Auditory cortex lesions prevent the extinction of Pavlovian differential heart rate conditioning to tonal stimuli in rabbits

The present study examined the role of the auditory cortex in the extinction of differentially conditioned heart rate (HR) responses in rabbits. Lesions were placed bilaterally in wither the auditory cortex or the visual cortex. Three days after recovery from surgery, the auditory cortex lesion group and the visual cortex lesion control group were habituated to the tonal conditioned stimuli (CSs), and then given 2 days of Pavlovian differential conditioning (60 trials per day) in which one tone (CS+) was always paired with the unconditioned stimulus and another tone (CS−) was never paired with the uncondition stimulus. Animals that had demonstrated reliable differential conditioning (CS+ response at least 5 beats greater than the CS− response) were placed on an extinction schedule for 7 days. The extinction schedule was identical to the differential conditioning schedule with the exception that shock never followed the CS+. The results of the study indicate that auditory cortex lesions prevent the extinction of differential bradycardia conditioned responses (CRs) to tonal CSs. Whereas the bradycardia responses to the CS+ quickly extinguished in the group that had control lesions in the visual cortex, the auditory cortex lesion group continued to exhibit significantly larger bradycardiac HR CRs to the CS+ relative to the CS− during all 7 days of extinction. These results suggest that the animals in the auditory cortex lesioned group did not inhibit responses to a previously reinforced stimulus (i.e. CS+) as well as animals with control lesions in the visual cortex.     

Modulation of spatial attention by fear-conditioned stimuli: an event-related fMRI study

Stimuli that signal threat can capture subjects' attention, leading to more efficient detection of, and faster responses to, events occurring in that part of the environment. In the present study we explored the behavioural and anatomical correlates of the modulation of spatial attention by emotion using a fear conditioning paradigm, combined with a covert spatial orienting task. Reaction times for the detection of a peripheral target, which was preceded by brief (50ms) presentations of the visual conditioned stimulus (CS+) in either the same or opposite visual field, showed an interaction between stimulus emotionality and attention shifts. We used event-related functional magnetic resonance imaging (fMRI) to characterise the associated neural responses. Consistent with previous studies, conditioning-induced enhanced responses were observed in the amygdala and extrastriate visual cortex. The modulation of spatial attention by a conditioned stimulus was associated with enhanced activity in regions of frontal and parietal cortices previously implicated in spatial attention, as well as in the lateral orbitofrontal cortex (lOFC).     

Phasic and sustained brain responses in the amygdala and the bed nucleus of the stria terminalis during threat anticipation

Several lines of evidence suggest that the amygdala and the bed nucleus of the stria terminalis (BNST) are differentially involved in phasic and sustained fear. Even though, results from neuroimaging studies support this distinction, a specific effect of a temporal dissociation with phasic responses to onset versus sustained responses during prolonged states of threat anticipation has not been shown yet. To explore this issue, we investigated brain activation during anticipation of threat in 38 healthy participants by means of functional magnetic resonance imaging. Participants were presented different visual cues indicated the temporally unpredictable occurrence of a subsequent aversive or neutral stimulus. During the onset of aversive versus neutral anticipatory cues, results showed a differential phasic activation of amygdala, anterior cingulate cortex (ACC), and ventrolateral prefrontal cortex (PFC). In contrast, activation in the BNST and other brain regions, including insula, dorsolateral PFC, ACC, cuneus, posterior cingulate cortex, and periaqueductal grey was characterized by a sustained response during the threat versus neutral anticipation period. Analyses of functional connectivity showed phasic amygdala response as positively associated with activation, mainly in sensory cortex areas whereas sustained BNST activation was negatively associated with activation in visual cortex and positively correlated with activation in the insula and thalamus. These findings suggest that the amygdala is responsive to the onset of cues signaling the unpredictable occurrence of a potential threat while the BNST in concert with other areas is involved in sustained anxiety. Furthermore, the amygdala and BNST are characterized by distinctive connectivity patterns during threat anticipation. Hum Brain Mapp 37:1091–1102, 2016. © 2015 Wiley Periodicals, Inc .     

