Tobias Teichert

The dorsal medial frontal cortex is sensitive to time on task, not response conflict or error likelihood

The dorsal medial frontal cortex (dMFC) is highly active during choice behavior. Though many models have been proposed to explain dMFC function, the conflict monitoring model is the most influential. It posits that dMFC is primarily involved in detecting interference between competing responses thus signaling the need for control. It accurately predicts increased neural activity and response time (RT) for incompatible (high-interference) vs. compatible (low-interference) decisions. However, it has been shown that neural activity can increase with time on task, even when no decisions are made. Thus, the greater dMFC activity on incompatible trials may stem from longer RTs rather than response conflict. This study shows that (1) the conflict monitoring model fails to predict the relationship between error likelihood and RT, and (2) the dMFC activity is not sensitive to congruency, error likelihood, or response conflict, but is monotonically related to time on task.

Noninvasive, transient and selective blood-brain barrier opening in non-human primates in vivo.

The blood-brain barrier (BBB) is a specialized vascular system that impedes entry of all large and the vast majority of small molecules including the most potent central nervous system (CNS) disease therapeutic agents from entering from the lumen into the brain parenchyma. Microbubble-enhanced, focused ultrasound (ME-FUS) has been previously shown to disrupt noninvasively, selectively, and transiently the BBB in small animals in vivo. For the first time, the feasibility of transcranial ME-FUS BBB opening in non-human primates is demonstrated with subsequent BBB recovery. Sonications were combined with two different types of microbubbles (customized 4–5 µm and Definity®). 3T MRI was used to confirm the BBB disruption and to assess brain damage.

Feasibility of noninvasive cavitation-guided blood-brain barrier opening using focused ultrasound and microbubbles in nonhuman primates

In vivo transcranial and noninvasive cavitation detection with blood-brain barrier (BBB) opening in nonhuman primates is hereby reported. The BBB in monkeys was opened transcranically using focused ultrasound (FUS) in conjunction with microbubbles. A passive cavitation detector, confocal with the FUS transducer, was used to identify and monitor the bubble behavior. During sonication, the cavitation spectrum, which was found to be region-, pressure-, and bubble-dependent, provided real-time feedback regarding the opening occurrence and its properties. These findings demonstrate feasibility of transcranial, cavitation-guided BBB opening using FUS and microbubbles in noninvasive human applications.

Real-time, transcranial monitoring of safe blood-brain barrier opening in non-human primates.

The delivery of drugs to specific neural targets faces two fundamental problems: most drugs do not cross the blood-brain barrier and those that do spread to all parts of the brain. To date there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier disruption using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500 kHz spherical transducer ultrasound setup for use in the nonhuman primate. Here, we tested the accuracy of the system by targeting the caudate nucleus of the basal ganglia in two macaque monkeys. Our results show that average in-plane error of the system is on the order of 2 mm and targeting error in depth, i.e., along the ultrasound path, is even smaller averaging 1.2 mm. We have also developed a real-time treatment monitoring based on backscattered emissions spectral analyses. This technique helped us determining a safe and reliable acoustic parameters window for BBB opening.

Effects of heartbeat and respiration on macaque fMRI: implications for functional connectivity

The use of functional magnetic resonance imaging (fMRI) in non-human primates is on the increase. It is known that the blood-oxygen-level-dependent (BOLD) signal varies not only as a function of local neuronal energy consumption but also as a function of cardiac and respiratory activity. We mapped these cyclic cardiac and respiratory artifacts in anesthetized macaque monkeys and present an objective analysis of their impact on estimates of functional connectivity (fcMRI). Voxels with significant cardiac and respiratory artifacts were found in much the same regions as previously reported for awake humans. We show two example seeds where removing the artifacts clearly decreased the number of false positive and false negative correlations. In particular, removing the artifacts reduced correlations in the so-called resting state network. Temporal bandpass filtering or spatial smoothing may help to reduce the effects of artifacts in some cases but are not an adequate replacement for an algorithm that explicitly models and removes cyclic cardiac and respiratory artifacts.

Conflict, error likelihood, and RT: Response to Brown & Yeung et al.

