Computation, perception, and mind.

Advances in behavioral and brain sciences have engendered wide ranging efforts to help understand consciousness. The target article suggests that abstract computational models (such as integrated information theory [IIT]) are ill-advised. This commentary broadens the discussion to include mysteries of subjective experience that are inconsistent with current neuroscience. It also discusses progress being made through demystifying specific cases and pursuing evolutionary considerations.

Efficient Nef-mediated downmodulation of TCR-CD3 and CD28 is associated with high CD4+ T cell counts in viremic HIV-2 infection.

The role of the multifunctional accessory Nef protein in the immunopathogenesis of HIV-2 infection is currently poorly understood. Here, we performed comprehensive functional analyses of 50 nef genes from 21 viremic (plasma viral load, >500 copies/ml) and 16 nonviremic (<500) HIV-2-infected individuals. On average, nef alleles from both groups were equally active in modulating CD4, TCR-CD3, CD28, MHC-I, and Ii cell surface expression and in enhancing virion infectivity. Thus, many HIV-2-infected individuals efficiently control the virus in spite of efficient Nef function. However, the potency of nef alleles in downmodulating TCR-CD3 and CD28 to suppress the activation and apoptosis of T cells correlated with high numbers of CD4(+) T cells in viremic patients. No such correlations were observed in HIV-2-infected individuals with undetectable viral load. Further functional analyses showed that the Nef-mediated downmodulation of TCR-CD3 suppressed the induction of Fas, Fas-L, PD-1, and CTLA-4 cell surface expression as well as the secretion of gamma interferon (IFN-γ) by primary CD4(+) T cells. Moreover, we identified a single naturally occurring amino acid variation (I132T) in the core domain of HIV-2 Nef that selectively disrupts its ability to downmodulate TCR-CD3 and results in functional properties highly reminiscent of HIV-1 Nef proteins. Taken together, our data suggest that the efficient Nef-mediated downmodulation of TCR-CD3 and CD28 help viremic HIV-2-infected individuals to maintain normal CD4(+) T cell homeostasis by preventing T cell activation and by suppressing the induction of death receptors that may affect the functionality and survival of both virally infected and uninfected bystander cells.

Actionability and Simulation: No Representation without Communication.

There remains considerable controversy about how the brain operates. This review focuses on brain activity rather than just structure and on concepts of action and actionability rather than truth conditions. Neural Communication is reviewed as a crucial aspect of neural encoding. Consequently, logical inference is superseded by neural simulation. Some remaining mysteries are discussed.

Iodine -131 metaiodobenzylguanidine is an effective treatment for malignant pheochromocytoma and paraganglioma.

INTRODUCTION: Iodine 131-meta-iodobenzylguanidine ((131)I-MIBG) has been applied to the palliative treatment of metastatic pheochromocytoma in small studies. We report our institutional experience for the treatment of metastatic pheochromocytoma and paraganglioma. METHODS: We performed a retrospective review of 33 patients with metastatic pheochromocytoma (n=22) and paraganglioma (n=11) treated at our institution with (131)I-MIBG over a 10-year period. RESULTS: Patients received a mean dose of 388+/-131 mCi (131)I-MIBG. Median survival after treatment was 4.7 years. Most patients experienced a symptomatic response leading to an improved survival (4.7 years vs 1.8 years, P<.01). Patients with a measurable hormone response demonstrated an increased survival in comparison to those with no response (4.7 years vs 2.6 years, P=.01). Patients who received a high dose (>500 mCi) as their initial therapy also had improved survival (3.8 years vs 2.8 years, P=.02). CONCLUSION: These data support (131)I-MIBG treatment for select patients with metastatic pheochromocytoma. In our experience, prolonged survival was best predicted by symptomatic and hormone response to (131)I-MIBG treatment. An initial dose of 500 mCi may be optimal. The benefit of (131)I-MIBG treatment for metastatic pheochromocytoma must also be weighed against its side effects.

Carcinoid and chylous ascites: an unusual association.

Chylous ascites caused by carcinoid tumors is extremely rare. While carcinoid tumors usually have an indolent course, their association with chylous ascites is a harbinger of a poor outcome.

The neural binding problem(s).

The famous Neural Binding Problem (NBP) comprises at least four distinct problems with different computational and neural requirements. This review discusses the current state of work on General Coordination, Visual Feature-Binding, Variable Binding, and the Subjective Unity of Perception. There is significant continuing progress, partially masked by confusing the different versions of the NBP.

Comparison of refractive error measurements in adults with Z-View aberrometer, Humphrey autorefractor, and subjective refraction.

