Enhancing memory performance with rTMS in healthy subjects and individuals with Mild Cognitive Impairment: the role of the right dorsolateral prefrontal cortex

A debated question in the literature is the degree of anatomical and functional lateralization of the executive control processes sub-served by the dorsolateral prefrontal cortex (DLPFC) during recognition memory retrieval. We investigated if transient inhibition and excitation of the left and right DLPFC at retrieval by means of repetitive transcranial magnetic stimulation (rTMS) modulate recognition memory performance in 100 healthy controls (HCs) and in eight patients with Mild Cognitive Impairment (MCI). Recognition memory tasks of faces, buildings, and words were used in different experiments. rTMS-inhibition of the right DLPFC enhanced recognition memory in both HCs and MCIs. rTMS-excitation of the same region in HCs deteriorated memory performance. Inhibition of the right DLPFC could modulate the excitability of a network of brain regions, in the ipsilateral as well as in the contralateral hemisphere, enhancing function in HCs or restoring an adaptive equilibrium in MCI

The neuropsychology needs of a hyper-acute stroke unit

BACKGROUND AND AIM: Guidelines recommend routine assessment and management of mood and cognition after stroke, but little is known about the value or feasibility of providing neuropsychology input during the hyper-acute period. We aimed to identify and describe the extent and nature of neuropsychological needs and to investigate the feasibility of providing direct neuropsychology input within a hyper-acute setting. METHODS: Over a 7-month period, Multidisciplinary Team (MDT) members of a central London Hyper-Acute Stroke Unit (HASU) identified stroke patients who they believed would benefit from neuropsychology input, and categorised the nature of neuropsychology intervention required. We examined the demographic and clinical characteristics of the patients identified and the type of intervention required. RESULTS: 23% of patients (101/448) were identified as requiring neuropsychology input. Patients deemed to require input were younger, more likely to be male and more functionally disabled than those not requiring input. Cognitive assessment was the main identified need (93%) followed by mood (29%) and family support (9%). 30% of patients required two types of intervention. During a pilot of neuropsychology provision, 17 patients were seen; 15 completed a full cognitive assessment. All patients assessed presented with cognitive impairment despite three being deemed cognitively intact (> standardised cut-off) using a cognitive screening tool. CONCLUSION: We showed that direct neuropsychology input on a HASU is necessary for complex and varied interventions involving cognition, mood and family support. Furthermore, input is feasible and useful in detecting cognitive impairment not revealed by screening instruments

Additional Queen Square (QS) screening items improve the test accuracy of the Montreal Cognitive Assessment (MoCA) after acute stroke

BACKGROUND The Montreal Cognitive Assessment (MoCA) is a popular cognitive screening tool used in stroke, but lacks sensitivity for detecting impairment in stroke-relevant domains of processing speed, non-verbal memory and executive functions. Our aim was to assess whether the test accuracy of the MoCA can be improved with additional tailored screening items targeting these three domains. METHODS We included 196 patients admitted to an acute stroke unit at the National Hospital for Neurology and Neurosurgery, Queen Square (QS), London. Participants completed the MoCA as well as a series of additional QS-screening items designed to assess speed of processing, non-verbal memory and executive functions. Performance on the MoCA and QS screening items was compared with performance on “gold standard” neuropsychological assessment. RESULTS In our sample, 22% of patients were classified as “cognitively intact” on the traditional MoCA alone (≥ 25). However, when tested on the QS-screening items, 40% of these patients failed on speed of processing, 56% failed on non-verbal memory and 26% failed on executive functions. Compared with neuropsychological assessment, the QS-screening items had good sensitivity (QS-Speed: 0.85; QS-Vis: 0.71; QS-EF: 0.73) and modest specificity (QS-Speed: 0.59; QS-Vis: 0.39; QS-EF: 0.54), regardless of stroke lateralisation. CONCLUSION Additional screening items detected impairments in speed of processing, non-verbal memory and executive functions over and above those captured using the standard MoCA. The use of these QS-screening items improves the detection of post-stroke cognitive deficits in domains not adequately covered by the standard MoCA

Sensitivity and specificity of the ECAS in Parkinson’s disease and Progressive Supranuclear Palsy

Disentangling Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) may be a diagnostic challenge. Cognitive signs may be useful, but existing screens are often insufficiently sensitive or unsuitable for assessing people with motor disorders. We investigated whether the newly developed ECAS, designed to be used with people with even severe motor disability, was sensitive to the cognitive impairment seen in PD and PSP and able to distinguish between these two disorders. Thirty patients with PD, 11 patients with PSP, and 40 healthy controls were assessed using the ECAS, as well as an extensive neuropsychological assessment. The ECAS detected cognitive impairment in 30% of the PD patients, all of whom fulfilled the diagnostic criteria for mild cognitive impairment. The ECAS was also able to detect cognitive impairment in PSP patients, with 81.8% of patients performing in the impaired range. The ECAS total score distinguished between the patients with PSP and healthy controls with high sensitivity (91.0) and specificity (86.8). Importantly, the ECAS was also able to distinguish between the two syndromes, with the measures of verbal fluency offering high sensitivity (82.0) and specificity (80.0). In sum, the ECAS is a quick, simple, and inexpensive test that can be used to support the differential diagnosis of PSP

