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Biomedical subjects

Hans Forssberg

Publications and source records attributed to Hans Forssberg.

At least 19 recordsLinked to original sources
PubMed2005

Extensive piano practicing has regionally specific effects on white matter development.

Using diffusion tensor imaging, we investigated effects of piano practicing in childhood, adolescence and adulthood on white matter, and found positive correlations between practicing and fiber tract organization in different regions for each age period. For childhood, practicing correlations were extensive and included the pyramidal tract, which was more structured in pianists than in non-musicians. Long-term training within critical developmental periods may thus induce regionally specific plasticity in myelinating tracts.

Adolescent↗
PubMed2005

Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: association between striatal dopamine markers and motor hyperactivity.

BACKGROUND: The hypothesis that altered dopamine transmission underlies hyperactive-inattentive behavior in children with attention-deficit/hyperactivity disorder (ADHD) is based on genetic studies and the efficacy of psychostimulants. Most of previous positron emission tomography (PET) and single photon emission tomography (SPET) studies have shown altered binding of dopamine markers in the basal ganglia. Yet, the functional role of the neurochemical disturbances are poorly understood. The purpose of our study was to examine dopamine transporter (DAT) and dopamine D2 receptor (D2R) binding in adolescents with ADHD and to search for its relationship with cognitive functions as well as locomotor hyperactivity. METHODS: Twelve adolescents with ADHD and 10 young adults were examined with PET using the selective radioligands [11C]PE2I and [11C]raclopride, indexing DAT and D2R density. The simplified reference tissue model was used to calculate binding potential (BP) values. Attention and motor behavior were investigated with a continuous performance task (CPT) and motion measurements. RESULTS: The BP value for [11C]PE2I and [11C]raclopride in the striatum of children with ADHD did not differ from that of the young adult control subjects. In the midbrain, however, the BP values for DAT were significantly lower (16%; p = .03) in children with ADHD. Dopamine D2 receptor binding in the right caudate nucleus correlated significantly with increased motor activity (r = .70, p = .01). CONCLUSIONS: The lower BP values for DAT in the midbrain suggest that dopamine signaling in subjects with ADHD is altered. Altered dopamine signaling might have a causal relationship to motor hyperactivity and might be considered as a potential endophenotype of ADHD.

Adolescent↗
PubMed2005

Development of postural adjustments in sitting position during the first half year of life.

Little is known about the development of postural adjustments during early ontogeny. We examined postural adjustments due to sudden perturbations during sitting in 40 healthy term infants (28 males, 12 females) assessed in groups of eight at 1, 2, 3, 4, and 5 months of age. Surface electromyograms of neck, trunk, and leg muscles were recorded while the infants were exposed to a random series of horizontal forward and backward displacements of the surface of support. Video recordings of spontaneous motor behaviour were analyzed. For part of the analyses, previously collected data on 26 infants aged 6 to 10 months were included. In general, postural adjustments at all ages were direction specific and showed large variation. Within the variation developmental changes could be observed, revealing a transient decrease in postural activity at 3 months of age. After this transition, direction-specific postural activity was correlated with spontaneous motor behaviour. This was true, in particular, for dorsal postural activity. The clinical relevance of these findings is discussed.

Age Factors↗
PubMed2005

Computerized training of working memory in children with ADHD--a randomized, controlled trial.

OBJECTIVE: Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic practice of WM tasks. METHOD: Included in the trial were 53 children with ADHD (9 girls; 15 of 53 inattentive subtype), aged 7 to 12 years, without stimulant medication. The compliance criterion (>20 days of training) was met by 44 subjects, 42 of whom were also evaluated at follow-up 3 months later. Participants were randomly assigned to use either the treatment computer program for training WM or a comparison program. The main outcome measure was the span-board task, a visuospatial WM task that was not part of the training program. RESULTS: For the span-board task, there was a significant treatment effect both post-intervention and at follow-up. In addition, there were significant effects for secondary outcome tasks measuring verbal WM, response inhibition, and complex reasoning. Parent ratings showed significant reduction in symptoms of inattention and hyperactivity/impulsivity, both post-intervention and at follow-up. CONCLUSIONS: This study shows that WM can be improved by training in children with ADHD. This training also improved response inhibition and reasoning and resulted in a reduction of the parent-rated inattentive symptoms of ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Locomotor effects of a D1R agonist are DARPP-32 dependent in adult but not weanling mice.

