Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex

Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this “reversed” size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys

Encoding and Attentive Modulation of Dynamic Motion Stimuli

Several theoretical and experimental methods are employed to investigate the neural representation of dynamic motion stimuli. Starting out with an investigation of the behaviour of macaque area MT neurons, the key processing stage of visual motion, the current study presents single cell electrophysiological data that shows that the representation of dynamic motion stimuli is reliable over different stimulus statistics. Employing rapidly changing motion stimuli with different statistics of directional changes, performing extracellular recordings in area MT, reverse correlating spiketrains with the motion impulse sequence and computing direction tuning curves out of the resulting spike-triggered averages provides evidence that neural tuning curves obtained with random stimulus sequences can be directly used to predict neural tuning curves in quite different stimulus contexts (chapter 4).Extending this view on neural reliability, a reconstruction and modelling framework is applied to predict neural responses of area MT neurons. Reconstruction is useful in estimating how much information about a physical variable is present in the activity of a neuronal population. It is shown that neurons in area MT do not adapt to the statistics of dynamical stimuli, neither in direction nor in time domain (chapter 5).Having shown the reliability of neural coding for different stimulus statistics the modulatory influence of visual attention on spike-triggered averages and tuning curves is investigated (chapter 6). Using a visual stimulation paradigm similar to the one that has been used for the previous experiments, combining it with a spatial attention task; it is shown that attention alters the neural activity in macaque area MT in a multiplicative fashion, providing evidence in favour of a �gain modulation� effect of attention (McAdams and Maunsell 1999; Treue and Martinez Trujillo 1999).In a final functional imaging study (chapter 7) the functional network of cortical areas involved in representation of dynamic motion stimuli is presented. Two macaque monkeys have been trained to perform an attention task similar to the one described in chapter 6 within a 3T MR scanner. Investigation of the blood-oxygen-level-dependent signal change during performance of the attention task identified the whole set of brain areas modulated by spatial attention. In agreement with early selection accounts of visual attention (Broadbent 1958), modulated activity is found as early as V1 and continued along both parietal and temporal pathways

Functional and behavioral effects induced by electrical microstimulation of monkey FEF during selective spatial attention tasks

Several studies provided evidence for a prominent role of the frontal eye fields (FEF) in the allocation of attention. FEF is an area of the frontal cortex involved in linking visual information with saccade commands and is thought to modulate incoming sensory signals through feedback signals. For example, Moore and Fallah (2004) have shown that electrical microstimulation of macaque FEF (FEF-EM) increases performance for stimuli presented inside the stimulated movement field (MF) in a luminance contrast detection task. In a separate study, Moore and Armstrong (2003) also showed that FEF-EM enhances neural activity to visual stimuli in retinotopically corresponding sites in area V4 in a similar fashion to attention. A subsequent pharmacological study by Noudoost and Moore (2011) was able to identify dopamine D1 receptors in FEF as mediating prefrontal control of visual cortical signals. Ekstrom et al. (2008, 2009), on the other hand, showed that FEF-EM most strongly enhanced fMRI activity in voxels of visual cortex that were located adjacent to the voxels with the strongest visual response. Voxels activated strongest by a visual stimulus were unaffected or even suppressed by concurrent FEF-EM. In an attempt to directly link behavioral with functionally FEF-EM triggered effects in the same experiment, we chronically implanted 25 micron Pt/Ir micro-wires for FEF-EM in two monkeys performing a selective spatial attention task. The monkeys were trained to indicate the orientation of a peripherally presented low-contrast grating stimulus at threshold level while ignoring a similar grating stimulus in the opposite hemifield. Unilateral FEF-EM slightly decreased the monkey’s performance in this task. Given this surprising result, we also trained our monkeys on exactly the same contrast detection task as used by Moore and Fallah (2004). We ran 117 experiments at 20 different electrode positions in two monkeys. Out of these 20 sites 11 sites did not reveal any significant effect of FEF-EM on contrast detection thresholds for stimuli presented in the center of the MF. Only three sites showed a significant positive effect and 6 sites showed a significant negative effect on performance. Concurrent fMRI - FEF-EM experiments using the same tasks revealed inhibition of activity in early visual areas at the retinotopic location of the visual stimuli. Our data are in line with the passive viewing results from Ekstrom et al. (2008) and suggest that both suppressive and enhancement signals may be transmitted from FEF to occipital cortex.status: publishe

Increased visual stimulation systematically decreases activity in posterior superior temporal cortex

Previous fMRI studies have ascribed different roles to the posterior superior temporal cortex (pSTC). Some studies described a visually driven selectivity for biological motion and facial features in this region. Other studies showed a subdivision of the default mode network (DMN) in this general region, emphasizing internal (i.e. non-sensory) influences, including self-referential processing and theory of mind. To clarify the relationship between these differently-defined regions within pSTC, and the transition between sensory vs. non-sensory (i.e. external versus internal) processing here, we measured fMRI responses to systematic changes in exogenously driven salience, produced by varying the extent of stimulated visual field. Unlike the responses in occipito-temporal visual cortex, posterior Superior Temporal Cortex (pSTC) showed a paradoxically increased response to decreases in visual stimulus extent, based on variations in either object size or number. Such changes are consistent with a focus on internal (rather than external/sensory) processing in this region, as described for the DMN. Such inverted visual size responses were found across multiple categories of familiar objects and computer generated shapes, and this finding was independent of stimulus eccentricity. Testing the inverted size function across different states of spatial attention, we found that spatially distributed attention enhanced the size-inverted response in pSTC compared to centrally focused attention. Other experiments and a meta-analysis demonstrated partially overlapping subregions in pSTC based on previously reported functions (e.g. biological motion, facial features, and theory of mind), all sharing an inverted size preference. This suggests a combination of functions in pSTC, having in common a DMN-like bias against stronger visual salience. Consistent with a transitional function between sensory and more dominant non-sensory influences, pSTC showed strong functional connectivity with frontoparietal brain regions including mPFC and PCC, plus a weak but convergent connection with classic visual cortex. Interestingly, similar fMRI tests in monkeys based on analogous stimuli and tasks did not reveal a functional homologue of pSTC. This apparent discrepancy between the two species is consistent with the idea that DMN-like processing (including self-referential thinking and theory of mind) are relatively more prominent in humans, compared to macaques.status: publishe

