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The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task. 36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS. Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance. Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects.

Little is known about the pattern of subacute cognitive domain impairments after ischaemic stroke, nor the temporal evolution of such impairments. Our objective was to investigate the pattern of cognitive impairment in different neuropsychological domains up to a year after ischaemic stroke. We included prospectively collected data from an observational database of stroke patients at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. Patients were categorised into temporal groups according to the time between the index stroke and neuropsychological profiling. The prevalence of impairment in different cognitive domains was then compared between these categories. The final cohort consisted of 209 patients. Frontal executive function, perceptual and nominal skills all showed a strong trend, with levels of impairment of approximately 30 % at <1 month and less than half this at >3 months ( p  < 0.05). Speed and attention was the most impaired domain, but had the greatest trend for decreasing impairment, from 72.4 % acutely to 37.9 % after 3 months ( p  < 0.01). By contrast, we found that impairment in visual and verbal memory showed no statistically significant change over time. Our results suggest a domain-specific improvement in cognition after ischaemic stroke. Early assessments may overestimate longer term cognitive deficits, particularly in speed and attention and perceptual functions. The domain-specific improvement patterns may help to inform long-term rehabilitation plans, which should not be based solely on cognitive assessments undertaken within the first month after stroke.

Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the \"Reading the Mind in the Eyes\" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' \"Theory of Mind-network\", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life.

Akinetic mutism is a key diagnostic feature of prion diseases, however, their rapidly progressive nature makes detailed investigation of the language disorder in a large cohort extremely challenging. This study aims to position prion diseases in the nosology of language disorders and improve early clinical recognition. A systematic, prospective investigation of language disorders in a large cohort of patients diagnosed with prion diseases. 568 patients were included as a sub-study of the National Prion Monitoring Cohort. All patients had at least one assessment with the MRC Scale, a milestone-based functional scale with language and non-language components. Forty patients, with early symptoms and able to travel to the study site, were also administered a comprehensive battery of language tests (spontaneous speech, semantics, syntax, repetition, naming, comprehension and lexical retrieval under different conditions). 5/568 (0.9%) patients presented with leading language symptoms. Those with repeated measurements deteriorated at a slower rate in language compared to non-language milestones. Amongst the subgroup of 40 patients who underwent detailed language testing, only three tasks-semantic and phonemic fluency and sentence comprehension-were particularly vulnerable early in the disease. These tasks were highly correlated with performance on non-verbal executive tests. Patients were also impaired on a test of dynamic aphasia. These results provide evidence that the language disorder in prion disease is rarely an isolated clinical or cognitive feature. The language abnormality is indicative of a dynamic aphasia in the context of a prominent dysexecutive syndrome, similar to that seen in patients with the degenerative movement disorder progressive supranuclear palsy (PSP).

Part B of the Trail Making Test (TMT-B) is one of the most widely used neuropsychological tests of “executive” function. A commonly held assumption is that the TMT-B can be used to detect frontal executive dysfunction. However, so far, research evidence has been limited and somewhat inconclusive. In this retrospective study, performance on the TMT-B of 55 patients with known focal frontal lesions, 27 patients with focal non-frontal lesions and 70 healthy controls was compared. Completion time and the number of errors made were examined. Patients with frontal and non-frontal lesions performed significantly worse than healthy controls for both completion time and the number of errors. However, there was no significant difference for both completion time and the number of errors when patients with frontal and non-frontal lesions were compared. Performance was also not significantly different between patients with focal lesions within different regions of the frontal lobe (orbital, left lateral, right lateral, medial). Our findings suggest that the TMT-B is a robust test for detection of brain dysfunction. However, its capacity for detecting frontal executive dysfunction appears rather limited. Clinicians should be cautious when drawing conclusions from performance on the TMT-B alone. (JINS, 2015, 21, 169–174)

Background Fabry disease, an X-linked lysosomal storage disorder, leads to multi-organ dysfunction, including cerebrovascular disease and psychological disorders. However, the prevalence and pattern of associated cognitive dysfunction is not well understood. Objectives To investigate whether there is reliable evidence for neuropsychological impairment in patients with Fabry disease and which cognitive domains are affected. To estimate the prevalence of and factors associated with depression in patients with Fabry disease. Method Qualitative systematic review of the literature of studies conducting neuropsychological assessment or measuring the prevalence of depression in adults with Fabry disease using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines where appropriate. Results There is some evidence for neuropsychological impairment in Fabry disease in executive functioning, information processing speed and attention, with preservation of: general intellectual functioning, memory, naming, perceptual functioning and global cognitive functioning. Prevalence rates of depression in Fabry disease ranged from 15 % to 62 %, with the largest study to date reporting a prevalence rate of 46 %. The most common factor associated with depression was neuropathic pain, both directly and indirectly by affecting social and adaptive functioning. Conclusion Our review suggests that Fabry disease may be associated with a characteristic pattern of cognitive deficits and a high prevalence of psychological disorders such as depression but highlights the limited available data. Exploring the nature of cognitive impairment in Fabry disease using standardised neuropsychological assessment, brain imaging and measures of depression is an important task for future research.

