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Biomedical subjects

Hans-Jochen Heinze

Publications and source records attributed to Hans-Jochen Heinze.

At least 19 recordsLinked to original sources

Activation of midbrain structures by associative novelty and the formation of explicit memory in humans.

Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study, participants distinguished between familiar and novel configurations of pairs of items which had been studied together by either learning the location or the identity of the items. In the second study, participants studied words by either rating the words' pleasantness or counting syllables. The ventral tegmental area and medial substantia nigra showed increased activation by associative novelty (first study) and subsequent free recall performance (second study). In both studies, this activation accompanied hippocampal activation, but was unaffected by the study task. Thus midbrain regions seem to participate selectively in hippocampus-dependent processes of associative novelty and explicit memory formation, but appear to be unaffected by other task-relevant aspects.

Adolescent↗

Short-term plasticity of the primary somatosensory cortex during tool use.

Plastic changes within the primary somatosensory cortex (SI) related to tool use are reported. Subjects manipulated a small object with a pair of tongs or with their hand. Functional organization of SI during tool use was compared with that during executing the task with the fingers and during rest, respectively. Topography of SI was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digit (D5). We found that cortical representations of D1 and D5 are further apart during tool use than during non-tool use and rest. Our data suggest that somatosensory cortical maps are part of the neural network representing the modified schema of the hand in which the tool was incorporated.

Adult↗

Effects of GSM electromagnetic field on the MEG during an encoding-retrieval task.

Potential effects of GSM 1800 electromagnetic fields (EMF) on verbal memory encoding were investigated by recording event-related magnetic fields (ERMF) from the brain during subsequent memory retrieval. Twelve normal subjects participated in the study. After encoding words from a study list presented in the first phase they had to discriminate old from new words mixed together in a test list presented during the second phase. All subjects performed two experimental sessions, one with exposure to EMF during the study phase, and one without. Exposure to EMF changed an early (350-400 ms) task-specific component of the ERMF indicating an interference of EMF and item encoding. Behavioural measures were not significantly affected. Adverse health effects cannot be derived from these data.

Adolescent↗

Attention to features precedes attention to locations in visual search: evidence from electromagnetic brain responses in humans.

Single-unit recordings in macaque extrastriate cortex have shown that attentional selection of nonspatial features can operate in a location-independent manner. Here, we investigated analogous neural correlates at the neural population level in human observers by using simultaneous event-related potential (ERP) and event-related magnetic field (ERMF) recordings. The goals were to determine (1) whether task-relevant features are selected before attention is allocated to the location of the target, and (2) whether this selection reflects the locations of the relevant features. A visual search task was used in which the spatial distribution of nontarget items with attended feature values was varied independently of the location of the target. The presence of task-relevant features in a given location led to a change in ERP/ERMF activity beginning approximately 140 msec after stimulus onset, with a neural origin in the ventral occipito-temporal cortex. This effect was independent of the location of the actual target. This effect was followed by lateralized activity reflecting the allocation of attention to the location of the target (the well known N2pc component), which began at approximately 170 msec poststimulus. Current source localization indicated that the allocation of attention to the location of the target originated in more anterior regions of occipito-temporal cortex anterior than the feature-related effects. These findings suggest that target detection in visual search begins with the detection of task-relevant features, which then allows spatial attention to be allocated to the location of a likely target, which in turn allows the target to be positively identified.

Adult↗

Different cortical activations for subjects using allocentric or egocentric strategies in a virtual navigation task.

Subjects were required to navigate through a virtual 3D labyrinth presented on a screen while fMRI images were obtained. Contrasting the fMRI images obtained during the navigation trials with appropriate control conditions revealed a bilateral network comprising the parietal lobe (including the intraparietal sulcus) and various lateral and medial premotor areas. The subjects using an allocentric strategy showed stronger activation in the medial temporal areas including the parahippocampal region, the hippocampus, and the thalamus. In addition, the cerebellum was also active in those subjects. We believe that this activation pattern is related to visually guided memory retrieval based on generalized spatial maps. The stronger activation in the thalamic-basal ganglia-cerebellar-loop points to a more automatic support of memory and attentional processes possibly supporting memorization of spatial maps.

Adult↗

Popout modulates focal attention in the primary visual cortex.

