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Torsten Baldeweg

Publications and source records attributed to Torsten Baldeweg.

17 recordsLinked to original sources
PubMed2006

Impact of frontal white matter lesions on performance monitoring: ERP evidence for cortical disconnection.

We examined the impact of discrete white matter lesions in the frontal lobes on event-related potential (ERP) correlates of performance monitoring. We tested the hypothesis that abnormal performance monitoring may result from injury to white matter without evidence of injury to grey matter in the frontal lobes. It was predicted that such lesions may result in disconnection of the lateral and medial frontal cortices. The close interaction of these two areas has been implicated in performance monitoring. Two fast-choice response tasks were administered to patients with MRI-confirmed frontal white matter lesions due to sickle cell disease (SCD) vasculopathy (n = 11; age = 11-23 years; 6 unilateral left lesions and 5 bilateral lesions) and two control groups: SCD patients without brain lesions and non-sickle cell sibling controls (n = 11 each). Stimulus-locked ERP components N2 and P3 were not significantly affected by presence of lesions. The difference between response-locked components to correct trials (correct-response negativity--CRN) and erroneous trials (error-related negativity--ERN) was diminished in patients with unilateral and bilateral frontal white matter lesions. This finding was due to a significantly attenuated ERN amplitude in lesion patients compared with both sibling and non-lesion control groups. These ERP findings were not due to performance differences between groups and hence reflect a compromised neural substrate underlying performance monitoring. The latter may also contribute to the deficits in executive function tasks observed in these patients. As disruption to ERP markers of error processing was found in the absence of lesions to the lateral or medial frontal cortex, we conclude that a functional connection between these areas facilitates performance monitoring, possibly implemented via tracts traversing the deep frontal white matter.

Adolescent↗
PubMed2006

Human memory development and its dysfunction after early hippocampal injury.

Cognitive memory involves long-term memories for facts (semantic memory) and personal experiences (episodic memory) that can be brought to mind. There is consensus that the hippocampus and related medial temporal lobe (MTL) structures are crucial for adult cognitive memory, but much less is known about their contribution to memory during infancy and childhood. We argue that the MTL is involved in memory from early in life, supporting recognition memory within the first postnatal months and recall memory within the first year. We propose that normal development involves a sequence in which a form of semantic-like memory emerges first, whereas the characteristics of episodic memory develop only later with progressive development of the hippocampus. Early bilateral injury to the hippocampus disrupts this normal pattern such that memory skills cannot develop beyond the stage of semantic memories. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Brain Injuries↗
PubMed2006

Synaptic plasticity and dysconnection in schizophrenia.

Current pathophysiological theories of schizophrenia highlight the role of altered brain connectivity. This dysconnectivity could manifest 1) anatomically, through structural changes of association fibers at the cellular level, and/or 2) functionally, through aberrant control of synaptic plasticity at the synaptic level. In this article, we review the evidence for these theories, focusing on the modulation of synaptic plasticity. In particular, we discuss how dysconnectivity, observed between brain regions in schizophrenic patients, could result from abnormal modulation of N-methyl-D-aspartate (NMDA)-dependent plasticity by other neurotransmitter systems. We focus on the implication of the dysconnection hypothesis for functional imaging at the systems level. In particular, we review recent advances in measuring plasticity in the human brain using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) that can be used to address dysconnectivity in schizophrenia. Promising experimental paradigms include perceptual and reinforcement learning. We describe how theoretical and causal models of brain responses might contribute to a mechanistic understanding of synaptic plasticity in schizophrenia.

Acetylcholine↗
PubMed2006

Detecting white matter injury in sickle cell disease using voxel-based morphometry.

OBJECTIVE: Sickle cell disease (SCD) is associated with cerebrovascular disease, cerebral infarction, and cognitive dysfunction. This study aimed to detect the presence and extent of white matter abnormalities in individuals with SCD using voxel-based morphometry (VBM). METHODS: Thirty-six children and adolescents with SCD (age range, 9-24 years) and 31 controls (8-25 years) underwent magnetic resonance investigations using T1- and T2-weighted protocols. White and gray matter density maps were obtained from three-dimensional magnetic resonance imaging (MRI) data sets. Using VBM, we compared the maps between controls and SCD individuals with silent white matter infarct lesions (SCD+L; n = 16), and those without visible abnormality (SCD-L; n = 20). RESULTS: In comparison with controls, intelligence quotients (IQs) were lower in both SCD groups irrespective of presence of visible lesions. VBM showed widespread bilateral white matter abnormalities in the SCD+L group, extending beyond the regions of focal infarction in the deep anterior and posterior white matter borderzones. Bilateral white matter abnormalities were also observed in the SCD-L group, in locations similar to those in the SCD+L group. INTERPRETATION: VBM is sensitive to detection of widespread white matter injury in SCD patients in borderzones between arterial territories even in the absence of evidence of infarction. Those changes may contribute to cognitive deficits in this population.

