Search

This article discusses two cases of patients with advanced neurodegenerative parkinsonism who developed repetitive movements of the upper limbs. The authors suggest that these movements demonstrate clonic perseveration, which is more pronounced than the stereotyped movements commonly seen in patients with neurodegenerative dementias. The first patient's movements were triggered by holding a newspaper, while the second patient's movements seemed to evolve from his typical parkinsonian rest tremor. The authors acknowledge that there may be differing viewpoints on the phenomenology demonstrated in the videos, but they argue that the movements are suggestive of clonic perseveration rather than stereotypies. The text explores the possibility that clonic perseveration observed in patients could be misinterpreted as re-emergent tremor or other movement disorders. It suggests that clonic perseveration may be associated with frontal-subcortical circuit malfunction and is seen in conditions such as progressive supranuclear palsy and behavioral variant frontotemporal dementia. The text emphasizes the importance of recognizing clonic perseveration to avoid misdiagnosis and inappropriate treatment. [Extracted from the article]

X-Linked Myotubular Myopathy (XLMTM) is a severe congenital myopathy, potentially fatal within the first years. Patients present several complications and their cognitive development has never been explored deeply so far. An in-depth knowledge on the disease natural history, including the neurocognitive and adaptive profile, is essential in light of the promising new therapeutic perspectives. We included all XLMTM patients seen in our clinical Unit between January 2021 and December 2023, irrespective to their disease's severity. Demographic and clinical data, including motor, respiratory and swallowing functions were collected. Patients were assessed with gold-standard international scales, according to their age and communication skills. We assessed nine patients in total, four with a severe phenotype, four with an intermediate phenotype and one with mild phenotype. The cognitive profile was within the lower limits or lower than the norm, with a global adaptive deficit for the majority of patients. A perseverative behavioural trait was also observed in some patients. This study shows that XLMTM patients in the cohort had a neurodevelopmental profile within the lower limits of the norm, irrespective to the disease's severity, while the adaptive difficulties seems to be related to patients' global clinical impairment. Our observation would deserve a confirmation on a wider range of patients and we consider it essential for better defining the XLMTM phenotype, also considering the incoming promising therapeutic approaches. • Cognitive delay noted in XLMTM1, impacting adaptive functioning. • Communication severely impaired by motor and respiratory issues. • Potential positive trajectory in learning abilities observed. • Discrepancy in non-verbal cognitive abilities among older children. • Behavioral peculiarities explored, suggestive of neurodevelopmental traits. [ABSTRACT FROM AUTHOR]

Aims: This investigation aimed to clarify the intricate relationship among depression, cognitive function, adverse childhood experiences (ACEs), and their combined influence on methamphetamine use disorder (MUD). Methods: Utilizing a battery of psychological tests, this study ascertained the impact of ACEs on the condition of 76 people with MUD who meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, aged 42.17 on average. The Iowa Gambling Task (IGT), Conners' Continuous Performance-II (CPT-II), the self-report Severity of Dependence Scale (SDS), and the Beck Depression Inventory-II (BDI-II) were used for these evaluations. Individuals involved in the study were categorized into two discrete cohorts, mild (ME) and severe (SE), based on the extent of their ACEs exposure. This study employed the PROCESS regression, the independent t-test andχ2 tests for the analysis. Results: The findings revealed notable discrepancies in the psychological consequences between the two groups with different degrees of ACEs; however, no substantial differences were observed in the demographic parameters. The SE group exhibited elevated BDI-II scores, more evident indications of MUD, and a higher degree of CPT-II cognitive perseveration. The PROCESS model revealed that cognitive perseveration moderated the impact of depression on ACEs and subjective MUD severity, explaining 20.2% of the variance. The ACEs and depression predicted 28.6% of the variance in MUD symptoms. However, no statistically significant differences were detected between the two groups regarding the parameters in the IGT-2 assessment. Conclusions: These results indicate that the interaction between cognitive and depressive factors mediates the effect of ACEs on subjective MUD severity but not on MUD symptoms. The ACEs significant impact on mental health severity perception is explained by cognitive and depressive factors. This implies that MUD treatment and rehabilitation should address cognitive dysfunction and developmental trauma. [ABSTRACT FROM AUTHOR]

To acquire and process information, performers can frequently rely on both internal and extended cognitive strategies. However, after becoming acquainted with two strategies, performers in previous studies exhibited a pronounced behavioral preference for just one strategy, which we refer to as perseveration. What is the origin of such perseveration? Previous research suggests that a prime reason for cognitive strategy choice is performance: Perseveration could reflect the preference for a superior strategy as determined by accurately monitoring each strategy's performance. However, following our preregistered hypotheses, we conjectured that perseveration persisted even if the available strategies featured similar performances. Such persisting perseveration could be reasonable if costs related to decision making, performance monitoring, and strategy switching would be additionally taken into account on top of isolated strategy performances. Here, we used a calibration procedure to equalize performances of strategies as far as possible and tested whether perseveration persisted. In Experiment 1, performance adjustment of strategies succeeded in equating accuracy but not speed. Many participants perseverated on the faster strategy. In Experiment 2, calibration succeeded regarding both accuracy and speed. No substantial perseveration was detected, and residual perseveration was conceivably related to metacognitive performance evaluations. We conclude that perseveration on cognitive strategies is frequently rooted in performance: Performers willingly use multiple strategies for the same task if performance differences appear sufficiently small. Surprisingly, other possible reasons for perseveration like effort or switch cost avoidance, mental challenge seeking, satisficing, or episodic retrieval of previous stimulus-strategy-bindings, were less relevant in the present study. [ABSTRACT FROM AUTHOR]

Individuals with attention-deficit hyperactivity disorder (ADHD) sometimes experience "hyperfocus", which is characterized by extended moments of deep focus that are difficult to terminate. However, it is unclear whether hyperfocus is uniquely linked to the attention-dysfunction aspects of ADHD even when controlling for the potential contribution of comorbid symptoms of depression and anxiety and difficulties in regulating negative and positive emotions. To examine (1) the relations between hyperfocus and related attentional states (flow, perseveration, and ADHD symptoms of inattention); (2) the relations between hyperfocus and emotion dysregulation; (3) the relations between ADHD symptoms and affective dysfunction (emotion dysregulation, depression, and anxiety); and (4) the unique contributions of ADHD symptoms and several measures of affective dysfunction when predicting hyperfocus. Self-report measures of hyperfocus, flow, perseveration, and emotion dysregulation (negative and positive) and symptoms of ADHD, depression, and anxiety were collected online from 529 Canadian undergraduate participants. Increased hyperfocus was related to higher ADHD symptoms, perseveration, emotion dysregulation (negative and positive), depression, and anxiety, but inconsistently with flow. In regression analyses, hyperfocus scores were uniquely predicted by emotion dysregulation and ADHD symptoms; neither depression nor anxiety symptoms were unique predictors. Hyperfocus appears to be a state of deep concentration that is outside of a person's control. It can involve concurrent (mainly positive) emotion dysregulation, and is experienced more (or more acutely) by individuals higher in ADHD symptoms of inattention, irrespective of comorbid depression or anxiety symptoms. [ABSTRACT FROM AUTHOR]

