Hans Forssberg

Stockholm University, Stockholm, Stockholm, Sweden

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Publications (72)268.8 Total impact

  • Article: Cognitive Outcome in Adolescents and Young Adults after Repeat Courses of Antenatal Corticosteroids.
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    ABSTRACT: OBJECTIVE: To investigate whether repeat courses of antenatal corticosteroids have long-term effects on cognitive and psychological functioning. STUDY DESIGN: In a prospective cohort study, 58 adolescents and young adults (36 males) who had been exposed to 2-9 weekly courses of betamethasone in utero were assessed with neuropsychological tests and behavior self-reports. Unexposed subjects (n = 44, 25 males) matched for age, sex, and gestational age at birth served as a comparison group. In addition, individuals exposed in utero to a single course (n = 25, 14 males) were included for dose-response analysis. Group differences were investigated using multilevel linear modeling. RESULTS: Mean scores obtained in 2 measures of attention and speed were significantly lower in subjects exposed to 2 or more antenatal corticosteroids courses (Symbol Search, P = .009; Digit Span Forward, P = .02), but these were not dose-dependent. Exposure to repeat courses of antenatal corticosteroids was not associated with general deficits in higher cognitive functions, self-reported attention, adaptability, or overall psychological function. CONCLUSIONS: Although this study indicates that repeat exposure to antenatal corticosteroids may have an impact on aspects of executive functioning, it does not provide support for the prevailing concern that such fetal exposure will have a major adverse impact on cognitive functions and psychological health later in life.
    The Journal of pediatrics 02/2013; · 4.02 Impact Factor
  • Article: Neuroradiology Can Predict the Development of Hand Function in Children With Unilateral Cerebral Palsy.
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    ABSTRACT: BACKGROUND: . Much variation is found in the development of hand function in children with unilateral cerebral palsy (CP). OBJECTIVE: . To explore how anatomic brain abnormalities can be used to predict the development of hand function. METHODS: . A total of 32 children with unilateral CP (16 boys and 16 girls) were evaluated at least once a year by the Assisting Hand Assessment (AHA). The data collection covered an age range from 18 months to 8 years (mean time in study, 4 years and 6 months). Computerized tomography or magnetic resonance imaging of the brain were assessed for patterns of brain damage, including the location of gray and extent of white-matter damage. The children were divided into groups according to lesion characteristics, and a series of univariate models were analyzed with a nonlinear mixed-effects model. The rate and maximum limit of development were calculated. RESULTS: . The highest predictive power of better development of hand function was the absence of a concurrent lesion to the basal ganglia and thalamus, independent of the basic type of brain lesion. This model predicted both the rate of increasing ability and hand function at age 8 years. Hand function was also predicted by the basic pattern of damage and by the extent of white-matter damage. The presence of unilateral or bilateral damage had no predictive value. CONCLUSIONS: . Neuroradiological findings can be used to make a crude prediction of the future development of the use of the affected hand in young children with unilateral CP.
    Neurorehabilitation and neural repair 06/2012; · 4.49 Impact Factor
  • Article: Dissociation of brain areas associated with force production and stabilization during manipulation of unstable objects.
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    ABSTRACT: Multifinger dexterous manipulation of unstable or deformable objects requires control of both direction and magnitude of fingertip force vectors. Our aim was to study the neuroanatomical correlates of these two distinct control functions. Brain activity was measured using functional magnetic resonance imaging while 16 male subjects (age: 26-42, M = 32, SD ± 4 years) compressed four springs representing a 2 × 2 factorial design with two levels of force and instability requirements. Significant activations associated with higher instability were located bilaterally in the precentral gyri, the postcentral gyrus, and the cerebellum. In the main effect for high force, activity was found in areas located in the primary motor regions contralateral to the active hand and bilaterally in the cerebellum. An overlap in activation between the two main effects was found bilaterally in the cerebellum (lobule VI). This study not only confirms a recently described bilateral fronto-parieto-cerebellar network for manipulation of increasingly unstable objects, but critically extends our understanding by describing its differentiated modulation with both force magnitude and instability requirements. Our results, therefore, expose a previously unrecognized and context-sensitive system of brain regions that enable dexterous manipulation for different force magnitude and instability requirements of the task.
    Experimental Brain Research 12/2011; 215(3-4):359-67. · 2.39 Impact Factor
  • Article: Grip force coordination during bimanual tasks in unilateral cerebral palsy.
