Cingulate dynamics track depression recovery with deep brain stimulation.

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.

An exploration of dimensions of early adversity and the development of functional brain network connectivity during adolescence: Implications for trajectories of internalizing symptoms.

Different dimensions of adversity may affect mental health through distinct neurobiological mechanisms, though current supporting evidence consists largely of cross-sectional associations between threat or deprivation and fronto-limbic circuitry. In this exploratory three-wave longitudinal study spanning ages 9-19 years, we examined the associations between experiences of unpredictability, threat, and deprivation with the development of functional connectivity within and between three brain networks implicated in psychopathology: the salience (SAL), default mode (DMN), and fronto-parietal (FPN) networks, and tested whether network trajectories moderated associations between adversity and changes in internalizing symptoms. Connectivity decreased with age on average; these changes differed by dimension of adversity. Whereas family-level deprivation was associated with lower initial levels and more stability across most networks, unpredictability was associated with stability only in SAL connectivity, and threat was associated with stability in FPN and DMN-SAL connectivity. In youth exposed to higher levels of any adversity, lower initial levels and more stability in connectivity were related to smaller increases in internalizing symptoms. Our findings suggest that whereas deprivation is associated with widespread neurodevelopmental differences in cognitive and emotion processing networks, unpredictability is related selectively to salience detection circuitry. Studies with wider developmental windows should examine whether these neurodevelopmental alterations are adaptive or serve to maintain internalizing symptoms.

New functions of the rodent prelimbic and infralimbic cortex in instrumental behavior.

The prelimbic and infralimbic cortices of the rodent medial prefrontal cortex mediate the effects of context and goals on instrumental behavior. Recent work from our laboratory has expanded this understanding. Results have shown that the prelimbic cortex is important for the modulation of instrumental behavior by the context in which the behavior is learned (but not other contexts), with context potentially being broadly defined (to include at least previous behaviors). We have also shown that the infralimbic cortex is important in the expression of extensively-trained instrumental behavior, regardless of whether that behavior is expressed as a stimulus-response habit or a goal-directed action. Some of the most recent data suggest that infralimbic cortex may control the currently active behavioral state (e.g., habit vs. action or acquisition vs. extinction) when two states have been learned. We have also begun to examine prelimbic and infralimbic cortex function as key nodes of discrete circuits and have shown that prelimbic cortex projections to an anterior region of the dorsomedial striatum are important for expression of minimally-trained instrumental behavior. Overall, the use of an associative learning perspective on instrumental learning has allowed the research to provide new perspectives on how these two "cognitive" brain regions contribute to instrumental behavior.

Frontolimbic alpha activity tracks intentional rest BCI control improvement through mindfulness meditation.

Brain-computer interfaces (BCIs) are capable of translating human intentions into signals controlling an external device to assist patients with severe neuromuscular disorders. Prior work has demonstrated that participants with mindfulness meditation experience evince improved BCI performance, but the underlying neural mechanisms remain unclear. Here, we conducted a large-scale longitudinal intervention study by training participants in mindfulness-based stress reduction (MBSR; a standardized mind-body awareness training intervention), and investigated whether and how short-term MBSR affected sensorimotor rhythm (SMR)-based BCI performance. We hypothesize that MBSR training improves BCI performance by reducing mind wandering and enhancing self-awareness during the intentional rest BCI control, which would mainly be reflected by modulations of default-mode network and limbic network activity. We found that MBSR training significantly improved BCI performance compared to controls and these behavioral enhancements were accompanied by increased frontolimbic alpha activity (9-15 Hz) and decreased alpha connectivity among limbic network, frontoparietal network, and default-mode network. Furthermore, the modulations of frontolimbic alpha activity were positively correlated with the duration of meditation experience and the extent of BCI performance improvement. Overall, these data suggest that mindfulness allows participant to reach a state where they can modulate frontolimbic alpha power and improve BCI performance for SMR-based BCI control.

Infralimbic cortex controls fear memory generalization and susceptibility to extinction during consolidation.

