scholarly journals Access to Procedural Memories After One Year: Evidence for Robust Memory Consolidation in Tourette Syndrome

2021 ◽  
Vol 15 ◽  
Author(s):  
Eszter Tóth-Fáber ◽  
Zsanett Tárnok ◽  
Ádám Takács ◽  
Karolina Janacsek ◽  
Dezső Németh

Tourette syndrome is a childhood-onset neurodevelopmental disorder characterized by motor and vocal tics. On the neural level, tics are thought to be related to the disturbances of the cortico-basal ganglia-thalamo-cortical loops, which also play an important role in procedural learning. Several studies have investigated the acquisition of procedural information and the access to established procedural information in TS. Based on these, the notion of procedural hyperfunctioning, i.e., enhanced procedural learning, has been proposed. However, one neglected area is the retention of acquired procedural information, especially following a long-term offline period. Here, we investigated the 5-hour and 1-year consolidation of two aspects of procedural memory, namely serial-order and probability-based information. Nineteen children with TS between the ages of 10 and 15 as well as 19 typically developing gender- and age-matched controls were tested on a visuomotor four-choice reaction time task that enables the simultaneous assessment of the two aspects. They were retested on the same task 5 hours and 1 year later without any practice in the offline periods. Both groups successfully acquired and retained the probability-based information both when tested 5 hours and then 1 year later, with comparable performance between the TS and control groups. Children with TS did not acquire the serial-order information during the learning phase; hence, retention could not be reliably tested. Our study showed evidence for short-term and long-term retention of one aspect of procedural memory, namely probability-based information in TS, whereas learning of serial-order information might be impaired in this disorder.

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 297-297
Author(s):  
Joseph Jankovic ◽  
Barbara Coffey ◽  
Daniel O. Claassen ◽  
David Stamler ◽  
Barry J. Gertz ◽  
...  

Abstract:Background:Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the hyperkinetic movements of motor and phonic tics manifested in young age. Currently approved treatments in the United States are antipsychotics: haloperidol, pimozide, and aripiprazole, which are associated with serious side effects, including tardive dyskinesia (TD). Deutetrabenazine, a vesicular monoamine transporter type 2 (VMAT2) inhibitor, was approved in 2017 by the US FDA for the treatment of chorea associated with Huntington’s disease and TD. Three ongoing studies (Alternatives for Reducing Tics in TS [ARTISTS]) are evaluating the efficacy, safety, and tolerability of deutetrabenazine in reducing tics in TS in children and adolescents (age 6-16 years).Methods:ARTISTS 1, a phase 2/3, response-driven, dose-titration, placebo-controlled study, randomizes patients (N=116) 1:1 to deutetrabenazine or placebo for 12 weeks. ARTISTS 2, a phase 3, fixed-dose study, randomizes patients (N=150) 1:1:1 to deutetrabenazine high or low dose, or placebo for 8 weeks. The primary efficacy outcome in these pivotal studies is change from baseline to end of treatment in the Total Tic Score (TTS) of the Yale Global Tic Severity Scale (YGTSS). Additional efficacy endpoints and safety/tolerability are also evaluated. ARTISTS is a 56-week, open-label, single-arm, long-term safety/tolerability study in patients who have successfully completed either ARTISTS 1 or ARTISTS 2.Results:Not available yet.Conclusion:TS can have potentially long-term life impact, and there remains unmet medical need for effective and well-tolerated treatments. Three ARTISTS studies will evaluate the efficacy, safety, and tolerability of deutetrabenazine in patients with tics in TS.Funding Acknowledgements:The studies are sponsored by Teva Pharmaceuticals and operationalized by Teva’s development partner, Nuvelution TS Pharma INC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eszter Tóth-Fáber ◽  
Karolina Janacsek ◽  
Dezső Németh

AbstractExtraction of environmental patterns underlies human learning throughout the lifespan and plays a crucial role not only in cognitive but also perceptual, motor, and social skills. At least two types of regularities contribute to acquiring skills: (1) statistical, probability-based regularities, and (2) serial order-based regularities. Memory performance of probability-based and/or serial order-based regularities over short periods (from minutes to weeks) has been widely investigated across the lifespan. However, long-term (months or year-long) memory performance of such knowledge has received relatively less attention and has not been assessed in children yet. Here, we aimed to test the long-term memory performance of probability-based and serial order-based regularities over a 1-year offline period in neurotypical children between the age of 9 and 15. Participants performed a visuomotor four-choice reaction time task designed to measure the acquisition of probability-based and serial order-based regularities simultaneously. Short-term consolidation effects were controlled by retesting their performance after a 5-h delay. They were then retested on the same task 1 year later without any practice between the sessions. Participants successfully acquired both probability-based and serial order-based regularities and retained both types of knowledge over the 1-year period. The successful retention was independent of age. Our study demonstrates that the representation of probability-based and serial order-based regularities remains stable over a long period of time. These findings offer indirect evidence for the developmental invariance model of skill consolidation.