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    ABSTRACT: The aim of the study was to investigate coordination of fingertip forces during an asymmetrical bimanual task in children with unilateral cerebral palsy (CP). Twelve participants (six males, six females; mean age 14y 4mo, SD 3.3y; range 9-20y;) with unilateral CP (eight right-sided, four left-sided) and 15 age-matched typically developing participants (five males, 10 females; mean age 14y 3mo, SD 2.9y; range 9-18y,) were included. Participants were instructed to hold custom-made grip devices in each hand and place one device on top of the other. The grip force and load force were recorded simultaneously in both hands. Temporal coordination between the two hands was impaired in the participants with CP (compared with that in typically developing participants), that is they initiated the task by decreasing grip force in the releasing hand before increasing the force in the holding hand. The grip force increase in the holding hand was also smaller in participants with CP (involved hand/non-dominant hand releasing, p<0.001; non-involved hand/dominant hand releasing, p=0.007), indicating deficient scaling of force amplitude. The impairment was greater when participants with CP used their non-involved hand as the holding hand. Temporal coordination and scaling of fingertip forces were impaired in both hands in participants with CP. The non-involved hand was strongly affected by activity in the involved hand, which may explain why children with unilateral CP prefer to use only one hand during tasks that are typically performed with both hands.
    Developmental Medicine & Child Neurology 10/2011; 53(10):920-6. · 2.92 Impact Factor
  • Article: Validation of a new biomechanical model to measure muscle tone in spastic muscles.
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    ABSTRACT: There is no easy and reliable method to measure spasticity, although it is a common and important symptom after a brain injury. The aim of this study was to develop and validate a new method to measure spasticity that can be easily used in clinical practice. A biomechanical model was created to estimate the components of the force resisting passive hand extension, namely (a) inertia (IC), (b) elasticity (EC), (c) viscosity (VC), and (d) neural components (NC). The model was validated in chronic stroke patients with varying degree of hand spasticity. Electromyography (EMG) was recorded to measure the muscle activity induced by the passive stretch. The model was validated in 3 ways: (a) NC was reduced after an ischemic nerve block, (b) NC correlated with the integrated EMG across subjects and in the same subject during the ischemic nerve block, and (c) NC was velocity dependent. In addition, the total resisting force and NC correlated with the modified Ashworth score. According to the model, the neural and nonneural components varied between patients. In most of the patients, but not in all, the NC dominated. The results suggest that the model allows valid measurement of spasticity in the upper extremity of chronic stroke patients and that it can be used to separate the neural component induced by the stretch reflex from resistance caused by altered muscle properties.
    Neurorehabilitation and neural repair 04/2011; 25(7):617-25. · 4.49 Impact Factor
  • Article: Normal gut microbiota modulates brain development and behavior.
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    ABSTRACT: Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
    Proceedings of the National Academy of Sciences 02/2011; 108(7):3047-52. · 9.68 Impact Factor
  • Article: Antenatal corticosteroids for preterm birth: dose-dependent reduction in birthweight, length and head circumference.
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    ABSTRACT: This study was undertaken to evaluate the effects of repeated courses of antenatal corticosteroids (ACS) on foetal growth. We studied 94 infants exposed to 2-9 courses of ACS. Mean gestational age (GA) at first exposure was 29 and at birth 34 weeks. Exposure data were retrieved from case record files. Information on potential confounders was collected from the Swedish Medical Birth Registry. Standard deviation scores (SDS) for birthweight (BW), birthlength (BL) and head circumference (HC) were calculated and considered as outcomes. GA at start of ACS did not affect outcome. BW-SDS, BL-SDS and HC-SDS were -0.21, -0.19 and +0.25 in infants exposed to two courses, compared to -1.01, -1.04 and -0.23 in infants exposed to ≥ 4 courses of ACS (p = 0.04-0.07). In multiple regression analyses, ≥ 4 courses were associated with lower BW-SDS, BL-SDS and HC-SDS (p = 0.007-0.04) compared to SDS after 2-3 courses. The effects from ≥ 4 courses on BW and BL were comparable to reduction in birth size seen in twins and on HC to that observed after maternal smoking. Multiple courses of ACS are associated with a dose-dependent decline in foetal growth, which may affect later development and health.
    Acta Paediatrica 11/2010; 100(3):364-9. · 2.07 Impact Factor
  • Article: Evidence of validity in a new method for measurement of dexterity in children and adolescents.
