Publications by authors named "Christian A Kell"

31 Publications

Neurocognitive deficits in patients suffering from glioma in speech-relevant areas of the left hemisphere.

Clin Neurol Neurosurg 2021 08 10;207:106816. Epub 2021 Jul 10.

Department of Neurosurgery, University Hospital Frankfurt, Goethe University, Schleusenweg 2-16, 60528 Frankfurt/Main, Germany; University Cancer Center Frankfurt (UCT), University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, German Cancer Research Center (DKFZ), Stiftung des öffentlichen Rechts, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address:

Objective: Patients with brain tumors frequently present neurocognitive deficits. Aiming at better understanding the impact of tumor localization on neurocognitive processes, we evaluated neurocognitive function prior to glioma surgery within one of four specific regions in the left speech-dominant hemisphere.

Methods: Between 04/2011 and 12/2019, 43 patients undergoing neurocognitive evaluation prior to awake surgery for gliomas (WHO grade I: 2; II: 6; III: 23; IV: 11) in the inferior frontal gyrus (IFG; n = 20), the anterior temporal lobe (ATL; n = 6), the posterior superior temporal region/supramarginal gyrus (pST/SMG; n = 7) or the posterior middle temporal gyrus (pMTG; n = 10) of the language dominant left hemisphere were prospectively included in the study. Cognitive performances were analyzed regarding an influence of patient characteristics and tumor localization.

Results: Severe impairment in at least one neurocognitive domain was found in 36 (83.7%) patients. Anxiety and depression were observed most frequently, followed by verbal memory impairments. Verbal memory was more strongly affected in patients with ATL or pST/SMG tumors compared to IFG tumors (p = 0.004 and p = 0.013, resp.). Overall, patients suffering from tumors in the ATL were most frequently and severely impaired.

Conclusion: Patients suffering from gliomas involving different regions within the language dominant hemisphere frequently present impairments in neurocognitive domains also other than language. Considering individual functions at risk may help in better advising patients prior to treatment and in tailoring the individual therapeutic strategy to preserve patients' quality of life.
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http://dx.doi.org/10.1016/j.clineuro.2021.106816DOI Listing
August 2021

[Aphasia associated with lacunar infarctions].

Nervenarzt 2021 Aug 16;92(8):802-808. Epub 2021 Feb 16.

Klinik für Neurologie, Goethe-Universität Frankfurt, Schleusenweg 2-16, 60528, Frankfurt, Deutschland.

Background: Typical lacunar syndromes do not include aphasia but aphasia has been reported in rare atypical lacunar syndromes.

Objective: Description of the phenomenology and of affected fiber tracts.

Material And Methods: Case series of three patients with lacunar stroke as evidenced by magnetic resonance imaging. Identification of affected fiber tracts via fiber tracking from coregistered lesion sites in brains of two healthy participants.

Results: The lacunar strokes that produced aphasia were located in the very lateral territory of perforating branches of the middle cerebral artery and extended along the external capsule into its most rostrodorsal aspect. Even though the cortex, thalamus and most parts of the basal ganglia were unaffected, patients exhibited a mild to moderate nonfluent aphasia with syntactic deficits. Fiber tracking revealed that in contrast to the nonaphasic control patient with a neighboring lacunar stroke, the aphasic patient strokes involved particularly fibers of the left arcuate fascicle as well as fibers of the frontostriatal and frontal aslant tracts.

Conclusion: Left lateral lacunar stroke can cause clinically relevant aphasia through disruption of speech-relevant fiber tracts.
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http://dx.doi.org/10.1007/s00115-021-01072-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342334PMC
August 2021

Differential contributions of the two cerebral hemispheres to temporal and spectral speech feedback control.

Nat Commun 2020 06 5;11(1):2839. Epub 2020 Jun 5.

Cognitive Neuroscience Group, Brain Imaging Center and Department of Neurology, Goethe University, Schleusenweg 2-16, 60528, Frankfurt, Germany.

Proper speech production requires auditory speech feedback control. Models of speech production associate this function with the right cerebral hemisphere while the left hemisphere is proposed to host speech motor programs. However, previous studies have investigated only spectral perturbations of the auditory speech feedback. Since auditory perception is known to be lateralized, with right-lateralized analysis of spectral features and left-lateralized processing of temporal features, it is unclear whether the observed right-lateralization of auditory speech feedback processing reflects a preference for speech feedback control or for spectral processing in general. Here we use a behavioral speech adaptation experiment with dichotically presented altered auditory feedback and an analogous fMRI experiment with binaurally presented altered feedback to confirm a right hemisphere preference for spectral feedback control and to reveal a left hemisphere preference for temporal feedback control during speaking. These results indicate that auditory feedback control involves both hemispheres with differential contributions along the spectro-temporal axis.
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http://dx.doi.org/10.1038/s41467-020-16743-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275068PMC
June 2020

"Spontaneous" late recovery from stuttering: Dimensions of reported techniques and causal attributions.

J Commun Disord 2019 Sep - Oct;81:105915. Epub 2019 Jun 28.

Communication Sciences and Special Education, University of Georgia, Athens, GA, USA.

Purpose: (1) To survey the employed techniques and the reasons/occasions which adults who had recovered from stuttering after age 11 without previous treatment reported as causal to overcome stuttering, (2) to investigate whether the techniques and causal attributions can be reduced to coherent (inherently consistent) dimensions, and (3) whether these dimensions reflect common therapy components.

