Subclinical hypothyroidism and neurocognitive functioning in bipolar disorder

The aim of this study was to compare neurocognitive functioning between euthymic bipolar disorder (BD) patients with and without subclinical hypothyroidism (SCH). Patients with SCH had poorer performance than patients without SCH in measures of verbal memory, attention, language, and executive functions. These preliminary results suggest that SCH could have some impact on the neurocognitive performance of euthymic patients with BD and warrant further research in this field.     

Executive functions in adults with developmental dyslexia

BackgroundExecutive functioning (EF) deficits are well recognized in developmental dyslexia, yet the majority of studies have concerned children rather than adults, ignored the subjective experience of the individual with dyslexia (with regard to their own EFs), and have not followed current theoretical perspectives on EFs.Aims and MethodsThe current study addressed these shortfalls by administering a self-report measure of EF (BRIEF-A; Roth, Isquith, & Gioia, 2005) and experimental tasks to IQ-matched groups of adults with and without dyslexia. The laboratory-based tasks tested the three factors constituting the framework of EF proposed by Miyake et al. (2000).ResultsIn comparison to the group without dyslexia, the participants with dyslexia self-reported more frequent EF problems in day-to-day life, with these difficulties centering on metacognitive processes (working memory, planning, task monitoring, and organization) rather than on the regulation of emotion and behaviour. The participants with dyslexia showed significant deficits in EF (inhibition, set shifting, and working memory).Conclusions and ImplicationsThe findings indicated that dyslexia-related problems have an impact on the daily experience of adults with the condition. Further, EF difficulties are present in adulthood across a range of laboratory-based measures, and, given the nature of the experimental tasks presented, extend beyond difficulties related solely to phonological processing.     

Cerebellar morphology in developmental dyslexia

Recent evidence has suggested cerebellar anomalies in developmental dyslexia. Therefore, we investigated cerebellar morphology in subjects with documented reading disabilities. We obtained T1-weighted magnetic resonance images in the coronal and sagittal planes from 11 males with prior histories of developmental dyslexia, and nine similarly-aged male controls. Proton magnetic resonance spectra (TE=136ms, TR=2.4s) were obtained bilaterally in the cerebellum. Phonological decoding skill was measured using non-word reading. Handedness was assessed using both the Annett questionnaire of hand preference and Annett's peg moving task.Cerebellar symmetry was observed in the dyslexics but there was significant asymmetry (right grey matter>left grey matter) in controls. The interpretation of these results depended whether a motor- or questionnaire-based method was used to determine handedness. The degree of cerebellar symmetry was correlated with the severity of dyslexics' phonological decoding deficit. Those with more symmetric cerebella made more errors on a nonsense word reading measure of phonological decoding ability. Left cerebellar metabolite ratios were shown to correlate significantly with the degree of cerebellar asymmetry (P<0.05) in controls. This relationship was absent in developmental dyslexics.Cerebellar morphology reflects the higher degree of symmetry found previously in the temporal and parietal cortex of dyslexics. The relationship of cerebellar asymmetry to phonological decoding ability and handedness, together with our previous finding of altered metabolite ratios in the cerebellum of dyslexics, lead us to suggest that there are alterations in the neurological organisation of the cerebellum which relate to phonological decoding skills, in addition to motor skills and handedness.     

Impaired implicit sequence learning in children with developmental dyslexia

It has been proposed that an impairment of procedural memory underlies a range of linguistic, cognitive and motor impairments observed in developmental dyslexia (DD). However, studies designed to test this hypothesis using the implicit sequence learning paradigm have yielded inconsistent results. A fundamental aspect of procedural learning is that it takes place over an extended time-period that may be divided into distinct stages based on both behavioural characteristics and neural correlates of performance. Yet, no study of implicit sequence learning in children with DD has included learning stages beyond a single practice session. The present study was designed to fill this important gap by extending the investigation to include the effects of overnight consolidation as well as those of further practice on a subsequent day. The results suggest that the most pronounced procedural learning impairment in DD may emerge only after extended practice, in learning stages beyond a single practice session.     

