Biology subjects

Knakker, B.

Publications and source records attributed to Knakker, B..

7 recordsLinked to original sources

bioRxiv2026

Transcranial Magnetic Stimulation in Awake Rhesus macaques: Validation of a Novel Non-invasive Apparatus

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique widely employed in basic and clinical research. Non-human primates (NHPs) represent translationally valuable models due to their close anatomical and functional similarity to humans. However, significant technical challenges remain in implementing human-like TMS protocols in awake NHPs. Here we developed a non-invasive head- and arm-fixation apparatus that enables reliable stimulation and electromyography recordings in awake NHPs without surgical intervention and validated the apparatus with two TMS protocols in rhesus macaques. First, we implemented an adaptive motor threshold (MT) determination method developed recently for humans, which converged successfully to valid MTs as defined by the International Federation of Clinical Neurophysiology. Second, we measured a robust short-interval intracortical inhibition effect for the first time in awake NHPs. Successful implementation of human TMS protocols in awake NHPs provides proof-of-concept validation of our apparatus, paving the way to bidirectionally translatable, clinically relevant neuromodulation protocols.

neuroscience↗

bioRxiv2024

Assessment of cortical excitability in awake rhesus macaques with transcranial magnetic stimulation: translational insights from recruitment curves

Background and objectivesCortical excitability (CE) is commonly assessed by recording motor evoked potentials (MEPs) in response to single-pulse transcranial magnetic stimulation (sp-TMS). While the motor threshold (MT) remains the most widely used measure of CE, it provides a one-dimensional, criterion-based assessment. In contrast, the recruitment curve (RC) offers a more comprehensive characterization of the full dynamics of cortical recruitment. Yet, only a few preclinical studies involving translationally relevant non-human primates were conducted, and most were under anaesthesia. Hence, we aimed to characterise CE in awake rhesus macaques by recording traditionally defined MT and RCs. MethodsTraditional MT with a 100 {micro}V MEP criterion ( tradMT) was measured in 8 awake adult male rhesus macaques using C-B65 coil and MagVenture stimulator. RCs were recorded at nine relative intensity levels (0.5 - 1.5 x tradMT) in 4 macaques. A sigmoid function was fitted to obtain key CE parameters: the inflection point, lower ankle point, and plateau. ResultsTradMT values were stable and replicable, and aligned most closely with the inflection point of the RC. The lower ankle points were found around at 0.9 x tradMT, marking the transition from a constant to a logarithmic phase, representing a physiologically relevant threshold. Plateau MEP amplitudes were substantially smaller compared to those reported in humans. ConclusionFitted RC parameters revealed a distinction between tradMT and the physiologically relevant threshold. The overall RC shape was consistent with human data, suggesting similar recruitment processes, leading to high translational validity. However, the marked difference in maximal MEP magnitude emphasises the importance of species-specific adaptations.

neuroscience↗

bioRxiv2024

GLP-1 receptor agonist exenatide uncouples food intake from hedonic and anticipatory regulation in non-human primates: Insights from an operant meal schedule paradigm

Glucagon-like peptide 1 (GLP-1), a neuroendocrine signal of energy balance and satiety, has a major role in regulating food intake behaviour. Here we investigated the effects of the GLP-1 agonist exenatide on palatability-driven feeding regulation in adult male rhesus macaques (n=5) using a novel operant food intake paradigm with four meal schedule conditions where two types of pellets with different palatability values were offered as meal in all combinations in two consecutive daily feeding sessions (S1 and S2). In control conditions, a strong, palatability-driven anticipatory effect was found in S1, followed by a complementary positive contrast effect in S2. After acute subcutaneous treatment with 1 {micro}g/kg dose of exenatide 1 h before S1, food intake decreased to the same very low level in all meal schedule conditions in S1, completely erasing the previously observed anticipatory effect. Conversely, exenatide induced hypoglycaemia in an anticipatory meal schedule dependent pattern. Interestingly, the previously observed positive contrast effect was spared in S2, with a weaker residual effect specifically on the consumption of the more palatable pellet type. To conclude, the food intake reducing effects of exenatide may temporally evolve from strong anorectic to weak anhedonic modulations, where hedonic experience and anticipation during the early anorectic phase is conserved but uncoupled from food intake behaviour.

pharmacology and toxicology↗

bioRxiv2020

Delay-dependent cholinergic modulation of visual short-term memory in rhesus macaques

Cholinergic neuromodulation is known to play a key role in visual working memory (VWM) - keeping relevant stimulus representations available for cognitive processes for short time periods up to a few minutes. Despite the growing body of evidence on how the neural and cognitive mechanisms of VWM dynamically change over retention time, there is mixed evidence available on cholinergic effects as a function of VWM delay period in non-human primates. Using the delayed matching to sample VWM task in rhesus macaques (N=6), we aimed to characterize VWM maintenance in terms of performance changes as a function of delay duration (across a wide range of delays from 1 to 76 s). Then, we studied how cholinergic neuromodulation influences VWM maintenance using the muscarinic receptor antagonist scopolamine administered alone as transient amnestic treatment, and in combination with two doses of the acetylcholinesterase inhibitor donepezil, a widely used Alzheimers medication probing for the reversal of scopolamine-induced impairments. Results indicate that scopolamine-induced impairments of VWM maintenance are delay-dependent and specifically affect the 15-33 s time range, suggesting that scopolamine worsens the normal decay of VWM with the passage of time. Donepezil partially rescued the observed scopolamine-induced impairments of VWM performance. These results provide strong behavioral evidence for the role of increased cholinergic tone and muscarinic neuromodulation in the maintenance of VWM beyond a few seconds, in line with our current knowledge on the role of muscarinic acetylcholine receptors in sustained neural activity during VWM delay periods.