Lesioning or inactivating the infralimbic (IL) subregion of the medial prefrontal cortex before acquisition produces more generalized and extinction-resistant fear memories. However, whether and how it modulates memory specificity and extinction susceptibility while consolidation takes place is still unknown. The present study aims to investigate these questions using muscimol-induced temporary inactivation and anisomycin-induced protein synthesis inhibition in the rat IL following contextual fear conditioning. Results indicate that the IL activity immediately after acquisition, but not six hours later, controls memory generalization over a week, regardless of its strength. Such IL function depends on the context-shock pairing since muscimol induced no changes in animals exposed to immediate shocks or the conditioning context only. Animals in which the IL was inactivated during consolidation extinguished similarly to controls within the session but were unable to recall the extinction memory the following day. Noteworthy, these post-acquisition IL inactivation-induced effects were not associated with changes in anxiety, as assessed in the elevated plus-maze test. Anisomycin results indicate that the IL protein synthesis during consolidation contributes more to producing extinction-sensitive fear memories than memory specificity. Collectively, present results provide evidence for the IL's role in controlling generalization and susceptibility to extinction during fear memory consolidation.

Disorganized Attachment pattern affects the perception of Affective Touch.

Touch, such as affective caress, can be interpreted as being pleasant. The emotional valence that is assigned to touch is related to certain bottom-up factors, such as the optimal activation of C-tactile (CT) afferents. Tactile processing with a hedonic or emotional component has been defined as affective touch-a component that CT fibers are likely to convey. Tactile deficiencies are frequent in the psychiatric population but also in healthy people with disorganized attachment; accordingly, it is likely that affective difficulties in adults with disorganized attachment are reflected in altered perception of affective touch. To test this hypothesis, we combined methods from clinical psychology, psychophysics, and neuroimaging. We found that people with a history of traumatic parental bonds and a disorganized attachment pattern perceive a "caress-like" stimulus as being unpleasant, whereas participants with organized attachment consider the same tactile stimulation to be pleasant. Further, unlike in organized adults, the responses of disorganized adults to CT and non-CT stimulation activated limbic and paralimbic structures in a fight-or-flight manner, suggesting that early experiences with parental deficiencies shape the physiological responses of peripheral CT fibers and central nervous networks.

Movement context modulates neuronal activity in motor and limbic-associative domains of the human parkinsonian subthalamic nucleus.

The subthalamic nucleus (STN), a preferred target for treating movement disorders, has a crucial role in inhibition and execution of movement. To better understand the mechanism of movement regulation in the STN of Parkinson's disease patients, we compared the same movement with different context, facilitation vs. inhibition context. We recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (off medications, n = 43 patients, 173 recording sites) performed increasingly complex oddball paradigms with frequent and deviant tones: first, passive listening to tone series with no movement ('None-Go' task, n = 7, 28 recording sites); second, pressing a button after every tone ('All-Go' task, n = 7, 26 recording sites); and third, pressing a button only for frequent tones, thus adding inhibition of movement following deviant tones ('Go-NoGo' task, n = 29, 119 recording sites). The STN responded mainly to movement-involving tasks. In the limbic-associative STN, evoked response to the deviant tone (inhibitory cue) was not significantly different between the Go-NoGo and the All-Go task. However, the evoked response to the frequent tone (go cue) in the Go-NoGo task was significantly reduced. The reduction was mainly prominent in the negative component of the evoked response amplitude aligned to the press. Successful movement inhibition was correlated with higher baseline activity. We suggest that the STN in Parkinson's disease patients adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the limbic- associative STN domains in movement planning and in global movement regulation.

Dopamine receptors mediate strategy abandoning via modulation of a specific prelimbic cortex-nucleus accumbens pathway in mice.