Dissociation between exact and approximate addition in developmental dyslexia

Previous research has suggested that number sense and language are involved in number representation and calculation, in which number sense supports approximate arithmetic, and language permits exact enumeration and calculation. Meanwhile, individuals with dyslexia have a core deficit in phonological processing. Based on these findings, we thus hypothesized that children with dyslexia may exhibit exact calculation impairment while doing mental arithmetic. The reaction time and accuracy while doing exact and approximate addition with symbolic Arabic digits and non-symbolic visual arrays of dots were compared between typically developing children and children with dyslexia. Reaction time analyses did not reveal any differences across two groups of children, the accuracies, interestingly, revealed a distinction of approximation and exact addition across two groups of children. Specifically, two groups of children had no differences in approximation. Children with dyslexia, however, had significantly lower accuracy in exact addition in both symbolic and non-symbolic tasks than that of typically developing children. Moreover, linguistic performances were selectively associated with exact calculation across individuals. These results suggested that children with dyslexia have a mental arithmetic deficit specifically in the realm of exact calculation, while their approximation ability is relatively intact.     

Disrupted white matter connectivity underlying developmental dyslexia: A machine learning approach

Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white‐matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school‐aged dyslexic children with 33 age‐matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto‐occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well‐recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals. Hum Brain Mapp 37:1443‐1458, 2016. © 2016 Wiley Periodicals, Inc.     

A comparative study of the neuropsychiatric and neurocognitive phenotype in two microdeletion syndromes: Velocardiofacial (22q11.2 deletion) and Williams (7q11.23 deletion) syndromes

Purpose22q11.2 deletion syndrome (22q11.2DS) and Williams syndrome (WS) are common neurogenetic microdeletion syndromes. The aim of the present study was to compare the neuropsychiatric and neurocognitive phenotypes of 22q11.2DS and WS.MethodsForty-five individuals with 22q11.2DS, 24 with WS, 22 with idiopathic developmental disability (DD) and 22 typically developing (TD) controls were compared for the rates of psychiatric disorders as well as cognitive executive and visuospatial functions.ResultsWe found that while anxiety, mood and disruptive disorders had an equally high prevalence among individuals with 22q11.2DS, WS and DDs, the 22q11.2DS group had the highest rates of psychotic disorders and the WS group had the highest rates of specific phobia. We also found that the WS group demonstrated more severe impairments in both executive and visuospatial functions than the other groups. WS and 22q11.2DS subjects had worse Performance-IQ than Verbal-IQ, a feature typical of non-verbal learning disorders.ConclusionThese findings offer a wide perspective on unique versus common phenotypes in 22q11.2DS and WS.     

Phonological,temporal and spectral processing in vowel length discrimination is impaired in German primary school children with developmental dyslexia

It is still unclear whether phonological processing deficits are the underlying cause of developmental dyslexia, or rather a consequence of basic auditory processing impairments. To avoid methodological confounds, in the current study the same task and stimuli of comparable complexity were used to investigate both phonological and basic auditory (temporal and spectral) processing in dyslexia. German dyslexic children (Grades 3 and 4) were compared to age- and grade-matched controls in a vowel length discrimination task with three experimental conditions: In a phonological condition, natural vowels were used, differing both with respect to temporal and spectral information (in German, vowel length is phonemic, and vowel length differences are characterized by both temporal and spectral information). In a temporal condition, spectral information differentiating between the two vowels of a pair was eliminated, whereas in a spectral condition, temporal differences were removed. As performance measure, the sensitivity index d′ was computed. At the group level, dyslexic children's performance was inferior to that of controls for phonological as well as temporal and spectral vowel length discrimination. At an individual level, nearly half of the dyslexic sample was characterized by deficits in all three conditions, but there were also some children showing no deficits at all. These results reveal on the one hand that phonological processing deficits in dyslexia may stem from impairments in processing temporal and spectral information in the speech signal. On the other hand they indicate, however, that not all dyslexic children might be characterized by phonological or auditory processing deficits.     