Adolescent↗
PubMed2005

Nicotinic modulation of human auditory sensory memory: Evidence from mismatch negativity potentials.

Impairment in mismatch negativity (MMN) generation is a robust biological marker of schizophrenia. Understanding the physiological and pharmacological processes involved in its generation may therefore advance our understanding of this complex disorder. The present study tested if acute administration of nicotine modulates human auditory sensory memory as measured with MMN. ERP responses to tone duration deviants were recorded using a stimulation protocol with continuously changing (roving) standard stimuli in order to measure the effect of stimulus repetitions on encoding of new stimuli (MMN memory trace effect). Twenty healthy adult volunteers were randomly assigned to receive either a nicotine gum or placebo after a baseline ERP recording. Nicotine administration augmented MMN amplitude in the treatment group compared to the baseline recording, while no MMN change was found in the placebo group. The drug effect was due to a selective enhancement of a frontal positive potential to standard stimuli (from 80-200 ms post-stimulus), while the negativity to deviants remained unaffected. Furthermore, under nicotine stimulation this repetition positivity showed a more marked increase with stimulus repetition compared to baseline and placebo. These results have potential implications for schizophrenia by suggesting that nicotinic agonists could ameliorate patients' MMN deficits by improving stimulus encoding and sensory memory trace formation.

Acoustic Stimulation↗
PubMed2005

Event-related brain potential correlates of human auditory sensory memory-trace formation.

The event-related potential (ERP) component mismatch negativity (MMN) is a neural marker of human echoic memory. MMN is elicited by deviant sounds embedded in a stream of frequent standards, reflecting the deviation from an inferred memory trace of the standard stimulus. The strength of this memory trace is thought to be proportional to the number of repetitions of the standard tone, visible as the progressive enhancement of MMN with number of repetitions (MMN memory-trace effect). However, no direct ERP correlates of the formation of echoic memory traces are currently known. This study set out to investigate changes in ERPs to different numbers of repetitions of standards, delivered in a roving-stimulus paradigm in which the frequency of the standard stimulus changed randomly between stimulus trains. Normal healthy volunteers (n = 40) were engaged in two experimental conditions: during passive listening and while actively discriminating changes in tone frequency. As predicted, MMN increased with increasing number of standards. However, this MMN memory-trace effect was caused mainly by enhancement with stimulus repetition of a slow positive wave from 50 to 250 ms poststimulus in the standard ERP, which is termed here "repetition positivity" (RP). This RP was recorded from frontocentral electrodes when participants were passively listening to or actively discriminating changes in tone frequency. RP may represent a human ERP correlate of rapid and stimulus-specific adaptation, a candidate neuronal mechanism underlying sensory memory formation in the auditory cortex.

Acoustic Stimulation↗
PubMed2005

Hippocampal atrophy in temporal lobe epilepsy is correlated with limbic systems atrophy.

Hippocampal sclerosis in temporal lobe epilepsy (TLE) is often associated with hippocampal atrophy. This study assessed whether such atrophy is correlated with loss of gray matter volume in other brain regions. In 16 patients with TLE and clear magnetic resonance imaging-based evidence of hippocampal sclerosis, hippocampal volumes were determined manually and the local gray matter (LGM) amount was estimated throughout the entire brain using voxel-based morphometry. Voxelwise correlations between the volume of the sclerotic hippocampus and LGM were computed. The pattern of voxels whose LGM correlated with hippocampal volume outlined remarkably well the anatomy of the extended limbic system and included the parahippocampal region, cingulate gyrus throughout its extent, basal forebrain, thalamic nuclei, medial orbitofrontal areas and the insula. These correlations emerged mainly on the side ipsilateral to the affected hippocampus but were also found contralaterally. No such correlations were found in a group of 16 healthy controls. The present data show that hippocampal volume loss in TLE is associated with a widespread limbic systems atrophy. These findings are helpful to better understand the functional deficit and reorganization often found in temporal lobe epilepsy and will also provide a basis to assess neural plasticity in the limbic system for those patients who will undergo curative temporal lobe surgery.

Adult↗
PubMed2005

COMT Val108/158 Met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome.

