The Road Not Taken: Disconnection of a Human-Unique Cortical Pathway Underlying Naturalistic Social Perception in Schizophrenia.

Background: Efficient processing of complex and dynamic social scenes relies on intact connectivity of many underlying cortical areas and networks, but how connectivity anomalies affect the neural substrates of social perception remains unknown. Here we measured these relationships using functionally based localization of social perception areas, resting-state functional connectivity, and movie-watching data. Methods: In 42 participants with schizophrenia (SzPs) and 41 healthy control subjects, we measured the functional connectivity of areas localized by face-emotion processing, theory-of-mind (ToM), and attention tasks. We quantified the weighted shortest path length between visual and medial prefrontal ToM areas in both populations to assess the impact of these changes in functional connectivity on network structure. We then correlated connectivity along the shortest path in each group with movie-evoked activity in a key node of the ToM network (posterior temporoparietal junction [TPJp]). Results: SzPs had pronounced decreases in connectivity in TPJ/posterior superior temporal sulcus (TPJ-pSTS) areas involved in face-emotion processing (t81 = 4.4, p = .00002). In healthy control subjects, the shortest path connecting visual and medial prefrontal ToM areas passed through TPJ-pSTS, whereas in SzPs, the shortest path passed through the prefrontal cortex. While movie-evoked TPJp activity correlated with connectivity along the TPJ-pSTS pathway in both groups (r = 0.43, p = .002), it additionally correlated with connectivity along the prefrontal cortex pathway only in SzPs (rSzP = 0.56, p = .003). Conclusions: These results suggest that connectivity along the human-unique TPJ-pSTS pathway affects both the network architecture and functioning of areas involved in processing complex dynamic social scenes. These results demonstrate how focal connectivity anomalies can have widespread impacts across the cortex.

Spontaneous regression of a presumed orbital apex cavernous venous malformation.

A 42-year-old non-menopausal, non-pregnant woman presented with an incidentally noted right orbital apex lesion producing mild compressive optic neuropathy. Imaging revealed an apical, intraconal, inhomogenously enhancing mass consistent with a cavernous venous malformation displacing the optic nerve. The patient was monitored over a 15-year period with serial orbital imaging and clinical examinations and ultimately demonstrated significant regression in the size of the lesion, accompanied by the complete resolution of optic neuropathy. She was non-menopausal when the regression was noted and remained non-pregnant throughout the follow-up period.

The Arched Rainbow Brow in Thyroid Eye Disease.

PURPOSE: To morphologically describe and mathematically quantify a novel clinical feature of thyroid eye disease (TED). METHODS: A retrospective study was conducted of TED patients and age-sex-matched normal controls. The arched Rainbow Brow appearance in TED patients was determined by unanimous agreement of 3 oculoplastic surgeons. Eyebrow curvature was assessed by plotting 15 points along the eyebrow in ImageJ. The fourth-degree polynomial ( y = ax4 + bx3 + cx2 + dx + e ) was fitted to each eyebrow. RESULTS: Two hundred seventy-one eyes were analyzed (200 TED and 71 age-sex-matched normal controls). A Rainbow Brow was identified in 42% of TED patients. A unilateral Rainbow Brow was seen in 15% of patients. The fourth-degree polynomial coefficients yielded significant differences between Rainbow Brow patients and age-sex-matched normal controls for the coefficients a, b, c , and d . Similar analysis of TED patients with and without a Rainbow Brow showed differences in coefficients a and b . Age >50 years ( p = 0.009) and the presence of brow fat expansion ( p < 0.001) were associated with the presence of a Rainbow Brow. Proptosis >24 mm showed a trend toward association with the presence of a Rainbow Brow ( p = 0.057). When considering the contribution of these features in a multivariable analysis, only brow fat expansion was a significant contributing factor ( p = 0.009). CONCLUSIONS: The Rainbow Brow is a distinct entity in TED and is likely consequent to brow fat pad expansion. Patients with a Rainbow Brow have different eyebrow curvature as compared to both normal age-sex-matched controls and TED patients without a Rainbow Brow.

Angle Surgery in Pediatric Glaucoma Following Cataract Surgery.

