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Yaakub, S. N.

Publications and source records attributed to Yaakub, S. N..

4 recordsLinked to original sources

Ultrasound neuromodulation reveals distinct roles of the dorsal anterior cingulate cortex and anterior insula in Pavlovian biases

Pavlovian biases reflect the notorious influence of hard-wired, evolutionarily conserved cue-response tendencies on instrumental action selection: people show automatic action invigoration in face of potential rewards, but action suppression in face of potential punishments. The neural origin of these biases is unclear. Past evidence suggests dorsal anterior cingulate cortex (dACC) and anterior insula (aIns) as part of a "reset network" that rapidly responds to salient information and might contribute to these biases. We used transcranial ultrasonic stimulation (TUS) in 29 healthy participants to interfere with neural activity in these regions and test their causal role in a within-subject, counter-balanced design across three sessions (sham, TUS-dACC, TUS-aIns). Computational modelling revealed a double dissociation, with distinct roles of both regions in Pavlovian biases: while TUS to the aIns decreased peoples tendency to overly take credit for rewards following action and to ignore punishments following inaction, TUS to dACC increased participants tendency to take the cue valence as a reinforcer signal. Although the dACC and aIns are part of the same network and often co-activate during decision-making tasks, TUS interference reveals their distinct roles: the dACC mediates cue-dependence persistence while the aIns is critical for inferring whether outcomes are self-caused.

neuroscience↗

Non-invasive Ultrasound Deep Neuromodulation of the Human Nucleus Accumbens Increases Win-Stay Behaviour

Precisely neuromodulating deep brain regions could bring transformative advancements in both neuroscience and treatment. We demonstrate that non-invasive transcranial ultrasound stimulation (TUS) can selectively modulate deep brain activity and affect learning and decision making, comparable to deep brain stimulation (DBS). We tested whether TUS could causally influence neural and behavioural responses by targeting the nucleus accumbens (NAcc) using a reinforcement learning task. Twenty-six healthy adults completed a within-subject TUS-fMRI experiment with three conditions: TUS to the NAcc, dorsal anterior cingulate cortex (dACC), or Sham. After TUS, participants performed a probabilistic learning task during fMRI. TUS-NAcc altered BOLD responses to reward signals in the NAcc and surrounding areas. It also affected reward-related features, including win-stay strategy use, learning rate following rewards and learning curves. DBS-NAcc perturbed the same features, confirming target engagement. These findings establish TUS as a viable approach for non-invasive deep-brain neuromodulation.

neuroscience↗

Thalamic blood flow and EEG frequency band power during hyperventilation in idiopathic generalized epilepsy

Absence seizures in idiopathic generalised epilepsy (IGE) involve thalamo-cortical circuits. Hyperventilation (HV) is a standard technique to trigger epileptiform discharges and absence seizures in IGE. HV also increases electroencephalography (EEG) delta band power and decreases global cerebral blood flow (CBF). The relationships between HV, EEG band power, and regional CBF have not been investigated in the same patients at the same time. We compared the effects of hyperventilation between 13 individuals with IGE and 18 healthy controls on thalamic CBF assessed with pseudo-continuous Arterial Spin Labelling (pCASL) simultaneously to EEG frequency band power during three periods of hyperventilation interleaved with three periods of rest, normalised to each participants pre-HV values. Pre-HV, there were no differences between patients and controls. During the three rest periods combined, patients had higher normalised respiratory rates but no difference in CBF or EEG band power compared with controls. During HV, CBF decreases were similar in controls and IGE patients in cortical gray matter (37.1{+/-}1.3% in controls, 37.9{+/-}2.0% in patients) and basal ganglia (35.6{+/-}2.0% in controls, 33.3{+/-}2.3% in patients). In the thalamus, CBF decreased by 35.5{+/-}1.9% in controls, but only by 27.1{+/-}2.5% in patients (p=0.011). Delta band power increased by 42% in patients, but only by 27% in patients (p<0.045). Both controls and patients thalamic CBF significantly decreased as a function of respiratory rate, but the relationship was weaker in patients (rho -0.38 [0.95 confidence interval lower limit -0.629; upper limit -0.059] vs -0.51 [-0.698; -0.255] in controls). Delta power correlated with thalamic CBF only in controls (rho -0.21 [-0.388; -0.017]) but not in patients (rho -0.1 [-0.345; 0.157]). EEG power and respiratory rate were not significantly correlated in either group. This first study of the interrelationships between HV, blood flow, and EEG band power suggests that regional thalamic abnormalities of blood flow regulation, or a neurophysiological abnormality leading to smaller reactive blood flow changes, may underlie HV-associated EEG activation. Graphical abstract textIn this first investigation of combined hyperventilation, blood flow and EEG band power measurements in idiopathic generalised epileptic patients and healthy subjects, we revealed that localized thalamic blood flow regulatory problems or neurophysiological disorders caused minor reactive blood flow variations and may cause hyperventilation-associated EEG activation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/586742v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@12a5ebeorg.highwire.dtl.DTLVardef@b22944org.highwire.dtl.DTLVardef@b335dforg.highwire.dtl.DTLVardef@195c5e2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show for the first time in humans that theta-burst TUS selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition, that changes in TUS-mediated neuroplasticity last at least 50 minutes after stimulation, and that these effects may be state-dependent - a mechanism increasingly recognized to influence the brains response to neuromodulation.

neuroscience↗