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1.
J Psychiatr Res ; 175: 42-49, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38704980

ABSTRACT

Neurological soft signs (NSS) are subtle motor control impairments that include involuntary movements and abnormalities of motor coordination, sensory integration and lateralization. They engage different brain networks, including the prefrontal networks that support the higher cognitive functions that are dysfunctional in obsessive-compulsive disorder (OCD). This study investigated the relationships between the presence of NSS and patients' severity of OCD symptoms, insight, and treatment resistance in a sample of 63 patients. Treatment-resistance was assessed considering all the treatments the patients received during the course of their disease. The four dimensions of OCD defined in the dimensional obsessive-compulsive scale were considered. Links between the patients' cognitive abilities and NSS were assessed using tests targeting specifically the core components of executive functions. As expected, OCD patients displayed more NSS than individually matched control participants. In OCD patients, high NSS scores were associated with poor insight and lower cognitive abilities. Multiple regression analysis identified worse visuospatial working memory, attentional control, and verbal fluency as predictive factors of high NSS scores among cognitive functions. Unexpectedly, the patients displaying symptoms in the contamination/washing dimension displayed less NSS than the other patients. In contrast, neither the severity of OCD symptoms nor long-range treatment resistance was significantly related to patients' NSS scores. Altogether, our findings suggest that high NSS scores may be a trait marker of a subset of OCD patients with low insight and particularly altered cognitive abilities who would not express the contamination/washing dimension of the pathology.

2.
Front Psychiatry ; 14: 1017206, 2023.
Article in English | MEDLINE | ID: mdl-37215653

ABSTRACT

Around 50% of the patients with obsessive-compulsive disorder (OCD) are resistant to treatment, and patients with OCD show alterations in a broad range of cognitive abilities. The present study investigated the links between treatment-resistance, executive and working memory abilities, and the severity of OCD symptoms among 66 patients with OCD. The patients performed seven tests gauging their executive functions and working memory and filled in questionnaires for OCD severity and insight into their pathology. In addition, the executive and working memory abilities of a subset of these patients were compared with those of individually matched control participants. In contrast with previous studies, patients' treatment resistance was evaluated by considering the clinical outcomes of all the treatments that they received during the course of their disease. Higher treatment resistance was associated with lower performance in one particular executive test, the Stroop test, which assessed patients' ability to inhibit prepotent/automatic responses. Older age and more severe OCD symptoms were also associated with higher treatment resistance. Regardless of OCD severity, the patients displayed small to moderate deficits across most components of executive functions compared to control participants. Interestingly, patients with OCD took more time than control participants to perform speeded neuropsychological tests but never made more errors. Altogether, this study shows that the treatment-resistance of patients with OCD may be reliably quantified over the course of years and treatments using Pallanti and Quercioli's (2006) treatment resistance-related scales. The data suggest that the Stroop test could be used clinically to anticipate treatment outcomes in to-be-treated patients.

3.
Mem Cognit ; 51(7): 1562-1579, 2023 10.
Article in English | MEDLINE | ID: mdl-37079250

ABSTRACT

An eye-tracking experiment was conducted to examine whether the pre-activation of different word-processing pathways by means of semantic versus perceptual induction tasks could modify the way adults and 11- to 15-year-old adolescents searched for single target words within displays of nine words. The presence within the search displays of words either looking like the target word or semantically related to the target word was manipulated. The quality of participants' lexical representations was evaluated through three word-identification and vocabulary tests. Performing a semantic induction task rather than a perceptual one on the target word before searching for it increased search times by 15% in all age groups, reflecting an increase in both the number and duration of gazes directed to non-target words. Moreover, performing the semantic induction task increased the impact of distractor words that were semantically related to the target word on search efficiency. Participants' search efficiency increased with age because of a progressive increase in the quality of adolescents' lexical representations, which allowed participants to more quickly reject the distractors on which they fixated. Indeed, lexical quality scores explained 43% of the variance in search times independently of participants' age. In the simple visual search task used in this study, fostering semantic word processing through the semantic induction task slowed down visual search. However, the literature suggests that semantic induction tasks could, in contrast, help people find information more easily in more complex verbal environments where the meaning of words must be accessed to find task-relevant information.