Contribution of the anterior insula to temporal auditory processing deficits in developmental dyslexia

Developmental dyslexia has been assumed to arise from general auditory deficits, compromising rapid temporal integration both of linguistic and nonlinguistic acoustic stimuli. Because the effort of auditory temporal processing of speech and nonspeech test materials may depend on presentation rate, fMRI measurements were performed in dyslexics and controls during passive listening to series of syllable and click sounds, using a parametric approach. Controls showed a decrease of hemodynamic brain activation within the right and an increase within the left anterior insula as a function of the presentation rate both of click as well as syllable trains. By contrast, dyslexics exhibited this profile of hemodynamic responses under the nonspeech condition only. As concerns syllables, activation in dyslexics did not depend on presentation rate. Moreover, a subtraction analysis of hemodynamic main effects across conditions and groups revealed decreased activation both of the left and right anterior insula in dyslexics compared to controls during application both of click and syllables. These results indicate, in line with preceding studies, that the insula of both hemispheres is involved in auditory temporal processing of nonlinguistic auditory stimuli and demonstrate, furthermore, that these operations of intrasylvian cortex also extend to the linguistic domain. In addition, our data suggest that the anterior insula represents an important neural correlate of deficient temporal processing of speech and nonspeech sounds in dyslexia. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Impact of general cognition and executive function deficits on addiction treatment outcomes: Systematic review and discussion of neurocognitive pathways

This systematic review aims to examine growing evidence linking cognitive-executive functions with addiction treatment outcomes, and to discuss significant cognitive predictors drawing upon addiction neuroscience theory. We conducted a systematic search to identify studies using measures of general cognition and executive functions in patients with substance use disorders for the purpose of predicting two treatment outcomes: therapeutic adherence and relapse. Forty-six studies were selected, and sample characteristics, timing of assessments, and cognitive measures were analyzed. We observed significant methodological differences across studies, resulting in substantial variability in the relationships between cognitive-executive domains and treatment outcomes. Notwithstanding this variability, we found evidence of associations, of medium effect size, between general cognition and treatment adherence, and between reward-based decision-making and relapse. The link between general cognition and treatment adherence is consistent with emerging evidence linking limited cognitive-executive resources with less ability to benefit from talk therapies. The link between reward-based decision-making and relapse accords with decision neuroscience models of addiction. Findings may inform preclinical and clinical research concerning addiction treatment mechanisms.     

The neural substrates of cognitive control deficits in autism spectrum disorders

Executive function deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive function deficits in ASDs, and only one in adolescents. The current study examined cognitive control – the ability to maintain task context online to support adaptive functioning in the face of response competition – in 22 adolescents aged 12–18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7 and BA 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms.     

Implicit learning and reading: Insights from typical children and children with developmental dyslexia using the artificial grammar learning (AGL) paradigm

We examined implicit learning in school-aged children with and without developmental dyslexia based on the proposal that implicit learning plays a significant role in mastering fluent reading. We ran two experiments with 16 typically developing children (9 to 11-years-old) and 16 age-matched children with developmental dyslexia using the artificial grammar learning (AGL) paradigm. In Experiment 1 (non-transfer task), children were trained on stimuli that followed patterns (rules) unknown to them. Subsequently, they were asked to decide from a novel set which stimuli follow the same rules (grammaticality judgments). In Experiment 2 (transfer task), training and testing stimuli differed in their superficial characteristics but followed the same rules. Again, children were asked to make grammaticality judgments. Our findings expand upon previous research by showing that children with developmental dyslexia show difficulties in implicit learning that are most likely specific to higher-order rule-like learning. These findings are discussed in relation to current theories of developmental dyslexia and of implicit learning.     

Cytoarchitectonic abnormalities in developmental dyslexia: A case study

A patient is reported who had a well-documented history of developmental dyslexia. Reading difficulties were present in other male members of the immediate family. Gross anatomical and cytoarchitectonic analysis of the brain in serial sections showed a consistently wider left cerebral hemisphere, an area of polymicrogyria in the left temporal speech region, and mild cortical dysplasias in limbic, primary, and association cortices of the left hemisphere.     

Recovery in reading: A treatment study of acquired deep dyslexia in Spanish

Background: Adult oral reading in consistent orthographies, like Spanish, is argued to proceed through sublexical spelling-to-sound conversion. Hence, it was surprising that Davies and Cuetos (2005 Davies, R. and Cuetos, F. 2005. Acquired dyslexia in Spanish: A review and some observations on a new case of deep dyslexia. Behavioural Neurology,, 16: 85–101. [PubMed], [Web of Science ®] , [Google Scholar]) observed a Spanish-speaking aphasic patient, MJ, who showed some capacity to read words aloud—producing many semantic errors—alongside an inability to read nonwords. MJ's symptoms are congruent with deep dyslexia. We investigated whether her reading could be improved through therapy addressing those deep dyslexic symptoms (de Partz, 1986 de Partz, M-P. 1986. Re-education of a deep dyslexic patient: Rationale of the method and results. Cognitive Neuropsychology,, 3: 149–177. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]).

