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Functional magnetic resonance imaging was used to test whether odorants induce activation in the cerebellum of the human. The odorants vanillin and propionic acid both induced significant activation, primarily in the posterior lateral hemispheres. Activation was concentration-dependent, greater after stimulation with higher concentration odorants. By contrast, the action of sniffing nonodorized air induced significant activation in the anterior cerebellum, primarily in the central lobule. These findings demonstrate that the cerebellum plays a role in human olfaction. A hypothesis is proposed whereby the cerebellum maintains a feedback mechanism that regulates sniff volume in relation to odor concentration.

Current brain models of emotion processing hypothesize that positive (or approach-related) emotions are lateralized towards the left hemisphere, whereas negative (or withdrawal-related) emotions are lateralized towards the right hemisphere. Brain imaging studies, however, have so far failed to document such hemispheric lateralization. In a functional magnetic resonance imaging (fMRI) study, 14 female subjects viewed alternating blocks of emotionally valenced positive and negative pictures. When the experience of valence was equated for arousal, overall brain reactivity was lateralized towards the left hemisphere for positive pictures and towards the right hemisphere for negative pictures. This study provides direct support for the valence hypothesis, under conditions of equivalent arousal, by means of functional brain imaging.

Functional neuroimaging studies of episodic recognition memory consistently demonstrate retrieval-associated activation in right prefrontal regions, including the right anterior and right dorsolateral prefrontal cortices. In theory, these activations could reflect processes associated with retrieval success, retrieval effort or retrieval attempt; each of these hypotheses has some support from previous studies. In Experiment 1, we examined these functional interpretations using functional MRI to measure prefrontal activation across multiple levels of recognition performance. Results revealed similar patterns of right prefrontal activation across varying levels of retrieval success and retrieval effort, suggesting that these activations reflect retrieval attempt. Retrieval attempt may include initiation of retrieval search or evaluation of the products of retrieval, such as scrutiny of specific attributes of the test item in an effort to determine whether it was encountered previously. In Experiment 2, we examined whether engagement of retrieval attempt is context-dependent by varying the context in which retrieval was performed; this was done by changing test instructions. Importantly, study and test stimuli were held constant, with only the test instructions varying across conditions. Results revealed that the pattern of right prefrontal activation varied across retrieval contexts. Collectively, these experiments suggest that right prefrontal regions mediate processes associated with retrieval attempt, with the probability of engaging these regions depending upon the retrieval context. Conflicting results across previous studies may be reconciled if the influence of retrieval context on the adopted retrieval strategy is considered. Finally, these results suggest that right prefrontal regions activated during recognition are not critical for successful performance as similar magnitudes of activation were present across multiple levels of performance. These findings reconcile imaging results with the selective effects of prefrontal lesions on retrieval-intensive episodic memory tests.

During the decade following a functional neuroimaging study of language that showed cerebellar involvement in a cognitive task, PET and fMRI studies have continued to provide evidence that the role of the cerebellum extends beyond that of motor control and that this structure contributes in some way to cognitive operations. In this review, we describe neuroimaging evidence for cerebellar involvement in working memory, implicit and explicit learning and memory, and language, and we discuss some of the problems and limitations faced by researchers who use neuroimaging to investigate cerebellar function. We also raise a set of outstanding questions that need to be addressed through further neuroimaging and behavioral experiments before differing functional accounts of cerebellar involvement in cognition can be resolved.

Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.