Subject(s)
Reading , Semantics , Adult , Humans , Adolescent , Child
4.
Acta Psychol (Amst) ; 212: 103191, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33147538

ABSTRACT

The study examined how readers integrate information from and about multiple information sources into a memory representation. In two experiments, college students read brief news reports containing two critical statements, each attributed to a source character. In half of the texts, the statements were consistent with each other, in the other half they were discrepant. Each story also featured a non-source character (who made no statement). The hypothesis was that discrepant statements, as compared to consistent statements, would promote distinct attention and memory only for the source characters. Experiment 1 used short interviews to assess participants' ability to recognize the source of one of the statements after reading. Experiment 2 used eye-tracking to collect data during reading and during a source-content recognition task after reading. As predicted, discrepancies only enhanced memory of, and attention to source-related segments of the texts. Discrepancies also enhanced the link between the two source characters in memory as opposed to the non-source character, as indicated by the participants' justifications (Experiment 1) and their visual inspection of the recognition items (Experiment 2). The results are interpreted within current theories of text comprehension and document literacy.


Subject(s)
Comprehension , Memory , Reading , Attention , Humans , Recognition, Psychology
5.
Memory ; 28(4): 537-552, 2020 04.
Article in English | MEDLINE | ID: mdl-32216583

ABSTRACT

The main goal of this study was to explore the organizational strategies used by younger and older adults when encoding words, using eye-tracking. Participants had to learn a set of organizable words and then a set of non-organizable words, each presented on a single display. Participants were then asked to recall the words of each set in the order in which they came to their mind. Hence, the participants' encoding strategies revealed by eye-tracking could be directly related to their subsequent memory performance. The results confirmed the detrimental impact of aging on memory and the weaker use of organizational strategies by older adults during the recall phase. The eye-tracking data showed that when they encode the words, older adults do not look at them for as long as younger adults, probably because of slower eye movements. They also revealed that compared to younger adults, older adults were much less able to adapt their word scanning strategy according to whether the words to encode were organizable or not. Finally, the relationships that were found between the recall scores and the eye-tracking data suggest that the eye movement pattern at learning can predict how people will recall the words.


Subject(s)
Eye Movements , Mental Recall , Aged , Aging , Cognition , Humans , Learning
6.
Front Psychol ; 10: 642, 2019.
Article in English | MEDLINE | ID: mdl-30971984

ABSTRACT

Two eye-tracking experiments were conducted to assess the influence of words either looking like the target word (orthographic distractors) or semantically related to the target word (semantic distractors) on visual search for words within lists by adolescents of 11, 13, and 15 years of age. In Experiment 1 (literal search task), participants saw the target word before the search (e.g., "raven"), whereas in Experiment 2 (categorical task) the target word was only defined by its semantic category (e.g., "bird"). In both experiments, participants' search times decreased from fifth to ninth grade, both because older adolescents gazed less often at non-target words during the search and because they could reject non-target words more quickly once they were fixated. Progress in visual search efficiency was associated with a large increase in word identification skills, which were a strong determinant of average gaze durations and search times for the categorical task, but much less for the literal task. In the literal task, the presence of orthographic or semantic distractors in the list increased search times for all age groups. In the categorical task, the impact of semantic distractor words was stronger than in the literal task because participants needed to gaze at the semantic distractors longer than at the other words before rejecting them. Altogether, the data support the assumption that the progressive automation of word decoding up until the age of 12 and the better quality of older adolescents' lexical representations facilitate a flexible use of both the perceptual and semantic features of words for top-down guidance within the displays. In particular, older adolescents were better prepared to aim at or reject words without gazing at them directly. Finally, the overall similar progression of the maturation of single word visual search processes and that of more real-life information search within complex verbal documents suggests that the young adolescents' difficulties in searching the Web effectively could be due to their insufficiently developed lexical representations and word decoding abilities.