Two experiments and a dynamic model forhuman limb selection are reported. In Experiment 1, left-handed and right-handed participants (N = 36) repeatedly used one hand for grasping a small cube. After a clear switch in the cube’s location, perseverative limb selection was revealed in both handedness groups. In Experiment 2, the cubes were presented in a clockwise and counter-clockwise sequence to right-handed participants (N = 15). A spatial shift in the switch point between right-hand use and left-hand use was observed. The model simulates the experiments by implementing the nonlinear multiple-timescale dynamics of the action-selection process underlying limb selection. It integrates two mechanisms that were earlier proposed to underlie this selection aspect of manual activity: limb dominance and attentional information. Finally, the model is used to simulate an influential earlier experiment, by establishing a conceptual link between cross-lateral inhibition asymmetry and the direction and strength of handedness.

Iron is an important cofactor for many proteins and is used to create Fe-S clusters and heme prosthetic groups that enzymes use to catalyze enzymatic reactions. Proteins involved in the import, export, and sequestration of iron are regulated by Iron Regulatory Proteins (IRPs). Recently, a patient with bi-allelic loss of function mutations in IREB2 leading to the absence of IRP2 protein was discovered. The patient failed to achieve developmental milestones and was diagnosed with dystonic cerebral palsy, epilepsy, microcytic hypochromic anemia, and frontal lobe atrophy. Several more IREB2 deficient patients subsequently identified manifested similar neurological problems. To better understand the manifestations of this novel neurological disease, we subjected an Irp2-null mouse model to extensive behavioral testing. Irp2-null mice had a significant motor deficit demonstrated by reduced performance on rotarod and hanging wire tests. Somatosensory function was also compromised in hot and cold plate assays. Their spatial search strategy was impaired in the Barnes maze and they exhibited a difficulty in flexibly adapting their response in the operant touchscreen reversal learning task. The latter is a cognitive behavior known to require an intact prefrontal cortex. These results suggest that loss of Irp2 in mice causes motor and behavioral deficits that faithfully reflect the IREB2 patient's neurodegenerative disorder.

Two experiments and a dynamic model forhuman limb selection are reported. In Experiment 1, left-handed and right-handed participants (N = 36) repeatedly used one hand for grasping a small cube. After a clear switch in the cube's location, perseverative limb selection was revealed in both handedness groups. In Experiment 2, the cubes were presented in a clockwise and counter-clockwise sequence to right-handed participants (N = 15). A spatial shift in the switch point between right-hand use and left-hand use was observed. The model simulates the experiments by implementing the nonlinear multiple-timescale dynamics of the action-selection process underlying limb selection. It integrates two mechanisms that were earlier proposed to underlie this selection aspect of manual activity: limb dominance and attentional information. Finally, the model is used to simulate an influential earlier experiment, by establishing a conceptual link between cross-lateral inhibition asymmetry and the direction and strength of handedness. [ABSTRACT FROM AUTHOR]

BackgroundWorry increases risk for long-term health issues by prolonging the physiological stress response. In contrast, relaxation may ameliorate the psychological and physiological burden resulting from worry. This study examined the impact of experimentally induced worry and relaxation on cortisol, heart rate variability (HRV), and inflammation.MethodParticipants (N = 80) completed both a worry and relaxation induction (presented in a fixed order) while HRV was collected continuously. Three blood samples were taken (at baseline, after the worry induction, and after the relaxation induction) to measure IL-6, IFN-γ, TNF-α and serum cortisol.ResultsThere were significant changes in IL-6 (p < 0.001), IFN-γ (p < 0.01), HRV (p < .001), and cortisol (p

Introduction: Behavioral difficulties in individuals with fragile X Syndrome (FXS) are one of the primary reasons families seek medical and psychological support. Among these, behavioral inflexibility is very common, and when left untreated, can negatively impact quality of life for the individuals with FXS and their families. Behavioral inflexibility refers to the difficulty in changing one's behaviors based on environmental demands or social contexts, thus impeding daily functioning, opportunities for learning, and social interactions. In addition to the individual and family impact, behavioral inflexibility is often recognized as a defining phenotype of FXS and appears to be specific to FXS when compared to other genetic forms of intellectual disability. Despite the pervasiveness and severity of behavioral inflexibility in FXS, there are limited measures that adequately assess behavioral inflexibility in FXS. Methods: We conducted semi-structured virtual focus groups with 22 caregivers, 3 self-advocates, and 1 professional to gather key stakeholders' perspectives on and experiences of inflexible behavior observed in FXS. Audio-recordings from focus groups were transcribed using NVivo, then verified and coded. Two trained professionals reviewed codes to extract primary themes. Results: Six themes were extracted: (1) Intolerance of change, (2) Intolerance to uncertainty, (3) Repetitive interests and behaviors, (4) Family impact, (5) Change in behavior across the lifespan, and (6) Impact of the COVID pandemic. Our findings show common examples of these themes included intolerance to disruption to routine, perseverative questioning, watching the same things over and over, and caregivers having to extensively pre-plan for events. Discussion: The purpose of the current study was to gain key stakeholders' perspectives via focus groups to elicit information and understand patterns of inflexible behaviors in FXS, with the goal of developing a disorder-specific measure to accurately assess behavioral inflexibility across the lifespan and in response to treatment. We were able to capture several phenotypic examples of behavioral inflexibility in FXS as well as their impact on individuals with FXS and their families. The wealth of information gained through our study will aid in our next steps of item generation for measure development of Ratings of Inflexibility in Genetic Disorders associated with Intellectual Disability - Fragile X Syndrome (RIGID-FX). [ABSTRACT FROM AUTHOR]

