An integrative role for the superior colliculus in selecting targets for movements.

A fundamental goal of systems neuroscience is to understand the neural mechanisms underlying decision making. The midbrain superior colliculus (SC) is known to be central to the selection of one among many potential spatial targets for movements, which represents an important form of decision making that is tractable to rigorous experimental investigation. In this review, we first discuss data from mammalian models-including primates, cats, and rodents-that inform our understanding of how neural activity in the SC underlies the selection of targets for movements. We then examine the anatomy and physiology of inputs to the SC from three key regions that are themselves implicated in motor decisions-the basal ganglia, parabrachial region, and neocortex-and discuss how they may influence SC activity related to target selection. Finally, we discuss the potential for methodological advances to further our understanding of the neural bases of target selection. Our overarching goal is to synthesize what is known about how the SC and its inputs act together to mediate the selection of targets for movements, to highlight open questions about this process, and to spur future studies addressing these questions.

Model discovery to link neural activity to behavioral tasks.

Brains are not engineered solutions to a well-defined problem but arose through selective pressure acting on random variation. It is therefore unclear how well a model chosen by an experimenter can relate neural activity to experimental conditions. Here, we developed 'model identification of neural encoding (MINE).' MINE is an accessible framework using convolutional neural networks (CNNs) to discover and characterize a model that relates aspects of tasks to neural activity. Although flexible, CNNs are difficult to interpret. We use Taylor decomposition approaches to understand the discovered model and how it maps task features to activity. We apply MINE to a published cortical dataset as well as experiments designed to probe thermoregulatory circuits in zebrafish. Here, MINE allowed us to characterize neurons according to their receptive field and computational complexity, features that anatomically segregate in the brain. We also identified a new class of neurons that integrate thermosensory and behavioral information that eluded us previously when using traditional clustering and regression-based approaches.

Current Applications of Diffusion Tensor Imaging and Tractography in Intracranial Tumor Resection.

In the treatment of brain tumors, surgical intervention remains a common and effective therapeutic option. Recent advances in neuroimaging have provided neurosurgeons with new tools to overcome the challenge of differentiating healthy tissue from tumor-infiltrated tissue, with the aim of increasing the likelihood of maximizing the extent of resection volume while minimizing injury to functionally important regions. Novel applications of diffusion tensor imaging (DTI), and DTI-derived tractography (DDT) have demonstrated that preoperative, non-invasive mapping of eloquent cortical regions and functionally relevant white matter tracts (WMT) is critical during surgical planning to reduce postoperative deficits, which can decrease quality of life and overall survival. In this review, we summarize the latest developments of applying DTI and tractography in the context of resective surgery and highlight its utility within each stage of the neurosurgical workflow: preoperative planning and intraoperative management to improve postoperative outcomes.

Biopsy Confirmed Glioma Recurrence Predicted by Multi-Modal Neuroimaging Metrics.

Histopathological verification is currently required to differentiate tumor recurrence from treatment effects related to adjuvant therapy in patients with glioma. To bypass the complications associated with collecting neural tissue samples, non-invasive classification methods are needed to alleviate the burden on patients while providing vital information to clinicians. However, uncertainty remains as to which tissue features on magnetic resonance imaging (MRI) are useful. The primary objective of this study was to quantitatively assess the reliability of combining MRI and diffusion tensor imaging metrics to discriminate between tumor recurrence and treatment effects in histopathologically identified biopsy samples. Additionally, this study investigates the noise adjuvant radiation therapy introduces when discriminating between tissue types. In a sample of 41 biopsy specimens, from a total of 10 patients, we derived region-of-interest samples from MRI data in the ipsilateral hemisphere that encompassed biopsies obtained during resective surgery. This study compares normalized intensity values across histopathology classifications and contralesional volumes reflected across the midline. Radiation makes noninvasive differentiation of abnormal-nontumor tissue to tumor recurrence much more difficult. This is because radiation exhibits opposing behavior on key MRI modalities: specifically, on post-contrast T1, FLAIR, and GFA. While radiation makes noninvasive differentiation of tumor recurrence more difficult, using a novel analysis of combined MRI metrics combined with clinical annotation and histopathological correlation, we observed that it is possible to successfully differentiate tumor tissue from other tissue types. Additional work will be required to expand upon these findings.

Sex differences in aggression: Differential roles of 5-HT2, neuropeptide F and tachykinin.

Despite the conserved function of aggression across taxa in obtaining critical resources such as food and mates, serotonin's (5-HT) modulatory role on aggressive behavior appears to be largely inhibitory for vertebrates but stimulatory for invertebrates. However, critical gaps exist in our knowledge of invertebrates that need to be addressed before definitively stating opposing roles for 5-HT and aggression. Specifically, the role of 5-HT receptor subtypes are largely unknown, as is the potential interactive role of 5-HT with other neurochemical systems known to play a critical role in aggression. Similarly, the influence of these systems in driving sex differences in aggressive behavior of invertebrates is not well understood. Here, we investigated these questions by employing complementary approaches in a novel invertebrate model of aggression, the stalk-eyed fly. A combination of altered social conditions, pharmacological manipulation and 5-HT2 receptor knockdown by siRNA revealed an inhibitory role of this receptor subtype on aggression. Additionally, we provide evidence for 5-HT2's involvement in regulating neuropeptide F activity, a suspected inhibitor of aggression. However, this function appears to be stage-specific, altering only the initiation stage of aggressive conflicts. Alternatively, pharmacologically increasing systemic concentrations of 5-HT significantly elevated the expression of the neuropeptide tachykinin, which did not affect contest initiation but instead promoted escalation via production of high intensity aggressive behaviors. Notably, these effects were limited solely to males, with female aggression and neuropeptide expression remaining unaltered by any manipulation that affected 5-HT. Together, these results demonstrate a more nuanced role for 5-HT in modulating aggression in invertebrates, revealing an important interactive role with neuropeptides that is more reminiscent of vertebrates. The sex-differences described here also provide valuable insight into the evolutionary contexts of this complex behavior.

