Ernst Martin - Academia.edu (original) (raw)

Papers by Ernst Martin

We studied the development of visual processing in 58 children, ranging from 1 d to 12 y of age (... more We studied the development of visual processing in 58 children, ranging from 1 d to 12 y of age (median age 29 mo), using functional magnetic resonance imaging. All but nine children had either been sedated using chloral hydrate (n = 12) or pentobarbital (n = 28). Nine children were studied under a full halothane/ N2O:O2 anesthesia. In the first postnatal month, 30% of the neonates showed a positive blood oxygenation level-dependent (BOLD) contrast signal, whereas, for infants between the ages of 1 mo and 1 y, 27% did so. Thirty-one percent of children between 1 and 6 y of age and 71% of children aged 6 y and above showed a positive BOLD contrast signal change to our visual stimulation paradigm. Besides the usual positive BOLD contrast signal change, we also noted that a large portion of the children measured displayed a negative BOLD contrast signal change. This negative BOLD contrast signal change was observed in 30% of children up to 1 mo of age, in 27% between 1 mo and 1 y of age, in 47% between 1 and 6 y of age, and in 14% of children 6 y and older. In the children in which we observed a negative correlating BOLD contrast signal change, the locus was more anterior and more lateral than the positive BOLD contrast signal, placing it in the secondary visual cortical area. The results indicate that when using functional magnetic resonance imaging on children, the primary visual cortical area does not respond functionally in the same manner as that of the adult until 1.5 y of age. This supports earlier clinical and electrophysiologic findings that different cortical mechanisms seem to contribute to visual perception at different times postnatally.

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 3, 2015

Marked changes in brain physiology and structure take place between childhood and adulthood, incl... more Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABA+/Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H2O with age in the subcortical voxel and by significantly higher GABA...

NeuroImage, 2008

Developmental dyscalculia (DD) is a specific learning disability affecting the normal acquisition... more Developmental dyscalculia (DD) is a specific learning disability affecting the normal acquisition of arithmetic skills. Current studies estimate that 3-6% of the school population is affected by DD. Genetic, neurobiological, and epidemiologic evidence indicates that dyscalculia is a brain-based disorder. Imaging studies suggest the involvement of parietal and prefrontal cortices in arithmetic tasks. The aim of the present study was to analyze if children with DD show structural differences in parietal, frontal, and cingulate areas compared to typically achieving children. Magnetic resonance imaging was obtained from 12 children with DD aged 9.3+/-0.2 years and 12 age-matched control children without any learning disabilities on a 1.5 T whole-body scanner. Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures was applied to compare the two groups in order to find differences in cerebral gray and white matter. Compared to controls, ...

Pediatric Research, 1999

Magnetic resonance imaging with diffusion- and T2-weighted imaging and 31P magnetic resonance spe... more Magnetic resonance imaging with diffusion- and T2-weighted imaging and 31P magnetic resonance spectroscopy was used to investigate the relationship between development of brain edema and alterations of the brain energy metabolism after hypoxia-ischemia (HI) brain injury in 7-d-old rats. The results were correlated with histologic examinations at various times during recovery up to 5 d. Moderate HI, induced by right common carotid artery ligation and subsequent exposure to 8% O2 for 90 min, produced a cytotoxic edema of 52+/-9% brain volume and depressed the ratio of phosphocreatine to inorganic phosphate from 1.43+/-0.21 to 0.11+/-0.09. Within 1 h of reoxygenation, the edema decreased to 4+/-2% of brain volume, demarcating the core of the lesion. At 5 h of recovery, a secondary cytotoxic edema together with a newly developing vasogenic edema expanded again, reaching its maximal extent of 45+/-10% brain volume at around 24 h. The ratio of phosphocreatine to inorganic phosphate recovered slowly, reaching 1.12+/-0.27 around 13 h. Thereafter it declined again in a manner analogous to the observations made in human newborns after severe perinatal asphyxia, reaching trough values of 0.48+/-0.22 around 24 h after HI. At the cellular level, the vast majority of neuronal death occurred before 15 h. Subsequently, strong glial activation lasted 2-3 d after HI. At 5 d, a cystic infarction of 35+/-12% brain volume was found. We conclude that the biphasic evolution of brain edema and energy metabolism reflects early neuronal and late glial damage in response to moderate HI injury. Therefore, the secondary energy breakdown reflects glial activation and subsequent glial death.