Methods: 124 recovered persons from 8 countries responded by SurveyMonkey or paper-and-pencil to rating scale questions about 49 possible techniques and 15 causal attributions.

Results: A Principal Component Analysis of 110 questionnaires identified 6 components (dimensions) for self-assisted techniques (Speech Restructuring; Relaxed/Monitored Speech; Elocution; Stage Performance; Sought Speech Demands; Reassurance; 63.7% variance explained), and 3 components of perceived causal attributions of recovery (Life Change, Attitude Change, Social Support; 58.0% variance explained).

Discussion: Two components for self-assisted techniques (Speech Restructuring; Elocution) reflect treatment methods. Another component (Relaxed/Monitored Speech) consists mainly of items that reflect a common, non-professional understanding of effective management of stuttering. The components of the various perceived reasons for recovery reflect differing implicit theories of causes for recovery from stuttering. These theories are considered susceptible to various biases. This identification of components of reported techniques and of causal attributions is novel compared to previous studies who just list techniques and attributions.

Conclusion: The identified dimensions of self-assisted techniques and causal attributions to reduce stuttering as extracted from self-reports of a large, international sample of recovered formerly stuttering adults may guide the application of behavioral stuttering therapies.
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http://dx.doi.org/10.1016/j.jcomdis.2019.105915DOI Listing
August 2020

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

J Neurosci 2019 08 13;39(33):6498-6512. Epub 2019 Jun 13.

Department of Neurology, Goethe University, 60528 Frankfurt, Germany,

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation. Memory is an endogenous source of information based on experience. While neural oscillations encode autobiographic memories in the temporal domain, little is known on their contribution to memory representations of human speech. Our electrocortical recordings in participants who maintain sentences in memory identify the phase of left frontotemporal beta oscillations as the most prominent information carrier of sentence identity. These observations provide evidence for a theoretical model on speech memory representations and explain why interfering with beta oscillations in the left inferior frontal cortex diminishes verbal working memory capacity. The lack of sentence identity coding at the syllabic rate suggests that sentences are represented in memory in a more abstract form compared with speech coding during speech perception and production.
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http://dx.doi.org/10.1523/JNEUROSCI.0018-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697399PMC
August 2019

Cognitive effects of rhythmic auditory stimulation in Parkinson's disease: A P300 study.

Brain Res 2019 08 16;1716:70-79. Epub 2018 May 16.

Institute of Medical Psychology, Goethe University, 60528 Frankfurt am Main, Germany.

Rhythmic auditory stimulation (RAS) may compensate dysfunctions of the basal ganglia (BG), involved with intrinsic evaluation of temporal intervals and action initiation or continuation. In the cognitive domain, RAS containing periodically presented tones facilitates young healthy participants' attention allocation to anticipated time points, indicated by better performance and larger P300 amplitudes to periodic compared to random stimuli. Additionally, active auditory-motor synchronization (AMS) leads to a more precise temporal encoding of stimuli via embodied timing encoding than stimulus presentation adapted to the participants' actual movements. Here we investigated the effect of RAS and AMS in Parkinson's disease (PD). 23 PD patients and 23 healthy age-matched controls underwent an auditory oddball task. We manipulated the timing (periodic/random/adaptive) and setting (pedaling/sitting still) of stimulation. While patients elicited a general timing effect, i.e., larger P300 amplitudes for periodic versus random tones for both, sitting and pedaling conditions, controls showed a timing effect only for the sitting but not for the pedaling condition. However, a correlation between P300 amplitudes and motor variability in the periodic pedaling condition was obtained in control participants only. We conclude that RAS facilitates attentional processing of temporally predictable external events in PD patients as well as healthy controls, but embodied timing encoding via body movement does not affect stimulus processing due to BG impairment in patients. Moreover, even with intact embodied timing encoding, such as healthy elderly, the effect of AMS depends on the degree of movement synchronization performance, which is very low in the current study.
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http://dx.doi.org/10.1016/j.brainres.2018.05.016DOI Listing
August 2019

Endogenous modulation of human visual cortex activity improves perception at twilight.

Nat Commun 2018 04 10;9(1):1274. Epub 2018 Apr 10.

Cognitive Neuroscience Group, Brain Imaging Center, Goethe University, 60528, Frankfurt am Main, Germany.

Perception, particularly in the visual domain, is drastically influenced by rhythmic changes in ambient lighting conditions. Anticipation of daylight changes by the circadian system is critical for survival. However, the neural bases of time-of-day-dependent modulation in human perception are not yet understood. We used fMRI to study brain dynamics during resting-state and close-to-threshold visual perception repeatedly at six times of the day. Here we report that resting-state signal variance drops endogenously at times coinciding with dawn and dusk, notably in sensory cortices only. In parallel, perception-related signal variance in visual cortices decreases and correlates negatively with detection performance, identifying an anticipatory mechanism that compensates for the deteriorated visual signal quality at dawn and dusk. Generally, our findings imply that decreases in spontaneous neural activity improve close-to-threshold perception.
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http://dx.doi.org/10.1038/s41467-018-03660-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893589PMC
April 2018

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing.

Front Hum Neurosci 2017 30;11:582. Epub 2017 Nov 30.

Cognitive Neuroscience Group, Department of Neurology, Brain Imaging Center, Goethe University Frankfurt, Frankfurt am Main, Germany.

