Widespread Impairment Research Articles

Focal expression of adeno-associated viral-mutant tau induces widespread impairment in an APP mouse model

Adeno-associated virus serotype 6 (AAV6) viral vectors encoding mutant and normal tau were used to produce focal tau pathology. Two mutant forms of tau were used; the P301S tau mutation is associated with neurofibrillary tangle formation in humans, and the 3PO mutation leads to rapid tau aggregation and is associated with pathogenic phosphorylation and cytotoxicity in vitro. We show that adeno-associated viral injection into entorhinal cortex of normal and tau knockout animals leads to local overexpression of tau, and the presence of human tau in axons projecting to and emanating from the entorhinal cortex. Starting at 2 months and increasing by 6 months post-injection neurons expressing mutant tau developed hyperphosphorylated tau pathology, in addition to dystrophic neurites. There was neuronal loss in tau-expressing regions, which was similar in normal and in TASTPM mice injected with mutant tau. There was neuroinflammation around plaques, and in regions expressing mutant tau. We saw no evidence that mutant tau had affected amyloid-beta pathology or vice versa. Morris water maze behavioral tests demonstrated mild memory impairment attributable to amyloid-beta pathology at 2 and 4 months, with severe impairment at 6 months in animals receiving adeno-associated viral-3PO. Therefore, TASTPM mice injected with mutant tau displayed many of the main features characteristic of human Alzheimer's disease patients and might be used as a model to test new drugs to ameliorate clinical features of Alzheimer's disease.

IL-27-Induced Gene Expression Is Downregulated in HIV-Infected Subjects

ObjectiveTo characterize the effect of HIV infection on IL-27-induced gene expression.DesignDuring HIV infection, cytokine expression and function become deregulated. IL-27 is an important modulator of inflammatory responses. Interestingly, IL-27 can inhibit HIV replication in T cells and monocytes, implicating IL-27 as a potential adjunct to anti-viral treatment. Our previous work demonstrated that circulating HIV may suppress IL-27 expression, therefore, this study, in continuation of our previous work, aimed to understand how HIV affects expression levels of the IL-27 receptor and downstream functions of IL-27.MethodsPeripheral blood mononuclear cells (PBMC) were isolated from whole blood of HIV negative and HIV positive (viremic) individuals to assess IL-27-induced gene expression by flow cytometry and ELISA. PBMC were also processed for monocyte enrichment to assess IL-27 receptor expression by flow cytometry and real-time PCR.ResultsExpression of the IL-27 receptor subunit, gp130, was upregulated in response to IL-27 in HIV negative individuals, however, in HIV positive individuals, this IL-27 response was diminished. Furthermore, we observed downregulation of IL-27-induced IL-6, TNF-α, and IL-10 expression in HIV positive subjects.ConclusionIn HIV infection, IL-27-induced gene expression was impaired, indicating HIV-mediated dysregulation of IL-27 functions occurs during HIV infection. This study provides evidence for new viral pathogenic mechanisms contributing to the widespread impairment of immune responses observed in HIV pathogenesis.

Remission of positive symptoms according to the “remission in Schizophrenia Working Group” criteria: A longitudinal study of cognitive functioning

Schizophrenia patients in positive symptomatic remission (PSR; n=39) were assessed using a longitudinal research design. The patients were found to exhibit widespread cognitive impairments that were stable over the three-year follow-up period. The findings support a generalized and stable cognitive impairment profile among schizophrenia patients in partial symptomatic remission.

Cognitive Functioning in Prodromal Psychosis

A substantial proportion of people at clinical high risk (HR) of psychosis will develop a psychotic disorder over time. Cognitive deficits may predate the onset of psychosis and may be useful as markers of increased vulnerability to illness. To quantitatively examine the cognitive functioning in subjects at HR in the literature to date. Electronic databases were searched until January 2011. All studies reporting cognitive performance in HR subjects were retrieved. Nineteen studies met the inclusion criteria, comprising a total of 1188 HR subjects and 1029 controls. Neurocognitive functioning and social cognition as well as demographic, clinical, and methodological variables were extracted from each publication or obtained directly from its authors. Subjects at HR were impaired relative to controls on tests of general intelligence, executive function, verbal and visual memory, verbal fluency, attention and working memory, and social cognition. Processing speed domain was also affected, although the difference was not statistically significant. Later transition to psychosis was associated with even more marked deficits in the verbal fluency and memory domains. The studies included reported relatively homogeneous findings. There was no publication bias and a sensitivity analysis confirmed the robustness of the core results. The HR state for psychosis is associated with significant and widespread impairments in neurocognitive functioning and social cognition. Subsequent transition to psychosis is particularly associated with deficits in verbal fluency and memory functioning.

