Cortical Pathways Research Articles

Lack of cortical or Ia-afferent spinal pathway involvement in muscle force loss after passive static stretching.

This study investigated whether modulation of corticospinal-motoneuronal excitability and/or synaptic transmission of the Ia afferent spinal reflex contributes to decreases in voluntary activation and muscular force after an acute bout of prolonged static muscle stretching. Fifteen men performed five 60-s constant-torque stretches (15-s rest intervals; total duration 5 min) of the plantar flexors on an isokinetic dynamometer and a nonstretching control condition in random order on 2 separate days. Maximum isometric plantar flexor torque and triceps surae muscle electromyographic activity (normalized to M wave; EMG/M) were simultaneously recorded immediately before and after each condition. Motor-evoked potentials (using transcranial magnetic stimulation) and H-reflexes were recorded from soleus during EMG-controlled submaximal contractions (23.4 ± 6.9% EMG maximum). No changes were detected in the control condition. After stretching, however, peak torque (mean ± SD; -14.3 ± 7.0%) and soleus EMG/M (-17.8 ± 6.2%) decreased, and these changes were highly correlated (r = 0.83). No changes were observed after stretching in soleus MEP or H-reflex amplitudes measured during submaximal contractions, and interindividual variability of changes was not correlated with changes in EMG activity or maximum torque. During EMG-controlled submaximal contractions, torque production was significantly decreased after stretching (-22.7 ± 15.0%), indicating a compromised muscular output. These data provide support that changes in the excitability of the corticospinal-motoneuronal and Ia afferent spinal reflex pathways do not contribute to poststretch neural impairment.NEW & NOTEWORTHY This study is the first to specifically examine potential sites underlying the decreases in neural activation of muscle and force production after a bout of muscle stretching. However, no changes were found in either the H-reflex or motor-evoked potential amplitude during submaximal contractions.

Temporal Gating of Synaptic Competition in the Amygdala by Cannabinoid Receptor Activation.

The acquisition of fear memories involves plasticity of the thalamic and cortical pathways to the lateral amygdala (LA). In turn, the maintenance of synaptic plasticity requires the interplay between input-specific synaptic tags and the allocation of plasticity-related proteins. Based on this interplay, weakly activated synapses can express long-lasting forms of synaptic plasticity by cooperating with strongly activated synapses. Increasing the number of activated synapses can shift cooperation to competition. Synaptic cooperation and competition can determine whether two events, separated in time, are associated or whether a particular event is selected for storage. The rules that determine whether synapses cooperate or compete are unknown. We found that synaptic cooperation and competition, in the LA, are determined by the temporal sequence of cortical and thalamic stimulation and that the strength of the synaptic tag is modulated by the endocannabinoid signaling. This modulation is particularly effective in thalamic synapses, supporting a critical role of endocannabinoids in restricting thalamic plasticity. Also, we found that the availability of synaptic proteins is activity-dependent, shifting competition to cooperation. Our data present the first evidence that presynaptic modulation of synaptic activation, by the cannabinoid signaling, functions as a temporal gating mechanism limiting synaptic cooperation and competition.

Controlling consciousness.

In macaques, the central thalamus modulates cortical feedforward and feedback pathways to control levels of consciousness.

A Prototypical Template for Rapid Face Detection Is Embedded in the Monkey Superior Colliculus.

Human babies respond preferentially to faces or face-like images. It has been proposed that an innate and rapid face detection system is present at birth before the cortical visual pathway is developed in many species, including primates. However, in primates, the visual area responsible for this process is yet to be unraveled. We hypothesized that the superior colliculus (SC) that receives direct and indirect retinal visual inputs may serve as an innate rapid face-detection system in primates. To test this hypothesis, we examined the responsiveness of monkey SC neurons to first-order information of faces required for face detection (basic spatial layout of facial features including eyes, nose, and mouth), by analyzing neuronal responses to line drawing images of: (1) face-like patterns with contours and properly placed facial features; (2) non-face patterns including face contours only; and (3) nonface random patterns with contours and randomly placed face features. Here, we show that SC neurons respond stronger and faster to upright and inverted face-like patterns compared to the responses to nonface patterns, regardless of contrast polarity and contour shapes. Furthermore, SC neurons with central receptive fields (RFs) were more selective to face-like patterns. In addition, the population activity of SC neurons with central RFs can discriminate face-like patterns from nonface patterns as early as 50 ms after the stimulus onset. Our results provide strong neurophysiological evidence for the involvement of the primate SC in face detection and suggest the existence of a broadly tuned template for face detection in the subcortical visual pathway.

