Tracking the subprocesses of decision-based action in the human frontal lobes

Situationally adaptive behavior relies on the identification of relevant target stimuli, the evaluation of these with respect to the current context and the selection of an appropriate action. We used functional magnetic resonance imaging (fMRI) to disentangle the neural networks underlying these processes within a single task. Our results show that activation of mid-ventrolateral prefrontal cortex (PFC) reflects the perceived presence of a target stimulus regardless of context, whereas context-appropriate evaluation is subserved by mid-dorsolateral PFC. Enhancing demands on response selection by means of response conflict activated a network of regions, all of which are directly connected to motor areas. On the midline, rostral anterior paracingulate cortex was found to link target detection and response selection by monitoring for the presence of behaviorally significant conditions. In summary, we provide new evidence for process-specific functional dissociations in the frontal lobes. In target-centered processing, target detection in the VLPFC is separable from contextual evaluation in the DLPFC. Response-centered processing in motor-associated regions occurs partly in parallel to these processes, which may enhance behavioral efficiency, but it may also lead to reaction time increases when an irrelevant response tendency is elicited.

Increased NoGo-anteriorisation in first-episode schizophrenia patients during Continuous Performance Test

OBJECTIVE: NoGo-stimuli during a Continuous Performance Test (CPT) activate prefrontal brain structures such as the anterior cingulate gyrus and lead to an anteriorisation of the positive electrical field of the NoGo-P300 relative to the Go-P300, so-called NoGo-anteriorisation (NGA). NGA during CPT is regarded as a neurophysiological standard index for cognitive response control. While it is known that patients with chronic schizophrenia exhibit a significant reduction in NGA, it is unclear whether this also occurs in patients undergoing their first-episode. Thus, the aim of the present study was to determine NGA in a group of patients with first-episode schizophrenia by utilizing a CPT paradigm. METHODS: Eighteen patients with first-episode schizophrenia and 18 matched healthy subjects were investigated electrophysiologically during a cued CPT, and the parameters of the Go- and NoGo-P300 were determined using microstate analysis. Low resolution tomography analysis (LORETA) was used for source determination. RESULTS: Due to a more posterior Go- and a more anterior NoGo-centroid, NGA was greater in patients than in healthy controls. LORETA indicated the same sources for both groups after Go-stimuli, but a more anterior source in patients after NoGo-stimuli. In patients P300-amplitude responses to both Go- and NoGo-stimuli were decreased, and P300-latency to NoGo-stimuli was increased. After the Go-stimuli false reactions and reaction times were increased in patients. CONCLUSIONS: Attention was reduced in patients with first-episode schizophrenia, as indicated by more false reactions, prolongation of reaction time, P300-latencies and by a decrease in P300-amplitude. Significantly however, the NGA and prefrontal LORETA-sources indicate intact prefrontal brain structures in first-episode schizophrenia patients. Previously described changes in this indicator of prefrontal function may be related to a progressive decay in chronic schizophrenia. SIGNIFICANCE: The results support the idea of a possible new biological marker of first episode psychosis, which may be a useful parameter for the longitudinal measurement of changing prefrontal brain function in a single schizophrenia patient.

Hemispheric lateralization of the corticostriatal glutamatergic system in the rat

Little is known about hemispheric lateralization of subcortical structures. Here, we show a higher expression of the subunit NR2A of the NMDA receptor mRNA in the striatum and of vGluT1 mRNA in the cingulate cortex, in the left hemisphere compared to the right one. This suggests a lateralization of the glutamatergic cortico-subcortical system, at the level of postsynaptic receptors as well as at the level of corticostriatal projections. Such lateralization could play a role in asymmetric diseases like Parkinson's disease.

