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PubMed2002

Multiple movement representations in the human brain: an event-related fMRI study.

Neurovascular correlates of response preparation have been investigated in human neuroimaging studies. However, conventional neuroimaging cannot distinguish, within the same trial, between areas involved in response selection and/or response execution and areas specifically involved in response preparation. The specific contribution of parietal and frontal areas to motor preparation has been explored in electrophysiological studies in monkey. However, the associative nature of sensorimotor tasks calls for the additional contributions of other cortical regions. In this article, we have investigated the functional anatomy of movement representations in the context of an associative visuomotor task with instructed delays. Neural correlates of movement representations have been assessed by isolating preparatory activity that is independent from the performance of an actual motor act, or from the presence of a response's target. Movement instruction (specified by visual cues) and motor performance (specified by an auditory cue) were separated by a variable delay period. We have used whole-brain event-related fMRI to measure human brain activity during the performance of such a task. We have focused our analysis on specific preparatory activity, defined as a sustained response over variable delay periods between a transient visual instruction cue and a brief motor response, temporally independent from the transient events. Behavioral and electrophysiological controls ensured that preparatory activity was not contaminated by overt motor responses or working memory processes. We report suggestive evidence for multiple movement representations in the human brain. Specific sustained activity in preparation for an action was found not only in parieto-frontal regions but also in extrastriate areas and in the posterior portion of the superior temporal sulcus. We suggest that goal-directed preparatory activity relies on both visuomotor and visuoperceptual areas. These findings point to a functional-anatomical basis for the integration of perceptual and executive processes.

Adult↗
PubMed1986

Evidence from behavioural and in vitro receptor binding studies that the enkephalinergic system does not mediate acute ethanol effects.

The behavioural disturbances produced by acute exposure to ethanol have been related to changes in function of the opioid systems in the CNS. However, evidence in the literature is conflicting. The present report concerns the possible role of the enkephalinergic system in the mediation of acute ethanol effects. We used rats to study the ability of a selective opioid delta receptor antagonist (ICI 154129) to prevent the effect of ethanol on pain sensitivity, body temperature, sensorimotor performance and level of consciousness. Furthermore, in vitro receptor binding was measured to investigate whether or not ethanol, within a non-lethal concentration range, would change the binding parameters of the delta receptor ligand [3H][D-ala2, D-Leu5]enkephalin. ICI 154129 did not significantly influence the effects of ethanol in the behavioural experiments. Ethanol did not significantly change the binding parameters whether saturation or competition was measured in the receptor binding experiments. Thus, there was no evidence that the enkephalinergic system mediated the acute ethanol effects.

Animals↗
PubMed2006

Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats.

Human truncated tau protein is an active constituent of the neurofibrillary degeneration in sporadic Alzheimer's disease. We have shown that modified tau protein, when expressed as a transgene in rats, induced AD characteristic tau cascade consisting of tau hyperphosphorylation, formation of argyrophilic tangles and sarcosyl-insoluble tau complexes. These pathological changes led to the functional impairment characterized by a variety of neurobehavioural symptoms. In the present study we have focused on the behavioural alterations induced by transgenic expression of human truncated tau. Transgenic rats underwent a battery of behavioural tests involving cognitive- and sensorimotor-dependent tasks accompanied with neurological assessment at the age of 4.5, 6 and 9 months. Behavioural examination of these rats showed altered spatial navigation in Morris water maze resulting in less time spent in target quadrant (p<0.05) and fewer crossings over previous platform position (p<0.05) during probe trial. Spontaneous locomotor activity and anxiety in open field was not influenced by transgene expression. However beam walking test revealed that transgenic rats developed progressive sensorimotor disturbances related to the age of tested animals. The disturbances were most pronounced at the age of 9 months (p<0.01). Neurological alterations indicating impaired reflex responses were other added features of behavioural phenotype of this novel transgenic rat. These results allow us to suggest that neurodegeneration, caused by the non-mutated human truncated tau derived from sporadic human AD, result in the neuronal dysfunction consequently leading to the progressive neurobehavioural impairment.