Effectiveness of Thermal Annular Procedures in Treating Discogenic Low Back Pain

Background: Persistent low back pain refractory to conservative treatment is a common problem that leads to widespread impairment, resulting in significant costs to society. The intervertebral disc is a major source of persistent low back pain. Technologies developed to treat this problem, including various surgical instrumentation and fusion techniques, have not reliably provided satisfactory results in terms of either pain relief or increased function. Thermal annular procedures (TAPs) were first developed in the late 1990s in an attempt to treat discogenic pain. The hope was that they would provide greater value than fusion in terms of efficacy, morbidity, and cost. Three technologies have been developed to apply heat to the annulus: intradiscal electrothermal therapy (IDET), discTRODE, and biacuplasty. Since nerve ingrowth and tissue regeneration in the annulus is felt to be the source of pain in discogenic low back pain, when describing the 3 above techniques we use the term “thermal annular procedures” rather than “thermal intradiscal procedures.” We have specifically excluded studies treating the nucleus. TAPs have been the subject of significant controversy. Multiple reviews have been conducted resulting in varying conclusions. Study Design: A systematic review of TAPs for the treatment of discogenic low back pain. Objective: To evaluate the effectiveness of TAPs in treating discogenic low back pain and to assess complications associated with those procedures. Methods: The available literature on TAPs in treating discogenic low back pain was reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria for interventional techniques for randomized trials, and the criteria developed by the Newcastle-Ottawa Scale criteria for observational studies. The level of evidence was classified as good, fair, or limited (or poor) based on the quality of evidence developed by the U.S. Preventive Services Task Force. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 through December 2011, and manual searches of the bibliographies of known primary and review articles. Outcome Measures: The primary outcome measure was pain relief of at least 6 months. Secondary outcome measures were improvements in functional status. Results: For this systematic review, 43 studies were identified. Of these, 3 randomized controlled trials and one observational study met the inclusion criteria. Using current criteria for successful outcomes, the evidence is fair for IDET and limited (or poor) for discTRODE and biacuplasty procedures regarding whether they are effective in relieving discogenic low back pain. Since 2 randomized controlled trials are in progress on that procedure, assessment of biacuplasty may change upon publication of those studies. Limitations: The limitations of this systematic review include the paucity of literature and nonavailability of 2 randomized trials which are in progress for biacuplasty. Conclusion: In summary, the evidence is fair for IDET and limited (or poor) for discTRODE and biacuplasty is being evaluated in 2 ongoing randomized controlled trials. Key words: Spinal pain, chronic low back pain, discogenic pain, thermal procedures, annular procedures, IDET, biaculoplasty, disctrode

Mapping Symbols to Sounds: Electrophysiological Correlates of the Impaired Reading Process in Dyslexia

Dyslexic and control first-grade school children were compared in a Symbol-to-Sound matching test based on a non-linguistic audiovisual training which is known to have a remediating effect on dyslexia. Visual symbol patterns had to be matched with predicted sound patterns. Sounds incongruent with the corresponding visual symbol (thus not matching the prediction) elicited the N2b and P3a event-related potential (ERP) components relative to congruent sounds in control children. Their ERPs resembled the ERP effects previously reported for healthy adults with this paradigm. In dyslexic children, N2b onset latency was delayed and its amplitude significantly reduced over left hemisphere whereas P3a was absent. Moreover, N2b amplitudes significantly correlated with the reading skills. ERPs to sound changes in a control condition were unaffected. In addition, correctly predicted sounds, that is, sounds that are congruent with the visual symbol, elicited an early induced auditory gamma band response (GBR) reflecting synchronization of brain activity in normal-reading children as previously observed in healthy adults. However, dyslexic children showed no GBR. This indicates that visual symbolic and auditory sensory information are not integrated into a unitary audiovisual object representation in them. Finally, incongruent sounds were followed by a later desynchronization of brain activity in the gamma band in both groups. This desynchronization was significantly larger in dyslexic children. Although both groups accomplished the task successfully remarkable group differences in brain responses suggest that normal-reading children and dyslexic children recruit (partly) different brain mechanisms when solving the task. We propose that abnormal ERPs and GBRs in dyslexic readers indicate a deficit resulting in a widespread impairment in processing and integrating auditory and visual information and contributing to the reading impairment in dyslexia.

