Altered Sensitivity to Motion of Area MT Neurons Following Long-Term V1 Lesions.

Primates with primary visual cortex (V1) damage often retain residual motion sensitivity, which is hypothesized to be mediated by middle temporal area (MT). MT neurons continue to respond to stimuli shortly after V1 lesions; however, experimental and clinical studies of lesion-induced plasticity have shown that lesion effects can take several months to stabilize. It is unknown what physiological changes occur in MT and whether neural responses persist long after V1 damage. We recorded neuronal responses in MT to moving dot patterns in adult marmoset monkeys 6-12 months after unilateral V1 lesions. In contrast to results obtained shortly after V1 lesions, we found that fewer MT neurons were direction selective, including neurons expected to still receive projections from remaining parts of V1. The firing rates of most cells increased with increases in motion strength, regardless of stimulus direction. Furthermore, firing rates were higher and more variable than in control MT cells. To test whether these observations could be mechanistically explained by underlying changes in neural circuitry, we created a network model of MT. We found that a local imbalance of inhibition and excitation explained the observed firing rate changes. These results provide the first insights into functional implications of long-term plasticity in MT following V1 lesions.

Auditory motion does not modulate spiking activity in the middle temporal and medial superior temporal visual areas.

The integration of multiple sensory modalities is a key aspect of brain function, allowing animals to take advantage of concurrent sources of information to make more accurate perceptual judgments. For many years, multisensory integration in the cerebral cortex was deemed to occur only in high-level "polysensory" association areas. However, more recent studies have suggested that cross-modal stimulation can also influence neural activity in areas traditionally considered to be unimodal. In particular, several human neuroimaging studies have reported that extrastriate areas involved in visual motion perception are also activated by auditory motion, and may integrate audiovisual motion cues. However, the exact nature and extent of the effects of auditory motion on the visual cortex have not been studied at the single neuron level. We recorded the spiking activity of neurons in the middle temporal (MT) and medial superior temporal (MST) areas of anesthetized marmoset monkeys upon presentation of unimodal stimuli (moving auditory or visual patterns), as well as bimodal stimuli (concurrent audiovisual motion). Despite robust, direction selective responses to visual motion, none of the sampled neurons responded to auditory motion stimuli. Moreover, concurrent moving auditory stimuli had no significant effect on the ability of single MT and MST neurons, or populations of simultaneously recorded neurons, to discriminate the direction of motion of visual stimuli (moving random dot patterns with varying levels of motion noise). Our findings do not support the hypothesis that direct interactions between MT, MST and areas low in the hierarchy of auditory areas underlie audiovisual motion integration.

Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments.NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural basis of motion perception in the marmoset, a small primate species that is becoming increasingly popular as an experimental model.

Unilateral prefrontal lesions impair memory-guided comparisons of contralateral visual motion.

The contribution of the lateral prefrontal cortex (LPFC) to working memory is the topic of active debate. On the one hand, it has been argued that the persistent delay activity in LPFC recorded during some working memory tasks is a reflection of sensory storage, the notion supported by some lesion studies. On the other hand, there is emerging evidence that the LPFC plays a key role in the maintenance of sensory information not by storing relevant visual signals but by allocating visual attention to such stimuli. In this study, we addressed this question by examining the effects of unilateral LPFC lesions during a working memory task requiring monkeys to compare directions of two moving stimuli, separated by a delay. The lesions resulted in impaired thresholds for contralesional stimuli at longer delays, and these deficits were most dramatic when the task required rapid reallocation of spatial attention. In addition, these effects were equally pronounced when the remembered stimuli were at threshold or moved coherently. The contralesional nature of the deficits points to the importance of the interactions between the LPFC and the motion processing neurons residing in extrastriate area MT. Delay-specificity of the deficit supports LPFC involvement in the maintenance stage of the comparison task. However, because this deficit was independent of stimulus features giving rise to the remembered direction and was most pronounced during rapid shifts of attention, its role is more likely to be attending and accessing the preserved motion signals rather than their storage.

Breaking camouflage: responses of neurons in the middle temporal area to stimuli defined by coherent motion.

