Lifelong premature ejaculation (LPE) is associated with abnormal brain function, as evidenced by functional MRI (fMRI) studies. This study investigates the stability of brain network architectures in resting-state conditions following perturbation by erotic tasks in individuals with LPE. We assessed the resting-state fMRI in the task-free and task-modulated dataset in the 28 right-hand LPE and 17 age-matched normal controls (NCs). The dynamic functional connectome based on the phase-locking algorithm and ROI-wise gradient mapping was compared. The stability of dynamic functional gradient mapping was measure by linear mixed effects across the two datasets in the LPE and NCs. In both groups, the brain functional gradient exhibited a clear transition from unimodal to transmodal in the principal gradient. Additionally, there was a segregation of primary networks observed in the secondary gradient, either before or after the task. In LPE patients, we observed increased stability in the bilateral dorsal prefront...

Early life stress (ELS) increases susceptibility to cognitive and socioemotional dysfunction by disrupting the neurobiological systems that regulate these behaviors. Animal models provide a valuable tool for investigating the underlying mechanisms, enabling precise manipulation of stress exposure during development. The limited bedding and nesting (LBN) model, which induces maternal stress by restricting access to bedding and nesting materials in rodents, has been instrumental in advancing our understanding of chronic ELS. While this paradigm has been widely adopted, variations in apparatus designs and subtle differences in methodologies could impact consistency across studies. Here, we provide standardized guidelines for a cost-effective open–source mouse LBN apparatus design, which could further enhance the model's utility while supporting pup survival. We additionally present our findings observed during the duration of the LBN paradigm, which spans from postnatal day (PND) 2 to 10, for both dams and pu...

Perceptual localization of brief, high-contrast perisaccadic visual probes is grossly erroneous. While this phenomenon has been extensively studied in humans, more needs to be learned about its underlying neural mechanisms. This ideally requires running similar behavioral paradigms in animals. However, during neurophysiology, neurons encountered in the relevant sensory and sensory–motor brain areas for visual mislocalization can have arbitrary, noncardinal response field locations. This necessitates using mislocalization paradigms that can work with any saccade direction. Here, we first established such a paradigm in three male rhesus macaque monkeys. In every trial, the monkeys generated a saccade toward an eccentric target. Once a saccade onset was detected, we presented a brief flash at one of three possible locations ahead of the saccade target location. After an experimentally imposed delay, we removed the saccade target, and the monkeys were then required to generate a memory-guided saccade toward th...

Dmrta2 (also designated Dmrt5) is a transcriptional regulator expressed in cortical progenitors in a caudomedialhigh/rostrolaterallow gradient with important roles at different steps of cortical development. Dmrta2 has been suggested to act in cortex development mainly by differential suppression of Pax6 and other homeobox transcription factors such as the ventral telencephalic regulator Gsx2 , which remains to be fully demonstrated. Here we have addressed the epistatic relation between Pax6 and Dmrta2 by comparing phenotypes in mutant embryos or embryos overexpressing both genes in various allelic combinations. We show that Dmrta2 cooperates with Pax6 in the maintenance of cortical identity in dorsal telencephalic progenitors and that it acts as a transcriptional repressor of Pax6 to control cortical patterning. Mechanistically, we show that in P19 cells, Dmrta2 acts as a DNA binding-dependent repressor on the Pax6 E60 enhancer and that a point mutation that affects its DNA binding properties identified i...

Savings refers to the gain in performance upon relearning. In sensorimotor adaptation, savings is tested by having participants adapt to perturbed feedback and, following a washout block during which the system resets to baseline, presenting the same perturbation again. While savings has been observed with these tasks, we have shown that the contribution from implicit adaptation, a process that uses errors to recalibrate the sensorimotor map, is attenuated upon relearning ( [Avraham et al., 2021][1]). Here, we test the hypothesis that this attenuation is due to interference arising from the different relationship between the movement and the feedback during washout. Removing the perturbation at the start of the washout block typically results in a salient error signal in the opposite direction to that observed during learning. We first replicated the finding that implicit adaptation is attenuated following a washout period that introduces salient opposite errors. When we eliminated feedback during washout,...

