We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no he... more We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no hearing loss (n = 16) vs. a matched control group (n = 17) to further elucidate the role of excitatory and inhibitory neurotransmitters in tinnitus. Two-dimensional J-resolved spectroscopy (2D-JPRESS) was applied to disentangle Glutamate (Glu) from Glutamine and to estimate GABA levels in two bilateral voxels in the primary auditory cortex. Results indicated a lower Glu concentration (large effect) in right auditory cortex and lower GABA concentration (medium effect) in the left auditory cortex of the tinnitus group. Within the tinnitus group, Glu levels positively correlated with tinnitus loudness measures. While the GABA difference between groups is in line with former findings and theories about a dysfunctional auditory inhibition system in tinnitus, the novel finding of reduced Glu levels came as a surprise and is discussed in the context of a putative framework of inhibitory mechanism...
Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in ... more Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in the nucleus accumbens (NAcc), whereas drug‐seeking reinstatement is accompanied by enhanced glutamatergic transmission 1. However, little is known about such neurometabolic alterations in humans. We thus aim to investigate changes of the glutamate homeostasis in the NAcc of cocaine dependent individuals by means of a novel proton magnetic resonance spectroscopy (1H‐MRS) protocol that we have recently developed. Methods In 16 cocaine dependent individuals (CD) and 22 healthy controls (HC), non‐water suppressed PRESS localization 1H‐MRS preceded by a metabolite‐cycling pulse combined with inner‐volume saturation was performed on a 3T Philips Achieva System. MRS spectra were obtained from a voxel of 9.4x18.8x8.4mm, covering the anatomical dimensions of the left NAcc. For absolute quantification of the metabolites, a method based on the principle of reciprocity has been applied. Results An average signal‐to‐noise ratio of 16.97 and a mean line width of 6.93Hz (in single spectra) indicate good spectral quality. Metabolite concentrations of interest were quantified reliably using LCModel4 with Cramér‐Rao lower bounds<10. Moreover, glutamate concentrations in CDs (M=0.011, SD=0.001) were significantly reduced compared to HCs (M=0.013, SD=0.002), t(34)=3.81, p=.001, d=1.20. Discussion Despite the small voxel size, this novel 1H‐MRS protocol achieves high data quality and, thus, finally allows a reliable detection of glutamate in the human NAcc. For the first time this reveals that, in accordance with animal models, glutamatergic alterations occur in cocaine dependent humans and might play a decisive role in the development and maintenance of cocaine dependence
We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no he... more We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no hearing loss (n = 16) vs. a matched control group (n = 17) to further elucidate the role of excitatory and inhibitory neurotransmitters in tinnitus. Two-dimensional J-resolved spectroscopy (2D-JPRESS) was applied to disentangle Glutamate (Glu) from Glutamine and to estimate GABA levels in two bilateral voxels in the primary auditory cortex. Results indicated a lower Glu concentration (large effect) in right auditory cortex and lower GABA concentration (medium effect) in the left auditory cortex of the tinnitus group. Within the tinnitus group, Glu levels positively correlated with tinnitus loudness measures. While the GABA difference between groups is in line with former findings and theories about a dysfunctional auditory inhibition system in tinnitus, the novel finding of reduced Glu levels came as a surprise and is discussed in the context of a putative framework of inhibitory mechanism...
Beta weights of the amygdala ROI S1 S2 S3 S4 Feedback-group n=15 Graphical abstract Results of th... more Beta weights of the amygdala ROI S1 S2 S3 S4 Feedback-group n=15 Graphical abstract Results of the amygdala ROI analysis in the Feedback group: (a) Mean beta weights of the subjects' individual localizer amygdala ROI's. Conditions (regulate (green), view (red) and regulate > view (blue)) are presented over the four sessions (S1-S4). The blue regulate > view bar represents the effect of the training sessions with the decrease of amygdala activity through the mental intervention of reality check for emotion regulation in the regulate condition. Error bars represent standard deviations. (b) The mask of area in the amygdala region is covered by all individual ROIs of the Feedback group.
Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in ... more Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in the nucleus accumbens (NAcc), whereas drug‐seeking reinstatement is accompanied by enhanced glutamatergic transmission 1. However, little is known about such neurometabolic alterations in humans. We thus aim to investigate changes of the glutamate homeostasis in the NAcc of cocaine dependent individuals by means of a novel proton magnetic resonance spectroscopy (1H‐MRS) protocol that we have recently developed. Methods In 16 cocaine dependent individuals (CD) and 22 healthy controls (HC), non‐water suppressed PRESS localization 1H‐MRS preceded by a metabolite‐cycling pulse combined with inner‐volume saturation was performed on a 3T Philips Achieva System. MRS spectra were obtained from a voxel of 9.4x18.8x8.4mm, covering the anatomical dimensions of the left NAcc. For absolute quantification of the metabolites, a method based on the principle of reciprocity has been applied. Results An average signal‐to‐noise ratio of 16.97 and a mean line width of 6.93Hz (in single spectra) indicate good spectral quality. Metabolite concentrations of interest were quantified reliably using LCModel4 with Cramér‐Rao lower bounds<10. Moreover, glutamate concentrations in CDs (M=0.011, SD=0.001) were significantly reduced compared to HCs (M=0.013, SD=0.002), t(34)=3.81, p=.001, d=1.20. Discussion Despite the small voxel size, this novel 1H‐MRS protocol achieves high data quality and, thus, finally allows a reliable detection of glutamate in the human NAcc. For the first time this reveals that, in accordance with animal models, glutamatergic alterations occur in cocaine dependent humans and might play a decisive role in the development and maintenance of cocaine dependence
Beta weights of the amygdala ROI S1 S2 S3 S4 Feedback-group n=15 Graphical abstract Results of th... more Beta weights of the amygdala ROI S1 S2 S3 S4 Feedback-group n=15 Graphical abstract Results of the amygdala ROI analysis in the Feedback group: (a) Mean beta weights of the subjects' individual localizer amygdala ROI's. Conditions (regulate (green), view (red) and regulate > view (blue)) are presented over the four sessions (S1-S4). The blue regulate > view bar represents the effect of the training sessions with the decrease of amygdala activity through the mental intervention of reality check for emotion regulation in the regulate condition. Error bars represent standard deviations. (b) The mask of area in the amygdala region is covered by all individual ROIs of the Feedback group.
Social cognition is a crucial factor influencing development, progress, and treatment of psychiat... more Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition. In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test. The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy. These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.
Our fMRI study investigates auditory rhyme processing in spoken language to further elucidate the... more Our fMRI study investigates auditory rhyme processing in spoken language to further elucidate the topic of functional lateralization of language processing. During scanning, 14 subjects listened to four different types of versed word strings and subsequently performed either a rhyme or a meter detection task. Our results show lateralization to auditory-related temporal regions in the right hemisphere irrespective of task. As for the left hemisphere we report responses in the supramarginal gyrus as well as in the opercular part of the inferior frontal gyrus modulated by the presence of regular meter and rhyme. The interaction of rhyme and meter was associated with increased involvement of the superior temporal sulcus and the putamen of the right hemisphere. Overall, these findings support the notion of right-hemispheric specialization for suprasegmental analyses during processing of spoken sentences and provide neuroimaging evidence for the influence of metrics on auditory rhyme proc...
Proceedings of the National Academy of Sciences, 2014
Significance Social interaction deficits in drug users likely impede treatment, increase the burd... more Significance Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. However, the neural origin contributing to altered social interaction in drug users is unknown thus far. The present study illuminates the nature of basic social interaction deficits as exemplified by social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. The results suggest that basal social interaction impairments probably arise from blunted social reward processing that was again related to impaired real-life social behavior in cocaine users. These results point to the importance of reinstatement of social reward in the treatment of stimulant addiction.
Proceedings of the National Academy of Sciences, 2013
Significance Major depressive disorder is a significant contributor to the global burden of disea... more Significance Major depressive disorder is a significant contributor to the global burden of disease, affecting 350 million people according to an estimation of the World Health Organization. Today, no valid biomarkers of depression, which could predict the efficacy of a certain treatment in a certain group of patients, exist. Sleep deprivation is an effective and rapid-acting antidepressive treatment. However, the biomechanism of this effect is largely unknown. This study shows the effects of sleep deprivation on human brain functional connectivity alterations via the dorsal nexus, an area which is crucial in major depressive disorder. Here, we offer a neurobiological explanation for the known antidepressive action of sleep deprivation.