Human brain imaging studies have found that increases in functional activation in left-frontal cortex during cognitive tasks are often accompanied by similar increases in right-cerebellar regions. The present study used functional magnetic resonance imaging (fMRI) to investigate the distinctive contributions of these regions using a word stem completion task. Stems with many possible completions (MANY condition) were alternately presented with stems that had few possible completions (FEW condition), and subjects were asked to covertly complete each stem with a word and press a response switch for each successful completion. Prominent increases in activation in the MANY, relative to the FEW, condition were observed in the left middle frontal gyrus (Brodmann areas 9/10) and left caudate nucleus. In contrast, portions of the right-cerebellar hemisphere (posterior quadrangular lobule and superior semilunar lobule) and cerebellar vermis exhibited increases in the FEW, relative to the MANY, condition. This double dissociation suggests that the frontal and cerebellar regions make distinctive contributions to cognitive performance, with left-frontal (and striatal) activations reflecting response selection, which increases in difficulty when there are many appropriate responses, and right-cerebellar activation reflecting the search for responses, which increases in difficulty when even a single appropriate response is hard to retrieve.

The sensation and perception of smell (olfaction) are largely dependent on sniffing, which is an active stage of stimulus transport and therefore an integral component of mammalian olfaction. Electrophysiological data obtained from study of the hedgehog, rat, rabbit, dog and monkey indicate that sniffing (whether or not an odorant is present) induces an oscillation of activity in the olfactory bulb, driving the piriform cortex in the temporal lobe, in other words, the piriform is driven by the olfactory bulb at the frequency of sniffing. Here we use functional magnetic resonance imaging (fMRI) that is dependent on the level of oxygen in the blood to determine whether sniffing can induce activation in the piriform of humans, and whether this activation can be differentiated from activation induced by an odorant. We find that sniffing, whether odorant is present or absent, induces activation primarily in the piriform cortex of the temporal lobe and in the medial and posterior orbito-frontal gyri of the frontal lobe. The source of the sniff-induced activation is the somatosensory stimulation that is induced by air flow through the nostrils. In contrast, a smell, regardless of sniffing, induces activation mainly in the lateral and anterior orbito-frontal gyri of the frontal lobe. The dissociation between regions activated by olfactory exploration (sniffing) and regions activated by olfactory content (smell) shows a distinction in brain organization in terms of human olfaction.

This article reviews attempts to characterize the mental operations mediated by left inferior prefrontal cortex, especially the anterior and inferior portion of the gyrus, with the functional neuroimaging techniques of positron emission tomography and functional magnetic resonance imaging. Activations in this region occur during semantic, relative to nonsemantic, tasks for the generation of words to semantic cues or the classification of words or pictures into semantic categories. This activation appears in the right prefrontal cortex of people known to be atypically right-hemisphere dominant for language. In this region, activations are associated with meaningful encoding that leads to superior explicit memory for stimuli and deactivations with implicit semantic memory (repetition priming) for words and pictures. New findings are reported showing that patients with global amnesia show deactivations in the same region associated with repetition priming, that activation in this region reflects selection of a response from among numerous relative to few alternatives, and that activations in a portion of this region are associated specifically with semantic relative to phonological processing. It is hypothesized that activations in left inferior prefrontal cortex reflect a domain-specific semantic working memory capacity that is invoked more for semantic than nonsemantic analyses regardless of stimulus modality, more for initial than for repeated semantic analysis of a word or picture, more when a response must be selected from among many than few legitimate alternatives, and that yields superior later explicit memory for experiences.

The learning of perceptual skills is thought to rely upon multiple regions in the cerebral cortex, but imaging studies have not yet provided evidence about the changes in neural activity that accompany visual skill learning. Functional magnetic resonance imaging (fMRI) was used to examine changes in activation of posterior brain regions associated with the acquisition of mirror-reading skill for novel and practiced stimuli. Multiple regions in the occipital lobe, inferior temporal cortex, superior parietal cortex and cerebellum were involved in the reading of mirror-reversed compared to normally oriented text. For novel stimuli, skilled mirror-reading was associated with decreased activation in the right superior parietal cortex and posterior occipital regions and increased activation in the left inferior temporal lobe. These results suggest that learning to read mirror-reversed text involves a progression from visuospatial transformation to direct recognition of transformed letters. Reading practiced, relative to unpracticed, stimuli was associated with decreased activation in occipital visual cortices, inferior temporal cortex and superior parietal cortex and increased activation in occipito-parietal and lateral temporal regions. By examining skill learning and item-specific repetition priming in the same task, this study demonstrates that both of these forms of learning exhibit shifts in the set of neural structures that contribute to performance.