IntroductionBehavioral difficulties in individuals with fragile X Syndrome (FXS) are one of the primary reasons families seek medical and psychological support. Among these, behavioral inflexibility is very common, and when left untreated, can negatively impact quality of life for the individuals with FXS and their families. Behavioral inflexibility refers to the difficulty in changing one’s behaviors based on environmental demands or social contexts, thus impeding daily functioning, opportunities for learning, and social interactions. In addition to the individual and family impact, behavioral inflexibility is often recognized as a defining phenotype of FXS and appears to be specific to FXS when compared to other genetic forms of intellectual disability. Despite the pervasiveness and severity of behavioral inflexibility in FXS, there are limited measures that adequately assess behavioral inflexibility in FXS.MethodsWe conducted semi-structured virtual focus groups with 22 caregivers, 3 self-advocates, and 1 professional to gather key stakeholders’ perspectives on and experiences of inflexible behavior observed in FXS. Audio-recordings from focus groups were transcribed using NVivo, then verified and coded. Two trained professionals reviewed codes to extract primary themes.ResultsSix themes were extracted: (1) Intolerance of change, (2) Intolerance to uncertainty, (3) Repetitive interests and behaviors, (4) Family impact, (5) Change in behavior across the lifespan, and (6) Impact of the COVID pandemic. Our findings show common examples of these themes included intolerance to disruption to routine, perseverative questioning, watching the same things over and over, and caregivers having to extensively pre-plan for events.DiscussionThe purpose of the current study was to gain key stakeholders’ perspectives via focus groups to elicit information and understand patterns of inflexible behaviors in FXS, with the goal of developing a disorder-specific measure to accurately assess behavioral inflexibility across the lifespan and in response to treatment. We were able to capture several phenotypic examples of behavioral inflexibility in FXS as well as their impact on individuals with FXS and their families. The wealth of information gained through our study will aid in our next steps of item generation for measure development of Ratings of Inflexibility in Genetic Disorders associated with Intellectual Disability – Fragile X Syndrome (RIGID-FX).

Background: Topic perseveration is often considered to be an autistic trait observable in more verbally able individuals with autism. However, the phenomenon has been subject to little empirical research. The aim of the present article is to explore the organization of perseverative talk within the context of autistic storytellings. Method: A conversation analytic approach offers insights into the ways in which two adults with autism initiate, develop, and pursue storytellings in naturally occurring interactions. Moreover, the co-participants' management of the apparently perseverative autistic talk is brought into focus. Results: The findings show that the two storytellings investigated here are successfully launched and initiated with a subtle sensitivity to the local environments of the ongoing interaction. Furthermore, the adults with autism develop and pursue their tellings with an orientation to the co-participants' display of structural support of the storytelling activity (alignment). However, the autistic tellers pursue their stories despite recipients' display of disinterest in their projects (disaffiliation). In both cases, story closure is initiated by the recipients, who treat the tellings as sequentially non-implicative actions. Discussion/conclusion: The findings propose that perseverative storytellings are locally and collaboratively managed social activities, developed on a turn-by-turn basis in natural interaction. The study argues that recipients' feedback, both midtelling and post-telling, contributes to the perseverative character of the tellings. This interpersonal approach to perseveration suggests that the most common intrapersonal conceptualizations of the phenomenon need to be refined to some extent. [ABSTRACT FROM AUTHOR]

Although humans acquire sophisticated and flexible tool-use skills rapidly throughout childhood, young children and adults still show difficulties using the same object for different functions, manifesting in, for example, perseveration or functional fixedness. This paper presents a novel model proposing bottom-up processes taking place during the acquisition of tool-use abilities through active interaction with objects, resulting in two kinds of cognitive representations of an object: a lower-level, action-centered representation and a higher-level, purpose-centered one. In situations requiring the use of an object to attain a goal, the purpose-centered representation is activated quickly, allowing for an immediate detection of suitable tools. In contrast, activation of the action-centered representation is slow and effortful, but comes with the advantage of offering wide-ranging information about the object's features and how they can be applied. This differential availability and activation of action-centered versus purpose-centered representations also contributes to a deeper understanding of the cognitive mechanisms underlying perseveration or functional fixedness during multifunctional tool use. When applied to the teaching and acquisition of tool use, the model indicates that the form in which object-related information is provided determines which of the two object representations is fostered, thereby either facilitating or complicating the flexible application of an object as a tool for different functions. • Tool use relies on interactions with objects and acquired object representations. • Object-specific knowledge is represented in an action- and a purpose-centered way. • Action-centered representations link object features, feasible movements, and effects. • Purpose-centered representations link the object directly to its familiar function(s). • Activation of the representations can explain perseveration and functional fixedness. [ABSTRACT FROM AUTHOR]

Acting and learning in unpredictable and volatile environments requires cognitive flexibility. However, the ability to flexibly adapt to the changing task environment can be reduced when people experience uncontrollability due to exposure to action – outcome non-contingency. In this research, we propose that flexible shifting of attention is affected by experiences of uncontrollability. In two studies, a lack of control was experimentally induced and subsequently cognitive flexibility was assessed either with a Wisconsin Card Sorting Task (Study 1) or a cognitive set-shifting paradigm (Study 2). Results showed a reduced tendency to flexibly shift attention and to overcome dominant response tendencies amongst participants who experienced uncontrollability. Modulation of the stability-flexibility balance by situationally induced experiences of uncontrollability is discussed. [ABSTRACT FROM AUTHOR]

