PyOKR: A Semi-Automated Method for Quantifying Optokinetic Reflex Tracking Ability.

The study of behavioral responses to visual stimuli is a key component of understanding visual system function. One notable response is the optokinetic reflex (OKR), a highly conserved innate behavior necessary for image stabilization on the retina. The OKR provides a robust readout of image tracking ability and has been extensively studied to understand visual system circuitry and function in animals from different genetic backgrounds. The OKR consists of two phases: a slow tracking phase as the eye follows a stimulus to the edge of the visual plane and a compensatory fast phase saccade that resets the position of the eye in the orbit. Previous methods of tracking gain quantification, although reliable, are labor intensive and can be subjective or arbitrarily derived. To obtain more rapid and reproducible quantification of eye tracking ability, we have developed a novel semi-automated analysis program, PyOKR, that allows for quantification of two-dimensional eye tracking motion in response to any directional stimulus, in addition to being adaptable to any type of video-oculography equipment. This method provides automated filtering, selection of slow tracking phases, modeling of vertical and horizontal eye vectors, quantification of eye movement gains relative to stimulus speed, and organization of resultant data into a usable spreadsheet for statistical and graphical comparisons. This quantitative and streamlined analysis pipeline, readily accessible via PyPI import, provides a fast and direct measurement of OKR responses, thereby facilitating the study of visual behavioral responses.

A Case Report of Spontaneous Vaginal Delivery Under General Anesthesia in a Patient With a Large Cerebral Aneurysm.

Cerebral aneurysms are rarely encountered in pregnancy. Their antepartum and intrapartum management remain clinically challenging, primarily due to concern regarding potential rupture. We present a case of a patient in preterm labor at risk for imminent delivery with a 10mm cerebral aneurysm. She was recommended for cesarean section (CS), yet delivered via spontaneous vaginal delivery in the operating room after induction of general anesthesia for the intended CS. Her aneurysm and neurologic function remained intact postpartum. Cerebral aneurysms <5mm are unlikely to undergo significant growth during pregnancy. The presence of a cerebral aneurysm is not automatically a contraindication to the Valsalva maneuver. The recommendation for which patients with unruptured cerebral aneurysms should deliver by CS, operative vaginal delivery, or unassisted vaginal delivery (i.e., which patients should avoid Valsalva maneuver intrapartum), is complex and requires multidisciplinary discussion.

Pituitary apoplexy as a mimicker of infectious meningitis in an adolescent female patient.

Pituitary apoplexy can cause a chemical meningitis and its mimicry in presentation with infectious meningitis poses a diagnostic challenge. Here we report an 18-year-old woman who presented with acute headache, altered mental status, and cerebral spinal fluid (CSF) pleocytosis, and clinically improved with antibiotics and steroids. Despite an unremarkable head computed tomography scan, brain magnetic resonance imaging showed a pituitary macroadenoma with apoplexy. This is one of the first reports of an adolescent with pituitary apoplexy masquerading as infectious meningitis and underscores the importance of keeping this rare condition, often missed on CT scans, on the differential for CSF pleocytosis.

A semi-automated method for quantifying optokinetic reflex tracking acuity.

The study of murine behavioral responses to visual stimuli is a key component of understanding mammalian visual circuitry. One notable response is the optokinetic reflex (OKR), a highly conserved innate behavior necessary for image stabilization on the retina. The OKR provides a robust readout of image tracking ability and has been extensively studied to understand the logic of visual system circuitry and function in mice from different genetic backgrounds. The OKR consists of two phases: a slow tracking phase as the eye follows a stimulus to the edge of the visual plane, and a compensatory fast phase saccade that maintains the image within the visual field. Assessment of the OKR has previously relied on counting individual compensatory eye saccades to estimate tracking speed. To obtain a more direct quantification of tracking ability, we have developed a novel, semi-automated analysis program that allows for rapid and reproducible quantification of unidirectional tracking gains, in addition to being adaptable to any video-oculography equipment. Our analysis program allows for the selection of slow tracking phases, modeling of the vertical and horizontal eye vectors, quantification of eye movement relative to the stimulus, and organization of resultant data into a usable spreadsheet for statistical and graphical comparisons. This quantitative and streamlined analysis pipeline provides a faster and more direct measurement of OKR responses, thereby facilitating further study of visual behavior responses. SUMMARY: We describe here a semi-automated quantitative analysis method that directly measures eye tracking resulting from murine visual system responses to two-dimensional image motion. A Python-based user interface and analysis algorithm allows for higher throughput and more quantitative measurements of eye tracking parameters than previous methods.