Modulation of auditory neural responses by a visual context in human fear conditioning.

Responses to a stimulus signaling danger depend not only on the nature of that stimulus, but also on the context in which it is presented. A large body of work has been conducted in experimental animals investigating the neural correlates of contextual modulation of fear responses. However, much less is known about this process in humans. In this study we used functional MRI in a fear conditioning paradigm to explore this phenomenon. Responses to acoustic conditioned stimuli in auditory cortex were modulated by the presence of a visual context which signaled the likelihood of receiving an aversive unconditioned stimulus. Furthermore, the presence of the aversive visual context was associated with enhanced activity in parietal cortex, which may reflect an increase in attention to the presence of environmental threat stimuli.     

Visually guided locomotion and computation of time-to-collision in the mongolian gerbil (Meriones unguiculatus): the effects of frontal and visual cortical lesions

Past research has indicated that many species use the time-to-collision variable but little is known about its neural underpinnings in rodents. In a set of three experiments we set out to replicate and extend the findings of Sun et al. (Sun H-J, Carey DP, Goodale MA. Exp Brain Res 1992;91:171-175) in a visually guided task in Mongolian gerbils, and then investigated the effects of lesions to different cortical areas. We trained Mongolian gerbils to run in the dark toward a target on a computer screen. In some trials the target changed in size as the animal ran toward it in such a way as to produce 'virtual targets' if the animals were using time-to-collision or contact information. In experiment 1 we confirmed that gerbils use time-to-contact information to modulate their speed of running toward a target. In experiment 2 we established that visual cortex lesions attenuate the ability of lesioned animals to use information from the visual target to guide their run, while frontal cortex lesioned animals are not as severely affected. In experiment 3 we found that small radio-frequency lesions, of either area VI or of the lateral extrastriate regions of the visual cortex also affected the use of information from the target to modulate locomotion.     

Initial neighborhood biases and the quality of motion stimulation jointly influence the rapid emergence of direction preference in visual cortex

Visual experience plays a critical role in the development of direction-selective responses in ferret visual cortex. In visually naive animals, presentation of a bidirectional "training" stimulus induces rapid increases in the direction-selective responses of single neurons that can be predicted by small but significant direction biases that are present in neighboring neurons at the onset of stimulation. In this study we used in vivo two-photon imaging of calcium signals to further explore the contribution of visual experience to the emergence of direction- selective responses in ferret visual cortex. The first set of experiments was designed to determine whether visual experience is required for the development of the initial neighborhood bias. In animals that were dark-reared until the time of eye opening, we found that individual neurons exhibited weak direction-selective responses accompanied by a reduced but statistically significant neighborhood bias, indicating that both features arise without the need for visual experience. The second set of experiments used a unidirectional training stimulus to assess the relative roles of the neighborhood bias and visual experience in determining the direction preference that cortical neurons acquire during direction training. We found that neurons became more responsive to the trained direction even when they were located in regions of the cortex with an initial neighborhood bias for the direction opposite the training stimulus. Together, these results suggest an adaptive developmental strategy for the elaboration of direction-selective responses, one in which experience-independent mechanisms provide a symmetry-breaking seed for the instructive effects of visual experience.     

Parallel pathways can conduct visual CS information during classical conditioning of the NM response

Single and combined lesions were made to the lateral geniculate nucleus (LGN), the superficial layers of the superior colliculus (SC), and the pretectal nuclei (Ptc) prior to conditioning of the nictitating membrane (NM) response in rabbit with a visual conditioned stimulus (CS). Due to technical considerations, lesions of the dorsal LGN were accompanied by lesions of the visual cortex, the only output of the dorsal LGN, in order to render the dorsal LGN nonfunctional. Single lesions to any one of the 3 target systems (LGN, SC, Ptc) did not alter the rate of conditioning. Furthermore, double lesions to any 2 of the systems did not prevent conditioning, although LGN + SC lesions significantly retarded acquisition. When all 3 systems were lesioned, however, animals never acquired to the visual CS, although they successfully conditioned to an auditory CS. The results indicate that in rabbit there are parallel visual pathways individually capable of supporting the acquisition of conditioned NM responses.     