Journal of Therapeutic Ultrasound, 2014

Background: Recent clinical studies confirmed the high potential of MR-guided focused ultrasound ... more Background: Recent clinical studies confirmed the high potential of MR-guided focused ultrasound (MRgFUS) in the field of functional neurosurgery. While its ability for precise thermo-ablation within soft tissue is widely recognized, the impact of high-intensity focused ultrasound (HIFU) on larger vessels is less explored. We used a bifurcation aneurysm model in rabbits to investigate the possible effects on the walls of vascular aneurysms and to assess the risk and prospect of this procedure for managing neurovascular disorders. Methods: Experimental bifurcation aneurysms were microsurgically created in New Zealand white rabbits and sonicated using MRgFUS. Results: A temperature of max. 54°C could be achieved close to the aneurysm, and the shape and size of the aneurysm were noticeably changed, as shown by MR angiography. Conclusions: The presented rabbit model proved suitable and capable of being extended to acquire data on the effect of HIFU on aneurysms and larger vessels. The fact that HIFU led to an alteration of the aneurysm without inducing rupture encourages further investigations.

Neuroimage, 2010

Phonological awareness refers to the ability to perceive and manipulate the sound structure of la... more Phonological awareness refers to the ability to perceive and manipulate the sound structure of language and is especially important when children learn to read. Poor phonological awareness is considered the major cause for the emergence of reading difficulties. In this functional magnetic resonance imaging (fMRI) study, we examined the brain correlates of phonological processing in young beginning readers (aged 8.3±0.4y,

Journal of therapeutic ultrasound, 2014

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation... more Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibi...

Neuropsychologia, 2015

Very low birth weight (VLBW) premature born infants have a high risk to develop visual perceptual... more Very low birth weight (VLBW) premature born infants have a high risk to develop visual perceptual and learning deficits as well as widespread functional and structural brain abnormalities during infancy and childhood. Whether and how prematurity alters neural specialization within visual neural networks is still unknown. We used functional and structural brain imaging to examine the visual semantic system of VLBW born (o 1250 g, gestational age 25-32 weeks) adolescents (13-15 years, n ¼ 11, 3 males) and matched term born control participants (13-15 years, n ¼11, 3 males). Neurocognitive assessment revealed no group differences except for lower scores on an adaptive visuomotor integration test. All adolescents were scanned while viewing pictures of animals and tools and scrambled versions of these pictures. Both groups demonstrated animal and tool category related neural networks. Term born adolescents showed tool category related neural activity, i.e. tool pictures elicited more activity than animal pictures, in temporal and parietal brain areas. Animal category related activity was found in the occipital, temporal and frontal cortex. VLBW born adolescents showed reduced tool category related activity in the dorsal visual stream compared with controls, specifically the left anterior intraparietal sulcus, and enhanced animal category related activity in the left middle occipital gyrus and right lingual gyrus. Lower birth weight of VLBW adolescents correlated with larger thickness of the pericalcarine gyrus in the occipital cortex and smaller surface area of the superior temporal gyrus in the lateral temporal cortex. Moreover, larger thickness of the pericalcarine gyrus and smaller surface area of the superior temporal gyrus correlated with reduced tool category related activity in the parietal cortex. Together, our data suggest that very low birth weight predicts alterations of higher order visual semantic networks, particularly in the dorsal stream. The differences in neural specialization may be associated with aberrant cortical development of areas in the visual system that develop early in childhood.

Gender differences in the visuo-spatial and mathematical cognitive domain seem to rely on the pre... more Gender differences in the visuo-spatial and mathematical cognitive domain seem to rely on the preferences for different cognitive strategies. Such differences may involve or reflect different neural circuits. In this study three number related tasks and a mental rotation fMRI-paradigm were used to examine whether different brain activation and performance patterns could be observed between genders. In a simple magnitude