Preserving integrity in the face of performance threat: self-affirmation enhances neurophysiological responsiveness to errors.

Self-affirmation produces large effects: Even a simple reminder of one's core values reduces defensiveness against threatening information. But how, exactly, does self-affirmation work? We explored this question by examining the impact of self-affirmation on neurophysiological responses to threatening events. We hypothesized that because self-affirmation increases openness to threat and enhances approachability of unfavorable feedback, it should augment attention and emotional receptivity to performance errors. We further hypothesized that this augmentation could be assessed directly, at the level of the brain. We measured self-affirmed and nonaffirmed participants' electrophysiological responses to making errors on a task. As we anticipated, self-affirmation elicited greater error responsiveness than did nonaffirmation, as indexed by the error-related negativity, a neural signal of error monitoring. Self-affirmed participants also performed better on the task than did nonaffirmed participants. We offer novel brain evidence that self-affirmation increases openness to threat and discuss the role of error detection in the link between self-affirmation and performance.

The transcription factor Tbx5 regulates direction-selective retinal ganglion cell development and image stabilization.

The diversity of visual input processed by the mammalian visual system requires the generation of many distinct retinal ganglion cell (RGC) types, each tuned to a particular feature. The molecular code needed to generate this cell-type diversity is poorly understood. Here, we focus on the molecules needed to specify one type of retinal cell: the upward-preferring ON direction-selective ganglion cell (up-oDSGC) of the mouse visual system. Single-cell transcriptomic profiling of up- and down-oDSGCs shows that the transcription factor Tbx5 is selectively expressed in up-oDSGCs. The loss of Tbx5 in up-oDSGCs results in a selective defect in the formation of up-oDSGCs and a corresponding inability to detect vertical motion. A downstream effector of Tbx5, Sfrp1, is also critical for vertical motion detection but not up-oDSGC formation. These results advance our understanding of the molecular mechanisms that specify a rare retinal cell type and show how disrupting this specification leads to a corresponding defect in neural circuitry and behavior.

Does antiretroviral therapy improve HIV-associated cognitive impairment? A quantitative review of the literature.

The development of antiretroviral therapy (ART) has dramatically improved survival for those living with human immunodeficiency virus (HIV), but whether ART improves cognitive functioning remains unclear. The aim of the present review was to examine systematically the extent to which ART improves cognition among individuals with HIV using meta-analytic methods. Twenty-three studies were included in the quantitative review. ART was associated with modest improvements in attention (mean d = .17; p < .001; 95% confidence interval [CI], .09/.25), executive function (mean d = .18; p < .001; 95% CI, .10/.26), and motor function (mean d = .24; p < .001; 95% CI, .16/.32). ART did not improve language, verbal memory, visual memory or visuospatial function. The extent to which cognition improved was correlated with the change in CD4 cell count following ART, suggesting a link between cognitive outcome and immune system integrity. Together, the present findings indicate that the neuropsychological test performance of most HIV patients taking ART is comparable to those not taking ART. Development of pharmaceutical treatments and rehabilitation strategies that target the cognitive effects of HIV infection is needed.

Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency characterized by the accumulation of blood in the subarachnoid space surrounding the brain. The acute treatment of aSAH is well documented but less is known about the long-term effects of aSAH on cognition and day-to-day functioning. METHODS: We reviewed all studies in the past 10 years that have focused on the effects of aSAH on cognition and day-to-day functioning. RESULTS: Sixty-one empirical studies examining cognitive and functional outcome in patients with aSAH met inclusion criteria. Survivors of aSAH commonly experience deficits in memory, executive function, and language. These cognitive impairments interact to affect patients' day-to-day functioning, including activities of daily living, instrumental activities of daily living, return to work, and quality of life. Deficits in cognition and day-to-day functioning are further compounded by depression, anxiety, fatigue, and sleep disturbances. CONCLUSIONS: Much remains to be learned about the brain changes underlying cognitive and functional deficits, including the role of diffuse brain damage and secondary complications like vasospasm and elevated intracranial pressure. A consideration of these issues is necessary to obtain a better understanding of how aSAH affects cognition and day-to-day functioning in the long-term.

Assessing the Effectiveness of Systemic Therapy after Stereotactic Radiosurgery on Cancer Recurrence and All-Cause Mortality.