Method for localizing intraoperative recordings from deep brain stimulation surgery using post-operative structural MRI.

BACKGROUND: Implantation of deep brain stimulation (DBS) electrodes for the treatment of involuntary movement disorders, such as Parkinson's disease, routinely relies on the use of intraoperative electrophysiological confirmation to identify the optimal therapeutic target in the brain. However, only a few options exist to visualize the relative anatomic localization of intraoperative electrophysiological recordings with respect to post-operative imaging. We have developed a novel processing pipeline to visualize intraoperative electrophysiological signals registered to post-operative neuroanatomical imaging. NEW METHOD: We developed a processing pipeline built on the use of ITK-SNAP and custom MATLAB scripts to visualize the anatomical localization of intraoperative electrophysiological recordings mapped onto the post-operative MRI following implantation of DBS electrodes. This method combines the user-defined relevant electrophysiological parameters measured during the surgery with a manual segmentation of the DBS electrode from post-operative MRI; mapping the microelectrode recording (MER) depths along the DBS lead track. RESULTS: We demonstrate the use of our processing pipeline on data from Parkinson's disease patients undergoing DBS implantation targeted to the subthalamic nucleus (STN). The primary processing components of the pipeline are: extrapolation of the lead wire and alignment of intraoperative electrophysiology. CONCLUSION: We describe the use of a processing pipeline to aid clinicians and researchers engaged in deep brain stimulation work to correlate and visualize the intraoperative recording data with the post-operative DBS trajectory.

Mesencephalic representations of recent experience influence decision making.

Decisions are influenced by recent experience, but the neural basis for this phenomenon is not well understood. Here, we address this question in the context of action selection. We focused on activity in the pedunculopontine tegmental nucleus (PPTg), a mesencephalic region that provides input to several nuclei in the action selection network, in well-trained mice selecting actions based on sensory cues and recent trial history. We found that, at the time of action selection, the activity of many PPTg neurons reflected the action on the previous trial and its outcome, and the strength of this activity predicted the upcoming choice. Further, inactivating the PPTg predictably decreased the influence of recent experience on action selection. These findings suggest that PPTg input to downstream motor regions, where it can be integrated with other relevant information, provides a simple mechanism for incorporating recent experience into the computations underlying action selection.

Assessment strategies and fighting patterns in animal contests: a role for serotonin?

Accurate assessment of the probability of success in an aggressive confrontation with a conspecific is critical to the survival and fitness of the individuals. Various game theory models have examined these assessment strategies under the assumption that contests should favor the animal with the greater resource-holding potential (RHP), body size typically being the proxy. Mutual assessment asserts that an individual can assess their own RHP relative to their opponent, allowing the inferior animal the chance to flee before incurring unnecessary costs. The model of self-determined persistence, however, assumes that an individual will fight to a set personal threshold, independent of their opponent's RHP. Both models have been repeatedly tested using size as a proxy for RHP, with neither receiving unambiguous support. Here we present both morphological and neurophysiological data from size-matched and mismatched stalk-eyed fly fights. We discovered differing fighting strategies between winners and losers. Winners readily escalated encounters to higher intensity and physical contact and engaged in less low-intensity, posturing behaviors compared with losers. Although these fighting strategies were largely independent of size, they were associated with elevated levels of 5-HT. Understanding the neurophysiological factors responsible for mediating the motivational state of opponents could help resolve the inconsistencies seen in current game theory models. Therefore, we contend that current studies using only size as a proxy for RHP may be inadequate in determining the intricacies of fighting ability and that future studies investigating assessment strategies and contest outcome should include neurophysiological data.

Optogenetic investigation of the role of the superior colliculus in orienting movements.

In vivo studies have demonstrated that the superior colliculus (SC) integrates sensory information and plays a role in controlling orienting motor output. However, how the complex microcircuitry within the SC, as documented by slice studies, subserves these functions is unclear. Optogenetics affords the potential to examine, in behaving animals, the functional roles of specific neuron types that comprise heterogeneous nuclei. As a first step toward understanding how SC microcircuitry underlies motor output, we applied optogenetics to mice performing an odor discrimination task in which sensory decisions are reported by either a leftward or rightward SC-dependent orienting movement. We unilaterally expressed either channelrhodopsin-2 or halorhodopsin in the SC and delivered light in order to excite or inhibit motor-related SC activity as the movement was planned. We found that manipulating SC activity predictably affected the direction of the selected movement in a manner that depended on the difficulty of the odor discrimination. This study demonstrates that the SC plays a similar role in directional orienting movements in mice as it does in other species, and provides a framework for future investigations into how specific SC cell types contribute to motor control.