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    ABSTRACT: many everyday activities involve manipulation of objects with the fingertips. Impaired performance in manipulative tasks is common in neurodevelopmental disorders. Thus accurate assessment of an individual's ability to coordinate fingertip forces is important for planning treatment. We evaluated a recently developed assessment tool (the Strength-Dexterity Test), which is based on manipulation of unstable objects, in a paediatric population. a Rasch model was used to examine the validity and reliability of the Strength-Dexterity Test in a sample of 56 typically developing children and adolescents (30 males, 26 females; age range 4y 10mo-17y 3mo; mean age 9y 8mo, SD 3y 8mo). In addition, we examined how performance on this test relates to widely used tests for assessment of gross manual dexterity (assessed with the Box and Blocks Test) and finger strength measured with a pinch meter. the constructs measured with the 78-item Strength-Dexterity Test include dexterity and strength, and form a unique unidimensional latent trait, named fingertip force coordination, that improves with age. The test has internal scale validity when applied to a typical paediatric population. Positive correlations (significant at p<0.001) were found among all three tests. we provide preliminary evidence of construct validity in the Strength-Dexterity Test. Our findings suggest that this test has the potential to be developed into a promising tool for assessing dexterity in children.
    Developmental Medicine & Child Neurology 05/2010; 52(10):948-54. · 2.92 Impact Factor
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    Article: Dopamine D2 receptor density in the limbic striatum is related to implicit but not explicit movement sequence learning.
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    ABSTRACT: A large body of literature suggests that motor sequence learning involves dopamine-modulated plastic processes in the basal ganglia. Sequence learning can occur both implicitly, without conscious awareness and intention to learn, and explicitly, i.e., under conscious control. Here, we investigated whether individual differences in implicit and explicit sequence learning of movement sequences in a group of 15 healthy participants are related to dopamine D2 receptor densities in functional subregions of the striatum. Sequence learning was assessed using the serial reaction time task, and measures of implicit and explicit knowledge were estimated using a process dissociation procedure. Correlation analyses were performed between these measures and D2 receptor densities, which had been measured previously with positron emission tomography. Striatal D2 densities were negatively related to measures of sequence learning. In the limbic subregion, D2 densities were specifically related to implicit but not explicit learning. These findings suggest that individual differences in striatal DA function underlie differences in sequence learning ability and support that implicit and explicit sequence learning depend on partly distinct neural circuitry. The findings are also in line with the general view that implicit learning systems are evolutionarily primitive and tend to rely more on phylogenetically old neural circuitry than does explicit learning and cognition.
    Proceedings of the National Academy of Sciences 04/2010; 107(16):7574-9. · 9.68 Impact Factor
  • Article: Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys.
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    ABSTRACT: Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC). Pregnant marmosets were exposed to DEX (5 mg/kg body weight) or vehicle during early (days 42-48) or late (days 90-96) stages of the 144-day pregnancy. In neonates, relative to controls, glucocorticoid receptor (GR) mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR) mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment. These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences.
    Behavioral and Brain Functions 03/2010; 6:18. · 2.13 Impact Factor
  • Article: Deficits in fine motor skills in a genetic animal model of ADHD.
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    ABSTRACT: In an attempt to model some behavioral aspects of Attention Deficit/Hyperactivity Disorder (ADHD), we examined whether an existing genetic animal model of ADHD is valid for investigating not only locomotor hyperactivity, but also more complex motor coordination problems displayed by the majority of children with ADHD. We subjected young adolescent Spontaneously Hypertensive Rats (SHRs), the most commonly used genetic animal model of ADHD, to a battery of tests for motor activity, gross motor coordination, and skilled reaching. Wistar (WIS) rats were used as controls. Similar to children with ADHD, young adolescent SHRs displayed locomotor hyperactivity in a familiar, but not in a novel environment. They also had lower performance scores in a complex skilled reaching task when compared to WIS rats, especially in the most sensitive measure of skilled performance (i.e., single attempt success). In contrast, their gross motor performance on a Rota-Rod test was similar to that of WIS rats. The results support the notion that the SHR strain is a useful animal model system to investigate potential molecular mechanisms underlying fine motor skill problems in children with ADHD.