Camouflaged animals remain inconspicuous only insofar as they remain static. This demonstrates that motion is a powerful cue for figure-ground segregation, allowing detection of moving objects even when their luminance and texture characteristics are matched to the background. We investigated the neural processes underlying this phenomenon by testing the responses of neurons in the middle temporal area (MT) to 'camouflaged' bars, which were rendered visible by motion. These responses were compared with those elicited by 'solid' bars, which also differed from background in terms of their mean luminance. Most MT neurons responded strongly to camouflaged bars, and signaled their direction of motion with precision, with direction-tuning curves being only slightly wider than those measured with solid bars. However, the tuning of most MT cells to stimulus length and speed depended on the type of stimulus - in comparison with solid bars, responses to camouflaged bars typically showed more extensive length summation, weak end-inhibition, and stronger attenuation at high speeds. Moreover, the emergence of direction selectivity was delayed in trials involving camouflaged bars, relative to solid bars. Comparison with results obtained in the first (V1) and second (V2) visual areas, using similar stimuli, indicates that neural computations performed in MT result in significantly stronger and more accurate signals about camouflaged objects, particularly in situations in which these are relatively large and slow moving. These computations are likely to represent an important step in enabling cue-invariant perception of moving objects, particularly in biologically relevant situations.

Representation of comparison signals in cortical area MT during a delayed direction discrimination task.

Visually guided behavior often involves decisions that are based on evaluating stimuli in the context of those observed previously. Such decisions are made by monkeys comparing two consecutive stimuli, sample and test, moving in the same or opposite directions. We examined whether responses in the motion processing area MT during the comparison phase of this task (test) are modulated by the direction of the preceding stimulus (sample). This modulation, termed comparison signal, was measured by comparing responses to identical test stimuli on trials when it was preceded by sample moving in the same direction (S-trials) with trials when it was preceded by sample moving in a different direction (D-trials). The test always appeared in the neuron's receptive field (RF), whereas sample could appear in the RF or in the contralateral visual field (remote sample). With sample in-RF, we found three types of modulation carried by different sets of neurons: early suppression on S-trials and late enhancement, one on S-trials, and the other on D-trials. Under these conditions, many neurons with and without comparison effects exhibited significant, choice-related activity. Response modulation was also present following the remote sample, even though the information about its direction could only reach MT indirectly via top-down influences. However, unlike on trials with in-RF sample, these signals were dominated by response suppression, shedding light on the contribution of top-down influences to the comparison effects. These results demonstrate that during the task requiring monkeys to compare two directions of motion, MT responses during the comparison phase of this task reflect similarities and differences between the two stimuli, suggesting participation in sensory comparisons. The nature of these signals provides insights into the operation of bottom-up and top-down influences involved in this process.

Spatial and temporal frequency tuning in striate cortex: functional uniformity and specializations related to receptive field eccentricity.

In light of anatomical evidence suggesting differential connection patterns in central vs. peripheral representations of cortical areas, we investigated the extent to which the response properties of cells in the primary visual area (V1) of the marmoset change as a function of eccentricity. Responses to combinations of the spatial and temporal frequencies of visual stimuli were quantified for neurons with receptive fields ranging from 3 degrees to 70 degrees eccentricity. Optimal spatial frequencies and stimulus speeds reflected the expectation that the responses of cells throughout V1 are essentially uniform, once scaled according to the cortical magnification factor. In addition, temporal frequency tuning was similar throughout V1. However, spatial frequency tuning curves depended both on the cell's optimal spatial frequency and on the receptive field eccentricity: cells with peripheral receptive fields showed narrower bandwidths than cells with central receptive fields that were sensitive to the same optimal spatial frequency. Although most V1 cells had separable spatial and temporal frequency tuning, the proportion of neurons displaying significant spatiotemporal interactions increased in the representation of far peripheral vision (> 50 degrees). In addition, of the fewer than 5% of V1 cells that showed robust (spatial frequency independent) selectivity to stimulus speed, most were concentrated in the representation of the far periphery. Spatiotemporal interactions in the responses of many cells in the peripheral representation of V1 reduced the ambiguity of responses to high-speed (> 30 degrees/s) signals. These results support the notion of a relative specialization for motion processing in the far peripheral representations of cortical areas, including V1.

Neuronal Correlations in MT and MST Impair Population Decoding of Opposite Directions of Random Dot Motion.

The study of neuronal responses to random-dot motion patterns has provided some of the most valuable insights into how the activity of neurons is related to perception. In the opposite directions of motion paradigm, the motion signal strength is decreased by manipulating the coherence of random dot patterns to examine how well the activity of single neurons represents the direction of motion. To extend this paradigm to populations of neurons, studies have used modelling based on data from pairs of neurons, but several important questions require further investigation with larger neuronal datasets. We recorded neuronal populations in the middle temporal (MT) and medial superior temporal (MST) areas of anaesthetized marmosets with electrode arrays, while varying the coherence of random dot patterns in two opposite directions of motion (left and right). Using the spike rates of simultaneously recorded neurons, we decoded the direction of motion at each level of coherence with linear classifiers. We found that the presence of correlations had a detrimental effect to decoding performance, but that learning the correlation structure produced better decoding performance compared to decoders that ignored the correlation structure. We also found that reducing motion coherence increased neuronal correlations, but decoders did not need to be optimized for each coherence level. Finally, we showed that decoder weights depend of left-right selectivity at 100% coherence, rather than the preferred direction. These results have implications for understanding how the information encoded by populations of neurons is affected by correlations in spiking activity.