Alzheimer Disease↗
PubMedDate not supplied

[Designation of symptoms in mental disorder].

In the author's opinion, language and clinical facts in psychiatry are misused and it is hypothesized that many malfunctions of psychiatric practise are symptomatic. It is indeed very hard to modelise mental illness: what terms should be chosen and how should they be articulated? Considering the complexity of the relationship between language, ideas and memory, an empirical and experimental approach has been chosen; working out structures of concepts isomorphic to psychiatric reality, either from observed phenomena or from words. In our view, language skills are sufficient to build these sophisticated models, and language skills can be trained as can be trained sensorimotor skills. Experimenting psychiatric language in using their encyclopedic knowledge will allow staff members to teach themselves and will have a heuristic value in changing their beliefs about reality. These experiments have been undertaken for a year and an half, in a general psychiatry ward, in a ward for retarded and autistic adults and in a rehabilitation ward. Rigour and perseverance are required but these experiments seem particularly promising.

Adult↗
PubMedDate not supplied

Mechanisms underlying somatosensory cortical dynamics: II. In vitro studies.

The response of the sensorimotor cortical slice to repetitive, single-site afferent drive is mapped using both evoked potential and metabolic mapping [2-deoxyglucose (2DG)] methods. Systematic changes (increases or decreases) in the evoked potential occur during repetitive 3-5 Hz stimulation. These resemble the changes in SI neuron response observed in the in vivo studies of the preceding companion article; they occur rapidly, recover within 1 min and are reproducible if stimulus parameters remain unchanged. Place, timing, and intensity of repetitive stimulation influence the amplitude and form of the response alterations observed at a given cortical locus. The neuron populations that exhibit different response modifications to the same repetitive stimulus are distributed nonrandomly in the slice: neurons occupying column-shaped aggregates undergo a common response alteration (either an increase or decrease) during repetitive stimulation, with sharp boundaries separating neighboring aggregates distinguishable on the basis of their dynamic behaviors. The distribution of stimulus-evoked 2DG uptake in the slice is "columnar," the dimensions of the 2DG columns corresponding to those mapped with neurophysiological methods. Taken together, the findings support the concept that repetitive stimulation causes the intrinsic network of somatosensory cortex to modify dynamically the network's response to extrinsic excitatory drive so that the local differences in the pattern of extrinsic excitatory drive to neighboring cortical columns are enhanced.

Afferent Pathways↗
PubMed2006

Dynamics of oscillatory activity during auditory decision making.

Perceptual decision making requires the comparison and integration of sensory evidence to generate a behavioral response. We used magnetoencephalography to investigate the temporal dynamics of decision making during an auditory task that required forced-choice decisions about whether a pair of syllables S1 and S2 differed either in their acoustic patterns or in the perceived position of their sound sources. Conditions with easy and difficult decisions were created by varying the similarity of S1 and S2. Statistical probability mapping showed enhanced gamma-band activity (GBA) over posterior parietal cortex for spatial and over left inferior frontal cortex for pattern changes (at approximately 120 to 220 ms after S2 onset). Activations were stronger for easy than difficult decisions. GBA over dorsolateral prefrontal cortex was more pronounced at approximately 280 to 430 ms for easy than difficult decisions regardless of type of change, possibly reflecting decision-relevant networks that integrate information from higher sensory areas representing the perceptual alternatives. Sensorimotor beta desynchronization as a measure of motor preparation peaked at approximately 460 ms for easy and at approximately 520 ms for difficult decisions, thus reflecting the reaction time difference between both conditions. In summary, the analysis of oscillatory activity in magnetoencephalogram served to elucidate the temporal dynamics of perceptual decision making in humans.

Adult↗
PubMed1982

Recovery time and sensorimotor cortex lesion effects.