The ability to abandon old strategies and adopt new ones is essential for survival in a constantly changing environment. While previous studies suggest the importance of the prefrontal cortex and some subcortical areas in the generation of strategy-switching flexibility, the fine neural circuitry and receptor mechanisms involved are not fully understood. In this study, we showed that optogenetic excitation and inhibition of the prelimbic cortex-nucleus accumbens (NAc) pathway in the mouse respectively enhances and suppresses strategy-switching ability in a cross-modal spatial-egocentric task. This ability is dependent on an intact dopaminergic tone in the NAc, as local dopamine denervation impaired the performance of the animal in the switching of tasks. In addition, based on a brain-slice preparation obtained from Drd2-EGFP BAC transgenic mice, we demonstrated direct innervation of D2 receptor-expressing medium spiny neurons (D2-MSNs) in the NAc by prelimbic cortical neurons, which is under the regulation by presynaptic dopamine receptors. While presynaptic D1-type receptor activation enhances the glutamatergic transmission from the prelimbic cortex to D2-MSNs, D2-type receptor activation suppresses this synaptic connection. Furthermore, manipulation of this pathway by optogenetic activation or administration of a D1-type agonist or a D2-type antagonist could restore impaired task-switching flexibility in mice with local NAc dopamine depletion; this restoration is consistent with the effects of knocking down the expression of specific dopamine receptors in the pathway. Our results point to a critical role of a specific prelimbic cortex-NAc subpathway in mediating strategy abandoning, allowing the switching from one strategy to another in problem solving.

Anteroventral bed nuclei of the stria terminalis neurocircuitry: Towards an integration of HPA axis modulation with coping behaviors - Curt Richter Award Paper 2017.

A network of interconnected cell groups in the limbic forebrain regulates hypothalamic-pituitary-adrenal (HPA) axis activation and behavioral responses to emotionally stressful experiences, and chronic disruption of these systems chronically is implicated in the pathogenesis of psychiatric illnesses. A significant challenge has been to unravel the circuitry and mechanisms providing for regulation of HPA activity, as these limbic forebrain regions do not provide any direct innervation of HPA effector cell groups in the paraventricular hypothalamus (PVH). Moreover, information regarding how endocrine and behavioral responses are integrated has remained obscure. Here we summarize work from our laboratory showing that anteroventral (av) bed nuclei of the stria terminalis (BST) acts as a point of convergence between the limbic forebrain and PVH, receiving and coordinating upstream influences, and restraining HPA axis output in response to inescapable stressors. Recent studies highlight a more expansive modulatory role for avBST as one that coordinates HPA-inhibitory influences while concurrently suppressing passive behavioral responses via divergent pathways. avBST is uniquely positioned to convey endocrine and behavioral alterations resulting from chronic stress exposure, such as HPA axis hyperactivity and increased passive coping strategies, that may result from synaptic reorganization in upstream limbic cortical regions. We discuss how these studies give new insights into understanding the systems-level organization of stress response circuitry, the neurobiology of coping styles, and BST circuit dysfunction in stress-related psychiatric disorders.

Greater cortical thickness within the limbic visceromotor network predicts higher levels of trait emotional awareness.

Previous studies of trait emotional awareness (EA) have not yet examined whether differences in cortical structure might account for differences in EA. Based on previous research on the relationship between EA and both emotion conceptualization and visceromotor control processes, we tested two hypotheses in a sample of 26 healthy participants: that higher EA would be predicted by greater cortical thickness within (1) regions of the default mode network (DMN; linked with conceptualization processes), and/or (2) regions of the limbic network (linked with affect generation and visceromotor control processes). A non-significant correlation was found between EA and cortical thickness in the DMN. In contrast, a significant positive correlation was observed between EA and cortical thickness within the limbic network. These findings suggest that the structural integrity of cortical regions involved in the generation of affective bodily reactions may play a more important role in explaining differences in EA than previously thought.

StimVision Software: Examples and Applications in Subcallosal Cingulate Deep Brain Stimulation for Depression.

