Biology subjects

Hassani, S. A.

Publications and source records attributed to Hassani, S. A..

5 recordsLinked to original sources

bioRxiv2023

Noradrenergic alpha-2a Receptor Stimulation Enhances Prediction Error Signaling in Anterior Cingulate Cortex and Striatum

The noradrenergic system is implicated to support behavioral flexibility by increasing exploration during periods of uncertainty and by enhancing working memory for goal-relevant stimuli. Possible sources mediating these pro-cognitive effects are 2A adrenoceptors (2AR) in prefrontal cortex or the anterior cingulate cortex facilitating fronto-striatal learning processes. We tested this hypothesis by selectively stimulating 2ARs using Guanfacine during feature-based attentional set shifting in nonhuman primates. We found that 2A stimulation improved learning from errors and facilitates updating the target feature of an attentional set. Neural recordings in the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex (dlPFC), and the striatum showed that 2A stimulation selectively enhanced the neural representation of negative reward prediction errors in neurons of the ACC and of positive prediction errors in the striatum, but not in dlPFC. This modulation was accompanied by enhanced encoding of the feature and location of the attended target across the fronto-striatal network. Enhanced learning was paralleled by enhanced encoding of outcomes in putative fast-spiking interneurons in the ACC, dlPFC, and striatum but not in broad spiking cells, pointing to an interneuron mediated mechanism of 2AR action. These results illustrate that 2A receptors causally support the noradrenergic enhancement of updating attention sets through an enhancement of prediction error signaling in the ACC and the striatum.

neuroscience↗

bioRxiv2021

Dose-dependent dissociation of pro-cognitive effects of donepezil on attention and cognitive flexibility in rhesus monkeys

BACKGROUNDDonepezil exerts pro-cognitive effects by non-selectively enhancing acetylcholine (ACh) across multiple brain systems. The brain systems that mediate pro-cognitive effects of attentional control and cognitive flexibility are the prefrontal cortex and the anterior striatum which have different pharmacokinetic sensitivities to ACh modulation. We speculated that these area-specific ACh profiles lead to distinct optimal dose-ranges for donepezil to enhance the cognitive domains of attention and flexible learning. METHODSTo test for dose-specific effects of donepezil on different cognitive domains we devised a multi-task paradigm for nonhuman primates (NHPs) that assessed attention and cognitive flexibility. NHPs received either vehicle or variable doses of donepezil prior to task performance. We measured donepezil intracerebral and how strong it prevented the breakdown of ACh within prefrontal cortex and anterior striatum using solid-phase-microextraction neurochemistry. RESULTSThe highest administered donepezil dose improved attention and made subjects more robust against distractor interference, but it did not improve flexible learning. In contrast, only a lower dose range of donepezil improved flexible learning and reduced perseveration, but without distractor-dependent attentional improvement. Neurochemical measurements confirmed a dose-dependent increase of extracellular donepezil and decreases in choline within the prefrontal cortex and the striatum. CONCLUSIONSThe donepezil dose for maximally improving attention functions differed from the dose range that enhanced cognitive flexibility despite the availability of the drug in the major brain systems supporting these cognitive functions. Thus, the non-selective acetylcholine esterase inhibitor donepezil inherently trades improvement in the attention domain for improvement in the cognitive flexibility domain at a given dose range.

pharmacology and toxicology↗

bioRxiv2021

A Kiosk Station for the Assessment of Multiple Cognitive Domains and Enrichment of Monkeys