High-definition transcranial direct current stimulation dissociates fronto-visual theta lateralization during visual selective attention.

Visual attention involves discrete multispectral oscillatory responses in visual and 'higher-order' prefrontal cortices. Prefrontal cortex laterality effects during visual selective attention are poorly characterized. High-definition transcranial direct current stimulation dynamically modulated right-lateralized fronto-visual theta oscillations compared to those observed in left fronto-visual pathways. Increased connectivity in right fronto-visual networks after stimulation of the left dorsolateral prefrontal cortex resulted in faster task performance in the context of distractors. Our findings show clear laterality effects in theta oscillatory activity along prefrontal-visual cortical pathways during visual selective attention. Studies of visual attention have implicated oscillatory activity in the recognition, protection and temporal organization of attended representations in visual cortices. These studies have also shown that higher-order regions such as the prefrontal cortex are critical to attentional processing, but far less is understood regarding prefrontal laterality differences in attention processing. To examine this, we selectively applied high-definition transcranial direct current stimulation (HD-tDCS) to the left or right dorsolateral prefrontal cortex (DLPFC). We predicted that HD-tDCS of the left versus right prefrontal cortex would differentially modulate performance on a visual selective attention task, and alter the underlying oscillatory network dynamics. Our randomized crossover design included 27 healthy adults that underwent three separate sessions of HD-tDCS (sham, left DLPFC and right DLPFC) for 20min. Following stimulation, participants completed an attention protocol during magnetoencephalography. The resulting oscillatory dynamics were imaged using beamforming, and peak task-related neural activity was subjected to dynamic functional connectivity analyses to evaluate the impact of stimulation site (i.e. left and right DLPFC) on neural interactions. Our results indicated that HD-tDCS over the left DLPFC differentially modulated right fronto-visual functional connectivity within the theta band compared to HD-tDCS of the right DLPFC and further, specifically modulated the oscillatory response for detecting targets among an array of distractors. Importantly, these findings provide network-specific insight into the complex oscillatory mechanisms serving visual selective attention.

Hippocampal and prefrontal cortical NMDA receptors mediate the interactive effects of olanzapine and lithium in memory retention in rats: the involvement of CAMKII-CREB signaling pathways.

Treatment of bipolar disorder (BPD) with lithium and olanzapine concurrent administration is a major medicine issue with the elusive neurobiological mechanisms underlying the cognitive function. To clarify the precise mechanisms involved, the possible role of the hippocampus (HPC) and prefrontal cortical (PFC) NMDA receptors and CAMKII-CREB signaling pathway in the interactive effects of lithium and olanzapine in memory consolidation was evaluated. The dorsal hippocampal CA1 regions of adult male Wistar rats were bilaterally cannulated and a step-through inhibitory avoidance apparatus was used to assess memory consolidation. The changes in p-CAMKII/CAMKII and p-CREB/CREB ratio in the HPC and the PFC were measured by Western blot analysis. Post-training administration of lithium (20, 30, and 40mg/kg, i.p.) dose-dependently decreased memory consolidation whereas post-training administration olanzapine (2 and 5mg/kg, i.p.) increased memory consolidation. Post-training administration of certain doses of olanzapine (1, 2, and 5mg/kg, i.p.) dose-dependently improved lithium-induced memory impairment. Post-training administration of ineffective doses of the NMDA (10-5 and 10-4μg/rat, intra-CA1) plus an ineffective dose of olanzapine (1mg/kg, i.p.) dose-dependently improved the lithium-induced memory impairment. Post-training microinjection of ineffective doses of the NMDA (10-5 and 10-4μg/rat, intra-CA1) dose-dependently potentiated the memory improvement induced by olanzapine (1mg/kg, i.p.) on lithium-induced memory impairment which was associated with the enhancement of the levels of p-CAMKII and p-CREB in the HPC and the PFC. Post-training microinjection of ineffective doses of the noncompetitive NMDA receptor antagonist, MK-801 (0.0625 and 0.0125μg/rat, intra-CA1), dose-dependently decreased the memory improvement induced by olanzapine (5mg/kg, i.p.) on lithium-induced memory impairment which was related to the reduced levels of HPC and PFC CAMKII-CREB. The results strongly revealed that there is a functional interaction among lithium and olanzapine through the HPC and the PFC NMDA receptor mechanism in memory consolidation which is mediated with the CAMKII-CREB signaling pathway.