We would like to thank our reviewers and the authors of the commentaries on our paper. Though we may have scientific differences, the criticisms raised in the commentaries will undoubtedly improve our understanding of the neural basis of decision making and provide a springboard for future experiments. In our response, we clarify why our data are incompatible with both the error likelihood and the conflict monitoring models presented by Brown and by Yeung et al., respectively.

Performance monitoring in monkey frontal eye field.

The frontal eye fields (FEF) are thought to mediate response selection during oculomotor decision tasks. In addition, many FEF neurons have robust postsaccadic responses, but their role in postchoice evaluative processes (online performance monitoring) is only beginning to become apparent. Here we report error-related neural activity in FEF while monkeys performed a biased speed-categorization task that enticed the animals to make impulsive errors. Twenty-three percent of cells in macaque FEF coded an internally generated error-related signal, and many of the same cells also coded task difficulty. The observed responses are primarily consistent with three related concepts that have been associated with performance monitoring: (1) response conflict; (2) uncertainty; and (3) reward prediction. Overall, our findings suggest a novel role for the FEF as part of the neural network that evaluates the preceding choice to optimize behavior in the future.

Perisaccadic mislocalization as optimal percept.

The spatially uniform mislocalization of stimuli flashed around the onset of fast eye-movements (perisaccadic shift) has previously been explained by an inaccurate internal representation of current eye position. However, this hypothesis does not account for the observation that continuously presented stimuli are correctly localized during saccades. Here we show that the two findings are not mutually exclusive. The novelty of our approach lies in our interpretation of the extraretinal signal which, in contrast to other models, is not considered an (erroneous) estimate of current eye-position. Based on the reafference principle, our model assumes that the extraretinal signal is optimal in that it accurately predicts the neural representation of the retinal position of a continuously present stimulus. Perisaccadic shift arises as a consequence of maintaining stable perisaccadic position estimates for continuously present stimuli under the physiologically plausible assumption of temporal low-pass filtering in the afferent visual pathway. Consequently, our model reconciles the reafference principle with the finding of perisaccadic shift.

Scale-invariance of receptive field properties in primary visual cortex

BackgroundOur visual system enables us to recognize visual objects across a wide range of spatial scales. The neural mechanisms underlying these abilities are still poorly understood. Size- or scale-independent representation of visual objects might be supported by processing in primary visual cortex (V1). Neurons in V1 are selective for spatial frequency and thus represent visual information in specific spatial wavebands. We tested whether different receptive field properties of neurons in V1 scale with preferred spatial wavelength. Specifically, we investigated the size of the area that enhances responses, i.e., the grating summation field, the size of the inhibitory surround, and the distance dependence of signal coupling, i.e., the linking field.ResultsWe found that the sizes of both grating summation field and inhibitory surround increase with preferred spatial wavelength. For the summation field this increase, however, is not strictly linear. No evidence was found that size of the linking field depends on preferred spatial wavelength.ConclusionOur data show that some receptive field properties are related to preferred spatial wavelength. This speaks in favor of the hypothesis that processing in V1 supports scale-invariant aspects of visual performance. However, not all properties of receptive fields in V1 scale with preferred spatial wavelength. Spatial-wavelength independence of the linking field implies a constant spatial range of signal coupling between neurons with different preferred spatial wavelengths. This might be important for encoding extended broad-band visual features such as edges.

Suboptimal Integration of Reward Magnitude and Prior Reward Likelihood in Categorical Decisions by Monkeys

Sensory decisions may be influenced by non-sensory information regarding reward magnitude or reward likelihood. Given identical sensory information, it is more optimal to choose an option if it is a priori more likely to be correct and hence rewarded (prior reward likelihood bias), or if it yields a larger reward, given that it is the correct choice (reward magnitude bias). Here, we investigated the ability of macaque monkeys to integrate reward magnitude and prior reward likelihood information into a categorical decision about stimuli with high signal strength but variable decision uncertainty. In the asymmetric reward magnitude condition, monkeys over-adjusted their decision criterion such that they chose the highly rewarded alternative far more often than was optimal; in contrast, monkeys did not adjust their decision criterion in response to asymmetric reward likelihood. This finding shows that in this setting, monkeys did not adjust their decision criterion based on the product of reward likelihood and reward magnitude as has been reported to be the case in value-based decisions that do not involve decision uncertainty due to stimulus categorization.