A method for generating olfactory stimuli for humans within a functional magnetic resonance imaging (fMRI) experimental design is described. The system incorporates a nasal-mask in which the change from odorant to no-odorant conditions occurs in less than 500 ms and is not accompanied by visual, auditory, tactile, or thermal cues. The mask provides an ordorant-free environment following prolonged ordorant presence. Specific imaging parameters that are conducive to the study of the human olfactory system are described. In a pilot study performed using these methods, the specific patterns of activation observed converged with published experimental and clinical findings.

The lobular distributions of functional activation of the cerebellum during verbal working-memory and finger movement tasks were investigated using functional magnetic resonance imaging (fMRI). Relative to a rest control, finger tapping of the right hand produced ipsilateral-increased activation in HIV/HV [Roman numeral designations based on Larsell's () nomenclature] and HVI and weaker activation in HVIII that was stronger on the ipsilateral side. For a working-memory task, subjects were asked to remember six (high load) or one (low load) visually presented letters across a brief delay. To assess the motoric aspects of rehearsal in the absence of working memory, we asked the subjects to repeatedly read subvocally six or one letters at a rate that approximated the internally generated rehearsal of working memory (motoric rehearsal task). For both tasks, bilateral regions of the superior cerebellar hemispheres (left superior HVIIA and right HVI) and portions of posterior vermis (VI and superior VIIA) exhibited increased activation during high relative to low load conditions. In contrast, the right inferior cerebellar hemisphere (HVIIB) exhibited this load effect only during the working-memory task. We hypothesize that HVI and superior HVIIA activation represents input from the articulatory control system of working memory from the frontal lobes and that HVIIB activation is derived from the phonological store in temporal and parietal regions. From these inputs, the cerebellum could compute the discrepancy between actual and intended phonological rehearsal and use this information to update a feedforward command to the frontal lobes, thereby facilitating the phonological loop.

Functional neuroimaging studies of single-word processing have demonstrated decreased activation in left inferior prefrontal cortex (LIPC) during repeated semantic processing relative to initial semantic processing. This item-specific memory effect occurs under implicit test instructions and represents word-toword semantic repetition priming. The present study examined the stimulus generality of LIPC function by measuring prefrontal cortical activation during repeated relative to initial semantic processing of words (word-to-word semantic repetition priming) and of pictures (picture-to-picture semantic repetition priming). For both words and pictures, LIPC activation decreased with repetition, suggesting that this area subserves semantic analysis of stimuli regardless of perceptual form. Decreased activation was greater in extent for words than for pictures. The LIPC area may act as a semantic executive system that mediates on-line retrieval of long-term conceptual knowledge necessary for guiding task performance.

Methodological issues have limited neuroimaging studies of cerebellar structures. In this article we describe a method that addresses some of these limitations and phantom studies that examine the validity of the image manipulations. We compared volumes derived from 3D Spoiled Gradient Recalled Acquisition MR images sliced with respect to three different alignment methods: one based on cerebellar landmarks, another on cerebral landmarks and a third on the plane of acquisition. Examination of coefficients of variation, coefficients of error and convergent validity suggests that although regional cerebellar volumes based on cerebellar landmarks provide the best estimates of the true volumes, observed differences between volume measurements from alignments based on cerebellar or cerebral landmarks were generally not significant and were inconsequential. In this case, the measure was improved with alignment along local, relevant cerebellar landmarks. A set of phantom experiments showed that realignment, reslicing and interpolation in 3-dimensional image processing exerted, at most, trivial distortion on the estimates of actual object volumes.