OBJECTIVE: Create a software tool to facilitate tractography-based deep brain stimulation (DBS) electrode targeting within the patient-specific stereotactic coordinate system used in the operating room. APPROACH: StimVision was developed with Visualization Toolkit libraries and integrates four major components: 1) medical image visualization, 2) tractography visualization, 3) DBS electrode positioning, and 4) DBS activation volume calculation with tractography intersection. RESULTS: Initial applications of StimVision are focused on the study of subcallosal cingulate (SCC) DBS for the treatment of depression. Retrospective modeling results on SCC DBS have suggested that direct stimulation of a specific collection of tractographic pathways are necessary for therapeutic benefit; thereby creating a tractography-based DBS surgical targeting hypotheses. StimVision is the tool we created to facilitate prospective clinical evaluation of that hypothesis. SIGNIFICANCE: Retrospective tractography-based analyses are common in DBS research; however, intraoperative software tools for interactive selection of a tractography-based DBS target are not readily available. StimVision provides an academic research tool to assist clinical implementation of new DBS targeting strategies and postoperative evaluation of targeting outcome.

A Cognition-Related Neural Oscillation Pattern, Generated in the Prelimbic Cortex, Can Control Operant Learning in Rats.

The prelimbic (PrL) cortex constitutes one of the highest levels of cortical hierarchy dedicated to the execution of adaptive behaviors. We have identified a specific local field potential (LFP) pattern generated in the PrL cortex and associated with cognition-related behaviors. We used this pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected θ to ß-γ (θ/ß-γ) transition pattern across training sessions. The selected LFP pattern appeared to coincide with a significant decrease in the firing of PrL pyramidal neurons and did not seem to propagate to other cortical or subcortical areas. An indication of the PrL cortex's cognitive nature is that the experimental disruption of this θ/ß-γ transition pattern prevented the proper performance of the acquired task without affecting the generation of other motor responses. The use of this LFP pattern to trigger an operant task evoked only minor changes in its electrophysiological properties. Thus, the PrL cortex has the capability of generating an oscillatory pattern for dealing with environmental constraints. In addition, the selected θ/ß-γ transition pattern could be a useful tool to activate the presentation of external cues or to modify the current circumstances.SIGNIFICANCE STATEMENT Brain-machine interfaces represent a solution for physically impaired people to communicate with external devices. We have identified a specific local field potential pattern generated in the prelimbic cortex and associated with goal-directed behaviors. We used the pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected field potential pattern across training. The selected pattern was not modified when used to activate the touch screen. Electrical stimulation of the recording site prevented the proper performance of the task. Our findings show that the prelimbic cortex can generate oscillatory patterns that rats can use to control their environment for achieving specific goals.

Neural Activity while Imitating Emotional Faces is Related to Both Lower and Higher-Level Social Cognitive Performance.

Imitation and observation of actions and facial emotional expressions activates the human fronto-parietal mirror network. There is skepticism regarding the role of this low-level network in more complex high-level social behaviour. We sought to test whether neural activation during an observation/imitation task was related to both lower and higher level social cognition. We employed an established observe/imitate task of emotional faces during functional MRI in 28 healthy adults, with final analyses based on 20 individuals following extensive quality control. Partial least squares (PLS) identified patterns of relationships between spatial activation and a battery of objective out-of-scanner assessments that index lower and higher-level social cognitive performance, including the Penn emotion recognition task, reading the mind in the eyes, the awareness of social inference test (TASIT) parts 1, 2, and 3, and the relationships across domains (RAD) test. Strikingly, activity in limbic, right inferior frontal, and inferior parietal areas during imitation of emotional faces correlated with performance on emotion evaluation (TASIT1), social inference - minimal (TASIT2), social inference - enriched (TASIT3), and the RAD tests. These results show a role for this network in both lower-level and higher-level social cognitive processes which are collectively critical for social functioning in everyday life.

[Spatial Cognition and Episodic Memory Formation in the Limbic Cortex].