Dopaminergic modulation of the reward system in schizophrenia: A placebo-controlled dopamine depletion fMRI study

Background The brain reward circuitry innervated by dopamine is critically disturbed in schizophrenia. This study aims to investigate the role of dopamine-related brain activity during prediction of monetary reward and loss in first episode schizophrenia patients. Methods We measured blood–oxygen-level dependent (BOLD) activity in 10 patients with schizophrenia (SCH) and 12 healthy controls during dopamine depletion with α-methylparatyrosine (AMPT) and during a placebo condition (PLA). Results AMPT reduced the activation of striatal and cortical brain regions in SCH. In SCH vs. controls reduced activation was found in the AMPT condition in several regions during anticipation of reward and loss, including areas of the striatum and frontal cortex. In SCH vs. controls reduced activation of the superior temporal gyrus and posterior cingulate was observed in PLA during anticipation of rewarding stimuli. PLA patients had reduced activation in the ventral striatum, frontal and cingulate cortex in anticipation of loss. The findings of reduced dopamine-related brain activity during AMPT were verified by reduced levels of dopamine in urine, homovanillic-acid in plasma and increased prolactin levels. Conclusions Our results indicate that dopamine depletion affects functioning of the cortico-striatal reward circuitry in SCH. The findings also suggest that neuronal functions associated with dopamine neurotransmission and attribution of salience to reward predicting stimuli are altered in schizophrenia.

Cerebral hemodynamic and oxygenation changes induced by inner and heard speech: a study combining functional near-infrared spectroscopy and capnography

The aim of this study was to investigate the effects of inner and heard speech on cerebral hemodynamics and oxygenation in the anterior prefrontal cortex (PFC) using functional near-infrared spectroscopy and to test whether potential effects were caused by alterations in the arterial carbon dioxide pressure (PaCO2). Twenty-nine healthy adult volunteers performed six different tasks of inner and heard speech according to a randomized crossover design. During the tasks, we generally found a decrease in PaCO2 (only for inner speech), tissue oxygen saturation (StO2), oxyhemoglobin ([O2Hb]), total hemoglobin ([tHb]) concentration and an increase in deoxyhemoglobin concentration ([HHb]). Furthermore, we found significant relations between changes in [O2Hb], [HHb], [tHb], or StO2 and the participants’ age, the baseline PETCO2, or certain speech tasks. We conclude that changes in breathing during the tasks led to lower PaCO2 (hypocapnia) for inner speech. During heard speech, no significant changes in PaCO2 occurred, but the decreases in StO2, [O2Hb], and [tHb] suggest that changes in PaCO2 were also involved here. Different verse types (hexameter and alliteration) led to different changes in [tHb], implying different brain activations. In conclusion, StO2, [O2Hb], [HHb], and [tHb] are affected by interplay of both PaCO2 reactivity and functional brain activity.

The effects of catecholamine depletion on the neural response to fearful faces in remitted depression

Recent evidence suggests that increased psychophysiological response to negatively valenced emotional stimuli found in major depressive disorder (MDD) may be associated with reduced catecholaminergic neurotransmission. Fourteen unmedicated, remitted subjects with MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover trial. Subjects were exposed to fearful (FF) and neutral faces (NF) during a scan with [15O]H2O positron emission tomography to assess the brain-catecholamine interaction in brain regions previously associated with emotional face processing. Treatment with AMPT resulted in significantly increased, normalized cerebral blood flow (CBF) in the left inferior temporal gyrus (ITG) and significantly decreased CBF in the right cerebellum across conditions and groups. In RMDD, flow in the left posterior cingulate cortex (PCC) increased significantly in the FF compared to the NF condition after AMPT, but remained unchanged after placebo, whereas healthy controls showed a significant increase under placebo and a significant decrease under AMPT in this brain region. In the left dorsolateral prefrontal cortex (DLPFC), flow decreased significantly in the FF compared to the NF condition under AMPT, and increased significantly under placebo in RMDD, whereas healthy controls showed no significant differences. Differences between AMPT and placebo of within-session changes in worry-symptoms were positively correlated with the corresponding changes in CBF in the right subgenual prefrontal cortex in RMDD. In conclusion, this study provided evidence for a catecholamine-related modulation of the neural responses to FF expressions in the left PCC and the left DLPFC in subjects with RMDD that might constitute a persistent, trait-like abnormality in MDD.