7.
Q J Exp Psychol (Hove) ; 72(7): 1805-1826, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30340451

ABSTRACT

During visual search for simple items, the amount of information that can be processed in parafoveal vision depends on the cognitive resources that are available. However, whether this applies to the semantic processing of words remains controversial. This work was designed to manipulate simultaneously two sources of cognitive load to study their impact on the depth of parafoveal word processing during a modified visual search task. The participants had to search for target words among parafoveally presented semantic, orthographic or target-unrelated distractor words while their electroencephalogram was recorded. The task-related load was manipulated by either giving target words in advance (literal task) or giving only a semantic clue to define them (categorical task). The foveal load was manipulated by displaying either a word or hash symbols at the centre of the screen. Parafoveal orthographic and semantic distractors had an impact on the early event-related potential component P2a only in the literal task and when hash symbols were displayed at the fovea, i.e., when both the task-related and foveal loads were low. The data show that all sources of cognitive load must be considered to understand how parafoveal words are processed in visual search contexts.


Subject(s)
Evoked Potentials, Visual , Eye Movements , Pattern Recognition, Visual , Reaction Time , Reading , Adult , Attention , Electroencephalography/methods , Female , Fovea Centralis/physiology , Humans , Male , Memory, Short-Term , Semantics , Task Performance and Analysis
8.
J Exp Psychol Appl ; 24(4): 476-489, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30346193

ABSTRACT

This study examined the effect of the number of citations attributed to documents on third year psychology students' selection of bibliographical references. Our main assumption was that students would take high numbers of citations as accessible relevance cues and use them heuristically to facilitate decision making, potentially bypassing deeper relevance assessment based on semantic processing. Experiment 1 presented the students with a reference selection task while manipulating the number of citations attributed to references, and found that the number of citations had a strong impact on reference selection. Moreover, the effect was independent from topic familiarity and even from students' prior knowledge of what the number of citations meant. Experiment 2 used eye-tracking data to show that this "big number" effect was contingent upon the participants fixating the numbers of citations attributed to documents. Experiment 3 manipulated the semantic relevance of references to the search topic, and demonstrated that the less relevant references were 3 times more likely to be selected when they came with a high number of citations. Overall, the study shows that the number of citations significantly influences students' selections, competing with the semantic relevance of references. Implications for the teaching of online search skills are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Subject(s)
Bibliographies as Topic , Decision Making , Heuristics , Students , Adolescent , Adult , Female , Humans , Knowledge , Male , Middle Aged , Young Adult
9.
Psychiatry Res ; 264: 244-253, 2018 06.
Article in English | MEDLINE | ID: mdl-29655967

ABSTRACT

This study aimed at investigating attentional mechanisms in obsessive-compulsive disorder (OCD) by analysing how visual search processes are modulated by normal and obsession-related distracting information in OCD patients and whether these modulations differ from those observed in healthy people. OCD patients were asked to search for a target word within distractor words that could be orthographically similar to the target, semantically related to the target, semantically related to the most typical obsessions/compulsions observed in OCD patients, or unrelated to the target. Patients' performance and eye movements were compared with those of individually matched healthy controls. In controls, the distractors that were visually similar to the target mostly captured attention. Conversely, patients' attention was captured equally by all kinds of distractor words, whatever their similarity with the target, except obsession-related distractors that attracted patients' attention less than the other distractors. OCD had a major impact on the mostly subliminal mechanisms that guide attention within the search display, but had much less impact on the distractor rejection processes that take place when a distractor is fixated. Hence, visual search in OCD is characterized by abnormal subliminal, but not supraliminal, processing of obsession-related information and by an impaired ability to inhibit task-irrelevant inputs.


Subject(s)
Attention/physiology , Eye Movements/physiology , Obsessive-Compulsive Disorder/psychology , Reading , Verbal Behavior/physiology , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/physiopathology , Semantics , Visual Perception/physiology , Young Adult
10.
Mem Cognit ; 45(1): 151-167, 2017 01.
Article in English | MEDLINE | ID: mdl-27531139

ABSTRACT

According to the documents model framework (Britt, Perfetti, Sandak, & Rouet, 1999), readers' detection of contradictions within texts increases their integration of source-content links (i.e., who says what). This study examines whether conflict may also strengthen the relationship between the respective sources. In two experiments, participants read brief news reports containing two critical statements attributed to different sources. In half of the reports, the statements were consistent with each other, whereas in the other half they were discrepant. Participants were tested for source memory and source integration in an immediate item-recognition task (Experiment 1) and a cued recall task (Experiments 1 and 2). In both experiments, discrepancies increased readers' memory for sources. We found that discrepant sources enhanced retrieval of the other source compared to consistent sources (using a delayed recall measure; Experiments 1 and 2). However, discrepant sources failed to prime the other source as evidenced in an online recognition measure (Experiment 1). We argue that discrepancies promoted the construction of links between sources, but that integration did not take place during reading.