Avances neurofisiológicos en el síndrome del túnel del carpo: proceso de sensibilización central o neuropatía local

Carpal tunnel syndrome (CTS) is considered a simple entrapment of the median nerve at the carpal tunnel. In the last years, several studies have demonstrated the presence of peripheral and central sensitization mechanisms.To review the basis neurophysiology of peripheral and central sensitization by applying them to CTS and to determine their clinical repercussions.Several studies have revealed that patients with CTS exhibit somato-sensory changes in areas innervated by the median nerve and also in areas non-related with the median nerve. Individuals with CTS exhibited widespread mechanical and thermal pain hyperalgesia, although they suffered from unilateral symptoms. Further, patients also showed wide-spread impairments in vibration conduction, deficits in fine motor control and changes in the somato-sensory cortex. These evidences support the presence of a complex process of peripheral and central sensitization in patients with CTS which may constitute a negative prognosis factor for the management of these patients.The advances in neurosciences in the last years support the presence of peripheral and central sensitization mechanisms in CTS. These mechanisms justify the necessity of conceptual changes and in the management, both conservative and surgical, of this syndrome. Additionally, central sensitization can also play a relevant role in the prognosis of CTS since it can constitute a negative prognosis factor for its treatment.

Long term clinical course of Tourette syndrome

Background: Recent studies using cluster analysis and factor analysis have suggested that Tourette Syndrome (TS) should no longer be considered a unitary condition. Material and methods: We retrospectively studied the long term clinical course of 100 TS patients. The patients were assessed at the onset and after 10years follow-up to evaluate the severity of tic, the Obsessive Compulsive Disorder (OCD), the Attention Deficit Hyperactivity Disorder (ADHD) and the presence of anxiety and depression, rage attacks, self injuries behavior. Moreover at the follow-up they completed an evaluation scale on quality of life to assess the impairment in everyday life after 10years of illness. Results: The “pure TS” clinical group (38 subjects) showed after 10years follow-up that 58% carried on with the same clinical phenotype, whereas 42% changed in “TS+OCD” phenotype. Fifty-five percentage required pharmacological treatment. All the “TS+ADHD” clinical group (48 subjects) showed after 10years follow-up a different clinical phenotype: 62% “TS pure” phenotype, 35% “TS+OCD” phenotype, 2% “TS+ADHD+OCD” phenotype. Sixty-five percentage of the subject required pharmacological treatment. The “TS+ADHD+OCD” clinical group (14 subjects) after 10years follow-up showed that 14% carried on with the same clinical phenotype, whereas 8.3% presented “TS pure” phenotype and 92% presented “TS+OCD” phenotype. Seventy-one percentage were in need of therapy. With regards to quality of life, patients presented widespread impairment correlated to the presence of comorbid conditions. Conclusion: Our findings suggest that pure TS has quite a good long-term clinical course. By contrast, those who presented comorbid condition at the onset showed a more severe prognosis.

Implications of Hypothalamic–Pituitary–Adrenal Axis Functioning in Posttraumatic Stress Disorder

Cortisol secretions serve as the barometer of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates and controls responses to stress. Studies of cortisol secretions in patients with posttraumatic stress disorder (PTSD) reveal inconsistent results. Current research on HPA axis functioning in PTSD is examined to elucidate the neuroendocrine contributions in the disorder, identify current treatment's impact on the HPA axis, and consider implications for nursing care and areas for future research. There is evidence for HPA dysregulation in PTSD, which contributes to widespread impairment in functions such as memory and stress reactivity and to physical morbidity via processes such as allostatic load. There is limited, but building, evidence that dehydroepiandrosterone (DHEA), which is released simultaneously with cortisol, may provide anti-glucocorticoid and neuroprotective effects. Current treatments such as selective serotonin reuptake inhibitors and psychotherapy may have a beneficial impact on the HPA axis in PTSD populations. Somatic approaches to treating PTSD have not yet been studied in relation to their impact on HPA axis parameters in PTSD patients. Treatment studies of DHEA or glucocorticoids have not yet used HPA axis endpoints. PTSD treatment studies that include measures of HPA axis target mechanisms and consider HPA axis regulation as an additional treatment outcome are warranted.

