The ontogeny of hemispheric specialization: some old hypotheses revisited

This paper re-examines two hypotheses on the ontogeny of hemispheric specialization that long ago fell into disfavor in neuropsychology. It is argued that these hypotheses, equipotentiality and progressive lateralization, may have suffered from misinterpretation that fostered premature acceptance of the developmental invariance view of hemispheric specialization. An alternative view is presented that incorporates both hypotheses within a neurodevelopmental context using anatomical (postmortem) and childhood aphasia data.     

Predicate-argument structure as a link between linguistic and nonlinguistic representations

We present a study wherein a severe Broca's aphasic patient was trained to learn symbols representing both pure transitive and dative predicates--predicates differing in argument structure--in a visually based artificial language (c-ViC). We found a decrease in performance when two symbols, rather than one, were used to depict these "verbs." However, this decrease in performance was more pronounced for symbols representing pure transitive verbs--those that allow only one argument structure--than for symbols representing dative verbs--those that allow two different argument structures. Also, dative "verbs" yielded better performance when they were inserted in more complex, three-argument "sentences" than when they were inserted in two-argument "sentences." The opposite pattern was found for pure transitives. These results are discussed in terms of our claim that argument structure serves as a point of connection between linguistic information and non-linguistic visual information and in terms of the possibility that argument structure entries are shaped by the form in which visual information is parsed.     

Range and regression, loudness scales, and loudness processing: toward a context-bound psychophysics

How does context affect basic processes of sensory integration and the implicit psychophysical scales that underlie those processes? Five experiments examined how stimulus range and response regression determine characteristics of (a) psychophysical scales for loudness and (b) 3 kinds of intensity summation: binaural loudness summation, summation of loudness between tones widely spaced in frequency, and temporal loudness summation. Context affected the overt loudness scales in that smaller power-function exponents characterized larger versus smaller range of stimulation and characterized magnitude estimation versus magnitude production. More important, however, context simultaneously affected the degree of loudness integration as measured in terms of matching stimulus levels. Thus, stimulus range and scaling procedure influence not only overt response scales, but measures of underlying intensity processing.     

Benzodiazepine receptor ligand influences on acquisition: suggestion of an endogenous modulatory mechanism mediated by benzodiazepine receptors

In rats, pretraining ip administration of the central benzodiazepine receptor antagonist, flumazenil (5.0 mg/kg), or of the inverse agonist, n-butyl-beta-carboline-3-carboxylate (BCCB) (0.2 or 0.5 mg/kg), facilitated retention of a step-down inhibitory avoidance task; the central agonists, clonazepam and diazepam (0.4 or 1.0 mg/kg), had an opposite effect, and the peripheral agonist, 4'-chlordiazepam (1.25 or 6.25 mg/kg), was without effect. Pre- but not post-training flumazenil (2.0 mg/kg) blocked the effect of BCCB (0.5 mg/kg), clonazepam (1.0 mg/kg), or diazepam (1.0 mg/kg) given also pretraining. The post-training administration of all of these drugs had no effect on retention of the avoidance task. Flumazenil (5.0 mg/kg) and BCCB (0.5 mg/kg), given before training, enhanced retention test performance of habituation to a buzzer but not of habituation to an open field. In the three tasks studied, none of the drugs used had any appreciable effect on training session parameters. These results suggest that there is an endogenous mechanism mediated by benzodiazepine agonists, sensitive to inverse agonists, that normally down-regulates acquisition of certain behaviors; this mechanism becomes activated only when the tasks involve or occur with a certain degree of stress or anxiety (i.e., inhibitory avoidance or habituation to the buzzer) and not in less stressful or anxiogenic tasks (i.e., habituation to an open field).     

Cholinergic-dopaminergic interactions in cognitive performance

Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.     