BACKGROUND: Microdeletions at 22q11.2 greatly increase the risk of schizophrenia in early adulthood (relative risk approximately 25-30). We hypothesized that before the onset of schizophrenia, individuals with 22q11DS would manifest specific cognitive and neurophysiological anomalies (endophenotypes) in common with individuals at high risk for schizophrenia in the general population. We further predicted that the catechol-O-methyltransferase Val(108/158)Met polymorphism, located within the deleted chromosomal segment, would modify the severity of endophenotypic features. METHODS: 22q11DS adolescents and young adults (aged 13-21) were compared with age- and IQ-matched control subjects on measures that are associated with risk of idiopathic schizophrenia. RESULTS: 22q11DS subjects displayed poorer verbal working memory and expressive language performance than control subjects. Auditory mismatch negativity (MMN) event-related potentials were reduced at frontal electrodes but were intact at temporal sites. Presence of the COMT(108/158)Met allele on the single intact chromosome 22 was associated with more marked MMN amplitude reduction and poorer neuropsychological performance. Neither COMT Val(108/158)Met allele influenced psychiatric symptoms. CONCLUSIONS: 22q11DS is associated with neurodevelopmental characteristics that are similar to idiopathic schizophrenia. The COMT Val(108/158)Met polymorphism modifies the severity of endophenotypes for schizophrenia, indicating that impaired catecholamine regulation contributes to neuropsychiatric risk in 22q11DS.

Acoustic Stimulation↗
PubMed2005

Extra-hippocampal grey matter density abnormalities in paediatric mesial temporal sclerosis.

The aim of this study was to identify grey matter density abnormalities in children with temporal lobe epilepsy and mesial temporal sclerosis. Magnetic resonance T1 weighted 3D datasets were obtained in children with temporal lobe epilepsy (20 left and 10 right sided, mean age 11.9 years, range 6.6-17.5) and compared to scans obtained from age-matched controls (n = 22, mean age 12.8 years, range 7.1-17.5) using voxel-based morphometry. This method detected reduced grey matter ipsilateral to the seizure focus not only in the hippocampus, but also in the lateral temporal lobe and in extra-temporal regions including the thalamus, posterior cingulate cortex and cerebellum. Bilateral differences were present in the frontal and parietal opercular cortices and lateral temporal regions. These grey matter density reductions broadly reflect the pattern of hippocampal connections and may be caused by the disruption of cortical development by the recurrent seizures, as well as by loss of functional input from the sclerotic hippocampus.

Adolescent↗
PubMed2005

Maturation of action monitoring from adolescence to adulthood: an ERP study.

This study investigated the development of the frontal lobe action-monitoring system from late childhood and adolescence to early adulthood using ERP markers of error processing. Error negativity (ERN) and correct response negativity (CRN) potentials were recorded while adolescents and adults (aged 12-22 years, n = 23) performed two forced-choice visual reaction time tasks of differing complexity. Significant age differences were seen for behavioural and ERP responses to complex (infrequent, incompatible) trials: adolescents elicited an error negativity of reduced magnitude compared with adults. Furthermore, in contrast to adults, adolescents showed a non-significant differentiation between response-locked ERP components elicited by correct (CRN) and error responses (ERN). Behaviourally, adolescents corrected fewer errors in incompatible trials, and with increasing age there was greater post-error slowing. In conclusion, the neural systems underlying action-monitoring continue to mature throughout the second decade of life, and are associated with increased efficiency for fast error detection and correction during complex tasks.

Adolescent↗
PubMed2004

Mismatch negativity potentials and cognitive impairment in schizophrenia.

Cognitive impairment in schizophrenia is an important predictor of clinical and social outcome. In this preliminary study, the correlation between cognitive status and deficits in mismatch negativity (MMN) generation was explored. The MMN response to tone duration deviants was recorded using a new stimulation protocol with continuously changing ('roving') standard stimuli in order to measure the effect of standard repetitions on MMN (memory trace effect). Cognitive status of the patient group (n=28) was assessed using neuropsychological screening. Healthy participants (n=20) served as age-matched comparison group. In patients, MMN amplitude in frontal electrodes as well as the MMN memory trace effect was diminished compared to controls. While both measures were inversely related to patient's age and disease severity, only the MMN memory trace effect was robustly correlated with the degree of neuropsychological impairment. This suggests that ERP measures of auditory system adaptability more appropriately characterise the pathophysiological processes underlying cognitive impairment in schizophrenia than static measures of ERP magnitude.

Acoustic Stimulation↗
PubMed2004

Mismatch negativity in schizophrenia: a family study.