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region.
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http://dx.doi.org/10.3389/fnhum.2017.00582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714933PMC
November 2017

Assisted and unassisted recession of functional anomalies associated with dysprosody in adults who stutter.

J Fluency Disord 2018 03 9;55:120-134. Epub 2017 Sep 9.

Brain Imaging Center and Department of Neurology, Goethe University Frankfurt, Frankfurt am Main, Germany.

Purpose: Speech in persons who stutter (PWS) is associated with disturbed prosody (speech melody and intonation), which may impact communication. The neural correlates of PWS' altered prosody during speaking are not known, neither is how a speech-restructuring therapy affects prosody at both a behavioral and a cerebral level.

Methods: In this fMRI study, we explored group differences in brain activation associated with the production of different kinds of prosody in 13 male adults who stutter (AWS) before, directly after, and at least 1 year after an effective intensive fluency-shaping treatment, in 13 typically fluent-speaking control participants (CP), and in 13 males who had spontaneously recovered from stuttering during adulthood (RAWS), while sentences were read aloud with 'neutral', instructed emotional (happy), and linguistically driven (questioning) prosody. These activations were related to speech production acoustics.

Results: During pre-treatment prosody generation, the pars orbitalis of the left inferior frontal gyrus and the left anterior insula were activated less in AWS than in CP. The degree of hypo-activation correlated with acoustic measures of dysprosody. Paralleling the near-normalization of free speech melody following fluency-shaping therapy, AWS normalized the inferior frontal hypo-activation, sooner after treatment for generating emotional than linguistic prosody. Unassisted recovery was associated with an additional recruitment of cerebellar resources.

Conclusions: Fluency shaping therapy may restructure prosody, which approaches that of typically fluent-speaking people. Such a process may benefit from additional training of instructed emotional and linguistic prosody by inducing plasticity in the inferior frontal region which has developed abnormally during childhood in PWS.
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http://dx.doi.org/10.1016/j.jfludis.2017.09.003DOI Listing
March 2018

Speaking-related changes in cortical functional connectivity associated with assisted and spontaneous recovery from developmental stuttering.

J Fluency Disord 2018 03 13;55:135-144. Epub 2017 Feb 13.

Département des Neuroscience Fondamentales, Université de Genève, Switzerland.

We previously reported speaking-related activity changes associated with assisted recovery induced by a fluency shaping therapy program and unassisted recovery from developmental stuttering (Kell et al., Brain 2009). While assisted recovery re-lateralized activity to the left hemisphere, unassisted recovery was specifically associated with the activation of the left BA 47/12 in the lateral orbitofrontal cortex. These findings suggested plastic changes in speaking-related functional connectivity between left hemispheric speech network nodes. We reanalyzed these data involving 13 stuttering men before and after fluency shaping, 13 men who recovered spontaneously from their stuttering, and 13 male control participants, and examined functional connectivity during overt vs. covert reading by means of psychophysiological interactions computed across left cortical regions involved in articulation control. Persistent stuttering was associated with reduced auditory-motor coupling and enhanced integration of somatosensory feedback between the supramarginal gyrus and the prefrontal cortex. Assisted recovery reduced this hyper-connectivity and increased functional connectivity between the articulatory motor cortex and the auditory feedback processing anterior superior temporal gyrus. In spontaneous recovery, both auditory-motor coupling and integration of somatosensory feedback were normalized. In addition, activity in the left orbitofrontal cortex and superior cerebellum appeared uncoupled from the rest of the speech production network. These data suggest that therapy and spontaneous recovery normalizes the left hemispheric speaking-related activity via an improvement of auditory-motor mapping. By contrast, long-lasting unassisted recovery from stuttering is additionally supported by a functional isolation of the superior cerebellum from the rest of the speech production network, through the pivotal left BA 47/12.
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http://dx.doi.org/10.1016/j.jfludis.2017.02.001DOI Listing
March 2018

Phonetic detail and lateralization of reading-related inner speech and of auditory and somatosensory feedback processing during overt reading.

Hum Brain Mapp 2017 01 13;38(1):493-508. Epub 2016 Sep 13.

Center for General Linguistics, Schuetzenstrasse 18, Berlin, 10117, Germany.

Phonetic detail and lateralization of inner speech during covert sentence reading as well as overt reading in 32 right-handed healthy participants undergoing 3T fMRI were investigated. The number of voiceless and voiced consonants in the processed sentences was systematically varied. Participants listened to sentences, read them covertly, silently mouthed them while reading, and read them overtly. Condition comparisons allowed for the study of effects of externally versus self-generated auditory input and of somatosensory feedback related to or independent of voicing. In every condition, increased voicing modulated bilateral voice-selective regions in the superior temporal sulcus without any lateralization. The enhanced temporal modulation and/or higher spectral frequencies of sentences rich in voiceless consonants induced left-lateralized activation of phonological regions in the posterior temporal lobe, regardless of condition. These results provide evidence that inner speech during reading codes detail as fine as consonant voicing. Our findings suggest that the fronto-temporal internal loops underlying inner speech target different temporal regions. These regions differ in their sensitivity to inner or overt acoustic speech features. More slowly varying acoustic parameters are represented more anteriorly and bilaterally in the temporal lobe while quickly changing acoustic features are processed in more posterior left temporal cortices. Furthermore, processing of external auditory feedback during overt sentence reading was sensitive to consonant voicing only in the left superior temporal cortex. Voicing did not modulate left-lateralized processing of somatosensory feedback during articulation or bilateral motor processing. This suggests voicing is primarily monitored in the auditory rather than in the somatosensory feedback channel. Hum Brain Mapp 38:493-508, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866884PMC
January 2017

Actively but not passively synchronized motor activity amplifies predictive timing.

