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Network Dynamics In The Healthy And Epileptic Developing Brain [article]

Richard E. Rosch, Torsten Baldeweg, Friederike Moeller, Gerold Baier
2017 bioRxiv   pre-print
Electroencephalography (EEG) allows recording of cortical activity at high temporal resolution. EEG recordings can be summarised along different dimensions using network-level quantitative measures, e.g. channel-to-channel correlation, or band power distributions across channels. These reveal network patterns that unfold over a range of different time scales and can be tracked dynamically. Here we describe the dynamics of network-state transitions in EEG recordings of spontaneous brain activity
more » ... in normally developing infants and infants with severe early infantile epileptic encephalopathies (n=8, age: 1-8 months). We describe differences in measures of EEG dynamics derived from band power, and correlation-based summaries of network-wide brain activity. We further show that EEGs from different patient groups and controls can be distinguished based on a small set of the novel quantitative measures introduced here, which describe dynamic network state switching. Quantitative measures related to the smoothness of switching from one correlation pattern to another show the largest differences between groups. These findings reveal that the early epileptic encephalopathies are associated with characteristic dynamic features at the network level. Quantitative network-based analyses like the one presented here may in future inform the clinical use of quantitative EEG for diagnosis.
doi:10.1101/133488 fatcat:d7zesti6jbedboggvty2gami5e

Synaptic Plasticity and Dysconnection in Schizophrenia

Klaas E. Stephan, Torsten Baldeweg, Karl J. Friston
2006 Biological Psychiatry  
modulatory effects of serotonin and dopamine (reviewed in Umbricht and Krljes 2005) , converging evidence shows that cholinergic stimulation increases and cholinergic blockage decreases the MMN amplitude (Baldeweg  ... 
doi:10.1016/j.biopsych.2005.10.005 pmid:16427028 fatcat:wdyyckhlgnfglda42kuo453244

Network dynamics in the healthy and epileptic developing brain

Richard Rosch, Torsten Baldeweg, Friederike Moeller, Gerold Baier
2018 Network Neuroscience  
Electroencephalography (EEG) allows recording of cortical activity at high temporal resolution. EEG recordings can be summarised along different dimensions using network-level quantitative measures, e.g. channel-tochannel correlation, or band power distributions across channels. These reveal network patterns that unfold over a range of different time scales and can be tracked dynamically. Here we describe the dynamics of network-state transitions in EEG recordings of spontaneous brain activity
more » ... n normally developing infants and infants with severe early infantile epileptic encephalopathies (n=8, age: 1-8 months). We describe differences in measures of EEG dynamics derived from band power, and correlationbased summaries of network-wide brain activity. We further show that EEGs from different patient groups and controls may be distinguishable based on a small set of the novel quantitative measures introduced here, which describe dynamic network state switching. Quantitative measures related to the sharpness of switching from one correlation pattern to another show the largest differences between groups. These findings reveal that the early epileptic encephalopathies are associated with characteristic dynamic features at the network level. Quantitative network-based analyses like the one presented here may in future inform the clinical use of quantitative EEG for diagnosis.
doi:10.1162/netn_a_00026 pmid:29911676 pmcid:PMC5989999 fatcat:aowsw5jk65abzh23eznmpbv7qq

NMDA-receptor antibodies alter cortical microcircuit dynamics [article]

Richard E Rosch, Sukhvir Wright, Gerald Cooray, Margarita Papadopoulou, Sushma Goyal, Ming Lim, Angela Vincent, Louise A Upton, Torsten Baldeweg, Karl J Friston
2017 bioRxiv   pre-print
NMDA-receptor antibodies (NMDAR-Ab) cause an autoimmune encephalitis with a diverse range of electroencephalographic (EEG) abnormalities. NMDAR-Ab are believed to disrupt receptor function, but how blocking this excitatory neurotransmitter can lead to paroxysmal EEG abnormalities - or even seizures - is poorly understood. Here, we show that NMDAR-Ab change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity, and
more » ... to paroxysmal EEG abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in paediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab-related changes render microcircuitry critically susceptible to overt EEG paroxysms, when these key parameters are changed. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.
doi:10.1101/160309 fatcat:gltzcl6kbnc2fh6dr6pawz75ii

Planning sEEG implantation using automated lesion detection: retrospective feasibility study [article]

