Habituation of human limbic neuronal response to sensory stimulation

Hippocampal, parahippocampal gyrus, and amygdalar neuronal responses to visual and acoustic stimuli were analyzed during trains of several hundred stimulus repetitions as part of an investigation of sensory pathways to medial temporal lobe structures in complex-partial epilepsy patients who were being monitored with depth electrodes. Ten percent of more than 500 single and multiple units tested were responsive to simple sensory stimuli. The majority of the responsive units were recorded in the posterior parahippocampal gyrus (HG) during visual stimulation. Although neurons in pes hippocampi (PH; Ammons's horn) were also responsive to photic stimuli, no visually responsive units were found in amygdala. Very few units were responsive to acoustic stimuli, and these were found only in PH and amygdala, and not in HG. Significant trends of increase or decrease in response amplitude during trains of stimuli were found in all acoustically responsive units. Significant trends of visual response amplitude increase or decrease were found in 20% of PH units, and in 44% of HG units. Mean latencies of acoustically responsive units were longer than those of visually responsive units, and latencies of PH sensory units showing decremental response were longer than nondecremental PH units. Rate of response decrement was usually linear for acoustic responses and exponential for visual responses. The response dynamics of medial temporal lobe neurons are compared with those described in the animal limbic system and are related to habituation of human sensory evoked scalp potentials.     

Brain representation of habituation to repeated complex visual stimulation studied with PET

To investigate CNS habituation (i.e. response decrement due to stimulus repetition) the present study used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in eight healthy women during two repetitions of complex visual stimuli. Repeated visual stimulation resulted in neural habituation bilaterally in the secondary visual cortex and in the right medial temporal cortex including the amygdala and the hippocampus. Regional CBF in the left thalamus was elevated as a function of repeated stimuli presentations. Thus, repeated presentation of complex visual stimuli result in rCBF habituation in later stages of the visual processing chain. The elevated neural activity in the thalamus might be associated with interruption of further neural transmission related to suppression of non-meaningful behavior.     

Pulvinar lesions in monkeys produce abnormal scanning of a complex visual array.

Eye movements of normal monkeys and monkeys with pulvinar lesions were recorded on video tape as the animals spontaneously scanned a complex stimulus array. During the test session, color was added to one stimulus in the array. Although monkeys with pulvinar lesions were not impaired in either visual orientation or habituation to this novel stimulus, their eye movements were abnormal in two ways. First, they appeared visually captured by the stimuli, making few saccades off the array. Second, their fixations were abnormally prolonged. These eye-movement abnormalities appeared to be associated with a disorder in visual processing rather than an impairment in oculomotor control.     

Adaptive anterior hippocampal responses to oddball stimuli.

An efficient memory system requires the ability to detect and preferentially encode novel stimuli. Human electrophysiological recordings demonstrate differential hippocampal responses to novel vs. familiar stimuli, as well as to oddball stimuli. Although functional imaging experiments of novelty detection have demonstrated hippocampal activation, oddball-evoked hippocampal activation has not been demonstrated. Here we use event-related functional magnetic resonance imaging (fMRI) to measure hippocampal responses to three types of oddball words: perceptual, semantic, and emotional. We demonstrate left anterior hippocampal sensitivity to all three oddball types, with adaptation of responses across multiple oddball presentations. This adaptive hippocampal oddball response was not modulated by depth of processing, suggesting a high degree of automaticity in the underlying process. However, an interaction with depth of encoding for semantic oddballs was evident in a more lateral left anterior hippocampal region. We conclude that the hippocampal response to oddballs demonstrates a second-order novelty effect, being sensitive to the "novelty of novelty" of oddball stimuli. The data provide support for a more general theory that a function of the anterior hippocampus is to register mismatches between expectation and experience.     

No decrement in visual P300 amplitude during extended performance of the oddball task

Research indicates that in visual sustained attention paradigms, the amplitude of the P300 component of the event-related potential invoked by target (critical) stimuli shows a decrement in amplitude. This amplitude decrement parallels decrements in vigilance performance that result from the difficult discrimination that is typically required between the infrequent targets and the frequent nontargets (neutral stimuli). In contrast, target stimulus P300 does not appear to show a decrement across large numbers of trials during performance of the "oddball" paradigm, in which targets and nontargets are highly discriminable. The present study measured target and nontarget P300 amplitude during performance of a visual oddball paradigm extended over an interval of some 3 1/2 hours, a period well in excess of the 3/4 hour intervals employed in previous research. The results indicated no decrement in P300 amplitude as a function of time for either targets or nontargets. The only significant relationship between P300 and behavioral data was an inverse correlation across oddball runs between average nontarget P300 amplitude and total number of targets missed.     