2021 ◽  
Author(s):  
Benjamin Kowialiewski ◽  
Benoit Lemaire ◽  
Steve Majerus ◽  
Sophie Portrat

The maintenance of serial order information is a core component of Working Memory (WM). Many theoretical models assume the existence of specific serial order mechanisms. Those are considered to be independent from the linguistic system supporting maintenance of item information. This is based on studies showing that psycholinguistic factors strongly affect the ability to maintain item information, while leaving order recall relatively unaffected. Recent language-based accounts suggest however that the linguistic system could provide mechanisms that are sufficient for serial order maintenance. A strong version of these accounts postulates serial order maintenance as emerging from the pattern of activation occurring in the linguistic system. In the present study, we tested this assumption via a computational modeling approach, by implementing a purely activation-based architecture. We tested this architecture against several experiments involving the manipulation of semantic relatedness, a psycholinguistic variable that has been shown to interact with serial order processing in a complex manner. We show that this activation-based architecture struggles to account for interactions between semantic knowledge and serial order processing. This study fails to support activated long-term memory as an exclusive mechanism supporting serial order maintenance.


Author(s):  
Benjamin Kowialiewski ◽  
Benoît Lemaire ◽  
Steve Majerus ◽  
Sophie Portrat

AbstractThe maintenance of serial order information is a core component of working memory (WM). Many theoretical models assume the existence of specific serial order mechanisms. Those are considered to be independent from the linguistic system supporting maintenance of item information. This is based on studies showing that psycholinguistic factors strongly affect the ability to maintain item information, while leaving order recall relatively unaffected. Recent language-based accounts suggest, however, that the linguistic system could provide mechanisms that are sufficient for serial order maintenance. A strong version of these accounts postulates serial order maintenance as emerging from the pattern of activation occurring in the linguistic system. In the present study, we tested this assumption via a computational modeling approach by implementing a purely activation-based architecture. We tested this architecture against several experiments involving the manipulation of semantic relatedness, a psycholinguistic variable that has been shown to interact with serial order processing in a complex manner. We show that this activation-based architecture struggles to account for interactions between semantic knowledge and serial order processing. This study fails to support activated long-term memory as an exclusive mechanism supporting serial order maintenance.


2017 ◽  
Author(s):  
Peter Simor ◽  
Zsofia Zavecz ◽  
Kata Horváth ◽  
Noémi Éltető ◽  
Csenge Török ◽  
...  

AbstractProcedural learning is a fundamental cognitive function that facilitates efficient processing of and automatic responses to complex environmental stimuli. Here, we examined training-dependent and off-line changes of two sub-processes of procedural learning: namely, sequence learning and statistical learning. Whereas sequence learning requires the acquisition of order-based relationships between the elements of a sequence, statistical learning is based on the acquisition of probabilistic associations between elements. Seventy-eight healthy young adults (58 females and 20 males) completed the modified version of the Alternating Serial Reaction Time task that was designed to measure Sequence and Statistical Learning simultaneously. After training, participants were randomly assigned to one of three conditions: active wakefulness, quiet rest, or daytime sleep. We examined off-line changes in Sequence and Statistical Learning as well as further improvements after extended practice. Performance in Sequence Learning increased during training, while Statistical Learning plateaued relatively rapidly. After the off-line period, both the acquired sequence and statistical knowledge was preserved, irrespective of the vigilance state (awake, quiet rest or sleep). Sequence Learning further improved during extended practice, while Statistical Learning did not. Moreover, within the sleep group, cortical oscillations and sleep spindle parameters showed differential associations with Sequence and Statistical Learning. Our findings can contribute to a deeper understanding of the dynamic changes of multiple parallel learning and consolidation processes that occur during procedural memory formation.