BACKGROUND: Mismatch negativity (MMN) is a measure of cortical activity that occurs in response to a change in auditory stimuli. We investigated whether MMN is a potential marker of genetic vulnerability to schizophrenia by comparing MMN in a group of patients with schizophrenia, their unaffected relatives, and controls. METHOD: There are 25 schizophrenic patients, 37 of their unaffected first-degree relatives, and 20 unrelated controls that performed the MMN task. Linear regression with robust standard errors, and accounting for correlations within families, was employed to test for differences in MMN amplitude between the groups. RESULTS: Patients had significantly smaller MMN amplitudes compared to both their unaffected relatives and controls at FZ (P<0.01) and at F3 (P=0.01), whereas relatives and controls did not differ at FZ or at F3. No differences were found between any of the groups at F4. Furthermore, we found no strong evidence that the MMN amplitude is a familial trait. CONCLUSIONS: Our results confirm that the MMN amplitude is reduced in schizophrenia. However, the MMN does not show a significant familial influence and is normal among the unaffected relatives. We conclude that while the MMN is abnormal in patients with schizophrenia, it is a weak or unreliable marker of vulnerability when applied to subclinical populations, and therefore is unlikely to be an endophenotype for the disorder.

Acoustic Stimulation↗
PubMed2004

Cortical lateralization during verb generation: a combined ERP and fMRI study.

Lateralization of scalp-recorded event-related potentials (ERPs) and functional MRI (fMRI) activation was investigated using a verb generation task in 10 healthy right-handed adults. ERPs showed an early transient positivity in the left inferior temporal region (500-1250 ms) following auditory presentation of the stimulus noun. A sustained slow cortical negativity of later onset (1250-3000 ms) was then recorded, most pronounced over left inferior frontal regions. fMRI data were in agreement with both ERP effects, showing left lateralized activation in inferior and superior temporal as well as inferior frontal cortices. Lateralized ERP effects occurred during the verb generation task but not during passive word listening or during word- and nonword repetition. Thus, ERPs and fMRI provided convergent evidence regarding language lateralization, with ERPs revealing the temporal sequence of posterior to anterior cortical activation during semantic retrieval.

Acoustic Stimulation↗
PubMed2003

Language fMRI abnormalities associated with FOXP2 gene mutation.

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 distribution 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.

Brain Mapping↗
PubMed2002

Impairment in frontal but not temporal components of mismatch negativity in schizophrenia.

Impairment in mismatch negativity (MMN) potentials is a robust finding in schizophrenia. While previous studies suggested that MMN in man is generated by a single dipole source bilaterally in the primary auditory cortex, more recent data modified this assumption by showing differential modulation of MMN components over the frontal and temporal scalp. Here we used a roving standard experiment to record mismatch potentials to tone duration deviants with the aim to detect robust temporal and frontal mismatch components. Fourteen schizophrenic patients with normal intelligence and without overt cognitive deficits and age- and sex-matched controls were studied. In agreement with previous findings MMN recorded from the frontal scalp was markedly attenuated in patients. However, in contrast to previous reports, positive mismatch potentials of normal magnitude were recorded from temporal (mastoid) electrodes. This finding raises the possibility of a selective impairment in multiple mismatch generators in schizophrenia and may lend support for the notion of impaired cortico-cortical connectivity in schizophrenia.

Acoustic Stimulation↗
PubMed2002

Axonal gap junctions between principal neurons: a novel source of network oscillations, and perhaps epileptogenesis.

We hypothesized in 1998 that gap junctions might be located between the axons of principal hippocampal neurons, based on the shape of spikelets (fast prepotentials), occurring during gap junction-mediated very fast (to approximately 200 Hz) network oscillations in vitro. More recent electrophysiological, pharmacological and dye-coupling data indicate that axonal gap junctions exist; so far, they appear to be located about 100 microm from the soma, in CA1 pyramidal neurons. Computer modeling and theory predict that axonal gap junctions can lead to very fast network oscillations under three conditions: a) there are spontaneous axonal action potentials; b) the number of gap junctions in the network is neither too low (not less than to approximately 1.5 per cell on average), nor too high (not more than to approximately 3 per cell on average); c) action potentials can cross from axon to axon via gap junctions. Simulated oscillations resemble biological ones, but condition (c) remains to be demonstrated directly. Axonal network oscillations can, in turn, induce oscillatory activity in larger neuronal networks, by a variety of mechanisms. Axonal networks appear to underlie in vivo ripples (to approximately 200 Hz field potential oscillations superimposed on physiological sharp waves), to drive gamma (30-70 Hz) oscillations that appear in the presence of carbachol, and to initiate certain types of ictal discharge. If axonal gap junctions are important for seizure initiation in humans, there could be practical consequences for antiepileptic therapy: at least one gap junction-blocking compound, carbenoxolone, is already in clinical use (for treatment of ulcer disease), and it crosses the blood-brain barrier.

Animals↗