The limbic lobe defined by Broca is a cortical region with highly diverse structure and functions, and comprises the paleo-, archi-, and neocortices as well as their transitional zones. In the limbic lobe, Brodmann designated areas 27, 28, 34, 35, and 36 adjacent to the hippocampus, and areas 23, 24, 25, 26, 29, 30, 31, 32, and 33 around the corpus callosum. In the current literature, areas 27 and 28 correspond to the presubiculum and entorhinal cortex, respectively. Area 34 represents the cortico-medial part of the amygdaloid complex. Areas 35 and 36 roughly cover the perirhinal and parahippocampal cortices. Areas 24, 25, 32, and 33 belong to the anterior cingulate gyrus, while areas 23, 26, 29, 30, and 31 to the posterior cingulate gyrus. Areas 25, 32, and the anteroinferior portion of area 24 are deeply involved in emotional responses, particularly in their autonomic functions, through reciprocal connections with the amygdaloid complex, anterior thalamus and projections to the brainstem and spinal visceral centers. Areas 29 and 30 have dense reciprocal connections with areas 23 and 31, the dorsolateral prefrontal areas, and the regions related to the hippocampus. They play pivotal roles in mediating spatial cognition, working memory processing, and episodic memory formation.

Individual variation in intentionality in the mind-wandering state is reflected in the integration of the default-mode, fronto-parietal, and limbic networks.

Mind-wandering has a controversial relationship with cognitive control. Existing psychological evidence supports the hypothesis that episodes of mind-wandering reflect a failure to constrain thinking to task-relevant material, as well the apparently alternative view that control can facilitate the expression of self-generated mental content. We assessed whether this apparent contradiction arises because of a failure to consider differences in the types of thoughts that occur during mind-wandering, and in particular, the associated level of intentionality. Using multi-modal magnetic resonance imaging (MRI) analysis, we examined the cortical organisation that underlies inter-individual differences in descriptions of the spontaneous or deliberate nature of mind-wandering. Cortical thickness, as well as functional connectivity analyses, implicated regions relevant to cognitive control and regions of the default-mode network for individuals who reported high rates of deliberate mind-wandering. In contrast, higher reports of spontaneous mind-wandering were associated with cortical thinning in parietal and posterior temporal regions in the left hemisphere (which are important in the control of cognition and attention) as well as heightened connectivity between the intraparietal sulcus and a region that spanned limbic and default-mode regions in the ventral inferior frontal gyrus. Finally, we observed a dissociation in the thickness of the retrosplenial cortex/lingual gyrus, with higher reports of spontaneous mind-wandering being associated with thickening in the left hemisphere, and higher repots of deliberate mind-wandering with thinning in the right hemisphere. These results suggest that the intentionality of the mind-wandering state depends on integration between the control and default-mode networks, with more deliberation being associated with greater integration between these systems. We conclude that one reason why mind-wandering has a controversial relationship with control is because it depends on whether the thoughts emerge in a deliberate or spontaneous fashion.

Distinct memory engrams in the infralimbic cortex of rats control opposing environmental actions on a learned behavior.

Conflicting evidence exists regarding the role of infralimbic cortex (IL) in the environmental control of appetitive behavior. Inhibition of IL, irrespective of its intrinsic neural activity, attenuates not only the ability of environmental cues predictive of reward availability to promote reward seeking, but also the ability of environmental cues predictive of reward omission to suppress this behavior. Here we report that such bidirectional behavioral modulation in rats is mediated by functionally distinct units of neurons (neural ensembles) that are concurrently localized within the same IL brain area but selectively reactive to different environmental cues. Ensemble-specific neural activity is thought to function as a memory engram representing a learned association between environment and behavior. Our findings establish the causal evidence for the concurrent existence of two distinct engrams within a single brain site, each mediating opposing environmental actions on a learned behavior.

Lower neighborhood quality in adolescence predicts higher mesolimbic sensitivity to reward anticipation in adulthood.

