Besides controlling eye movements, the brain's oculomotor system has been implicated in the control of covert spatial attention and the rehearsal of spatial information in working memory. We investigated whether the oculomotor system also contributes to rehearsing visual objects in working memory when object location is never asked about. To address this, we tracked the incidental use of locations for mnemonic rehearsal via directional biases in microsaccades while participants maintained two visual objects (colored oriented gratings) in working memory. By varying the stimulus configuration (horizontal, diagonal, and vertical) at encoding, we could quantify whether microsaccades were more aligned with the configurational axis of the memory contents, as opposed to the orthogonal axis. Experiment 1 revealed that microsaccades continued to be biased along the axis of the memory content several seconds into the working memory delay. In Experiment 2, we confirmed that this directional microsaccade bias was spec...

Although animal research implicates a central role for dopamine in motor skill learning, a direct causal link has yet to be established in neurotypical humans. Here, we tested if a pharmacological manipulation of dopamine alters motor learning, using a paradigm which engaged explicit, goal-directed strategies. Participants (27 females; 11 males; aged 18–29 years) first consumed either 100 mg of levodopa ( n  = 19), a dopamine precursor that increases dopamine availability, or placebo ( n  = 19). Then, during training, participants learnt the explicit strategy of aiming away from presented targets by instructed angles of varying sizes. Targets jumped mid-movement by the instructed aiming angle. Task success was thus contingent upon aiming accuracy and not speed. The effect of the dopamine manipulations on skill learning was assessed during training and after an overnight follow-up. Increasing dopamine availability at training improved aiming accuracy and lengthened reaction times, particularly for larger, m...

Genome wide association study (GWAS) uncovered Alzheimer's disease (AD) risk genes linked to the endo-lysosomal pathway. This pathway seems to be the gateway of protein aggregates, such as tau and α-synuclein, to the cytoplasm. Furthermore, we and others reported that the amyloid precursor protein (APP) C99 is predominantly processed by γ-secretase in the endo-lysosomal compartments, and β-amyloid (Aβ) peptides are enriched in the same subcellular loci. While the role(s) of APP/Aβ in the endo-lysosomal pathway has not been fully established, a recent study reported that Aβ, in particular Aβ42, inhibits cathepsin D (CTSD) activity. Here, we show using a cell-free in vitro assay that Aβ42 also blocks cathepsin B (CTSB) activity. Furthermore, we uncovered that the autocatalytic processing (i.e., conversion of single chain to heavy/light chains) of CTSB and CTSD is accelerated in APP-deficient cells compared with wild-type controls. Taken together, our findings further support the negative regulation of cathep...

Stereotypical isocortical tau protein pathology along the Braak stages has been described as an instigator of neurodegeneration in Alzheimer's disease (AD). Less is known about tau pathology in motor regions, although higher-order motor deficits such as praxis dysfunction are part of the clinical description. Here, we examined how tau pathology in cytoarchitectonically mapped regions of the primary and higher-order motor network in comparison to primary visual and sensory regions varies across the clinical spectrum of AD. We analyzed tau PET scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort in patients with mild cognitive impairment (MCI; N  = 84) and dementia of the Alzheimer's disease type (DAD; N  = 25). Additionally, an amyloid-negative sample of healthy older individuals (HC; N  = 26) were included. Standard uptake ratio values (SUVRs) were extracted in native space from the left and the right hemispheres. A repeated measurement analysis of variance was conducted to assess the e...