The influence of context-dependent interactions on attention-related neural activity was studied in the human primary visual cortex (V1) with event-related fMRI. Retinotopic field-sign mapping was used to determine the localization of V1 with respect to adjacent retinotopic areas. Observers reported the orientation of a Gabor patch at pre-cued extrafoveal locations when it was salient among distractor Gabors and when it was not. Saliency was caused by local orientation contrast between Gabors-a mechanism that is thought to arise from context-dependent interactions in the V1 proper. A comparison of the attention-related BOLD response for salient and non-salient stimuli in V1 revealed that salient Gabors caused a significantly smaller BOLD response than non-salient Gabors. This differential effect was not observed in higher-order visual areas (V3/V3A, MT+/LO, IPS). When attention was not focused onto the target, the size of the BOLD response was generally reduced in all visual areas, and no difference was seen in V1 for salient and non-salient Gabors. These findings suggest that contextual interactions underlying saliency influence attentional modulations in V1 and support the view that perceptual and attentional mechanisms share neural circuits at this early stage of visual processing.

Adult↗

Human hippocampal and parahippocampal activity during visual associative recognition memory for spatial and nonspatial stimulus configurations.

Evidence from animal studies points to the importance of the parahippocampal region (PHR) [including entorhinal, perirhinal, and parahippocampal (PHC) cortices] for recognition of visual stimuli. Recent findings in animals suggest that PHR may also be involved in visual associative recognition memory for configurations of stimuli. Thus far, however, such involvement has not been demonstrated in humans. In fact, it has been argued that associative recognition in humans is critically dependent on the hippocampal formation (HF). To better understand the division of function between HF and PHR during recognition memory in humans, we measured the activity of both areas in healthy young adults during an associative recognition memory task using functional magnetic resonance imaging. To more precisely characterize the nature of the associations that might be coded by the HF and PHR during recognition, subjects were required to learn and were later tested for associations based on either the spatial arrangements of two stimuli or the identity of two stimuli (a face and a tool). An area in the PHC was found to be more active for recognized old configurations than new configurations in both the spatial and identity conditions. The HF, on the other hand, was more active for recognition of new configurations than old configurations and also more active in the spatial than the identity condition. These data highlight the involvement of PHR in the long-term coding of associative relationships between stimuli and help to clarify the nature of its functional distinction from the HF.

Adult↗

Focal thinning of the cerebral cortex in multiple sclerosis.

Brain atrophy as determined by quantitative MRI can be used to characterize disease progression in multiple sclerosis. Many studies have addressed white matter (WM) alterations leading to atrophy, while changes of the cerebral cortex have been studied to a lesser extent. In vivo, the cerebral cortex has been difficult to study due to its complex structure and regional variability. Measurement of cerebral cortex thickness at different disease stages may provide new insights into grey matter (GM) pathology. In the present investigation, we evaluated in vivo cortical thickness and its relationship to disability, disease duration, WM T2 hyper-intense and T1 hypo-intense lesion volumes. High-resolution MRI brain scans were obtained in 20 patients with clinically definite multiple sclerosis and 15 age-matched normal subjects. A novel method of automated surface reconstruction yielded measurements of the cortical thickness for each subject's entire brain and computed cross-subject statistics based on the cortical anatomy. Statistical thickness difference maps were generated by performing t-tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between cortical thickness and clinical variables. The mean overall thickness of the cortical ribbon was reduced in multiple sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients). In patients, we found significant main effects for disability, disease duration, T2 and T1 lesion volumes. The visualization of statistical difference maps of the cortical GM thickness on inflated brains across the cortical surface revealed a distinct distribution of significant focal thinning of the cerebral cortex in addition to the diffuse cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)] brain regions was observed, even early in the course of the disease or in patients with mild disability. Patients with longstanding disease or severe disability, however, presented additionally with focal thinning of the motor cortex area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)]. We conclude that in vivo measurement of cortical thickness is feasible in patients suffering from multiple sclerosis. The data provide new insight into the cortical pathology in multiple sclerosis patients, revealing focal cortical thinning beside an overall reduction of the cortical thickness with disease progression.

Adult↗

Hippocampal N-acetyl aspartate levels do not mirror neuronal cell densities in creatine-supplemented epileptic rats.

