Brain activation during anticipation of sound sequences

Music consists of sound sequences that require integration over time. As we become familiar with music, associations between notes, melodies, and entire symphonic movements become stronger and more complex. These associations can become so tight that, for example, hearing the end of one album track can elicit a robust image of the upcoming track while anticipating it in total silence. Here, we study this predictive “anticipatory imagery” at various stages throughout learning and investigate activity changes in corresponding neural structures using functional magnetic resonance imaging. Anticipatory imagery (in silence) for highly familiar naturalistic music was accompanied by pronounced activity in rostral prefrontal cortex (PFC) and premotor areas. Examining changes in the neural bases of anticipatory imagery during two stages of learning conditional associations between simple melodies, however, demonstrates the importance of fronto-striatal connections, consistent with a role of the basal ganglia in “training” frontal cortex (Pasupathy and Miller, 2005). Another striking change in neural resources during learning was a shift between caudal PFC earlier to rostral PFC later in learning. Our findings regarding musical anticipation and sound sequence learning are highly compatible with studies of motor sequence learning, suggesting common predictive mechanisms in both domains.

Outer skull landmark-based coordinates for measurement of cerebral blood flow and intracranial pressure in rabbits

Despite the increased use of intracranial neuromonitoring during experimental subarachnoid hemorrhage (SAH), coordinates for probe placement in rabbits are lacking. This study evaluates the safety and reliability of using outer skull landmarks to identify locations for placement of cerebral blood flow (CBF) and intraparenchymal intracranial pressure (ICP) probes. Experimental SAH was performed in 17 rabbits using an extracranial-intracranial shunt model. ICP probes were placed in the frontal lobe and compared to measurements recorded from the olfactory bulb. CBF probes were placed in various locations in the frontal cortex anterior to the coronary suture. Insertion depth, relation to the ventricular system, and ideal placement location were determined by post-mortem examination. ICP recordings at the time of SAH from the frontal lobe did not differ significantly from those obtained from the right olfactory bulb. Ideal coordinates for intraparenchymal CBF probes in the left and right frontal lobe were found to be located 4.6±0.9 and 4.5±1.2 anterior to the bregma, 4.7±0.7mm and 4.7±0.5mm parasagittal, and at depths of 4±0.5mm and 3.9±0.5mm, respectively. The results demonstrate that the presented coordinates based on skull landmarks allow reliable placement of intraparenchymal ICP and CBF probes in rabbit brains without the use of a stereotactic frame.

Comparison of brain PrPd distribution in ovine BSE and scrapie

Scrapie and bovine spongiform encephalopathy (BSE) are both prion diseases affecting ruminants, and these diseases do not share the same public health concerns. Surveillance of the BSE agent in small ruminants has been a great challenge, and the recent identification of diverse prion diseases in ruminants has led to the development of new methods for strain typing. In our study, using immunohistochemistry (IHC), we assessed the distribution of PrP(d) in the brains of 2 experimentally BSE-infected sheep with the ARQ/ARQ genotype. Distribution of PrP(d) in the brain, from the spinal cord to the frontal cortex, was remarkably similar in the 2 sheep despite different inoculation routes and incubation periods. Comparatively, overall PrP(d) brain distribution, evaluated by IHC, in 19 scrapie cases with the ARQ/ARQ, ARQ/VRQ, and VRQ/VRQ genotypes, in some cases showed similarities to the experimentally BSE-infected sheep. There was no exclusive neuroanatomical site with a characteristic and specific PrP(d) type of accumulation induced by the BSE agent. However, a detailed analysis of the topography, types, and intensity of PrP(d) deposits in the frontal cortex, striatum, piriform cortex, hippocampus, mesencephalon, and cerebellum allowed the BSE-affected sheep group to be distinguished from the 19 scrapie cases analyzed in our study. These results strengthen and emphasize the potential interest of PrP(d) brain mapping to help in identifying prion strains in small ruminants.

Amino acids in cerebrospinal and brain interstitial fluid in experimental pneumococcal meningitis

Excitatory amino acids are increasingly implicated in the pathogenesis of neuronal injury induced by a variety of CNS insults, such as ischemia, trauma, hypoglycemia, and epilepsy. Little is known about the role of amino acids in causing CNS injury in bacterial meningitis. Several amino acids were measured in cerebrospinal fluid and in microdialysis samples from the interstitial fluid of the frontal cortex in a rabbit model of pneumococcal meningitis. Cerebrospinal fluid concentrations of glutamate, aspartate, glycine, taurine, and alanine increased significantly in infected animals. Among the amino acids with known excitatory or inhibitory function, interstitial fluid concentrations of glutamate were significantly elevated (by 470%). Alanine, a marker for anaerobic glycolysis, also increased in the cortex of infected rabbits. The elevated glutamate concentrations in the brain extracellular space suggest that excitotoxic neuronal injury may play a role in bacterial meningitis.