Rats received one-stage, bilateral lesions of the individual sensorimotor cortex areas (Sm-1, Sm-2) and were compared to sham operated rats or rats with lesions of Sm1 + 2 in learning a series of 5 ridge-smooth tactile discriminations. Some rats began testing 1 or 2 weeks after surgery, while others remained in their home cages for 1 month, 6 months, 1 year or 2 years before beginning testing. The rats with combined Sm1 + 2 lesions performed very poorly regardless of recovery time, and those with sham operations performed extremely well even when tested late in life. The animals with either Sm-1 or Sm-2 lesions did not do well after the shorter recovery periods, but obtained scores within the sham operated group range when given 1 year. (Sm-2) or 2 years (Sm-1) for recovery. These data show that spared parts of the damaged system are important in mediating tactile discriminative behavior. However, the reasons for the long delays in recovery are not clear.

Animals↗
PubMed2000

Prominent axonopathy and disruption of axonal transport in transgenic mice expressing human apolipoprotein E4 in neurons of brain and spinal cord.

The epsilon 4 allele of the human apolipoprotein E gene (ApoE4) constitutes an important genetic risk factor for Alzheimer's disease. Recent experimental evidence suggests that human ApoE is expressed in neurons, in addition to being synthesized in glial cells. Moreover, brain regions in which neurons express ApoE seem to be most vulnerable to neurofibrillary pathology. The hypothesis that the expression pattern of human ApoE might be important for the pathogenesis of Alzheimer's disease was tested by generating transgenic mice that express human ApoE4 in neurons or in astrocytes of the central nervous system. Transgenic mice expressing human ApoE4 in neurons developed axonal degeneration and gliosis in brain and in spinal cord, resulting in reduced sensorimotor capacities. In these mice, axonal dilatations with accumulation of synaptophysin, neurofilaments, mitochondria, and vesicles were documented, suggesting impairment of axonal transport. In contrast, transgenic mice expressing human ApoE4 in astrocytes remained normal throughout life. These results suggest that expression of human ApoE in neurons of the central nervous system could contribute to impaired axonal transport and axonal degeneration. The possible contribution of hyperphosphorylation of protein Tau to the resulting phenotype is discussed.

Animals↗
PubMed2003

Neurophysiological correlates of error correction in sensorimotor-synchronization.

In a sensorimotor synchronization task requiring subjects to tap in synchrony with an auditory stimulus, occasional perturbations (i.e., interval changes) in an otherwise isochronous sequence of auditory metronome stimuli are known to be compensated remarkably swift and with surprising precision, even when they are too small to be consciously perceived. To investigate the neural substrate and the informational basis of error correction in sensorimotor synchronization, we recorded movement-related, auditory-evoked, and error-related EEG potentials. Experiment 1 confirmed rapid adjustment to stimulus phase shifts, with faster correction of large (50 ms) compared to small (15 ms) shifts. In addition to being corrected faster, there was overcorrection of the 50 ms shifts, attributed to engagement of period correction mechanisms. For +50 ms shifts, a neural correlate of period correction was identified in the form of medial frontal cortex activation, preceded by an error-related brain potential (ERN). Auditory-evoked potential (AEP) amplitudes were sensitive to stimulus phase shifts of both large and small magnitude. Further experiments with a smaller magnitude 10 ms phase shift (Experiment 2) and passive auditory stimulation (Experiment 3) provided evidence that the modulation of AEP amplitudes is not due to metronome interval changes, but may represent auditory-somatosensory activation. Together, behavioral and neurophysiological data support the hypothesis that phase correction is a largely automatic process, not dependent on conscious perception of changes in timing. By contrast, perceivable phase shifts may invoke timekeeper adjustments accompanied by medial frontal cortex activity.

Acoustic Stimulation↗
PubMed1999

A positron emission tomography study of self-paced finger movements at different frequencies.