Demonstration of Intracortical Chronic Recording and Acute Microstimulation Using Novel Floating Neural Probes

This paper presents long-term stable multichannel recording of neural activity using novel intracortical floating probes implanted chronically in rat cortex. The novel flexible probe design approach allows recording of action potentials for at least 38 days after implantation. Furthermore the capability of the PEDOT: PSS coated microelectrodes for electrical stimulation is characterized in vitro and in an acute in vivo experiment. The in vitro results show a charge injection capacity of 2 mC/cm2 and the in vivo results demonstrate reproducible response of the neural network to charge injection up to 1 mC/cm2. The optical inspection of the explanted neural probe reveals sufficient stability of the PEDOT: PSS microelectrode coating for the acute microstimulation experiment. These preliminary results indicate the capability for long-term stable microstimulation

Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex

Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this "reversed" size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys.status: publishe

Silicon-Based Microfabrication of Free-Floating Neural Probes and Insertion Tool for Chronic Applications

Bidirectional neural interfaces for multi-channel, high-density recording and electrical stimulation of neural activity in the central nervous system are fundamental tools for neuroscience and medical applications. Especially for clinical use, these electrical interfaces must be stable over several years, which is still a major challenge due to the foreign body response of neural tissue. A feasible solution to reduce this inflammatory response is to enable a free-floating implantation of high-density, silicon-based neural probes to avoid mechanical coupling between the skull and the cortex during brain micromotion. This paper presents our latest development of a reproducible microfabrication process, which allows a monolithic integration of a highly-flexible, polyimide-based cable with a silicon-stiffened neural probe at a high resolution of 1 µm. For a precise and complete insertion of the free-floating probes into the cortex, a new silicon-based, vacuum-actuated insertion tool is presented, which can be attached to commercially available electrode drives. To reduce the electrode impedance and enable safe and stable microstimulation an additional coating with the electrical conductive polymer PEDOT:PSS is used. The long-term stability of the presented free-floating neural probes is demonstrated in vitro and in vivo. The promising results suggest the feasibility of these neural probes for chronic applications

Electrical microstimulation of the ventral tegmental area reinforces cue selection in monkeys

Activity within the ventral tegmental area (VTA) correlates with increased dopamine concentrations and modulation of neural activity throughout a widespread network of VTA-projections sites. Electrical and optogenetic stimulation in rodents have causally demonstrated that these VTA-mediated dopamine signals play a key role in motivational behavior, reinforcement learning and cortical plasticity. In contrast, while electrophysiological experiments in monkeys have greatly enhanced our understanding of VTA’s response properties, there has been a lack of causal investigations selectively targeting primate VTA. This gap in understanding is further compounded by the fact that the dopamine system of primates is greatly expanded relative to that of rodents (Berger et al., 1991), suggesting that the primate VTA may exert an even greater influence over cortical function than what has been found in rodents. In an effort to bridge the gap between refined perturbation studies in rodents and monkey electrophysiology, we developed a technique for chronic, neuronavigation-guided electrical microstimulation of macaque VTA (VTA-EM). After electrode implantation, we tested the hypothesis that VTA plays a causal role in positive reinforcement by electrically stimulating this region during Pavlovian and operant conditioning paradigms. Stimulation of this mesolimbic ventral midbrain region caused pronounced stimulus-driven reinforcement effects during both of these paradigms. More specifically, the delivery of VTA-EM directly following the selection of a specific visual cue by the monkey (operant conditioning) or after the consistent temporal association of a visual cue and VTA-EM (Pavlovian conditioning) increased the likelihood that that cue would be selected during subsequent trials. In an effort to determine the functional network modulated by reinforcing VTA-EM, we then combined VTA-EM with concurrent functional magnetic resonance imaging (fMRI). This allowed us to visualize the brain-wide cortical and subcortical structures directly influenced by VTA stimulation. Importantly, several nodes in the primate dopamine system were among the regions significantly modulated by VTA-EM. These results establish for the first time a causal role for primate VTA in stimulus-driven positive reinforcement and help elucidate the functional network of cortical and subcortical regions involved in this process.status: publishe

Functionally defined white matter of the macaque monkey brain reveals a dorso-ventral attention network - Data -

Classical studies of attention have identified areas of parietal and frontal cortex as sources of attentional control. Recently, a ventral region in the macaque temporal cortex, the posterior infero-temporal dorsal area PITd, has been suggested as a third attentional control area. This raises the question of whether and how spatially distant areas coordinate a joint focus of attention. Here we tested the hypothesis that parieto-frontal attention areas and PITd are directly interconnected. By combining functional MRI with ex-vivo high-resolution diffusion MRI, we found that PITd and dorsal attention areas are all directly connected through three specific fascicles. These results ascribe a new function, the communication of attention signals, to two known fiber-bundles, highlight the importance of vertical interactions across the two visual streams, and imply that the control of endogenous attention, hitherto thought to reside in macaque dorsal cortical areas, is exerted by a dorso-ventral network