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At least 1,207 records · Page 67Linked to original sources
PubMed2000

Can a generalized kindling seizure induce a reward state?

The postictal behavioral depression (PBD), characterized by behavioral immobility and unresponsiveness to environmental stimuli, observed after a stage 5 kindling seizure is opioid dependent. Morphine injection prolongs while naloxone and naltrexone (opioid antagonists) reduce or eliminate PBD. Opioids have clear rewarding actions that can be easily detected by place preference conditioning (PPC). In the present study, we evaluated if the opioid release after a stage 5 kindling seizure that produces PBD could induce PPC. Male rats were kindled in the medial preoptic area (MPOA), the amygdala (AMG) or insular cortex (IC). After kindling was established their initial preference in a three-compartment chamber was determined. During conditioning, subjects received a standard kindling stimuli that evoked a stage 5 seizure. At the end of the after discharge and during the PBD the animals were placed in the non-preferred chamber for 30 min. On alternate days they were placed without stimulation in the preferred chamber. At the end of conditioning the kindled groups showed a clear change of preference. This change of preference was completely blocked by injection of naloxone. These results suggest that opioid release after a stage 5 kindling seizure can induce a positive affect of sufficient intensity and duration to induce conditioning.

Amygdala↗
PubMed2006

Affordance-controlled bifurcations of action patterns in martial arts.

Effects of participant-target distance and perceived handstriking efficiency on emergent behavior in the martial art of boxing were investigated, revealing affordance-controlled nonlinear dynamical effects (i.e. bifurcations) within the participant--target system. Results established the existence of critical values of scaled distances for emergence of first time excitations and annihilations of a diverse range of boxing actions i.e. on the appearance and dissolution of jabs, hooks and uppercuts. Reasons for the action diversity were twofold: (a) topological discontinuous changes (bifurcations) in the number of possible handstrikes, i.e. motor solutions to the hitting task; (b) fine modification of probabilities of emergence of striking patterns. Exploitation of a 'strikeability' affordance available in scaled distance-to-target information by boxers led to a diversity of emergent actions through a cascade of bifurcations in the task perceptual-motor work space. Data suggested that perceived efficiency (E) of an action changed as a function of scaled distance (D) and was correlated with the probability of occurrence of action patterns (P), exhibiting the following dependence P = P(E(D)). The implication is that probability of occurrence (P) depends on efficiency (E), which in turn depends on scaled distance (D) to the target. Accordingly, scaled distance-dependent perceived efficiency seems a viable candidate for a contextual (control) parameter to describe the nonlinear dynamics of striking actions in boxing.

Adult↗
PubMed2006

Modulation of brain and behavioural responses to cognitive visual stimuli with varying signal-to-noise ratios.

OBJECTIVE: To study behavioral and brain responses to variations in signal-to-noise ratio (SNR) of cognitive visual stimuli. METHODS: We presented meaningful words visually, embedded in varying amounts of dynamic noise, and utilized magnetoencephalography (MEG) to measure responses to the words. A multidipole model of the evoked fields was constructed to quantify the strengths and latencies of the neuronal sources at each noise level. The recognition rates of the words were measured in separate behavioral sessions. RESULTS: MEG revealed sequential activation of occipital and occipito-temporal areas (latencies 130-250 and 170-350 ms, respectively) followed by activity in superior temporal cortex (230-640 ms). The strengths and latencies of all identified sources followed functions similar to the SNR of the stimulus. The peak amplitudes and shortest latencies of all sources coincided with the maximum SNR of the stimulus. The occipito-temporal and temporal sources as well as the word recognition rate accurately followed the SNR of the stimulus whereas the early occipital source exhibited a more peaked dependence on the SNR. CONCLUSIONS: Evoked responses expectedly peaked at the maximum SNR of the stimulus. Interestingly, early visual responses showed sharper peaks than longer-latency sources as a function of the noise level. This can be understood as the higher-level processes analyzing the stimuli more holistically and thus being less sensitive to the salience of simple visual features. The similar noise-dependence of the longer-latency sources and the recognition rate provides new evidence for the relevance of these activations in the recognition of written words. SIGNIFICANCE: This study contributes to the understanding of brain activity evoked by degraded stimuli with cognitive content.