Developmental dynamics of the periventricular parietal crossroads of growing cortical pathways in the fetal brain – In vivo fetal MRI with histological correlation

The periventricular crossroads have been described as transient structures of the fetal brain where major systems of developing fibers intersect. The triangular parietal crossroad constitutes one major crossroad region. By combining in vivo and post-mortem fetal MRI with histological and immunohistochemical methods, we aimed to characterize these structures.Data from 529 in vivo and 66 post-mortem MRI examinations of fetal brains between gestational weeks (GW) 18–39 were retrospectively reviewed. In each fetus, the area adjacent to the trigone of the lateral ventricles at the exit of the posterior limb of the internal capsule (PLIC) was assessed with respect to signal intensity, size, and shape on T2-weighted images. In addition, by using in vivo diffusion tensor imaging (DTI), the main fiber pathways that intersect in these areas were identified. In order to explain the in vivo features of the parietal crossroads (signal intensity and developmental profile), we analyzed 23 post-mortem fetal human brains, between 16 and ​40 GW of age, processed by histological and immunohistochemical methods. The parietal crossroads were triangular-shaped areas with the base in the continuity of the PLIC, adjacent to the germinal matrix and the trigone of the lateral ventricles, with the tip pointing toward the subplate. These areas appeared hyperintense to the subplate, and corresponded to a convergence zone of the developing external capsule, the PLIC, and the fronto-occipital association fibers. They were best detected between GW 25–26, and, at term, they became isointense to the adjacent structures. The immunohistochemical results showed a distinct cellular, fibrillar, and extracellular matrix arrangement in the parietal crossroads, depending on the stage of development, which influenced the MRI features.The parietal crossroads are transient, but important structures in white matter maturation and their damage may be indicative of a poor prognosis for a fetus with regard to neurological development. In addition, impairment of this region may explain the complex neurodevelopmental deficits in preterm infants with periventricular hypoxic/ischemic or inflammatory lesions.

Restoration of cortical symmetry and binaural function: Cortical auditory evoked responses in adult cochlear implant users with single sided deafness.

BackgroundCochlear implantation for single-sided deafness (SSD) is the only treatment option with the potential to restore binaural hearing cues. Significant binaural benefit has been measured in adults by speech in noise and localisation tests, who receive a cochlear implant for SSD, however, little is known on the cortical changes that help provide this benefit. In the present study, detection of sound in the auditory cortex, speech testing and localisation was used to investigate the ability of a cochlear implant (CI) to restore auditory cortical latencies and improve binaural benefit in the adult SSD population.MethodsTwenty-nine adults with acquired single-sided deafness who received a CI in adulthood were studied. Speech perception in noise was tested using the Bamford-Kowal-Bench speech-in-noise test, localisation ability was measured using the auditory speech sounds evaluation (AδE) localisation test and cortical auditory evoked responses, comparing N1-P2 latencies recorded from the normal hearing ear and cochlear implant were used to investigate the synchrony of the cortical pathway from the CI and normal hearing ear (NHe) with binaural hearing function.ResultsThere was a significant improvement in speech perception in noise in all spatial configurations S0/N0 (Z = -3.066, p<0.002), S0/NHE (Z = -4.031, p<0.001), SCI/NHE (Z = -3.851, p<0.001). Localization significantly improved when tested with the cochlear implant on (p<0.001) with a shorter duration of deafness correlating to a greater improvement in localisation ability F(1:18) = 6.854; p = 0.017). There was no significant difference in N1-P2 latency recorded from the normal hearing ear and the CI.ConclusionCortical auditory evoked response latencies recorded from the CI and NHe showed no significant difference, indicating that the detection of sound in the auditory cortex occurred simultaneously, providing the cortex with auditory information for binaural hearing.