Pediatric Research, 2002

Hypothermia may be an ideal neuroprotective intervention in hypoxic-ischemic encephalopathy after... more Hypothermia may be an ideal neuroprotective intervention in hypoxic-ischemic encephalopathy after perinatal asphyxia. The present study describes the long-term effects of prolonged resuscitative whole-body hypothermia initiated 2 h after hypoxic-ischemic injury on brain morphology and neuropsychological behavior in 7-d-old rats. After right common carotid artery ligation and exposure to hypoxia of 8% O(2) for 105 min, 10 animals were kept normothermic at 37 degrees C and 10 animals were cooled to 30 degrees C rectal temperature for 26 h, starting 2 h after the hypoxic-ischemic insult. All hypoxic-ischemic animals were gavage fed to guarantee long-term survival. Neuroprotection was evaluated by magnetic resonance imaging and behavioral testing. Hypothermia significantly reduced the final size of cerebral infarction by 23% at 6 wk after the insult. The most extended tissue rescue was found in the hippocampus (21%, p = 0.031), followed by the striatum (13%, p = 0.143) and the cortex (11%, p = 0.160). Cooling salvaged spatial memory deficits verified at 5 wk of recovery with Morris Water Maze test; whereas circling abnormalities after apomorphine injection and sensory motor dysfunctions on rotating treadmill improved, yet did not reach statistical significance. When compared with controls, hypoxic-ischemic animals performed worse in all behavioral tests. Hypothermia did not influence functional outcome in controls. Significant correlations between behavioral performance and corresponding regional brain volumes were found. We conclude that 26 h of mild to moderate resuscitative hypothermia leads not only to brain tissue rescue, but most important to long-lasting behavioral improvement throughout brain maturation despite severity of injury and delayed onset of cooling.

JAMA, 2014

Premature infants are at risk of developing encephalopathy of prematurity, which is associated wi... more Premature infants are at risk of developing encephalopathy of prematurity, which is associated with long-term neurodevelopmental delay. Erythropoietin was shown to be neuroprotective in experimental and retrospective clinical studies. To determine if there is an association between early high-dose recombinant human erythropoietin treatment in preterm infants and biomarkers of encephalopathy of prematurity on magnetic resonance imaging (MRI) at term-equivalent age. A total of 495 infants were included in a randomized, double-blind, placebo-controlled study conducted in Switzerland between 2005 and 2012. In a nonrandomized subset of 165 infants (n=77 erythropoietin; n=88 placebo), brain abnormalities were evaluated on MRI acquired at term-equivalent age. Participants were randomly assigned to receive recombinant human erythropoietin (3000 IU/kg; n=256) or placebo (n=239) intravenously before 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth. The primary outcome of the trial, neurodevelopment at 24 months, has not yet been assessed. The secondary outcome, white matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method. The resulting white matter injury and gray matter injury scores were categorized as normal or abnormal according to thresholds established in the literature by correlation with neurodevelopmental outcome. At term-equivalent age, compared with untreated controls, fewer infants treated with recombinant human erythropoietin had abnormal scores for white matter injury (22% [17/77] vs 36% [32/88]; adjusted risk ratio [RR], 0.58; 95% CI, 0.35-0.96), white matter signal intensity (3% [2/77] vs 11% [10/88]; adjusted RR, 0.20; 95% CI, 0.05-0.90), periventricular white matter loss (18% [14/77] vs 33% [29/88]; adjusted RR, 0.53; 95% CI, 0.30-0.92), and gray matter injury (7% [5/77] vs 19% [17/88]; adjusted RR, 0.34; 95% CI, 0.13-0.89). In an analysis of secondary outcomes of a randomized clinical trial of preterm infants, high-dose erythropoietin treatment within 42 hours after birth was associated with a reduced risk of brain injury on MRI. These findings require assessment in a randomized trial designed primarily to assess this outcome as well as investigation of the association with neurodevelopmental outcomes. clinicaltrials.gov Identifier: NCT00413946.

Neuropsychologia, 2009

Developmental dyslexia is a highly prevalent and specific disorder of reading acquisition charact... more Developmental dyslexia is a highly prevalent and specific disorder of reading acquisition characterised by impaired reading fluency and comprehension. We have previously identified fMRI-and ERP-based neural markers of impaired sentence reading in dyslexia that indicated both deviant basic word processing and deviant semantic incongruency processing. However, it remained unclear how specific these impairments are for dyslexia, as they occurred when children with dyslexia (DYS) were compared to chronological agematched controls (CA) who also differ in the amount of reading experience. Adding a younger control group at a similar reading level (RL) as the dyslexic group, we examined here which of these markers would be specific for dyslexia despite matched performance, and which would resemble a developmental delay. Both the RL group and the DYS group showed a similar reversal of incongruency effects in the inferior parietal region (fMRI data) and similarly reduced incongruency effects around 400 ms (ERP data) compared to the CA group, suggesting that the semantic impairment in dyslexia resembles a developmental delay. Furthermore, the DYS group showed reduced sentence reading-related activation in the inferior parietal cortex in the fMRI data, and at around 100 ms (trend) and 400 ms in the ERP data when compared to both CA and RL groups, suggesting dyslexia-specific deficits in basic word processing during sentence reading. Low reading skills due to young age and due to dyslexia-specific word processing deficits thus reflect different pathways which impair semantic processing in similar ways.

