Peter Klaver

Human memory formation is accompanied by rhinal–hippocampal coupling and decoupling

In humans, distinct processes within the hippocampus and rhinal cortex support declarative memory formation. But do these medial temporal lobe (MTL) substructures directly cooperate in encoding new memories? Phase synchronization of gamma-band electroencephalogram (EEG) oscillations (around 40 Hz) is a general mechanism of transiently connecting neural assemblies. We recorded depth-EEG from within the MTL of epilepsy patients performing a memorization task. Successful as opposed to unsuccessful memory formation was accompanied by an initial elevation of rhinal–hippocampal gamma synchronization followed by a later desynchronization, suggesting that effective declarative memory formation is accompanied by a direct and temporarily limited cooperation between both MTL substructures.

Oxytocin Makes a Face in Memory Familiar

Social recognition is the basis of all social interactions. Here, we show that, in humans, the evolutionarily highly conserved neuropeptide oxytocin, after intranasal administration, specifically improves recognition memory for faces, but not for nonsocial stimuli. With increased oxytocin levels, previously presented faces were more correctly assessed as “known,” whereas the ability of recollecting faces was unchanged. This pattern speaks for an immediate and selective effect of the peptide strengthening neuronal systems of social memory.

Intrasubject reproducibility of presurgical language lateralization and mapping using fMRI.

Background: fMRI is becoming a standard tool for the presurgical lateralization and mapping of brain areas involved in language processing. However, its within-subject reproducibility has yet to be fully explored. Objective: To evaluate within-test and test–retest reliability of language fMRI in consecutive patients undergoing evaluation for epilepsy surgery. Methods: Thirty-four unselected patients were investigated once (within-test reliability) and 12 patients twice (test–retest reliability). The imaging series consisted of an alternating 25-second synonym judgment condition with a 25-second letter-matching condition repeated 15 times. Reproducibility of activation maps of the first and second half of session 1 or activation maps of sessions 1 and 2 was evaluated by comparing one global and three regional lateralization indexes (Broca’s area, remaining prefrontal cortex, temporoparietal area) and on a voxel-by-voxel basis (intraclass correlation coefficient, percentage overlap, correlation of t-values). Results: Global and regional language lateralization was achieved with high reliability within and across sessions. Reproducibility was evenly distributed across both hemispheres but not within each hemisphere. Frontal activations were more reliable than temporoparietal ones. Depending on the statistical threshold chosen, the voxel-by-voxel analysis revealed a mean overlap of activations derived from the first and second investigation of up to 48.9%. Conclusion: Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

Is synchronized neuronal gamma activity relevant for selective attention

Today, much evidence exists that sensory feature binding is accomplished by phase synchronization of induced neuronal gamma activity (30-80 Hz). Recent studies furthermore suggest that phase synchronization of induced gamma activity may represent a general mechanism enabling transient associations of neural assemblies and thus may play a central role in cortical information processing. Here, we describe findings indicating that synchronized gamma activity is moreover specifically involved in selective attention. While feature binding appears to depend primarily on induced gamma synchronization, attentional processes seem to involve both induced and evoked gamma oscillations. Yet it is still an open question, as to which top-down and bottom-up processes are associated with attentional modulation of gamma activity. A possible mechanism to project influences from attentional control structures to areas concerned with stimulus representation and vice versa, may be neuronal synchronization and the resulting firing rate changes of coincidence-detecting neurons in target areas.

Language mapping in less than 15 minutes: Real-time functional MRI during routine clinical investigation

Neurosurgical interventions often require the presurgical determination of language dominance or mapping of language areas. Results obtained by fMRI are closely correlated with invasive procedures such as electrical stimulation mapping or the intracarotid amobarbital test. However, language fMRI is not used routinely, because postprocessing is time-consuming. We utilized a real-time analysis software installed directly on the MR console computer and SPM99 as reference postprocessing software. We assessed the reliability of the immediate determination of language dominance based on individual activation maps by comparing the results of the visual analysis of images derived from conventional postprocessing with those produced by the real-time tool. All images were rated independently by six senior neurologists blinded to other data. We validated the robustness of the real-time method statistically by comparing global and regional lateralization indices derived from real-time and postprocessing analysis. Functional MRI was performed with a standard 1.5-T whole-body scanner. Brain activity was contrasted between an alternating semantic judgment and letter matching task. Twelve right-handed, healthy control subjects and 12 consecutive patients with drug-resistant, localization-related epilepsy were investigated. The semantic condition induced almost invariably left hemispheric activations in Brocas area, the premotor cortex, the dorsolateral prefrontal cortex, and the temporoparietal region. Although real-time analysis reduced noise less effectively than SPM99, visual ratings and lateralization indices produced highly concordant results with both methods. In conclusion, real-time fMRI, as used here, allowed reliable language lateralization and mapping in less than 15 min during routine clinical MRI investigation with no need for postprocessing.

Rhinal-hippocampal theta coherence during declarative memory formation: interaction with gamma synchronization?

The hippocampus and the rhinal cortex, two substructures of the medial temporal lobe, together play a crucial role in human declarative memory formation. To investigate in detail the mechanism connecting these two structures transiently during memory formation we recorded depth EEG in epilepsy patients from within the hippocampus and the rhinal cortex. During this recording, patients performed a single‐trial word list‐learning paradigm with a free recall memory test following a distraction task. Rhinal–hippocampal EEG coherence and spectral power at both locations in the time interval up to 2 s after onset of word presentation were analysed in the frequency range 1–19 Hz. Successful as opposed to unsuccessful memory formation was associated with a general rhinal–hippocampal coherence enhancement, but without alterations in spectral power. Coherence increases in the theta range were correlated with the previously reported memory‐related changes in rhinal–hippocampal gamma phase synchronization. This correlation may suggest an interaction of the two mechanisms during declarative memory formation. While theta coherence might be associated with slowly modulated coupling related to an encoding state, rhinal–hippocampal gamma synchronization may be more closely related to actual memory processes by enabling fast coupling and decoupling of the two structures.