The effect of inner speech on arterial CO2 and cerebral hemodynamics and oxygenation: a functional NIRS study

The aim of the present study was (i) to investigate the effect of inner speech on cerebral hemodynamics and oxygenation, and (ii) to analyze if these changes could be the result of alternations of the arterial carbon dioxide pressure (PaCO2). To this end, in seven adult volunteers, we measured changes of cerebral absolute [O2Hb], [HHb], [tHb] concentrations and tissue oxygen saturation (StO2) (over the left and right anterior prefrontal cortex (PFC)), as well as changes in end-tidal CO2 (PETCO2), a reliable and accurate estimate of PaCO2. Each subject performed three different tasks (inner recitation of hexameter (IRH) or prose (IRP) verses) and a control task (mental arithmetic (MA)) on different days according to a randomized crossover design. Statistical analysis was applied to the differences between pre-baseline, two tasks, and four post-baseline periods. The two brain hemispheres and three tasks were tested separately. During the tasks, we found (i) PETCO2 decreased significantly (p < 0.05) during the IRH ( ~ 3 mmHg) and MA ( ~ 0.5 mmHg) task. (ii) [O2Hb] and StO2 decreased significantly during IRH ( ~ 1.5 μM; ~ 2 %), IRP ( ~ 1 μM; ~ 1.5 %), and MA ( ~ 1 μM; ~ 1.5 %) tasks. During the post-baseline period, [O2Hb] and [tHb] of the left PFC decreased significantly after the IRP and MA task ( ~ 1 μM and ~ 2 μM, respectively). In conclusion, the study showed that inner speech affects PaCO2, probably due to changes in respiration. Although a decrease in PaCO2 is causing cerebral vasoconstriction and could potentially explain the decreases of [O2Hb] and StO2 during inner speech, the changes in PaCO2 were significantly different between the three tasks (no change in PaCO2 for MA) but led to very similar changes in [O2Hb] and StO2. Thus, the cerebral changes cannot solely be explained by PaCO2.

Changes in cerebral hemodynamics and oxygenation induced by different speech tasks – an assessment by combining functional near‐infrared spectroscopy and capnography

Introduction In several studies, we found that during guided rhythmic speech exercises, a decrease in cerebral hemodynamics and oxygenation occurred as the result of a decrease in the partial pressure of carbon dioxide in the arterial blood (PaCO2) during speaking. To further explore the effect of PaCO2 variations on cerebral hemodynamics and oxygenation, the aim of the present study was to investigate the impact of spoken, inner and heard speech tasks on these parameters. Material and Methods Speech tasks included recitation or inner recitation or listening to hexameter, alliteration, prose, or performing mental arithmetic. The following physiological parameters were measured: tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin, deoxyhemoglobin, total hemoglobin (over the left and right anterior prefrontal cortex, using an ISS OxiplexTS frequency domain near-infrared spectrometer) and end-tidal CO2 (PETCO2; using Nellcor N1000 and Datex NORMOCAP capnographs). Statistical analysis was applied to the differences between baseline, 2 tasks, and 3 post-baseline periods. Data of 3 studies with 24, 7 and 29 healthy subjects, respectively, were combined, and linear regression analyses were calculated. Results Linear regression analyses revealed significant relations between changes in oxyhemoglobin, deoxyhemoglobin, total hemoglobin or StO2 and the participants’ age, the baseline PETCO2 or certain speech tasks. While hexameter verses affected changes during the tasks, alliteration verses only affected changes during the recovery phase. Discussion and Conclusion The observed effects in hemodynamics and oxygenation indicate a combination of neurovascular coupling (increased neuronal activity leading to an increase in the cerebral metabolic rate of oxygen resulting in an increase in cerebral flood flow/volume) and CO2 reactivity (increased breathing during speech tasks causing a decrease in PaCO2 leading to vasoconstriction and decrease in cerebral blood flow). The neurovascular coupling characteristics are task-dependent. References Scholkmann F, Gerber U, Wolf M, Wolf U. End-tidal CO2: An important parameter for a correct interpretation in functional brain studies using speech tasks. Neuroimage 2013;66:71-79. Scholkmann F, Wolf M, Wolf U. The effect of inner speech on arterial CO2, cerebral hemodynamics and oxygenation – A functional NIRS study. Adv Exp Med Biol 2013;789:81-87.