BACKGROUND: The aim of this study was to evaluate whether measurements obtained with the Ophthonix Z-View aberrometer (Vista, California) and a Humphrey autorefractor (Zeiss Humphrey, Dublin, California) correlate with standard subjective refraction measurements, based on visual acuity results. METHODS: A retrospective data analysis was completed for 97 patients, age range 18 to 66 years, without evidence of systemic or ocular disease. All data were collected without dilation or cycloplegia. Refractive correction measurements (sphere, cylinder, axis) were converted to power vectors for analysis. RESULTS: Differences-versus-means plots show generally excellent agreement between the results of each instrument and subjective refraction, all r(2) > 0.77, with the Z-View consistently exhibiting less variability than the autorefractor (AR). Nonetheless, the Z-View tends to undercorrect myopia, whereas the AR tends to overcorrect myopia, with statistically significant mean differences (±SD) in spherical equivalents with respect to subjective refraction of 0.118 (±0.311) and -0.193 (±0.474) diopters (D), respectively. Both instruments tend to overcorrect astigmatism of less than -1.25 and -0.75 D, respectively, in some cases by as much as -0.87 D. Both instruments also tend to err in cylinder axis measurement for low astigmatism, often by more than 10°. CONCLUSIONS: The Ophthonix Z-View aberrometer is a useful objective clinical instrument that provides better accuracy than an AR, and its results can be used as a good starting point for a subjective refraction for most patients. It also measures higher-order aberrations not identified by other techniques. However, as with AR results, a spectacle prescription based solely on its measurements may not be appropriate for all patients.

Ecological expected utility and the mythical neural code.

Neural spikes are an evolutionarily ancient innovation that remains nature's unique mechanism for rapid, long distance information transfer. It is now known that neural spikes sub serve a wide variety of functions and essentially all of the basic questions about the communication role of spikes have been answered. Current efforts focus on the neural communication of probabilities and utility values involved in decision making. Significant progress is being made, but many framing issues remain. One basic problem is that the metaphor of a neural code suggests a communication network rather than a recurrent computational system like the real brain. We propose studying the various manifestations of neural spike signaling as adaptations that optimize a utility function called ecological expected utility.

Embodied language, best-fit analysis, and formal compositionality.

This review brings together two fundamental, but unreconciled, aspects of human language: embodiment and compositionality. One major scientific advance in recent decades has been Embodiment - the realization that scientific understanding of mind and language entails detailed modeling of the human brain and how it evolved to control a physical body in a social community. The ability to learn and use language is one of the most characteristically human traits. Many animals signal, but only people can express and understand an essentially unbounded range of messages. The technical term for the ability of human language to support all these messages from a few dozen alphabetic symbols is Compositionality. Rigor is essential for the advancement of any science, but there has been essentially no overlap between efforts to formalize language compositionality and the manifest embodiment of thought. Recent developments suggest that it is feasible to formalize the compositionality of embodied language, but that this requires a focus on conceptual composition and better understanding of contextual best-fit.

Reduction of symptoms in binocular anomalies using computerized home therapy-HTS.

BACKGROUND: Asthenopic symptoms often are associated with various accommodative/vergence disorders. Recent studies have found that symptoms associated with convergence insufficiency are reduced by in-office vision therapy with supplemental home therapy. No studies have used standardized symptom questionnaires to evaluate the effectiveness of either in-office or home-based vision therapy in binocular anomalies other than convergence insufficiency. This retrospective study was designed to evaluate the changes in symptoms using an automated, home computer vision therapy program (HTS) in accommodative/vergence disorders. METHODS: A retrospective study of 43 prepresbyopic patients who completed the HTS was performed. Before and immediately after treatment all patients in this study completed a 15-question symptom questionnaire (Convergence Insufficiency Symptom Survey). Treatment consisted of various accommodative and vergence activities. RESULTS: Initial symptoms scores on the scaled questionnaire were 32.8 (SD = 8.1); after therapy they were 20.6 (SD = 11.5). These changes were both clinically and statistically significant. Forty percent were "normalized" and 55% improved. Convergence amplitude improved from 22Delta to 53Delta after treatment, and divergence amplitudes improved from 15Delta to 25Delta. These findings were clinically significant. Lastly, more than 75% of the patients finished the program by 40 sessions (equivalent to 8 weeks). CONCLUSION: Automated vision therapy delivered by the HTS system improved convergence and divergence amplitudes with a concomitant reduction in symptoms. The HTS system should be used on those patients with symptoms associated with an accommodative/vergence anomaly when in-office vision therapy supplemented with home therapy is not practical.

A (somewhat) new solution to the variable binding problem.

To perform automatic, unconscious inference, the human brain must solve the binding problem by correctly grouping properties with objects. Temporal binding models like SHRUTI already suggest much of how this might be done in a connectionist and localist way by using temporal synchrony. We propose a set of alternatives to temporal synchrony mechanisms that instead use short signatures. This serves two functions: it allows us to explore an additional biologically plausible alternative, and it allows us to extend and improve the capabilities of these models. These extensions model the human ability to both perform unification and handle multiple instantiations of logical terms. To verify our model's feasibility, we simulate it with a computer system modeling simple, neuron-like computations.

