Changes In Behavioral Performance Research Articles

Temporal modeling demonstrates preserved overlearning processes in schizophrenia: An fMRI study

Working memory (WM) deficits are a core feature of schizophrenia. However, it has not been examined whether these deficits are related to altered temporal dynamics of information acquisition and changes in executive cognitive control. Therefore, the present study intended to quantify and model the dynamic process of information acquisition during continuous overlearning of WM information. It also aimed at investigating the relation between overlearning-associated change in behavioral performance and brain activity. Thirteen schizophrenic patients and 13 healthy volunteers were studied with functional magnetic resonance imaging (fMRI) while performing a recently developed overlearning paradigm [Koch K, Wagner G, von Consbruch K, Nenadic I, Schultz C, Ehle C, Reichenbach J, Sauer H, Schlösser R (2006) Temporal changes in neural activation during practice of information retrieval from short-term memory: An fMRI study. Brain Res 1107:140–150]. Consistent with the earlier study, short-term learning of stimulus material was associated with significant performance improvements and exponential signal decreases in a fronto-parieto-cerebellar network both in schizophrenic patients and in healthy volunteers. Against expectation patients exhibited stronger signal decreases relative to controls in anterior cingulate (Brodmann area (BA) 32), middle and superior temporal (BA 37, BA 22), superior frontal (BA 8/9, BA 6) and posterior parietal regions (BA 40). Furthermore, the individually modeled exponential decay rate of the blood oxygenation level-dependent signal in the right dorsolateral prefrontal cortex was significantly correlated with exponential decrease in mean behavioral response times in healthy controls while a statistical trend emerged in patients. A relative hyperactivation in the patient group was observable only at the start of the learning process and diminished with continued overlearning. This effect might indicate a gradual reduction of recruited neuronal resources and a practice-associated activation normalization in patients with schizophrenia. Our data suggest that in subacute patients learning and associated decreases in cerebral activation brought about by short-term practice are left unimpaired.

Functional neural networks underlying response inhibition in adolescents and adults

This study provides the first description of neural network dynamics associated with response inhibition in healthy adolescents and adults. Functional and effective connectivity analyses of whole brain hemodynamic activity elicited during performance of a Go/No-Go task were used to identify functionally integrated neural networks and characterize their causal interactions. Three response inhibition circuits formed a hierarchical, inter-dependent system wherein thalamic modulation of input to premotor cortex by fronto-striatal regions led to response suppression. Adolescents differed from adults in the degree of network engagement, regional fronto-striatal-thalamic connectivity, and network dynamics. We identify and characterize several age-related differences in the function of neural circuits that are associated with behavioral performance changes across adolescent development.

Recovery from aphasia as a function of language therapy in an early bilingual patient demonstrated by fMRI

Knowledge about the recovery of language functions in bilingual aphasic patients who suffer from left-hemispheric stroke is scarce. Here, we present the case of an early bilingual patient (German/French) with chronic aphasia. Functional magnetic resonance imaging (fMRI) was used to investigate neural correlates of language performance during an overt picture naming task in German and French (a) 32 months after stroke to assess differential recovery of both languages as a function of the preceding language therapy that was provided exclusively in German and (b) after additional short-term intensive (German) language training. At the first investigation behavioral performance confirmed selective recovery of German naming ability which was associated with increased functional brain activation compared to the French naming condition. Changes in behavioral performance and brain activation pattern as disclosed by fMRI after an additional experimental treatment were confined to the trained (German) language and indicate bilateral neuroplastic reorganization. No generalization to the untrained (French) language was observed. The present case results demonstrate use and/or training-dependent differential recovery of expressive language functions and an enhanced pattern of brain activation as a function of the rehabilitation efforts that were focussed exclusively on the patient's German language abilities.