Lactate and glucose concentrations in brain interstitial fluid, cerebrospinal fluid, and serum during experimental pneumococcal meningitis

Metabolic abnormalities during bacterial meningitis include hypoglycorrhachia and cerebrospinal fluid (CSF) lactate accumulation. The mechanisms by which these alterations occur within the central nervous system (CNS) are still incompletely delineated. To determine the evolution of these changes and establish the locus of abnormal metabolism during meningitis, glucose and lactate concentrations in brain interstitial fluid, CSF, and serum were measured simultaneously and sequentially during experimental pneumococcal meningitis in rabbits. Interstitial fluid samples were obtained from the frontal cortex and hippocampus by using in situ brain microdialysis, and serum and CSF were directly sampled. There was an increase of CSF lactate concentration, accompanied by increased local production of lactate in the brain, and a decrease of CSF-to-serum glucose ratio that was paralleled by a decrease in cortical glucose concentration. Brain microdialysate lactate concentration was not affected by either systemic lactic acidosis or artificially elevated CSF lactate concentration. These data support the hypothesis that the brain is a locus for anaerobic glycolysis during meningitis, resulting in increased lactate production and perhaps contributing to decreased tissue glucose concentration.

White matter anisotropy related to electrophysiology of first episode schizophrenia during NoGo inhibition

Patients with schizophrenia have reduced execution functions and white matter alterations indicating cerebral disconnectivity. Here we investigated the relationship between white matter integrity and event related potentials (ERP) during a continuous performance test (CPT). Anisotropy values were correlated with the brain electrical P300 microstate duration and P300 latency associated to the NoGo- and the Go-stimuli of the CPT in 11 patients with first episode schizophrenia and 11 matched healthy controls. Both groups showed significant positive correlations of the NoGo-microstate duration with the white matter signal in the superior frontal region, the optic radiation, the posterior cingulate, and the inferolateral fascicle. In addition, patients with first episode schizophrenia had significant correlations with the right radiation and the left genu of the corpus callosum, bilateral geniculate, and the left middle and the superior temporal regions. We interpreted these findings as a sign of functional correlates of extended circuits for the active inhibition of a motor response in the visual CPT as compared to controls.

Using transcranial magnetic stimulation to probe decision-making and memory

Decision-making and memory are fundamental processes for successful human behaviour. For eye movements, the frontal eye fields (FEF), the supplementary eye fields (SEF), the dorsolateral prefrontal cortex (DLPFC), the ventrolateral frontal cortex and the anterior cingulum are important for these cognitive processes. The online approach of transcranial magnetic stimulation (TMS), i.e., the application of magnetic pulses during planning and performance of saccades, allows interfering specifically with information processing of the stimulated region at a very specific time interval (chronometry of cortical processing). The paper presents studies, which showed the different roles of the FEF and DLPFC in antisaccade control. The critical time interval of DLPFC control seems to be before target onset since TMS significantly increased the percentage of antisaccade errors at that time interval. The FEF seems to be important for the triggering of correct antisaccades. Bilateral stimulation of the DLPFC could demonstrate parallel information-processing transfer in spatial working memory during memory-guided saccades.

"Old proverbs in new skins – an fMRI study on defamiliarization"

We investigated how processing fluency and defamiliarization (the art of rendering familiar notions unfamiliar) contribute to the affective and esthetic processing of reading in an event-related functional magnetic-resonance-imaging experiment.We compared the neural correlates of processing (a) familiar German proverbs, (b) unfamiliar proverbs, (c) defamiliarized variations with altered content relative to the original proverb (proverb-variants), (d) defamiliarized versions with unexpected wording but the same content as the original proverb (proverb-substitutions), and (e) non-rhetorical sentences. Here, we demonstrate that defamiliarization is an effectiveway of guiding attention, but that the degree of affective involvement depends on the type of defamiliarization: enhanced activation in affect-related regions (orbito-frontal cortex, medPFC) was found only if defamiliarization altered the content of the original proverb. Defamiliarization on the level of wording was associated with attention processes and error monitoring. Although proverb-variants evoked activation in affect-related regions, familiar proverbs received the highest beauty ratings.