Neural correlates of visual motion processing without awareness in patients with striate cortex and pulvinar lesions

Patients with striate cortex lesions experience visual perception loss in the contralateral visual field. In few patients, however, stimuli within the blind field can lead to unconscious (blindsight) or even conscious perception when the stimuli are moving (Riddoch syndrome). Using functional magnetic resonance imaging (fMRI), we investigated the neural responses elicited by motion stimulation in the sighted and blind visual fields of eight patients with lesions of the striate cortex. Importantly, repeated testing ensured that none of the patients exhibited blindsight or a Riddoch syndrome. Three patients had additional lesions in the ipsilesional pulvinar. For blind visual field stimulation, great care was given that the moving stimulus was precisely presented within the borders of the scotoma. In six of eight patients, the stimulation within the scotoma elicited hemodynamic activity in area human middle temporal (hMT) while no activity was observed within the ipsilateral lesioned area of the striate cortex. One of the two patients in whom no ipsilesional activity was observed had an extensive lesion including massive subcortical damage. The other patient had an additional focal lesion within the lateral inferior pulvinar. Fiber‐tracking based on anatomical and functional markers (hMT and Pulvinar) on individual diffusion tensor imaging (DTI) data from each patient revealed the structural integrity of subcortical pathways in all but the patient with the extensive subcortical lesion. These results provide clear evidence for the robustness of direct subcortical pathways from the pulvinar to area hMT in patients with striate cortex lesions and demonstrate that ipsilesional activity in area hMT is completely independent of conscious perception. Hum Brain Mapp 36:1585–1594, 2015. © 2014 Wiley Periodicals, Inc.     

Ipsilesional biases in saccades but not perception after lesions of the human inferior parietal lobule

We examined the effects of chronic unilateral lesions to either the inferior parietal lobe, or to the dorsolateral prefrontal cortex including the frontal eye fields (FEFs), upon human visual perception and saccades in temporal-order-judgment (TOJ) tasks. Two visual events were presented on each trial, one in each hemifield at various stimulus onset asynchronies (SOAs). In the saccade task, patients moved their eyes to whichever stimulus attracted gaze first. In the perceptual-manual task, they pressed a button to indicate which stimulus was perceived first. Frontal patients showed appropriate TOJs for visual targets in both tasks. Parietal patients showed appropriate TOJs in the perceptual-manual but not the saccade task; their saccades tended to be ipsilesional unless the contralesional target led substantially. This reveals a bias in saccade choice after parietal damage that cannot be attributed to deficient visual perception. These results challenge previous claims that only anterior lesions produce motoric spatial biases in humans. However, they are in accord with recent neurophysiological evidence for parietal involvement in saccade generation, and also with suggestions that visuomotor transformations in the parietal lobe serving direct spatial motor responses can dissociate from conscious perception as indicated by indirect arbitrary responses.     

Unseen stimuli modulate conscious visual experience: evidence from inter-hemispheric summation

Emotional facial expression can be discriminated despite extensive lesions of striate cortex. Here we report differential performance with recognition of facial stimuli in the intact visual field depending on simultaneous presentation of congruent or incongruent stimuli in the blind field. Three experiments were based on inter-hemispheric summation. Redundant stimulation in the blind field led to shorter latencies for stimulus detection in the intact field. Recognition of the expression of a half-face expression in the intact field was faster when the other half of the face presented to the blind field had a congruent expression. Finally, responses to the expression of whole faces to the intact field were delayed for incongruent facial expressions presented in the blind field. These results indicate that the neuro-anatomical pathways (extra-striate cortical and sub-cortical) sustaining inter-hemispheric summation can operate in the absence of striate cortex.     