Adult↗
PubMed1999

Deficit in selective and divided attention associated with cholinergic basal forebrain immunotoxic lesion produced by 192-saporin; motoric/sensory deficit associated with Purkinje cell immunotoxic lesion produced by OX7-saporin.

The immunotoxin 192-saporin, infused intracerebroventricularly into rats, destroys cholinergic neurons in the basal forebrain nuclei. Doses required for complete cholinergic loss also kill some Purkinje cells. The immunotoxin OX7-saporin, when infused intraventricularly into rats, destroys Purkinje cells in a pattern similar to that produced by 192-saporin, without affecting cholinergic neurons. Thus, we used OX7-saporin to distinguish behavioral effects of 192-saporin due to cerebellar damage versus those due to cholinergic cell loss. Three doses of 192-saporin (1.6, 2.6, and 3.3 micrograms/rat) were chosen along with a dose of OX7-saporin (2.0 micrograms/rat) that produced Purkinje loss equivalent to the two highest doses of 192-saporin. Groups of Fischer-344 rats were trained in the multiple choice reaction time task and retested with more complex tasks after lesioning. They were also tested in the water maze, passive avoidance, acoustic startle, and open field. The OX7-saporin group exhibited changes in many tests suggesting hypermotility and sensory deficits. The 192-saporin groups differed from the OX7-saporin group when they displayed deficits in multiple choice reaction time tasks in which novel challenges were introduced, including sessions with a noise distractor, shortened and lengthened intertrial intervals, and use of nine instead of five sources of light stimulus. The 192-saporin groups showed no impairment in the other tasks. The cholinergic basal forebrain lesion may mask some of the effects of cerebellar damage up to a threshold after which effects of Purkinje cell loss predominate when 192-saporin is administered intraventricularly.

Animals↗
PubMed2004

Role of tumor necrosis factor-alpha in methamphetamine-induced drug dependence and neurotoxicity.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is now emerging as an important modulator of the function of the CNS. Methamphetamine (METH) is a widely abused psychostimulant that causes euphoria, hyperactivity, and drug dependence. High doses of METH cause long-term neurotoxicity in dopaminergic neurons. In this study, we investigated a role of TNF-alpha in METH-induced dependence and neurotoxicity. Repeated treatment with METH (2 mg/kg for 5 d) in rats induced a significant increase in TNF-alpha mRNA and protein expression in the brain. Exogenous TNF-alpha (1-4 microg) blocked locomotor-stimulating and rewarding effects of METH, as well as METH (4 mg/kg; four times at 2 hr intervals)-induced dopaminergic neurotoxicity in mice. To examine a role of endogenous TNF-alpha in behavioral and neurochemical effects of METH, we used mice with targeted deletions of the TNF-alpha gene. TNF-alpha-(-/-) mice showed enhanced responses to the locomotor-sensitizing, rewarding, and neurotoxic effects of METH compared with wild-type mice. We also examined the role of TNF-alpha in METH-induced dopamine (DA) release and uptake in vitro and in vivo in C57BL/6 mice. Exogenous TNF-alpha (4 microg) attenuated the METH-induced increase in extracellular striatal DA in vivo and potentiated striatal DA uptake into synaptosomes in vitro and in vivo. Furthermore, TNF-alpha activated vesicular DA uptake by itself and diminished the METH-induced decrease in vesicular DA uptake. Our findings suggest that TNF-alpha plays a neuroprotective role in METH-induced drug dependence and neurotoxicity by activating plasmalemmal and vesicular DA transporter as well as inhibiting METH-induced increase in extracellular DA levels.