Auditory and Visual Motion Processing and Integration in the Primate Cerebral Cortex.

The ability of animals to detect motion is critical for survival, and errors or even delays in motion perception may prove costly. In the natural world, moving objects in the visual field often produce concurrent sounds. Thus, it can highly advantageous to detect motion elicited from sensory signals of either modality, and to integrate them to produce more reliable motion perception. A great deal of progress has been made in understanding how visual motion perception is governed by the activity of single neurons in the primate cerebral cortex, but far less progress has been made in understanding both auditory motion and audiovisual motion integration. Here we, review the key cortical regions for motion processing, focussing on translational motion. We compare the representations of space and motion in the visual and auditory systems, and examine how single neurons in these two sensory systems encode the direction of motion. We also discuss the way in which humans integrate of audio and visual motion cues, and the regions of the cortex that may mediate this process.

Neural plasticity following lesions of the primate occipital lobe: The marmoset as an animal model for studies of blindsight.

For nearly a century it has been observed that some residual visually guided behavior can persist after damage to the primary visual cortex (V1) in primates. The age at which damage to V1 occurs leads to different outcomes, with V1 lesions in infancy allowing better preservation of visual faculties in comparison with those incurred in adulthood. While adult V1 lesions may still allow retention of some limited visual abilities, these are subconscious-a characteristic that has led to this form of residual vision being referred to as blindsight. The neural basis of blindsight has been of great interest to the neuroscience community, with particular focus on understanding the contributions of the different subcortical pathways and cortical areas that may underlie this phenomenon. More recently, research has started to address which forms of neural plasticity occur following V1 lesions at different ages, including work using marmoset monkeys. The relatively rapid postnatal development of this species, allied to the lissencephalic brains and well-characterized visual cortex provide significant technical advantages, which allow controlled experiments exploring visual function in the absence of V1. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 314-327, 2017.

Neuronal degeneration in the dorsal lateral geniculate nucleus following lesions of primary visual cortex: comparison of young adult and geriatric marmoset monkeys.

Neuronal loss in the lateral geniculate nucleus (LGN) is a consequence of lesions of the primary visual cortex (V1). Despite the importance of this phenomenon in understanding the residual capacities of the primate visual system following V1 damage, few quantitative studies are available, and the effect of age at the time of lesion remains unknown. We compared the volume, neuronal number, and neuronal density in the LGN, 6-21 months after unilateral V1 lesions in marmoset monkeys. Stereological sampling techniques and neuronal nuclei (NeuN) staining were used to assess the effects of similar-sized lesions in adult (2-4 years) and geriatric (10-14 years) animals. We found that lesions involving the opercular and caudal calcarine parts of V1 caused robust loss of neurons in topographically corresponding regions of the ipsilateral LGN (lesion projection zones), concomitant with a substantial reduction in the volume of this nucleus. Neuronal density was markedly reduced in the lesion projection zones, relative to the corresponding regions of the contralateral LGN, or the LGN in non-lesioned animals. Moreover, the percentage decrease in neuronal density within the lesion projection zones was significantly greater in the geriatric group, compared with the adult groups. The volume and neuronal density in the contralateral LGN of lesioned adult and geriatric marmosets were similar to those in non-lesioned animals. These results show that the primate LGN becomes more vulnerable to degeneration with advancing age. However, even in geriatric primates there is a population of LGN neurons which survives degeneration, and which could play a role in blindsight.

Structure and function of the middle temporal visual area (MT) in the marmoset: Comparisons with the macaque monkey.

Although macaque monkeys have been dominant models in visual neuroscience, recent scientific advances suggest that marmosets provide a valuable alternative in the context of many types of experiments. Here we focus on the middle temporal area (MT), the most extensively studied extrastriate area in primates, and discuss similarities and differences between marmosets and macaques. The basic response properties of MT cells are similar in these species, including direction selectivity, speed tuning, and receptive field centre-surround organization. However, there are differences associated with spatial processing: receptive fields are larger in the marmoset than in the macaque, and MT neurons have preferences for lower spatial frequencies. Comparative analysis of anatomical connections show neural projections from several higher-order association areas to marmoset MT, which seem to be absent or reduced in the macaque. This suggests that cognitive processes could influence the activity of marmoset MT cells more directly. Despite a relative reduction in visual acuity, the present knowledge about the anatomy and physiology of MT in the marmoset suggests that simple low-level visual tasks, which are standard in the literature, are well within the capabilities of marmosets, opening the way for comparative studies of perception and cognition in primate brains of different sizes.