Evidence suggests that dopamine regulation of motor activity undergoes postnatal maturation. To examine the role of the dopamine 1 receptor (D1R)/dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) signaling pathway for this maturation, we studied the effects of a D1R agonist on motor activity in weanling and adult wild-type (WT) mice and mice that lack DARPP-32, a key messenger in the D1R signaling pathway. Locomotor activity was not affected by D1R activation in WT weanling mice but was significantly stimulated in WT adult mice. This stimulation was absent in DARPP-32 (-/-) adult mice. In contrast, the inhibitory effects that were observed on rearing activity in WT weanling and adult mice were present in DARPP-32 (-/-) mice. DARPP-32 plays a key role for development of D1R motor stimulatory effects.

Analysis of Variance↗
PubMed2004

Brain activity during predictable and unpredictable weight changes when lifting objects.

When humans repetitively lift the same object, the fingertip forces are targeted to the weight of the object. The anticipatory programming of the forces depends on sensorimotor memory representations that provide information on the object weight. In the present study, we investigate the neural substrates of these sensorimotor memory systems by recording the neural activity during predictable or unpredictable changes in the weight of an object in a lifting task. An unpredictable change in weight leads to erroneous programming of the fingertip forces. This triggers corrective mechanisms and an update of the sensorimotor memories. In the present fMRI study, healthy right-handed subjects repetitively lifted an object between right index finger and thumb. In the constant condition, which served as a control, the weight of the object remained constant (either 230 or 830 g). The weight alternated between 230 and 830 g during the regular condition and was irregularly changed between the two weights during the irregular condition. When we contrasted regular minus constant and irregular minus constant, we found activations in the right inferior frontal gyrus pars opercularis (area 44), the left parietal operculum and the right supramarginal gyrus. Furthermore, irregular was associated with stronger activation in the right inferior frontal cortex as compared with regular. Taken together, these results suggest that the updating of sensorimotor memory representations and the corrective reactions that occur when we manipulate different objects correspond to changes in synaptic activity in these fronto-parietal circuits.

Adult↗
PubMed2004

Postural adjustments due to external perturbations during sitting in 1-month-old infants: evidence for the innate origin of direction specificity.

The aim of the study was to examine whether infants, at an age when they have no or little experience in sitting, can produce direction specific postural adjustments, i.e. synergies of muscle activity on the ventral side of the body during backward sway and on the dorsal side during forward sway. In addition, we addressed the question whether postural adjustments at this young age are restricted to single muscle responses or consist of a variable repertoire of muscle activation patterns including one during which all direction specific muscles participate ('complete' pattern). Postural adjustments due to external perturbations in a sitting position were studied in eight healthy infants aged 1 month. Multiple surface EMGs of neck, trunk and leg muscles and kinematics were recorded while the infants were exposed to horizontal forward (Fw) and backward (Bw) displacements of the surface of support. Direction specific postural adjustments, defined as adjustments during which agonist activation or antagonist inhibition preceded antagonist activation, were present in 85% of Bw and 72% of Fw translations. The direction specific adjustments showed a large variability with the repertoire of adjustments including the activation of one, two or all of the recorded direction specific muscles. The finding of direction specific adjustments at 1 month of age support the opinion that the basic level of organisation of postural adjustments has an innate origin. The finding of a variable repertoire of muscle response patterns, including the 'complete' pattern, refutes the idea that the development of postural adjustments results from gradual addition of appropriate muscles to the synergies.