Gordon Holmes syndrome (GHS) is a neurological disorder associated with neuroendocrine, cognitive, and motor impairments with corresponding neurodegeneration. Mutations in the E3 ubiquitin ligase RNF216 are strongly linked to GHS. Previous studies show that deletion of Rnf216 in mice led to sex-specific neuroendocrine dysfunction due to disruptions in the hypothalamic-pituitary-gonadal axis. To address RNF216 action in cognitive and motor functions, we tested Rnf216 knockout (KO) mice in a battery of motor and learning tasks for a duration of one year. Although male and female KO mice did not demonstrate prominent motor phenotypes, KO females displayed abnormal limb clasping. KO mice also showed age-dependent strategy and associative learning impairments with sex-dependent alterations of microglia in the hippocampus and cortex. Additionally, KO males but not females had more negative resting membrane potentials in the CA1 hippocampus without any changes in miniature excitatory postsynaptic current (mEPSC) ...

The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in their connection strength with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert distinct influences on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1 in male and female mice, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that M1 and S1 dually innervate SPNs and FSIs, however there is a consistent bia...

Voluntary motor control is thought to be predicated on the ability to efficiently integrate and process somatosensory afferent information. However, current approaches in the field of motor control have not factored in objective markers of how the brain tracks incoming somatosensory information. Here, we asked whether motor performance relates with such markers obtained with an analysis of the coupling between peripheral kinematics and cortical oscillations during continuous movements, best known as corticokinematic coherence (CKC). Motor performance was evaluated by measuring both gross and fine motor skills using the Box and Blocks Test (BBT) and the Purdue Pegboard Test (PPT), respectively, and with a biomechanics measure of coordination. Sixty-one participants completed the BBT, while equipped with electroencephalography and electromyography, and the PPT. We evaluated CKC, from the signals collected during the BBT, as the coherence between movement rhythmicity and brain activity, and coordination as th...

Declaring the 1990's as The Decade of the Brain put the field of neuroscience at the forefront of public attention, with the nervous system becoming a subject of increasing interest in popular media. Although this has generally brought large swaths of the public closer to neuroscience, most current research is published and disseminated in a single language: English. This is unsurprising as English is indeed the lingua franca in scientific circles, but people around the world communicate in many other languages. To make neuroscience accessible to a larger audience, we share an initiative to translate the Knowing Neurons platform into a second language: Spanish. This collaborative project integrates Humanities and STEM academic programs to make use of bilingual university students, in association with professional linguists and neuroscientists, to translate scientific content into a relatable format to Spanish speakers regardless of their country of origin. The translation effort was piloted within the fram...

Humans use tactile feedback to perform skillful manipulation. When tactile sensory feedback is unavailable, for instance, if the fingers are anesthetized, dexterity is severely impaired. Imaging the deformation of the finger pad skin when in contact with a transparent plate provides information about the tactile feedback received by the central nervous system. Indeed, skin deformations are transduced into neural signals by the mechanoreceptors of the finger pad skin. Understanding how this feedback is used for active object manipulation would improve our understanding of human dexterity. In this paper, we present a new device for imaging the skin of the finger pad of one finger during manipulation performed with a precision grip. The device’s mass (300 g) makes it easy to use during unconstrained dexterous manipulation. Using this device, we reproduced the experiment performed in Delhaye et al. 2021a. We extracted the strains aligned with the object’s movement, i.e., the vertical strains in the ulnar and r...

Stereotypical isocortical tau protein pathology along the Braak-Stages has been described as an instigator of neurodegeneration in Alzheimer's Disease (AD). Less is known about tau pathology in motor regions, although higher-order motor deficits such as praxis dysfunction are part of the clinical description. Here, we examined how tau pathology in cytoarchitectonically mapped regions of the primary and higher-order motor network in comparison to primary visual and sensory regions varies across the clinical spectrum of AD. We analyzed tau PET scans from the ADNI-cohort in patients with mild cognitive impairment (MCI; N  = 84) and dementia of the Alzheimer's Disease type (DAD; N  = 25). Additionally, an amyloid-negative sample of healthy older individuals (HC; N  = 26) were included. Standard-uptake ratio values (SUVR) were extracted in native space from the left and the right hemispheres. A repeated measurement analysis of variance was conducted to assess the effect of diagnostic disease category on tau pat...