    Behavioral and Brain Functions 01/2010; 6:51. · 2.13 Impact Factor
  • Article: Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys
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    ABSTRACT: Abstract Background Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. Methods In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC). Pregnant marmosets were exposed to DEX (5 mg/kg body weight) or vehicle during early (days 42-48) or late (days 90-96) stages of the 144-day pregnancy. Results In neonates, relative to controls, glucocorticoid receptor (GR) mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR) mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment. Conclusion These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences.
    Behavioral and Brain Functions. 01/2010;
  • Article: Structural correlates of preterm birth in the adolescent brain.
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    ABSTRACT: The Stockholm Neonatal Project involves a prospective, cross-sectional, population-based, cohort monitored for 12 to 17 years after birth; it was started with the aim of investigating the long-term structural correlates of preterm birth and comparing findings with reports on similar cohorts. High-resolution anatomic and diffusion tensor imaging data measuring diffusion in 30 directions were collected by using a 1.5-T MRI scanner. A total of 143 adolescents (12.18-17.7 years of age) participated in the study, including 74 formerly preterm infants with birth weights of <or=1500 g (range: 645-1486 g) and 69 term control subjects. The 2 groups were well matched with respect to demographic and socioeconomic data. The anatomic MRI data were used for calculation of total brain volumes and voxelwise comparison of gray matter (GM) volumes. The diffusion tensor imaging data were used for voxelwise comparison of white matter (WM) microstructural integrity. The formerly preterm individuals possessed 8.8% smaller GM volume and 9.4% smaller WM volume. The GM and WM volumes of individuals depended on gestational age and birth weight. The reduction in GM could be attributed bilaterally to the temporal lobes, central, prefrontal, orbitofrontal, and parietal cortices, caudate nuclei, hippocampi, and thalami. Lower fractional anisotropy was observed in the posterior corpus callosum, fornix, and external capsules. Although preterm birth was found to be a risk factor regarding long-term structural brain development, the outcome was milder than in previous reports. This may be attributable to differences in social structure and neonatal care practices.
    PEDIATRICS 11/2009; 124(5):e964-72. · 4.47 Impact Factor
  • Article: Hand function in relation to brain lesions and corticomotor-projection pattern in children with unilateral cerebral palsy.
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    ABSTRACT: To investigate relationships between hand function, brain lesions, and corticomotor projections in children with unilateral cerebral palsy (CP). The study included 17 children (nine males, eight females; mean age 11.4 [SD 2.4] range 7-16 y), with unilateral CP at Gross Motor Function Classification System level I and Manual Ability Classification System level I or II. Hand function was assessed with the Box and Blocks test and Assisting Hand Assessment (AHA). Conventional structural magnetic resonance images were assessed visually for type, location, and extent of brain lesions. Single-pulse transcranial magnetic stimulation (TMS) provided information on organization of corticomotor projections. The most favourable hand function was seen in children who had white-matter damage of immaturity with mild white-matter loss and contralateral motor projections. Children with ipsilateral projections had the most impaired function. Nevertheless, in this subgroup a range of ability was seen (AHA 29-59%). Motor-projection patterns appeared to be influenced by lesion extent and location, but not by lesion type. Combining information from structural magnetic resonance images and TMS can improve prediction of hand function. A wide variation in hand function was seen within all motor-projection patterns. Although the most impaired hand function was seen in the ipsilateral motor-projection group, some children in this group had fairly good ability. Such information is important for treatment planning.
    Developmental Medicine & Child Neurology 10/2009; 52(2):145-52. · 2.92 Impact Factor
  • Article: Cortical activity in relation to velocity dependent movement resistance in the flexor muscles of the hand after stroke.
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    ABSTRACT: The role of spinal networks in spasticity is well investigated, but little is known about possible cortical contributions to hypertonicity across a joint. The authors hypothesized that there are cortical activation correlates to spasticity in stroke patients with increased muscle tone of the wrist flexors. Stroke patients and controls were scanned using event-related functional magnetic resonance imaging (fMRI) during slow and fast passive movements of the hand with simultaneous recording of passive movement resistance (PMR). Control participants had velocity-dependent activity (greater for slow than fast movements) of 2 types, in areas that were also more active in passive movement than rest (eg, relative increase in activation in contralateral S1 and M1 was greater for slow than fast) and in areas that were also more active in rest than passive movement (eg, relative decrease in activation in occipital areas and ipsilateral precentral gyrus was greater for fast than slow). In the patient group, with large interindividual variation of spasticity, we found an association between PMR and the velocity-dependent activity in ipsilateral S1 (area 3b) extending into M1 (area 4a), contralateral cingulate cortex, supplementary motor area (SMA), Brodmann Area 45 (BA 45), and cerebellum. Post hoc testing also revealed a similar correlation in S1 and M1 bilaterally in controls and showed that patients activated ipsilateral S1 and M1 more than controls in the velocity-dependent condition. The findings suggest the possibility of ipsilateral sensory and motor cortical involvement in spasticity after stroke, which warrant further investigation.
