Lateral orbitofrontal cortex promotes trial-by-trial learning of risky, but not spatial, biases

Individual choices are not made in isolation but are embedded in a series of past experiences, decisions, and outcomes. The effects of past experiences on choices, often called sequential biases, are ubiquitous in perceptual and value-based decision-making, but their neural substrates are unclear. We trained rats to choose between cued guaranteed and probabilistic rewards in a task in which outcomes on each trial were independent. Behavioral variability often reflected sequential effects, including increased willingness to take risks following risky wins, and spatial ‘win-stay/lose-shift’ biases. Recordings from lateral orbitofrontal cortex (lOFC) revealed encoding of reward history and receipt, and optogenetic inhibition of lOFC eliminated rats’ increased preference for risk following risky wins, but spared other sequential effects. Our data show that different sequential biases are neurally dissociable, and the lOFC’s role in adaptive behavior promotes learning of more abstract biases (here, biases for the risky option), but not spatial ones

Beyond traditional understanding of gender measurement: the gender (re)presentation approach

This paper considers different approaches to measuring gender. It critically reviews gender role theorising and describes how this has informed two approaches to measuring gender as an individual phenomenon: gender orientation (the assessment of individual traits) and gender ideology (assessing individual endorsement, and internalisation, of social norms). It is argued here that social constructionist perspectives offer a viable alternative to gender role theory and that these inform an alternative approach to measuring gender as a social phenomenon: gender (re)presentation. This approach assesses group level endorsement of dominant gender representations. Endorsement is not seen to reflect individual traits or internalised social norms. Rather, it is understood as a social practice, made meaningful through shared understanding of dominant gender representation. This approach is introduced through a critique of the traditional concept of attitudes and a reformulation thereof. The practical measurement implications and benefit of this reformulation are outlined

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

<p>Abstract</p> <p>Background</p> <p>The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.</p> <p>Methods</p> <p>Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.</p> <p>Results</p> <p>All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (<it>p </it>< 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.</p> <p>Conclusions</p> <p>Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.</p

Prefrontal Cortex HCN1 Channels Enable Intrinsic Persistent Neural Firing and Executive Memory Function

In many cortical neurons, HCN1 channels are the major contributors to I(h), the hyperpolarization-activated current, which regulates the intrinsic properties of neurons and shapes their integration of synaptic inputs, paces rhythmic activity, and regulates synaptic plasticity. Here, we examine the physiological role of I(h) in deep layer pyramidal neurons in mouse prefrontal cortex (PFC), focusing on persistent activity, a form of sustained firing thought to be important for the behavioral function of the PFC during working memory tasks. We find that HCN1 contributes to the intrinsic persistent firing that is induced by a brief depolarizing current stimulus in the presence of muscarinic agonists. Deletion of HCN1 or acute pharmacological blockade of I(h) decreases the fraction of neurons capable of generating persistent firing. The reduction in persistent firing is caused by the membrane hyperpolarization that results from the deletion of HCN1 or I(h) blockade, rather than a specific role of the hyperpolarization-activated current in generating persistent activity. In vivo recordings show that deletion of HCN1 has no effect on up states, periods of enhanced synaptic network activity. Parallel behavioral studies demonstrate that HCN1 contributes to the PFC-dependent resolution of proactive interference during working memory. These results thus provide genetic evidence demonstrating the importance of HCN1 to intrinsic persistent firing and the behavioral output of the PFC. The causal role of intrinsic persistent firing in PFC-mediated behavior remains an open question

Dynamic Effective Connectivity of Inter-Areal Brain Circuits

Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity (or, more precisely, causal connectivity), related to the elusive question “Which areas cause the present activity of which others?”. Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study mesoscale network motifs of interacting cortical areas, modeled as large random networks of spiking neurons or as simple rate units. Through a causal analysis of time-series of model neural activity, we show that different dynamical states generated by a same structural connectivity motif correspond to distinct effective connectivity motifs. Such effective motifs can display a dominant directionality, due to spontaneous symmetry breaking and effective entrainment between local brain rhythms, although all connections in the considered structural motifs are reciprocal. We show then that transitions between effective connectivity configurations (like, for instance, reversal in the direction of inter-areal interactions) can be triggered reliably by brief perturbation inputs, properly timed with respect to an ongoing local oscillation, without the need for plastic synaptic changes. Finally, we analyze how the information encoded in spiking patterns of a local neuronal population is propagated across a fixed structural connectivity motif, demonstrating that changes in the active effective connectivity regulate both the efficiency and the directionality of information transfer. Previous studies stressed the role played by coherent oscillations in establishing efficient communication between distant areas. Going beyond these early proposals, we advance here that dynamic interactions between brain rhythms provide as well the basis for the self-organized control of this “communication-through-coherence”, making thus possible a fast “on-demand” reconfiguration of global information routing modalities

Masculinity—Femininity

Six areas of research in developmental and personality psychology concerning sex-typed traits, attitudes, and interests are identified as elements of a common “masculinity-femininity” paradigm needing reexamination. The masculinity-femininity paradigm is defined in relationship to Money and Ehrhardt's model for gender identity differentiation and dimorphism. The six lines of research in the masculinity-femininity paradigm are then briefly critically examined: (1) the measurability of masculinity-femininity as a trait, (2) the identification model of masculinity-femininity development, (3) the effects of father absence on boys, (4) correlates of masculinity-femininity in life adjustment, (5) cross-sex identity in males, and (6) sex role identity problems in black males. The empirical and conceptual problems in each line of research are explored, and are substantial enough to suggest the need for alternate paradigms. Two alternate models for masculinity-femininity development are briefly sketched. First, masculinity-femininity development is analogized to moral development, as a phasic process ideally leading to sex role transcendence and androgyny. Second, the acquisition of masculinity-femininity is analogized to language acquisition, as a highly symbol-dependent learning process contingent upon the interaction between an innate acquisition apparatus and a corpus of observed sex role behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45567/1/11199_2004_Article_BF00288009.pd