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Karl Zilles

Publications and source records attributed to Karl Zilles.

At least 109 records · Page 6Linked to original sources
PubMed2003

Activation of Broca's area during the production of spoken and signed language: a combined cytoarchitectonic mapping and PET analysis.

Broca's area in the inferior frontal gyrus consists of two cytoarchitectonically defined regions-Brodmann areas (BA) 44 and 45. Combining probabilistic maps of these two areas with functional neuroimaging data obtained using PET, it is shown that BA45, not BA44, is activated by both speech and signing during the production of language narratives in bilingual subjects fluent from early childhood in both American Sign Language (ASL) and English when the generation of complex movements and sounds is taken into account. It is BA44, not BA45, that is activated by the generation of complex articulatory movements of oral/laryngeal or limb musculature. The same patterns of activation are found for oral language production in a group of English speaking monolingual subjects. These findings implicate BA45 as the part of Broca's area that is fundamental to the modality-independent aspects of language generation.

Adult↗
PubMed2003

Expansion of the neocerebellum in Hominoidea.

Technological and conceptual breakthroughs have led to more serious consideration of the cerebellum as an essential element in cognition. Recent studies show the lateral cerebellum, seat of the neocerebellum, to be most active in cognitive tasks. An examination of the relative volumes of the cerebellar hemispheres in anthropoids would reveal whether some groups show greater neocerebellar development through hemispheric expansion beyond expected allometry, implying a greater contribution of the lateral hemispheres to cognition. This study expands the existing data on primate brain and brain part volumes by incorporating data from both magnetic resonance scans and histological sections for a total sample size of 97 specimens, including 42 apes, 14 humans and 41 monkeys. The resulting volumes of whole brain, cerebellum, vermis, and hemisphere enable a reliable linear regression contrast between hominoids and monkeys, and demonstrate a striking increase in the lateral cerebellum in hominoids. The uniformity of the grade shift suggests that this increase took place in the common ancestor to the hominoids. The importance of the neocerebellum in visual-spatial skills, planning of complex movements, procedural learning, attention switching, and sensory discrimination in manipulation would facilitate the adaptation of these early hominoids to frugivory and suspensory feeding.

Anatomy, Comparative↗
PubMed2003

Comparison of fluorotyrosines and methionine uptake in F98 rat gliomas.

The transport mechanisms of O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) and 2-[(18)F]fluoro-L-tyrosine (FTyr) were compared to those of [(3)H]-Methyl-L-methionine (MET) in F98 rat glioma cells in vitro and by tumor imaging by ex vivo dual tracer autoradiography in F98 rat gliomas. Both, FET and FTyr exhibited similar transport characteristics in F98 glioma cells compared to MET, i.e. mainly a sodium dependent transport similar to system B(0,+) and sodium independent transport via system L. Radioactivity of FET in the acid precipitable fraction was <1% after 120 min incubation time while FTyr and MET exhibited a 15-18% incorporation into proteins. Comparison of FET and FTyr with MET uptake in F98 rat gliomas demonstrated a significant correlation of tumor to brain ratios and a similar intratumoral tracer distribution pattern.

Animals↗
PubMed2003

Are action and perception in near and far space additive or interactive factors?

Functional imaging has revealed differential neural mechanisms underlying action directed toward near or far space. Because some neuropsychological studies of patients with visuospatial neglect failed to show near/far dissociations with perceptual tasks, we investigated whether action and perception elicit distinct cerebral representations in near and far space. We measured regional cerebral blood flow with positron emission tomography in normal volunteers who performed manual line bisection (action) and made line bisection judgments (perception). Stimuli were presented in near space or far space. Far space presentation enhanced activations in occipital cortex extending into the medial occipitotemporal cortex bilaterally, while near space presentation enhanced left occipital-parietal, parietal, and premotor cortex activity. Manual bisection activated the extrastriate, superior parietal, and premotor cortex bilaterally, while bisection judgments activated the right inferior parietal cortex, anterior cingulate, right dorsolateral prefrontal cortex, and extrastriate and superior temporal cortex bilaterally. The neural mechanisms responsible for the two tasks (perceptual/motor) were not differentially modulated by space of presentation.

Adult↗
PubMed2003

In search of the hidden: an fMRI study with implications for the study of patients with autism and with acquired brain injury.