Responses of striatal neurons in the behaving monkey. 2. Visual processing in the caudal neostriatum

The activity of single neurons was recorded in the tail of the caudate nucleus and adjoining part of the ventral putamen, which receive projections from the inferior temporal visual cortex, in order to investigate the functions of these regions. Of 195 neurons analyzed in two macaque monkeys, 109 (56%) responded to visual stimuli, with latencies of 90-150 ms for the majority of the neurons. The neurons responded to a limited range of complex visual stimuli, and in some cases responded to simpler stimuli such as bars and edges. Typically (in 75% of cases) the neurons habituated rapidly, within 1-8 exposures, to each visual stimulus, but remained responsive to other visual stimuli with a different pattern. This habituation was orientation specific, in that the neurons responded to the same pattern shown in an orthogonal orientation. The habituation was also relatively short-term, in that at least partial dishabituation to one stimulus could be produced by a single intervening presentation of a different visual stimulus. These neurons were relatively unresponsive in a visual discrimination task, having habituated to the stimuli which had been presented in the task on many previous trials. It is suggested on the basis of these results and other studies that these neurons are involved in pattern-specific habituation to repeated visual stimuli, and in attention an orientation to a changed visual stimulus pattern. Changes in attention and orientation to stimuli as a result of damage to the striatum and its afferent and efferent pathways may arise in part because of damage to neurons with responses of this type.     

Stimulus-specific adaptation: can it be a neural correlate of behavioral habituation?

Habituation is the most basic form of learning, yet many gaps remain in our understanding of its underlying neural mechanisms. We demonstrate that in the owl's optic tectum (OT), a single, low-level, relatively short auditory stimulus is sufficient to induce a significant reduction in the neural response to a stimulus presented up to 60 s later. This type of neural adaptation was absent in neurons from the central nucleus of the inferior colliculus and from the auditory thalamus; however, it was apparent in the OT and the forebrain entopallium. By presenting sequences that alternate between two different auditory stimuli, we show that this long-lasting adaptation is stimulus specific. The response to an odd stimulus in the sequence was not smaller than the response to the same stimulus when it was first in the sequence. Finally, we measured the habituation of reflexive eye movements and show that the behavioral habituation is correlated with the neural adaptation. The finding of a long-lasting specific adaptation in areas related to the gaze control system and not elsewhere suggests its involvement in habituation processes and opens new directions for research on mechanisms of habituation.     

Touch gives new life: mechanosensation modulates spinal cord adult neurogenesis

The ability to respond to a wide range of novel touch sensations and to habituate upon repeated exposures is fundamental for effective sensation. In this study we identified adult spinal cord neurogenesis as a potential novel player in the mechanism of tactile sensation. We demonstrate that a single exposure to a novel mechanosensory stimulus induced immediate proliferation of progenitor cells in the spinal dorsal horn, whereas repeated exposures to the same stimulus induced neuronal differentiation and survival. Most of the newly formed neurons differentiated toward a GABAergic fate. This touch-induced neurogenesis reflected the novelty of the stimuli, its diversity, as well as stimulus duration. Introducing adult neurogenesis as a potential mechanism of response to a novel stimulus and for habituation to repeated sensory exposures opens up potential new directions in treating hypersensitivity, pain and other mechanosensory disorders.     

Changes in neuronal activity related to the repetition and relative familiarity of visual stimuli in rhinal and adjacent cortex of the anaesthetised rat

Employing the same techniques as have been used with conscious rats, this study describes neuronal responses signalling information concerning the prior occurrence of visual stimuli in unconscious rats. Recordings of the activity of 387 neurones were made while anaesthetised rats were shown objects. Changes in neuronal responses related to stimulus repetition and the relative familiarity of visual stimuli were sought. The areas sampled were lateral occipital cortex, area TE of temporal cortex, perirhinal cortex and the hippocampal formation. The response to the first presentations of unfamiliar objects was significantly different from that to their second presentations for 30 (35%) of 86 visually responsive neurones; for 23 of the neurones was smaller when the stimulus was repeated, whereas for 7 it was larger. For all of these neurones the response change was maintained across intervening trials on which other stimuli were shown. For 4 (25%) of 16 neurones so tested, the response decrement persisted across at least 10 intervening trials. The activity of 63 neurones was recorded while rats were shown highly familiar as well as unfamiliar objects. The response to unfamiliar objects was significantly different from that to highly familiar objects for 3 (23%) of 13 visually responsive neurones. The types of neuronal response and their incidence expressed as a proportion of the number of visually responsive neurones were similar to those found in unanaesthetised rats (though the proportion of visually responsive neurones encountered in the anaesthetised rat was lower). The results indicate that information concerning the prior occurrence of stimuli is processed even under anaesthesia.     