Life history theory suggests that adult reward sensitivity should be best explained by childhood, but not current, socioeconomic conditions. In this functional magnetic resonance imaging (fMRI) study, 83 participants from a larger longitudinal sample completed the monetary incentive delay (MID) task in adulthood (∼25 years old). Parent-reports of neighborhood quality and parental SES were collected when participants were 13 years of age. Current income level was collected concurrently with scanning. Lower adolescent neighborhood quality, but neither lower current income nor parental SES, was associated with heightened sensitivity to the anticipation of monetary gain in putative mesolimbic reward areas. Lower adolescent neighborhood quality was also associated with heightened sensitivity to the anticipation of monetary loss activation in visuo-motor areas. Lower current income was associated with heightened sensitivity to anticipated loss in occipital areas and the operculum. We tested whether externalizing behaviors in childhood or adulthood could better account for neighborhood quality findings, but they did not. Findings suggest that neighborhood ecology in adolescence is associated with greater neural reward sensitivity in adulthood above the influence of parental SES or current income and not mediated through impulsivity and externalizing behaviors.

Identifying the Neural Substrates of Procrastination: a Resting-State fMRI Study.

Procrastination is a prevalent problematic behavior that brings serious consequences to individuals who suffer from it. Although this phenomenon has received increasing attention from researchers, the underpinning neural substrates of it is poorly studied. To examine the neural bases subserving procrastination, the present study employed resting-state fMRI. The main results were as follows: (1) the behavioral procrastination was positively correlated with the regional activity of the ventromedial prefrontal cortex (vmPFC) and the parahippocampal cortex (PHC), while negatively correlated with that of the anterior prefrontal cortex (aPFC). (2) The aPFC-seed connectivity with the anterior medial prefrontal cortex and the posterior cingulate cortex was positively associated with procrastination. (3) The connectivity between vmPFC and several other regions, such as the dorsomedial prefrontal cortex, the bilateral inferior prefrontal cortex showed a negative association with procrastination. These results suggested that procrastination could be attributed to, on the one hand, hyper-activity of the default mode network (DMN) that overrides the prefrontal control signal; while on the other hand, the failure of top-down control exerted by the aPFC on the DMN. Therefore, the present study unravels the biomarkers of procrastination and provides treatment targets for procrastination prevention.

Genetic-Based Dissection Unveils the Inputs and Outputs of Striatal Patch and Matrix Compartments.

The striatum contains neurochemically defined compartments termed patches and matrix. Previous studies suggest patches preferentially receive limbic inputs and project to dopamine neurons in substantia nigra pars compacta (SNc), whereas matrix neurons receive sensorimotor inputs and do not innervate SNc. Using BAC-Cre transgenic mice with viral tracing techniques, we mapped brain-wide differences in the input-output organization of the patch/matrix. Findings reveal a displaced population of striatal patch neurons termed "exo-patch," which reside in matrix zones but have neurochemistry, connectivity, and electrophysiological characteristics resembling patch neurons. Contrary to previous studies, results show patch/exo-patch and matrix neurons receive both limbic and sensorimotor information. A novel inhibitory projection from bed nucleus of the stria terminalis to patch/exo-patch neurons was revealed. Projections to SNc were found to originate from patch/exo-patch and matrix neurons. These findings redefine patch/matrix beyond traditional neurochemical topography and reveal new principles about their input-output connectivity, providing a foundation for future functional studies.

A quantitative comparison of the hemispheric, areal, and laminar origins of sensory and motor cortical projections to the superior colliculus of the cat.

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a substantial projection. Conversely, only one area of the auditory orienting system, the auditory field of the anterior ectosylvian sulcus (fAES), and no area involved in somatosensory orienting, shows significant corticotectal inputs. Although small relative to visual inputs, the projection from the fAES is of particular interest, as it represents the only bilateral cortical input to the SC. This detailed, quantitative study allows for comparison across modalities in an animal that serves as a useful model for both auditory and visual perception. Moreover, the differences in patterns of corticotectal projections between modalities inform the ways in which orienting systems are modulated by cortical feedback. J. Comp. Neurol. 524:2623-2642, 2016. © 2016 Wiley Periodicals, Inc.