Neuroimage 2016 Oct 18;139:211-217. Epub 2016 Jun 18.

Institute of Medical Psychology, Goethe University, 60528 Frankfurt am Main, Germany. Electronic address:

Previous studies have shown that the effect of temporal predictability of presented stimuli on attention allocation is enhanced by auditory-motor synchronization (AMS). The present P300 event-related potential study (N=20) investigated whether this enhancement depends on the process of actively synchronizing one's motor output with the acoustic input or whether a passive state of auditory-motor synchrony elicits the same effect. Participants silently counted frequency deviants in sequences of pure tones either during a physically inactive control condition or while pedaling on a cycling ergometer. Tones were presented either at fixed or variable intervals. In addition to the pedaling conditions with fixed or variable stimulation, there was a third condition in which stimuli were adaptively presented in sync with the participants' spontaneous pedaling. We replicated the P300 enhancement for fixed versus variable stimulation and the amplification of this effect by AMS. Synchronization performance correlated positively with P300 amplitude in the fixed stimulation condition. Most interestingly, P300 amplitude was significantly reduced for the passive synchronization condition by adaptive stimulus presentation as compared to the fixed stimulation condition. For the first time we thus provide evidence that it is not the passive state of (even perfect) auditory-motor synchrony that facilitates attention allocation during AMS but rather the active process of synchronizing one's movements with external stimuli.
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http://dx.doi.org/10.1016/j.neuroimage.2016.06.033DOI Listing
October 2016

Asymmetric intra- and interhemispheric interactions during covert and overt sentence reading.

Neuropsychologia 2016 Dec 4;93(Pt B):448-465. Epub 2016 Apr 4.

Brain Imaging Center and Department of Neurology, Goethe University, Frankfurt, Germany. Electronic address:

Covert and overt sentence reading evoke lateralized activations in overall bihemispheric networks. We assumed that the study of functional connectivity may reveal underlying principles of functional lateralization. Left-lateralized activations could relate to stronger reading-related modulation of intrahemispheric functional connectivity in the left than the right hemisphere. Alternatively, left-lateralization could result from suppression of contralateral processing and thus reflect asymmetric interhemispheric interactions. To address this issue, this functional MRI study investigated the regional lateralization of covert and overt German sentence reading in 39 healthy participants. Further, it revealed the modulation of the lateralized brain regions' functional connectivity and their contralateral homotopes by covert and overt reading (psychophysiological interactions). Left-lateralization during covert reading was associated with stronger intrahemispheric coupling particularly in the left dorsal stream rather than with suppression of contralateral processing. Lateralization during overt sentence reading instead went along with additional recruitment of right perisylvian cortices involved in articulation by asymmetric positive heterotopic interhemispheric interactions. Given the paucity of interhemispheric anti-correlations with homotopic regions, functional lateralization is likely a consequence of a task-dependent interplay between asymmetric positive intra- and interhemispheric coupling.
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http://dx.doi.org/10.1016/j.neuropsychologia.2016.04.002DOI Listing
December 2016

Brain Mapping-Based Model of Δ(9)-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix.

Neuropsychopharmacology 2016 May 30;41(6):1659-69. Epub 2015 Oct 30.

Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.

Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers. A general linear model (GLM) analysis identified reduced activations in the hippocampus and the anterior insula following THC administration. However, assessment of psychophysiological interaction (PPI) revealed that the effects of THC first consisted in a weakening of the interaction between the thalamus and the secondary somatosensory cortex (S2). From there, dynamic causal modeling (DCM) was employed to infer that THC attenuated the connections to the hippocampus and to the anterior insula, suggesting that the reduced activations in these regions are secondary to a reduction of the connectivity from somatosensory regions by THC. These findings may have consequences for the way THC effects are currently interpreted: as cannabinoids are increasingly considered in pain treatment, present results provide relevant information about how THC interferes with the affective component of pain. Specifically, the present experiment suggests that THC does not selectively affect limbic regions, but rather interferes with sensory processing which in turn reduces sensory-limbic connectivity, leading to deactivation of affective regions.
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http://dx.doi.org/10.1038/npp.2015.336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832029PMC
May 2016

Left dorsal speech stream components and their contribution to phonological processing.

J Neurosci 2015 Jan;35(4):1411-22

Department of Neurology, Goethe University, Frankfurt am Main, D-60528, Germany, Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University, Tübingen, D-72076, Germany