Temporal changes in neural activation during practice of information retrieval from short-term memory: An fMRI study

Several findings indicate that practice in working memory tasks leads to signal decreases in task-relevant regions. However, the precise dynamics underlying these signal decreases and how they are correlated with improvements in behavioral performance are still matters of debate. We used functional magnetic resonance imaging (fMRI) to assess the cerebral correlates of the practice-related transition from controlled to automatic processing for the retrieval of information maintained in working memory storage. Exponential signal decreases and increases were modeled as covariates of interest. In addition, a bivariate regression analysis on the change in BOLD signal for two a priori hypothesized prefrontal regions (VLPFC, DLPFC) and the change in behavioral performance was conducted to examine the relationship between practice-related changes in cerebral activation and performance. We found exponential practice-related signal decreases mainly in the right superior frontal gyrus/DLPFC (BA 8/9/46), the middle frontal gyrus bilaterally (BA 10/11), the left precentral gyrus (BA 4/6) and the dorsal part of the right anterior cingulate cortex (BA 32). An exponential signal increase was detectable in the posterior cingulate cortex adjacent to the corpus callosum. In addition, there was a correlation between the practice-related change in BOLD signal in the DLPFC (BA 8/9) and the practice-related change in behavioral performance. These results suggest that the transition from controlled to automatic working memory processing is associated with exponential signal decreases in task-relevant regions. The temporal changes in brain activation patterns could be attributed to enhanced efficiency of information processing as a result of cognitive practice.

Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories

Learning to perform a behavioural procedure as a well-ingrained habit requires extensive repetition of the behavioural sequence, and learning not to perform such behaviours is notoriously difficult. Yet regaining a habit can occur quickly, with even one or a few exposures to cues previously triggering the behaviour. To identify neural mechanisms that might underlie such learning dynamics, we made long-term recordings from multiple neurons in the sensorimotor striatum, a basal ganglia structure implicated in habit formation, in rats successively trained on a reward-based procedural task, given extinction training and then given reacquisition training. The spike activity of striatal output neurons, nodal points in cortico-basal ganglia circuits, changed markedly across multiple dimensions during each of these phases of learning. First, new patterns of task-related ensemble firing successively formed, reversed and then re-emerged. Second, task-irrelevant firing was suppressed, then rebounded, and then was suppressed again. These changing spike activity patterns were highly correlated with changes in behavioural performance. We propose that these changes in task representation in cortico-basal ganglia circuits represent neural equivalents of the explore-exploit behaviour characteristic of habit learning.

Bilateral activation of the prefrontal cortex after strategic semantic cognitive training

The prefrontal cortex (PFC) has been implicated in the ability to apply semantic organizational strategies during verbal encoding and episodic learning. However, there has been no direct evidence demonstrating which specific areas in the PFC are engaged after cognitive training using semantic organizational strategies in healthy adult human subjects. In this study, we investigated the effects of semantic strategic training on brain activity and changes in behavioral performance, after cognitive training, using functional MRI (fMRI). There was a significant activation in bilateral dorsolateral prefrontal (DLPF) and orbitofrontal (OFC) areas after cognitive training. These results demonstrate the engagement of bilateral DLPF and OFC cortex during strategic memory processes, particularly when mobilization and effort of effective use of strategies are required. The functional adaptations observed here may also shed light on some of the processes underlying recovery with cognitive rehabilitation in patient populations with brain injury.

Functional imaging of working memory in obstructive sleep-disordered breathing

Functional magnetic resonance imaging was used to map cerebral activation in 16 patients with obstructive sleep-disordered breathing (OSDB) and 16 healthy subjects, during the performance of a 2-back verbal working memory task. Six patients with OSDB were reimaged after a minimum period of 8 wk of treatment with positive airway pressure. Working memory speed in OSDB was significantly slower than in healthy subjects, and a group average map showed absence of dorsolateral prefrontal activation, regardless of nocturnal hypoxia. After treatment, resolution of subjective sleepiness contrasted with no significant change in behavioral performance, persistent lack of prefrontal activation, and partial recovery of posterior parietal activation. These findings suggest that working memory may be impaired in OSDB and that this impairment is associated with disproportionate impairment of function in the dorsolateral prefrontal cortex. Nocturnal hypoxia may not be a necessary determinant of cognitive dysfunction, and sleep fragmentation may be sufficient. There may be dissociations between respiratory vs. cortical recovery and objective vs. subjective recovery. Hypofrontality may provide a plausible biological mechanism for a clinical overlap with disorders of mood and attention.