Visuospatial working memory in very preterm and term born children - Impact of age and performance

Working memory is crucial for meeting the challenges of daily life and performing academic tasks, such as reading or arithmetic. Very preterm born children are at risk of low working memory capacity. The aim of this study was to examine the visuospatial working memory network of school-aged preterm children and to determine the effect of age and performance on the neural working memory network. Working memory was assessed in 41 very preterm born children and 36 term born controls (aged 7–12 years) using functional magnetic resonance imaging (fMRI) and neuropsychological assessment. While preterm children and controls showed equal working memory performance, preterm children showed less involvement of the right middle frontal gyrus, but higher fMRI activation in superior frontal regions than controls. The younger and low-performing preterm children presented an atypical working memory network whereas the older high-performing preterm children recruited a working memory network similar to the controls. Results suggest that younger and low-performing preterm children show signs of less neural efficiency in frontal brain areas. With increasing age and performance, compensational mechanisms seem to occur, so that in preterm children, the typical visuospatial working memory network is established by the age of 12 years.

The emotional power of music: How music enhances the feeling of affective pictures

Music is an intriguing stimulus widely used in movies to increase the emotional experience. However, no brain imaging study has to date examined this enhancement effect using emotional pictures (the modality mostly used in emotion research) and musical excerpts. Therefore, we designed this functional magnetic resonance imaging study to explore how musical stimuli enhance the feeling of affective pictures. In a classical block design carefully controlling for habituation and order effects, we presented fearful and sad pictures (mostly taken from the IAPS) either alone or combined with congruent emotional musical excerpts (classical pieces). Subjective ratings clearly indicated that the emotional experience was markedly increased in the combined relative to the picture condition. Furthermore, using a second-level analysis and regions of interest approach, we observed a clear functional and structural dissociation between the combined and the picture condition. Besides increased activation in brain areas known to be involved in auditory as well as in neutral and emotional visual-auditory integration processes, the combined condition showed increased activation in many structures known to be involved in emotion processing (including for example amygdala, hippocampus, parahippocampus, insula, striatum, medial ventral frontal cortex, cerebellum, fusiform gyrus). In contrast, the picture condition only showed an activation increase in the cognitive part of the prefrontal cortex, mainly in the right dorsolateral prefrontal cortex. Based on these findings, we suggest that emotional pictures evoke a more cognitive mode of emotion perception, whereas congruent presentations of emotional visual and musical stimuli rather automatically evoke strong emotional feelings and experiences.

Neural correlate of spatial presence in an arousing and noninteractive virtual reality: an EEG and psychophysiology study

Using electroencephalography (EEG), psychophysiology, and psychometric measures, this is the first study which investigated the neurophysiological underpinnings of spatial presence. Spatial presence is considered a sense of being physically situated within a spatial environment portrayed by a medium (e.g., television, virtual reality). Twelve healthy children and 11 healthy adolescents were watching different virtual roller coaster scenarios. During a control session, the roller coaster cab drove through a horizontal roundabout track. The following realistic roller coaster rides consisted of spectacular ups, downs, and loops. Low-resolution brain electromagnetic tomography (LORETA) and event-related desynchronization (ERD) were used to analyze the EEG data. As expected, we found that, compared to the control condition, experiencing a virtual roller coaster ride evoked in both groups strong SP experiences, increased electrodermal reactions, and activations in parietal brain areas known to be involved in spatial navigation. In addition, brain areas that receive homeostatic afferents from somatic and visceral sensations of the body were strongly activated. Most interesting, children (as compared to adolescents) reported higher spatial presence experiences and demonstrated a different frontal activation pattern. While adolescents showed increased activation in prefrontal areas known to be involved in the control of executive functions, children demonstrated a decreased activity in these brain regions. Interestingly, recent neuroanatomical and neurophysiological studies have shown that the frontal brain continues to develop to adult status well into adolescence. Thus, the result of our study implies that the increased spatial presence experience in children may result from the not fully developed control functions of the frontal cortex.

Neural representation and clinically relevant moderators of individualised self-criticism in healthy subjects

Many people routinely criticise themselves. While self-criticism is largely unproblematic for most individuals, depressed patients exhibit excessive self-critical thinking, which leads to strong negative affects. We used functional magnetic resonance imaging in healthy subjects (N = 20) to investigate neural correlates and possible psychological moderators of self-critical processing. Stimuli consisted of individually selected adjectives of personally negative content and were contrasted with neutral and negative non-self-referential adjectives. We found that confrontation with self-critical material yielded neural activity in regions involved in emotions (anterior insula/hippocampus-amygdala formation) and in anterior and posterior cortical midline structures, which are associated with self-referential and autobiographical memory processing. Furthermore, contrasts revealed an extended network of bilateral frontal brain areas. We suggest that the co-activation of superior and inferior lateral frontal brain regions reflects the recruitment of a frontal top-down pathway, representing cognitive reappraisal strategies for dealing with evoked negative affects. In addition, activation of right superior frontal areas was positively associated with neuroticism and negatively associated with cognitive reappraisal. Although these findings may not be specific to negative stimuli, they support a role for clinically relevant personality traits in successful regulation of emotion during confrontation with self-critical material.