Fixel-Based Diffusion Magnetic Resonance Imaging Reveals Novel Associations Between White Matter Microstructure and Childhood Aggressive Behavior

BackgroundChildhood aggression has been linked to white matter abnormalities, but research has been inconsistent with regard to both regions of alterations and directionality of the associations. We examined white matter microstructure correlates of aggression using a novel diffusion imaging analysis technique, fixel-based analysis, which leverages connectivity and crossing-fiber information to assess fiber bundle density. MethodsThe sample included 70 children with aggressive behavior and 25 healthy control children without aggressive behavior. Aggression was measured by the parent-rated Aggressive Behavior scale of the Child Behavior Checklist. Fixel-based analysis was conducted at the whole-brain and region-of-interest levels, including the uncinate fasciculus, inferior longitudinal fasciculus, fornix, cingulum bundle, and genu, body, isthmus, and splenium of the corpus callosum. ResultsWhole-brain analysis of covariance revealed that children with aggressive behavior, relative to control children, had lower fiber density in a cluster of limbic and cortical pathways, including the inferior fronto-occipital fasciculus, fornix, middle cerebellar peduncle, and superior thalamic radiations (familywise error–corrected p < .01), and had higher fiber density in the corpus callosum (body and splenium) (familywise error–corrected p < .05). Region-of-interest analyses showed decreased fiber density in cingulum bundles associated with aggression. These effects were independent of age, sex, IQ, symptoms of attention-deficit/hyperactivity disorder, medications, and head motion. In children with aggressive behavior, co-occurring callous-unemotional traits and anxiety did not moderate the association between aggression and white matter density. ConclusionsDiminished white matter density in pathways connecting limbic and cortical regions is associated with childhood aggression. Abnormal interhemispheric connectivity via corpus callosum may also reflect a potential neural mechanism involved in aggression.

What we can learn from the complex architecture of single axons.

Anterogradely labeled connections at the single-axon level provide unparalleled spatial and quantitative data as well as a novel perspective on laminar, columnar, hierarchical and other aspects of cortical organization. Here, I briefly summarize single-axon results from representative examples of thalamocortical, corticocortical, callosal, and lateral intrinsic connections, with attention to implications for cortical organization. Particularly worth emphasizing is the intricate spatial configuration and striking morphometric heterogeneity of individual axons even within the same system of connections. A short section touches on patterns of axonal trajectories in the distal, preterminal few millimeters. Emphasis is on studies in nonhuman primates from about 1983 to present, with non-viral tracers and 2-D reconstruction (i.e., compressed z-axis) in the early visual cortical pathway. The last section recapitulates what this approach can tell us about inter-areal communication and cortical organization, and possible implications for dynamics and effective connectivity, and concludes with comments on open questions and future directions.