Visual Recognition Is Heralded by Shifts in Local Field Potential Oscillations and Inhibitory Networks in Primary Visual Cortex

Learning to recognize and filter familiar, irrelevant sensory stimuli eases the computational burden on the cerebral cortex. Inhibition is a candidate mechanism in this filtration process, and oscillations in the cortical local field potential (LFP) serve as markers of the engagement of different inhibitory neurons. We show here that LFP oscillatory activity in visual cortex is profoundly altered as male and female mice learn to recognize an oriented grating stimulus—low-frequency (∼15 Hz peak) power sharply increases, whereas high-frequency (∼65 Hz peak) power decreases. These changes report recognition of the familiar pattern as they disappear when the stimulus is rotated to a novel orientation. Two-photon imaging of neuronal activity reveals that parvalbumin-expressing inhibitory neurons disengage with familiar stimuli and reactivate to novelty, whereas somatostatin-expressing inhibitory neurons show opposing activity patterns. We propose a model in which the balance of two interacting interneuron circuits shifts as novel stimuli become familiar.SIGNIFICANCE STATEMENT Habituation, familiarity, and novelty detection are fundamental cognitive processes that enable organisms to adaptively filter meaningless stimuli and focus attention on potentially important elements of their environment. We have shown that this process can be studied fruitfully in the mouse primary visual cortex by using simple grating stimuli for which novelty and familiarity are defined by orientation and by measuring stimulus-evoked and continuous local field potentials. Altered event-related and spontaneous potentials, and deficient habituation, are well-documented features of several neurodevelopmental psychiatric disorders. The paradigm described here will be valuable to interrogate the origins of these signals and the meaning of their disruption more deeply.     

Event-related potentials for 7-month-olds’ processing of animals and furniture items

Event-related potentials (ERPs) to single visual stimuli were recorded in 7-month-old infants. In a three-stimulus oddball paradigm, infants watched one frequently occurring standard stimulus (either an animal or a furniture item) and two infrequently occurring oddball stimuli, presenting one exemplar from the same and one from the different superordinate category as compared to the standard stimulus. Additionally, visual attributes of the stimuli were controlled to investigate whether infants focus on category membership or on perceptual similarity when processing the stimuli. Infant ERPs indicated encoding of the standard stimulus and discriminating it from the two oddball stimuli by larger Nc peak amplitude and late-slow-wave activity for the infrequent stimuli. Moreover, larger Nc latency and positive-slow-wave activity indicated increased processing for the different-category as compared to the same-category oddball. Thus, 7-month-olds seem to encode single stimuli not only by surface perceptual features, but they also regard information of category membership, leading to facilitated processing of the oddball that belongs to the same domain as the standard stimulus.     

Stimulus specific adaptation in excited but not in inhibited cells in inferotemporal cortex of Macaque

Many cells in inferotemporal cortex respond more actively to a novel presentation than to a subsequent re-presentation of the same image, exhibiting stimulus specific adaptation (SSA). Previously, analysis of this adaptation was limited to visually excited cells, excluding visually inhibited cells. In the present experiment we studied 654 cells in four macaques performing visual tasks. Strong SSA (P < 0.0001) was observed in those cells which were excited by visual stimuli. This adaptation was also seen in the subset of such cells which, though excited by visual stimuli, failed to show visual specificity in their responses. Interestingly, no SSA (P > 0.1) was observed in the group of cells inhibited by visual stimuli. Furthermore, most inhibited cells failed to show visual specificity. This lack of visual specificity and SSA suggest that the visually inhibited cells have a limited role in the detailed information processing of visual perception and memory activated by the tasks used in the present experiments.     