Regardless of discipline, quantitative literacy is a critical component of any scientist's skill set. A recent push from the NINDS has focused on enhancing and maintaining this expertise in trainees to enhance scientific fluency and to combat the reproducibility crisis. T32-funded programs often include off-campus retreats, providing opportunities to integrate a quantitative literacy component, or thematic focus. Here we will discuss the lessons and considerations learned from organizing a retreat focused on quantitative aspects of diagnostics for spinal cord injury. Survey results regarding retreat events and workshops reveal elements that were perceived to be successful by attendees. Events developed with active learning that focused on collaborative problem-solving and cross-discipline quantitative measures were well received by trainees. On the other hand, lectures and panel discussions were found to be less effective in boosting long-lasting improvements in quantitative literacy. Taken as a whole, the...

Paying attention to a target talker in multitalker scenarios is associated with its more accurate neural tracking relative to competing non-target speech. This “neural bias” to target speech has largely been demonstrated in experimental setups where target and non-target speech are acoustically controlled and interchangeable. However, in real-life situations this is rarely the case. For example, listeners often look at the talker they are paying attention to while non-target speech is heard (but not seen) from peripheral locations. To enhance the ecological-relevance of attention research, here we studied whether neural bias toward target speech is observed in a spatially realistic audiovisual context and how this is affected by switching the identity of the target talker. Group-level results show robust neural bias toward target speech, an effect that persisted and generalized after switching the identity of the target talker. In line with previous studies, this supports the utility of the speech-tracking...

The rodent brain contains 70,000,000+ neurons interconnected via complex axonal circuits with varying architectures. Neural pathologies are often associated with anatomical changes in these axonal projections and synaptic connections. Notably, axonal density variations of local and long-range projections increase or decrease as a function of the strengthening or weakening, respectively, of the information flow between brain regions. Traditionally, histological quantification of axonal inputs relied on assessing the fluorescence intensity in the brain region of interest. Despite yielding valuable insights, this conventional method is notably susceptible to background fluorescence, postacquisition adjustments, and inter-researcher variability. Additionally, it fails to account for nonuniform innervation across brain regions, thus overlooking critical data such as innervation percentages and axonal distribution patterns. In response to these challenges, we introduce AxoDen, an open-source semiautomated platfo...

α-Synuclein is a synaptic protein that accumulates primarily in synucleinopathies and secondarily in certain lysosomal storage disorders. However, its physiological roles in health and disease are not fully understood. In part, this has been hampered by the inability to visualize α-synuclein and its cellular localization, due to the lack of specific antibodies and faithful reporters. Here, we used CRISPR/Cas9-based genome editing to generate human-induced pluripotent stem cell (iPSC) lines in which the α-synuclein ( SNCA ) gene has been tagged with the short HA peptide either at the N-terminus or C-terminus or with the fluorescent protein mCherry at the C-terminus of the protein. These diverse strategies revealed the C-terminus HA-tag as the best option. C-Terminus HA-tagged α-synuclein had unchanged protein expression and did not generate degradation by-products. Importantly, we show that following differentiation to neurons, the C-terminus HA-tagged iPSC line had unaffected electrophysiological propertie...

Understanding the ability to self-evaluate decisions is an active area of research. This research has primarily focused on the neural correlates of self-evaluation during visual tasks and whether neural correlates before or after the primary decision contribute to self-reported confidence. This focus has been useful, yet the reliance on subjective confidence reports may confound our understanding of key everyday features of metacognitive self-evaluation: that decisions must be rapidly evaluated without explicit feedback and unfold in a multisensory world. These considerations led us to hypothesize that an automatic domain-general metacognitive signal may be shared between sensory modalities, which we tested in the present study with multivariate decoding of electroencephalographic (EEG) data. Participants ( N  = 21, 12 female) first performed a visual task with no request for self-evaluations of performance, prior to an auditory task that included rating decision confidence on each trial. A multivariate cl...