Electrical stimulation of insular cortex elicits cardiac inhibition but insular lesions do not abolish conditioned bradycardia in rabbits

Conscious rabbits received electrical stimulation of insular and more posterior perirhinal cortex through chronically implanted electrodes. Active sites for cardiovascular responses were found in both anterior and posterior insular cortex as well as more posterior perirhinal regions. Although differential response topographies occurred related to anterior versus posterior insular cortex, all heart rate responses consisted of bradycardia. Pharmacological manipulations revealed that this bradycardia was due to a combination of vagal and sympatho-inhibitory mechanisms. Some posterior sites yielded pressor responses, and bradycardia which was sensitive to phentolamine, suggesting that the bradycardia in these instances was due to activation of the baroreceptor reflex. All other blood pressure changes were depressor responses. In a second experiment two different groups of rabbits with lesions of either anterior or posterior agranular insular cortex were compared with a third group of animals with sham lesions in a differential Pavlovian conditioning experiment. No lesion completely abolished the classically conditioned bradycardia associated with tone/shock contingencies. However, anterior insular lesions attenuated the magnitude of the conditioned bradycardia compared to the posterior and sham lesions. Control experiments suggested that this attenuation was due to the lesion's effects on the conditioned stimulus/unconditioned stimulus association and not to its effects on unconditioned responding to the conditioned stimulus or unconditioned stimulus alone.     

Contribution of the retrosplenial cortex to temporal discrimination learning

The retrosplenial cortex (RSC) has an important role in contextual learning and memory. While the majority of experiments have focused on the physical context, the present study asked whether the RSC is involved in processing the temporal context. Rats were trained in a temporal discrimination procedure where the duration of the intertrial interval (ITI) signaled whether or not the next tone conditioned stimulus would be paired with food pellet reinforcement. When the tone was presented after a 16‐min ITI it was reinforced, but when it was presented after a 4‐min ITI it was not. Rats demonstrated successful discrimination in this procedure by responding more to the tone on reinforced trials than on non‐reinforced trials. Pre‐training electrolytic lesions of the RSC attenuated acquisition of the temporal discrimination. The results are the first to demonstrate a role for the RSC in processing temporal information and in turn extend the role of the RSC beyond the physical context to now include the temporal context. © 2014 Wiley Periodicals, Inc.     

Contribution of striate cortex and the superior colliculus to visual function in area MT, the superior temporal polysensory area and the inferior temporal cortex

We studied the visual responses of single neurons in three extra-striate visual areas of the macaque following lesions of striate cortex, lesions of the tecto-pulvinar system or both. After striate lesions, there was (a) considerable specific activity remaining in area MT including direction selectivity, (b) only non-specific activity in the superior temporal polysensory area (STP), and (c) no visual responsiveness at all in inferior temporal cortex (IT). In animals with striate lesions, interruption of the tecto-pulvinar pathway eliminated the residual visual activity in MT and STP that survived the striate lesions. Interruption of the tecto-pulvinar pathway alone had little or no effect on visual evoked activity in any of the three areas. These results are related to the relative dependence of visual responsiveness in MT, STP and IT on striate cortex and the superior colliculus, to differences between the dorsal and ventral cortical processing streams, and to neural mechanisms underlying blind sight.     

Directed information flow: a model free measure to analyze causal interactions in event related EEG-MEG-experiments

In a study that combined event related potential (ERP) and magnetic field (ERMF) data, we analyzed the timing and direction of information flow between striate (S) and extrastriate (ES) cortex by applying a generalized mutual information measure (DIT for "directed information transfer") during a visual spatial attention task. ERP and ERMF recordings showed that selective attention to stimulus arrays in one visual field enhanced late responses (around 200 ms after the stimulus presentation) that were localized in S (ERMF) and ES (ERP) cortex. The results of the DIT analysis indicate there is a significant attention related increase in the flow of information back from ES to S cortex at around 220 ms, with an associated decrease in the flow of information forward from S cortex to ES cortex. These results support the hypothesis that a feedback mechanism guides attention-related processing in primary visual cortex and provide evidence that DIT can by used to evaluate the direction of information flow between cortical areas.     