Subject(s)
Conflict, Psychological , Cues , Memory, Short-Term/physiology , Mental Recall/physiology , Recognition, Psychology/physiology , Adult , Female , Humans , Male , Young Adult
11.
Q J Exp Psychol (Hove) ; 69(6): 1145-63, 2016.
Article in English | MEDLINE | ID: mdl-26176489

ABSTRACT

During visual search for words, the impact of the visual and semantic features of words varies as a function of the search task. This event-related potential (ERP) study focused on the way these features of words are used to detect similarities between the distractor words that are glanced at and the target word, as well as to then reject the distractor words. The participants had to search for a target word that was either given literally or defined by a semantic clue among words presented sequentially. The distractor words included words that resembled the target and words that were semantically related to the target. The P2a component was the first component to be modulated by the visual and/or semantic similarity of distractors to the target word, and these modulations varied according to the task. The same held true for the later N300 and N400 components, which confirms that, depending on the task, distinct processing pathways were sensitized through attentional modulation. Hence, the process that matches what is perceived with the target acts during the first 200 ms after word presentation, and both early detection and late rejection processes of words depend on the search task and on the representation of the target stored in memory.


Subject(s)
Attention/physiology , Brain/physiology , Evoked Potentials, Visual/physiology , Semantics , Vocabulary , Adolescent , Adult , Analysis of Variance , Electroencephalography , Electrooculography , Eye Movements/physiology , Female , Humans , Male , Photic Stimulation , Reaction Time/physiology , Young Adult
12.
Exp Psychol ; 62(2): 98-109, 2015.
Article in English | MEDLINE | ID: mdl-25384639

ABSTRACT

In many visual displays such as virtual environments, human tasks involve objects superimposed on both complex and moving backgrounds. However, most studies investigated the influence of background complexity or background motion in isolation. Two experiments were designed to investigate the joint influences of background complexity and lateral motion on a simple shooting task typical of video games. Participants had to perform the task on the moving and static versions of backgrounds of three levels of complexity, while their eye movements were recorded. The backgrounds displayed either an abstract (Experiment 1) or a naturalistic (Experiment 2) virtual environment. The results showed that performance was impaired by background motion in both experiments. The effects of motion and complexity were additive for the abstract background and multiplicative for the naturalistic background. Eye movement recordings showed that performance impairments reflected at least in part the impact of the background visual features on gaze control.


Subject(s)
Eye Movements/physiology , Motion Perception/physiology , Pattern Recognition, Visual/physiology , Perceptual Masking , Video Games , Adult , Attention/physiology , Discrimination, Psychological , Female , Humans , Male , Photic Stimulation/methods , Task Performance and Analysis
13.
Ergonomics ; 56(12): 1863-76, 2013.
Article in English | MEDLINE | ID: mdl-24168472

ABSTRACT

The visual interfaces of virtual environments such as video games often show scenes where objects are superimposed on a moving background. Three experiments were designed to better understand the impact of the complexity and/or overall motion of two types of visual backgrounds often used in video games on the detection and use of superimposed, stationary items. The impact of background complexity and motion was assessed during two typical video game tasks: a relatively complex visual search task and a classic, less demanding shooting task. Background motion impaired participants' performance only when they performed the shooting game task, and only when the simplest of the two backgrounds was used. In contrast, and independently of background motion, performance on both tasks was impaired when the complexity of the background increased. Eye movement recordings demonstrated that most of the findings reflected the impact of low-level features of the two backgrounds on gaze control.