Ethanol-mediated taste aversions and state-dependency in preweanling (16-day-old) rats

Requirements for conditioning of an ethanol-mediated taste aversion in 16-day-old rat pups were examined. Experiment 1 demonstrated that preweanling rats are capable of acquiring, in two trials, an aversion to a 15% sucrose solution when followed by intragastric intubation of a 1.2 g/kg dose of 17% v/v ethanol, but not when followed by a 0.4 g/kg dose. Comparison was with control animals given sucrose followed by an equivalent volume isocaloric Half and Half. When the 0.4 g/kg dose of ethanol preceded sucrose presentation by 30 min (Experiment 2), the aversion was learned, suggesting that the effective delay between the sucrose and the critical consequences of the ethanol had been too long with the former procedure. Expression of the sucrose aversion required, however, the reinstatement of the context of intoxication--state-dependent retention. Finally, the results of Experiment 3B indicated that, in addition to the association between the sucrose and the aversive consequences of alcohol intoxication, the orosensory cues resulting from alcohol's direct elimination, via such processes as respiration and salivation, became associated with the appetitive properties of the sucrose. This was evidenced by a conditioned increase in preference for ethanol odor. Possible age-related differences in the ability to associate stimuli with alcohol's unconditioned consequences, and in state dependency are discussed.     

Glucose and physostigmine effects on morphine- and amphetamine-induced increases in locomotor activity in mice

Recent findings indicate that glucose antagonizes several behavioral effects of cholinergic antagonists and augments those of cholinergic agonists. For example, scopolamine elicits increased locomotor activity, an action which is attenuated by glucose and by combined treatment with glucose and physostigmine at doses which are individually without effect. Opiate and catecholamine agonists, such as morphine and amphetamine, also elicit hyperactivity. The present study examined interactions of glucose and physostigmine with morphine- and amphetamine-induced hyperactivity. Mice received saline, morphine (10 mg/kg), or amphetamine (1 mg/kg) 50 min prior to testing, followed by saline, physostigmine (0.01, 0.05, 0.1, or 0.2 mg/kg), or glucose (10, 50, 100, or 500 mg/kg) administered 20 min prior to activity testing in an open field. Physostigmine significantly attenuated both morphine- and amphetamine-induced increases in activity, but higher doses were required to attenuate the effects of amphetamine. Like physostigmine, glucose significantly attenuated morphine-induced activity levels, but unlike physostigmine, glucose did not attenuate amphetamine-induced activity. Thus, the behavioral effects of morphine were more susceptible to modification by physostigmine and glucose than were the effects of amphetamine. The attenuation of morphine-induced hyperactivity demonstrates a similarity between glucose and cholinergic agonists, and also indicates that glucose may inhibit, directly or indirectly, opiate functions. More generally, these findings add to the evidence that circulating glucose levels selectively influence a growing list of behavioral and neurobiological functions.     

Detectability as a function of target location: effects of spatial configuration

Marked differences in detectability as a function of spatial location, a "detectability gradient," are observed when subjects are required to detect a briefly exposed target pattern of uncertain location in the presence of a number of nontarget patterns. Target detectability also is inversely related to the number of nontarget patterns which are present in this search paradigm. These previous findings provide strong evidence for a serial process in which increasing probability of error occurs during a scan of a rapidly degrading neural representation of the visual image following a brief exposure to the stimuli. It is not yet established whether this scan is attentional or perceptual in nature. The present experiments test the hypothesis of an attentional scan by presenting the target and nontarget patterns in spatially segregated groups. If the scan is attentional, then target detectability under these circumstances would be expected to exhibit the characteristic phenomenon of "group processing"--a close clustering of detection performance for targets located within a group and large differences in detectability across groups. As no evidence for group processing was observed, the results fail to support the view that the scan is attentional in nature but are fully consistent with a nonattentional scan.     

Serial processing of visual spatial patterns in a search paradigm

Previous experiments in this laboratory employing a search paradigm have found highly significant differences in the detectability of a briefly exposed target pattern as a function of the spatial location of the target when it is presented simultaneously with a number of discriminably different nontarget patterns. These detectability differences, at loci equidistant from the fovea, could not be accounted for by any known variation in retinal spatial resolution or by differential lateral masking effects of the target by nearby nontarget patterns. These observations led to the hypothesis that the target in these experiments was detected by a serial mechanism which "scanned" a persisting but rapidly degrading neural representation of the visual scene with increasing detection failures the later in time the scan processed the location occupied by the target. If this hypothesis is correct, then target detectability should vary inversely with the number of stimuli which must be examined. The present experiment confirmed this expectation. A mathematical model of such a serial scanning process also predicts other, less obvious, effects on target detectability which were observed when the number of nontarget patterns was changed.