    Neurorehabilitation and neural repair 06/2009; 23(8):800-10. · 4.49 Impact Factor
  • Article: Long-term effects of botulinum toxin A in children with cerebral palsy.
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    ABSTRACT: The long-term effects of botulinum toxin A (BoNT-A) treatment in children with cerebral palsy (CP) are still elusive. We studied a prospective clinical cohort of 94 children with different subtypes (50% spastic diplegic CP, 22% hemiplegic CP, 25% tetraplegic CP, 3% dyskinetic CP), sex (55% male, 45% female), severity according to Gross Motor Function Classification System (29% Level I, 15% Level II, 16% Level III, 17% Level IV, 23% Level V), and age (median 5y 4mo, range 11mo-17y 8mo). The longest follow-up time was 3 years 7 months (median 1y 6mo) and included a maximum of eight injections per muscle (median two injections to a specific muscle). Outcome measurements were muscle tone (Modified Ashworth Scale) and joint range of motion (ROM). Assessments were made at a minimum before and 3 months after each injection. Ninety-five per cent confidence intervals for differences from baseline were used to identify significant changes. BoNT-A injections induced reduction of long-term spasticity in all muscle-groups examined: the gastrocnemius, hamstring, and adductor muscles. The reduction in tone was most distinct in the gastrocnemius muscle, and each repeated injection produced an immediate reduction in muscle tone. However, improvement in ROM was brief and measured only after the first injections, whereupon the ROM declined. Thus, the results suggest that BoNT-A can be effective in reducing muscle tone over a longer period, but not in preventing development of contractures in spastic muscles. The dissociation between the effects on muscle tone and ROM indicates that development of contractures is not coupled to increased muscle tone only, but might be caused by other mechanisms.
    Developmental Medicine & Child Neurology 03/2009; 51(2):120-7. · 2.92 Impact Factor
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    Article: Changes in cortical dopamine D1 receptor binding associated with cognitive training.
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    ABSTRACT: Working memory is a key function for human cognition, dependent on adequate dopamine neurotransmission. Here we show that the training of working memory, which improves working memory capacity, is associated with changes in the density of cortical dopamine D1 receptors. Fourteen hours of training over 5 weeks was associated with changes in both prefrontal and parietal D1 binding potential. This plasticity of the dopamine D1 receptor system demonstrates a reciprocal interplay between mental activity and brain biochemistry in vivo.
    Science 03/2009; 323(5915):800-2. · 31.20 Impact Factor
  • Article: Listening to rhythms activates motor and premotor cortices.
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    ABSTRACT: We used functional magnetic resonance imaging (fMRI) to identify brain areas involved in auditory rhythm perception. Participants listened to three rhythm sequences that varied in temporal predictability. The most predictable sequence was an isochronous rhythm sequence of a single interval (ISO). The other two sequences had nine intervals with unequal durations. One of these had interval durations of integer ratios relative to the shortest interval (METRIC). The other had interval durations of non-integer ratios relative to the shortest interval (NON-METRIC), and was thus perceptually more complex than the other two. In addition, we presented unpredictable sequences with randomly distributed intervals (RAN). We tested two hypotheses. Firstly, that areas involved in motor timing control would also process the temporal predictability of sensory cues. Therefore, there was no active task included in the experiment that could influence the participant perception or induce motor preparation. We found that dorsal premotor cortex (PMD), SMA, preSMA, and lateral cerebellum were more active when participants listen to rhythm sequences compared to random sequences. The activity pattern in supplementary motor area (SMA) and preSMA suggested a modulation dependent on sequence predictability, strongly suggesting a role in temporal sensory prediction. Secondly, we hypothesized that the more complex the rhythm sequence, the more it would engage short-term memory processes of the prefrontal cortex. We found that the superior prefrontal cortex was more active when listening to METRIC and NON-METRIC compared to ISO. We argue that the complexity of rhythm sequences is an important factor in modulating activity in many of the rhythm areas. However, the difference in complexity of our stimuli should be regarded as continuous.