Models propose an auditory-motor mapping via a left-hemispheric dorsal speech-processing stream, yet its detailed contributions to speech perception and production are unclear. Using fMRI-navigated repetitive transcranial magnetic stimulation (rTMS), we virtually lesioned left dorsal stream components in healthy human subjects and probed the consequences on speech-related facilitation of articulatory motor cortex (M1) excitability, as indexed by increases in motor-evoked potential (MEP) amplitude of a lip muscle, and on speech processing performance in phonological tests. Speech-related MEP facilitation was disrupted by rTMS of the posterior superior temporal sulcus (pSTS), the sylvian parieto-temporal region (SPT), and by double-knock-out but not individual lesioning of pars opercularis of the inferior frontal gyrus (pIFG) and the dorsal premotor cortex (dPMC), and not by rTMS of the ventral speech-processing stream or an occipital control site. RTMS of the dorsal stream but not of the ventral stream or the occipital control site caused deficits specifically in the processing of fast transients of the acoustic speech signal. Performance of syllable and pseudoword repetition correlated with speech-related MEP facilitation, and this relation was abolished with rTMS of pSTS, SPT, and pIFG. Findings provide direct evidence that auditory-motor mapping in the left dorsal stream causes reliable and specific speech-related MEP facilitation in left articulatory M1. The left dorsal stream targets the articulatory M1 through pSTS and SPT constituting essential posterior input regions and parallel via frontal pathways through pIFG and dPMC. Finally, engagement of the left dorsal stream is necessary for processing of fast transients in the auditory signal.
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http://dx.doi.org/10.1523/JNEUROSCI.0246-14.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308592PMC
January 2015

Dopaminergic Modulation of Cognitive Preparation for Overt Reading: Evidence from the Study of Genetic Polymorphisms.

Cereb Cortex 2016 Apr 16;26(4):1539-1557. Epub 2015 Jan 16.

Cognitive Neuroscience Group, Brain Imaging Center, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.

Choosing and implementing the rules for contextually adequate behavior depends on frontostriatal interactions. Observations in Parkinson's disease and pharmacological manipulations of dopamine transmission suggest that these corticobasal loops are modulated by dopamine. To determine, therefore, the physiological contributions of dopamine to task-rule-related processing, we performed a cue-target fMRI reading paradigm in 71 healthy participants and investigated the effects of COMT Val158Met, DAT1 VNTR 9/10, and DRD2/ANKK1 polymorphisms. The DRD2/ANKK1 polymorphism did not affect results. Intermediate prefrontal dopamine concentrations in COMT Val158Met heterozygotes facilitated preparatory interactions between the mesial prefrontal cortex and the left striatum during preparation for overt reading. To our knowledge, this is the first report of an inverted U-shaped curve modulation of cognition-related brain activity by prefrontal dopamine levels. In contrast, a linear effect of COMT Val158Met and DAT1 VNTR 9/10 polymorphisms on preparatory activity in the left inferior frontal gyrus pointed to a negative interaction between tonic lateral prefrontal and phasic subcortical dopamine. The COMT Val158Met polymorphism affected also feedforward and feedback processing in the sensorimotor speech system. Our results suggest that dopamine modulates corticobasal interactions on both the cortical and subcortical level but differently depending on the specific cognitive subprocesses involved.
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http://dx.doi.org/10.1093/cercor/bhu330DOI Listing
April 2016

Pathomechanisms and compensatory efforts related to Parkinsonian speech.

Neuroimage Clin 2014 31;4:82-97. Epub 2013 Oct 31.

Cognitive Neuroscience Group, Brain Imaging Center, Goethe University, Frankfurt, Germany ; Department of Neurology, Goethe University, Frankfurt, Germany.

Voice and speech in Parkinson's disease (PD) patients are classically affected by a hypophonia, dysprosody, and dysarthria. The underlying pathomechanisms of these disabling symptoms are not well understood. To identify functional anomalies related to pathophysiology and compensation we compared speech-related brain activity and effective connectivity in early PD patients who did not yet develop voice or speech symptoms and matched controls. During fMRI 20 PD patients ON and OFF levodopa and 20 control participants read 75 sentences covertly, overtly with neutral, or with happy intonation. A cue-target reading paradigm allowed for dissociating task preparation from execution. We found pathologically reduced striato-prefrontal preparatory effective connectivity in early PD patients associated with subcortical (OFF state) or cortical (ON state) compensatory networks. While speaking, PD patients showed signs of diminished monitoring of external auditory feedback. During generation of affective prosody, a reduced functional coupling between the ventral and dorsal striatum was observed. Our results suggest three pathomechanisms affecting speech in PD: While diminished energization on the basis of striato-prefrontal hypo-connectivity together with dysfunctional self-monitoring mechanisms could underlie hypophonia, dysarthria may result from fading speech motor representations given that they are not sufficiently well updated by external auditory feedback. A pathological interplay between the limbic and sensorimotor striatum could interfere with affective modulation of speech routines, which affects emotional prosody generation. However, early PD patients show compensatory mechanisms that could help improve future speech therapies.
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http://dx.doi.org/10.1016/j.nicl.2013.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853351PMC
May 2015

Affective and sensorimotor components of emotional prosody generation.

J Neurosci 2013 Jan;33(4):1640-50

Laboratory for Behavioral Neurology and Imaging of Cognition, Department of Neuroscience, Medical School, University of Geneva, 1211 Geneva 4, Switzerland.

Although advances have been made regarding how the brain perceives emotional prosody, the neural bases involved in the generation of affective prosody remain unclear and debated. Two models have been forged on the basis of clinical observations: a first model proposes that the right hemisphere sustains production and comprehension of emotional prosody, while a second model proposes that emotional prosody relies heavily on basal ganglia. Here, we tested their predictions in two functional magnetic resonance imaging experiments that used a cue-target paradigm, which allows distinguishing affective from sensorimotor aspects of emotional prosody generation. Both experiments show that when participants prepare for emotional prosody, bilateral ventral striatum is specifically activated and connected to temporal poles and anterior insula, regions in which lesions frequently cause dysprosody. The bilateral dorsal striatum is more sensitive to cognitive and motor aspects of emotional prosody preparation and production and is more strongly connected to the sensorimotor speech network compared with the ventral striatum. Right lateralization during increased prosodic processing is confined to the posterior superior temporal sulcus, a region previously associated with perception of emotional prosody. Our data thus provide physiological evidence supporting both models and suggest that bilateral basal ganglia are involved in modulating motor behavior as a function of affective state. Right lateralization of cortical regions mobilized for prosody control could point to efficient processing of slowly changing acoustic speech parameters in the ventral stream and thus identify sensorimotor processing as an important factor contributing to right lateralization of prosody.
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http://dx.doi.org/10.1523/JNEUROSCI.3530-12.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618741PMC
January 2013

Resting-state MRI: a peek through the keyhole on therapy for stuttering.

