Peter Klaver - Academia.edu (original) (raw)

Papers by Peter Klaver

NeuroImage, 2008

Little is known about the neural development underlying high order visual perception. For example... more Little is known about the neural development underlying high order visual perception. For example, in detection of structures by coherently moving dots, motion information must interact with shape-based information to enable object recognition. Tasks involving these different motion-based discriminations are known to activate distinct specialized brain areas in adults. Here, we investigate neural development of normally developing children using functional magnetic resonance imaging (fMRI) during perception of randomly moving point-light dots (RM), coherently moving dots that formed a 3D rotating object (SFM) and static dots. Perception of RM enhanced neural activity as compared with static dots in motion processing-related visual areas, including visual area 3a (V3a), and middle temporal area (hMT+) in 10 adults (age 20-30 years). Children (age 5-6 years) showed less pronounced activity in area V3a than adults. Perception of SFM induced enhanced neural activity as compared to RM in adults in the left parietal shape area (PSA), whereas children increased neural activity within dorsal (V3a) and ventral brain areas (lingual gyrus) of the occipital cortex. These findings provide evidence of neural development within the dorsal pathway. First, maturation was associated with enhanced activity in specialized areas within the dorsal pathway during RM perception (V3a) and SFM perception (PSA). Secondly, high order visual perception-related neural development was associated with a shift in neural activity from low level shape and motion specialized areas in children, including partially immature area V3a, to high order areas in the parietal lobule (PSA) in adults.

Human declarative memory formation crucially depends on processes within the medial temporal lobe... more Human declarative memory formation crucially depends on processes within the medial temporal lobe (MTL). These processes can be monitored in real-time by recordings from depth electrodes implanted in the MTL of patients with epilepsy who undergo presurgical evaluation. In our studies, patients performed a word memorization task during depth EEG recording. Afterwards, the difference between event-related potentials (ERPs) corresponding to subsequently remembered versus forgotten words was analyzed. These kind of studies revealed that successful memory encoding is characterized by an early process generated by the rhinal cortex within 300 ms following stimulus onset. This rhinal process precedes a hippocampal process, which starts about 200 ms later. Further investigation revealed that the rhinal process seems to be a correlate of semantic preprocessing which supports memory formation, whereas the hippocampal process appears to be a correlate of an exclusively mnemonic operation. These studies yielded only indirect evidence for an interaction of rhinal cortex and hippocampus. Direct evidence for a memory related cooperation between both structures, however, has been found in a study analyzing so called gamma activity, EEG oscillations of around 40 Hz. This investigation showed that successful as opposed to unsuccessful memory formation is accompanied by an initial enhancement of rhinal-hippocampal phase synchronization, which is followed by a later desynchronization. Present knowledge about the function of phase synchronized gamma activity suggests that this phase coupling and decoupling initiates and later terminates communication between the two MTL structures. Phase synchronized rhinal-hippocampal gamma activity may, moreover, accomplish Hebbian synaptic modifications and thus provide an initial step of declarative memory formation on the synaptic level.

PLoS ONE, 2012

Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but chan... more Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.

Neuropsychologia, 2009

The underlying neural mechanisms of developmental dyscalculia (DD) are still far from being clear... more The underlying neural mechanisms of developmental dyscalculia (DD) are still far from being clearly understood. Even the behavioral processes that generate or influence this heterogeneous disorder are a matter of controversy. To date, the few studies examining functional brain activation in children with DD mainly focus on number and counting related tasks, whereas studies on more general cognitive domains that are involved in arithmetical development, such as working memory are virtually absent. There are several studies showing a close relationship between DD and spatial working memory . Low working memory capacity impedes both efficiency and learning of number transcoding in children. . The development of working memory in normally achieving and subtypes of learning disabled children. Child Development, 60(4), 973-980]. The relationship between these two mechanisms is still matter of debate, but this study follows the assumption that poor spatial working memory capacity may hinder the acquisition of spatial number representations in children with DD [Geary, D. C. (1993). Mathematical disabilities: Cognitive, neuropsychological, and genetic components. Psychological Bulletin, 114(2), 345-362; von Aster, M., & Shalev, R. S. (2007). Number development and developmental dyscalculia. Developmental Medicine and Child Neurology, 49(11), 868-873].