Scene-selective cortical regions in human and nonhuman primates

fMRI studies have revealed three scene-selective regions in human visual cortex [the parahippocampal place area (PPA), transverse occipital sulcus (TOS), and retrosplenial cortex (RSC)], which have been linked to higher-order functions such as navigation, scene perception/recognition, and contextual association. Here, we document corresponding (presumptively homologous) scene-selective regions in the awake macaque monkey, based on direct comparison to human maps, using identical stimuli and largely overlapping fMRI procedures. In humans, our results showed that the three scene-selective regions are centered near-but distinct from-the gyri/sulci for which they were originally named. In addition, all these regions are located within or adjacent to known retinotopic areas. Human RSC and PPA are located adjacent to the peripheral representation of primary and secondary visual cortex, respectively. Human TOS is located immediately anterior/ventral to retinotopic area V3A, within retinotopic regions LO-1, V3B, and/or V7. Mirroring the arrangement of human regions fusiform face area (FFA) and PPA (which are adjacent to each other in cortex), the presumptive monkey homolog of human PPA is located adjacent to the monkey homolog of human FFA, near the posterior superior temporal sulcus. Monkey TOS includes the region predicted from the human maps (macaque V4d), extending into retinotopically defined V3A. A possible monkey homolog of human RSC lies in the medial bank, near peripheral V1. Overall, our findings suggest a homologous neural architecture for scene-selective regions in visual cortex of humans and nonhuman primates, analogous to the face-selective regions demonstrated earlier in these two species.     

Unconscious and conscious processing of color rely on activity in early visual cortex: a TMS study

Chromatic information is processed by the visual system both at an unconscious level and at a level that results in conscious perception of color. It remains unclear whether both conscious and unconscious processing of chromatic information depend on activity in the early visual cortex or whether unconscious chromatic processing can also rely on other neural mechanisms. In this study, the contribution of early visual cortex activity to conscious and unconscious chromatic processing was studied using single-pulse TMS in three time windows 40-100 msec after stimulus onset in three conditions: conscious color recognition, forced-choice discrimination of consciously invisible color, and unconscious color priming. We found that conscious perception and both measures of unconscious processing of chromatic information depended on activity in early visual cortex 70-100 msec after stimulus presentation. Unconscious forced-choice discrimination was above chance only when participants reported perceiving some stimulus features (but not color).     

Mechanism of directional selectivity of neurons with complex receptive fields in the visual cortex of the cat

Spatio-temporal interactions within complex receptive fields were investigated in the visual cortex of a cat by means of sequential presentation of two stationary stimuli. When two stimuli were presented in the phase (on-on or off-off) and sequential presentation corresponded to preferred movement direction, the response to second stimulus was enhanced (or less inhibited). When sequential presentation corresponded to opposite movement direction, the response was inhibited. Sequential presentation of two stimuli with opposite phase (on-off or off-on) in preferred direction inhibited the response to the second stimulus, but in nonpreferred direction the response was enhanced (or less inhibited). The strength of interactions depended on distance between stimuli presented in the receptive field and interstimulus time interval. It is concluded that direction selectivity is provided by asymmetry of spatio-temporal interactions between on-inputs and between off-inputs. Interactions between on- and off-inputs, which occur in case of multiedge stimulus movement may be used by the visual system for detecting an object from visual environment, for estimating object size and relative movement velocity.     