Effects of inner and heard speech in arts speech therapy on cerebral oxygenation and hemodynamics

Background: The aim of the present study was to contributing to researching physiological effects of arts speech therapy by (i) investigating effects of inner and heard speech on cerebral hemodynamics and oxygenation, and (ii) analyzing if these changes were affected by alterations of the arterial carbon dioxide pressure (PaCO2). Methods: In 29 healthy adult volunteers we measured changes in cerebral absolute oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]), total hemoglobin ([tHb]) concentrations and tissue oxygen saturation (StO2) (over the left and right anterior prefrontal cortex (PFC)) using functional near-infrared spectroscopy (fNIRS) as well as changes in end-tidal CO2 (PETCO2) using capnography. Each subject performed six different tasks: three types of task modalities, i.e. inner speech, heard speech from a person and heard speech from a record, and, two recitation texts, i.e. hexameter and alliteration on different days according to a randomized crossover design. Statistical analysis was applied to the differences between the baseline, two task and four recovery periods. The two brain hemispheres, i.e. left and right PFC, and six tasks were tested separately. Results: During the tasks we found in general a decrease in PETCO2 (significantly only for inner speech), StO2, [O2Hb], [tHb] as well as in an increase in [HHb]. There was a significant difference between hexameter and alliteration. Particularly, the changes in [tHb] at the left PFC during tasks and after them were statistically different. Furthermore we found significant relations between changes in [O2Hb], [HHb], [tHb] or StO2 and the participants’ age, the baseline PETCO2, or certain speech tasks. Conclusions: Changes in breathing (hyperventilation) during the tasks led to lower PaCO2 (hypocapnia) for inner speech. During heard speech no significant changes in PaCO2 occurred, but the decreases in StO2, [O2Hb], [tHb] suggest that changes in PaCO2 were also relevant here. Different verse types (hexameter, alliteration) led to different changes in [tHb]. Consequently, StO2, [O2Hb], [HHb] and [tHb] are affected by interplay of both PaCO2 reactivity and task dependent functional brain activity.

Comparative Behavioral and Neural Effects of Tryptophan and Catecholamine Depletion in Remitted Depression

Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and catecholamines play common and differential roles in the pathophysiology of depression.

Zazen meditation and no-task resting EEG compared with LORETA intracortical source localization

Meditation is a self-induced and willfully initiated practice that alters the state of consciousness. The meditation practice of Zazen, like many other meditation practices, aims at disregarding intrusive thoughts while controlling body posture. It is an open monitoring meditation characterized by detached moment-to-moment awareness and reduced conceptual thinking and self-reference. Which brain areas differ in electric activity during Zazen compared to task-free resting? Since scalp electroencephalography (EEG) waveforms are reference-dependent, conclusions about the localization of active brain areas are ambiguous. Computing intracerebral source models from the scalp EEG data solves this problem. In the present study, we applied source modeling using low resolution brain electromagnetic tomography (LORETA) to 58-channel scalp EEG data recorded from 15 experienced Zen meditators during Zazen and no-task resting. Zazen compared to no-task resting showed increased alpha-1 and alpha-2 frequency activity in an exclusively right-lateralized cluster extending from prefrontal areas including the insula to parts of the somatosensory and motor cortices and temporal areas. Zazen also showed decreased alpha and beta-2 activity in the left angular gyrus and decreased beta-1 and beta-2 activity in a large bilateral posterior cluster comprising the visual cortex, the posterior cingulate cortex and the parietal cortex. The results include parts of the default mode network and suggest enhanced automatic memory and emotion processing, reduced conceptual thinking and self-reference on a less judgmental, i.e., more detached moment-to-moment basis during Zazen compared to no-task resting.

