arkan Al-Zubaidi
In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) go beyond DRT effects including highly beneficial tremor suppression.
Objectives
Here, we aimed to determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN DBS.
Methods
In a repeated-measurement design, 26 medicated PD patients (60.9 years (SD 8.9)) were investigated using resting state fMRI while bipolar STN stimulation was (i) active or (ii) switched off, and dynamic causal modelling was subsequently performed.
Results
DBS improved the MDS-UPDRS-III score by 26.4% (DBS ON/Med ON vs. DBS OFF/Med ON). Active stimulation resulted in an increased effective connectivity from cerebellum to putamen (p = 0.00118). In addition, there was a stronger coupling from PFC to cerebellum (p = 0.021), as well as from cerebellum to SMA (p = 0.043) on an uncorrected level. Coupling strength from PFC to cerebellum correlated with the DBS-related change of the resting tremor subscore (r = 0.54, p = 0.031). Self-connections increased as a function of DBS in the right PFC, PMC, SMA, M1, thalamus and left cerebellum.
Conclusions
DBS-related improvement of Parkinsonian signs appears to be driven by an interaction between the cerebellum and the putamen. Resting tremor suppression may be related to an enhanced prefronto-cerebellar network. Activation of the mesial premotor loop (PFC-SMA) as seen in DRT may thus be secondary due to the primary modulation of cerebellar networks.
of ingestive behaviour. However, this has mostly been seen in studies using external administration of hormones
or glucose. We therefore studied endocrine-brain interaction in a physiological setting with hormone levels determined
by metabolic conditions such as normal food intake vs. prolonged fasting.
Methods: 24 healthy, normalweightmen participated in two sessions, one involving a 38-hour fasting period and
one a non-fasting control condition with standardized meals. Functional magnetic resonance imaging was performed
at the end of the experiment with participants being required to rate pictures of food. Brain activation
was compared between conditions in predefined regions of interest (ROIs). Multiple blood samples were
taken to determine levels of insulin, C-peptide, cortisol, ACTH, glucose and adiponectin. Thesewere used as a predictor
variable in a regression analysis on brain activations in the different ROIs.
Results: Food pictureswere rated asmore desirable in the fasting condition. Univariate analysis of ROI activations
revealedmainly effects of food rating and no significant effects of the metabolic state.Multiple regression analysis
revealed associations between orbitofrontal cortex activation and blood glucose in the non-fasting condition. In
the fasting condition adiponectin was associated with the signal from the caudate nucleus and insulin and Cpeptide
were associated with functional activity of orbitofrontal regions.
Discussion: Associations of endocrine signals and functional neural regions could be demonstrated in a realistic
setting without external administration of hormones. As the current approach was correlational, further studies
need to address the causal role of hormonal signals.
Different metabolic conditions can affect what and how much we eat. Hormones of glucose metabolism and adipokines such as adiponectin take part in the control of these decisions and energy balance of the body. However, a comprehensive understanding of how these endocrine and metabolic factors influence food intake has not been reached. We hypothesised that the amount of food a person consumes differs substantially after a fasting period even after the energy deficit was partially removed by glucose ingestion and endocrine signals like insulin and C-peptide indicated a high glucose metabolic status. Furthermore, the macronutrient composition of the consumed food and a possible association with adiponectin under the influence of glucose ingestion was assessed.
Methods
In a within-subject design, 24 healthy males participated in both a fasting (42 h) and control (non-fasting) condition. A total of 20 blood samples from each subject were collected during each condition to assess serum levels of adiponectin, insulin, C-peptide, cortisol and ACTH. At the end of each condition food intake was measured with an ad libitum buffet after the acute energy deficit was compensated using a carbohydrate-rich drink.
Results
The total amount of caloric intake and single macronutrients was higher after the fasting intervention after replenishment with glucose. All recorded hormone levels, except for adiponectin, were significantly different for at least one of the study intervals. The relative proportions of the macronutrient composition of the consumed food were stable in both conditions under the influence of glucose ingestion. In the non-fasting condition, the relative amount of protein intake correlated with adiponectin levels during the experiment.
Discussion and conclusion
An anabolic glucose metabolism after glucose ingestion following a fasting intervention did not even out energy ingestion compared to a control group with regular food intake and glucose ingestion. Anorexigenic hormones like insulin in this context were not able despite higher levels than in the control condition to ameliorate the drive for food intake to normal or near normal levels. Relative macronutrient intake remains stable under these varying metabolic conditions and glucose influence. Serum adiponectin levels showed a positive association with the relative protein intake in the non-fasting condition under the influence of glucose although adiponectin levels overall did not differ in between the conditions.