Iron is an important cofactor for many proteins and is used to create Fe-S clusters and heme prosthetic groups that enzymes use to catalyze enzymatic reactions. Proteins involved in the import, export, and sequestration of iron are regulated by Iron Regulatory Proteins (IRPs). Recently, a patient with bi-allelic loss of function mutations in IREB2 leading to the absence of IRP2 protein was discovered. The patient failed to achieve developmental milestones and was diagnosed with dystonic cerebral palsy, epilepsy, microcytic hypochromic anemia, and frontal lobe atrophy. Several more IREB2 deficient patients subsequently identified manifested similar neurological problems. To better understand the manifestations of this novel neurological disease, we subjected an Irp2-null mouse model to extensive behavioral testing. Irp2-null mice had a significant motor deficit demonstrated by reduced performance on rotarod and hanging wire tests. Somatosensory function was also compromised in hot and cold plate assays. Their spatial search strategy was impaired in the Barnes maze and they exhibited a difficulty in flexibly adapting their response in the operant touchscreen reversal learning task. The latter is a cognitive behavior known to require an intact prefrontal cortex. These results suggest that loss of Irp2 in mice causes motor and behavioral deficits that faithfully reflect the IREB2 patient's neurodegenerative disorder., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Figural fluency tests were originally developed as a measure of right frontal lobe integrity and are presently a standard component of neuropsychological evaluation. To better understand the clinical interpretation of figural fluency scores (design output and perseverative errors), the current study investigated two trials from the Ruff Figural Fluency Test (RFFT) and their correlations with other neuropsychological variables in examinees who were being evaluated for cognitive difficulties (N = 84). Design output was significantly correlated (rs >.4) with psychomotor speed, non-verbal memory, and false positive recognition errors on a verbal memory test, while perseverative errors did not show a significant correlation with these variables or with design output. Design output also showed a significant correlation with phonemic fluency (rs >.3) as well as correlations (rs >.25) with semantic fluency and intellectual functioning. In a sample of examinees with mild (n = 33), complicated-mild (n = 11), and moderate-severe (n = 16) traumatic brain injuries (TBI), group differences in design output did not reach significance, whereas perseverative errors were significantly related to the severity of injury. This study suggests that design output and perseverative errors on figural fluency may be separate measures, and their clinical interpretations are discussed. [ABSTRACT FROM AUTHOR]

There is a potential for a long‐lasting psychological and social impact from the COVID‐19 pandemic. Recently, the COVID‐19 Anxiety Syndrome Scale (C19‐ASS) has been developed, which measures individuals' coping mechanisms in relation to the fear or threat of COVID‐19. The C19‐ASS was developed and has been used so far only in Western samples. Further psychometric evaluation is needed in ethnically diverse samples. Therefore, the current study sought to test the psychometric properties in a large sample of Iranians (n = 1429; female = 52.1%; Mean age = 35.83, ±12.89) who completed a cross‐sectional survey. Exploratory factor analysis revealed that the Persian C19‐ASS has a two‐factor structure corresponding to the perseveration and avoidance subscales of the original scale. Confirmatory factor analyses also supported a two‐factor solution, which showed a firm model fit and high internal consistencies. Furthermore, it showed excellent divergent validity from generalized anxiety, indicating that it is concerned explicitly with COVID‐19, supported by correlational analyses and exploratory factor analysis. Test of incremental validity indicated the Persian C19‐ASS explained more variance in functional impairment and COVID‐19 anxiety than the gender, marital and educational status, generalized anxiety, neuroticism, openness, consciousness and having lost someone close due to COVID‐19. Also, based on a mediation test, it was found that C19‐ASS mediates the relationship between the Big Five personality traits (except openness and consciousness) and health anxiety, generalized anxiety, depression and COVID‐19 anxiety. Overall, the current findings provide further evidence for the construct of the COVID‐19 anxiety syndrome. The COVID‐19 anxiety syndrome is discussed in light of the S‐REF model that provides an explanatory framework for this pandemic‐related construct. [ABSTRACT FROM AUTHOR]

First described by Boissier and Simon in (Ther Recreat J 17:1225–1232, 1962), the hole-board has become a recognized test of anxiety and spatial memory. Benzodiazepines acting at the GABAA-BZD site increase hole-pokes in rats and mice, indicating a loss in behavioral inhibition concordant with the behavior of mutant mice deficient in the GABA transporter. Hole-poking also depends on arousal mechanisms dependent on dopaminergic transmission, as indicated by drug and null mutant studies. In addition, the behavior is modified in natural and null mutants affecting the cerebellum as well as null mutants affecting neuropeptides, growth factors, cell adhesion, and inflammation. Further research is required to determine convergences between genetic and pharmacological effects. [ABSTRACT FROM AUTHOR]

Dopamine neurons in the ventral tegmental area (VTA) encode reward prediction errors and can drive reinforcement learning through their projections to striatum, but much less is known about their projections to prefrontal cortex (PFC). Here, we studied these projections and observed phasic VTA-PFC fiber photometry signals after the delivery of rewards. Next, we studied how optogenetic stimulation of these projections affects behavior using conditioned place preference and a task in which mice learn associations between cues and food rewards and then use those associations to make choices. Neither phasic nor tonic stimulation of dopaminergic VTA-PFC projections elicited place preference. Furthermore, substituting phasic VTA-PFC stimulation for food rewards was not sufficient to reinforce new cue-reward associations nor maintain previously learned ones. However, the same patterns of stimulation that failed to reinforce place preference or cue-reward associations were able to modify behavior in other ways. First, continuous tonic stimulation maintained previously learned cue-reward associations even after they ceased being valid. Second, delivering phasic stimulation either continuously or after choices not previously associated with reward induced mice to make choices that deviated from previously learned associations. In summary, despite the fact that dopaminergic VTA-PFC projections exhibit phasic increases in activity that are time locked to the delivery of rewards, phasic activation of these projections does not necessarily reinforce specific actions. Rather, dopaminergic VTA-PFC activity can control whether mice maintain or deviate from previously learned cue-reward associations.SIGNIFICANCE STATEMENT Dopaminergic inputs from ventral tegmental area (VTA) to striatum encode reward prediction errors and reinforce specific actions; however, it is currently unknown whether dopaminergic inputs to prefrontal cortex (PFC) play similar or distinct roles. Here, we used bulk Ca2+ imaging to show that unexpected rewards or reward-predicting cues elicit phasic increases in the activity of dopaminergic VTA-PFC fibers. However, in multiple behavioral paradigms, we failed to observe reinforcing effects after stimulation of these fibers. In these same experiments, we did find that tonic or phasic patterns of stimulation caused mice to maintain or deviate from previously learned cue-reward associations, respectively. Therefore, although they may exhibit similar patterns of activity, dopaminergic inputs to striatum and PFC can elicit divergent behavioral effects.