Exploring the Relationship between Semantics and Space

The asymmetric distribution of human spatial attention has been repeatedly documented in both patients and healthy controls. Biases in the distribution of attention and/or in the mental representation of space may also affect some aspects of language processing. We investigated whether biases in attention and/or mental representation of space affect semantic representations. In particular, we investigated whether semantic judgments could be modulated by the location in space where the semantic information was presented and the role of the left and right parietal cortices in this task. Healthy subjects were presented with three pictures arranged horizontally (one middle and two outer pictures) of items belonging to the same semantic category. Subjects were asked to indicate the spatial position in which the semantic distance between the outer and middle pictures was smaller. Subjects systematically overestimated the semantic distance of items presented in the right side of space. We explored the neural correlates underpinning this bias using rTMS over the left and right parietal cortex. rTMS of the left parietal cortex selectively reduced this rightward bias. Our findings suggest the existence of an attentional and/or mental representational bias in semantic judgments, similar to that observed for the processing of space and numbers. Spatial manipulation of semantic material results in the activation of specialised attentional resources located in the left hemisphere

Semantic Dementia: a specific network-opathy

Semantic dementia (SD) is a unique syndrome in the frontotemporal lobar degeneration spectrum. Typically presenting as a progressive, fluent anomic aphasia, SD is the paradigmatic disorder of semantic memory with a characteristic anatomical profile of asymmetric, selective antero-inferior temporal lobe atrophy. Histopathologically, most cases show a specific pattern of abnormal deposition of protein TDP-43. This relatively close clinical, anatomical and pathological correspondence suggests SD as a promising target for future therapeutic trials. Here, we discuss outstanding nosological and neurobiological challenges posed by the syndrome and propose a pathophysiological model of SD based on sequential, regionally determined disintegration of a vulnerable neural network

How Are ‘Barack Obama’ and ‘President Elect’ Differentially Stored in the Brain? An ERP Investigation on the Processing of Proper and Common Noun Pairs

BACKGROUND:One of the most debated issues in the cognitive neuroscience of language is whether distinct semantic domains are differentially represented in the brain. Clinical studies described several anomic dissociations with no clear neuroanatomical correlate. Neuroimaging studies have shown that memory retrieval is more demanding for proper than common nouns in that the former are purely arbitrary referential expressions. In this study a semantic relatedness paradigm was devised to investigate neural processing of proper and common nouns. METHODOLOGY/PRINCIPAL FINDINGS:780 words (arranged in pairs of Italian nouns/adjectives and the first/last names of well known persons) were presented. Half pairs were semantically related ("Woody Allen" or "social security"), while the others were not ("Sigmund Parodi" or "judicial cream"). All items were balanced for length, frequency, familiarity and semantic relatedness. Participants were to decide about the semantic relatedness of the two items in a pair. RTs and N400 data suggest that the task was more demanding for common nouns. The LORETA neural generators for the related-unrelated contrast (for proper names) included the left fusiform gyrus, right medial temporal gyrus, limbic and parahippocampal regions, inferior parietal and inferior frontal areas, which are thought to be involved in the conjoined processing a familiar face with the relevant episodic information. Person name was more emotional and sensory vivid than common noun semantic access. CONCLUSIONS/SIGNIFICANCE:When memory retrieval is not required, proper name access (conspecifics knowledge) is not more demanding. The neural generators of N400 to unrelated items (unknown persons and things) did not differ as a function of lexical class, thus suggesting that proper and common nouns are not treated differently as belonging to different grammatical classes

Early predictors of impaired social functioning in male rhesus macaques (Macaca mulatta)

Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus monkeys are highly social, possess complex social cognition abilities, and exhibit pronounced individual differences in social functioning. Moreover, we have previously shown that Low-Social (LS) vs. High-Social (HS) adult male monkeys exhibit lower social motivation and poorer social skills. It is not known, however, when these social deficits first emerge. The goals of this study were to test whether juvenile LS and HS monkeys differed as infants in their ability to process social information, and whether infant social abilities predicted later social classification (i.e., LS vs. HS), in order to facilitate earlier identification of monkeys at risk for poor social outcomes. Social classification was determined for N = 25 LS and N = 25 HS male monkeys that were 1–4 years of age. As part of a colony-wide assessment, these monkeys had previously undergone, as infants, tests of face recognition memory and the ability to respond appropriately to conspecific social signals. Monkeys later identified as LS vs. HS showed impairments in recognizing familiar vs. novel faces and in the species-typical adaptive ability to gaze avert to scenes of conspecific aggression. Additionally, multivariate logistic regression using infant social ability measures perfectly predicted later social classification of all N = 50 monkeys. These findings suggest that an early capacity to process important social information may account for differences in rhesus monkeys’ motivation and competence to establish and maintain social relationships later in life. Further development of this model will facilitate identification of novel biological targets for intervention to improve social outcomes in at-risk young monkeys