Regional cerebral blood flow was measured in six right-handed volunteers using positron emission tomography during tasks involving repetitive self-paced finger tapping at five different frequencies. The contralateral primary sensorimotor cortex, the pre-supplementary motor area and the cingulate motor area showed significant activation during self-paced finger tapping tasks, compared with the resting state. A positive correlation between the regional cerebral blood flow and the movement frequency was found only in the primary sensorimotor cortex. In the pre-supplementary motor area and the cingulate motor area, however, activity increased when the subject employed movement frequencies faster or slower than his own pace. The same tendency was noted with respect to the relative variability of the inter-tapping interval. The results therefore indicate that the activity of the pre-supplementary motor area and the cingulate motor area may well be related to the increased difficulty in motor control rather than to the execution of the movement itself.

Adolescent↗
PubMed2003

Attenuation of neuropathic manifestations by local block of the activities of the ventrolateral orbito-frontal area in the rat.

Clinical and recent imaging reports demonstrate the involvement of various cerebral prefrontal areas in the processing of pain. This has received further confirmation from animal experimentation showing an alteration of the threshold of acute nociceptive reflexes by various manipulations in the orbito-frontal cortical areas. The present study investigates the possible involvement of this area in the modulation of neuropathic manifestations in awake rats. Several groups of rats were subjected to mononeuropathy following the spared nerve injury model, known to produce evident tactile and cold allodynia and heat hyperalgesia. The activity of the ventrolateral orbital areas was selectively blocked by using either chronic or acute injection of lidocaine, electrolytic lesion, or chemical lesion with kainic acid or 6-hydroxydopamine (6-OHDA). The effects of these manipulations were compared with those following lesion of the somatic sensorimotor cortical areas. Local injection of lidocaine resulted in a reversible depression of all neuropathic manifestations while electrolytic or chemical lesions elicited transient attenuation affecting mainly the heat hyperalgesia and to a lesser extent the cold allodynia. The magnitude of the observed effects with the different procedures used can be ranked as follows: 6-OHDA<lesion<electrolytic lesion<kainic acid lesion<lidocaine injection. The observed effects were transient despite the permanence of the lesions while lesion of the somatosensorimotor cortices produced sustained reduction of the neuropathic manifestations. Our results correlate well with the established connections of the ventrolateral orbital area with the thalamic nucleus subnucleus involved in the procession of thermal nociception. The transient effects reported following permanent lesions in the orbital areas may reflect its flexible role in pain modulation. This observation provides further evidence on the plasticity of the neural networks involved in the regulation of nociceptive behavior.

Adrenergic Agents↗
PubMed1999

Fos-like immunoreactivity in the brain stem following oral quinine stimulation in decerebrate rats.

The present study compared the distribution of Fos-like immunoreactivity (FLI) following intraoral stimulation with quinine monohydrochloride (QHCl) in awake intact rats to the pattern obtained in chronic supracollicular decerebrate (CD) rats. Because the behavioral rejection response to QHCl is evident in the CD rat, it was hypothesized that the pattern of FLI in the lower brain stem should be similar in both groups. Overall, the distribution of FLI in the brain stem was quite similar in both intact and CD groups, and QHCl stimulation increased FLI in the rostral (gustatory) nucleus of the solitary tract, the parabrachial nucleus (PBN), and the lateral reticular formation (RF) compared with an unstimulated control group. The CD group differed from the intact group, however, with a trend toward less FLI in the RF and a shift in the pattern of label away from the external subdivision of the PBN. CD rats also had increased FLI in the caudal nucleus of the solitary tract, with or without intraoral infusions. The distribution of QHCl-induced FLI in the brain stem of intact rats thus indicates both local sensorimotor processing as well as the influence of forebrain structures.

Administration, Oral↗
PubMed2004

Song selectivity in the song system and in the auditory forebrain.