Glaucoma is a common and sight-threatening complication of pediatric cataract surgery Reported incidence varies due to variability in study designs and length of follow-up. Consistent and replicable risk factors for developing glaucoma following cataract surgery (GFCS) are early age at the time of surgery, microcornea, and additional surgical interventions. The exact mechanism for GFCS has yet to be completely elucidated. While medical therapy is the first line for treatment of GFCS, many eyes require surgical intervention, with various surgical modalities each posing a unique host of risks and benefits. Angle surgical techniques include goniotomy and trabeculotomy, with trabeculotomy demonstrating increased success over goniotomy as an initial procedure in pediatric eyes with GFCS given the success demonstrated throughout the literature in reducing IOP and number of IOP-lowering medications required post-operatively. The advent of microcatheter facilitated circumferential trabeculotomies lead to increased success compared to traditional <180° rigid probe trabeculotomy in GFCS. The advent of two-site rigid-probe trabeculotomy indicated that similar results could be attained without the use of the more expensive microcatheter system. Further studies of larger scale, with increased follow-up, and utilizing randomization would be beneficial in determining optimum surgical management of pediatric GFCS.

Deficits and compensation: Attentional control cortical networks in schizophrenia.

Visual processing and attention deficits are responsible for a substantial portion of the disability caused by schizophrenia, but the source of these deficits remains unclear. In 35 schizophrenia patients (SzP) and 34 healthy controls (HC), we used a rapid serial visual presentation (RSVP) visual search task designed to activate/deactivate the cortical components of the attentional control system (i.e. the dorsal and ventral attention networks, lateral prefrontal regions in the frontoparietal network, and cingulo-opercular/salience networks), along with resting state functional connectivity, to examine the integrity of these components. While we find that behavioral performance and activation/deactivation of the RSVP task are largely similar between groups, SzP exhibited decreased functional connectivity within late visual components and between prefrontal and other components. We also find that performance correlates with the deactivation of the ventral attention network in SzP only. This relationship is mediated by the functional connectivity of critical components of the attentional control system. In summary, our results suggest that the attentional control system is potentially used to compensate for visual cortex deficits. Furthermore, prefrontal deficits in SzP may interfere with this compensatory use of the attentional control system. In addition to highlighting focal deficits and potential compensatory mechanisms in visual processing and attention, our findings point to the attentional control system as a potential target for rehabilitation and neuromodulation-based treatments for visual processing deficits in SzP.

Collector Channels: Role and Evaluation in Schlemm's Canal Surgery.

OBJECTIVES: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. METHODS: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency. RESULTS: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities. CONCLUSIONS: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.

Role of Matrix Metalloproteinase 9 in Ocular Surface Disorders.

OBJECTIVES: (1) To explore the role and significance of Matrix Metalloproteinase 9 (MMP-9), a proteolytic enzyme, in various ocular surface diseases of inflammatory, infectious, and traumatic etiology (2), to further elucidate the molecular mechanisms responsible for its overexpression in ocular surface disease states, and (3) to discuss possible targets of therapeutic intervention. METHODS: A literature review was conducted of primary sources from 1995 onward using search results populated from the US National Library of Medicine search database. RESULTS: MMP-9 overexpression has been found in in vitro and in vivo models of dry eye disease (DED), corneal ulceration, microbial keratitis, corneal neovascularization, ultraviolet light-induced radiation, and a host of additional surface pathologies. MMP-9 is involved in an intricate signal transduction cascade that includes induction by many proinflammatory molecules including interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-a), nuclear factor kappa light chain enhancer of activated B cells (NF-kB), platelet-activating factor, activator protein 1 (AP-1), and transforming growth factor beta (TGF-B). MMP-9 expression is blunted by a diverse array of molecular factors, such as tissue inhibitors of metalloproteinases, cyclosporine A (CyA), PES_103, epigalloccatechin-3-gallate (EGCG), N-acetylcysteine (NaC), ascorbate, tetracyclines, and corticosteroids. Inhibition of MMP-9 frequently led to improvement of ocular surface disease. CONCLUSIONS: Novel insights into the mechanistic action of MMP-9 provide potential for new therapeutic modulations of ocular surface diseases mediated by its overexpression.

Functional evolution of new and expanded attention networks in humans.

Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.