Introduction 54-year-old female patient who came to hospital due to psychopathological decompensation of her Obsessive-Compulsive Disorder (OCD), after 35 years under follow-up. Parkinson´s disease. Psychopharmacological treatment: sertraline 100 mg (1-0-0); lorazepam 2 mg (1-1-1); Levodopa/carbidopa 100/25 mg (1-1-1). Distressed at first examination. She described increase in rituals, important intake restriction, weight impact and difficulties in home management with functional repercussions. Psychopathological exploration: conscious, oriented, and approachable. Circumstantial speech with no obsessive ideas. Increased frequency of repetitive behaviours led to a functional deterioration, becoming dependent for activities of daily living. Elevated anxiety. No major mood disorder. No psychotic symptoms. Bradykinesia. Hypophagia without anorexia. Admission is carried out. Good evolution: improvement in motor symptoms and intake restoration. No changes in repetitive behaviours. Objectives To discuss the differential diagnosis between OCD and Frontotemporal Dementia. Methods Repetitive behaviours were initially understood as rituals typical of OCD. However, the absence of both a fixed pattern of behaviour and a structured obsessive ideation, made us consider the possibility of frontal perseveration behaviours. For this reason, a neuropsychological evaluation and a functional neuroimaging test were performed: Test Mo-CA: 9/30 with striking failures in executive functions. SPECT: mild uptake defect in the left frontotemporal region. Results Finally, in view of the impairment in executive functions and the frontal defects in neuroimaging, we change the initial diagnosis of OCD towards a Neurocognitive Disorder of probable frontotemporal origin. Conclusions The presented case evidenced the importance of differentiating obsessive compulsions from frontal perseverance to guide the differential diagnosis, given the implications for therapeutic management and prognosis. Disclosure No significant relationships.

In probabilistic and nonstationary environments, individuals must use internal and external cues to flexibly make decisions that lead to desirable outcomes. To gain insight into the process by which animals choose between actions, we trained mice in a task with time-varying reward probabilities. In our implementation of such a two-armed bandit task, thirsty mice use information about recent action and action-outcome histories to choose between two ports that deliver water probabilistically. Here we comprehensively modeled choice behavior in this task, including the trialto-trial changes in port selection, i.e., action switching behavior. We find that mouse behavior is, at times, deterministic and, at others, apparently stochastic. The behavior deviates from that of a theoretically optimal agent performing Bayesian inference in a hidden Markov model (HMM). We formulate a set of models based on logistic regression, reinforcement learning, and sticky Bayesian inference that we demonstrate are mathematically equivalent and that accurately describe mouse behavior. The switching behavior of mice in the task is captured in each model by a stochastic action policy, a history-dependent representation of action value, and a tendency to repeat actions despite incoming evidence. Themodels parsimoniously capture behavior across different environmental conditionals by varying the stickiness parameter, and like the mice, they achieve nearly maximal reward rates. These results indicate that mouse behavior reaches near-maximal performance with reduced action switching and can be described by a set of equivalent models with a small number of relatively fixed parameters. [ABSTRACT FROM AUTHOR]

Does motor behavior early in development have the same signatures of habituation, dishabituation, and Spencer-Thompson dishabituation known from infant perception and cognition? And do these signatures explain the choice preferences in A not B motor decision tasks? We provide new empirical evidence that gives an affirmative answer to the first question together with a unified neural dynamic model that gives an affirmative answer to the second question.In the perceptual and cognitive domains, habituation is the weakening of an orientation response to a stimulus over perceptual experience. Switching to a novel stimulus leads to dishabituation, the re-establishment of the orientation response. In Spencer-Thompson dishabituation, the renewed orientation response transfers to the original (familiar) stimulus. The change in orientation responses over perceptual experience explains infants' behavior in preferential looking tasks: Familiarity preference (looking longer at familiar than at novel stimuli) early during exposure and novelty preference (looking longer at novel than at familiar stimuli) late during exposure. In the motor domain, perseveration in the A not B task could be interpreted as a form of familiarity preference. There are hints that this preference reverses after enough experience with the familiar movement. We provide a unified account for habituation and patterns of preferential selection in which neural dynamic fields generate perceptual or motor representations. The build-up of activation in excitatory fields leads to familiarity preference, the build-up of activation in inhibitory fields leads to novelty preference. We show that the model accounts for the new experimental evidence for motor habituation, but is also compatible with earlier accounts for perceptual habituation and motor perseveration. We discuss how excitatory and inhibitory memory traces may regulate exploration and exploitation for both orientation to objects and motor behaviors. [ABSTRACT FROM AUTHOR]

Formal thought disorders (FTD) are a hallmark diagnostic feature of schizophrenia (SZ) and (bipolar) mania (MA). FTD can be separated into positive (pFTD) and negative dimensions. It is unclear whether there are differences in pFTD on a single symptom level between acutely ill patients with SZ and MA, which cannot be attributed to cognitive impairment. We compared single pFTD symptoms in two groups of acutely ill patients with ICD-10 bipolar mania and schizophrenia, closely matched for age, sex, pFTD TALD score, verbal IQ and neuropsychological test performance (executive function, verbal fluency, attention, and working memory). SZ patients had higher severity of the TALD symptoms "perseverations" and "poverty of content of speech" than those with MA (Mann–Whitney U, significant, Bonferroni corrected). Speech in acute SZ patients differs from MA in that it conveys little information and adheres to previously mentioned ideas and topics. Matching for confounding variables, such as IQ and cognition, is important when comparing patients with different diagnoses. [ABSTRACT FROM AUTHOR]

Many American and Dutch adolescents use marijuana regularly. There is concern that such use may impair cognitive function more in adolescents than adults. We examined effects of regular marijuana use on long-term memory and perseveration among American and Dutch adolescents. We administered Buschke's Selective Reminding Test (BSRT) to assess long-term memory and the Wisconsin Card Sorting Test (WCST) to assess perseveration in male teenagers. Usable test data were obtained for 12 American marijuana users, 13 American controls, 9 Dutch marijuana users, and 12 Dutch controls. In BSRT, users showed lower overall long-term storage than controls (adjusted means ± SE's for numbers of words per trial of 9.4 ± 0.2, 13.4 ± 0.3, 11.7 ± 0.2, and 12.4 ± 0.2 for American users, Dutch users, American controls, and Dutch controls, respectively). Marijuana was associated with memory effects only in American, not Dutch, users. Bivariate Pearson correlations for American and Dutch users combined showed associations of lower total recall with more uses in the previous year and lifetime (r = –0.61 and r = –0.53, respectively); and more perseverative errors with more uses in the previous year (r = 0.55). Some findings were consistent with the possibility that regular adolescent marijuana use causes deficits in cognition, especially memory. However, a causal interpretation cannot be inferred from our findings and is challenging to reconcile with the observation of memory deficits only in American users. Our study was novel in examining the influence of nationality on marijuana's cognitive effects. More studies of this topic should compare effects across nationalities or cultures. [ABSTRACT FROM AUTHOR]