Altered salience processing in attention deficit hyperactivity disorder

Attentional problems in patients with attention deficit hyperactivity disorder (ADHD) have often been linked with deficits in cognitive control. Whether these deficits are associated with increased sensitivity to external salient stimuli remains unclear. To address this issue, we acquired functional brain images (fMRI) in 38 boys with and without ADHD (age: 11–16 years). To differentiate the effects of item novelty, contextual rareness and task relevance, participants performed a visual oddball task including four stimulus categories: a frequent standard picture (62.5%), unique novel pictures (12.5%), one repeated rare picture (12.5%), and a target picture (12.5%) that required a specific motor response. As a main finding, we can show considerable overlap in novelty‐related BOLD responses between both groups, but only healthy participants showed neural deactivation in temporal as well as frontal regions in response to novel pictures. Furthermore, only ADHD patients, but not healthy controls, engaged wide parts of the novelty network when processing the rare but familiar picture. Our results provide first evidence that ADHD patients show enhanced neural activity in response to novel but behaviorally irrelevant stimuli as well as reduced habituation to familiar items. These findings suggest an inefficient use of neuronal resources in children with ADHD that could be closely linked to increased distractibility. Hum Brain Mapp 36:2049–2060, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Features of responses of the neurons of the caudate nucleus to various localizations of a photic stimulus in the visual field of the alert cat

The responses of caudate neurons to restricted light stimuli differently located in the visual field were studied during natural fixation of the gaze on the visual target in awake cats. 71% of visually responsive neurons were sensitive to changing of stimulus location. It indicates that some neurons (17%) had restricted receptive fields in the centre of the gaze, other neurons (17%) had decreasing sensitivity to stimuli removed from the centre of the field and 37% of responsive neurons received information of different quality from different parts of the visual field. It is suggested that caudate nucleus neurons participate in the analysis of visual sensory information.     

Does surprise enhancement or repetition suppression explain visual mismatch negativity?

A long tradition of electrophysiological studies, using oddball sequences, showed that the neural responses to a given stimulus differ when their presentation occurs frequently (standards) as compared to rare, infrequent presentations (deviants). This difference, originally described in acoustic perception, can also be detected in the visual modality and is termed as visual mismatch negativity (vMMN). Also, a large number of studies detected the reduction of the neuronal response after the repetition of a given stimulus (repetition suppression – RS) and it was suggested that RS is the major mechanism of MMN, an explanation currently also supported by animal studies. However, human studies have proposed that a surprise‐related response enhancement for the deviant stimuli might also underlie vMMN. Therefore, the aim of the current study was to disentangle which neural mechanism explains vMMN better: the surprise related response enhancement for the presentation of rare deviants or the RS related to the frequent presentation of the standards. Since the MMN depends strongly on the applied categories, we tested the neural mechanisms of vMMN for different stimulus categories (faces, chairs, real and false characters) using a visual oddball paradigm. We found significant vMMN for every stimulus category. Interestingly, the neural mechanisms behind vMMN were found to be category dependent (assuming no cross‐adaptation effects): for faces and chairs it was largely driven by RS, whereas for real and false characters it was mainly due to surprise‐related changes.     

Afferent basis of visual response properties in area MT of the macaque. II. Effects of superior colliculus removal

In a previous study (Rodman et al., 1989), we found that many neurons in the middle temporal area (MT) of the macaque monkey remain visually responsive and directionally selective after striate cortex lesions or cooling. In the present study, we examined the effects of superior colliculus (SC) lesions and combined lesions of striate cortex and the SC on the visual properties of MT neurons. Removal of the SC alone had no effect on the proportion of visually responsive cells, strength of direction selectivity and direction tuning, orientation tuning, receptive field size, or binocularity in MT. There was, however, a slight increase in response strength to both stationary and moving slit stimuli. In contrast to the minor effects of SC lesions alone, addition of an SC lesion to striate cortex damage abolished all visual responsiveness in area MT. The results indicate that pathways damaged by the SC lesion are not necessary for most of the properties of MT neurons found in the intact animal, although these pathways are capable of sustaining considerable visual responsiveness and direction selectivity when striate input is removed.     

Nonassociative learning in the leech Hirudo medicinalis.

In the present study we examined nonassociative learning of the induction of swimming which was evoked by weak electrical stimulation in the leech Hirudo medicinalis. The behavioural response to stimuli applied repeatedly to the body wall at an inter-trial interval (ITI) of 1 min decreased, eventually ceased, and then recovered spontaneously. More rapid reduction of the behavioural response occurred in repeated training sessions. This decrement of response conformed to the operational definition of habituation. Moreover, a noxious stimulus (i.e. brushing on the skin) facilitated the decremented response (dishabituation). In addition, we compared response decrement in naive animals with decrement in dishabituated and in sensitized animals. The analysis of the best fitting functions of the habituation, the habituation of dishabituation and the habituation of sensitization revealed interesting differences in these processes.     