Conference Presentations by Arkan Al-Zubaidi
In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) go beyond DRT effects including highly beneficial tremor suppression.
Objectives
Here, we aimed to determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN DBS.
Methods
In a repeated-measurement design, 26 medicated PD patients (60.9 years (SD 8.9)) were investigated using resting state fMRI while bipolar STN stimulation was (i) active or (ii) switched off, and dynamic causal modelling was subsequently performed.
Results
DBS improved the MDS-UPDRS-III score by 26.4% (DBS ON/Med ON vs. DBS OFF/Med ON). Active stimulation resulted in an increased effective connectivity from cerebellum to putamen (p = 0.00118). In addition, there was a stronger coupling from PFC to cerebellum (p = 0.021), as well as from cerebellum to SMA (p = 0.043) on an uncorrected level. Coupling strength from PFC to cerebellum correlated with the DBS-related change of the resting tremor subscore (r = 0.54, p = 0.031). Self-connections increased as a function of DBS in the right PFC, PMC, SMA, M1, thalamus and left cerebellum.
Conclusions
DBS-related improvement of Parkinsonian signs appears to be driven by an interaction between the cerebellum and the putamen. Resting tremor suppression may be related to an enhanced prefronto-cerebellar network. Activation of the mesial premotor loop (PFC-SMA) as seen in DRT may thus be secondary due to the primary modulation of cerebellar networks.
of ingestive behaviour. However, this has mostly been seen in studies using external administration of hormones
or glucose. We therefore studied endocrine-brain interaction in a physiological setting with hormone levels determined
by metabolic conditions such as normal food intake vs. prolonged fasting.
Methods: 24 healthy, normalweightmen participated in two sessions, one involving a 38-hour fasting period and
one a non-fasting control condition with standardized meals. Functional magnetic resonance imaging was performed
at the end of the experiment with participants being required to rate pictures of food. Brain activation
was compared between conditions in predefined regions of interest (ROIs). Multiple blood samples were
taken to determine levels of insulin, C-peptide, cortisol, ACTH, glucose and adiponectin. Thesewere used as a predictor
variable in a regression analysis on brain activations in the different ROIs.
Results: Food pictureswere rated asmore desirable in the fasting condition. Univariate analysis of ROI activations
revealedmainly effects of food rating and no significant effects of the metabolic state.Multiple regression analysis
revealed associations between orbitofrontal cortex activation and blood glucose in the non-fasting condition. In
the fasting condition adiponectin was associated with the signal from the caudate nucleus and insulin and Cpeptide
were associated with functional activity of orbitofrontal regions.
Discussion: Associations of endocrine signals and functional neural regions could be demonstrated in a realistic
setting without external administration of hormones. As the current approach was correlational, further studies
need to address the causal role of hormonal signals.
Different metabolic conditions can affect what and how much we eat. Hormones of glucose metabolism and adipokines such as adiponectin take part in the control of these decisions and energy balance of the body. However, a comprehensive understanding of how these endocrine and metabolic factors influence food intake has not been reached. We hypothesised that the amount of food a person consumes differs substantially after a fasting period even after the energy deficit was partially removed by glucose ingestion and endocrine signals like insulin and C-peptide indicated a high glucose metabolic status. Furthermore, the macronutrient composition of the consumed food and a possible association with adiponectin under the influence of glucose ingestion was assessed.
Methods
In a within-subject design, 24 healthy males participated in both a fasting (42 h) and control (non-fasting) condition. A total of 20 blood samples from each subject were collected during each condition to assess serum levels of adiponectin, insulin, C-peptide, cortisol and ACTH. At the end of each condition food intake was measured with an ad libitum buffet after the acute energy deficit was compensated using a carbohydrate-rich drink.
Results
The total amount of caloric intake and single macronutrients was higher after the fasting intervention after replenishment with glucose. All recorded hormone levels, except for adiponectin, were significantly different for at least one of the study intervals. The relative proportions of the macronutrient composition of the consumed food were stable in both conditions under the influence of glucose ingestion. In the non-fasting condition, the relative amount of protein intake correlated with adiponectin levels during the experiment.
Discussion and conclusion
An anabolic glucose metabolism after glucose ingestion following a fasting intervention did not even out energy ingestion compared to a control group with regular food intake and glucose ingestion. Anorexigenic hormones like insulin in this context were not able despite higher levels than in the control condition to ameliorate the drive for food intake to normal or near normal levels. Relative macronutrient intake remains stable under these varying metabolic conditions and glucose influence. Serum adiponectin levels showed a positive association with the relative protein intake in the non-fasting condition under the influence of glucose although adiponectin levels overall did not differ in between the conditions.