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Biomedical subjects

Hans Forssberg

Publications and source records attributed to Hans Forssberg.

At least 19 recordsLinked to original sources
PubMed2006

Altered pattern of brain dopamine synthesis in male adolescents with attention deficit hyperactivity disorder.

BACKGROUND: Limited data from positron emission tomography (PET) studies of subjects with attention-deficit/hyperactivity disorder (ADHD) indicate alterations in brain dopamine neurotransmission. However, these studies have used conventional univariate approaches that are less sensitive to detect complex interactions that may exist between different brain dopamine pathways and individual symptoms of ADHD. We aimed to investigate these potential interactions in adolescents with ADHD. METHODS: We used a 3D PET scan to measure utilization of native L-[11C]-DOPA to map dopamine presynaptic function in various cortical, striatal and midbrain regions in a group of 8 male adolescents with ADHD and 6 age matched controls. To evaluate the interactions between the studied brain regions, multivariate statistical methods were used. RESULTS: Abnormal dopaminergic function was found in multiple brain regions of patients with ADHD. A main finding was lower L-[11C]-DOPA utilization in adolescent with ADHD as compared to control subjects, especially in subcortical regions. This pattern of dopaminergic activity was correlated specifically with symptoms of inattention. CONCLUSION: Dopamine signalling in the brain plays an important modulatory role in a variety of motor and cognitive functions. We have identified region-specific functional abnormalities in dopaminergic function, which may help better account for the symptoms of ADHD.

Journal Article↗
PubMed2006

Early development of postural adjustments in standing with and without support.

This study investigates the early development of postural adjustments during external perturbations in two different standing positions: standing with support and standing without support. The aim of the study was to assess a group of 13 infants four times during the period in life when independent standing is achieved; at 8, 10, 12 and 14 months. However, longitudinal data could be achieved only in four infants. Muscle activations of the neck, hip and ankle were recorded using surface electromyography. Based on earlier studies and controversies, three main issues were addressed: (1) Is direction specificity present before independent standing is established? (2) How do postural adjustments change with increasing age (8-14 months)? (3) Are postural adjustments task-specific in the young child? The results showed that our small sample of infants aged 8 and 10 months, who were not yet able to stand independently, exhibited direction-specific postural adjustments both during standing with and without support, though not consistently during all trials and at all body levels. Therefore, we argue that direction specificity might constitute a prerequisite for the development of independent standing. We also found that the development of postural adjustments in standing with support resembles that of sitting, i.e. great variation in the postural adjustments at early age, and fine-tuning to the situation with increasing age and experience. This, we find that this is in agreement with the proposal that postural control develops through a selection process of the most suitable postural adjustments for the situation from a repertoire of direction-specific postural adjustments. The development of postural adjustments during standing without support is discussed. Additionally, differences in response rates were noted between the two standing positions, indicating that even before independent standing is established, sophisticated sensorimotor integration enables task-specific postural adjustments.

Age Factors↗
PubMed2006

Lighter or heavier than predicted: neural correlates of corrective mechanisms during erroneously programmed lifts.

A central concept in neuroscience is that the CNS signals the sensory discrepancy between the predicted and actual sensory consequences of action. It has been proposed that the cerebellum and parietal cortex are involved in this process. A discrepancy will trigger preprogrammed corrective responses and update the engaged sensorimotor memories. Here we use functional magnetic resonance imaging with an event-related design to investigate the neuronal correlates of such discrepancies. Healthy adults repeatedly lifted an object between their right index fingers and thumbs, and on some lifting trials, the weight of the object was unpredictably changed between light (230 g) and heavy (830 g). Regardless of whether the weight was heavier or lighter than predicted, activity was found in the right inferior parietal cortex (supramarginal gyrus). This suggests that this region is involved in the comparison of the predicted and actual sensory input and the updating of the sensorimotor memories. When the object was lighter or heavier than predicted, two different types of preprogrammed force corrections occurred. There was a slow force increase when the weight of the object was heavier than predicted. This corrective response was associated with activity in the left primary motor and somatosensory cortices. The fast termination of the excessive force when the object was lighter than predicted activated the right cerebellum. These findings show how the parietal cortex, cerebellum, and motor cortex are involved in the signaling of the discrepancy between predicated and actual sensory feedback and the associated corrective mechanisms.

Adult↗
PubMed2006

Holding an object: neural activity associated with fingertip force adjustments to external perturbations.

When you hold an object, a sudden unexpected perturbation can threaten the stability of your grasp. In such situations grasp stability is maintained by fast reflexive-like grip-force responses triggered by the somatosensory feedback. Here we use functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms involved in the grip-force responses associated with unexpected increases (loading) and decreases (unloading) in the load force. Healthy right-handed subjects held an instrumented object (of mass 200 g) between the tips of right index finger and thumb. At some time during an interval of 8 to 45 s the weight of the object was suddenly increased or decreased by 90 g. We analyzed the transient increases in the fMRI signal that corresponded precisely in time to these grip-force responses. Activity in the left primary motor cortex was associated with the loading response, but not with unloading, suggesting that sensorimotor processing in this area mediates the sensory-triggered reflexive increase in grip force during loading. Both the loading and the unloading events activated the cingulate motor area and the medial cerebellum. We suggest that these regions could participate in the updating of the sensorimotor representations of the fingertip forces. Finally, the supplementary somatosensory area located on the medial wall of the parietal lobe showed an increase in activity only during unloading, indicating that this area is involved in the sensorimotor processing generating the unloading response. Taken together, our findings suggest different central mechanisms for the grip-force responses during loading and unloading.