Subject(s)
Motion , Nystagmus, Optokinetic/physiology , Task Performance and Analysis , Video Games , Adolescent , Female , Humans , Male , Pattern Recognition, Visual , Perceptual Masking , Photic Stimulation , Young Adult
14.
World J Biol Psychiatry ; 13(3): 164-77, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21623668

ABSTRACT

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a chronic, often severe, neuropsychiatric disorder leading to a dramatic impairment in interpersonal and occupational functions. rTMS has been tried out in several studies in patients with OCD with different characteristics. In this paper, we review the safety and efficacy of rTMS in the treatment of mostly severe resistant OCD. METHODS: A review of the English literature from 1966 to 2010 pertaining to rTMS in the treatment of OCD was conducted using MEDLINE by selectively entering the search terms "transcranial magnetic stimulation", "repetitive transcranial magnetic stimulation", "obsessive-compulsive disorder" and "OCD". Twelve studies including open and randomized, sham-controlled trials were included in this review. RESULTS: Although available data about the use of rTMS in OCD treatment are quite heterogeneous in terms of sample size, study design, stimulus parameters used and stimulation areas targeted, promising findings regarding rTMS efficacy appeared for two structures based on recent controlled studies: the supplementary motor area and the orbitofrontal cortex. On the other hand, rTMS of the dorsolateral prefrontal cortex is not significantly effective when compared to sham rTMS. CONCLUSIONS: Three target areas have already been selected of which the supplementary motor area in particular and the orbitofrontal cortex seem to be the most promising in terms of potential efficacy and could more accurately be targeted with the help of neuronavigational techniques. Larger randomized controlled trials should be conducted in order to better clarify the therapeutic role of rTMS in OCD.


Subject(s)
Obsessive-Compulsive Disorder/physiopathology , Obsessive-Compulsive Disorder/therapy , Transcranial Magnetic Stimulation , Frontal Lobe , Humans , Prefrontal Cortex , Transcranial Magnetic Stimulation/adverse effects , Transcranial Magnetic Stimulation/methods , Treatment Outcome
15.
Mem Cognit ; 40(3): 450-65, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22086649

ABSTRACT

In two experiments, we examined the role of discrepancy on readers' text processing of and memory for the sources of brief news reports. Each story included two assertions that were attributed to different sources. We manipulated whether the second assertion was either discrepant or consistent with the first assertion. On the basis of the discrepancy-induced source comprehension (D-ISC) assumption, we predicted that discrepant stories would promote deeper processing and better memory for the sources conveying the messages, as compared to consistent stories. As predicted, readers mentioned more sources in summaries of discrepant stories, recalled more sources, made more fixations, and displayed longer gaze times in source areas when reading discrepant than when reading consistent stories. In Experiment 2, we found enhanced memory for source-content links for discrepant stories even when intersentential connectors were absent, and regardless of the reading goals. Discussion was focused on discrepancies as one mechanism by which readers are prompted to encode source-content links more deeply, as a method of integrating disparate pieces of information into a coherent mental representation of a text.


Subject(s)
Association Learning , Attention , Comprehension , Conflict, Psychological , Mental Recall , Reading , Adolescent , Female , Fixation, Ocular , Generalization, Psychological , Humans , Male , Reaction Time , Young Adult
16.
Can J Exp Psychol ; 66(1): 32-43, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22148903

ABSTRACT

An eye-tracking experiment was performed to assess the influence of orthographic and semantic distractor words on visual search for words within lists. The target word (e.g., "raven") was either shown to participants before the search (literal search) or defined by its semantic category (e.g., "bird", categorical search). In both cases, the type of words included in the list affected visual search times and eye movement patterns. In the literal condition, the presence of orthographic distractors sharing initial and final letters with the target word strongly increased search times. Indeed, the orthographic distractors attracted participants' gaze and were fixated for longer times than other words in the list. The presence of semantic distractors related to the target word also increased search times, which suggests that significant automatic semantic processing of nontarget words took place. In the categorical condition, semantic distractors were expected to have a greater impact on the search task. As expected, the presence in the list of semantic associates of the target word led to target selection errors. However, semantic distractors did not significantly increase search times any more, whereas orthographic distractors still did. Hence, the visual characteristics of nontarget words can be strong predictors of the efficiency of visual search even when the exact target word is unknown. The respective impacts of orthographic and semantic distractors depended more on the characteristics of lists than on the nature of the search task.