Behavioural flexibility allows animals to adjust to changes in their environment. Although the cognitive processes that explain flexibility have been relatively well studied in psychology, this is less true for animals in the wild. Here we use data collected automatically during self-administered discrimination-learning trials for two passerine species, and during four phases (habituation, initial learning, first reversal and second reversal) in order to decompose sources of consistent among-individual differences in reversal learning, a commonly used measure for cognitive flexibility. First, we found that, as expected, proactive interference was significantly repeatable and had a negative effect on reversal learning, confirming that individuals with poor ability to inhibit returning to a previously rewarded feeder were also slower to reversal learn. Second, to our knowledge for the first time in a natural population, we examined how sampling of non-rewarding options post-learning affected reversal-learning performance. Sampling quantity was moderately repeatable in blue tits but not great tits; sampling bias, the variance in the proportion of visits to each non-rewarded feeder, was not repeatable for either species. Sampling behaviour did not predict variation in reversal-learning speed to any significant extent. Finally, the repeatability of reversal learning was explained almost entirely by proactive interference for blue tits; in great tits, the effects of proactive interference and sampling bias on the repeatability of reversal learning were indistinguishable. Our results highlight the value of proactive interference as a more direct measurement of cognitive flexibility and shed light on how animals respond to changes in their environment. [ABSTRACT FROM AUTHOR]

The capacity for voluntary control is seen as essential to human movements; the sense that one intended to move (willing) and those actions were self-generated (self-agency) gives the sense of voluntariness and of being in control. While the mechanisms underlying voluntary movement have long been unclear, recent neuroscientific tools have identified networks of different brain areas, namely, the prefrontal cortex, supplementary motor area, and parietal cortex, that underlie voluntary action. Dysfunction in these brain areas can result in different forms of semivoluntary movement as the borderland of voluntary and involuntary movement where a person may experience a disordered sense of will or agency, and thus the movement is experienced as unexpected and involuntary, for an otherwise voluntary-appearing movement. Tics, functional movement disorders, stereotypies, perseveration, compulsions, utilization behaviors, and motor mannerism have been described elsewhere in the context of psychoses, and are often mistaken for each other. Yet, they reflect an impairment of prefrontal cortices and related circuits rather than simple motor systems, which results in the absence of subjective recognition of the movements, in contrast to other neurological movement disorders where principal abnormalities are located within the basal ganglia and its connections. Therefore, their recognition is clinically important since they are usually associated with neurodevelopmental and neurodegenerative disorders. In this review, we first defined a conceptual framework, from both a neuroanatomical and a neurophysiological point of view, for the generation of voluntary movement. We then examined the evidence linking dysfunctions in different motor pathways to each type of movement disorder. We looked at common semivoluntary movement disorders providing an overview, where possible, of their phenomenology and brain network abnormalities for each condition. We also emphasized important clinical feature similarities and differences to increase recognition of each condition in practice. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) and fragile X syndrome (FXS) are neurodevelopmental disorders with overlapping pragmatic language impairments. Prior work suggests pragmatic language differences may run in families. This study examined specific pragmatic difficulties (i.e., linguistic mazes and perseverations) in boys (9–18 years) with idiopathic ASD (n = 26) and FXS+ASD (n = 29), and relationships with maternal maze use. Language samples were obtained separately for boys and mothers. Nonparametric analyses suggested that boys largely did not differ in their rates of mazes, but that boys with FXS+ASD exhibited more perseverations. Mazes were correlated between fragile X dyads. Maternal mazes were correlated with child perseverations among idiopathic ASD dyads. These findings have implications for the etiological significance of ASD-related language phenotypes. [ABSTRACT FROM AUTHOR]

Does motor behavior early in development have the same signatures of habituation, dishabituation, and Spencer-Thompson dishabituation known from infant perception and cognition? And do these signatures explain the choice preferences in A not B motor decision tasks? We provide new empirical evidence that gives an affirmative answer to the first question together with a unified neural dynamic model that gives an affirmative answer to the second question.In the perceptual and cognitive domains, habituation is the weakening of an orientation response to a stimulus over perceptual experience. Switching to a novel stimulus leads to dishabituation, the re-establishment of the orientation response. In Spencer-Thompson dishabituation, the renewed orientation response transfers to the original (familiar) stimulus. The change in orientation responses over perceptual experience explains infants' behavior in preferential looking tasks: Familiarity preference (looking longer at familiar than at novel stimuli) early during exposure and novelty preference (looking longer at novel than at familiar stimuli) late during exposure. In the motor domain, perseveration in the A not B task could be interpreted as a form of familiarity preference. There are hints that this preference reverses after enough experience with the familiar movement. We provide a unified account for habituation and patterns of preferential selection in which neural dynamic fields generate perceptual or motor representations. The build-up of activation in excitatory fields leads to familiarity preference, the build-up of activation in inhibitory fields leads to novelty preference. We show that the model accounts for the new experimental evidence for motor habituation, but is also compatible with earlier accounts for perceptual habituation and motor perseveration. We discuss how excitatory and inhibitory memory traces may regulate exploration and exploitation for both orientation to objects and motor behaviors.

Early life adversity is associated with increased risk for mental and physical health problems, including substance abuse. Changes in neural development caused by early life insults could cause or complicate these conditions. Maternal separation (MS) is a model of early adversity for rodents. Clear effects of MS have been shown on behavioral flexibility in rats, but studies of effects of MS on cognition in mice have been mixed. We hypothesized that previous studies focused on adult mice may have overlooked a developmental transition point when juvenile mice exhibit greater flexibility in reversal learning. Here, using a 4-choice reversal learning task we find that early MS leads to decreased flexibility in post-weaning juvenile mice, but no significant effects in adults. In a further study of voluntary ethanol consumption, we found that adult mice that had experienced MS showed greater cumulative 20% ethanol consumption in an intermittent access paradigm compared to controls. Our data confirm that the MS paradigm can reduce cognitive flexibility in mice and may enhance risk for substance abuse. We discuss possible interpretations of these data as stress-related impairment or adaptive earlier maturation in response to an adverse environment.