Broca's area intraoperative mapping with cortico-cortical evoked potentials

Mapping of effective speech connections between the frontal and temporal lobes with cortico-cortical evoked potentials. There were 3 patients with brain tumors in the left frontoparietal region. The neoplasms were localized in the dominant hemisphere near cortical speech centers and pathways. Cortico-cortical evoked potentials were intraoperatively recorded in response to bipolar stimulation with a direct current delivered through the subdural electrodes (single rectangular biphasic impulses with duration of 300 μs and frequency of 1 Hz). Stimulation intensity was gradually increased from 2 mA within 3-4 mA. Registration was carried out by averaging ECoG (30-50 stimuli in each session) in the 300-ms epoch after stimulus. Direct cortical stimulation was used to validate the results of cortico-cortical speech mapping with cortico-cortical evoked potentials. In our cases, we obtained cortico-cortical evoked potentials from inferior frontal gyrus after stimulation of superior temporal gyrus. In one case, this effective relationship was unidirectional, in the other two patients reciprocal. Mean latency of N1 peak was 65 ms (range 49.6-90 ms), mean amplitude 71 µV (range 50-100 µV). Cortico-cortical mapping data were confirmed by detection of Broca's area in 2 out of 3 cases out during direct cortical stimulation with maximum amplitude of N1 wave. «Awake craniotomy» protocol was applied. In one case, Broca's area was not detected during direct stimulation. No postoperative speech impairment was noted. Initial results of cortical mapping with cortico-cortical evoked potentials in a small sample confirmed its practical significance for analysis of cortical projections of effective speech communications between the frontal and temporal lobes. Further study of this method in large samples is required.

Niedowidzenie – terapie standardowe kontra nowoczesne

According to the World Health Organization, amblyopia and associated uncorrected refractive errors are the most common causes of visual disorders. Amblyopia is defined as the reduction of the best-corrected visual acuity in one or, less frequently, in both eyes. It is a neurodevelopmental disorder that occurs in childhood and results in the discontinuation of normal cortical visual pathways. Until recently, it was believed that due to the lack of sufficient plasticity of the central nervous system in adults, amblyopia is incurable after the end of the critical period, i.e. around 7 years of age. However, recent research results undermined this view, revealing underestimated recovery potential even in adulthood. Traditional methods of amblyopia treatment include correction of refractive errors and stimulation of the visually impaired eye by covering the dominant eye, most often by obturation or pharmacological penalisation with atropine. Preliminary results of research on modern methods of therapy, such as video games, perceptual learning or dichoptic training, provide opportunities not only to improve visual acuity, but also to relieve other visual deficiencies associated with ambliopia, such as reduced sensitivity to contrast or spatial vision.

Alterations to dual stream connectivity predicts response to aphasia therapy following stroke

BackgroundPredicting aphasia recovery is difficult due to a high variability in treatment response. Detailed measures of treatment response are compounded by a dearth of information that examine brain connections that contribute to clinical improvement. In this study we measure alterations to cortical connectivity pathways during a therapy paradigm to detect whether key brain connections that contribute to language recovery can be detected prior to therapy. MethodsWe conducted a case–control trial with twenty-three adults including eight adults with chronic, post-stroke aphasia. Aphasia patients underwent 12 naming therapy sessions over 4 weeks, consisting of semantic and phonological treatment approaches. High-density electroencephalography (128 channel EEG) was measured prior to therapy and immediately following treatment in patients with aphasia. Analysis via a dynamic causal modelling (DCM) was used to assess which cortical connections significantly correlated with therapy response. ResultsAltered cortical responses in aphasia patients measured bilaterally in a dual stream DCM connectivity model were predictive of treatment-induced improvement in naming. Pre-treatment DCM coupling (i.e., strength of cortical connections) significant correlated with naming improvement for items treated with semantic therapy, as indicated by increased connection strengths between left inferior parietal lobule (LIPL) and inferior frontal gyrus (LIFG, r = .63, pFDR = .016). In particular, the mediating role of contralateral regions significantly influences overall treatment improvement in the latter stages of stroke recovery. ConclusionsOur findings identify a potential means to stratify larger cohorts of patients in neurorehabilitation settings into distinct treatments that are tailored to their individual language deficit.

The anatomo-functional organization of the hyperdirect cortical pathway to the subthalamic area using in vivo structural connectivity imaging in humans.