We examined brain activation, as measured by functional magnetic resonance imaging, during problem solving in seven young, healthy participants. Participants solved problems selected from the Raven's Progressive Matrices Test, a test known to predict performance on a wide range of reasoning tasks. In three conditions, participants solved problems requiring (1) analytic reasoning; (2) figural or visuospatial reasoning; or (3) simple pattern matching that served as a perceptual-motor control. Right frontal and bilateral parietal regions were activated more by figural than control problems. Bilateral frontal and left parietal, occipital, and temporal regions were activated more by analytic than figural problems. All of these regions were activated more by analytic than match problems. Many of these activations occurred in regions associated with working memory. Figural reasoning activated areas involved in spatial and object working memory. Analytic reasoning activated additional areas involved in verbal working memory and domain-independent associative and executive processes. These results suggest that fluid reasoning is mediated by a composite of working memory systems.

The participation of medial temporal-lobe structures in memory performance was examined by functional magnetic resonance imaging of local blood oxygenation level-dependent signals. Signals were measured during encoding into memory complex scenes or line drawings and during retrieval from memory of previously studied line drawings or words. Encoding tasks yielded increased signals for unfamiliar information in a posterior medial-temporal region that were focused in the parahippocampal cortex. Retrieval tasks yielded increased signals for successfully remembered information in an anterior medial-temporal region that were focused in the subiculum. These results indicate that separate components of the human medial temporal-lobe memory system are active during distinct memory processes.

We present a method for registering a brain in the Talairach coordinate system that can be performed either "online," i.e., in real time while a subject is in a magnetic resonance scanner, or "offline" on a previously acquired three-dimensional (3D) data set. The method is applicable to functional magnetic resonance imaging (MRI) studies because slices can be specified in Talairach coordinates and acquired in Talairach planes. Once functional data are obtained, pixels in a functional map can then be converted into Talairach coordinates, thereby facilitating brain averaging and communication of results. The method can also be used to align 3D data sets and perform volumetric analyses of regions of interest after correcting for head tilt, or to compute averaged structural brain images. Online and offline registration can be combined such that a series of sections can be interactively selected and visualized ahead of time using offline analyses and then replicated online at a later time. Hum. Brain Mapping 5:58-73, 1997. (c) 1997 Wiley-Liss, Inc.

A brain image averaging technique was applied to three-dimensional magnetic resonance images to identify visually detectable brain volume abnormalities in chronically alcoholic men, compared with healthy control men. This technique, which was based on pixel-by-pixel statistical probability mapping, revealed a dramatic reduction in the area of the corpus callosum in older alcoholics (age 45 years or older), relative to age-matched controls. Subsequent analysis used anatomical landmarks to outline the borders of midsagittal sections of the corpus callosum in a larger group of alcoholics and controls, who spanned the adult age range from 23 to 71 years. This analysis revealed significant reduction, most prominent in the genu and body, of total callosal area in the alcoholic group relative to the control group; the results were the same whether raw area measures or head size plus age adjusted measure were analyzed. Significant thinning of the callosal body in alcoholics is usually attributed to the relatively rare, nutritional-deficient condition, Marchiafava-Bignami disease. However, callosal thinning was present in vivo in chronic alcoholics without clinical symptoms of severe liver disease, amnesia, or alcoholic dementia. These data suggest that chronic alcoholism can be characterized by a continuum of graded brain dysmorphology, rather than classical alcoholic-related subsyndromes, such as Marchiafava-Bignami disease.