Animals↗
PubMed2004

Behavioral studies of auditory-visual spatial recognition and integration in rats.

Rodents are useful animal models in the study of the molecular and cellular mechanisms underlying various neural functions. For studying behavioral properties associated with multisensory functions in rats, we measured the speed and accuracy of target detection by the reaction-time procedure. In the first experiment, we utilized simple two-alternative-choice tasks, in which spatial cues are visual or auditory modalities, and conducted a cross-modal transfer test in order to determine whether rats recognize amodal spatial information. Rats showed successful performance in the cross-modal transfer test and the speed to respond to sensory stimuli was constant under a rule-consistent condition despite the change in cue modality. In the second experiment, we developed audiovisual two-alternative-choice tasks, in which both auditory and visual stimuli were simultaneously presented but one of the two modalities was task-relevant, in order to determine whether the response to the sensory stimulation of one modality is enhanced by the stimulation of a different modality. If bimodal stimuli were spatially coincident, the speed for detecting the relevant stimulus was shortened and the extent of the effect was comparable to those in past studies of humans and other mammals. These results indicate the cross-modal spatial abilities of rats and our present paradigms may provide useful behavioral tasks for studying the neural bases of multisensory processing and integration in rats.

Acoustic Stimulation↗
PubMed1984

Differential perceptual-spatial impairment in Huntington's and Alzheimer's dementias.

Because the severity of memory disorders exhibited by neuropsychiatric patients overshadows other cognitive deficiencies, we explored the visuoperceptual and constructive abilities of patients with Alzheimer's (AD) or Huntington's (HD) disease. The tasks assessed directional sense with reference to egocentric space, as well as visuodiscriminative and constructive skills of patients and matched controls. A double dissociation was found: the performance of patients with AD was found to be significantly impaired on tasks involving extrapersonal perception and construction but not on the test of egocentric space. In contrast, visuoconstructive performance by patients with HD was not significantly impaired, while salient deficits were apparent when manipulation of personal space was required. These differential patterns of defects may have been aligned with neuropathologic changes in different cortical and subcortical structures, respectively, in patients with AD and HD.

Adult↗
PubMed1990

Electrophysiologic comparisons between two groups of patients with Alzheimer's disease.

Two groups of patients with Alzheimer's disease were compared using brain electrical activity mapping. The patients were selected on the basis of their cognitive history. The initial symptom of disease of the patients in group 1 was a significant and profound memory deficit, whereas the patients in group 2 initially presented with a gradually progressive spatial impairment. Fourteen topographic features distinguished the groups. Eleven of the 14 features pertained to electrical activity differences in parietal regions, and 9 were bilateral. These features were highly correlated with cognitive measures that are also useful in distinguishing the groups.

Aged↗
PubMed1992

Psychometric discrimination of moderate senile dementia of the Alzheimer type.

A brief psychometric battery was used to differentiate a sample of 56 individuals classified as having mild senile dementia of the Alzheimer type (SDAT) from 38 individuals with moderate SDAT. Using discriminant analysis techniques, a modest differentiation was obtained. It was noted that specific ability domains, namely, short-term recognition memory, visuospatial reasoning, and verbal ability, contributed to the discriminant function. Although the same domains have been found to differentiate SDAT at earlier stages, individual tests varied in the current sample as a function of marked decrements in ability levels at this advanced stage of the disease. The results suggest that the effectiveness of specific psychometrics for differentiating individuals with SDAT may vary as a function of relative disease stage.

Aged↗
PubMed1994

Impairment of spatially directed attention in patients with probable Alzheimer's disease as measured by eye movements.