We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no he... more We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no hearing loss (n = 16) vs. a matched control group (n = 17) to further elucidate the role of excitatory and inhibitory neurotransmitters in tinnitus. Two-dimensional J-resolved spectroscopy (2D-JPRESS) was applied to disentangle Glutamate (Glu) from Glutamine and to estimate GABA levels in two bilateral voxels in the primary auditory cortex. Results indicated a lower Glu concentration (large effect) in right auditory cortex and lower GABA concentration (medium effect) in the left auditory cortex of the tinnitus group. Within the tinnitus group, Glu levels positively correlated with tinnitus loudness measures. While the GABA difference between groups is in line with former findings and theories about a dysfunctional auditory inhibition system in tinnitus, the novel finding of reduced Glu levels came as a surprise and is discussed in the context of a putative framework of inhibitory mechanism...
Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in ... more Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in the nucleus accumbens (NAcc), whereas drug‐seeking reinstatement is accompanied by enhanced glutamatergic transmission 1. However, little is known about such neurometabolic alterations in humans. We thus aim to investigate changes of the glutamate homeostasis in the NAcc of cocaine dependent individuals by means of a novel proton magnetic resonance spectroscopy (1H‐MRS) protocol that we have recently developed. Methods In 16 cocaine dependent individuals (CD) and 22 healthy controls (HC), non‐water suppressed PRESS localization 1H‐MRS preceded by a metabolite‐cycling pulse combined with inner‐volume saturation was performed on a 3T Philips Achieva System. MRS spectra were obtained from a voxel of 9.4x18.8x8.4mm, covering the anatomical dimensions of the left NAcc. For absolute quantification of the metabolites, a method based on the principle of reciprocity has been applied. Results An average signal‐to‐noise ratio of 16.97 and a mean line width of 6.93Hz (in single spectra) indicate good spectral quality. Metabolite concentrations of interest were quantified reliably using LCModel4 with Cramér‐Rao lower bounds<10. Moreover, glutamate concentrations in CDs (M=0.011, SD=0.001) were significantly reduced compared to HCs (M=0.013, SD=0.002), t(34)=3.81, p=.001, d=1.20. Discussion Despite the small voxel size, this novel 1H‐MRS protocol achieves high data quality and, thus, finally allows a reliable detection of glutamate in the human NAcc. For the first time this reveals that, in accordance with animal models, glutamatergic alterations occur in cocaine dependent humans and might play a decisive role in the development and maintenance of cocaine dependence
We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no he... more We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no hearing loss (n = 16) vs. a matched control group (n = 17) to further elucidate the role of excitatory and inhibitory neurotransmitters in tinnitus. Two-dimensional J-resolved spectroscopy (2D-JPRESS) was applied to disentangle Glutamate (Glu) from Glutamine and to estimate GABA levels in two bilateral voxels in the primary auditory cortex. Results indicated a lower Glu concentration (large effect) in right auditory cortex and lower GABA concentration (medium effect) in the left auditory cortex of the tinnitus group. Within the tinnitus group, Glu levels positively correlated with tinnitus loudness measures. While the GABA difference between groups is in line with former findings and theories about a dysfunctional auditory inhibition system in tinnitus, the novel finding of reduced Glu levels came as a surprise and is discussed in the context of a putative framework of inhibitory mechanism...
Beta weights of the amygdala ROI S1 S2 S3 S4 Feedback-group n=15 Graphical abstract Results of th... more Beta weights of the amygdala ROI S1 S2 S3 S4 Feedback-group n=15 Graphical abstract Results of the amygdala ROI analysis in the Feedback group: (a) Mean beta weights of the subjects' individual localizer amygdala ROI's. Conditions (regulate (green), view (red) and regulate > view (blue)) are presented over the four sessions (S1-S4). The blue regulate > view bar represents the effect of the training sessions with the decrease of amygdala activity through the mental intervention of reality check for emotion regulation in the regulate condition. Error bars represent standard deviations. (b) The mask of area in the amygdala region is covered by all individual ROIs of the Feedback group.
Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in ... more Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in the nucleus accumbens (NAcc), whereas drug‐seeking reinstatement is accompanied by enhanced glutamatergic transmission 1. However, little is known about such neurometabolic alterations in humans. We thus aim to investigate changes of the glutamate homeostasis in the NAcc of cocaine dependent individuals by means of a novel proton magnetic resonance spectroscopy (1H‐MRS) protocol that we have recently developed. Methods In 16 cocaine dependent individuals (CD) and 22 healthy controls (HC), non‐water suppressed PRESS localization 1H‐MRS preceded by a metabolite‐cycling pulse combined with inner‐volume saturation was performed on a 3T Philips Achieva System. MRS spectra were obtained from a voxel of 9.4x18.8x8.4mm, covering the anatomical dimensions of the left NAcc. For absolute quantification of the metabolites, a method based on the principle of reciprocity has been applied. Results An average signal‐to‐noise ratio of 16.97 and a mean line width of 6.93Hz (in single spectra) indicate good spectral quality. Metabolite concentrations of interest were quantified reliably using LCModel4 with Cramér‐Rao lower bounds<10. Moreover, glutamate concentrations in CDs (M=0.011, SD=0.001) were significantly reduced compared to HCs (M=0.013, SD=0.002), t(34)=3.81, p=.001, d=1.20. Discussion Despite the small voxel size, this novel 1H‐MRS protocol achieves high data quality and, thus, finally allows a reliable detection of glutamate in the human NAcc. For the first time this reveals that, in accordance with animal models, glutamatergic alterations occur in cocaine dependent humans and might play a decisive role in the development and maintenance of cocaine dependence
Beta weights of the amygdala ROI S1 S2 S3 S4 Feedback-group n=15 Graphical abstract Results of th... more Beta weights of the amygdala ROI S1 S2 S3 S4 Feedback-group n=15 Graphical abstract Results of the amygdala ROI analysis in the Feedback group: (a) Mean beta weights of the subjects' individual localizer amygdala ROI's. Conditions (regulate (green), view (red) and regulate > view (blue)) are presented over the four sessions (S1-S4). The blue regulate > view bar represents the effect of the training sessions with the decrease of amygdala activity through the mental intervention of reality check for emotion regulation in the regulate condition. Error bars represent standard deviations. (b) The mask of area in the amygdala region is covered by all individual ROIs of the Feedback group.
Social cognition is a crucial factor influencing development, progress, and treatment of psychiat... more Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition. In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test. The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy. These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.
Our fMRI study investigates auditory rhyme processing in spoken language to further elucidate the... more Our fMRI study investigates auditory rhyme processing in spoken language to further elucidate the topic of functional lateralization of language processing. During scanning, 14 subjects listened to four different types of versed word strings and subsequently performed either a rhyme or a meter detection task. Our results show lateralization to auditory-related temporal regions in the right hemisphere irrespective of task. As for the left hemisphere we report responses in the supramarginal gyrus as well as in the opercular part of the inferior frontal gyrus modulated by the presence of regular meter and rhyme. The interaction of rhyme and meter was associated with increased involvement of the superior temporal sulcus and the putamen of the right hemisphere. Overall, these findings support the notion of right-hemispheric specialization for suprasegmental analyses during processing of spoken sentences and provide neuroimaging evidence for the influence of metrics on auditory rhyme proc...
Proceedings of the National Academy of Sciences, 2014
Significance Social interaction deficits in drug users likely impede treatment, increase the burd... more Significance Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. However, the neural origin contributing to altered social interaction in drug users is unknown thus far. The present study illuminates the nature of basic social interaction deficits as exemplified by social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. The results suggest that basal social interaction impairments probably arise from blunted social reward processing that was again related to impaired real-life social behavior in cocaine users. These results point to the importance of reinstatement of social reward in the treatment of stimulant addiction.
Proceedings of the National Academy of Sciences, 2013
Significance Major depressive disorder is a significant contributor to the global burden of disea... more Significance Major depressive disorder is a significant contributor to the global burden of disease, affecting 350 million people according to an estimation of the World Health Organization. Today, no valid biomarkers of depression, which could predict the efficacy of a certain treatment in a certain group of patients, exist. Sleep deprivation is an effective and rapid-acting antidepressive treatment. However, the biomechanism of this effect is largely unknown. This study shows the effects of sleep deprivation on human brain functional connectivity alterations via the dorsal nexus, an area which is crucial in major depressive disorder. Here, we offer a neurobiological explanation for the known antidepressive action of sleep deprivation.
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