Musical imagery is the voluntary internal hearing of music in the mind without the need for physical action or external stimulation. Numerous studies have already revealed brain areas activated during imagery. However, it remains unclear to what extent imagined music responses preserve the detailed temporal dynamics of the acoustic stimulus envelope and, crucially, whether melodic expectations play any role in modulating responses to imagined music, as they prominently do during listening. These modulations are important as they reflect aspects of the human musical experience, such as its acquisition, engagement, and enjoyment. This study explored the nature of these modulations in imagined music based on EEG recordings from 21 professional musicians (6 females and 15 males). Regression analyses were conducted to demonstrate that imagined neural signals can be predicted accurately, similarly to the listening task, and were sufficiently robust to allow for accurate identification of the imagined musical pie...

Human language learning differs significantly across individuals in the process and ultimate attainment. Although decades of research exploring the neural substrates of language learning have identified distinct and overlapping neural networks subserving learning of different components, the neural mechanisms that drive the large interindividual differences are still far from being understood. Here we examine to what extent the neural dynamics of multiple brain networks in men and women across sessions of training contribute to explaining individual differences in learning multiple linguistic components (i.e., vocabulary, morphology, and phrase and sentence structures) of an artificial language in a 7 d training and imaging paradigm with functional MRI. With machine-learning and predictive modeling, neural activation patterns across training sessions were highly predictive of individual learning success profiles derived from the four components. We identified four neural learning networks (i.e., the Perisy...

Progress in understanding the neural bases of cognitive control has been supported by the paradigmatic color-word Stroop task, in which a target response (color name) must be selected over a more automatic, yet potentially incongruent, distractor response (word). For this paradigm, models have postulated complementary coding schemes: dorsomedial frontal cortex (DMFC) is proposed to evaluate the demand for control via incongruency-related coding, whereas dorsolateral PFC (DLPFC) is proposed to implement control via goal and target-related coding. Yet, mapping these theorized schemes to measured neural activity within this task has been challenging. Here, we tested for these coding schemes relatively directly, by decomposing an event-related color-word Stroop task via representational similarity analysis. Three neural coding models were fit to the similarity structure of multivoxel patterns of human fMRI activity, acquired from 65 healthy, young-adult males and females. Incongruency coding was predominant in...

The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. CNGA3 -achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of gray. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two CNGA3 -achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI-based measurements to assess participants' early visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed, including reduction in photoaver...

Cell-to-cell transmission of α-synuclein (α-syn) pathology is considered to underlie the spread of neurodegeneration in Parkinson's disease (PD). Previous studies have demonstrated that α-syn is secreted under physiological conditions in neuronal cell lines and primary neurons. However, the molecular mechanisms that regulate extracellular α-syn secretion remain unclear. In this study, we found that inhibition of monoamine oxidase-B (MAO-B) enzymatic activity facilitated α-syn secretion in human neuroblastoma SH-SY5Y cells. Both inhibition of MAO-B by selegiline or rasagiline and siRNA-mediated knock-down of MAO-B facilitated α-syn secretion. However, TVP-1022, the S-isomer of rasagiline that is 1000 times less active, failed to facilitate α-syn secretion. Additionally, the MAO-B inhibition-induced increase in α-syn secretion was unaffected by brefeldin A, which inhibits endoplasmic reticulum (ER)/Golgi transport, but was blocked by probenecid and glyburide, which inhibit ATP-binding cassette (ABC) transpor...

In the article “Control of Motoneuron Survival by Angiogenin,” by Dairín Kieran, Jordi Sebastia, Matthew J. Greenway, Matthew A. King, Dervla Connaughton, Caoimhin G. Concannon, Beau Fenner, Orla Hardiman, and Jochen H. M. Prehn, which appeared on pages [14056–14061][1] of the December 24,

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles. Aβ oligomers cause synaptic dysfunction early in AD by enhancing long-term depression (LTD; a paradigm for forgetfulness) via metabotropic glutamate receptor (mGluR)-dependent regulation of striatal-enriched tyrosine phosphatase (STEP61). Reelin is a neuromodulator that signals through ApoE (apolipoprotein E) receptors to protect the synapse against Aβ toxicity ([Durakoglugil et al., 2009][1]) Reelin signaling is impaired by ApoE4, the most important genetic risk factor for AD, and Aβ-oligomers activate metabotropic glutamate receptors ([Renner et al., 2010][2]). We therefore asked whether Reelin might also affect mGluR-LTD. To this end, we induced chemical mGluR-LTD using DHPG (Dihydroxyphenylglycine), a selective mGluR5 agonist. We found that exogenous Reelin reduces the DHPG-induced increase in STEP61, prevents the dephosphorylation of GluA2, and concomita...

The transcription factor cAMP response element-binding protein (CREB) is involved in a myriad of cellular functions in the central nervous system. For instance, the role of CREB via phosphorylation at the amino-acid residue Serine (Ser)133 in expressing plasticity-related genes and activity-dependent neuronal plasticity processes has been extensively demonstrated. However, much less is known about the role of CREB phosphorylation at Ser142 and Ser143. Here, we employed a viral vector containing a dominant negative form of CREB, with serine-to-alanine mutations at residue 142 and 143 to specifically block phosphorylation at both sites. We then transfected this vector into primary neurons in vitro or intracortically injected it into mice in vivo , to test whether these phosphorylation events were important for activity-dependent plasticity. We demonstrated by immunohistochemistry of cortical neuronal cultures that the expression of Arc, a known plasticity-related gene, requires triple phosphorylation of CREB...

Visual representations can be generated via feedforward or feedback processes. The extent to which these processes result in overlapping representations remains unclear. Previous work has shown that imagined stimuli elicit similar representations as perceived stimuli throughout the visual cortex. However, while representations during imagery are indeed only caused by feedback processing, neural processing during perception is an interplay of both feedforward and feedback processing. This means that any representational overlap could be because of overlap in feedback processes. In the current study, we aimed to investigate this issue by characterizing the overlap between feedforward- and feedback-initiated category representations during imagined stimuli, conscious perception, and unconscious processing using fMRI in humans of either sex. While all three conditions elicited stimulus representations in left lateral occipital cortex (LOC), significant similarities were observed only between imagery and consci...