Maturation of escape circuit function during the early adulthood of cockroaches Periplaneta americana.

During postembryonic development of insects, sensorimotor pathways, which generate specific behaviors, undergo maturational changes. It is less clear whether such pathways are typically stable, or undergo further maturation, during the adult stage. In the present study, we have examined this issue by multilevel analysis of a simple model system, the escape behavior of the cockroach, from identified synapses to behavior. We show that the escape system is highly responsive immediately after the molt to adulthood, but that the latency of escape responses was not at its typical value immediately after the molt to adult. The latency of escape behavior increased over the first 30 days of adult life, perhaps indicating maturational adjustments of the escape sensorimotor pathway. The first station in the escape circuitry is the synaptic connections between the cercal wind receptors and the giant interneurons. We measured unitary excitatory synaptic potentials between single sensory neurons and an identified giant interneuron (GI(2)). We found a decrease in the synaptic strength between identified cercal hairs from a single column and GI(2) over the first month after the adult molt. Consequently, the latency and the number of action potentials of GI(2) in response to natural stimuli increased and decreased respectively during this time. Thus, we show that both behavioral performance and the wind sensitivity of GI(2) decreased over the first month after molt. We conclude that the cockroach escape system undergoes further sensorimotor maturation over a period of 1 month, and that cellular changes correlate with, or predict, some changes in behavioral performance.

Endogenous glucocorticoids inhibit scratching behavior induced by the administration of compound 48/80 in mice

In this study, we investigated the effects of endogenous glucocorticoids on the compound 48/80 (a condensation product of N-methyl- p-methoxyphenethylamine with formaldehyde)-induced mouse scratching behavior using either RU-486 (mifepristone), a glucocorticoid receptor antagonist, or a surgical resection of the adrenal glands. Subcutaneous injection of compound 48/80 induced not only a corticosterone elevation in the plasma but also an enhanced expression of corticotropin releasing hormone (CRH) mRNA in the paraventricular nucleus, which thus suggests that hypothalamic–pituitary–adrenal axis is activated by the compound 48/80-induced cutaneous reaction. Inhibition of such an endogenous glucocorticoid activity by RU-486 significantly increased the degree of scratching behavior at not only the early-phase (<60 min) but also the late-phase (>60 min) time course after the injection of compound 48/80. Since the elevation of the histamine levels in the plasma in the RU-486-treated mice was no longer found in late-phase scratching behavior, these results thus indicate that histamine is a dominant mediator responsible for early-phase scratching behavior, while different mediators other than histamine may be also involved in the induction of late-phase scratching behavior. Moreover, surgical removal of adrenal glands also significantly increased the compound 48/80-induced scratching behavior without affecting anxiety and locomotor parameters, indicating that endogenous glucocorticoids exert their anti-pururitogenic effects independently of changes in behavioral performance. In conclusion, endogenous glucocorticoid activity was found to suppress the compound 48/80-induced scratching behavior in mice.

Prior exposure to methylenedioxyamphetamine (MDA) induces serotonergic loss and changes in spontaneous exploratory and amphetamine-induced behaviors in rats

