Frontal-Sensory Cortical Projections Become Dispensable for Attentional Performance Upon a Reduction of Task Demand in Mice

Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and improve promote goal-directed attention performance during fluctuating attentional demand. Previous studies have shown that frontal top-down neurons projecting from the anterior cingulate area (ACA) to the visual cortex (VIS; ACAVIS) are required for visual attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice. However, it is unknown whether the contribution of these projecting neurons is dependent on the extent of task demand. Here, we first examined how behavior outcomes depend on the number of locations for mice to pay attention and touch for successful performance, and found that the 2-choice serial reaction time task (2CSRTT) is less task demanding than the 5CSRTT. We then employed optogenetics to demonstrate that suppression ACAVIS projections immediately before stimulus presentation has no effect during the 2CSRTT in contrast to the impaired performance during the 5CSRTT. These results suggest that ACAVIS projections are necessary when task demand is high, but once a task demand is lowered, ACAVIS neuron activity becomes dispensable to adjust attentional performance. These findings support a model that the frontal-sensory ACAVIS projection regulates visual attention behavior during specific high task demand conditions, pointing to a flexible circuit-based mechanism for promoting attentional behavior.

Роль интерференции в имплицитном усвоении последовательностей Струп-стимулов

Введение. Феномен интерференции позволяет выявлять существенные характеристики процесса формирования нового знания. Новизна данного исследования заключается в использовании эффекта интерференции для диссоциации эксплицитного и имплицитного научения. Проверялось предположение о том, что эффект интерференции, возникающий при реагировании на Струп-стимулы, снижает продуктивность приобретения эксплицитного знания последовательности, но не оказывает значимого влияния на имплицитное усвоение последовательности. Методы. В исследовании приняли участие 80 человек (средний возраст 22,7 лет). В эксперименте использовались задачи «the serial reaction time task», в которых требуется быстро и точно реагировать на последовательно предъявляемые стимулы. Одним испытуемым (n = 40) предъявлялись названия цветов, написанные шрифтом конгруэнтного (соответствующего) цвета, другим испытуемым (n = 40) демонстрировались названия цветов, написанные шрифтом неконгруэнтного (несоответствующего) цвета (Струп-стимулы). Требовалось, не читая слова, реагировать на цвет шрифта, которым оно написано. Для выявления эксплицитного знания последовательности использовался тест узнавания фрагментов последовательности (the recognition test). Результаты. Полученные результаты выявили статистически значимый эффект усвоения последовательности у испытуемых, выполнявших задание в конгруэнтных и неконгруэнтных условиях. При этом все испытуемые продемонстрировали низкий уровень эксплицитного знания последовательности (не более 51,9 % правильных ответов в тесте узнавания). Установлено, что имплицитное выучивание последовательности позволяет устранить эффект интерференции (задержку во времени реакции на неконгруэнтные стимулы). Обсуждение результатов. Результаты подтвердили предположение о том, что эффект интерференции не снижает продуктивность имплицитного усвоения последовательности. Отсутствие значимых различий между группами, реагировавшими на конгруэнтные и неконгруэнтные стимулы, не позволяет в полной мере оценить влияние эффекта интерференции на эксплицитное усвоение последовательности. В целом данные проведенного исследования свидетельствуют в поддержку того, что эффект интерференции затрудняет экспликацию структуры последовательности.

#3071 Acute escitalopram administration increases premature responding as a function of reward magnitude in healthy male volunteers

ObjectivesImpulsivity is a multifaceted construct that involves a tendency to act prematurely with little foresight, reflection or control. Waiting impulsivity is one aspect of action impulsivity and is commonly studied in animals using tasks such as the 5-choice serial reaction time task (5CSRTT).1 It is neurochemically distinct from motor response inhibition defined as the ability to restrain or cancel a pre-potent motor response and measured with no-go and stop-signal tasks respectively.1 Serotonin modulates waiting impulsivity as decreased serotonergic transmission promotes premature responding in the rodent 5CSRT and the human analogue 4CSRT task.2 Potential mechanisms contributing to waiting impulsivity include proactive or tonic inhibition, motivational processes and sensitivity to feedback and delay.3 Higher waiting impulsivity in response to high reward cues was previously associated with greater subthalamic nucleus connectivity with orbitofrontal cortex and greater subgenual cingulate connectivity with anterior insula.4MethodsWe administered a clinically relevant dose of escitalopram (20mg) in healthy subjects in a double-blind, placebo-controlled, parallel-groups design study and assessed its effect on waiting impulsivity using the well-validated 4CSRT task. Compared to previous studies,2 4 we added another test block with increased potential gain to assess the interaction between premature responding and reward processing. We recruited sixty-six healthy participants who completed an extensive neuropsychological test battery assessing probabilistic reversal learning, set-shifting, response inhibition, emotional processing and waiting impulsivity. Sixty participants (N=60, 26 females, 34 males) completed the 4CSRT task with N=30 in the escitalopram and N=30 in the placebo group, due to technical errors and experienced side-effects for the remaining six participants. The results of the other cognitive tasks are reported separately.5ResultsEscitalopram increased premature responding in the high incentive condition of the 4CSRT task, p=.028, t= 2.275, this effect being driven by male participants, p=.019, t=2.532 (for females, p>.05). We further show that escitalopram increased premature responses after a premature response in the same block again in male participants only, p=.034, Mann-Whitney U= 61.500. We found no correlation between premature responding in the 4CSRT task, in any test block, and the Stop-signal reaction time, the primary measure of the stop-signal task completed by the same participants (reported in [5]).ConclusionsWe show that acute escitalopram increased premature responding in healthy male participants only in high incentive conditions potentially mediated potentially through an effect on increased incentive salience. We also show that acute escitalopram increased perseverative responding thus producing a maladaptive response strategy. We show no correlation between SSRT and premature responding in the same participants consistent with these two forms of impulsivity being neurochemically and anatomically distinct. We interpret our findings in the context of acute escitalopram decreasing serotonergic transmission in some brain areas through inhibitory actions on terminal 5-HT release mediated by auto-receptors on raphe 5-HT neurons analogous to the presumed transient reduction in 5-HT activity caused by ATD.5Our findings provide further insights in the relationship of premature responding and reward processing and our understanding of pathological impulse control behaviours.References Eagle DM, Bari A, Robbins TW. The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks. Psychopharmacology 2008;199(3):439456. Worbe Y, Savulich G, Voon V, Fernandez-Egea E, Robbins TW. Serotonin depletion induces waiting impulsivityon the human four-choice serial reaction time task: cross-species translational significance. Neuropsychopharmacology 2014;39(6):15191526. Voon V. Models of impulsivity with a focus on waiting impulsivity: translational potential for neuropsychiatric disorders. Current Addiction Reports 2014;1(4):281288. Mechelmans DJ, Strelchuk D, Doamayor N, Banca P, Robbins TW, Baek K, et al. Reward sensitivity and waiting impulsivity: shift towards reward valuation away from action control. International Journal of Neuropsychopharmacology 2017;20(12):971978. Skandali N, Rowe JB, Voon V, Deakin JB, Cardinal RN, Cormack F, et al. Dissociable effects of acute SSRI (escitalopram) on executive, learning and emotional functions in healthy humans. Neuropsychopharmacology 2018;43(13):26452651.