Subject(s)
Eye Movements , Pattern Recognition, Visual , Reaction Time , Reading , Semantics , Analysis of Variance , Female , Humans , Male , Young Adult
17.
Hum Factors ; 53(2): 103-17, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21702329

ABSTRACT

OBJECTIVE: Two experiments were conducted to investigate elements of the spatial design of video game interfaces. BACKGROUND: In most video games, both the objects and the background scene are moving. Players must pay attention to what appears in the background to anticipate events while looking at head-up displays. According to the proximity-compatibility principle, game-related information should be placed as close as possible to the anticipation zone. METHOD: Participants played a video game where they had to anticipate the upward movement of obstacles. The score location was manipulated. The average vertical gaze position and dispersion were used to assess anticipation and extent of visual scanning, respectively. RESULTS: Putting the score at the bottom rather than the top of the game window, within the anticipation zone, was expected to minimize attentional moves. Experiment I revealed lower average gaze positions and reduced extent of visual scanning in that condition, but the score performance did not improve significantly. Experiment 2 demonstrated that players' performance increased compared with the bottom condition when the score was displayed just below but outside the game window, despite an increased extent of visual scanning. CONCLUSION: Positioning the score just outside the anticipation zone facilitated anticipation of the movement of obstacles and led to better performance than when the score overlapped with the game anticipation zone. APPLICATION: For games requiring visual anticipation, contextual information should be located in the direction of anticipation but not within the anticipation zone. This recommendation complements the proximity compatibility principle for simple dynamic displays.


Subject(s)
Anticipation, Psychological , Data Display , Video Games , Adult , Eye Movement Measurements , Female , Humans , Male , Play and Playthings , Software Design , Young Adult
18.
Ann N Y Acad Sci ; 1164: 180-7, 2009 May.
Article in English | MEDLINE | ID: mdl-19645897

ABSTRACT

Mutant mice are a good model to study to what extent the postnatal activity of sensory afferents is necessary for the maturation of central neurons. In particular, the question arises whether the signals carried by the first-order vestibular neurons, which encode information on the head movement of pups, are necessary for the maturation of second-order vestibular neurons. To address that question, juvenile and adult transgenic, vestibular-deficient mutants where a null mutation of the KCNE1 potassium-channel gene leads to degeneration of all hair cells of the inner ear just after birth were studied. These KCNE1(-/-) mutants are deaf and show quasi-constant head bobbing and a permanent shaker/waltzer phenotype. This behavior is not due to persistent abnormalities of the membrane properties of central vestibular neurons, because their maturation is delayed but not impaired by the absence of sensory vestibular information. On the other hand, the data shed light on how the membrane properties of vestibular neurons might be modified according to functional requirements or following lesions. The expression levels of the protein calretinin that regulates the intracellular free-calcium concentration in central vestibular neurons could play a major role both in intact animals and following labyrinthectomy. By comparing the KCNE1(-/-) mutant mice to other vestibular-deficient animals, it was concluded that the suppression of vestibular inputs during a "critical period" of postnatal development can induce a permanent circling behavior, but that this phenotype is not always due to congenital vestibular deficiency.


Subject(s)
Locomotion , Neurons/cytology , Vestibule, Labyrinth/cytology , Animals , Mice , Mice, Transgenic , Phenotype , Potassium Channels, Voltage-Gated/genetics , Potassium Channels, Voltage-Gated/physiology
19.
Neurogenetics ; 9(4): 237-48, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18604572