Responses of neurons in the marmoset primary auditory cortex to interaural level differences: comparison of pure tones and vocalizations.

Interaural level differences (ILDs) are the dominant cue for localizing the sources of high frequency sounds that differ in azimuth. Neurons in the primary auditory cortex (A1) respond differentially to ILDs of simple stimuli such as tones and noise bands, but the extent to which this applies to complex natural sounds, such as vocalizations, is not known. In sufentanil/N2O anesthetized marmosets, we compared the responses of 76 A1 neurons to three vocalizations (Ock, Tsik, and Twitter) and pure tones at cells' characteristic frequency. Each stimulus was presented with ILDs ranging from 20 dB favoring the contralateral ear to 20 dB favoring the ipsilateral ear to cover most of the frontal azimuthal space. The response to each stimulus was tested at three average binaural levels (ABLs). Most neurons were sensitive to ILDs of vocalizations and pure tones. For all stimuli, the majority of cells had monotonic ILD sensitivity functions favoring the contralateral ear, but we also observed ILD sensitivity functions that peaked near the midline and functions favoring the ipsilateral ear. Representation of ILD in A1 was better for pure tones and the Ock vocalization in comparison to the Tsik and Twitter calls; this was reflected by higher discrimination indices and greater modulation ranges. ILD sensitivity was heavily dependent on ABL: changes in ABL by ±20 dB SPL from the optimal level for ILD sensitivity led to significant decreases in ILD sensitivity for all stimuli, although ILD sensitivity to pure tones and Ock calls was most robust to such ABL changes. Our results demonstrate differences in ILD coding for pure tones and vocalizations, showing that ILD sensitivity in A1 to complex sounds cannot be simply extrapolated from that to pure tones. They also show A1 neurons do not show level-invariant representation of ILD, suggesting that such a representation of auditory space is likely to require population coding, and further processing at subsequent hierarchical stages.

Relationship between size summation properties, contrast sensitivity and response latency in the dorsomedial and middle temporal areas of the primate extrastriate cortex.

Analysis of the physiological properties of single neurons in visual cortex has demonstrated that both the extent of their receptive fields and the latency of their responses depend on stimulus contrast. Here, we explore the question of whether there are also systematic relationships between these response properties across different cells in a neuronal population. Single unit recordings were obtained from the middle temporal (MT) and dorsomedial (DM) extrastriate areas of anaesthetized marmoset monkeys. For each cell, spatial integration properties (length and width summation, as well as the presence of end- and side-inhibition within 15° of the receptive field centre) were determined using gratings of optimal direction of motion and spatial and temporal frequencies, at 60% contrast. Following this, contrast sensitivity was assessed using gratings of near-optimal length and width. In both areas, we found a relationship between spatial integration and contrast sensitivity properties: cells that summated over smaller areas of the visual field, and cells that displayed response inhibition at larger stimulus sizes, tended to show higher contrast sensitivity. In a sample of MT neurons, we found that cells showing longer latency responses also tended to summate over larger expanses of visual space in comparison with neurons that had shorter latencies. In addition, longer-latency neurons also tended to show less obvious surround inhibition. Interestingly, all of these effects were stronger and more consistent with respect to the selectivity for stimulus width and strength of side-inhibition than for length selectivity and end-inhibition. The results are partially consistent with a hierarchical model whereby more extensive receptive fields require convergence of information from larger pools of "feedforward" afferent neurons to reach near-optimal responses. They also suggest that a common gain normalization mechanism within MT and DM is involved, the spatial extent of which is more evident along the cell's preferred axis of motion.

Spatial and temporal frequency selectivity of neurons in the middle temporal visual area of new world monkeys (Callithrix jacchus).