Animal electrocorticogram (ECoG) studies have shown that spatial patterns in the gamma band (>20 Hz) reflect perceptual categorization. Spatio-temporal correlations were investigated in the 20-50 Hz range in search for similar phenomena in human ECoG. ECoGs were recorded in a somatosensory discrimination task from 64-electrode subdural grid arrays, with inter-electrode spacing of 1 cm, overlying somatosensory, motor and superior temporal cortices in 2 patients with intractable epilepsy. Bootstrap techniques were devised to analyze the spatial and temporal characteristics of the correlations. Despite an extensive search, no evidence was found for globally correlated activity related to behavior either in narrow (1.e., 35-45 Hz) or broad (i.e., 20-50 Hz) bands. Spatial patterns, extracted using principal component analysis, could not be classified with respect to stimulus type in any time interval. Instead, spatially and temporally intermittent synchronization was observed between pairs of electrodes in 1 cm X 1 cm regions with high variability within and across trials. The distribution of correlation coefficients differed substantially from background levels at inter-electrode distances of 1 cm and 1.4 cm but not 2 cm or more. The minimum duration of correlation, the decorrelation time, of the ECoG was about 50 msec; the average correlation duration at 1 cm inter-electrode distance was about 150 msec; and the recurrence rate of significant correlation peaks was about 1.3/sec. The findings suggest that the surface diameters of domains of spatially correlated activity underlying perceptual categorization in human gamma band ECoG are limited to less than 2 cm and that the intermittent synchronization observed across separations of 1 cm and 1.4 cm is not solely due to volume conduction. Thus, if such gamma band spatial patterns exist in the human brain, no existing technology would be capable of measuring them at the scalp, and subdural electrode arrays for cortical surface recording would have to have spacings under 5 mm.

In this study the use of functional MRI (fMRI) for measuring language lateralization non-invasively was examined. The subjects were seven patients with histories of temporal lobe epilepsy who had undergone Wada testing for pre-surgical evaluation. Four patients were left-hemisphere-dominant and three were right-hemisphere-dominant for language. They received fMRI scans while they made semantic or perceptual judgments about visually presented words. Regions of the inferior frontal gyrus (pars triangularis and pars orbitalis) and neighbouring orbital cortex, corresponding to portions of Brodmann areas 45, 46 and 47, exhibited significant increases in activation during semantic relative to perceptual judgments. Lateralization of the increases in activation were consistent with the Wada test assessments of hemispheric language dominance in each of the seven patients. These results suggest that, in addition to providing a tool for investigating human cognitive processes, fMRI has significant clinical potential as a non-invasive measure of language lateralization.

Alcoholics often suffer from motor incoordination resulting from alcohol-related cerebellar damage. However, the effect of cerebellar structural damage on cognitive functioning has not been clearly demonstrated. It is not known if the relationships observed between cerebellar damage and functional impairments persist with abstinence from alcohol. Cell death may cause permanent loss of function, whereas tissue shrinkage without permanent cell loss might represent the potential for recovery. This article examines research on the interrelationship of alcohol-related abnormalities in cerebellar structure and function. Research such as this may provide knowledge to guide future rehabilitation efforts.

Previous investigations have suggested that the cerebellum and associated brainstem structures, including the red nucleus, are essential for the expression of the classically conditioned nictitating membrane (NM) response. The present study examined the firing patterns of extracellularly-recorded single units in the red nucleus of the awake rabbit during differential conditioning. Tones were used as conditioned stimulus (CS+ and CS-) and periocular electrostimulation was used as the unconditioned stimulus (US). Most units exhibited one or more changes in firing rate during the presentation of the CS, and increases in firing were much more common than decreases. The onset of some of these changes appeared to be time-locked to the onset of the CS ('CS-locked' responses), while other changes were time-locked to the onset of the CR ('CR-locked' responses). About one-third of all CS-locked changes were CR-dependent, meaning that the neuronal response was reduced when the CR did not occur. About two-thirds of all CR-locked responses preceded the onset of the CR, and lead times varied considerably across units. Many CR-locked units were located in what has been described as a dorsal face region of the red nucleus. Most units responded to the US, and some of the US responses were CR-dependent: i.e., a smaller US response was evoked when a CR preceded the US than when the CR was absent. Our results support the notion that cerebellum-brainstem circuits are involved in generating NM CRs.