The substituted amphetamine 3,4 methylenedioxyamphetamine (MDA) is a popular recreational drug of abuse. Administration of MDA to experimental animals has been shown to induce damage to serotonergic axons and nerve terminals. However, there is a lack of information on whether these treatments can produce any long-term changes in behavioural performance particularly under stressful conditions. In the present study, MDA (7.5 mg/kg; i.p.) was administered twice daily to adult male Sprague Dawley rats for four days. Four weeks following the last dose, spontaneous behaviors of these animals were tracked and scored in a novel “open field” environment using an automated video registration and computer interpretation system. Changes in behavior were observed in MDA treated animals including reductions in exploratory oriented behaviors (locomotion and rearing) and increases in grooming behavior when compared to vehicle treated controls. MDA-treated animals also displayed an enhanced locomotor and stereotyped response to d-amphetamine (12 mg/kg; i.p.). Significant reductions in 5-HT concentrations (20–30%) were observed in the frontal cortex, amygdala, striatum, and hypothalamus as a result of MDA treatment. In addition, [ 3H] paroxetine binding was reduced by (40%) in the cortex of MDA treated rats indicating that the decrease in 5-HT concentrations were accompanied by a reduction in intact presynaptic 5-HT nerve terminals. Changes in behavioural performance in a novel “open field” environment and following d-amphetamine challenge might be considered as a behavioural model of serotonergic deficit induced by MDA. The findings of this study also suggest that MDA use may increase both the abuse potential, and the propensity to develop psychosis as a result of abusing other psychostimulants such as d-amphetamine.

Prolonged Exposure to Low Doses of Ozone: Short- and Long-Term Changes in Behavioral Performance in Mice

Two separate experiments were designed to assess the effects of ozone exposure on outbred CD-1 mice. In the first experiment, adult males were exposed continuously to O3 at 0, 0.3, or 0.6 ppm for 30 days and their behavior was assessed in a 5-min open-field test on exposure days 4 and 19 and on day 3 after the end of the exposure phase. In addition, mice performed a Morris water maze task from exposure day 24 to 28. In the second experiment, adult females were exposed from 30 days prior to the formation of breeding pairs until gestational day 17 to the same doses used in the first experiment. Litters were fostered at birth to untreated dams and neurobehavioral development of the offspring was investigated until adulthood. Specifically, somatic and sensorimotor development [postnatal day (PND) 2–20], homing performance (PND 12), motor activity (PND 21), passive avoidance (PND 22–23), water maze performances (PND 70–74), and response to a nociceptive stimulus (PND 100) were assessed. Results from both experiments confirm that exposure to O3 slightly but selectively affected neurobehavioral performance in rodents. Exposure to O3 did not grossly affect neurobehavioral development, whereas it consistently impaired reversal learning in the Morris water maze test in both prenatally and adult exposed mice. Moreover, longer latency to step-through in the first trial of the passive avoidance test and a decrease in wall rearing in the hot-plate test were recorded in O3 prenatally exposed mice. Except for the first open-field test, altered responses were observed only in animals exposed at the intermediate concentration of the gas. Adaptation and/or onset of compensatory mechanisms might be responsible for the lack of linear dose–response relationships.

On your mark, get set: Brainstem circuitry underlying saccadic initiation

Saccades are rapid eye movements that are used to move the visual axis toward targets of interest in the visual field. The time to initiate a saccade is dependent upon many factors. Here we review some of the recent advances in our understanding of the these processes in primates. Neurons in the superior colliculus and brainstem reticular formation are organised into a network to control saccades. Some neurons are active during visual fixation, while others are active during the preparation and execution of saccades. Several factors can influence the excitability levels of these neurons prior to the appearance of a new saccadic target. These pre-target changes in excitability are correlated to subsequent changes in behavioural performance. Our results show how neuronal signals in the superior colliculus and brainstem reticular formation can be shaped by contextual factors and demonstrate how situational experience can expedite motor behaviour via the advanced preparation of motor programs.Key words: superior colliculus, reticular formation, eye movement, saccade, motor preparation, motor control.

On your mark, get set: Brainstem circuitry underlying saccadic initiation

Saccades are rapid eye movements that are used to move the visual axis toward targets of interest in the visual field. The time to initiate a saccade is dependent upon many factors. Here we review some of the recent advances in our understanding of the these processes in primates. Neurons in the superior colliculus and brainstem reticular formation are organised into a network to control saccades. Some neurons are active during visual fixation, while others are active during the preparation and execution of saccades. Several factors can influence the excitability levels of these neurons prior to the appearance of a new saccadic target. These pre-target changes in excitability are correlated to subsequent changes in behavioural performance. Our results show how neuronal signals in the superior colliculus and brainstem reticular formation can be shaped by contextual factors and demonstrate how situational experience can expedite motor behaviour via the advanced preparation of motor programs.