ABSTRACT

Small-conductance Ca(2+)-activated potassium (SK) channels are heteromeric complexes of SK alpha-subunits and calmodulin that modulate membrane excitability, are responsible for part of the after-hyperpolarization (AHP) following action potentials, and thus control the firing patterns and excitability of most central neurons. An engineered knockout allele for the SK2 subunit has previously been reported. The hippocampal neurons of these mice lacked the medium latency component of the AHP, but the animals were not described as presenting any overt behavioral phenotype. In this report, we describe a deletion in the 5' region of the Kcnn2 gene encoding the SK2 subunit in the mouse neurological frissonnant (fri) mutant. The frissonnant mutant phenotype is characterized by constant rapid tremor and locomotor instability. It has been suggested, based merely on its phenotype, as a potential model for human Parkinson disease. We used a positional cloning strategy to identify the mutation underlying the frissonnant phenotype. We narrowed the genetic disease interval and identified a 3,441-bp deletion in the Kcnn2 gene, one of the three candidate genes present in the interval. Expression studies showed complete absence of normal Kcnn2 transcripts while some tissue-specific abnormal truncated variants were detected. Intracellular electrophysiological recordings of central vestibular neurons revealed permanent alterations of the AHP and firing behavior that might cause the tremor and associated locomotor deficits. Thus, the fri mutation suggests a new, potentially important physiological role, which had not been described, for the SK2 subunit of small-conductance Ca(2+)-activated potassium channels.


Subject(s)
Behavior, Animal/physiology , Sequence Deletion , Small-Conductance Calcium-Activated Potassium Channels/genetics , Small-Conductance Calcium-Activated Potassium Channels/physiology , Action Potentials , Amino Acid Sequence , Animals , Base Sequence , Brain/metabolism , Chromosome Mapping , DNA Primers/genetics , Electrophysiological Phenomena , Female , Gene Expression , Haplotypes , In Situ Hybridization , Liver/metabolism , Locomotion/genetics , Locomotion/physiology , Male , Mice , Mice, Inbred C3H , Mice, Mutant Strains , Molecular Sequence Data , Phenotype , Sequence Homology, Amino Acid , Tremor/genetics , Tremor/physiopathology
20.
J Neurosci ; 27(16): 4283-96, 2007 Apr 18.
Article in English | MEDLINE | ID: mdl-17442812

ABSTRACT

Central vestibular neurons process head movement-related sensory signals over a wide dynamic range. In the isolated frog whole brain, second-order vestibular neurons were identified by monosynaptic responses after electrical stimulation of individual semicircular canal nerve branches. Neurons were classified as tonic or phasic vestibular neurons based on their different discharge patterns in response to positive current steps. With increasing frequency of sinusoidally modulated current injections, up to 100 Hz, there was a concomitant decrease in the impedance of tonic vestibular neurons. Subthreshold responses as well as spike discharge showed classical low-pass filter-like characteristics with corner frequencies ranging from 5 to 20 Hz. In contrast, the impedance of phasic vestibular neurons was relatively constant over a wider range of frequencies or showed a resonance at approximately 40 Hz. Above spike threshold, single spikes of phasic neurons were synchronized with the sinusoidal stimulation between approximately 20 and 50 Hz, thus showing characteristic bandpass filter-like properties. Both the subthreshold resonance and bandpass filter-like discharge pattern depend on the activation of an I(D) potassium conductance. External current or synaptic stimulation that produced impedance increases (i.e., depolarization in tonic or hyperpolarization in phasic neurons) had opposite and complementary effects on the responses of the two types of neurons. Thus, membrane depolarization by current steps or repetitive synaptic excitation amplified synaptic inputs in tonic vestibular neurons and reduced them in phasic neurons. These differential, opposite membrane response properties render the two neuronal types particularly suitable for either integration (tonic neurons) or signal detection (phasic neurons), respectively, and dampens variations of the resting membrane potential in the latter.


Subject(s)
Potassium Channels, Voltage-Gated/metabolism , Rhombencephalon/physiology , Semicircular Canals/physiology , Synaptic Transmission/physiology , Vestibule, Labyrinth/physiology , 4-Aminopyridine/pharmacology , Animals , Brain Stem , Electric Impedance , In Vitro Techniques , Kv1.1 Potassium Channel/analysis , Membrane Potentials/physiology , Neurons/chemistry , Neurons/physiology , Potassium Channel Blockers/pharmacology , Rana temporaria , Temperature , Vestibular Nerve/physiology , Vestibule, Labyrinth/cytology
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