A previously described neural-network model (Desmond 1991; Desmond and Moore 1988; Moore et al. 1989) predicts that both CS-onset-evoked and CS-offset-evoked stimulus trace processes acquire associative strength during classical conditioning, and that CR waveforms can be altered by manipulating the time at which the processes are activated. In a trace conditioning paradigm, where CS offset precedes US onset, the model predicts that onset and offset traces act in synchrony to generate unimodal CR waveforms. However, if the CS duration is subsequently lengthened on CS-alone probe trials, the model predicts that onset and offset traces will asynchronously contribute to CR output and bimodal CRs will be generated. In a delay conditioning paradigm, in which US onset occurs prior to CS offset, the model predicts that only the onset process will gain associative strength, and hence, only unimodal CRs will occur. Using the rabbit conditioned nictitating membrane response preparation, we found experimental support for these predictions.

A conditioned response not only reflects knowledge of an association between two events, a CS and a US, it also reflects knowledge about the timing of these events. A neural network and set of learning rules that generates appropriately timed conditioned response waveforms is presented. The model is capable of simulating some of the basic temporal properties of conditioned responses exhibited in biological systems, including (1) decreasing onset latency during acquisition training, (2) peak amplitude occurring at the temporal locus of the US, (3) inhibition of delay, and (4) trace conditioning. The model is also capable of simulating complex CR waveforms under certain conditions, and these simulations are compared with the results of behavioral experiments. The temporally adaptive responses are achieved by virtue of stimulus trace processes that are built into the network architecture.

Previous investigations have suggested that the dorsolateral pontine tegmentum (DLP) may be part of a system essential for classical conditioning of the nictitating membrane response. The present study examined CR-related firing patterns of extracellularly-recorded single units in the DLP. Differential conditioning, using tonal CSs and periocular electrostimulation as the US, was employed so that firing patterns on CR and non-CR trials could be compared. Cells that exhibited CR-related increases in firing (excitatory cells) were found in reticular formation surrounding the motor trigeminal nucleus (zone h), including the supra-trigeminal region, and in a region dorsal and dorsomedial to the brachium conjunctivum. Cells that exhibited CR-related decreases in firing (inhibitory cells) were observed in subcoeruleus/medial parabrachial regions and dorsal nucleus reticularis pontis oralis and caudalis. A third class of cells (temporal cells) exhibited CR-related shifts in the temporal distribution of spikes; these cells were located in various brain stem regions. The firing of many of the excitatory, inhibitory, and temporal cells preceded the behavioral CR by an amount of time sufficient for causal involvement. In light of evidence indicating that the cerebellum is critically involved in conditioning, the present study suggests that two systems, the cerebellum and the DLP, may be in control of CRs. The relationship of the two systems and their possible roles in conditioning are discussed.

A neuron-like adaptive element with computational features suitable for classical conditioning, the Sutton-Barto (S-B) model, was extended to simulate real-time aspects of the conditioned nictitating membrane (NM) response. The aspects of concern were response topography, CR-related neuronal firing, and interstimulus interval (ISI) effects for forward-delay and trace conditioning paradigms. The topography of the NM CR has the following features: response latency after CS onset decreases over trials; response amplitude increases gradually within the ISI and attains its maximum coincidentally with the UR. A similar pattern characterizes the firing of some (but not all) neurons in brain regions demonstrated experimentally to be important for NM conditioning. The variant of the S-B model described in this paper consists of a set of parameters and implementation rules based on 10-ms computational time steps. It differs from the original S-B model in a number of ways. The main difference is the assumption that CS inputs to the adaptive element are not instantaneous but are instead shaped by unspecified coding processes so as to produce outputs that conform with the real-time properties of NM conditioning. The model successfully simulates the aforementioned features of NM response topography. It is also capable of simulating appropriate ISI functions, i.e. with maximum conditioning strength with ISIs of 250 ms, for forward-delay and trace paradigms. The original model's successful treatment of multiple-CS phenomena, such as blocking, conditioned inhibition, and higher-order conditioning, are retained by the present model.