Adult↗
PubMed2006

Development of hand function and precision grip control in individuals with cerebral palsy: a 13-year follow-up study.

OBJECTIVE: Although children with cerebral palsy display large developmental differences in hand function from that of typically developing children by the age of 6 to 10 years, little is known about the developmental processes underlying hand function during subsequent development. In this study we investigated the development of manual dexterity in a timed motor task, the timing and amplitude of fingertip-force application during a precision grasping task, and the relationship between changes in these measures. We applied highly quantitative analytical approaches to determine if the fingertip-force application pattern and trial-to-trial variation of fingertip-force application change during development. METHODS: Twelve subjects with cerebral palsy (aged 6-8 years) participated in the first data-collection session conducted between 1989 and 1990. Ten of these subjects (5 with hemiplegia and 5 with diplegia, aged 19-21 years) returned between 2002 and 2003. Manual dexterity was measured by using timed tasks of the Jebsen-Taylor test of hand function. Subjects also lifted an object instrumented with force transducers while we measured the temporal coordination of fingertip coordination and the path ratio between the grip and vertical load-force trajectory (straightness). We used generalized procrustes analysis to determine if there were changes in shape of the force trajectory and intertrial variability. RESULTS: The Jebsen-Taylor test times decreased 45% from the first to the second data session. The overall time to complete the grip-lift task decreased 22%, mainly because of a faster transition from grasp to lift. The grip-force/load-force path ratios decreased from 1.7 to 1.35 (1 = straight line). Generalized procrustes analysis indicated a change in the shape and a decrease in variability in shape of the force-ratio path. CONCLUSIONS: Our results demonstrate that the efficiency in grasping had developed during a 13-year period for this small group of participants with cerebral palsy, which suggests that improvement in hand function occurs over a longer time frame than commonly would be expected.

Adult↗
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

Effector-independent voluntary timing: behavioural and neuroimaging evidence.

We investigated effector-independent aspects of voluntary motor timing, using behavioural measurements and functional magnetic resonance imaging. Two types of temporal pattern were investigated; one isochronous, the other a metric, rhythmic sequence of six temporal intervals. Each pattern was performed using tapping movements with the left or right index fingers, or rhythmic speech on one syllable. Deviations from the ideal temporal pattern in the rhythmic sequence tasks were consistent between the three different effectors, within subjects. This suggests that the same representation of the rhythm was used to time the movements with all effectors. To reveal brain regions involved in such effector-independent timing, we localized the overlap in brain activity when the rhythmic sequence was performed with the different effectors. Activity was found in the mesial and lateral premotor cortices, posterior and anterior regions of the superior temporal gyrus and the inferior frontal cortex. Subcortical activations were in the left globus pallidus, the vermis and bilaterally in the cerebellar hemispheres (lobule VI) and the thalamus. The overlap in activity between the isochronous tasks included the same set of brain regions, except for the basal ganglia and the thalamus. Rhythmic sequences had significantly higher activity in mesial premotor cortex, the left superior temporal gyrus and the cerebellum, than had isochronous movements. These findings reveal a set of brain regions likely to be involved in effector-independent representations of temporal patterns in voluntary motor timing. A subset of these regions plays important roles for the organization of rhythmic sequences of several intervals.

Adult↗
PubMed2005

Neural control of rhythmic sequences.

We investigated whether the temporal structure of movement sequences can be represented and learned independently of their ordinal structure, and whether some brain regions are particularly important for temporal sequence performance. Using a learning transfer design, we found evidence for independent temporal representations: learning a spatiotemporal sequence facilitated learning its temporal and ordinal structure alone; learning a temporal and an ordinal structure facilitated learning of a sequence where the two were coupled. Second, learning of temporal structures was found during reproduction of sequential stimuli with random ordinal structure, suggesting independent mechanisms for temporal learning. We then used functional magnetic resonance imaging to investigate the neural control of sequences during well-learned performance. The temporal and ordinal structures of the sequences were varied in a 2 x 2 factorial design. A dissociation was found between brain regions involved in ordinal and temporal control, the latter mainly involving the presupplementary motor area, the inferior frontal gyrus and precentral sulcus, and the superior temporal gyri. Finally, in a second fMRI experiment, well-learned temporal sequences were performed with the left or right index fingers, or using rhythmic speech. The overlap in brain activity during performance with the different effectors included a similar set of brain regions as that found in the first fMRI experiment: the supplementary motor area (SMA), the superior temporal gyrus, and the inferior frontal cortex. We thus suggest that this set of regions is important for abstract, movement-independent, temporal sequence control. This organization may be important for increased flexibility in voluntarily timed motor tasks.

Brain Mapping↗
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↗