    Cortex 11/2008; 45(1):62-71. · 6.08 Impact Factor
  • Article: Effects of prenatal dexamethasone treatment on physical growth, pituitary-adrenal hormones, and performance of motor, motivational, and cognitive tasks in juvenile and adolescent common marmoset monkeys.
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    ABSTRACT: Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to prevent respiratory distress syndrome in preterm infants, but there is emerging evidence of subsequent neurobehavioral abnormalities (e.g. problems with inattention/hyperactivity). In the present study, we exposed pregnant common marmosets (Callithrix jacchus, primates) to daily repeated DEX (5 mg/kg by mouth) during either early (d 42-48) or late (d 90-96) pregnancy (gestation period of 144 days). Relative to control, and with a longitudinal design, we investigated DEX effects in offspring in terms of physical growth, plasma ACTH and cortisol titers, social and maintenance behaviors, skilled motor reaching, motivation for palatable reward, and learning between infancy and adolescence. Early DEX resulted in reduced sociability in infants and increased motivation for palatable reward in adolescents. Late DEX resulted in a mild transient increase in knee-heel length in infants and enhanced reversal learning of stimulus-reward association in adolescents. There was no effect of either early or late DEX on basal plasma ACTH or cortisol titers. Both treatments resulted in impaired skilled motor reaching in juveniles, which attenuated in early DEX but persisted in late DEX across test sessions. The increased palatable-reward motivation and decreased social motivation observed in early DEX subjects provide experimental support for the clinical reports that prenatal glucocorticoid treatment impairs social development and predisposes to metabolic syndrome. These novel primate findings indicate that fetal glucocorticoid overexposure can lead to abnormal development of motor, affective, and cognitive behaviors. Importantly, the outcome is highly dependent upon the timing of glucocorticoid overexposure.
    Endocrinology 09/2008; 149(12):6343-55. · 4.46 Impact Factor
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    Article: Phonological working memory with auditory presentation of pseudo-words -- an event related fMRI Study.
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    ABSTRACT: Phonological working memory (PWM) tasks consist of a sequence of stimulus-encoding, maintenance and response. Few previous functional magnetic resonance imaging (fMRI) studies of PWM have employed event-related designs that make it possible to analyze the activations associated with each phase of such a task. The exploration of the cortical activation that takes place during the maintenance of PWM has been of particular interest to us. It has been suggested that temporary storage is served by the inferior parietal cortex. However, to the best of our knowledge earlier studies have used visual stimuli that might generate different cortical activations than auditory stimuli, which, presumably, would be more dependent on the auditory association cortex in the temporal lobe. This study involved an auditory stimulus presentation and a forced two-choice task. We used a parametric event-related design with fMRI. The stimuli consisted of pseudo-words of five, seven and nine syllables in length. In the control task, acoustically analogous stimuli without phonetic or linguistic content were used for passive listening. The left inferior frontal gyrus was activated during the stimulus-encoding, maintenance and response, in agreement with previous studies. However, in contrast to previous studies using visual presentation of verbal material, the inferior parietal cortex was not activated during the maintenance in the present study, but only active in the comparison and decision phase. Significant activation of the auditory cortex in the middle temporal gyrus was observed during the maintenance phase, which, together with the inferior frontal gyrus activation might underly the maintenance of phonological information.
    Brain Research 06/2008; 1212:48-54. · 2.73 Impact Factor

Institutions

  • 2013
    • Stockholm University
      • Department of Psychology
      Stockholm, Stockholm, Sweden
  • 2009–2011
    • Stockholm Environment Institute
      Stockholm, Stockholm, Sweden
  • 2001–2011
    • Karolinska Institute
      Stockholm, Stockholm, Sweden
    • Karolinska University Hospital
      Stockholm, Stockholm, Sweden
  • 1999–2011
    • Karolinska Institutet
      • • Institutionen för kvinnors och barns hälsa
      • • Institutionen för neurovetenskap
      Solna, Stockholm, Sweden
  • 2004–2009
    • Uppsala University
      Uppsala, Uppsala, Sweden
    • Uppsala University Hospital
      • Department of Neuroscience
      Uppsala, Uppsala, Sweden
  • 2003
    • University College London
      London, ENG, United Kingdom