2019 ◽  
Vol 62 (10) ◽  
pp. 3790-3807 ◽  
Author(s):  
Sara Ferman ◽  
Liat Kishon-Rabin ◽  
Hila Ganot-Budaga ◽  
Avi Karni

Purpose The purpose of this study was to delineate differences between children with specific language impairment (SLI), typical age–matched (TAM) children, and typical younger (TY) children in learning and mastering an undisclosed artificial morphological rule (AMR) through exposure and usage. Method Twenty-six participants (eight 10-year-old children with SLI, 8 TAM children, and ten 8-year-old TY children) were trained to master an AMR across multiple training sessions. The AMR required a phonological transformation of verbs depending on a semantic distinction: whether the preceding noun was animate or inanimate. All participants practiced the application of the AMR to repeated and new (generalization) items, via judgment and production tasks. Results The children with SLI derived significantly less benefit from practice than their peers in learning most aspects of the AMR, even exhibiting smaller gains compared to the TY group in some aspects. Children with SLI benefited less than TAM and even TY children from training to judge and produce repeated items of the AMR. Nevertheless, despite a significant disadvantage in baseline performance, the rate at which they mastered the task-specific phonological regularities was as robust as that of their peers. On the other hand, like 8-year-olds, only half of the SLI group succeeded in uncovering the nature of the AMR and, consequently, in generalizing it to new items. Conclusions Children with SLI were able to learn language aspects that rely on implicit, procedural learning, but experienced difficulties in learning aspects that relied on the explicit uncovering of the semantic principle of the AMR. The results suggest that some of the difficulties experienced by children with SLI when learning a complex language regularity cannot be accounted for by a broad, language-related, procedural memory disability. Rather, a deficit—perhaps a developmental delay in the ability to recruit and solve language problems and establish explicit knowledge regarding a language task—can better explain their difficulties in language learning.


2021 ◽  
pp. 1-23
Author(s):  
Eszter Tóth-Fáber ◽  
Zsanett Tárnok ◽  
Karolina Janacsek ◽  
Andrea Kóbor ◽  
Péter Nagy ◽  
...  

Author(s):  
Joshua Buffington ◽  
Alexander P. Demos ◽  
Kara Morgan-Short

Abstract 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.


Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 86
Author(s):  
Mathis Hildonen ◽  
Amanda M. Levy ◽  
Christina Dahl ◽  
Victoria A. Bjerregaard ◽  
Lisbeth Birk Møller ◽  
...  

Gilles de la Tourette syndrome (GTS) is a complex neurodevelopmental disorder characterized by motor and vocal tics. Most of the GTS individuals have comorbid diagnoses, of which obsessive-compulsive disorder (OCD) and attention deficit-hyperactivity disorder (ADHD) are the most common. Several neurotransmitter systems have been implicated in disease pathogenesis, and amongst these, the dopaminergic and the serotonergic pathways are the most widely studied. In this study, we aimed to investigate whether the serotonin transporter (SERT) gene (SLC6A4) was differentially expressed among GTS individuals compared to healthy controls, and whether DNA variants (the SERT-linked polymorphic region 5-HTTLPR, together with the associated rs25531 and rs25532 variants, and the rare Ile425Val variant) or promoter methylation of SLC6A4 were associated with gene expression levels or with the presence of OCD as comorbidity. We observed that SLC6A4 expression is upregulated in GTS individuals compared to controls. Although no specific genotype, allele or haplotype was overrepresented in GTS individuals compared to controls, we observed that the LAC/LAC genotype of the 5-HTTLPR/rs25531/rs25532 three-locus haplotype was associated with higher SLC6A4 mRNA expression levels in GTS individuals, but not in the control group.


2017 ◽  
Vol 54 (4) ◽  
pp. 540-561 ◽  
Author(s):  
Robert Lemelson ◽  
Annie Tucker

In the past two decades, ethnographic, epidemiological and interdisciplinary research has robustly established that culture is significant in determining the long-term outcomes of people with neurodevelopmental, neuropsychiatric and mood disorders. Yet these cultural factors are certainly not uniform across discrete individual experiences. Thus, in addition to illustrating meaningful differences for people with neuropsychiatric disorder between different cultures, ethnography should also help detail the variations within a culture. Different subjective experiences or outcomes are not solely due to biographical idiosyncrasies—rather, influential factors arising from the same culture can have different impacts on different people. When taking a holistic and intersectional perspective on lived experience, it is crucial to understand the interaction of these factors for people with neuropsychiatric disorders. This paper teases apart such interactions, utilizing comparative case studies of the disparate subjective experiences and illness trajectories of two Balinese people with Tourette syndrome who exhibit similar symptoms. Based on longitudinal person-centered ethnography integrating clinical, psychological, and visual anthropology, this intersectional approach goes beyond symptom interpretation and treatment modalities to identify gendered embodiment and marital practices as influenced by caste to be significant determinants in subjective experience and long-term outcome.


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