Objective: The objective of this research was to compare the verbal fluency skills of patients diagnosed as having amnestic mild cognitive impairment (aMCI) with the participants without neurologic or psychiatric problems through quantitative and qualitative analysis, and to determine in which aspects patients with aMCI differed from the control group. Materials and Methods: The sample of this study consisted of 20 individuals who presented to Özel Acıbadem Eskisehir Hospital with the symptom of forgetfulness and were diagnosed as having aMCI, and a healthy control group of the same size (n=20). All participants were administered preplanned verbal fluency tests that are valid and reliable, specifically for the mother language. Intergroup comparisons were made in the light of quantitative and qualitative assessments. Through the quantitative analysis, the total number of words produced in a limited amount of time under certain conditions was evaluated, and through the qualitative analysis, clustering and switching skills and error patterns such as perseveration and category violation were assessed. Results: It was determined that the aMCI group showed a deterioration in verbal fluency skills, and individuals with aMCI had significantly lower scores on both phonemic (u=296.5, p0.05 for all comparisons). In phonemic verbal fluency tests, word switching skills of the patient group were significantly lower than those of the control group (u=279, p

Abstract Cognitive dysfunction including disrupted behavioral flexibility is central to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A cognitive measure that assesses relational memory, and the ability to flexibly assimilate and transfer learned information is transitive inference. Transitive inference is highly conserved across vertebrates and disrupted in cognitive disorders. Here, we examined how mutations in the synaptic cell-adhesion molecule neuroligin-3 (Nlgn3) that have been documented in ASD impact relational memory and behavioral flexibility. We first refined a rodent touchscreen assay to measure visual transitive inference, then assessed two mouse models of Nlgn3 dysfunction (Nlgn3 −/y and Nlgn3 R451C). Deep analysis of touchscreen behavioral data at a trial level established we could measure trajectories in flexible responding and changes in processing speed as cognitive load increased. We show that gene mutations in Nlgn3 do not disrupt relational memory, but significantly impact flexible responding. Our study presents the first analysis of reaction times in a rodent transitive inference test, highlighting response latencies from the touchscreen system are useful indicators of processing demands or decision-making processes. These findings expand our understanding of how dysfunction of key components of synaptic signaling complexes impact distinct cognitive processes disrupted in neurodevelopmental disorders, and advance our approaches for dissecting rodent behavioral assays to provide greater insights into clinically relevant cognitive symptoms.

Psychological distress is an inevitable part of life. Research drawing on theories from clinical psychology, health psychology, and psychoneuroimmunology (PNI) has identified relationships between negative emotions such as anxiety and sadness with inflammation. When not regulated properly, negative emotions can create biological wear and tear on the body that can increase risk for morbidity and mortality. This review discusses previously available research on relationships between negative emotions and emotion regulation with inflammation among both physically healthy adults and those with chronic illnesses. I then present a novel comprehensive biobehavioral model of negative emotionality. This model emphasizes the influence of negative emotions and their contribution to heightened inflammation. Further, I also discuss how emotion regulation (including perseverative processes such as worry and rumination) mediates this association. The relationships between negative emotionality and emotion regulation may be bidirectional, and empirical investigation of this model should specifically seek to disentangle these relationships. The proposed model offers the opportunity to advance PNI research through understanding how emotional factors alter inflammation and contribute to accelerated biological aging and disease risk.

Aims: This investigation aimed to clarify the intricate relationship among depression, cognitive function, adverse childhood experiences (ACEs), and their combined influence on methamphetamine use disorder (MUD)., Methods: Utilizing a battery of psychological tests, this study ascertained the impact of ACEs on the condition of 76 people with MUD who meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, aged 42.17 on average. The Iowa Gambling Task (IGT), Conners' Continuous Performance-II (CPT-II), the self-report Severity of Dependence Scale (SDS), and the Beck Depression Inventory-II (BDI-II) were used for these evaluations. Individuals involved in the study were categorized into two discrete cohorts, mild (ME) and severe (SE), based on the extent of their ACEs exposure. This study employed the PROCESS regression, the independent t-test andχ2 tests for the analysis., Results: The findings revealed notable discrepancies in the psychological consequences between the two groups with different degrees of ACEs; however, no substantial differences were observed in the demographic parameters. The SE group exhibited elevated BDI-II scores, more evident indications of MUD, and a higher degree of CPT-II cognitive perseveration. The PROCESS model revealed that cognitive perseveration moderated the impact of depression on ACEs and subjective MUD severity, explaining 20.2% of the variance. The ACEs and depression predicted 28.6% of the variance in MUD symptoms. However, no statistically significant differences were detected between the two groups regarding the parameters in the IGT-2 assessment., Conclusions: These results indicate that the interaction between cognitive and depressive factors mediates the effect of ACEs on subjective MUD severity but not on MUD symptoms. The ACEs significant impact on mental health severity perception is explained by cognitive and depressive factors. This implies that MUD treatment and rehabilitation should address cognitive dysfunction and developmental trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ko, Lu, Lee and Liao.)

The study investigated set-shifting impairment differences in children by Attention Deficit Hyperactive Disorder (ADHD) subtype compared to neurotypical peers. The sample consisted of 156 primary school children from the Limpopo Province of South Africa (ADHD = 78, neurotypical = 78). The children were assessed on the computerised Wisconsin Card Sorting Test, which provides set-shifting error scores as follows: total errors, perseverating responses, perseverating errors, and non-perseverating errors. Following Multivariate Analysis of Variance (MANOVA) for between-group differences, results showed that children with ADHD subtypes, across subtypes, were with more set-shifting deficits than the neurotypical comparison group on total errors, perseverative responses, perseverative errors, and non-perseverative errors. Sex and age did not influence the performance of set-shifting tasks. From these findings, we conclude that children with ADHD present with set-shifting difficulties that could be the target of early interventions. [ABSTRACT FROM AUTHOR]

We studied changes to the pattern of speech errors as afunction of selectively attending to one word in a sequence tolearn how attention is implemented in language production.Three hypotheses were tested: (1) attention specificallyinhibits the past, (2) attention enhances the activation of thepresent without affecting the past or the future, and (3)attention decreases priming of the future. In Experiment 1,using a model of sequential word production, we simulatedthe pattern of anticipatory and perseveratory errors on theattended words, and compared them to empirical error data.Our findings support a model in which attention only affectsthe present. Experiment 2 tested the prediction of this modelregarding the error patterns on the word following theattended word. These results were also compatible with atransient enhancement in the activation of present that doesnot affect the production of the future words.