Authors:
Christian A Kell

Neurology 2012 Aug 8;79(7):614-5. Epub 2012 Aug 8.

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http://dx.doi.org/10.1212/WNL.0b013e31826357feDOI Listing
August 2012

Setting up the speech production network: how oscillations contribute to lateralized information routing.

Front Psychol 2012 6;3:169. Epub 2012 Jun 6.

Cognitive Neuroscience Group, Department of Neurology, Brain Imaging Center, Goethe University Frankfurt, Germany.

Speech production involves widely distributed brain regions. This MEG study focuses on the spectro-temporal dynamics that contribute to the setup of this network. In 21 participants performing a cue-target reading paradigm, we analyzed local oscillations during preparation for overt and covert reading in the time-frequency domain and localized sources using beamforming. Network dynamics were studied by comparing different dynamic causal models of beta phase coupling in and between hemispheres. While a broadband low frequency effect was found for any task preparation in bilateral prefrontal cortices, preparation for overt speech production was specifically associated with left-lateralized alpha and beta suppression in temporal cortices and beta suppression in motor-related brain regions. Beta phase coupling in the entire speech production network was modulated by anticipation of overt reading. We propose that the processes underlying the setup of the speech production network connect relevant brain regions by means of beta synchronization and prepare the network for left-lateralized information routing by suppression of inhibitory alpha and beta oscillations.
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http://dx.doi.org/10.3389/fpsyg.2012.00169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368321PMC
October 2012

Three stages and four neural systems in time estimation.

J Neurosci 2009 Nov;29(47):14803-11

Laboratoire de Neurosciences Cognitives, Inserm Unité 960, Département d'Etudes Cognitives, Ecole Normale Supérieure, 75005 Paris, France.

Gibbon's scalar expectancy theory assumes three processing stages in time estimation: a collating level in which event durations are automatically tracked, a counting level that reads out the time-tracking system, and a comparing level in which event durations are matched to abstract temporal references. Pöppel's theory, however, postulates a dual system for perception of durations below and above 2 s. By testing the neurophysiological plausibility of Gibbon's proposal using functional magnetic resonance imaging, we validate a three-staged model of time estimation and further show that the collating process is duplicated. Although the motor system automatically tracks durations below 2 s, mesial brain regions of the so-called "default mode network" keep track of longer events. Our results further support unique counting and comparing systems, involving prefrontal and parietal cortices in collators' readout, and the temporal cortex in contextual time estimation. These findings provide a coherent neuroanatomical framework for two theories of time perception.
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http://dx.doi.org/10.1523/JNEUROSCI.3222-09.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666014PMC
November 2009

Dual neural routing of visual facilitation in speech processing.

J Neurosci 2009 Oct;29(43):13445-53

Inserm U960, Laboratoire de Neurosciences Cognitives, Département d'Etudes Cognitives, Ecole Normale Supérieure, Paris, France.

Viewing our interlocutor facilitates speech perception, unlike for instance when we telephone. Several neural routes and mechanisms could account for this phenomenon. Using magnetoencephalography, we show that when seeing the interlocutor, latencies of auditory responses (M100) are the shorter the more predictable speech is from visual input, whether the auditory signal was congruent or not. Incongruence of auditory and visual input affected auditory responses approximately 20 ms after latency shortening was detected, indicating that initial content-dependent auditory facilitation by vision is followed by a feedback signal that reflects the error between expected and received auditory input (prediction error). We then used functional magnetic resonance imaging and confirmed that distinct routes of visual information to auditory processing underlie these two functional mechanisms. Functional connectivity between visual motion and auditory areas depended on the degree of visual predictability, whereas connectivity between the superior temporal sulcus and both auditory and visual motion areas was driven by audiovisual (AV) incongruence. These results establish two distinct mechanisms by which the brain uses potentially predictive visual information to improve auditory perception. A fast direct corticocortical pathway conveys visual motion parameters to auditory cortex, and a slower and indirect feedback pathway signals the error between visual prediction and auditory input.
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http://dx.doi.org/10.1523/JNEUROSCI.3194-09.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6665008PMC
October 2009

How the brain repairs stuttering.

Brain 2009 Oct 26;132(Pt 10):2747-60. Epub 2009 Aug 26.

Brain Imaging Center, Department of Neurology, Theodor Stern Kai 7, Frankfurt, Germany.