The sensorimotor neurons found in the song-system nuclei are responsive to the sounds of the bird's own song. This selectivity emerges during vocal learning and appears to follow the development of the bird's song vocalization in two ways: at each stage, the neurons are most selective for the bird's current vocalizations and this selectivity increases as the bird learns to produce a stable adult song. Also, because of their location in the sensori-vocal pathway and because their physiological properties are correlated with the motor program, it is postulated that these neurons play a crucial role in interpreting the auditory feedback during song to preserve a desirable vocal output. The neurons found in presynaptic auditory areas lack this selectivity for the bird's own song. Auditory neurons in the secondary auditory areas caudal nidopallium and caudal mesopallium show specific responses to familiar songs or behaviorally relevant songs. These auditory areas might therefore be involved in perceptual tasks. Neurons in the primary forebrain auditory area are selective for the spectrotemporal modulations that are common in song, yielding an efficient neural representation of those sounds. Neurons that are particularly selective for the tutor song at the end of the sensory period have not yet been described in any areas. Although these three levels of selectivity found in the primary auditory forebrain areas, the secondary auditory forebrain areas, and the song system suggest a form of hierarchical sensory processing, the functional connectivity between these areas and the mechanisms generating the specific selectivity for songs that are behaviorally relevant or crucial in song learning and production have yet to be revealed.

Animals↗
PubMed1991

Paternal alcohol consumption in the rat impairs spatial learning performance in male offspring.

Pubescent (30 day old) male rats were maintained on an alcohol liquid diet containing 35% ethanol-derived calories (ALC) for 39 days or were pairfed an isocaloric control diet (PF). The concentration of alcohol in the diet was gradually increased to permit adaptation, then stabilized and then gradually tapered to prevent an alcohol withdrawal syndrome. Following a drug-free period (2 weeks), the males were mated with nontreated females. Offspring were evaluated on several developmental indices and on various learning/memory tasks to assess functional deficits in adulthood. Offspring sired by ALC-treated males did not differ from the offspring of PF males on several developmental parameters including body weights, when developmental landmarks appeared, or on tests of sensorimotor development. As adults, male offspring groups did not differ on tests of activity or on an object exploration/recognition task. However, male offspring of ALC-treated males demonstrated impaired acquisition performance (days and errors to criterion) on a win-shift spatial discrimination in an eight-arm radial maze and on a win-stay discrimination (days to criterion) conducted in a T-maze at a later age. The radial maze results were replicated in a subsequent experiment using different groups of rats.

Alcohol Drinking↗
PubMed1990

Towards a developmental cognitive science. The implications of cross-modal matching and imitation for the development of representation and memory in infancy.

This chapter began with a query about whether there was any content to an enterprise called "developmental cognitive science," and if so, whether the findings could inform work in adult cognition and neuropsychology. Both questions can now be answered in the affirmative. Evidence has been marshaled from infant studies concerning five topics of enduring interest in the cognitive and neuro-sciences: cross-modal integration, imitation, the coordination of perception and action, memory, and representation. The data show that young human infants can detect equivalences between information picked up by different sensory modalities. This was demonstrated both in tactual-visual perception of objects and auditory-visual perception of speech. Results also show that perception and production are intertwined literally from the earliest phases of infancy, with 4-month-olds demonstrating vocal imitation and newborns reproducing elementary gestures they saw an adult perform. There seems to be a transparency between the perceptual and motor systems, and it is conceivable that they may draw on the same internal code. Infants' proclivity to imitate was used to investigate early memory. It was found that young infants were not constrained to immediate mimicry, but could imitate after significant delays. The findings support the inference that infants, perhaps as early as birth, have a functioning memory system that cannot be reduced to "habit formation" or an exclusively "procedural memory." It was proposed instead that there is a kernel of some higher level memory system right from the earliest phases of human infancy. This does not imply that there is no development in the representational world of infants. Data were reviewed suggesting that there is a watershed transformation in childhood cognition at about 18 months of age. However, this is not a change from a stage in which there was a purely sensorimotor or habit-based system. Rather the development was characterized as a shift from using empirical or experience-based representations to using hypothetical representations, which concern possible realities. This developmental shift allows children to project into the future "what must be" and deduce from the past "what must have been," in advance of, and sometimes in the absence of, strictly perceptual evidence. This capacity provides the underpinnings for the conduct of science itself. Its origins are to be found in infancy.

Aging↗
PubMed2001

Dendritic arborizations of the rat substantia nigra pars reticulata neurons: spatial organization and relation to the lamellar compartmentation of striato-nigral projections.