Aims: We expected to see joint improvement in word and nonword reading if therapy aimed at facilitating improvement in nonword reading succeeded, due to the consistency of the orthography. We hypothesised that occurrence of semantic paralexias in reading should decrease as reading skills improved. Alternatively, if therapy had led to the establishment of a lexical-semantic reading strategy not available to the patient before injury, then we anticipated the possibility that semantic errors could actually increase in occurrence as more therapy was received over time.

Methods & Procedures: Our study began 18 months after MJ's brain injury, and continued over 2 years. Training was given in completing spelling–sound mappings at the level of grapheme–phoneme correspondences, syllables and words, in phoneme awareness and the combination of phonemes, and in word–picture association. We tested oral reading with the same word and nonword stimuli at four time points through the period of our investigation. We analysed accuracy and error types.

Outcomes & Results: By the end of our investigation, MJ presented near-normal word reading and greatly improved, though still impaired, nonword reading. Production of semantic errors disappeared. Thus, adding to some previous case studies (Friedman, 1996 Friedman, R. B. 1996. Recovery from deep alexia to phonological alexia: Points on a continuum. Brain and Language,, 52: 114–128. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]), our patient's symptoms evolved from those typical of deep dyslexia to those typical of phonological dyslexia.

Conclusions: Our findings show that, even in a language with a transparent orthography, readers can be aided by therapy addressing both lexical and non-lexical reading. The implication is that premorbid reading in a transparent orthography may depend on lexical and non-lexical reading. This conclusion is supported by the superior improvement of word compared to nonword reading, and by the decline in production of semantic paralexias accompanying the improvement in reading performance.     

Implicit phonological and semantic processing in children with developmental dyslexia: Evidence from event-related potentials

Dyslexia is characterized by a core phonological deficit, although recent studies indicate that semantic impairment also contributes to this condition. In this study, event-related potentials (ERP) were used to examine whether the N400 wave in dyslexic children is modulated by phonological or semantic priming, similarly to age-matched controls. ERPs were recorded while children listened to word lists in which the semantic and phonological congruency of the terminal words were manipulated. No overt judgments were made by participants. In control children the N400 amplitude to both semantically and phonologically incongruent words was enlarged relative to congruent words. Dyslexic children exhibited a dissociation of priming effects depending on whether semantic or phonological primes were used. Semantic priming elicited an N400 effect comparable to controls, though delayed. In phonological priming, the dyslexics differed from controls in both the phonologically incongruent and congruent conditions showing reduced N400 amplitude in the former and enhanced N400 in the latter. This pattern suggests that when faced with phonological priming, dyslexics show abnormal neural responses related to both integration of similarities between the consecutive stimuli and the ability to detect incongruent stimuli. Semantic priming seems relatively intact in dyslexics, however neural responses to contextual incongruency are delayed.     

Multiple system atrophy with early cognitive deficits: A case report

We present the case of a patient with multiple system atrophy with predominant cerebellar ataxia (MSA-C) in the early stage of the disease, who was assessed using a comprehensive neuropsychological test battery. Many studies have found cognitive deficits in MSA patients assessed after 2–3 years, but not in the first stages of the disease. The aim of this paper is to stress the importance of a complete neuropsychological assessment, even at the initial stage of the disease, when instrumental examinations are not able to show cortical involvement and daily life activities have not been affected. The neuropsychological tests examined general cognition, verbal and visual memory, visuospatial and constructional ability, language, executive function, depression and functional autonomy. Results showed cognitive deficits in executive functions, above all in the control and inhibition of automatic response, planning and reasoning abilities, memory and visuoconstructional functions. However, these problems did not affect the patient’s autonomy in everyday life. MRI scan showed the involvement of the cerebellum and the fibers of the pons and raphe, with normal cerebral ventricles and sulci. The cognitive deficits in our patient could be explained by a disruption in cerebrocerebellum connections between the frontal areas and the cerebellar structures. These results show that a more comprehensive cognitive evaluation is necessary to detect early the onset of neuropsychological deficits, also in order to begin in time adequate rehabilitation programs.     