BACKGROUND: Patients with cancer often present with brain metastases in the setting of controlled extracranial disease, for which they receive stereotactic radiosurgery (SRS) and surgical resection. The role of systemic therapy after SRS is unclear. Brain metastasis indicates active cancer dissemination, and microscopic systemic disease may be present despite absence of gross disease as assessed by conventional imaging modalities. OBJECTIVE: The aim was to determine if post-SRS systemic therapy reduces the risk of brain relapse, systemic relapse, and death in patients with brain metastases and controlled extracranial disease. METHODS: We retrospectively reviewed the medical records of 67 patients with controlled extracranial disease who received SRS for brain metastases. Kaplan-Meier analysis and Cox proportional hazards regression were used to assess how post-SRS systemic therapy affected the risk of brain relapse, systemic relapse, and all-cause mortality. RESULTS: In our sample, 31% of patients received systemic therapy after SRS. Post-SRS systemic therapy did not affect median time to brain relapse (P = 0.43), systemic relapse (P = 0.16), or death (P = 0.33) by univariate analysis. After accounting for confounding factors such as cancer histology and age, post-SRS systemic therapy significantly reduced the risk of brain relapse (hazard ratio [HR], 0.22; P = 0.002) but not systemic relapse (HR, 0.38; P = 0.09) or all-cause mortality (HR, 2.16; P = 0.09). CONCLUSIONS: Only a minority of patients with brain metastases and controlled extracranial disease receive adjuvant systemic therapy after SRS, but those that do have a reduced risk of brain relapse. Post-SRS systemic therapy may act prophylactically to reduce the risk of intracranial cancer recurrence.

Genetic access to neurons in the accessory optic system reveals a role for Sema6A in midbrain circuitry mediating motion perception.

The accessory optic system (AOS) detects retinal image slip and reports it to the oculomotor system for reflexive image stabilization. Here, we characterize two Cre lines that permit genetic access to AOS circuits responding to vertical motion. The first (Pcdh9-Cre) labels only one of the four subtypes of ON direction-selective retinal ganglion cells (ON-DS RGCs), those preferring ventral retinal motion. Their axons diverge from the optic tract just behind the chiasm and selectively innervate the medial terminal nucleus (MTN) of the AOS. Unlike most RGC subtypes examined, they survive after optic nerve crush. The second Cre-driver line (Pdzk1ip1-Cre) labels postsynaptic neurons in the MTN. These project predominantly to the other major terminal nucleus of the AOS, the nucleus of the optic tract (NOT). We find that the transmembrane protein semaphorin 6A (Sema6A) is required for the formation of axonal projections from the MTN to the NOT, just as it is for the retinal innervation of the MTN. These new tools permit manipulation of specific circuits in the AOS and show that Sema6A is required for establishing AOS connections in multiple locations.

Functional assembly of accessory optic system circuitry critical for compensatory eye movements.

Accurate motion detection requires neural circuitry that compensates for global visual field motion. Select subtypes of retinal ganglion cells perceive image motion and connect to the accessory optic system (AOS) in the brain, which generates compensatory eye movements that stabilize images during slow visual field motion. Here, we show that the murine transmembrane semaphorin 6A (Sema6A) is expressed in a subset of On direction-selective ganglion cells (On DSGCs) and is required for retinorecipient axonal targeting to the medial terminal nucleus (MTN) of the AOS. Plexin A2 and A4, two Sema6A binding partners, are expressed in MTN cells, attract Sema6A(+) On DSGC axons, and mediate MTN targeting of Sema6A(+) RGC projections. Furthermore, Sema6A/Plexin-A2/A4 signaling is required for the functional output of the AOS. These data reveal molecular mechanisms underlying the assembly of AOS circuits critical for moving image perception.

Decision-making deficits persist after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Effective decision-making is critical for resuming day-to-day activities after aneurysmal subarachnoid hemorrhage (aSAH). Little is known, however, about how decision-making is affected after aSAH, particularly under ambiguous conditions in which neither the outcome nor the outcome probabilities are known. METHOD: Here we examined the integrity of decision-making under ambiguity in a cohort of aSAH patients classified as having made a "good outcome" according to the Glasgow Outcome Scale. Thirty aSAH survivors and 33 healthy controls completed the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART). Mean time of assessment poststroke was 30 months. RESULTS: Although patients and controls had similar decision-making strategies on the IGT, patients made significantly fewer switches between decks, suggesting perseveration and cognitive inflexibility. On the BART, aSAH patients demonstrated significantly enhanced risk-taking behavior relative to controls. Examination of effect sizes revealed cognitive inflexibility in 33% to 35% of aSAH patients and enhanced risk-taking behavior in 35% to 40% of aSAH patients. CONCLUSION: Approximately one third of "good outcome" aSAH patients experience cognitive inflexibility and enhanced risk-taking behavior over 2 years poststroke, illustrating the persistence of aSAH-associated cognitive impairment.