Stuttering is a neurodevelopmental disorder associated with left inferior frontal structural anomalies. While children often recover, stuttering may also spontaneously disappear much later after years of dysfluency. These rare cases of unassisted recovery in adulthood provide a model of optimal brain repair outside the classical windows of developmental plasticity. Here we explore what distinguishes this type of recovery from less optimal repair modes, i.e. therapy-induced assisted recovery and attempted compensation in subjects who are still affected. We show that persistent stuttering is associated with mobilization of brain regions contralateral to the structural anomalies for compensation attempt. In contrast, the only neural landmark of optimal repair is activation of the left BA 47/12 in the orbitofrontal cortex, adjacent to a region where a white matter anomaly is observed in persistent stutterers, but normalized in recovered subjects. These findings show that late repair of neurodevelopmental stuttering follows the principles of contralateral and perianomalous reorganization.
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http://dx.doi.org/10.1093/brain/awp185DOI Listing
October 2009

Ongoing activity fluctuations in hMT+ bias the perception of coherent visual motion.

J Neurosci 2008 Dec;28(53):14481-5

INSERM, Unité 562, Cognitive Neuroimaging, Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, NeuroSpin, 91191 Gif-sur-Yvette, France.

We have recently shown that intrinsic fluctuations of ongoing activity during baseline have an impact on perceptual decisions reported for an ambiguous visual stimulus (Hesselmann et al., 2008). To test whether this result generalizes from the visual object domain to other perceptual and neural systems, the current study investigated the effect of ongoing signal fluctuations in motion-sensitive brain regions on the perception of coherent visual motion. We determined motion coherence thresholds individually for each subject using a dynamic random dot display. During functional magnetic resonance imaging (fMRI), brief events of subliminal, supraliminal, and periliminal coherent motion were presented with long and variable interstimulus intervals between them. On each trial, subjects reported whether they had perceived "coherent" or "random" motion, and fMRI signal time courses were analyzed separately as a function of stimulus and percept type. In the right motion-sensitive occipito-temporal cortex (hMT+), coherent percepts of periliminal stimuli yielded a larger stimulus-evoked response than random percepts. Prestimulus baseline activity in this region was also significantly higher in these coherent trials than in random trials. As in our previous study, however, the relation between ongoing and evoked activity was not additive but interacted with perceptual outcome. Our data thus suggest that endogenous fluctuations in baseline activity have a generic effect on subsequent perceptual decisions. Although mainstream analytical techniques used in functional neuroimaging do not capture this nonadditive effect of baseline on evoked response, it is in accord with postulates from theoretical frameworks as, for instance, predictive coding.
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http://dx.doi.org/10.1523/JNEUROSCI.4398-08.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671252PMC
December 2008

Spontaneous local variations in ongoing neural activity bias perceptual decisions.

Proc Natl Acad Sci U S A 2008 Aug 29;105(31):10984-9. Epub 2008 Jul 29.

Unité 562, Cognitive Neuroimaging, Institut National de la Santé et de la Recherche Médicale, 91191 Gif-sur-Yvette Cedex, France.

Neural variability in responding to identical repeated stimuli has been related to trial-by-trial fluctuations in ongoing activity, yet the neural and perceptual consequences of these fluctuations remain poorly understood. Using functional neuroimaging, we recorded brain activity in subjects who reported perceptual decisions on an ambiguous figure, Rubin's vase-faces picture, which was briefly presented at variable intervals of > or = 20 s. Prestimulus activity in the fusiform face area, a cortical region preferentially responding to faces, was higher when subjects subsequently perceived faces instead of the vase. This finding suggests that endogenous variations in prestimulus neuronal activity biased subsequent perceptual inference. Furnishing evidence that evoked sensory responses, we then went on to show that the pre- and poststimulus activity interact in a nonlinear way and the ensuing perceptual decisions depend upon the prestimulus context in which they occur.
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http://dx.doi.org/10.1073/pnas.0712043105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504783PMC
August 2008

Graded size sensitivity of object-exemplar-evoked activity patterns within human LOC subregions.

J Neurophysiol 2008 Oct 16;100(4):2038-47. Epub 2008 Jul 16.

INSERM U562, Neuroimagerie Cognitive, CEA/NeuroSpin, Bât 145, Point Courrier 156, F-91191 Gif/Yvette, France.

A central issue for understanding visual object recognition is how the cortical hierarchy represents incoming sensory information and transforms it across successive processing stages. The format of object representation in the human brain has thus far mostly been studied using adaptation paradigms because the neuronal layout of object selectivities was thought to be beyond the resolution of conventional functional MRI (fMRI). Recently, however, multivariate pattern recognition succeeded in discriminating fMRI responses of object-selective cortex to different object exemplars within a given category. Here, we use increased spatial fMRI resolution to explore size sensitivity and tolerance to size change of response patterns evoked by object exemplars across a range of three sizes. Results from Support Vector Classification on responses of the human lateral occipital complex (LOC) show that discrimination of size (for a given object) and discrimination of objects across changes in size depended on the amount of size difference. Even across the largest amount of size change, accuracy for generalization was still significant in LOC, whereas the same comparison was at chance performance in early visual (calcarine) cortex. Analyzing subregions, we further found an anterior-posterior gradient in the degree of size sensitivity and size generalization within the posterior-dorsal and anterior-ventral parts of LOC. These results speak against fully size-invariant representation of object information in human LOC and are hence congruent with findings in monkeys showing object identity and size information in population activity of inferotemporal cortex. Moreover, these results provide evidence for a fine-grained functional heterogeneity within human LOC beyond the commonly used LO/fusiform subdivision.
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http://dx.doi.org/10.1152/jn.90305.2008DOI Listing
October 2008

Simulation of talking faces in the human brain improves auditory speech recognition.