The Embedded Figures Task involves a search for a target hidden in a more complex visual pattern. The task has been used to study local perception and visual search in a range of normal and pathological populations. After acquired brain damage, impairment on embedded figures is strongly associated with aphasia; in the context of developmental disorder, people with autism or with Asperger's syndrome are reliably found to be better than normal controls on the task. The current study employed functional MRI with healthy volunteers to elucidate the brain regions that are specifically involved in the local search aspects of the Embedded Figures Task. We did so by analyzing the neural activations that are implicated in the task over and above those involved in an easier visual search task and in a straightforward shape recognition task. Significant activations (P < 0.05, corrected) specific in the above sense to the Embedded Figures Task were found in left inferior and left superior parietal cortex and in left ventral premotor cortex (inferior frontal gyrus). By contrast, comparing the overall effect of visual search within geometric figures to pure recognition of geometric shapes revealed more widespread activations in parietal, occipital, cerebellar, and frontal areas bilaterally. The implications of these findings for some developmental and acquired pathologies of perceptual functioning are outlined. We also relate our results to studies of local/global processing in other tasks.

Adult↗
PubMed2003

Functional anatomy and differential time courses of neural processing for explicit, inferred, and illusory contours. An event-related fMRI study.

The perception of shape does not necessarily require viewing an explicit outline figure. Using event-related functional magnetic resonance imaging we examined the time courses of neural activations provoked by shapes defined by (1) lines, (2) illusory contour inducers, and (3) reversed inducers. SPM99 was used to analyze the common and differential neural responses associated with the stimuli and their temporal derivatives. Illusory figures versus reversed inducers activated extrastriate cortex. Reversed inducers versus illusory figures activated the right parietal cortex. For both illusory and line contours versus reversed inducers, analysis of the temporal derivatives showed earlier activations in extrastriate and left parietal cortex and for line contours also in the extrastriate cortex bilaterally and in the right parietal cortex; these earlier activations were mirrored by differences in reaction times with subjects responding more slowly to shapes defined by reversed inducers. The results show substantial bottom-up effects (in occipital cortex) in the recognition of illusory and explicit shapes. By contrast, in stimuli where the shape must be inferred, there is greater reliance on right parietal cortex, consistent with increased attentional demands and top-down processing. The temporal derivatives provide useful information on the differential timing of the associated hemodynamic responses in occipital, parietal, and motor cortex.

Adult↗
PubMed2003

In vivo imaging of adenosine A1 receptors in the human brain with [18F]CPFPX and positron emission tomography.

The important roles played by the A(1) adenosine receptor (A(1)AR) in brain physiology and pathology make this receptor a target for in vivo imaging. Here we describe the distribution of A(1)ARs in the living human brain with PET, made possible for the first time by the highly potent and selective A(1)AR antagonist 8-cyclopentyl-3-(3-[(18)F]fluoropropyl)-1-propylxanthine ([(18)F]CPFPX). In vivo data demonstrate a rapid cerebral uptake, peaking at 2.9 +/- 0.6% injected dose/liter at 3.3 +/- 1.3 min, followed by a gradual washout. Consistent with the results of autoradiography, high receptor densities occurred in the putamen and the mediodorsal thalamus. Neocortical regions showed regional differences in [(18)F]CPFPX binding, with high accumulation in temporal > occipital > parietal > frontal lobes and a lower level of binding in the sensorimotor cortex. Ligand accumulation was low in cerebellum, midbrain, and brain stem. Metabolism of [(18)F]CPFPX is rapid outside the central nervous system, but the metabolites do not penetrate the blood-brain barrier. In conclusion, in vivo application of [(18)F]CPFPX, a highly potent and selective PET ligand, for the first time allows the imaging of A(1)ARs in the living human brain.

Adult↗
PubMed2003

Quantitative T1 mapping of hepatic encephalopathy using magnetic resonance imaging.