The subthalamic nucleus (STN) receives direct cortical inputs which constitute the so-called hyperdirect pathway. In monkeys, motor cortices innervate the whole extent of the STN whereas limbic cortices innervate only its anteromedial part extending more medially outside the nucleus. Tractography studies in humans have also identified motor cortical inputs to the STN, but little is known about the associative and limbic cortical projections. Therefore, the aim of this study was to investigate the anatomo-functional organization of the cortical projections to the STN and to the adjacent medial subthamic region (MSR). We used diffusion-weighted imaging-based tractography acquired from 30 subjects from the Human Connectome Project. We performed a whole-brain probabilistic tractography using MRTrixand extracted streamlines of interest between 39 cortical masks and both the STN and the MSR to provide track-density maps. Agglomerative clustering method was used to classify the voxels of the regions of interest. We found that the STN receives major inputs from the sensorimotor cortices and few inputs from the limbic cortices. On the other hand, the MSR receives mainly cortical limbic projections and few from the sensorimotor cortices. Weak connections were found between the associative cortices and both the STN and the MSR. We found a dominant motor cluster located in the posterolateral STN, a limbic cluster located medially in the MSR, and an intermediate motor-limbic cluster in between. Our findings show that the hyperdirect pathway is anatomo-functionally organized with a poor participation of associative cortices.

Feasibility of Near-infrared Spectroscopy to Measure Cortical Pain Pathway (Brain) Activation During Dry Needling

Feasibility of Near-infrared Spectroscopy to Measure Cortical Pain Pathway (Brain) Activation During Dry Needling

A Critical Role for Neocortical Processing of Threat Memory

Memory of cues associated with threat is critical for survival and a leading model for elucidating how sensory information is linked to adaptive behavior by learning. Although the brain-wide circuits mediating auditory threat memory have been intensely investigated, it remains unclear whether the auditory cortex is critically involved. Here we use optogenetic activity manipulations in defined cortical areas and output pathways, viral tracing, pathway-specific invivo 2-photon calcium imaging, and computational analyses of population plasticity to reveal that the auditory cortex is selectively required for conditioning to complex stimuli, whereas the adjacent temporal association cortex controls all forms of auditory threat memory. More temporal areas have a stronger effect on memory and more neurons projecting to the lateral amygdala, which control memory to complex stimuli through a balanced form of population plasticity that selectively supports discrimination of significant sensory stimuli. Thus, neocortical processing plays a critical role in cued threat memory.

The relationship between episodic detail generation and anterotemporal, posteromedial, and hippocampal white matter tracts

Episodic details populate autobiographical memories with vivid representations of people, objects, and event happenings, and they link events to a specific time and place. Episodic detail generation is believed to be a function of medial temporal lobe (MTL)-cortical interaction, but much remains unclear about how this retrieval process unfolds. In the present study, we combined an autobiographical interview and diffusion magnetic resonance imaging to investigate the relationships of two types of episodic detail, namely details about entities of an event (people and objects) or “event elements” and details about spatiotemporal context, to the integrity of anterotemporal (uncinate fasciculus; UF) and posteromedial (cingulum bundle; CB) cortical pathways. We also measured the relationships of these detail types to the fornix, and the relationship between non-episodic details and these tracts. We found that only episodic detail generation was significantly related to cortical and hippocampal pathways. Notably, the UF was more strongly related to event element details than it was to spatiotemporal context details. In contrast, CB was significantly and similarly related to the generation of event element and spatiotemporal context details (when not controlling for age and global diffusion). The fornix was also significantly related to both types of episodic detail, although the relationship to spatiotemporal context was particularly robust. These findings support the idea that anterotemporal cortical regions are related to the retrieval of episodic details about the entities that are incorporated into autobiographical events. Our findings also align with the notion that posteromedial and hippocampal-cortical involvement support the retrieval of episodic details.

High Angular Resolution Diffusion MRI Reveals Conserved and Deviant Programs in the Paths that Guide Human Cortical Circuitry.