Modulation of the FFA and PPA by language related to faces and places.

Does sentence comprehension related to faces modulate activity in the fusiform face area (FFA) and does sentence comprehension related to places modulate activity in the parahippocampal place area (PPA)? We investigated this question in an fMRI experiment. Participants listened to sentences describing faces, places, or objects, with the latter serving as a control condition. In a separate run, we localized the FFA and PPA in each participant using a perceptual task. We observed a significant interaction between the region of interest (FFA vs. PPA) and sentence type (face vs. place). Activity in the left FFA was modulated by face sentences and in the left PPA was modulated by place sentences. Surprisingly, activation in each region of interest was reduced when listening to sentences requiring semantic analysis related to that region's domain specificity. No modulation was found in the corresponding right hemisphere ROIs. We conclude that processing sentences may involve inhibition of some visual processing areas in a content-specific manner. Furthermore, our data indicate that this semantic-based modulation is restricted to the left hemisphere. We discuss how these results may constrain neural models of embodied semantics.

Detecting pheochromocytoma: defining the most sensitive test.

OBJECTIVE: To define the most sensitive biochemical test to establish the diagnosis of pheochromocytoma and also to assess the potential role of iodine 131-labeled metaiodobenzylguanidine scintigraphy (I-MIBG) in the diagnosis of this tumor. SUMMARY BACKGROUND DATA: Pheochromocytoma is a rare, catecholamine-producing tumor with preferential localization in the adrenal gland. Despite its importance, the most sensitive test to establish the diagnosis remains to be defined. METHODS: Prospective data collection was done on patients with pheochromocytoma treated at the Duke University Medical Center and the Durham Veterans Affairs Medical Center, Durham, NC. All urinary, plasma, and platelet analyses were highly standardized and supervised by one investigator (J.M.F.). I-MIBG scans were independently reviewed by 2 nuclear medicine physicians. RESULTS: A total of 152 patients (55.3% female) were enrolled in the present analysis. Patients were predominantly white (73.7%). Spells (defined as profuse sweating, tachycardia, and headache) and hypertension at diagnosis were present in 51.4% and 66.6%, respectively. Bilateral disease was found in 12.5%, malignant pheochromocytoma in 29.6%, and hereditary forms in 23.0%. The most sensitive tests were total urinary normetanephrine (96.9%), platelet norepinephrine (93.8%), and I-MIBG scintigraphy (83.7%). In combination with I-MIBG scintigraphy, platelet norepinephrine had a sensitivity of 100%, plasma norepinephrine/MIBG of 97.1%, total urine normetanephrine/MIBG of 96.6%, and urine norepinephrine/MIBG of 95.3%. CONCLUSIONS: The tests of choice to establish the diagnosis of pheochromocytoma are urinary normetanephrine and platelet norepinephrine. A combination of I-MIBG scintigraphy and diagnostic tests in urine, blood, or platelets does further improve the sensitivity. We thus advocate performing an MIBG scan if the diagnosis of pheochromocytoma is clinically suspected and catecholamine measurements are within the normal range.

Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients.

BACKGROUND: Iodine-131 metaiodobenzylguanidine (131I-MIBG) is useful for imaging carcinoid tumors and recently has been applied to the palliative treatment of metastatic carcinoid in small studies. The authors now report their results on the therapeutic utility of high-dose 131I-MIBG treatment in a large group of patients with metastatic carcinoid tumors. METHODS: The authors performed a retrospective review of 98 patients with metastatic carcinoid who were treated at their institution with 131I-MIBG over a 15-year period. Endpoints examined included the World Health Organization criteria for treatment response: symptoms, hormone (5-hydroxyindoleacetic acid [5-HIAA]) production, and clinical tumor response. RESULTS: Patients received a median dose of 401 +/- 202 millicuries (mCi) 131I-MIBG. The median survival after treatment was 2.3 years. Patients who experienced a symptomatic response had improved survival (5.76 years vs. 2.09 years; P < 0.01). For the 56 patients who had 5-HIAA levels monitored, the mean urine 5-HIAA levels decreased significantly after 131I-MIBG treatment (126 +/- 122 ng/mL vs. 91 +/- 125 ng/mL; P < 0.01); however, the patients with reduced 5-HIAA levels did not experience improved survival (4.11 years vs. 3.42 years; P = 0.2). Patients who received an initial 131I-MIBG dose > 400 mCi lived longer than patients who received < 400 mCi (4.69 years vs. 1.86 years; P = 0.05). Radiographic tumor response did not predict survival. Toxicity included pancytopenia, thrombocytopenia, nausea, and emesis. CONCLUSIONS: The current data support 131I-MIBG treatment in select patients with metastatic carcinoid who progress despite optimal medical management. Improved survival was predicted best by symptomatic response to 131I-MIBG treatment, but not by hormone or radiographic response.