Optimized voxel-based morphometry in children with developmental dyscalculia.

Developmental dyscalculia (DD) is a specific learning disability affecting the normal acquisition of arithmetic skills. Current studies estimate that 3-6% of the school population is affected by DD. Genetic, neurobiological, and epidemiologic evidence indicates that dyscalculia is a brain-based disorder. Imaging studies suggest the involvement of parietal and prefrontal cortices in arithmetic tasks. The aim of the present study was to analyze if children with DD show structural differences in parietal, frontal, and cingulate areas compared to typically achieving children. Magnetic resonance imaging was obtained from 12 children with DD aged 9.3+/-0.2 years and 12 age-matched control children without any learning disabilities on a 1.5 T whole-body scanner. Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures was applied to compare the two groups in order to find differences in cerebral gray and white matter. Compared to controls, children with DD show significantly reduced gray matter volume in the right intraparietal sulcus (IPS), the anterior cingulum, the left inferior frontal gyrus, and the bilateral middle frontal gyri. White matter comparison demonstrates clusters with significantly less volume in the left frontal lobe and in the right parahippocampal gyrus in dyscalculic children. The decreased gray and white matter volumes in the frontoparietal network might be the neurological substrate of impaired arithmetic processing skills. The white matter volume decrease in parahippocampal areas may have influence on fact retrieval and spatial memory processing.

Neural Bases of Cognitive ERPs: More than Phase Reset

Up to now, two conflicting theories have tried to explain the genesis of averaged event-related potentials (ERPs): Whereas one hypothesis claims that ERPs originate from an event-related activation of neural assemblies distinct from background dynamics, the other hypothesis states that ERPs are produced by phase resetting of ongoing oscillatory activity. So far, this question has only been addressed for early ERP components. Late ERP components, however, are generally thought to represent superimposed activities of several anatomically distinct brain areas. Thus, the question of which mechanism underlies the genesis of late ERP components cannot be easily answered based on scalp recordings. In contrast, two well-investigated late ERP components recorded invasively from within the human medial temporal lobe (MTL) in epilepsy patients, the so-called MTL-P300 and the anterior MTL-N400 (AMTL-N400), are based on single source activity. Hence, we investigated whether the MTL-P300 and the AMTL-N400 are based on an event-related activity increase, a phase reset of ongoing oscillatory activity or both. ERPs were recorded from the hippocampus and rhinal cortex in subjects performing a visual oddball paradigm and a visual word recognition paradigm. With wavelet techniques, stimulus-related phase-locking and power changes were analyzed in a frequency range covering 2 to 48 Hz. We found that the MTLP300 is accompanied by both phase reset and power increase and that both effects overlap partly in time. In contrast, the AMTL-N400 is initially associated with phase locking without power increase and only later during the course of the AMTL-N400 we observed an additional power increase. In conclusion, both aspects, event-related activation of neural assemblies and phase resetting of ongoing activity seem to be involved in the generation of late ERP components as recorded in cognitive tasks. Therefore, separate analysis of event-related power and phase-locking changes might reveal specific insights into the mechanisms underlying different cognitive functions.

An event-related brain potential correlate of visual short-term memory

Event-related potentials (ERPs) were recorded as 12 subjects performed a delayed matching to sample task. We presented two bilateral abstract shapes and cued spatially which had to be memorized for a subsequent matching task: left, right or both. During memorization a posterior slow negative ERP wave developed over the hemisphere contralateral to the memorized shape. This effect was similar in high and low memory load trials while the memory figures were visible (for 1000 ms). As the figures disappeared (for 1500 ms), the effect persisted only in the low memory load conditions. We suggest that the contralateral negativity reflects a visual short-term memory process and that capacity limitation in the high memory load condition causes this process to collapse.

Simultaneous EEG-fMRI during a Working Memory Task: Modulations in Low and High Frequency Bands

Background EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown. Methodology In 16 healthy adult subjects, we first investigated EEG-BOLD signal correlations for theta (5–7 Hz), alpha1 (8–10), alpha2 (10–12 Hz), beta1 (13–20), beta2 (20–30 Hz), and gamma (30–40 Hz) during the retention period of a WM task with set size 2 and 5. Secondly, we investigated whether load sensitive brain regions are characterised by effects that relate frequency bands to BOLD signals effects. Principal Findings We found negative theta-BOLD signal correlations in the MPFC, PPC, and cingulate cortex (ACC and PCC). For alpha1 positive correlations with the BOLD signal were found in ACC, MPFC, and PCC; negative correlations were observed in DLPFC, PPC, and inferior frontal gyrus (IFG). Negative alpha2-BOLD signal correlations were observed in parieto-occipital regions. Beta1-BOLD signal correlations were positive in ACC and negative in precentral and superior temporal gyrus. Beta2 and gamma showed only positive correlations with BOLD, e.g., in DLPFC, MPFC (gamma) and IFG (beta2/gamma). The load analysis revealed that theta and—with one exception—beta and gamma demonstrated exclusively positive load effects, while alpha1 showed only negative effects. Conclusions We conclude that the directions of EEG-BOLD signal correlations vary across brain regions and EEG frequency bands. In addition, some brain regions show both load sensitive BOLD and frequency band effects. Our data indicate that lower as well as higher frequency brain oscillations are linked to neurovascular processes during WM.