Association of long-term nicotine abstinence with normal metabotropic glutamate receptor-5 binding

BACKGROUND Nicotine addiction is a major public health problem and is associated with primary glutamatergic dysfunction. We recently showed marked global reductions in metabotropic glutamate receptor type 5 (mGluR5) binding in smokers and recent ex-smokers (average abstinence duration of 25 weeks). The goal of this study was to examine the role of mGluR5 downregulation in nicotine addiction by investigating a group of long-term ex-smokers (abstinence >1.5 years), and to explore associations between mGluR5 binding and relapse in recent ex-smokers. METHODS Images of mGluR5 receptor binding were acquired in 14 long-term ex-smokers, using positron emission tomography with radiolabeled [11C]ABP688, which binds to an allosteric site with high specificity. RESULTS Long-term ex-smokers and individuals who had never smoked showed no differences in mGluR5 binding in any of the brain regions examined. Long-term ex-smokers showed significantly higher mGluR5 binding than recent ex-smokers, most prominently in the frontal cortex (42%) and thalamus (57%). CONCLUSIONS Our findings suggest that downregulation of mGluR5 is a pathogenetic mechanism underlying nicotine dependence and the high relapse rate in individuals previously exposed to nicotine. Therefore, mGluR5 receptor binding appears to be an effective biomarker in smoking and a promising target for the discovery of novel medication for nicotine dependence and other substance-related disorders.

Distinct roles of cortical and pallidal β and γ frequencies in hemiparkinsonian and dyskinetic rats.

Enhanced β band (βB) activity, which is suppressed by levodopa (LD) treatment, has been demonstrated within the basal ganglia (BG) of Parkinson's disease (PD) patients. However, some data suggest that Parkinsonian symptoms are not directly related to this brain frequency and therefore, its causative role remains questionable. A less explored phenomenon is the link between the γ band (γB) and PD phenomenology. Here, we monitored the development of the oscillatory activity during chronic LD depletion and LD treatment in Parkinsonian and levodopa-induced dyskinesia (LID) in rats. We found a significant and bilateral power increase in the high βB frequencies (20-30Hz) within the first 10days after 6-hydroxydopamine (6-OHDA) lesion, which was in accordance with a significant depletion of dopaminergic fibers in the striatum. We also observed a clear-cut γB increase during LD treatment. The development of LID was characterized by a slight increase in the cumulative power of βB accompanied by a large augmentation in the γB frequency (60-80Hz). This latter effect reached a plateau in the frontal cortex bilaterally and the left globus pallidus after the second week of LD treatment. Our data suggest that the βB parallels the emergence of Parkinsonian signs and can be taken as a predictive sign of DA depletion, matching TH-staining reduction. On the other hand, the γB is strictly correlated to the development of LID. LD treatment had an opposite effect on βB and γB, respectively.

Remote Effects of Hippocampal Sclerosis on Effective Connectivity during Working Memory Encoding: A Case of Connectional Diaschisis?

Accumulating evidence suggests a role for the medial temporal lobe (MTL) in working memory (WM). However, little is known concerning its functional interactions with other cortical regions in the distributed neural network subserving WM. To reveal these, we availed of subjects with MTL damage and characterized changes in effective connectivity while subjects engaged in WM task. Specifically, we compared dynamic causal models, extracted from magnetoencephalographic recordings during verbal WM encoding, in temporal lobe epilepsy patients (with left hippocampal sclerosis) and controls. Bayesian model comparison indicated that the best model (across subjects) evidenced bilateral, forward, and backward connections, coupling inferior temporal cortex (ITC), inferior frontal cortex (IFC), and MTL. MTL damage weakened backward connections from left MTL to left ITC, a decrease accompanied by strengthening of (bidirectional) connections between IFC and MTL in the contralesional hemisphere. These findings provide novel evidence concerning functional interactions between nodes of this fundamental cognitive network and sheds light on how these interactions are modified as a result of focal damage to MTL. The findings highlight that a reduced (top-down) influence of the MTL on ipsilateral language regions is accompanied by enhanced reciprocal coupling in the undamaged hemisphere providing a first demonstration of “connectional diaschisis.”