animal behavior and cognition↗

bioRxiv2019

Dissociating cholinergic influence on alertness andtemporal attention in primates in a simple reaction-timeparadigm

The ability to promptly respond to behaviourally relevant events depends on both general alertness and phasic changes in attentional state driven by temporal expectations. Using a variable foreperiod simple reaction time (RT) task in four adult male rhesus macaques, we investigated the role of the cholinergic system in alertness and temporal expectation. Foreperiod-effects on RT reflect temporal expectation, while alertness is quantified as overall response speed. We measured these RT parameters under vehicle treatment and systemic administration of the muscarinic receptor antagonist scopolamine. We also investigated whether and to what extent the effects of scopolamine were reversed by donepezil, a cholinesterase inhibitor widely used for the treatment of dementia. In the control condition, RT showed a continuous decrease as the foreperiod duration increased, which clearly indicated the effect of temporal expectation on RT. This foreperiod effect was mainly detectable on the faster tail of the RT distribution and was eliminated by scopolamine. Furthermore, scopolamine treatment slowed down the average RT. Donepezil treatment was efficient on the slower tail of the RT distribution and improved scopolamine-induced impairments only on the average RT reflecting a general beneficial effect on alertness without any improvement in temporal expectation. The present results highlight the role of the cholinergic system in temporal expectation and alertness in primates and help delineate the efficacy and scope of donepezil and other cholinomimetic agents as cognitive enhancers in present and future clinical practice.

animal behavior and cognition↗

bioRxiv2018

Short-term radiofrequency exposure from new generation mobile phones reduces EEG alpha power with no effects on cognitive performance

Although mobile phone (MP) use has been steadily increasing in the last decades and similar positive trends are expected for the near future, systematic investigations on neurophysiological and cognitive effects caused by recently developed technological standards for MPs are scarcely available. Here, we investigated the effects of radiofrequency (RF) fields emitted by new-generation mobile technologies, specifically, Universal Mobile Telecommunications System (UMTS) and Long-Term Evolution (LTE), on intrinsic scalp EEG activity in the alpha band (8-12 Hz) and cognitive performance in the Stroop test. The study involved 60 healthy, young-adult university students (34 for UMTS and 26 for LTE) with double-blind administration of Real and Sham exposure in separate sessions. EEG was recorded before, during and after RF exposure, and Stroop performance was assessed before and after EEG recording. Both RF exposure types caused a notable decrease in the alpha power over the whole scalp that persisted even after the cessation of the exposure, whereas no effects were found on any aspects of performance in the Stroop test. The results imply that the brain networks underlying global alpha oscillations might require minor reconfiguration to adapt to the local biophysical changes caused by focal RF exposure mimicking MP use.

neuroscience↗

bioRxiv2017

Face inversion reveals holistic processing of peripheral faces

Face perception is accomplished by face-selective neural processes, involving holistic processing that enables highly efficient integration of facial features into a whole face representation. It has been shown that in face-selective regions of the ventral temporal cortex, neural resources involved in holistic processing are primarily dedicated to the central portion of the visual field. These findings raise the intriguing possibility that holistic processing might be the privilege of centrally presented faces and could be strongly diminished in the case of peripheral faces. We addressed this question using the face inversion effect, a well established marker of holistic face processing. The behavioral results revealed impaired identity discrimination performance for inverted peripheral faces scaled according to the V1 magnification factor, compared to upright presented faces. The size of peripheral face inversion effect (FIE) was comparable to that found for centrally displayed faces. Face inversion affected the early ERP responses to faces in two time intervals. The earliest FIE was most pronounced in the time window between 130-140 ms following stimulus presentation, for both centrally and peripherally displayed faces and in the latter case, it was present only over the contralateral hemisphere. The timing of the next component FIE corresponded closely with the temporal interval of the N170 ERP component and showed strong right hemisphere lateralization, both when faces were displayed in the left or right visual field. Furthermore, we also showed that centrally presented face masks impaired peripheral face identity discrimination performance, but did not reduce the magnitude of the FIE. These findings revealed robust behavioral and neural inversion effects for peripheral faces and thus suggest that faces are processed holistically throughout the visual field.\n\nHighlightsRobust behavioral and neural inversion effect was found for peripheral faces.\n\nP1 ERP component is modulated by inverted central and contralateral faces.\n\nN170 ERP component is modulated by centrally and peripherally presented faces.\n\nNeural face inversion effect shows strong right hemisphere lateralization.\n\nFaces are processed holistically throughout the visual field.

neuroscience↗