For neuroprotective therapy of neurodegenerative diseases creatine treatment has gained special interest because creatine has been shown to cross the blood-brain barrier, accumulate in the human brain in vivo and cause delayed neuronal cell death in a large number of animal models. Here, we used the pilocarpine model of temporal lobe epilepsy to determine whether creatine administration is able to attenuate the epilepsy-associated decrease in hippocampal N-acetyl aspartate (NAA) concentrations, impairment of mitochondrial function and neuronal cell loss. In vivo1H-NMR spectroscopy showed, in epileptic rats after creatine administration, higher hippocampal NAA concentrations, suggesting improved neuronal survival. However, in vitro observation of hippocampal slices from creatine-treated epileptic rats revealed a more pronounced loss of pyramidal neurons and decrease in activity of mitochondrial enzymes in hippocampal subfields. This indicates that NAA concentrations measured by in vivo1H-NMR spectroscopy reflect alterations of metabolism rather than neuronal cell densities. Our data indicate an adverse effect of creatine on neuronal survival under conditions of enhanced neuronal activity.

Animals↗

Delayed striate cortical activation during spatial attention.

Recordings of event-related potentials (ERPs) and event-related magnetic fields (ERMFs) were combined with functional magnetic resonance imaging (fMRI) to study visual cortical activity in humans during spatial attention. While subjects attended selectively to stimulus arrays in one visual field, fMRI revealed stimulus-related activations in the contralateral primary visual cortex and in multiple extrastriate areas. ERP and ERMF recordings showed that attention did not affect the initial evoked response at 60-90 ms poststimulus that was localized to primary cortex, but a similarly localized late response at 140-250 ms was enhanced to attended stimuli. These findings provide evidence that the primary visual cortex participates in the selective processing of attended stimuli by means of delayed feedback from higher visual-cortical areas.

Adult↗

Perceptual priming versus explicit memory: dissociable neural correlates at encoding.

We addressed the hypothesis that perceptual priming and explicit memory have distinct neural correlates at encoding. Event-related potentials (ERPs) were recorded while participants studied visually presented words at deep versus shallow levels of processing (LOPs). The ERPs were sorted by whether or not participants later used studied words as completions to three-letter word stems in an intentional memory test, and by whether or not they indicated that these completions were remembered from the study list. Study trials from which words were later used and not remembered (primed trials) and study trials from which words were later used and remembered (remembered trials) were compared to study trials from which words were later not used (forgotten trials), in order to measure the ERP difference associated with later memory (DM effect). Primed trials involved an early (200-450 msec) centroparietal negative-going DM effect. Remembered trials involved a late (900-1200 msec) right frontal, positive-going DM effect regardless of LOP, as well as an earlier (600-800 msec) central, positive-going DM effect during shallow study processing only. All three DM effects differed topographically, and, in terms of their onset or duration, from the extended (600-1200 msec) fronto-central, positive-going shift for deep compared with shallow study processing. The results provide the first clear evidence that perceptual priming and explicit memory have distinct neural correlates at encoding, consistent with Tulving and Schacter's (1990) distinction between brain systems concerned with perceptual representation versus semantic and episodic memory. They also shed additional light on encoding processes associated with later explicit memory, by suggesting that brain processes influenced by LOP set the stage for other, at least partially separable, brain processes that are more directly related to encoding success.

Adult↗

GABA-ergic modulation of prefrontal spatio-temporal activation pattern during emotional processing: a combined fMRI/MEG study with placebo and lorazepam.

Various prefrontal cortical regions have been shown to be activated during emotional stimulation, whereas neurochemical mechanisms underlying emotional processing in the prefrontal cortex remain unclear. We therefore investigated the influence of the GABA-A potentiator lorazepam on prefrontal cortical emotional-motor spatio-temporal activation pattern in a combined functional magnetic resonance imaging/magnetoencephalography study. Lorazepam led to the reversal in orbito-frontal activation pattern, a shift of the early magnetic field dipole from the orbito-frontal to medial prefrontal cortex, and alterations in premotor/motor cortical function during negative and positive emotional stimulation. It is concluded that negative emotional processing in the orbito-frontal cortex may be modulated either directly or indirectly by GABA-A receptors. Such a modulation of orbito-frontal cortical emotional function by lorazepam has to be distinguished from its effects on cortical motor function as being independent from the kind of processing either emotional or nonemotional.

Adult↗

Brain potential and functional MRI evidence for how to handle two languages with one brain.