Biomechanical Phenomena↗
PubMed2004

Disturbances in programming goal-directed arm movements in children with ADHD.

We investigated in children with attention-deficit-hyperactivity disorder (ADHD) the ability to programme and execute goal-directed arm movements. The sample consisted of 25 males with ADHD (mean age 11 years 6 months, SD 1 year 11 months, range 8 to 15 years) and 25 age-matched typically developing males. The children moved a cursor on a screen by moving a hand-held indicator on a horizontal digitizing tablet. Start and target positions on the screen were always visible during the movement. The screen cursor, however, could either be visible throughout the movement (visual feedback) or blanked at movement initiation (without visual feedback). Analysis showed that movement control was impaired in children with ADHD and that their problems were especially pronounced during the without-visual-feedback condition. In this condition, the children with ADHD exhibited large end-point errors and prolonged movement durations. As there can be no visual corrections of the movement during this condition, results indicate poorer motor programming in children with ADHD. Moreover, children with ADHD performed jerky movements and showed a reduced capacity to select a movement speed that met with the accuracy demands of the movement.

Adolescent↗
PubMed2004

Visuo-spatial working memory span: a sensitive measure of cognitive deficits in children with ADHD.

Working memory (WM) has been hypothesised to be impaired in attention-deficit/hyperactivity disorder (ADHD). However, there are few studies reported on tests measuring visuo-spatial WM (VSWM) in ADHD. Some of these studies used paradigms including episodic memory, others only used low memory loads. In the present study we used a VSWM test that has not been used previously in ADHD research. The sensitivity of the VSWM test and a choice reaction time (CRT) test was evaluated in a pilot study by comparing them to two commonly used tests in ADHD-research; the Continuous Performance Test (CPT) and a Go/no-go test, in children with and without ADHD. The groups differed significantly in performance on the VSWM test (P < .01) and CRT (P < .05) but not on the CPT (P > .1) or on the Go/no-go test (P > .1). The results from the VSWM and CRT tests were replicated in a larger sample of participants (80 boys; 27 boys with ADHD and 53 controls, mean age 11.4 years). The difference between the groups was significant for both the VSWM test (P < .01) and the CRT test (P < .01). The effect size (ES) of the VSWM test was 1.34. There was a significant age-by-group interaction on the VSWM test, with larger group differences for the older children (P < .01). Our results show that the VSWM test is a sensitive measure of cognitive deficits in ADHD and it supports the hypothesis that deficits in VSWM is a major component of ADHD.

Adolescent↗
PubMed2004

Alteration of dopamine D1 receptor-mediated motor inhibition and stimulation during development in rats is associated with distinct patterns of c-fos mRNA expression in the frontal-striatal circuitry.

Dopamine D1 receptors have been implicated in various neurodevelopmental disorders, including attention-deficit/hyperactivity disorder. However, little is known about potential late maturational changes of the motor inhibitory and stimulatory role of these receptors. Here, we investigated the effects of a full and selective D1 receptor agonist, SKF-81297, on motor activity and expression of the plasticity-associated gene, c-fos, in the prefrontal cortex and striatum of juvenile and adolescent male rats. In general, SKF-81297 produced a biphasic effect on motor activity (locomotor and rearing activity), which consisted of an initial short inhibition followed by a long-lasting stimulation. These effects were dose- and age- dependent. The inhibitory phase was more pronounced in adolescent than in juvenile rats whereas the opposite was true for the stimulatory phase. During the initial inhibitory phase of the drug, c-fos mRNA expression was increased in the prefrontal cortex of juvenile rats but reduced in adolescent rats. There was also an increase in c-fos mRNA expression in the medial-dorsal striatum and olfactory tubercle, which was more evident in juvenile rats. In contrast, during the stimulatory phase, c-fos mRNA expression was increased in both the dorsal and ventral striatum, especially in the nucleus accumbens, as well as in the prefrontal cortex, in both age groups. The increase of c-fos mRNA in the dorsal striatum, however, was more pronounced in juvenile rats. These results indicate the presence of two distinct D1 receptor populations within the frontal-striatal circuitry, which have opposite effects on motor activity, and which have different maturational profiles.