Rivastigmine effects on EEG spectra and three-dimensional LORETA functional imaging in Alzheimer's disease

OBJECTIVE The objective of the study is to investigate the electrocortical and the global cognitive effects of 3 months rivastigmine medication in a group of mild to moderate Alzheimer's disease patients. MATERIALS AND METHODS Multichannel EEG and cognitive performances measured with the Mini Mental State Examination in a group of 16 patients with mild to moderate Alzheimer's Disease were collected before and 3 months after the onset of rivastigmine medication. RESULTS Spectral analysis of the EEG data showed a significant power decrease in the delta and theta frequency bands during rivastigmine medication, i.e., a shift of the power spectrum towards 'normalization'. Three-dimensional low resolution electromagnetic tomography (LORETA) functional imaging localized rivastigmine effects in a network that includes left fronto-parietal regions, posterior cingulate cortex, bilateral parahippocampal regions, and the hippocampus. Moreover, a correlation analysis between differences in the cognitive performances during the two recordings and LORETA-computed intracortical activity showed, in the alpha1 frequency band, better cognitive performance with increased cortical activity in the left insula. CONCLUSION The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.

Neural correlates of anticipation risk reflect risk preferences

Individual risk preferences have a large influence on decisions, such as financial investments, career and health choices, or gambling. Decision making under risk has been studied both behaviorally and on a neural level. It remains unclear, however, how risk attitudes are encoded and integrated with choice. Here, we investigate how risk preferences are reflected in neural regions known to process risk. We collected functional magnetic resonance images of 56 human subjects during a gambling task (Preuschoff et al., 2006). Subjects were grouped into risk averters and risk seekers according to the risk preferences they revealed in a separate lottery task. We found that during the anticipation of high-risk gambles, risk averters show stronger responses in ventral striatum and anterior insula compared to risk seekers. In addition, risk prediction error signals in anterior insula, inferior frontal gyrus, and anterior cingulate indicate that risk averters do not dissociate properly between gambles that are more or less risky than expected. We suggest this may result in a general overestimation of prospective risk and lead to risk avoidance behavior. This is the first study to show that behavioral risk preferences are reflected in the passive evaluation of risky situations. The results have implications on public policies in the financial and health domain.

I feel good whether my friends win or my foes lose: brain mechanisms underlying feeling similarity.

People say they enjoy both seeing a preferred social group succeed and seeing an adversary social group fail. At the same time, they state they dislike seeing a preferred social group fail and seeing an adversary social group succeed. The current magnetic resonance imaging study investigated whether-and if so, how-such similarities in reported feeling states are reflected in neural activities. American football fans anticipated success and failure situations for their favorite or their adversary teams. The data support the idea that feeling similarities and divergences expressed in verbal reports carry with them significant neural similarities and differences, respectively. Desired (favorite team likely to win and adversary team likely to lose) rather than undesired (favorite team likely to lose and adversary team likely to win) outcomes were associated with heightened activity in the supramarginal gyrus, posterior cingulate cortex, insula, and cerebellum. Precuneus activity additionally distinguished anticipated desirable outcomes for favorite versus adversary teams.

Cortical control of facial expression.

The present topical review deals with the motor control of facial expressions in humans. Facial expressions are a central part of human communication. Emotional face expressions have a crucial role in human non-verbal behavior, allowing a rapid transfer of information between individuals. Facial expressions can be both voluntarily or emotionally controlled. Recent studies in non-human primates and humans revealed that the motor control of facial expressions has a distributed neural representation. At least 5 cortical regions on the medial and lateral aspects of each hemisphere are involved: the primary motor cortex, the ventral lateral premotor cortex, the supplementary motor area on the medial wall, and, finally, the rostral and caudal cingulate cortex. The results of studies in humans and non-human primates suggest that the innervation of the face is bilaterally controlled for the upper part, and mainly contralaterally controlled for the lower part. Furthermore, the primary motor cortex, the ventral lateral premotor cortex, and the supplementary motor area are essential for the voluntary control of facial expressions. In contrast, the cingulate cortical areas are important for emotional expression, since they receive input from different structures of the limbic system. This article is protected by copyright. All rights reserved.