Konrad Wagstyl, Sophie Adler, Birgit Pimpel, Aswin Chari, Kiran Seunarine, Sara Lorio, Rachel Thornton, Torsten Baldeweg, Martin Tisdall
2019 medRxiv   pre-print
Objective: A retrospective, cross-sectional study to evaluate the feasibility and potential benefits of incorporating deep-learning on structural MRI into planning stereoelectroencephalography (sEEG) implantation in paediatric patients with diagnostically complex drug-resistant epilepsy. This study aims to assess the degree of co-localisation between automated lesion detection and the seizure onset zone (SOZ) as assessed by sEEG. Methods: A neural network classifier was applied to cortical
more » ... res from MRI data from three cohorts. 1) The network was trained and cross-validated using 34 patients with visible focal cortical dysplasias (FCDs). 2) Specificity was assessed in 20 paediatric healthy controls. 3) Feasibility for incorporation into sEEG implantation plans was evaluated in 38 sEEG patients. Coordinates of sEEG contacts were coregistered with classifier-predicted lesions. sEEG contacts in seizure onset and irritative tissue were identified by clinical neurophysiologists. A distance of <10mm between SOZ contacts and classifier-predicted lesions was considered co-localisation. Results: In patients with radiologically-defined lesions, classifier sensitivity was 74% (25/34 lesions detected). No clusters were detected in the controls (specificity 100%). Of 34 sEEG patients, 21 patients had a focal cortical SOZ. Of these there was co-localisation between classifier output and SOZ contacts in 62%. The algorithm detected 7/8 histopathologically-confirmed FCDs (86%). Conclusions: There was a high degree of co-localisation between automated lesion detection and sEEG. We have created a framework for incorporation of deep-learning based MRI lesion detection into sEEG implantation planning. Our findings demonstrate that automated MRI analysis could be used to plan optimal electrode trajectories.
doi:10.1101/2019.12.08.19013979 fatcat:iaf7w7gs2rhdnb5xyijsy7i6zm

NMDA receptor blockade causes selective prefrontal disinhibition in a roving auditory oddball paradigm [article]

Richard E Rosch, Ryszard Auksztulewicz, Pui Duen Leung, Karl J Friston, Torsten Baldeweg
2017 bioRxiv   pre-print
N-methyl-D-aspartate receptors (NMDARs) are expressed widely throughout the human cortex. Yet disturbances in NMDAR transmission - as implicated in patients with schizophrenia or pharmacologically induced - can cause a regionally specific set of electrophysiological effects. Here, we present a double-blind placebo-controlled study of the effects of the NMDAR blocker ketamine in human volunteers. We employ a marker of auditory learning and putative synaptic plasticity - the mismatch negativity -
more » ... in a roving auditory oddball paradigm. Using recent advances in Bayesian modelling of group effects in dynamic causal modelling, we fit biophysically plausible network models of the auditory processing hierarchy to whole-scalp evoked response potential recordings. This allowed us to identify the regionally specific effects of ketamine in a distributed network of interacting cortical sources. Under placebo, our analysis replicated previous findings regarding the effects of stimulus repetition and deviance on connectivity within the auditory hierarchy. Crucially, we show that the effect of ketamine is best explained as a selective change in intrinsic inhibition, with a pronounced ketamine-induced reduction of inhibitory interneuron connectivity in frontal sources. These results are consistent with findings from invasive recordings in animal models exposed to NMDAR blockers, and provide evidence that inhibitory-interneuron specific NMDAR dysfunction may be sufficient to explain electrophysiological abnormalities of sensory learning induced by ketamine in human subjects.
doi:10.1101/133371 fatcat:bjzbxcu3ozc7dlwy2wkgd4owb4

Developmental conduction aphasia after neonatal stroke

Gemma B. Northam, Sophie Adler, Kathrin C. J. Eschmann, Wui K. Chong, Frances M. Cowan, Torsten Baldeweg
2018 Annals of Neurology  
Objective: Impairment of speech repetition following injury to the dorsal language stream is feature of conduction aphasia -a well-described 'disconnection syndrome' in adults. The impact of similar lesions sustained in infancy has not been established. Methods: We compared language outcomes in term-born individuals with confirmed neonatal stroke (n=30; age: 7-18 years, left-sided lesions in 21 cases) to matched controls (n=40). Injury to the dorsal and/or ventral language streams was assessed
more » ... sing T 1 -and T 2weighted MRI and diffusion tractography. Language lateralization was determined using functional MRI. Results: At the group level, left dorsal language stream injury was associated with selective speech repetition impairment for non-words (p=0.021) and sentences (p<0.0001). The majority of children with significant repetition impairment had retained left hemisphere language representation, but right hemisphere dominance was correlated with minimal or absent repetition deficits. Post-hoc analysis of the repetition-impaired group revealed additional language-associated deficits, but these were more subtle and variable. Interpretation: We conclude that (i) despite the considerable plasticity of the infant brain, early dorsal language stream injury can result in specific and long-lasting problems with speech repetition that are similar to the syndrome of conduction aphasia seen in adults, and that (ii) language reorganization to the contralateral hemisphere has a protective effect.
doi:10.1002/ana.25218 pmid:29572915 fatcat:xcdbe6xiazak3mbpeprczr5n4q