Emotion down-regulation diminishes cognitive control: a neurophysiological investigation.

Traditional models of cognitive control have explained performance monitoring as a "cold" cognitive process, devoid of emotion. In contrast to this dominant view, a growing body of clinical and experimental research indicates that cognitive control and its neural substrates, in particular the error-related negativity (ERN), are moderated by affective and motivational factors, reflecting the aversive experience of response conflict and errors. To add to this growing line of research, here we use the classic emotion regulation paradigm-a manipulation that promotes the cognitive reappraisal of emotion during task performance-to test the extent to which affective variation in the ERN is subject to emotion reappraisal, and also to explore how emotional regulation of the ERN might influence behavioral performance. In a within-subjects design, 41 university students completed 3 identical rounds of a go/no-go task while electroencephalography was recorded. Reappraisal instructions were manipulated so that participants either down-regulated or up-regulated emotional involvement, or completed the task normally, without engaging any reappraisal strategy (control). Results showed attenuated ERN amplitudes when participants down-regulated their emotional experience. In addition, a mediation analysis revealed that the association between reappraisal style and attenuated ERN was mediated by changes in reported emotion ratings. An indirect effects model also revealed that down-regulation predicted sensitivity of error-monitoring processes (difference ERN), which, in turn, predicted poorer task performance. Taken together, these results suggest that the ERN appears to have a strong affective component that is associated with indices of cognitive control and behavioral monitoring.

ERN and the placebo: a misattribution approach to studying the arousal properties of the error-related negativity.

Performance monitoring in the anterior cingulate cortex (ACC) has largely been viewed as a cognitive, computational process devoid of emotion. A growing body of research, however, suggests that performance is moderated by motivational engagement and that a signal generated by the ACC, the error-related negativity (ERN), may partially reflect a distress response to errors. Although suggestive, this past work is hampered by use of correlational designs or by designs that confound affect and cognitive performance. Here we use the misattribution of arousal paradigm--an experimental paradigm that pilot research shows can dissociate affect from cognitive performance--to investigate the extent to which the ERN has arousal properties. Forty university students completed a misattribution of arousal paradigm by consuming a beverage they believed would either increase their anxiety or would have no side effects and then completed a go/no-go task while we recorded ERNs. Results indicate that participants who were given the opportunity to misattribute arousal exhibited a reduced ERN compared with participants who were not given any misattribution cues. This occurred despite no measurable differences in performance on the go/no-go task. In addition, correlations between the ERN and behavior were observed only for participants who did not misattribute their arousal to the placebo beverage. Taken together, these results suggest that the ERN is dissociable from cognitive performance but not negative affect.

Mini-Mental State Examination versus Montreal Cognitive Assessment: rapid assessment tools for cognitive and functional outcome after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Recent studies suggest that the Montreal Cognitive Assessment (MoCA) is more sensitive to stroke-associated cognitive dysfunction than the Mini-Mental State Examination (MMSE), but little is known about how these screening measures relate to neurocognitive test performance or real-world functioning in patients with good recovery after aneurysmal subarachnoid hemorrhage (aSAH). The aim of the present study was to determine how MoCA and MMSE scores relate to neurocognitive impairment and return to work after aSAH. METHODS: Thirty-two patients with aSAH who had made a good recovery completed the MoCA, the MMSE, and a battery of neurocognitive tests. RESULTS: 42% and 0% of aSAH patients were impaired on the MoCA and MMSE, respectively. The MoCA had acceptable sensitivity (40-100%) and specificity (54-68%) (Table 3). The MMSE failed to detect impairment in any cognitive domain. The MoCA, but not the MMSE, predicted performance on tests of verbal learning, executive function, working memory, visuospatial function, and motor function. Superior performance on the Animal naming and Abstraction subtests of the MoCA score were associated with return to work following aSAH. CONCLUSION: Compared to the MMSE, the MoCA is more sensitive to aSAH-associated cognitive impairment. Certain MoCA subtests are also sensitive to functional difficulties after aSAH such as return to work. These findings support the utility of the MoCA as a brief bedside assessment of cognitive and real-world outcome in aSAH survivors.