Animals↗
PubMed2004

Dissociating brain regions controlling the temporal and ordinal structure of learned movement sequences.

We used functional magnetic resonance imaging to investigate if different brain regions are controlling the temporal and ordinal structure of movement sequences during performance. Human subjects performed overlearned spatiotemporal sequences of key-presses using the right index finger. Under different conditions, the temporal and the ordinal structure of the sequences were varied systematically in relation to each other, using a factorial design: COMBINED had a rhythm of eight temporal intervals and a serial order of eight keys; TEMPORAL had an eight-interval rhythm produced on one key; ORDINAL had an isochronous rhythm and an eight-key serial order; two control conditions had an isochronous pulse performed on one or two keys, respectively. Brain regions involved in rhythmic and ordinal control of the sequences were revealed by analysing main effect contrasts for the corresponding factors. TEMPORAL and ORDINAL were also compared directly to test for significant differences. A dissociation was found between largely the presupplementary motor area, the right inferior frontal gyrus and precentral sulcus, and the bilateral superior temporal gyri, involved in temporal control, and lateral fronto-parietal areas, the basal ganglia and the cerebellum, which were implicated in ordinal control. The vermis and the superior colliculus were the only regions with an activity increase specifically related to combining long temporal and ordinal sequences. We conclude that humans use different brain networks for temporal and ordinal sequence control, and that the performance of combined sequences activates both networks, the medial cerebellum, and the superior colliculus.

Adolescent↗
PubMed2004

Effects of passive-active movement training on upper limb motor function and cortical activation in chronic patients with stroke: a pilot study.

OBJECTIVE: To explore how repetitive passive-active movement training effects upper limb motor function and cortical activation in patients with stroke. DESIGN: Single-group treatment trial with baseline comparisons. PATIENTS: Ten chronic patients with stroke with paresis of the upper limb. METHODS: Assessments were performed during a 4-week baseline period before and once after 4 weeks of training using the Motor Assessment Scale of the upper limb, Nine Hole Peg Test, goniometer for range of movement and the modified Ashworth scale for muscle tone. Two patients underwent functional magnetic resonance imaging pre- and post-training. The treatment consisted of daily sessions of repeated functional reaching and grasping movements guided passively and attempted actively during 4 weeks. RESULTS: The group improved in range of motion and Motor Assessment Scale scores. Subjects reported improvements in a variety of daily tasks requiring the use of the affected upper limb. Increases in cortical activation in prefrontal and sensorimotor areas were observed in parallel with improvements of upper limb motor function in the 2 patients scanned. CONCLUSION: The 4-week training programme improved hand motor function and ability. Cortical activation on functional magnetic resonance imaging changed in parallel suggesting reorganization of areas related to movements of the paretic limb.

Cerebral Cortex↗
PubMed2003

[Rehabilitation after stroke. Imaging techniques show how the cortical reorganization is affected by training].

It is widely accepted that reorganisation of the brain occurs after a focal brain lesion such as stroke. Neuroimaging methods are used to study such reorganisation in vivo. Improvements in arm and hand motor function during recovery post-stroke have been related to reorganisation in primary and secondary sensorimotor areas by indirect measure of synaptic activity with functional MRI. Reorganisation occurs in both the affected and the unaffected hemispheres. Preliminary training studies post-stroke have shown correlations between improvements in motor function and brain activity changes. Recent research findings are reviewed herein. Further understanding of the neurobiological mechanisms of post-stroke recovery will lead to development of optimal treatment strategies during rehabilitation of stroke survivors.

Brain↗
PubMed2003

Preterm children have disturbances of white matter at 11 years of age as shown by diffusion tensor imaging.