Cortical thickness in neuropsychologically near-normal schizophrenia

Schizophrenia is a severe psychiatric illness with widespread impairments of cognitive functioning; however, a certain percentage of subjects are known to perform in the normal range on neuropsychological measures. While the cognitive profiles of these individuals have been examined, there has been relatively little attention to the neuroanatomical characteristics of this important subgroup. The aims of this study were to statistically identify schizophrenia subjects with relatively normal cognition, examine their neuroanatomical characteristics relative to their more impaired counterparts using cortical thickness mapping, and to investigate relationships between these characteristics and demographic variables to better understand the nature of cognitive heterogeneity in schizophrenia. Clinical, neuropsychological, and MRI data were collected from schizophrenia (n=79) and healthy subjects (n=65). A series of clustering algorithms on neuropsychological scores was examined, and a 2-cluster solution that separated subjects into neuropsychologically near-normal (NPNN) and neuropsychologically impaired (NPI) groups was determined most appropriate. Surface-based cortical thickness mapping was utilized to examine differences in thinning among schizophrenia subtypes compared with the healthy participants. A widespread cortical thinning pattern characteristic of schizophrenia emerged in the NPI group, while NPNN subjects demonstrated very limited thinning relative to healthy comparison subjects. Analysis of illness duration indicated minimal effects on subtype classification and cortical thickness results. Findings suggest a strong link between cognitive impairment and cortical thinning in schizophrenia, where subjects with near-normal cognitive abilities also demonstrate near-normal cortical thickness patterns. While generally supportive of distinct etiological processes for cognitive subtypes, results provide direction for further examination of additional neuroanatomical differences.

Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome

Szmulewicz, David J.*; Merchant, Saumil N.†; Halmagyi, Gabor Michael‡ Author Information

Chronic Degenerative Pain

Rheumatic diseases comprise a heterogeneous group of highly prevalent, usually chronic and progressively disabling disorders associated with poor patient quality of life and high healthcare resource utilization. The pain associated with these degenerative or inflammatory conditions represent some of the most important and complex problems of modern medicine, demanding an increasingly attentive, multidisciplinary, and continuous therapeutic approach. Extra-articular syndromes, notably fibromyalgia, can be a lifelong rheumatic condition characterized by widespread musculoskeletal pain and functional impairment, without any known structural or inflammatory cause. Irritable bowel syndrome (IBS) occurs in around half of patients with fibromyalgia raising the possibility of a possible overlapping or underlying pathophysiology. The dysfunction of bidirectional neural pathways and viscerovisceral cross-interactions within the central nervous system has been proposed as a possible central hypersensitization disorder responsible for the extraintestinal manifestations of IBS. Common inflammatory and molecular pathways may also be present in which a dysregulation of the immune system leads to a chronic inflammatory response. Given that the treatment of degenerative chronic pain remains suboptimal, these findings may suggest new treatment strategies.

Changes in interhemispheric inhibition following successful epilepsy surgery: a TMS study

Epileptic foci can influence cortical excitability, brain perfusion and metabolism not only directly in the focus or perifocally, but also in remote areas. Effects of successful epilepsy surgery on cortical networks and changes in excitability have rarely been addressed. We report a study on changes in interhemispheric inhibition following successful surgical removal of an epileptic focus. Eighteen patients (11 females, 7 males, mean age 34.2 years) were enrolled in this transcranial magnetic stimulation (TMS) study. All patients were seizure free after surgery and had identical antiepileptic medication pre- and postsurgically. Investigations were performed before and at least 3 months after surgery. Motor thresholds (MT) and motor evoked potentials (MEPs) of interhemispheric paired pulse paradigms were investigated on both hemispheres. Resection of the epileptic focus resulted in a significant change in interhemispheric inhibition (IHI). The ability of the non-focal hemisphere to inhibit the motor cortex (M1) of the focal hemisphere significantly increased (p=0.02) and normalized to the level of the other hemisphere. In summary, this TMS study suggests that an epileptic focus can modulate interhemispheric inhibitory interactions between the motor cortices. A decreased susceptibility of M1 of the focal hemisphere or alterations in the non-focal hemispheric inhibitory output may be underlying mechanisms. These findings may contribute to a better understanding of widespread functional impairments in focal epilepsy.