Inhibitory interaction between X and Y units in the cat lateral geniculate nucleus

Intracellular and extracellular recordings were obtained from X and Y type relay neurons in the cat lateral geniculate nucleus (LGN). In both cell populations, unit responses to visual and electrical stimuli were studied. Stimulation electrodes were placed in the optic chiasm (OX), the optic radiation (OR), the homolateral superior colliculus (SC) and the homolateral mesencephalic reticular formation (MRF).X neurons have a different response to certain visual stimuli than Y neurons; when the visual stimulus exceeds the receptive field center (RFC) X neurons show a delayed response more often than do Y neurons. This differential delay between X and Y responses is partly because of short latency postsynaptic inhibition in the LGN. For fast, moving visual stimuli, Y cells respond with a brisk burst at stimulus velocities of 300°/sec; X cells are inhibited by such stimuli.The EPSP threshold for OX stimuli is higher in X cells than in Y cells. At stimulus intensities close to the EPSP threshold, X cells show a near maximal IPSP whereas in Y cells, the IPSP is minimal. The IPSP latency to OX stimulation is between 1.8 and 2.5 msec in X and Y cells; because the EPSP latency in X cells is significantly longer than in Y cells, X cell EPSPs frequently start at the same time as the IPSP.75% of the Y cells could be orthodromically driven from both the OX and SC stimuli. Analysis of the EPSP shape and correlation of the latencies suggests that the activation from SC is mediated via bifurcating optic tract fibers which project to both SC and LGN. X cells were never activated from SC; however, there was an IPSP in X and Y cells after stimulation of the SC. IPSP amplitude increased with the eccentricity of the neuron's RFC and was comparable to the IPSP that followed an OX stimulus set at the estimated threshold of the Y fibers.These results suggest an inhibitory convergence of the X and Y system in the LGN. The analysis of EPSPs shows that quite frequently several OT fibers converge onto a single X or Y relay cell; often, however, one fiber appears to provide the dominant input. With a few exceptions, the converging fibers have similar conduction velocities.     

Structure of receptive fields of visually sensitive neurons of the cat hippocampus

Structure of receptive fields of visually sensitive neurons in areas CA1 and CA3 of the dorsal hippocampus was investigated in alert cats with the brain-stem pretrigeminal section. The receptive field (RF) structure of 76 hippocampal neurons was analyzed by methods of scanning the RF by moving stimuli and mapping all their surface by a stationary flashing spot. According to presented data the neurons were classified into three groups: neurons with homogeneous structure of the RF (54%), with nonhomogeneous (28%) and neurons more sensitive to stimulus motion (18%) than to a stationary flashing light. Experiments have shown that responses of hippocampal neurons are highly specific ones. Thus, 9% of neurons with the nonhomogeneous RF structure have shown specific responses to variation of the contrast and contours of moving stimuli. The presented results show that hippocampal visually driven neurons have well developed mechanism for processing visual sensory information and apparently this quality ensures participation of the limbic system in visually controlled behavior of the animal.     

The effect of hemidecortication on the inhibitory interactions in the superior colliculus of the cat.

Single neurons were recorded extracellularly from the superficial layers of the superior colliculus (SC) in 21 curarized cats. Four animals were normal unoperated cats, 17 were animals in which all cortical visual areas were ablated on one side from 7 to 69 days before the electrophysiological experiments. After cortical ablation all animals were blind in the visual field contralateral to the ablated side. In both normal and hemianopsic cats the effect of a visual stimulus located very far from the excitatory part of the unit receptive field, on the neuron responses to visual stimuli was studied. The remote stimulus (extra-field stimulus) was a hand moved black spot 10 degrees in diameter. In normal animals the introduction of the extra-field stimulus in the hemifield contralateral or ipsilateral to the recorded SC produced a marked reduction of unit responses to visual stimuli presented in their receptive field. This effect was particularly strong when the extra-field stimuli were introduced in the hemifield contralateral to the recorded side. In the hemianopsic animals the neurons of the SC ipsilateral to the lesion (receptive fields in the behaviorally blind hemifield) responded well to visual stimuli, but were only weakly inhibited by the extra-field stimuli presented in the blind hemifield. The neurons of this colliculus with the exception of those in the upper part of stratum griseum superficiale were normally inhibited by stimuli presented in the normal hemifield. The neurons of the SC contralateral to the lesion responded well to visual stimuli and were normally inhibited by stimuli presented in the normal hemifield; they were virtually not affected by stimuli presented in the blind hemifield. Mechanisms responsible for the abnormal inhibitory interactions between and within colliculi after cortical lesions and the possible behavioral implications of the findings are discussed.