The Pair Test: A computerised measure of learning and memory

Sarah Buck, Filipa Bastos, Torsten Baldeweg, Faraneh Vargha-Khadem
2020 Behavior Research Methods  
There is increasing interest in the assessment of learning and memory in typically developing children as well as in children with neurodevelopmental disorders. However, neuropsychological assessments have been hampered by the dearth of standardised tests that enable direct comparison between distinct memory processes or between types of stimulus materials. We developed a tablet-based paired-associate learning paradigm, the Pair Test, based on neurocognitive models of learning and memory. The
more » ... ms are to (i) establish the utility of this novel memory tool for use with children across a wide age range, and (ii) examine test validity, reliability and reproducibility of the construct. The convergent validity of the test was found to be adequate, and higher test reliability was shown for the Pair Test compared to standardised measures. Moderate test–retest reproducibility was shown, despite a long time interval between sessions (14 months). Moreover, the Pair Test is able to capture developmental changes in memory, and can therefore chart the developmental trajectory of memory and learning functions across childhood and adolescence. Finally, we used this novel instrument to acquire normative data from 130 typically developing children, aged 8–18 years. Age-stratified normative data are provided for learning, delayed recall and delayed recognition, for measures of verbal and non-verbal memory. The Pair Test thus provides measures of learning and memory accounting for encoding, consolidation and retrieval processes. As such, the standardised test results can be used to determine the status of learning and memory in healthy children, and also to identify deficits in paediatric patients at risk of damage to the neural network underlying mnemonic functions.
doi:10.3758/s13428-020-01470-9 pmid:32909110 pmcid:PMC8062426 fatcat:h465bs65gffinnr6ilk7ymz3uq

Repetition suppression and plasticity in the human brain

Marta I. Garrido, James M. Kilner, Stefan J. Kiebel, Klaas E. Stephan, Torsten Baldeweg, Karl J. Friston
2009 NeuroImage  
Baldeweg et al., 2004; Dyson et al., 2005; Haenschel et al., 2005) .  ...  This result is consistent with previous findings (Sams et al., 1985; Näätänen and Rinne, 2002; Baldeweg et al., 2004) .  ... 
doi:10.1016/j.neuroimage.2009.06.034 pmid:19540921 pmcid:PMC2821573 fatcat:f5fxmgc3dfgilk6npr554anoe4

Does sleep benefit memory consolidation in children with focal epilepsy?

Samantha Chan, Ronit Pressler, Stewart G. Boyd, Torsten Baldeweg, J. Helen Cross
2017 Epilepsia  
Running title: Sleep and memory in children with epilepsy Abbreviations: REM=rapid eye movement sleep, NREM=non-rapid eye movement sleep, 2D=two-dimensional, IED=interictal epileptiform discharges, CSWS=continuous spike waves during sleep, SWI=spike wave index Key points  Sleep in children who have focal epilepsy with structural or presumed structural etiology enhances memory consolidation to the same degree as in healthy children  This mechanism is resilient to both chronic seizures and
more » ... sleep disruption, though impaired by frequent nocturnal discharges  Harnessing this ability may enhance learning in children with epilepsy
doi:10.1111/epi.13668 pmid:28111743 fatcat:s2qlagjr5zhxbjfsxqtanooofy

Language fMRI abnormalities associated with FOXP2 gene mutation

Frédérique Liégeois, Torsten Baldeweg, Alan Connelly, David G Gadian, Mortimer Mishkin, Faraneh Vargha-Khadem
2003 Nature Neuroscience  
Half the members of the KE family suffer from a speech and language disorder caused by a mutation in the FOXP2 gene. We examined functional brain abnormalities associated with this mutation using two fMRI language experiments, one involving covert (silent) verb generation and the other overt (spoken) verb generation and word repetition. The unaffected family members showed a typical left-dominant distribution of activation involving Broca's area in the generation tasks and a more bilateral
more » ... ibution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported bilateral morphological abnormalities, the affected members showed significant underactivation relative to the unaffected members in Broca's area and its right homolog, as well as in other cortical language-related regions and in the putamen. Our findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language.
doi:10.1038/nn1138 pmid:14555953 fatcat:xcp6se6atjg4nj6q3pealb72ai

Bayesian Belief Updating of Spatiotemporal Seizure Dynamics [article]