The clinical manifestations of anoxic brain injury

AbstractAnoxic brain injury can cause diffuse injury to the brain resulting in widespread neurological, behavioural and cognitive impairments. In this article, the authors describe the principal clinical manifestations of anoxic brain injury and illustrate this with two case histories. Copyright © 2010 Wiley Interface Ltd

Rate and acceleration of whole-brain atrophy in premanifest and early Huntington's disease

Huntington's disease (HD) produces progressive and ultimately widespread impairment of brain function. Neostriatal atrophy alone cannot account for whole-brain losses seen postmortem, and the mutant huntingtin protein and its neuropathologic sequelae are evident throughout the brain. Whole-brain atrophy quantification encompasses the totality of mutant huntingtin's effects on brain volume and may be useful in tracking progression in trials. We studied whole-brain atrophy in HD using a 2-year follow-up design, with three annual MRI scans. We recruited 20 control subjects, 21 premanifest mutation carriers, and 40 patients with early HD and used the brain boundary shift integral to study rate and acceleration of atrophy. Among subjects with an acceptable quality 2-year scan pair, age- and gender-standardized mean brain atrophy rate was greater (P < 0.001) in the patients with HD (n = 21; 0.88%/yr; 95% confidence interval: 0.62-1.13%/yr) than that in controls (n = 13; 0.16%/yr; 0.00-0.32%/yr). In the 12 patients with early HD in whom acceleration could be directly assessed there was evidence (P= 0.048) of acceleration year-on-year (mean acceleration = 0.69% yr(-2); 95% confidence interval: 0.01% yr(-2) to 1.37% yr(-2)), although this was not formally significantly different from that in controls (n = 7, P = 0.055). Statistically significantly increased atrophy rates and acceleration were not seen overall in the premanifest group, who were on average 18 years from predicted disease onset. We conclude that the study of whole-brain atrophy has the potential to inform our understanding of the neurobiology of HD and warrants further study as one means of assessing the outcomes of future clinical trials.

Is semantic memory impaired in schizophrenia? A systematic review and meta-analysis of 91 studies

Introduction. Semantic memory impairments in schizophrenia have been reported across a wide range of neuropsychological tests. Set against a backdrop of fairly widespread cognitive impairments, it is difficult to know whether there is a primary, or secondary, impairment of semantic memory in schizophrenia. Also, whether there is a profile of differential impairment across the range of neuropsychological tests. Methods. Employing a systematic search strategy, 91 papers were identified which have assessed participants with schizophrenia on a measure of semantic memory. A series of meta-analyses were then conducted which provided combined weighted means for performance on tasks of naming, word–picture matching, verbal fluency, priming, and categorisation. Results. An uneven profile of impairment is reported with large effect sizes for tests of naming and verbal fluency, medium effect sizes for word–picture matching and association and small effect sizes for categorisation and priming tests. Conclusions. This uneven profile supports the claim that a degradation of semantic knowledge may not be adequate in explaining the semantic memory impairment in schizophrenia. This conclusion is supported by the data which report a relationship between an executive dysfunction and poor priming and fluency performance particularly. The data support a link between Formal Thought Disorder and semantic memory impairments on tests of naming and verbal fluency but on other tests evidence is equivocal.

Reading and Spelling Disabilities in Children with and Without a History of Early Language Delay: A Neuropsychological and Linguistic Study

Language delay is a frequent antecedent of literacy problems, and both may be linked to phonological impairment. Studies on developmental dyslexia have led to contradictory results due to the heterogeneity of the pathological samples. The present study investigated whether Italian children with dyslexia showed selective phonological processing deficits or more widespread linguistic impairment and whether these deficits were associated with previous language delay. We chose 46 children with specific reading deficits and divided them into two groups based on whether they had language delay (LD) or not (NoLD). LD and NoLD children showed similar, severe deficits in reading and spelling decoding, but only LD children showed a moderate impairment in reading comprehension. LD children were more impaired in phonological working memory and phonological fluency, as well as in semantic fluency, grammatical comprehension, and verbal IQ. These findings indicate the presence of a moderate but widespread linguistic deficit (not limited to phonological processing) in a subset of dyslexic children with previous language delay that does not generalize to all children with reading difficulties.