THE RELIABILITY AND VALIDITY OF PROCEDURAL MEMORY ASSESSMENTS USED IN SECOND LANGUAGE ACQUISITION RESEARCH

Evidence for the role of procedural memory in second language (L2) acquisition has emerged in our field. However, little is known about the reliability and validity of the procedural memory measures used in this research. The present study (N = 119) examined the reliability and the convergent and discriminant validity of three assessments that have previously been used to examine procedural memory learning ability in L2 acquisition, the dual-task Weather Prediction Task (DT-WPT), the Alternating Serial Reaction Time Task (ASRT), and the Tower of London (TOL). Measures of declarative memory learning ability were also collected. For reliability, the DT-WPT and TOL tasks met acceptable standards. For validity, an exploratory factor analysis did not provide evidence for convergent validity, but the ASRT and the TOL showed reasonable discriminant validity with declarative memory measures. We argue that the ASRT may provide the purest engagement of procedural memory learning ability, although more reliable dependent measures for this task should be considered. The Serial Reaction Time task also appears promising, although we recommend further consideration of this task as the present analyses were post hoc and based on a smaller sample. We discuss these results regarding the assessment of procedural memory learning ability as well as implications for implicit language aptitude.

The reliability and validity of procedural memory assessments used in second language acquisition research

Evidence for the role of procedural memory in second language (L2) acquisition has emerged in our field. However, little is known about the reliability and validity of the procedural memory measures used in this research. The present study (N = 99) examined the reliability and the convergent and discriminant validity of three assessments that have previously been used to examine procedural memory learning ability in L2 acquisition, the dual-task Weather Prediction Task (DT-WPT), the Alternating Serial Reaction Time Task (ASRT), and the Tower of London (TOL). Measures of declarative memory learning ability were also collected. For reliability, the DT-WPT and TOL tasks met acceptable standards. For validity, an exploratory factor analysis did not provide evidence for convergent validity, but the ASRT and the TOL showed reasonable discriminant validity with declarative memory measures. We argue that the ASRT may provide the purest engagement of procedural memory learning ability, although more reliable dependent measures for this task should be considered. The Serial Reaction Time task also appears promising, although we recommend further consideration of this task as the present analyses were post hoc and based on a smaller sample. We discuss these results in regard to the assessment of procedural memory learning ability as well as implications for implicit learning aptitude.

Adaptive aspects of impulsivity and interactions with effects of catecholaminergic agents in the 5-choice serial reaction time task: implications for ADHD

Background Work in humans has shown that impulsivity can be advantageous in certain settings. However, evidence for so-called functional impulsivity is lacking in experimental animals. Aims This study investigated the contexts in which high impulsive (HI) rats show an advantage in performance compared with mid- (MI) and low impulsive (LI) rats. We also assessed the effects of dopaminergic and noradrenergic agents to investigate underlying neurotransmitter mechanisms. Methods We tested rats on a variable inter-trial interval (ITI) version of the 5-choice serial reaction time task (5CSRTT). Rats received systemic injections of methylphenidate (MPH, 1 mg/kg and 3 mg/kg), atomoxetine (ATO, 0.3 mg/kg and 1 mg/kg), amphetamine (AMPH, 0.2 mg/kg), the alpha-2a adrenoceptor antagonist atipamezole (ATI, 0.3 mg/kg) and the alpha-1 adrenoceptor agonist phenylephrine (PHEN, 1 mg/kg) prior to behavioural testing. Results Unlike LI rats, HI rats exhibited superior performance, earning more reinforcers, on short ITI trials, when the task required rapid responding. MPH, AMPH and ATI improved performance on short ITI trials and increased impulsivity in long ITI trials, recapitulating the behavioural profile of HI. In contrast, ATO and PHEN impaired performance on short ITI trials and decreased impulsivity, thus mimicking the behavioural profile of LI rats. The effects of ATO were greater on MI rats and LI rats. Conclusions These findings indicate that impulsivity can be advantageous when rapid focusing and actions are required, an effect that may depend on increased dopamine neurotransmission. Conversely, activation of the noradrenergic system, with ATO and PHEN, led to a general inhibition of responding.