The processing of edge information in visual areas of the cortex as evidenced by evoked potentials

Using averaged visually evoked potentials (VEPs), recorded from bipolar cortical electrodes, as indicators of sensory information processing, the sensitivity to stimulus differences of parafoveal and foveal striate, foveal prestriate, and inferotemporal cortex was measured in 3 rhesus monkeys. The stimuli used were a blank field and a series of 5 checkerboard patterns in which check size was varied from 2°24′ to 9′ of retinal arc subtended per check. All stimuli had equal luminance (5.0 ft.-Lamberts) and duration (9 μsec).The results of this study indicate that: (1) VEPs obtained in all of the cortical regions were sensitive to stimulus differences simultaneously at several points along the temporal continuum following the stimulus; (2) the earliest signs of sensitivity to stimulus differences in the VEPs generally appeared initially in the parafoveal striate cortex at about 70 msec post stimulus and tended to be followed in succession by foveal striate, foveal prestriate, and inferotemporal cortex; (3) sensitivity was found for at least 190 msec and as long as 400 msec after stimulus presentation for all of the cortical regions examined and was generally maintained in foveal and parafoveal striate cortex for longer periods than in foveal prestriate and inferotemporal cortex; (4) the most significant signs of sensitivity were found in the parafoveal striate cortex and a simple transformation of edge information into VEP amplitude was shown to occur there; and (5) none of the cortical regions demonstrated long-term habituation of sensitivity to stimulus differences.These data give evidence for both serial and parallel processing of edge information between and within the different regions of the primary visual and visual association cortex with an apparent focus of edge information processing in parafoveal striate cortex.     

Hippocampus and medial temporal cortex: neuronal activity related to behavioural responses during the performance of memory tasks by primates

Neuronal activity was recorded in the hippocampal formation, the parahippocampal gyrus and medial inferotemporal cortex of monkeys performing memory tasks. In a modified delayed matching to sample task in which 2 sequentially presented stimuli were compared on each trial, a match condition required a right panel press, whereas a non-match condition required a left panel press. The activity of 336/736 (45.7%) neurons was related to the behavioural responses (left or right panel presses) in this task. The incidence of response-related activity was 57.4% in cortical areas adjacent to the rhinal sulcus plus medial inferotemporal cortex, and 40.2% for the hippocampal formation. For 58.9% of these response-related neurons, the activity change associated with the behavioural response was greater than that during presentation of the sensory stimuli, though neurons commonly responded (33.2% of all recorded neurons) to both sensory and motor events. The activity of 198 neurons (26.9%) differed between go-left and go-right trials; such neurons were found in all areas but were nearly twice as common in the posterior as in the anterior hippocampal formation. The importance of visual stimuli for the response-related neuronal activity was examined during the performance of a delayed alternation task without visual cues indicating direction of response. The response-related activity of 8 neurons recorded during the delayed alternation and the delayed matching tasks was similar in both tasks, indicating that memory for the behavioural responses influences the activity of the response-related neurons. In order to test the effects of stimulus familiarity and non-spatial responses on medial temporal neurons, recognition memory and visual discrimination tasks requiring lick responses were performed. The activity of 2/375 (0.5%) neurons was related to the lick responses; 3/68 neurons in the inferomedial temporal cortex responded on the basis of stimulus novelty and none reflected their reinforcement value. It is concluded that the hippocampal formation, the parahippocampal gyrus and medial inferotemporal cortex all have a role in the utilisation of sensory, mnemonic and motor information underlying the selection of spatially-directed behavioural responses.     

Fleeting images: rapid affect discrimination in the visual cortex

Converging electrophysiological and hemodynamic findings indicate sensory processing of emotional pictures is preferred to that of neutral pictures. Whereas neuroimaging studies of emotional picture perception have employed stimulus durations lasting several seconds, recent electrocortical investigations report early visual cortical discrimination between emotionally arousing and neutral picture processing. Here, we use a hybrid picture presentation paradigm covering a range of rapid presentation rates (0.75-6 Hz), while visual system activity is recorded with functional magnetic resonance imaging. Results demonstrate widespread sensitivity to emotional arousal in the secondary and inferior temporal visual cortex. Furthermore, activity in the lateral inferior occipital and medial inferior temporal visual cortex revealed equivalent emotion-sensitive activation across all presentation rates. Results further support the notion that attention and perceptual processing are in part directed by underlying motivational systems.