Gray matter alteration in dyslexia: converging evidence from volumetric and voxel-by-voxel MRI analyses

Affecting up to 4-10% of the population, dyslexia is a highly prevalent, childhood onset developmental disorder adversely influencing multiple domains of adaptive functioning throughout the lifespan. The present brain imaging study was conducted in order to investigate the neuroanatomical correlates of developmental dyslexia. The MRI brain scans of 10 males with dyslexia and 14 matched controls were analyzed with (1) a classical volumetric method measuring gray and white matter lobar volumes and (2) a voxel-by-voxel method. The voxel-by-voxel method identifies changes in tissue density and localizes morphologic alterations without limiting the analyses to predefined regions. Subsequent correlations between gray matter density and neuropsychological performance on specific phonological processing tasks (rhyme judgment) were conducted. Volumetric analyses revealed significantly reduced gray matter volumes in both temporal lobes in dyslexic individuals. The voxel-by-voxel analyses further localized changes to the left temporal lobe, revealing reduced gray matter density in the middle and inferior temporal gyri. Conversely, increased gray matter density was found in the precentral gyri bilaterally. As a combined group, the dyslexic and control subjects demonstrated positive correlations between performance on the rhyme judgment tasks and gray matter density in the middle and inferior frontal gyri, and the middle temporal gyri bilaterally. The current study indicates that dyslexia is associated with a structural gray matter deficit involving a complex fronto-temporal network implicated in phonological processing.     

The neurocognitive basis of insight into illness in anorexia nervosa: A pilot metacognitive study

The primary goal of the present study was to explore the neuropsychological basis of insight into illness in anorexia nervosa by evaluating its differential and joint links with cognitive vs. metacognitive performance. Participants in the study were 25 women with anorexia nervosa (AN) and 25 healthy comparisons (HC). All participants completed a computerized version of the Wisconsin Card Sorting Task (WCST) and the Computerized Body-Size Discrimination task (CBSD). In addition to the standard administration of the tasks, subjects were also asked to rate their level of confidence in the correctness of each sort and to choose whether they wanted each sort to be “counted” toward their overall performance score on the test. Insight into illness in the AN group was assessed with the Scale of Unawareness of Mental Disorder (SUMD). Prediction of poor insight was significantly improved when adding the new, free-choice metacognitive measures to the conventional measures in both tasks, but not the other way around. These preliminary results suggest that metacognition might be an important mediator between basic cognitive deficits and poor insight and that it might be even more relevant to poor insight than cognitive deficits per se.     

Scaffolded instruction remediates Wisconsin Card Sorting Test deficits in schizophrenia: A comparison to other techniques

Errorless learning without fading (ELWF) and the method of vanishing cues (MVC) have been widely researched in rehabilitation contexts, but little is known about their effectiveness relative to each other. With respect to explicit memory, it was hypothesised that the MVC can lead to better performance than ELWF for those with less severe memory difficulties, provided that it elicits effortful but successful study‐trial recall. This hypothesis was supported in two studies involving participants with less severe memory difficulties following acquired brain injuries, using free recall as the measure of explicit memory. With respect to implicit memory, it was suggested, on the basis of the transfer appropriate processing approach, that the relative effectiveness of the two methods will depend on the way in which memory is tested. Specifically, it was hypothesised that the MVC would be more effective than ELWF on a stem completion task, equally effective on a free association task, and less effective on a perceptual identification task. These hypotheses were supported in the two studies involving participants with brain injuries, and in two larger studies involving university students. The implications of these findings for the use of these methods in rehabilitation are discussed. It is argued that the MVC may be more effective when the task can be learnt explicitly, the learner retains significant explicit memory ability and the study‐trial recall is effortful but successful. With respect to implicit memory, one interpretation of the findings is that, in most practical contexts, neither method will have any intrinsic advantage, although ELWF may be preferable because it is more effective in eliminating errors. However, this suggestion is very tentative because of issues concerning the generalisability of the present findings, and further research is recommended.