Changes are shown in the spin-lattice (T1) relaxation time caused by the putative deposition of manganese in various brain regions of hepatic encephalopathy (HE) patients using a novel and fast magnetic resonance imaging (MRI) method for quantitative relaxation time mapping. A new method, T1 mapping with partial inversion recovery (TAPIR), was used to obtain a series of T1-weighted images to produce T1 maps. Imaging of 15 control subjects and 11 patients was performed on a 1.5T MRI scanner. The measurement time per patient with this technique, including adjustments, was approximately 5 minutes. Regions of interest in the globus pallidus, the caudate nucleus, the posterior and anterior limbs of the internal capsule, the putamen, the frontal and occipital white matter, the white matter of the corona radiata, the occipital visual and frontal cortices, and the thalamus were interactively defined in the left hemisphere and analyzed with respect to their T1 values. T1 changes in the brains of HE patients can be determined quantitatively with TAPIR in short, clinically relevant measurement times. Significant correlations between the change in T1 and HE severity have been shown in the globus pallidus, the caudate nucleus, and the posterior limb of the internal capsule. No significant correlation of T1 with grade of HE was found in the putamen, frontal white matter, white matter of the corona radiata, white matter in the occipital lobe, the anterior limb of the internal capsule, visual cortex, thalamus, or frontal cortex. In conclusion, these measurements show that T1 mapping is feasible in short, clinically relevant acquisition times.

Adult↗
PubMed2003

Differential remoteness and emotional tone modulate the neural correlates of autobiographical memory.

Autobiographical memory relies on complex interactions between episodic memory contents, associated emotions and a sense of self-continuity along the time axis of one's life history. The neural correlates underlying autobiographical memory are known to primarily comprise areas of prefrontal cortex, medial and lateral temporal cortex, as well as posterior cingulate and retrosplenial cortex. By contrast, the effect of encoding and/or storage parameters such as the emotional tone of the memories retrieved or the length of the time-interval between the initial encoding of information and retrieval remains to be clarified. Using blocked design functional MRI and statistical parametric mapping, we investigated the impact of remoteness (factor 1: recent, remote) and emotional valence (factor 2: positive, negative) on the neural correlates of autobiographical memory retrieval. Changes in neural activity (P < 0.05, corrected) related to autobiographical memory retrieval (irrespective of remoteness and emotional tone) relative to baseline were observed bilaterally in medial and lateral temporal, temporal-occipital, posterior cingulate and frontal cortices. Recent (relative to remote) memories were associated with differentially increased neural activity bilaterally in the retrosplenial cortex and the hippocampal region, whereas remote (relative to recent) memories did not show any statistically significant differential neural activations. Positive (relative to negative) memories bilaterally activated the orbitofrontal cortex, the temporal pole, as well as medial temporal areas, with the activation peak being in the entorhinal region. By contrast, negative (relative to positive) memories differentially increased neural activity in the right middle temporal gyrus only. The data suggest differential functional roles for temporal, prefrontal and retrosplenial regions during autobiographical memory retrieval depending on the remoteness and the emotional valence of the memories retrieved. In particular, our findings support the 'classic' model of long-term memory processing, which suggests a time-limited differential involvement of the hippocampus in memory consolidation. Interestingly, the observation of such a time-dependent involvement of the hippocampal region in memory consolidation corresponds to the course of retrograde amnesia observed in demented patients, with the loss of recent memories appearing during early stages of the disease when conspicuous neurofibrillary changes are restricted mainly to the hippocampal and parahippocampal regions. Only during later stages, as the neurofibrillary changes spread out to neocortical association areas, do remote memories also become impaired. We conclude that the brain regions involved in autobiographical memory retrieval are influenced by the triggered memories' emotional significance and their relationship to the individual time axis.

Adult↗
PubMed2003

Evaluation of 18F-CPFPX, a novel adenosine A1 receptor ligand: in vitro autoradiography and high-resolution small animal PET.