Transgenic mice in drug dependence research

Transgenic mice with null mutation of specific genes of the central nervous system obtained by homologous recombination, called also knock-out mice, have been recentlyused by behavioural neuroscientists to understand better the relevance of certain biological mechanisms of drug dependence or addiction. This article reviews some of the main contributions to this fastly developing field. As addictive drugs exert similar reinforcing effects both in humans and other mammals, changes in behavioural performance produced by the motivational effects of the addictive drugs in knock-out mice can give important information about the relevance of that particular gene product (eg a neurotransmitter receptor) for the pathogenecity of substance abuse disorders. In same cases the deletion of a given gene for a neurotransmitter receptor involved in the action of addictive drugs is associated with a phenotype that reproduces the effects obtained by the pharmacological administration of an antagonist for the same receptor. In other instances, surprising results are obtained, the most striking being the evidence that mice lacking the dopamine transporter gene, the most important binding site of cocaine, retain the capability to self-administer cocaine intravenously. Because the gene deletion is operative during embryogenesis, some adaptive compensatory mechanisms may produce unexpected results, suggesting caution in the interpretation of these results. The advent of tissue-specific inducible knock-out mice will soon produce a second revolution in the field of substance abuse research.

Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys

This study was undertaken to document plastic changes in the functional topography of primary motor cortex (M1) that are generated in motor skill learning in the normal, intact primate. Intracortical microstimulation mapping techniques were used to derive detailed maps of the representation of movements in the distal forelimb zone of M1 of squirrel monkeys, before and after behavioral training on two different tasks that differentially encouraged specific sets of forelimb movements. After training on a small-object retrieval task, which required skilled use of the digits, their evoked-movement digit representations expanded, whereas their evoked-movement wrist/forearm representational zones contracted. These changes were progressive and reversible. In a second motor skill exercise, a monkey pronated and supinated the forearm in a key (eyebolt)-turning task. In this case, the representation of the forearm expanded, whereas the digit representational zones contracted. These results show that M1 is alterable by use throughout the life of an animal. These studies also revealed that after digit training there was an areal expansion of dual-response representations, that is, cortical sectors over which stimulation produced movements about two or more joints. Movement combinations that were used more frequently after training were selectively magnified in their cortical representations. This close correspondence between changes in behavioral performance and electrophysiologically defined motor representations indicates that a neurophysiological correlate of a motor skill resides in M1 for at least several days after acquisition. The finding that cocontracting muscles in the behavior come to be represented together in the cortex argues that, as in sensory cortices, temporal correlations drive emergent changes in distributed motor cortex representations.

学習記憶実験と抗痴呆薬

Discoveries of long-term potentiation and immediate early gene in the central nervous system have enabled new developments in experiments on learning and memory. These experiments are conducted in many kinds of animals with different procedures, physiology, chemistry and pharmacology. However, there is still some confusion when these various procedures are discussed. Memory is defined as information storage of an animal's previous experiences. The memory induces changes in behavioral performance. This means that memory must be observed in whole animals, and one question that can occur is how does long-term potentiation, for example, correlate with memory. Furthermore, memory has been divided into two major classifications, declarative and non-declarative, from the comparison of amnesias observed in humans and animals. The declarative memory can be observed in human subjects, but not in animals. This article presents a neuronal circuit concerning memory formation and some results obtained from benzodiazepines, and it discusses some problems encountered executing when experiments on learning and memory. In addition, the discussion speculates over the possibility for an "anti-dementia drug".