Proc Natl Acad Sci U S A 2008 May 24;105(18):6747-52. Epub 2008 Apr 24.

Wellcome Trust Centre for Neuroimaging, University College London, Queen Square, London WC1N 3BG, United Kingdom.

Human face-to-face communication is essentially audiovisual. Typically, people talk to us face-to-face, providing concurrent auditory and visual input. Understanding someone is easier when there is visual input, because visual cues like mouth and tongue movements provide complementary information about speech content. Here, we hypothesized that, even in the absence of visual input, the brain optimizes both auditory-only speech and speaker recognition by harvesting speaker-specific predictions and constraints from distinct visual face-processing areas. To test this hypothesis, we performed behavioral and neuroimaging experiments in two groups: subjects with a face recognition deficit (prosopagnosia) and matched controls. The results show that observing a specific person talking for 2 min improves subsequent auditory-only speech and speaker recognition for this person. In both prosopagnosics and controls, behavioral improvement in auditory-only speech recognition was based on an area typically involved in face-movement processing. Improvement in speaker recognition was only present in controls and was based on an area involved in face-identity processing. These findings challenge current unisensory models of speech processing, because they show that, in auditory-only speech, the brain exploits previously encoded audiovisual correlations to optimize communication. We suggest that this optimization is based on speaker-specific audiovisual internal models, which are used to simulate a talking face.
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http://dx.doi.org/10.1073/pnas.0710826105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365564PMC
May 2008

Just the two of us: melatonin and adenosine in rodent pituitary function.

Ann Med 2005 ;37(2):105-20

Department of Neurology, Johann Wolfgang Goethe-University, Frankfurt, Germany.

The function of the pituitary gland is tightly controlled by neuronal and hormonal afferents of the brain. In this review, the role of the neurohormone melatonin and the neuromodulator adenosine for rodent pituitary function will be elucidated. Adenosine is known as an important paracrine modulator for pituitary endocrine and folliculostellate cells, with availability regulated by local metabolic cellular activity. In general, adenosine inhibits the cyclic adenosine monophosphate (AMP) pathway in pituitary cells by binding to A1-, and A3-adenosinergic receptors, and activates it via A2-adenosinergic receptors. The neurohormone melatonin integrates time-of-day and time-of-year into pituitary function via binding to MT1-melatonin receptors. Melatonin impacts at the hypothalamic level neurons that synthesize releasing and release-inhibiting hormones, and at the pituitary level only cells of the hypophyseal pars tuberalis (PT). Thereby, the daily changes in the duration of the nocturnal melatonin surge are decoded and subsequently relayed to the pars distalis to adapt gonadotropin and prolactin release, respectively, to season. An exciting integration of time within the regulation of pituitary function was deciphered by analysing transmembrane signalling events in cells of the hypophyseal PT: a consecutive daily impact of initially the neurohormone melatonin and later the neuromodulator adenosine on rodent PT cells leads to a circadian rhythm in the transcription of cyclic-AMP-sensitive genes.
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http://dx.doi.org/10.1080/07853890510007296DOI Listing
August 2005

The sensory cortical representation of the human penis: revisiting somatotopy in the male homunculus.

J Neurosci 2005 Jun;25(25):5984-7

Brain Imaging Center and Department of Neurology, Johann Wolfgang Goethe University, 60590 Frankfurt, Germany.

Pioneering mapping studies of the human cortex have established the notion of somatotopy in sensory representation, which transpired into Penfield and Rasmussen's famous sensory homunculus diagram. However, regarding the primary cortical representation of the genitals, classical and modern findings appear to be at odds with the principle of somatotopy, often assigning it to the cortex on the mesial wall. Using functional neuroimaging, we established a mediolateral sequence of somatosensory foot, penis, and lower abdominal wall representation on the contralateral postcentral gyrus in primary sensory cortex and a bilateral secondary somatosensory representation in the parietal operculum.
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http://dx.doi.org/10.1523/JNEUROSCI.0712-05.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724806PMC
June 2005

Distribution of transcription factor inducible cyclicAMP early repressor (ICER) in rodent brain and pituitary.

J Comp Neurol 2004 Oct;478(4):379-94

Dr. Senckenbergische Anatomie, Institute of Anatomy II, University of Frankfurt, 60590 Frankfurt, Germany.

In morphogenetic dynamics of neurons, and in adaptive physiology of brain function, transcription factors of the cyclicAMP signaling pathway, such as activator cyclicAMP responsive element binding protein (CREB) and inhibitor inducible cyclicAMP early repressor (ICER), play an important role. In particular, the presence of the transcription factor ICER in neurons or neuroendocrine cells suggests the need for the gating of an up-regulated gene expression. Little is known, however, about the natural distribution of the inhibitory transcription factor ICER. We, therefore, mapped the rodent brain and pituitary for an ICER immunoreaction and found a nuclear staining for this transcription factor. ICER-positive glial cells were found throughout the brain. ICER-positive neurons were found in sensory input centers, like the olfactory bulb, or sensory brain stem nuclei, and in hypothalamic nuclei involved in central neuroendocrine control. In addition, neuroendocrine/endocrine transducers, like the pituitary and the pineal gland showed a high basal presence of ICER. Our data show that a basic ICER level is required by many cell systems and can be seen as an anticipatory and/or a protective measure in systems with superior reactive dynamics.
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http://dx.doi.org/10.1002/cne.20290DOI Listing
October 2004
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