Preterm birth frequently involves white matter injury and affects long-term neurologic and cognitive outcomes. Diffusion tensor imaging has been used to show that the white matter microstructure of newborn, preterm children is compromised in a regionally specific manner. However, until now it was not clear whether these lesions would persist and be detectible on long-term follow-up. Hence, we collected diffusion tensor imaging data on a 1.5-T scanner, and computed fractional anisotropy and coherence measures to compare the white matter integrity of children born preterm to that of control subjects. The subjects for the preterm group (10.9 +/- 0.29 y; n = 9; birth weight or= 2500; gestational age, >or= 37 wk). We found that the preterm group had lower fractional anisotropy values in the posterior corpus callosum and bilaterally in the internal capsules. In the posterior corpus callosum this difference in fractional anisotropy values may partially be related to a difference in white matter volume between the groups. An analysis of the coherence measure failed to indicate a group difference in the axonal organization. These results are in agreement with previous diffusion tensor imaging findings in newborn preterm children, and indicate that ex-preterm children with attention deficits have white matter disturbances that are not compensated for or repaired before 11 y of age.

Anisotropy↗
PubMed2003

Deficient coordination of associated postural adjustments during a lifting task in children with neurodevelopmental disorders.

Precision grip and concomitant anticipatory postural adjustments were investigated in 11 children (three females, eight males; mean age 9 years 1 month, SD 11 months) with attention-deficit-hyperactivity disorder (ADHD); 12 children (three females, nine males; mean age 9 years, SD 7 months) with developmental coordination disorder (DCD), and 13 children (two females, 11 males; mean age 9 years 9 months, SD 11 months) with a combination of ADHD and DCD (ADHD+). There were two comparison groups: an age-matched group (four females, 11 males; mean age 9 years 1 month, SD 14 months) and a younger age group (five females, six males; mean age 6 years 5 months, SD 8 months). Adaptation to different weights was evaluated by lifting a specialized grip instrument monitoring grip force, load force, and centre of foot pressure displacements. Children with ADHD+ showed: (1) excessive grip forces, (2) decreased amplitude and prolonged onset of postural adjustments, and (3) reduced ability to adapt the motor output. Children with ADHD and DCD did not scale manual and postural forces in amplitude and time domains. Children with DCD also differed in delayed timing of postural adjustments. Results indicate that children with ADHD and DCD show a spectrum of neural dysfunctions underlying poor motor coordination, which are not specific to the clinical disorder.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Can a therapeutic dose of amphetamine during pre-adolescence modify the pattern of synaptic organization in the brain?

Stimulant drugs such as amphetamine have, for many decades, been the drugs of choice in the treatment of children with attention-deficit/hyperactivity disorder. However, little is known about their therapeutic mechanisms or about the consequences of their long-term exposure. In the present study we investigated whether repeated exposure of a low dose of amphetamine (0.5 mg/kg) to juvenile rats could induce long-term morphological alterations in the prefrontal cortex. In addition, to assess possible behavioural consequences of prolonged exposure to this drug, we examined whether changes in the motor response to various dopamine agonists occurred after this treatment. We found that this dose of amphetamine promotes plasma concentrations of amphetamine sulphate in juvenile rats to levels corresponding to the clinical range used for children with attention-deficit/hyperactivity disorder. Amphetamine (0.5 mg/kg; s.c.) was administered twice daily during postnatal days 22-34, and then the brains of the animals were evaluated 2 weeks later. This treatment produced an increase in dendritic length and branches of pyramidal neurons of the medial prefrontal cortex, but not in the nucleus accumbens. These changes were associated with an increase in the expression of calcium/calmodulin-dependent protein kinase II, a highly abundant signalling protein in the postsynaptic densities of excitatory synapses. Interestingly, amphetamine pre-treatment did not alter the motor response to various dopamine agonists, including amphetamine. These data suggest that clinical doses of stimulant drugs may be acting as a trophic support at the glutamatergic synapses, thereby enhancing dopamine-glutamate interactions in the prefrontal cortex.

Amphetamine↗