Dysfunctions of Cortical Excitability in Drug-Naïve Posttraumatic Stress Disorder Patients

The investigation of a wide set of transcranial magnetic stimulation (TMS)-related variables in both hemispheres might help to identify a pattern of cortical excitability changes in posttraumatic stress disorder (PTSD) patients, reflecting gamma-amino-butiric acid (GABA)/glutamate balance and dysfunction, and to determine whether some of these variables are related to clinical features. In 20 drug-naive PTSD patients without comorbidity and 16 matched healthy control subjects we tested bilaterally with standard TMS procedures: resting motor threshold (RMT) to single-pulse TMS (reflecting ion channel function), paired-pulse short-latency intracortical inhibition (SICI; mainly reflecting GABA(A) function) and intracortical facilitation (ICF; mainly reflecting glutamatergic function), single-pulse cortical silent period (CSP; mainly reflecting GABA(B)-ergic function), and paired-pulse short-latency afferent inhibition (SAI; reflecting cholinergic mechanisms and their presynaptic GABA(A)-mediated modulation). The PTSD patients showed widespread impairment of GABA(A)-ergic SICI, which was reversed toward facilitation in both hemispheres in one-half of the patients, marked increase of glutamatergic ICF in the right hemisphere, and right-sided impairment of SAI. Illness duration and avoidance symptoms but not anxiety correlated with right-lateralized dysfunctions of cortical excitability. Although the neurobiological complexity of each TMS variable makes current results theoretical, the pattern of cortical excitability accompanying PTSD symptoms suggests a bilateral decrease of the GABA(A)-ergic function. This prevails in the right hemisphere, in association with a relative prevalence of the glutamatergic tone, a new finding that current neuroimaging investigations cannot provide due to the lack of reliable glutamate tracers. Results might help to disclose new pathophysiological aspects of PTSD symptoms, providing a rationale for future neuromodulatory strategies of treatment.

Widespread impairment of cell proliferation in the neonate Ts65Dn mouse, a model for Down syndrome

Among the many pathological aspects of Down syndrome, brain hypoplasia and mental retardation have been recently ascribed to defective proliferation of neural precursors during central nervous system development. By analogy, other features of Down syndrome, such as heart defects, gastrointestinal abnormalities, craniofacial dystrophy and reduced growth rate could be related, at least in theory, to similar proliferation impairment in peripheral tissues. In order to test this hypothesis, we evaluated cell proliferation in peripheral tissues of the Ts65Dn mouse, one of the animal models most commonly used to investigate Down syndrome. In fibroblast cultures from neonatal Ts65Dn mice, we found that cell proliferation was notably impaired. While length of the cell cycle was similar in fibroblasts from Ts65Dn and control mice, the number of actively proliferating cells was significantly smaller in Ts65Dn mice. Moreover, fibroblasts from Ts65Dn animals exhibited limited population-doubling capacity, decreased proliferative lifespan and premature senescence. Analysis of cell proliferation in the skin of neonates, in vivo, showed that in Ts65Dn mice, cell proliferation was significantly reduced compared to control mice. Our results suggest that defective proliferation may be a generalized feature of trisomic mice. In view of the genetic and phenotypic similarities between Ts65Dn mice and individuals with Down syndrome, proliferation impairment in various organs may also occur in subjects with Down syndrome. Thus, perturbation of a basic developmental function, cell proliferation, may be a critical determinant that contributes to the many aspects of pathology of this condition.

Impaired Working Memory Duration But Normal Learning Abilities Found in Mice That Are Conditionally Deficient in the Close Homolog of L1

In addition to its role in axon growth and neuronal migration, the close homolog of L1 (CHL1), a member of the L1 family of cell adhesion molecules, is involved in synaptic plasticity. To date, little has been done to disassociate the role of CHL1 during adulthood from its role during development. To address this issue, mice conditionally deficient in CHL1 (lacking CHL1 only after the third postnatal week) were tested relative to littermate controls as adults in five learning tasks and several tests of working memory (including duration and selective attention). CHL1-deficient mice showed no impairments in the learning tasks compared with wild-type controls. CHL1 deletion had no effect on selective attention despite its widespread impairment of working memory duration. These results suggest a role for CHL1 in the adult-brain in the short-term maintenance of information.