The cerebral cortex provides a major source of inputs to the basal ganglia. As has been well documented, the topography of corticostriatal projections subdivides the striatum into a mosaic of functionally distinct sectors. How information flow from these striatal sectors remains segregated or not within basal ganglia output nuclei has to be established. Electrophysiologically identified neurons of the rat substantia nigra pars reticulata were labeled by juxtacellular injection of Neurobiotin, and the spatial organization of their dendritic arborizations was analyzed in relation to the projection fields of individual striatal sectors. Thirty-nine nigral neurons located in the projection territory of the distinct striatal sensorimotor sectors were reconstructed. The data show that the dendritic arborizations of nigral neurons conform to the geometry of striato-nigral projections. Like striatal projections, the arborizations formed a series of curved laminas enveloping a dorsolaterally located core. Although dendritic fields of the neurons lying in the laminae were flat, those located in the core were spherical or cylindrical, thereby conforming to the shape of the striatal projection fields. This remarkable alignment between the dendritic arborizations of nigral neurons and the projection fields from individual striatal districts supports the concept of a parallel architecture of the striato-nigral circuits. However, pars reticulata neurons usually extend part of their dendrites within adjacent striatal projection fields, thereby ensuring a continuum between channels. The extension of the dendritic arborizations within the striatal projection fields suggests that nigral neurons integrate the information that is relevant for the completion of the specific motor behavior they control.

Action Potentials↗
PubMed1992

Occupational adaptation: toward a holistic approach for contemporary practice, Part 2.

This paper introduces a practice model based on the occupational adaptation frame of reference (Schkade & Schultz, 1992). The occupational adaptation practice model emphasizes the creation of a therapeutic climate, the use of occupational activity, and the importance of relative mastery. Practice based on occupational adaptation differs from treatment that focuses on acquisition of functional skills because the practice model directs occupational therapy interventions toward the patient's internal processes and how such processes are facilitated to improve occupational functioning. The occupational adaptation practice model is holistic. The patient's occupational environments (as influenced by physical, social, and cultural properties) are as important as the patient's sensorimotor, cognitive, and psychosocial functioning and the patient's experience of personal limitations and potential is validated. The integration of these concepts drives the treatment process. Through a description of treatment with a variety of patients, this paper presents the model's diversity and illustrates the relationship between the concepts. The occupational adaptation practice model reflects the uniqueness of occupational therapy and integrates the profession's historical practice with contemporary interventions and methods.

Activities of Daily Living↗
PubMed2001

Neonatal Borna disease virus infection (BDV)-induced damage to the cerebellum is associated with sensorimotor deficits in developing Lewis rats.

Neonatal Borna disease virus (BDV) infection of the brain produces developmental damage to the cerebellum in Lewis rats, with minimal classical inflammatory responses. In the present study, we assessed the consequences of this damage by measuring motor coordination and postural skills in developing (postnatal days 4 to 30) Lewis rats that were neonatally infected with BDV. Neonatal BDV infection-induced motor impairments were selective and correlated with the time course of BDV damage to cerebellar development. BDV-induced motor deficits were not seen until the end of postnatal week 2. By postnatal week 3, BDV-infected rats had deficits in negative geotropism, fore- and hind limb placing and grasping. BDV-infected rats also exhibited deficits in the ability to hold on to a bar and to cross a suspended bar. Neonatal BDV infection induced impairments in the acoustic startle response. Compared to controls, neonatally BDV-infected rats exhibited attenuated habituation of the acoustic startle at postnatal day (PND) 23 and decreased startle responsiveness at PND 30. Prepulse inhibition of the acoustic startle remained unaltered in BDV-infected rats. The data demonstrate that neonatal BDV brain infection of rats can be a valuable animal model system for studying the relationship between abnormal brain development and resultant behavioral deficits. Further studies of this model may elucidate specific pathogenic mechanisms that that may have implications in the study of neurodevelopmental human disorders.

Animals↗