Information about the responses of neurons to the spatial and temporal frequencies of visual stimuli is important for understanding the types of computations being performed in different visual areas. We characterized the spatiotemporal selectivity of neurons in the middle temporal area (MT), which is deemed central for the processing of direction and speed of motion. Recordings obtained in marmoset monkeys using high-contrast sine-wave gratings as stimuli revealed that the majority of neurons had bandpass spatial and temporal frequency tuning, and that the selectivity for these parameters was largely separable. Only in about one-third of the cells was inseparable spatiotemporal tuning detected, this typically being in the form of an increase in the optimal temporal frequency as a function of increasing grating spatial frequency. However, most of these interactions were weak, and only 10% of neurons showed spatial frequency-invariant representation of speed. Cells with inseparable spatiotemporal tuning were most commonly found in the infragranular layers, raising the possibility that they form part of the feedback from MT to caudal visual areas. While spatial frequency tuning curves were approximately scale-invariant on a logarithmic scale, temporal frequency tuning curves covering different portions of the spectrum showed marked and systematic changes. Thus, MT neurons can be reasonably described as similarly built spatial frequency filters, each covering a different dynamic range. The small proportion of speed-tuned neurons, together with the laminar position of these units, are compatible with the idea that an explicit neural representation of speed emerges from computations performed in MT.

Spatial summation, end inhibition and side inhibition in the middle temporal visual area (MT).

We investigated the responses of single neurons in the middle temporal area (MT) of anesthetized marmoset monkeys to sine-wave gratings of various lengths and widths. For the vast majority of MT cells maximal responses were obtained on presentation of gratings of specific dimensions, which were typically asymmetrical along the length and width axes. The strength of end inhibition was dependent on the width of the stimulus, with many cells showing clear end inhibition only when wide gratings were used. Conversely, the strength of side inhibition was dependent on stimulus length. Furthermore, for over one third of MT cells length summation properties could not be defined without consideration of stimulus width and vice versa. These neurons, which we refer to as "length-width inseparable" (LWI) cells, were rare in layer 4. The majority of LWI neurons was strongly inhibited by wide-field stimuli and responded preferentially to gratings that were elongated, along either the length or width dimensions. However, rather than forming a homogeneous and entirely distinct group, LWI cells represented the upper end of a continuum of complexity in spatial summation response properties, which characterized the population of MT cells. Only a minority of MT neurons (22.3%) showed no evidence of inhibition by wide-field stimuli, with this type of response being common among layer 5 cells. These results demonstrate distinct patterns of spatial selectivity in MT, supporting the notion that neurons in this area can perform various roles in terms of grouping and segmentation of motion signals.

Development of non-phosphorylated neurofilament protein expression in neurones of the New World monkey dorsolateral frontal cortex.

We studied developmental changes in the expression of non-phosphorylated neurofilament protein (NNF) (a marker of the structural maturation of pyramidal neurones) in the dorsolateral frontal cortex of marmoset monkeys, between embryonic day 130 and adulthood. Our focus was on cortical fields that send strong projections to extrastriate cortex, including the dorsal and ventral subdivisions of area 8A, area 46 and area 6d. For comparison, we also investigated the maturation of prefrontal area 9, which has few or no connections with visual areas. The timing of expression of NNF immunostaining in early life can be described as the result of the interaction of two developmental gradients. First, there is an anteroposterior gradient of maturation in the frontal lobe, whereby neurones in caudal areas express NNF earlier than those in rostral areas. Second, there is a laminar gradient, whereby the first NNF-immunoreactive neurones emerge in layer V, followed by those in progressively more superficial parts of layer III. Following a peak in density of NNF-immunopositive cell numbers in layer V at 2-3 months of age, there is a gradual decline towards adulthood. In contrast, the density of immunopositive cells in layer III continues to increase throughout the first postnatal year in area 6d and until late adolescence (> 1.5 years of age) in prefrontal areas. The present results support the view that the maturation of visual cognitive functions involves relatively late processes linked to structural changes in frontal cortical areas.

Functional response properties of neurons in the dorsomedial visual area of New World monkeys (Callithrix jacchus).

The dorsomedial visual area (DM), a subdivision of extrastriate cortex located near the dorsal midline, is characterized by heavy myelination and a relative emphasis on peripheral vision. To date, DM remains the least understood of the three primary targets of projections from the striate cortex (V1) in New World monkeys. Here, we characterize the responses of DM neurons in anaesthetized marmosets to drifting sine wave gratings. Most (82.4%) cells showed bidirectional sensitivity, with only 6.9% being strongly direction selective. The distribution of orientation sensitivity was bimodal, with a distinct population (corresponding to over half of the sample) formed by neurons with very narrow selectivity. When compared with a sample of V1 units representing a comparable range of eccentricities, DM cells revealed a preference for much lower spatial frequencies, and higher speeds. End inhibition was extremely rare, and the responses of many cells summated over distances as large as 30 degrees. Our results suggest clear differences between DM and the two other main targets of V1 projections, the second (V2) and middle temporal (MT) areas, with cells in DM emphasizing aspects of visual information that are likely to be relevant for motor control.