Schizophrenia Research, 2005

Background: Based on animal data, NMDA receptor hypofunction has been suggested as a model for po... more Background: Based on animal data, NMDA receptor hypofunction has been suggested as a model for positive symptoms in schizophrenia. NMDA receptor hypofunction affects several corticolimbic brain regions, of which the posterior cingulate seems to be the most sensitive. However, empirical support for a crucial role of posterior cingulate NMDA hypofunction in the pathophysiology of positive symptoms is still missing in humans. We therefore conducted an fMRI study using the NMDA antagonist ketamine in healthy human subjects during episodic memory retrieval, which is supposed to activate the posterior cingulate. Methods: We investigated 16 healthy subjects which were assigned to either placebo (n=7; saline) or ketamine (n=9; 0.6 mg/kg/ h) group in a double-blind study design. All subjects received their infusion while performing an episodic memory retrieval task in the scanner. Immediately after the fMRI session, psychopathological effects of ketamine were measured using the Altered States of Consciousness Questionnaire. Results: The placebo group showed BOLD signal increases in the posterior and anterior cingulate during retrieval. Signal increases were significantly lower in the ketamine group. Lower signal increases in the posterior cingulate correlated significantly with positive (i.e. psychosis-like) symptoms induced by ketamine. 0920-9964/$ -see front matter D (G. Northoff). Schizophrenia Research 72 (2005) 235 -248 www.elsevier.com/locate/schres Conclusion: The present study for the first time demonstrates a relationship between NMDA receptors, posterior cingulate and positive (i.e. psychosis-like) symptoms in humans. Confirming findings from animal studies, it supports the hypothesis of a pathophysiological role of NMDA receptor hypofunction in the posterior cingulate in schizophrenia. D

PLoS ONE, 2012

In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding wo... more In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was -in contrast to EEG power-positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that these opposite correlations with different distributions undergo similar and significant neuronal developments with brain maturation.

Pediatric Research, 1995

Diffusion-weighted and transversal relaxation time (T2)-weighted magnetic resonance imaging were ... more Diffusion-weighted and transversal relaxation time (T2)-weighted magnetic resonance imaging were used to study the relationship between the duration of hypoxia-ischemia [unilateral common carotid artery (CCA) ligation and exposure to 8% oxygen] and the in vivo visualization of brain edema in 7-d-old rats. After CCA ligation, 35 animals were divided into five groups according to the length of exposure to 8% oxygen: no exposure (n = 9), 15 min (n = 12), 30 min (n = 5), and 1 h (n = 9) exposure; six animals served as controls. Diffusion weighted images were acquired 2 h after the hypoxic-ischemic insult, sequential T2 weighted images were recorded for up to 7 d and the outcome was documented by histologic examination at 21 d. The apparent diffusion coefficient of water in the ipsilateral cortex was significantly decreased in all animals recovering from prolonged hypoxic-ischemic insult (30 min and longer), whereas this was the case in only 40% of animals exposed to 15 min of hypoxia. Moreover, T2 prolongation of brain tissue occurred only in the former group. These results indicate transient and reversible alterations of physiologic water compartmentation for short term hypoxia-ischemia, but irreversible edema formation for long term hypoxia-ischemia. They support the hypothesis that the duration of hypoxia-ischemia determines whether a vasogenic edema and infarction follows the initial cytotoxic edema.