UNLABELLED: Adenosine modulates brain activity through 4 G protein-coupled receptors, primarily adenosine A(1) receptors (A(1)ARs). A(1)ARs are heterogeneously distributed throughout the brain and participate in many physiologic processes-for example, the induction of sleep and feedback inhibition of excitatory neurotransmission. There is also evidence that A(1)ARs are involved in brain pathologies, including cerebral ischemia, epilepsy, and neurodegeneration. Therefore, measuring A(1)ARs in the living brain has been a long-standing goal. This report describes the preclinical evaluation of (18)F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ((18)F-CPFPX), a novel A(1)AR PET ligand. METHODS: CPFPX, a xanthine-based A(1)AR antagonist, was labeled with either (18)F or (3)H, maintaining identical chemical structures, and evaluated in rats as a putative radioligand for in vivo or in vitro imaging of brain A(1)ARs by quantitative receptor autoradiography and the combination of high-resolution small animal PET and MRI. RESULTS: (3)H-CPFPX bound with nanomolar affinity (K(d), 4.4 nmol/L) to A(1)ARs and showed a distribution typical of cerebral A(1)ARs. In extensive in vitro competition studies, (3)H-CPFPX proved to be a highly selective and specific A(1)AR radioligand. Neither the nonxanthine-type adenosine A(2A) receptor antagonist ZM 241385 nor multiple cholinergic, serotoninergic, and glutamatergic receptor compounds competed for (3)H-CPFPX below the micromolar level. In vivo animal PET and ex vivo autoradiographic experiments measured radioactivity in discrete brain regions after intravenous injection of (18)F-CPFPX. (18)F-CPFPX had excellent in vivo stability and penetrated the blood-brain barrier immediately after injection due to its high lipophilicity. Brain uptake was rapid and particularly high in gray matter regions. Retention of (18)F-CPFPX was highest in the cerebellum, thalamus, and neocortex with evidence of saturable binding. Low binding potentials were found in the midbrain. In vivo displacement PET experiments with the A(1)AR antagonist 8-cyclopentyl-1,3-dipropylxanthine showed a 72% +/- 8% displacement of (18)F-CPFPX. CONCLUSION: (18)F-CPFPX is a highly selective and specific ligand for A(1)ARs and a suitable radioligand for noninvasive PET imaging of A(1)ARs in the living brain. These studies also support the application of high-resolution animal PET as an effective in vivo imaging tool in the evaluation process of new radioligands.

Animals↗
PubMed2002

Transient postnatal thyroxine treatment leads to variation in transmitter binding site densities in the hippocampus of rats.

Newborn rats were treated daily with thyroid hormone (TH) until postnatal day 12. In the adult animals we measured the densities of glutamatergic (N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainic acid (KA)), cholinergic (muscarinic subtype 1 and 2 (M1, M2)), gamma-aminobutyric acid (GABA)ergic (GABA(A)) and serotonergic (5-hydroxytryptamine (5-HT(1A))) binding sites using quantitative receptor-autoradiography with tritiated ligands. In the TH-treated rats the KA binding site density was increased in the stratum oriens of cornu ammonis (CA)3, the terminal field of the infrapyramidal mossy fibers (IPMF). Densities of M2 and 5-HT(1A) were increased in the CA1 region. In contrast, binding site densities for NMDA in the entire hippocampus and for AMPA in the dentate gyrus were reduced, whereas binding site densities for M2 and GABA(A) remained unchanged. From this study we conclude that concomitant with the increase of the IPMF zone the density of the KA binding sites is specifically enhanced. In addition, we found a general shift from binding sites receiving cortical to those receiving subcortical input in the hippocampus.

Age Factors↗
PubMed2002

Differential involvement of parietal and precentral regions in movement preparation and motor intention.

Flexible goal-oriented behavior relies on spatial coordinate transformations and motor control mechanisms, but also on the capability to take advantage of contextual information for steering the sensorimotor machinery. Although accurate performance of a sensorimotor task requires parietal and frontal regions, their differential contribution and functional relationship with other associative regions remains obscure. We have used event-related functional magnetic resonance imaging to measure human cerebral activity associated with motor cognitive processes in the context of delayed performance of an associative visuomotor task. Movement instruction (specified by visual cues) and motor performance (specified by an auditory cue) were separated by a variable delay period. By manipulating the predictive value of the instruction cue, we distinguished delay-related activity influenced by response probabilities (motor preparation and motor inhibition) from delay-related activity unaffected by the likelihood of providing a motor response (motor intention). We found delay-related activity distributed across a cerebral network involving not only frontal circuitry, but also extrastriate and mediotemporal regions. Areas showing motor intentions and preparatory responses were spatially intermingled. Posterior parietal cortex deviated from this pattern, showing delay-related activity regardless of movement probability, but no specific preparatory responses. These results suggest that posterior parietal cortex and dorsal precentral cortex play different strategic roles in handling associative visuomotor problems. While parietal regions cover a range of potential responses defined by the task setting, precentral regions focus on a likely movement. Temporo-prefrontal regions might incorporate contextual information in the visuomotor process by defining potential and probable responses on the basis of the task contingencies.