BackgroundNonhuman primates (NHPs) are self-motivated to perform cognitive tasks on touchscreens in their animal housing setting. To leverage this ability, fully integrated hardware and software solutions are needed, that work within housing and husbandry routines while also spanning cognitive task constructs of the Research Domain Criteria (RDoC). New MethodWe describe a Kiosk Station (KS-1) that provides robust hardware and software solutions for running cognitive tasks in cage-housed NHPs. KS-1 consists of a frame for mounting flexibly on housing cages, a touchscreen animal interface with mounts for receptables, reward pumps and cameras, and a compact computer cabinet with an interface for controlling behavior. Behavioral control is achieved with a unity3D program that is virtual-reality capable, allowing semi-naturalistic visual tasks to assess multiple cognitive domains. ResultsKS-1 is fully integrated into the regular housing routines of monkeys. A single person can operate multiple KS-1s. Monkeys engage with KS-1 at high motivation and cognitive performance levels at high intra-individual consistency. Comparison with Existing MethodsKS-1 is optimized for flexible mounting onto standard apartment cage systems. KS-1 has a robust animal interface with options for gaze/reach monitoring. It has an integrated user interface for controlling multiple cognitive task using a common naturalistic object space designed to enhance task engagement. All custom KS-1 components are open-sourced. ConclusionsKS-1 is a versatile tool for cognitive profiling and enrichment of cage-housed monkeys. It reliably measures multiple cognitive domains which promises to advance our understanding of animal cognition, inter-individual differences and underlying neurobiology in refined, ethologically meaningful behavioral foraging contexts.

animal behavior and cognition↗

bioRxiv2018

Asymmetric effective connectivity between primate anterior cingulate and lateral prefrontal cortex revealed by electrical microstimulation.

The anterior cingulate cortex (ACC) and lateral prefrontal cortex (IPFC) of the non-human primate show neural firing correlations and synchronize at theta and beta frequencies during the monitoring and shifting of attention. These functional interactions might be based on synaptic connectivity that is equally efficacious in both directions, but it might be that there are systematic asymmetries in connectivity consistent with reports of more effective inhibition within the ACC than IPFC, or with a preponderance of ACC projections synapsing onto inhibitory neurons in the IPFC. Here, we tested effective ACC-IPFC connectivity in awake monkeys and report systematic asymmetries in the temporal patterning and latencies of effective connectivity as measured using electrical microstimulation. We found that ACC stimulation triggered evoked fields (EFPs) were more likely to be multiphasic in the IPFC than in the reverse direction, with a large proportion of connections showing 2-4 inflection points resembling resonance in the 20-30 Hz beta frequency range. Stimulation of ACC [->] IPFC resulted, on average, in shorter-latency EFPs than IPFC [->] ACC. Overall, latencies and connectivity strength varied more than two-fold depending on the precise anterior-to-posterior location of the connections. These findings reveal systematic asymmetries in effective connectivity between ACC and IPFC in the awake non-human primate and document the spatial and temporal patchiness of effective synaptic connections. We speculate that measuring effective connectivity profiles will be essential for understanding how local synaptic efficacy and synaptic connectivity translates into functional neuronal interactions to support adaptive behaviors.

neuroscience↗

bioRxiv2018

Feature Specific Prediction Errors and Surprise across Macaque Fronto-Striatal Circuits during Attention and Learning

Prediction errors signal unexpected outcomes indicating that expectations need to be adjusted. For adjusting expectations efficiently prediction errors need to be associated with the precise features that gave rise to the unexpected outcome. For many visual tasks this credit assignment proceeds in a multidimensional feature space that makes it ambiguous which object defining features are relevant. Here, we report of a potential solution by showing that neurons in all areas of the medial and lateral fronto-striatal networks encode prediction errors that are specific to separate features of attended multidimensional stimuli, with the most ubiquitous prediction error occurring for the reward relevant features. These feature specific prediction error signals (1) are different from a non-specific prediction error signal, (2) arise earliest in the anterior cingulate cortex and later in lateral prefrontal cortex, caudate and ventral striatum, and (3) contribute to feature-based stimulus selection after learning. These findings provide strong evidence for a widely-distributed feature-based eligibility trace that can be used to update synaptic weights for improved feature-based attention.\n\nHighlightsO_LINeural reward prediction errors carry information for updating feature-based attention in all areas of the fronto-striatal network.\nC_LIO_LIFeature specific neural prediction errors emerge earliest in anterior cingulate cortex and later in lateral prefrontal cortex.\nC_LIO_LIVentral striatum neurons encode feature specific surprise strongest for the goal-relevant feature.\nC_LIO_LINeurons encoding feature-specific prediction errors contribute to attentional selection after learning.\nC_LI

neuroscience↗