Diffusion magnetic resonance (MR) tractography represents a novel opportunity to investigate conserved and deviant developmental programs between humans and other species such as mice. To that end, we acquired high angular resolution diffusion MR scans of mice [embryonic day (E) 10.5 to postnatal week 4] and human brains [gestational week (GW) 17-30] at successive stages of fetal development to investigate potential evolutionary changes in radial organization and emerging pathways between humans and mice. We compare radial glial development as well as commissural development (e.g., corpus callosum), primarily because our findings can be integrated with previous work. We also compare corpus callosal growth trajectories across primates (i.e., humans and rhesus macaques) and rodents (i.e., mice). One major finding is that the developing cortex of humans is predominated by pathways likely associated with a radial glial organization at GW 17-20, which is not as evident in age-matched mice (E 16.5, 17.5). Another finding is that, early in development, the corpus callosum follows a similar developmental timetable in primates (i.e., macaques and humans) as in mice. However, the corpus callosum grows for an extended period of time in primates compared with rodents. Taken together, these findings highlight deviant developmental programs underlying the emergence of cortical pathways in the human brain.

What Neuroscientific Studies Tell Us about Inhibition of Return.

An inhibitory aftermath of orienting, inhibition of return (IOR), has intrigued scholars since its discovery about 40 years ago. Since then, the phenomenon has been subjected to a wide range of neuroscientific methods and the results of these are reviewed in this paper. These include direct manipulations of brain structures (which occur naturally in brain damage and disease or experimentally as in TMS and lesion studies) and measurements of brain activity (in humans using EEG and fMRI and in animals using single unit recording). A variety of less direct methods (e.g., computational modeling, developmental studies, etc.) have also been used. The findings from this wide range of methods support the critical role of subcortical and cortical oculomotor pathways in the generation and nature of IOR.

2784. Increased Frontal Lobe Volume and Density in Macaques Exposed to Zika Virus In Utero

BackgroundIn utero Zika virus (ZIKV) infection causes birth defects and neurodevelopmental deficits in neonates. We reasoned that a translational macaque model of congenital ZIKV infection could define disease pathophysiology not possible in human clinical studies.MethodsWe inoculated 5 pregnant rhesus macaques with a Puerto Rican isolate of ZIKV (ZIKV-PRVABC59) during the first trimester, monitored infection with plasma viral RNA (vRNA) loads, and evaluated infants for birth defects and neurodevelopmental deficits during their first week of life. Assessments included neurobehavioral assessments, ophthalmic examinations, optical coherence tomography, electroretinography with visual evoked potentials, hearing examinations, brain magnetic resonance imaging (MRI), and tissue histopathological analyses.ResultsAll five pregnant dams demonstrated plasma viremia and seroconversion following ZIKV inoculation. One of the five pregnancies resulted in a stillbirth. All liveborn infants had decreased feeding volumes and weight gain compared with control infants. A comprehensive voxel-based morphometric comparison of ZIKV-exposed and control infant brain MRIs identified increased gray matter volume and density in the frontal lobe in the ZIKV-exposed infant group, which corresponds to the pharyngeal motor cortex responsible for coordinating swallowing. Ocular studies identified differences between ZIKV-exposed and control infants in retinal layer thicknesses (inner plexiform, outer nuclear layers, photoreceptor outer segment) and visual evoked potentials (increased amplitude of waveforms). While ZIKV vRNA was detected in the decidua of 2/5 pregnancies, no ZIKV vRNA was identified in infant tissues and none of the infants developed an anti-ZIKV IgM response.ConclusionIn utero ZIKV exposure resulted in decreased feeding volumes and weight gain, which may be related to the gray matter changes identified in the pharyngeal motor cortex. Changes in retinal layer thicknesses and increased cortical visual pathway waveform amplitude suggest vision may be impaired. These changes occurred despite the lack of evidence of vertical transmission, suggesting that ZIKV exposure without measurable vertical transmission affects fetal brain development.Disclosures All authors: No reported disclosures.