OBJECTIVE: To investigate changes in spatially directed attention in patients with a diagnosis of probable Alzheimer's disease (AD). BACKGROUND: Impaired attention in patients with probable AD has not been the subject of extensive research. Yet recent reports suggest that attentional deficits may be an important early feature of the disease in a subset of patients. SETTING: University hospital center studying dementia and aging. SUBJECTS: Ten mild to moderately impaired patients diagnosed as having probable AD, by National Institute of Neurologic and Communicative Diseases and Stroke criteria, and 11 healthy age- and education-matched controls. MEASURES: Eye movements were recorded as subjects participated in two experiments designed to measure spatially directed attention. Subjects were instructed to (1) attend to and fixate a target appearing randomly to the right or left of a central marker and (2) direct attention to and fixate a target appearing randomly in one of four peripheral locations. RESULTS: Patients with probable AD exhibited fewer accurate trials and longer saccade latencies in both tasks. As a group, patients performed worse in the second task that placed increased demands on attention. However, the performance of patients in this second experiment varied. Four patients performed significantly worse than all other patients, while three patients performed as well as controls. Errors in the second task were reviewed to identify specific types of attentional deficits. Six empirically derived error patterns were classified into one of two major categories: perseveration and impersistence. Seven of 10 patients made greater than 50% errors of perseveration, and three of 10 made greater than 50% errors of impersistence. CONCLUSIONS: Impairment of attention may be an early feature of AD and a prominent clinical characteristic of some patients. The differences observed in error types made by patients may reflect the varied distribution of neuropathologic changes affecting structures that mediate aspects of attention. The architecture of eye movements can be used as a physiologic measure that should provide useful information for the diagnosis and clinicopathologic subtyping of patients with AD.

Aged↗
PubMed1995

Visuospatial deficit in dementia of the Alzheimer type.

OBJECTIVE: To examine visuospatial impairment in a task that minimizes episodic memory demands in individuals with very mild or mild dementia of the Alzheimer type compared with a healthy control group. DESIGN: Initial scores on the Visual Form Discrimination Test enrolled in longitudinal studies of dementia of the Alzheimer type and healthy aging. SETTING: Alzheimer's Disease Research Center at Washington University, St Louis, Mo. PARTICIPANTS: Volunteer samples of 59 people (35 women and 24 men) with mild dementia of the Alzheimer type, 66 (39 women and 27 men) with mild dementia of the Alzheimer type, and 146 healthy nondemented individuals (90 women and 56 men) were recruited between 1988 and 1992. Ages ranged from 51 to 96 years. Persons with confounding medical, neurologic, or psychiatric disorders were excluded. Dementia severity was staged by means of the Clinical Dementia Rating. MAIN OUTCOME MEASURES: Total number correct on the Visual Form Discrimination Test as well as the numbers of three types of errors: peripheral figure movement or rotation, major figure distortion, and major figure rotation. RESULTS: Visuospatial deficit was apparent in very mild dementia of the Alzheimer type. Individuals with both very mild and mild dementia of the Alzheimer type made more errors involving peripheral figures and rotation of a major figure than did healthy, nondemented individuals. CONCLUSION: The initial effects of Alzheimer's disease on cognitive function are more pervasive than just episodic memory failure.

Aged↗
PubMed1995

Cognitive test performance in detecting, staging, and tracking Alzheimer's disease.

OBJECTIVES: To identify the specific cognitive deficits that characterize Alzheimer's disease (AD) and determine which cognitive tests, or combination of tests, are best for detecting AD (ie, distinguishing patients with AD from normal control subjects), staging AD (ie, distinguishing different severities of dementia), and tracking disease progression. SUBJECTS: Patients with AD (n = 123) and normal control subjects (n = 60) of comparable age, education, and gender distribution. SETTING: Outpatient care. MEASURES: Ten cognitive tests of memory, language, visuospatial abilities, and reasoning; the Information, Memory and Concentration subtest of the Blessed Dementia Scale, and the total score on an activities of daily living questionnaire. DESIGN: Patients with AD were tested every 6 to 24 months over a span of up to 5.5 years. RESULTS: Patients with AD were significantly inferior to normal control subjects on all cognitive tests. The scores of patients with AD worsened over time. Delayed recall of stories and figures showed sharp deterioration to an early floor, consistent with the finding that these tests discriminated patients with mild AD from normal control subjects well but were poor for staging. Confrontation naming, semantic fluency, and immediate recognition of geometric figures showed steady linear decline across time for patients with AD, consistent with these tests being found best for staging dementia severity. CONCLUSIONS: We postulate that the pathologic bases of impairment in delayed recall are atrophy of cholinergic ventral forebrain neurons and partial deafferentation of the hippocampus, both of which occur early in the course of AD. Worsening language and visuospatial abilities likely reflect progressive loss of neocortical neurons and their connections.