The Cognitive Estimation Test (CET) is widely used by clinicians and researchers to assess the ability to produce reasonable cognitive estimates. Although several studies have published normative data for versions of the CET, many of the items are now outdated and parallel forms of the test do not exist to allow cognitive estimation abilities to be assessed on more than one occasion. In the present study, we devised two new 9-item parallel forms of the CET. These versions were administered to 184 healthy male and female participants aged 18-79 years with 9-22 years of education. Increasing age and years of education were found to be associated with successful CET performance as well as gender, intellect, naming, arithmetic and semantic memory abilities. To validate that the parallel forms of the CET were sensitive to frontal lobe damage, both versions were administered to 24 patients with frontal lobe lesions and 48 age-, gender- and education-matched controls. The frontal patients' error scores were significantly higher than the healthy controls on both versions of the task. This study provides normative data for parallel forms of the CET for adults which are also suitable for assessing frontal lobe dysfunction on more than one occasion without practice effects.

Neuroimaging and lesion studies have documented the involvement of the frontal lobes in recognition memory. However, the precise nature of prefrontal contributions to verbal and non-verbal memory and to familiarity and recollection processes remains unclear. The aim of the current rTMS study was to investigate for the first time the role of the DLPFC in encoding and retrieval of non-verbal and verbal memoranda and its contribution to recollection and familiarity processes. Recollection and familiarity processes were studied using the ROC and unequal variance signal detection methodologies. We found that rTMS delivered over left and right DLPFC at encoding resulted in material specific laterality effects with a disruption of recognition of verbal and non-verbal memoranda. Interestingly, rTMS over DLPFCs at encoding significantly affected both recollection and familiarity. However, at retrieval rTMS did not affect recollection and familiarity. Our results suggest that DLPFC has a degree of functional specialisation and plays an important role in the encoding of verbal and non-verbal memoranda.

Objective. Several studies have reported that people with Parkinson’s disease (PD) perform poorly on tests of ‘Theory of Mind’ (ToM), suggesting impairment in the ability to understand and infer other people’s thoughts and feelings. However, few studies have sought to separate the processes involved in social reasoning from those involved in managing the inhibitory demands on these tests. In this study, we investigated the contribution of inhibition to ToM performance in PD. Methods. 18 PD patients and 22 age-matched healthy controls performed a ToM test that separates the ability to infer someone else’s perspective from the ability to inhibit one’s own. Participants also completed a battery of standard measures of social and executive functioning, including measures of inhibition. Results. The PD patients performed worse on the ToM test only when the inhibitory demands were high. When the level of inhibition required was reduced, there were no significant group differences. Furthermore, executive impairments in PD patients were limited to measures of inhibition, with disadvantages associated with poorer ToM performance in this group. Conclusions. This study provides convincing evidence that the apparent impairment observed on ToM tests in PD is explained by deficits in inhibition.

DBS is an increasingly offered advanced treatment for Parkinson’s disease (PD). Neuropsychological assessment is considered to be an important part of the screening for selection of candidates for this treatment. However, no standardised screening procedure currently exists. In this study, we examined the use of our standardised neuropsychological assessment for the evaluation of surgical candidates and to identify risk factors for subsequent decline in cognition and mood. A total of 40 patients were assessed before and after DBS. Evaluation of mood and case notes review was also undertaken. Before DBS, patients with PD demonstrated frequent impairments in intellectual functioning, memory, attention, and executive function, as well as high rates of mood disorder. Post-DBS, there was a general decline in verbal fluency only, and in one patient, we documented an immediate and irreversible global cognitive decline, which was associated with older age and more encompassing cognitive deficits at baseline. Case note review revealed that a high proportion of patients developed mood disorder, which was associated with higher levels of depression at baseline and greater reduction in levodopa medication. We conclude that our neuropsychological assessment is suitable for the screening of candidates and can identify baseline risk factors, which requires careful consideration before and after surgery.