Acetylcholine modulates averaged sensory evoked responses and perforant path evoked field potentials in the rat dentate gyrus

The effect of localized application of acetylcholine (ACh) on well chacracterized components of sensory evoked and electrically induced potentials in the dentate gyrus was investigated in rats while performing a tone discrimination task. Local pressure application of ACh to the granule cell layer of the dentate gyrus through the recording pipette increased the amoplitude of perforant path evoked population spikes without changing the amplitude of the field EPSP. When the pipette was relocated to the outer molecular layer of the dentate (OM), ACh application decreased the amplitude of the perforant path field EPSP. Two major components of the averaged auditory evoked potential (AEP) recorded during criterion performance of the discrimination task were significantly changed by dendritic application of ACh. The N 1 component of the OM AEP which has been shown to reflect perforant path synaptic activity decreased in amplitude while the N 2 component wich represent activity from septal connections, was significantly increased. These effects were not due to pressure ejection nor drug related changes in behavioral performance of the task. The results suggest that ACh may act to differentially modulate the synaptic excitability of dentate granule cells, allowing them to acquire responses to sensory stimulation during establishment and maintenance of discrimination learning.

Behavioral performance effects of verapamil in normotensive and renovascular hypertensive baboons.

Behavioral performances of normotensive and hypertensive adult male baboons were tested before, during, and following chronic oral dosing with verapamil. Performances during a five-color simultaneous match-to-sample task were measured for two doses (2.0, and 3.2 mg/kg/day) and vehicle. Each dose was administered for 21 consecutive days preceded and followed by 14-day baseline and recovery periods, respectively. Choice reaction times increased by 9% during the lower dose of verapamil, compared to vehicle; choice reaction times were unchanged at the higher dose. At baseline and during vehicle administration, the yellow and white stimuli were the most difficult to discriminate correctly; discrimination of these colors was slightly impaired by the lower, but not the higher dose of verapamil. Verapamil's behavioral effects were not modulated by blood pressure changes since both baboon groups showed equivalent changes in behavioral performance, but only renovascular hypertensive baboons showed blood pressure decreases. Verapamil appears to be an effective hypotensive and does not produce profound psychomotor impairment at clinically used doses during the first weeks of treatment.

Fractionating the Word Repetition Effect with Event-Related Potentials

Word repetition has been a staple paradigm for both psycholinguistic and memory research; several possible loci for changes in behavioral performance have been proposed. These proposals are discussed in light of the event-related brain potential (ERP) data reported here. ERPs were recorded as subjects read nonfiction articles drawn from a popular magazine. The effects of word repetition were examined in this relatively natural context wherein words were repeated as a consequence of normal discourse structure. Three distinct components of the ERP were found to be sensitive to repetition: a positive component peaking at 200 msec poststimulus, a negative one at 400 msec (N400), and a later positivity. The components were differentially sensitive to the temporal lag between repetitions, the number of repetitions, and the normative frequency of the eliciting word. The N400 responded similarly to repetition in text as it has in experimental lists of words, but the late positivity showed a different pattern of results than in list studies.

Effects of exposure to 30 kV/m, 60‐Hz electric fields on the social behavior of baboons

We tested the hypothesis that exposure to a 30-kV/m, 60-Hz electric field produces significant change (stress) in the social behavior of adult male baboons (Papio cynocephalus anubis). One group of eight baboons was exposed to an electric field (12 hours per day, 7 days per week for 6 weeks) while a second group of eight baboons was maintained in a sham-exposure (control) condition. Exposed subjects and control subjects were compared over three, six-week experimental periods (pre-exposure, exposure, and post-exposure). Performance rates of six categories of social behaviors (passive affinity, active affinity, approach, tension, threat, and attack) and four categories of nonsocial behaviors (forage, manipulate, posture, and stereotypy) were used to compare the two groups. The results of our study indicate that 1) there were no significant differences between the two groups during the pre-exposure or post-exposure periods; 2) during the exposure period, experimental and control groups exhibited statistically significant differences in the mean performance rates of three behavior categories; 3) within-group comparisons across periods indicate that the experimentally exposed group exhibited statistically significant changes in passive affinity, tension, and stereotypy; and 4) changes in behavior performance among the exposed subjects reflect a stress response to the electric field.