Abstract Genetic and pharmacological manipulations targeting metabotropic glutamate receptor 5 (mGluR5) affect performance in behavioural paradigms that depend on cognitive flexibility. Many of these studies involved exposing mice to highly stressful conditions including electric foot shocks or water immersion and forced swimming. Because mGluR5 is also implicated in resilience and stress responses, however, apparent impairments in inhibitory learning may have been an artifact of manipulation-induced changes in affective state. To address this, we present here a characterization of cognitive flexibility in mGluR5 knockout (KO) mice conducted with a rodent touchscreen cognitive assessment apparatus in which the animals experience significantly less stress. Our results indicate a significant reversal learning impairment relative to wild-type (WT) controls in the two-choice Visual Discrimination-Reversal (VDR) paradigm. Upon further analysis, we found that this deficit is primarily driven by a prolonged period of perseveration in the early phase of reversal. We also observed a similar perseveration phenotype in the KO mice in the Extinction (EXT) paradigm. In addition, mGluR5 KO mice show higher breakpoints in the touchscreen Progressive Ratio (PR) and altered decision making in the Effort-related Choice (ERC) tasks. Interestingly, this impairment in PR is an additional manifestation of an increased propensity to perseverate on the emission of relatively simplistic behavioural outputs. Together, these findings suggest that under conditions of low stress, mGluR5 KO mice exhibit a pronounced perseverative phenotype that blunts cognitive flexibility.

The ability to adapt to changing environments is crucial for survival and has evolved based on socio-ecological factors. Goats and sheep are closely related, with similar social structures, body sizes and domestication levels, but different feeding ecologies, i.e. goats are browsers and sheep are grazers. We investigated whether goats' reliance on more patchily distributed food sources predicted an increased behavioural flexibility compared to sheep. We tested 21 goats and 28 sheep in a spatial A-not-B detour task. Subjects had to navigate around a straight barrier through a gap at its edge. After one, two, three or four of these initial A trials, the gap was moved to the opposite end and subjects performed four B trials. Behaviourally more flexible individuals should move through the new gap faster, while those less behaviourally flexible should show greater perseveration. While both species showed an accuracy reduction following the change of the gap position, goats recovered from this perseveration error from the second B trial onwards, whereas sheep did so only in the fourth B trial, indicating differences in behavioural flexibility between the species. This higher degree of flexibility in goats compared to sheep could be linked to differences in their foraging strategies.

Aging causes perseveration (difficulty to switch between actions) in motor and cognitive tasks, suggesting that the same neural processes could govern these abilities in older adults. To test this, we evaluated the relation between independently measured motor and cognitive perseveration in young (21.4 ± 3.7 y/o) and older participants (76.5 ± 2.9 y/o). Motor perseveration was measured with a locomotor task in which participants had to transition between distinct walking patterns. Cognitive perseveration was measured with a card matching task in which participants had to switch between distinct matching rules. We found that perseveration in the cognitive and motor domains were positively related in older, but not younger individuals, such that participants exhibiting greater perseveration in the motor task also perseverated more in the cognitive task. Additionally, exposure reduces motor perseveration: older adults who had practiced the motor task could transition between walking patterns as proficiently as naïve, young individuals. Our results suggest an overlap in neural processes governing cognitive and motor perseveration with aging and that exposure can counteract the age-related motor perseveration. [ABSTRACT FROM AUTHOR]

Gambling disorder (GD) is a behavioral addiction associated with impairments in value-based decision-making and behavioral flexibility and might be linked to changes in the dopamine system. Maximizing long-term rewards requires a flexible tradeoff between the exploitation of known options and the exploration of novel options for information gain. This exploration exploitation trade-off is thought to depend on dopamine neurotransmission. We hypothesized that human gamblers would show a reduction in directed (uncertainty-based) exploration, accompanied by changes in brain activity in a fronto-parietal exploration-related network. Twenty-three frequent, non-treatment seeking gamblers and twenty-three healthy matched controls (all male) performed a four-armed bandit task during functional magnetic resonance imaging (fMRI). Computational modeling using hierarchical Bayesian parameter estimation revealed signatures of directed exploration, random exploration, and perseveration in both groups. Gamblers showed a reduction in directed exploration, whereas random exploration and perseveration were similar between groups. Neuroimaging revealed no evidence for group differences in neural representations of basic task variables (expected value, prediction errors). Our hypothesis of reduced frontal pole (FP) recruitment in gamblers was not supported. Exploratory analyses showed that during directed exploration, gamblers showed reduced parietal cortex and substantia-nigra/ventral-tegmental-area activity. Cross-validated classification analyses revealed that connectivity in an exploration-related network was predictive of group status, suggesting that connectivity patterns might be more predictive of problem gambling than univariate effects. Findings reveal specific reductions of strategic exploration in gamblers that might be linked to altered processing in a fronto-parietal network and/or changes in dopamine neurotransmission implicated in GD. [ABSTRACT FROM AUTHOR]

Mutations in hundreds of genes cause neurodevelopmental disorders with abnormal motor behavior alongside cognitive deficits. Boys with fragile X syndrome (FXS), a leading monogenic cause of intellectual disability, often display repetitive behaviors, a core feature of autism. By direct observation and manual analysis, we characterized spontaneous-motor-behavior phenotypes of Drosophila dfmr1 mutants, an established model for FXS. We recorded individual 1-day-old adult flies, with mature nervous systems and prior to the onset of aging, in small arenas. We scored behavior using open-source video-annotation software to generate continuous activity timelines, which were represented graphically and quantitatively. Young dfmr1 mutants spent excessive time grooming, with increased bout number and duration; both were rescued by transgenic wild-type dfmr1+. By two grooming-pattern measures, dfmr1-mutant flies showed elevated repetitions consistent with perseveration, which is common in FXS. In addition, the mutant flies display a preference for grooming posterior body structures, and an increased rate of grooming transitions from one site to another. We raise the possibility that courtship and circadian rhythm defects, previously reported for dfmr1 mutants, are complicated by excessive grooming. We also observed significantly increased grooming in CASK mutants, despite their dramatically decreased walking phenotype. The mutant flies, a model for human CASK-related neurodevelopmental disorders, displayed consistently elevated grooming indices throughout the assay, but transient locomotory activation immediately after placement in the arena. Based on published data identifying FMRP-target transcripts and functional analyses of mutations causing human genetic neurodevelopmental disorders, we propose the following proteins as candidate mediators of excessive repetitive behaviors in FXS: CaMKIIα, NMDA receptor subunits 2A and 2B, NLGN3, and SHANK3. Together, these fly-mutant phenotypes and mechanistic insights provide starting points for drug discovery to identify compounds that reduce dysfunctional repetitive behaviors. [ABSTRACT FROM AUTHOR]

On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).