Gerald K Cooray and Richard Rosch and Torsten Baldeweg and Louis Lemieux and Karl Friston and Biswa Sengupta
2017 arXiv   pre-print
Epileptic seizure activity shows complicated dynamics in both space and time. To understand the evolution and propagation of seizures spatially extended sets of data need to be analysed. We have previously described an efficient filtering scheme using variational Laplace that can be used in the Dynamic Causal Modelling (DCM) framework [Friston, 2003] to estimate the temporal dynamics of seizures recorded using either invasive or non-invasive electrical recordings (EEG/ECoG). Spatiotemporal
more » ... ics are modelled using a partial differential equation -- in contrast to the ordinary differential equation used in our previous work on temporal estimation of seizure dynamics [Cooray, 2016]. We provide the requisite theoretical background for the method and test the ensuing scheme on simulated seizure activity data and empirical invasive ECoG data. The method provides a framework to assimilate the spatial and temporal dynamics of seizure activity, an aspect of great physiological and clinical importance.
arXiv:1705.07278v2 fatcat:gmzb7fnpcvgedjbqnyfhpsazqi

Planning stereoelectroencephalography using automated lesion detection: Retrospective feasibility study

Konrad Wagstyl, Sophie Adler, Birgit Pimpel, Aswin Chari, Kiran Seunarine, Sara Lorio, Rachel Thornton, Torsten Baldeweg, Martin Tisdall
2020 Epilepsia  
AUTHOR CONTRIBUTIONS ORCID Konrad Wagstyl https://orcid.org/0000-0003-3439-5808 Sara Lorio https://orcid.org/0000-0002-1790-3586 Torsten Baldeweg https://orcid. org/0000-0002-5724-1679  ... 
doi:10.1111/epi.16574 pmid:32533794 fatcat:6utedvptyjckray6pwswdsfuwi

Vulnerability of the ventral language network in children with focal epilepsy

Louise J. Croft, Torsten Baldeweg, Leigh Sepeta, Lauren Zimmaro, Madison M. Berl, William D. Gaillard
2014 Brain  
Children with focal epilepsy are at increased risk of language impairment, yet the neural substrate of this dysfunction is not yet known. Using functional magnetic resonance imaging we investigated the impact of focal epilepsy on the developing language system using measures of network topology (spatial organization of activation) and synchrony (functional connectivity). We studied healthy children (n = 48, 4-12 years, 24 females) and children with focal epilepsy (n = 21, 5-12 years, nine
more » ... s) with left hemisphere language dominance. Participants performed an age-adjusted auditory description decision task during functional magnetic resonance imaging, to identify perisylvian language regions. Mean signal change was extracted from eight left perisylvian regions of interest and compared between groups. Paired region of interest functional connectivity analysis was performed on time course data from the same regions, to investigate left network synchrony. Two principal component analyses were performed to extract (i) patterns of activation (using mean signal change data); and (ii) patterns of synchronized regions (using functional connectivity data). For both principal component analyses two components (networks) were extracted, which mapped onto the functional anatomy of dorsal and ventral language systems. Associations among network variables, age, epilepsy-related factors and verbal ability were assessed. Activated networks were affected by age and epilepsy [F(2,60) = 3.74, P = 0.03]: post hoc analyses showed, for healthy children, activation in both ventral and dorsal networks decreased with age (P = 0.02). Regardless of age and task performance, children with epilepsy showed reduced activation of the ventral network (P 5 0.001). They also showed a trend for increased activation of the dorsal network (P = 0.08) associated with improved task performance (r = 0.62, P = 0.008). Crucially, decreased activation of the ventral network in patients predicted poorer language outcome (R 2 adjusted = 0.47, P = 0.002). This suggests childhood onset epilepsy preferentially alters maturation of the ventral language system, and this is related to poorer language ability.
doi:10.1093/brain/awu154 pmid:24941948 pmcid:PMC4107744 fatcat:gimflzokdjfotpwxbp2bakrxdy

Impaired auditory frequency discrimination in dyslexia detected with mismatch evoked potentials

Torsten Baldeweg, Alexandra Richardson, Sarah Watkins, Christine Foale, John Gruzelier
1999 Annals of Neurology  
Deficits in phonological skills appear to be at the heart of reading disability; however, the nature of this impairment is not yet known. The hypothesis that dyslexic subjects are impaired in auditory frequency discrimination was tested by using an attention-independent auditory brain potential, termed mismatch negativity (MMN) while subjects performed a visual distractor task. In separate blocks, MMN responses to graded changes in tone frequency or tone duration were recorded in 10 dyslexic
more » ... matched control subjects. MMN potentials to changes in tone frequency but not to changes in tone duration were abnormal in dyslexic subjects. This physiological deficit was corroborated by a similarly specific impairment in discriminating tone frequency, but not tone duration, which was assessed separately. Furthermore, the pitch discrimination and MMN deficit was correlated with the degree of impairment in phonological skills, as reflected in reading errors of regular words and nonwords. It is possible that in dyslexia a persistent sensory deficit in monitoring the frequency of incoming sound may impair the feedback control necessary for the normal development of phonological skills.
doi:10.1002/1531-8249(199904)45:4<495::aid-ana11>3.0.co;2-m pmid:10211474 fatcat:3c27735p2zfz7l4sitv6hd4mnu
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