Bilingual individuals need effective mechanisms to prevent interference from one language while processing material in the other. Here we show, using event-related brain potentials and functional magnetic resonance imaging (fMRI), that words from the non-target language are rejected at an early stage before semantic analysis in bilinguals. Bilingual Spanish/Catalan and monolingual Spanish subjects were instructed to press a button when presented with words in one language, while ignoring words in the other language and pseudowords. The brain potentials of bilingual subjects in response to words of the non-target language were not sensitive to word frequency, indicating that the meaning of non-target words was not accessed in bilinguals. The fMRI activation patterns of bilinguals included a number of areas previously implicated in phonological and pseudoword processing, suggesting that bilinguals use an indirect phonological access route to the lexicon of the target language to avoid interference.

Adult↗

Analysis of pathways mediating preserved vision after striate cortex lesions.

This study investigated the neural substrates of preserved visual functioning in a patient with homonymous hemianopsia and Riddoch syndrome after a posterior cerebral artery stroke affecting the primary visual cortex (area V1). The limited visual abilities of this patient included above-chance verbal reports of movement and color change as well as discrimination of movement direction in the hemianopic field. Functional magnetic resonance imaging showed that motion and color-change stimuli presented to the hemianopic field produced activation in several extrastriate areas of the lesioned hemisphere that were defined using retinotopic mapping. Magnetoencephalographic recordings indicated that evoked activity occurred earlier in the higher-tier visual areas V4/V8 and V5 than in the lower-tier areas V2/V3 adjacent to the lesion. In addition, the functional magnetic resonance imaging analysis showed an increased functional connectivity between areas V4/V8 and V5 of the lesioned hemisphere in comparison with the same areas in the intact hemisphere during the presentation of color changes. These results suggest that visual perception after the V1 lesion in Riddoch syndrome is mediated by subcortical pathways that bypass V1 and project first to higher-tier visual areas V5 and V4/V8 and subsequently to lower-tier areas V2/V3.

Adult↗

Facioscapulohumeral muscular dystrophy with EcoRI/BlnI fragment size of more than 32 kb.

Facioscapulohumeral muscular dystrophy (FSHD) is associated with the deletion of a variable number of 3.3-kb subunits of a tandemly arranged repeat (D4Z4) on chromosome 4q35. EcoRI/BlnI fragments in the range of 10-35 kb are currently defined as disease-associated. Diagnosis of FSHD is frequently complicated by interchromosomal exchange with a homologous locus on 10q26. We present clinical and laboratory data of six subjects from two unrelated families with a marked FSHD phenotype and EcoRI/BlnI fragments of 39 and 33 kb, respectively. Origin on chromosome 4q35 was confirmed by haplotype analysis in the first family and was supported by pulsed field gel electrophoresis data in the second family. Our data further confirm the existence of a region of overlap of normal and pathological fragments. Fragments from this region can obviously be associated with marked FSHD phenotypes. Furthermore, application of linked markers and resolution of all EcoRI/BlnI fragments by pulsed field gel electrophoresis in addition to routine laboratory tests considerably augments the information obtained from molecular tests, upon which genetic counselling can then be based.

Adult↗

Word order in sentence processing: an experimental study of verb placement in German.

We examine the question of whether the human comprehension device exhibits word-order preferences during on-line sentence comprehension. The focus is on the positioning of finite verbs and auxiliaries relative to subjects and objects in German. Results from three experiments (using self-paced reading and event-related brain potentials) show that native speakers of German prefer to process finite verbs in second position (i.e., immediately after the subject and before the object). We will account for this order preference in terms of the relative processing costs associated with SVfO and SOVf. Our finding that word-order preferences play an important role in the on-line comprehension of German sentences is compatible with results from previous studies on English and other languages.

Adult↗

Localizing visual discrimination processes in time and space.

Previous studies of visual processing in humans using event-related potentials (ERPs) have demonstrated that task-related modulations of an early component called the "N1" wave (140-200 ms) reflect the operation of a voluntary discrimination process. Specifically, this component is larger in tasks requiring target discrimination than in tasks requiring simple detection. The present study was designed to localize this discriminative process in both time and space by means of combined magnetoencephalographic (MEG) and ERP recordings. Discriminative processing led to differential ERP and MEG activity beginning within 150 ms of stimulus onset. Source localization of the combined ERP/MEG data was performed using anatomical constraints from structural magnetic resonance images. These analyses revealed highly reliable and focused activity in regions of inferior occipital-temporal cortex. These findings indicate that the earliest measurable correlates of discriminative operations in the visual system appear as neural activity in circumscribed regions of the ventral processing stream.

Adult↗