Brain projections to the accessory abducens region and dorsolateral pons were investigated in rabbit using implants of crystalline horseradish peroxidase (HRP). Following implantation of HRP in the accessory abducens region (N = 3), labeled cells were observed in the sensory trigeminal nuclei and other regions implicated in the reflex pathway of the defensive nictitating membrane (NM) response. Neurons in the supratrigeminal zone were also labeled, as were portions of the contralateral red nucleus. Implantation of HRP into the dorsolateral pons (N = 5) revealed ipsilateral projections from deep-cerebellar nuclei in some cases. In addition, the parvocellular reticular formation displayed bilateral labeling of cells and an ipsilateral network of fibers and apparent terminations. Many cells of the contralateral supratrigeminal zone were labeled in these cases. Results were discussed in relation to lesioning and electrophysiological studies implicating the supratrigeminal region and other structures in the control of the classically conditioned NM response. Specifically, the possibility that supratrigeminal neurons are premotor elements responsible for the conditioned response is considered. Alternative hypotheses are discussed, including pathways by which cerebellar nuclei could control conditioned responding.

Conditioned responses often reflect knowledge about the timing of a US. This knowledge is manifested in the dependence of response topography on the CS-US interval employed in training. A neural network model and set of learning rules capable of simulating temporally adaptive features of conditioned responses is reviewed, and simulations are presented. In addition, we present a neural network implementation of the model which is designed to reconcile empirical studies of long-term synaptic depression in the cerebellum with neurobiological evidence from studies of the classically conditioned nictitating membrane response of the rabbit.

The dorsolateral pontine brain stem was investigated as a possible locus of neural elements mediating the classically conditioned nictitating membrane (NM) response in rabbit. Recording and brain stimulation were employed for this purpose. Low-impedance tungsten monopolar microelectrodes were chronically implanted into the pontine brain stem. Multiple-unit recording during classical conditioning revealed a conditioned increase in multiple-unit activity (MUA) which developed and extinguished concurrently with the acquisition and extinction of the behavioral conditioned response. Pseudoconditioning and conditioned inhibition controls indicated that the increase in MUA was an associative learning phenomenon. Histology indicated that electrode tips recording the CR-associated electrical activity were located mostly adjacent or dorsal to the motor trigeminal nucleus. Periocular shock pulses elicited short latency evoked responses throughout most of the dorsolateral pons, suggesting that information concerning the unconditioned stimulus is relayed to this region. Furthermore, electrical stimulation of this region produced a robust ipsilateral nictitating membrane response in a number of cases, suggesting that neural elements of the dorsolateral pons project to the motoneurons that produce membrane extension. A consideration of several criteria based on these experiments implicates a supratrigeminal zone [22] as containing the neural elements of dorsolateral pons most intimately associated with the conditioned NM response. Other interpretations, concerning fibers of passage through this region and

The latency of the nictitating membrane response (NMR) in rabbit (Oryctolagus cuniculus) to periocular electro-stimulation is a negative exponential function of stimulus current with an asymptote of approximately 17 msec. The NMR was recorded by means of a precision low-torque potentiometer like that employed in previous studies of NMR latency, and the criterion of response initiation employed here was similar to that employed in studies of classical conditioning in this preparation. Using estimates from physiological studies on surgically acute preparations, the minimum latency of the NMR of 17 msec can be decomposed as follows: 4 msec to fire motoneurons of the accessory abducens nucleus; 9 msec for conduction, synaptic transmission, and recruitment of retractor bulbi muscle fibers; 4 msec for the nictitating membrane to initiate its sweep after eyeball retraction. The implications of these estimates for chronic unit-recording studies of the conditioned NMR are discussed.