NeuroImage, 2005

Amplitudes of the P3 recorded invasively from the medial temporal lobe (MTL-P3) have been reporte... more Amplitudes of the P3 recorded invasively from the medial temporal lobe (MTL-P3) have been reported to be reduced on the side of a mediotemporal epileptogenic focus. This reduction has been attributed to the massive cell loss within the hippocampus associated with hippocampal sclerosis. It has remained unclear how functional connectivity between the hippocampus and rhinal cortex, as well as within the hippocampus, is altered in hippocampal sclerosis. To investigate this issue, we analyzed to what extent stimulus-related phase-locking and power changes within the low-frequency range (2-30 Hz) and within the gamma band (32-48 Hz), as well as rhinal-hippocampal phase synchronization contribute to the averaged MTL-P3 potentials. Eventrelated responses were recorded via bilateral depth electrodes in epilepsy patients with unilateral hippocampal sclerosis, who performed a visual oddball experiment. On the contralateral (nonsclerotic) side, successful target detection was associated with an increase of power and phase locking of hippocampal activity in both the low-frequency range and in the gamma range. Besides, there were rhinal-hippocampal synchronization enhancements in the theta and gamma range. On the ipsilateral (sclerotic) side, the event-related power increase in the lowfrequency range had almost disappeared, a finding likely to be explained by the loss of principle neurons. However, low-frequency phase-locking, rhinal-hippocampal synchronization, as well as event-related power changes in the gamma range persisted ipsilaterally, although there were differences in temporal and spectral characteristics. These findings support the hypothesis that functional connectivity between hippocampus and rhinal cortex, as well as intrahippocampal connectivity, are partially preserved in hippocampal sclerosis. D 2004 Elsevier Inc. All rights reserved.

NeuroImage, 2009

Background: EEG studies of working memory (WM) have demonstrated load dependent frequency band mo... more 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.

NeuroImage, 2006

Concrete words that are readily imagined are better remembered than abstract words. Theoretical e... more Concrete words that are readily imagined are better remembered than abstract words. Theoretical explanations for this effect either claim a dual coding of concrete words in the form of both a verbal and a sensory code (dual-coding theory), or a more accessible semantic network for concrete words than for abstract words (contextavailability theory). However, the neural mechanisms of improved memory for concrete versus abstract words are poorly understood. Here, we investigated the processing of concrete and abstract words during encoding and retrieval in a recognition memory task using event-related functional magnetic resonance imaging (fMRI). As predicted, memory performance was significantly better for concrete words than for abstract words. Abstract words elicited stronger activations of the left inferior frontal cortex both during encoding and recognition than did concrete words. Stronger activation of this area was also associated with successful encoding for both abstract and concrete words. Concrete words elicited stronger activations bilaterally in the posterior inferior parietal lobe during recognition. The left parietal activation was associated with correct identification of old stimuli. The anterior precuneus, left cerebellar hemisphere and the posterior and anterior cingulate cortex showed activations both for successful recognition of concrete words and for online processing of concrete words during encoding. Additionally, we observed a correlation across subjects between brain activity in the left anterior fusiform gyrus and hippocampus during recognition of learned words and the strength of the concreteness effect. These findings support the idea of specific brain processes for concrete words, which are reactivated during successful recognition.

Brain Research Reviews, 2003

force of 2 N had to be maintained (pinch grip). Visual feedback was only provided between single ... more force of 2 N had to be maintained (pinch grip). Visual feedback was only provided between single recording trials, but not while EEG and EMG data were registered. Task-related coherence [TRCoh] was computed by subtracting coherence during rest from coherence during the motor task. The main result was a 47% increase of TRCoh between bipolar channels inside the STN. This task-related synchrony occurred specifically in a high frequency range from 60 to 100 Hz. The results in lower frequency bands showed high inter-subject variability. The STN high-frequency synchrony at 60-100 Hz was not present in the STN-cortex or cortex-muscle coherence data. We conclude that highfrequency synchrony occurs as a task-related neuronal firing pattern during voluntary motor behavior in the STN. Since this 60-100 Hz synchrony was restricted to the local signals (ie, local field potentials) in the STN, this finding would be consistent with local motor signal processing in the STN. These data support the concept that synchrony of neuronal assemblies is implemented at high frequencies in local or regional circuits while long-range synchrony occurs at lower frequencies (e.g., beta-or alpha band, cf.

Using event-related fMRI, we scanned young healthy subjects while they memorized real-world photo... more Using event-related fMRI, we scanned young healthy subjects while they memorized real-world photographs and subsequently tried to recognize them within a series of new photographs. We confirmed that activity in the medial temporal lobe (MTL) and inferior prefrontal cortex correlates with declarative memory formation as defined by the subsequent memory effect, stronger responses to subsequently remembered than forgotten items. Additionally, we confirmed that activity in specific regions within the parietal lobe, anterior prefrontal cortex, anterior cingulate and cerebellum correlate with recognition memory as measured by the conventional old/new effect, stronger responses for recognized old items (hits) than correctly identified new items (correct rejections). To obtain a purer measure of recognition success, we introduced two recognition effects by comparing brain responses to hits and old items misclassified as new (misses). The positive recognition effect (hits > misses) revealed prefrontal, parietal and cerebellar contributions to recognition, and in line with electrophysiological findings, the negative recognition effect (hits < misses) revealed an anterior medial temporal contribution. Finally, by inclusive masking, we identified temporal and cerebellar brain areas that support both declarative memory formation and retrieval. For matching operations during recognition, these areas may re-use representations formed and stored locally during encoding.