Aged↗
PubMed1997

Spatial training in a complex environment and isolation alter the spine distribution differently in rat CA1 pyramidal cells.

The hippocampus is critically involved in spatial learning. Spatial training in adult rats, which improved their spatial learning ability, increased the number of excitatory hippocampal CA1 spine synapses on basal dendrites as compared with either isolated or standardly housed animals (Moser et al. [1994] Proc. Natl. Acad. Sci. USA 91:12673-12675). In this article, we report that spine synapses on oblique apical dendritic branches do not increase in density or number after the same type of training. When examining the variability of the spine density on basal CA1 dendrites by using variance component analysis, the variance associated with the cells was twice as large in all three groups as that coupled to the rats. Analysis of the spine density plots shows that the enhanced spine density after spatial training is found in most cells recorded from the trained group but that a small subset of CA1 neurones are particularly well supplied with spines. The trained group had a significant right-skewed tail of the spine distribution, i.e., training caused high spine density to occur in a small subset of dendritic segments. Conversely, the isolated group had a significant left-skewed spine distribution, indicating that some of the dendritic segments were undersupplied with spines, whereas the paired group displayed no asymmetry.

Animals↗
PubMed1996

Hippocampal place cells connected by Hebbian synapses can solve spatial problems.

We propose that a cognitive map can be stored in the synapses between the pyramidal cells of CA3 in the form of the pattern of synaptic strengths connecting them. The model requires only that there are place cells in CA3 and that the connections between them are modifiable in a Hebbian manner. Given these suppositions, the synaptic strengths must evolve to represent the distance between firing centers of synaptically connected place cells. We argue that this arrangement of synaptic weights embodies all the formal properties of a map. We demonstrate that the information stored in such a structure is sufficient to solve several classic spatial problems including finding shortest paths, and negotiating detours. It is clear that much of the physiology and anatomy necessary to more precisely characterize the model is not known at this time. Nevertheless the model is robust under a variety of cell and connection densities. It also performs well under several different functions relating distance to synaptic strength. What is most remarkable in the model is that it is a logical consequence of the several key anatomical and physiological properties of the CA3 region of rats. Whether this information is used by the rat is difficult to assess at this time. Regardless of the outcome of this question, the model has promising applications to the field of robot navigation.

Animals↗
PubMed1996

Memory for places: a navigational model in support of Marr's theory of hippocampal function.

In this report we describe a model that applies Marr's theory of hippocampal function to the problem of map-based navigation. Like many others we attribute a spatial memory function to the hippocampus, but we suggest that the additional functional components required for map-based navigation are located elsewhere in the brain. One of the key functional components in this model is an egocentric map of space, located in the neocortex, that is continuously updated using ideothetic (self-motion) information. The hippocampus stores snapshots of this egocentric map. The modeled activity pattern of head direction cells is used to set the best egocentric map rotation to match the snapshots stored in the hippocampus, resulting in place cells with a nondirectional firing pattern. We describe an evaluation of this model using a mobile robot and demonstrate that with this model the robot can recognize an environment and find a hidden goal. This model is discussed in the context of prior experiments that were designed to discover the map-based spatial processing of animals. We also predict the results of further experiments.

Animals↗