Acoustic Stimulation↗
PubMed2002

Crossmodal processing of object features in human anterior intraparietal cortex: an fMRI study implies equivalencies between humans and monkeys.

The organization of macaque posterior parietal cortex (PPC) reflects its functional specialization in integrating polymodal sensory information for object recognition and manipulation. Neuropsychological and recent human imaging studies imply equivalencies between human and macaque PPC, and in particular, the cortex buried in the intraparietal sulcus (IPS). Using functional MRI, we tested the hypothesis that an area in human anterior intraparietal cortex is activated when healthy subjects perform a crossmodal visuo-tactile delayed matching-to-sample task with objects. Tactile or visual object presentation (encoding and recognition) both significantly activated anterior intraparietal cortex. As hypothesized, neural activity in this area was further enhanced when subjects transferred object information between modalities (crossmodal matching). Based on both the observed functional properties and the anatomical location, we suggest that this area in anterior IPS is the human equivalent of macaque area AIP.

Adult↗
PubMed2002

Multiple movement representations in the human brain: an event-related fMRI study.

Neurovascular correlates of response preparation have been investigated in human neuroimaging studies. However, conventional neuroimaging cannot distinguish, within the same trial, between areas involved in response selection and/or response execution and areas specifically involved in response preparation. The specific contribution of parietal and frontal areas to motor preparation has been explored in electrophysiological studies in monkey. However, the associative nature of sensorimotor tasks calls for the additional contributions of other cortical regions. In this article, we have investigated the functional anatomy of movement representations in the context of an associative visuomotor task with instructed delays. Neural correlates of movement representations have been assessed by isolating preparatory activity that is independent from the performance of an actual motor act, or from the presence of a response's target. Movement instruction (specified by visual cues) and motor performance (specified by an auditory cue) were separated by a variable delay period. We have used whole-brain event-related fMRI to measure human brain activity during the performance of such a task. We have focused our analysis on specific preparatory activity, defined as a sustained response over variable delay periods between a transient visual instruction cue and a brief motor response, temporally independent from the transient events. Behavioral and electrophysiological controls ensured that preparatory activity was not contaminated by overt motor responses or working memory processes. We report suggestive evidence for multiple movement representations in the human brain. Specific sustained activity in preparation for an action was found not only in parieto-frontal regions but also in extrastriate areas and in the posterior portion of the superior temporal sulcus. We suggest that goal-directed preparatory activity relies on both visuomotor and visuoperceptual areas. These findings point to a functional-anatomical basis for the integration of perceptual and executive processes.

Adult↗
PubMed2002

Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes.

Astrocytes play a key role in the pathogenesis of ammonia-induced neurotoxicity and hepatic encephalopathy. As shown here, ammonia induces protein tyrosine nitration in cultured rat astrocytes, which is sensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. A similar pattern of nitrated proteins is produced by NMDA. Ammonia-induced tyrosine nitration depends on a rise in [Ca2+]i, IkB degradation, and NO synthase (iNOS) induction, which are prevented by MK-801 and the intracellular Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). Moreover, the increase in tyrosine nitration is blunted by L-NMMA, 1400W, uric acid, Cu, Zn-superoxide dismutase/catalase treatment, and methionine-sulfoximine, which indicate the involvement of reactive nitrogen intermediates and intracellular glutamine accumulation. Such reactive nitrogen intermediates additionally mediate ammonia-induced phosphorylation of the MAP-kinases Erk-1/Erk-2 and p38MAPK. Among the proteins, which are tyrosine -nitrated by ammonia, glyceraldehyde-3-phosphate dehydrogenase, the peripheral-type benzodiazepine receptor, Erk-1, and glutamine synthetase are identified. Ammonia-induced nitration of glutamine synthetase is associated with a loss of enzymatic activity. Astroglial protein tyrosine nitration is found in brains from rats after acute ammonia-intoxication or after portacaval anastomosis, indicating the in vivo relevance of the present findings. The production of reactive nitrogen intermediates and protein tyrosine nitration may alter astrocyte function and contribute to ammonia neurotoxicity.

Ammonia↗