The Block Suppression Paradigm developed by is based on the Corsi Block tapping test and requires... more The Block Suppression Paradigm developed by is based on the Corsi Block tapping test and requires that a subject reproduces every 2nd block in a given sequence. Results from two studies of a standardized version, the Block Suppression Test (BST), are presented here. In Study 1 the BST was administered to 48 healthy subjects along with a battery of comprehensive neuropsychological tests. The reliability of the BST proved satisfactory under psychometric analysis, while Principal Component Analysis (PCA) confirmed its validity. In Study 2 the BST was administered to a clinical sample of 31 brain-damaged patients to demonstrate its clinical practicability.

& Up to now, two conflicting theories have tried to explain the genesis of averaged event-related... more & 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 eventrelated 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 MTL-P300 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 eventrelated power and phase-locking changes might reveal specific insights into the mechanisms underlying different cognitive functions. &

Our event-related functional MRI (efMRI) study investigates whether visual advance information (A... more Our event-related functional MRI (efMRI) study investigates whether visual advance information (AI) affects rather perceptual or central response-related processing areas. Twelve subjects were required to make a go/no-go decision to a conjunction of a specific color and motion direction. The stimuli were preceded by a cue, providing 100% valid advance information about motion direction. Partial and full advance information (PAI and FAI) predicted possible targets, respectively, certain nontargets, neutral cues (NAI) gave no prediction. The time between cue and stimulus (stimulus onset asynchrony, SOA) was varied. A response benefit was found after PAI as compared with NAI. The benefit was small with a short SOA (150 ms), increased with intermediate SOA (450 ms) and sustained with long SOA (750 ms). Perceptual and central processing areas were more active with increasing SOA, but only central response-related processing areas were selectively modulated by cue information. In particular, supplementary motor area and bilateral inferior parietal lobe were more active with PAI than with NAI. If comparing NAI with FAI, more errors were made and activity was larger in central processing areas. Our results suggest that, depending on the processing time, cues providing perceptual information modulate central response-related processes. D 2004 Elsevier B.V. All rights reserved.

In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity ... more In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly executed by one hemisphere. To search for neural correlates of hormonally mediated neural plasticity in humans, we thus conducted a functional magnetic resonance imaging study measuring brain activity related to a semantic decision task in the language domain. This was contrasted with a letter-matching task in the perceptual domain, in which we expected no steroid hormone-mediated effect. We investigated 12 young healthy women in a counterbalanced repeated-measure design during low-steroid menstruation and high-steroid midluteal phase. Steroid serum levels correlated with the volume and lateralization of particular brain activations related to the semantic task but not with brain activity related to the perceptual task. More specifically, bilateral superior temporal recruitment correlated positively with progesterone and medial superior frontal recruitment with both progesterone and estradiol serum levels, whereas activations in inferior and middle frontal cortex were unaffected by steroid levels. In contrast to these specific interactions, testosterone levels correlated nonselectively with overall activation levels by neural and/or vascular factor(s). In conclusion, our data demonstrate steroid hormone responsivity in the adult human brain by revealing neural plasticity in the language domain, which appears hormone, task, and region specific.

The medial temporal lobe (MTL) is the core structure of the declarative memory system, but which ... more The medial temporal lobe (MTL) is the core structure of the declarative memory system, but which specific operation is performed by anatomically defined MTL substructures? One hypothesis proposes that the hippocampus carries out an exclusively mnemonic operation during declarative memory formation that is insensitive to content, whereas the rhinal cortex carries out an operation supporting memory formation indirectly. To explore the interaction between a salient item feature and memory formation, we contrasted neural correlates of memory formation of high-and low-frequency words. Event-related potentials (ERPs) were recorded via depth electrodes from within the MTL in nine epilepsy patients while they memorized single words. To assess memory formation, ERPs to words subsequently recalled in a free recall test were contrasted with ERPs to forgotten words. More high-than low-frequency words were remembered. High-frequency words led to distinct ERP subsequent memory effects in rhinal cortex and hippocampus. Low-frequency words, however, were only associated with the hippocampal ERP effect. The anatomically restricted interaction between word frequency and memory formation might indicate a semantically affected operation in the parahippocampal region supporting memory formation indirectly. By contrast, the missing interaction in hippocampal recordings might suggest a direct correlate of declarative memory formation that is insensitive to item properties. Hippocampus 2002;12:514 -519.

The hippocampus and the rhinal cortex, two substructures of the medial temporal lobe, together pl... more 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.

This study investigated how different spectral and nonlinear EEG measures covaried with alpha pow... more This study investigated how different spectral and nonlinear EEG measures covaried with alpha power during auditory alpha biofeedback training, performed by 13 healthy subjects. We found a significant positive correlation of alpha power with the largest Lyapunov-exponent, pointing to an increased dynamical instability of the EEG accompanying alpha enhancement. Alpha power amplification, moreover, was significantly correlated with a decrease of spectral entropy within the alpha range. This outcome reflects a sharpening of the alpha peak during biofeedback training. The fact that the sharpening effect clearly preceded the increase of alpha amplitude could be exploited in future biofeedback settings.