Pediatric Research, 1997

Secondary brain damage after transient cerebral hypoxia-ischemia (HI) is caused by a cascade of c... more Secondary brain damage after transient cerebral hypoxia-ischemia (HI) is caused by a cascade of cellular events. In this study, complementary methods of magnetic resonance imaging and histochemistry were used to investigate the formation of cytotoxic and vasogenic edema during secondary brain damage induced by transient HI in 7-d-old rats. To elicit injury, 21 rats underwent right common carotid artery ligation followed by 1.5 h of 8% O2 exposure. Sequential apparent diffusion coefficient (ADC) and transversal relaxation time (T2) weighted magnetic resonance imaging were recorded for up to 3 d in 13 7-d-old rats. Eight animals were killed at various intervals between the end of HI and 21 h of recovery to perform histochemical assays using neuronal and astrocytic markers. Changes of the ADC revealed a biphasic function for the evolution of cytotoxic edema during the recovery period. At the end of HI, the ADC in the ipsilateral cortex was significantly decreased. Upon reoxygenation, it returned transiently to normal followed by a secondary, although less pronounced, decline after 8-48 h. After this, the ADC rose steadily. From 8 h of recovery, the proportion of vasogenic edema steadily increased as indicated by the T2 prolongation. At 21 h, the majority of glial cells showed immunoreactivity for glial fibrillary acidic protein and were of larger size, whereas the neurons were apoptotic. These results indicate that the delayed cerebral injury is accompanied by late glial swelling in conjunction with an enlarged interstitial space due to cell damage.

Pediatric Research, 1999

Pediatric Research, 2005

Developmental delay (DD) in children is a common socioeconomic problem with a prevalence of 1-2%.... more Developmental delay (DD) in children is a common socioeconomic problem with a prevalence of 1-2%. The cause of DD in children is often unknown, and magnetic resonance imaging plays an important role in evaluating children with DD, estimating long-term prognosis, and guiding therapeutic options. The aim of our study on children with DD was to elucidate 1) whether magnetic resonance spectroscopy (MRS) reveals abnormalities in cerebral metabolism and 2) whether there is a correlation between the cognitive performance and the concentration of brain metabolites, especially N-acetylaspartate (NAA), named in the literature a neuronal marker. Using proton MRS of deep gray and central white matter, we measured concentrations of brain metabolites in 48 children, who were aged 1 mo to 13 y and had unexplained DD [developmental quotient (DQ) between Ͻ50 and 85] and normal magnetic resonance imaging examinations, and compared them with those of 23 age-matched normal control children. Children with DD were divided into three groups: mild (DQ 76 -85), moderate (DQ 51-75), and severe (DQ Ͻ50). We found no significant differences in metabolite concentrations, neither among the three groups of children with DD nor between patients and age-matched normal control children. Independent of the degree of mental retardation, the NAA concentrations of handicapped patients and normal children were comparable. We conclude that 1) brain metabolites, especially NAA, in children with unexplained DD are within normal limits, and 2) in most cases, proton MRS adds little information concerning cause of unexplained DD. (Pediatr Res 58: 754-760, 2005) Abbreviations Cho, choline Cr, creatine DD, developmental delay DQ, developmental quotient Gln, glutamine Glu, glutamate mIns, myo-inositol MRI, magnetic resonance imaging MRS, magnetic resonance spectroscopy NAA, N-acetylaspartate NAAG, N-acetyl-aspartylglutamate ABSTRACT 754

Pediatric Radiology, 2003

NeuroReport, 2008

We explored the processing mechanisms of featural and con¢gural face information using event-rela... more We explored the processing mechanisms of featural and con¢gural face information using event-related functional magnetic resonance imaging. Featural information describes the information contained in the facial parts; con¢gural information conveys the spatial interrelationship between parts. In a delayed matching-to-sample task, participants decided whether an intact test face matched a precedent scrambled or blurred cue face. Scrambled faces primarily contain featural information whereas blurred faces preserve con¢gural information. Scrambled cue faces evoked enhanced activation in the left fusiform gyrus, left parietal lobe, and left lingual gyrus when viewing intact test faces. Following blurred cue faces, test faces enhanced activation bilaterally in the middle temporal gyrus. The results suggest that featural and con¢gural information is processed by following distinct neural pathways. NeuroReport 19:287^291

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 3, 2015

NeuroImage, 2008

Pediatric Research, 1999

Journal of Therapeutic Ultrasound, 2014

Neuroimage, 2010

Journal of therapeutic ultrasound, 2014

Neuropsychologia, 2015

Pediatric Research, 2002

JAMA, 2014

Neuropsychologia, 2009

Schizophrenia Research, 2005

PLoS ONE, 2012

Pediatric Research, 1995

Pediatric Research, 1997

Pediatric Research, 1999

Pediatric Research, 2005

Pediatric Radiology, 2003

NeuroReport, 2008