Mental health and behaviour in children with dystonia: Anxiety, challenging behaviour and the relationship to pain and self-esteem.

PURPOSE: To ascertain whether young people with dystonia are more likely than the general population to have mental health and/or behavioural difficulties, and to explore factors that may contribute to these difficulties. METHOD: Using a quasi-experimental design, 50 young people with dystonia aged 7-17 and their carers were recruited from the Evelina London Children's Hospital. Young people completed the Beck Youth Inventories and the Strengths and Difficulties Questionnaire. Carers completed the Strengths and Difficulties Questionnaire-Parent version and the Paediatric Pain Profile. Important medical factors, such as age of onset, motor severity and manual function were obtained from medical records. RESULTS: One sample z tests showed young people with dystonia self-reported significantly higher levels of anxiety (p < .001) and prosocial difficulties (p < .01), with 48% experiencing clinically significant anxiety levels. They experienced significantly lower levels of anger, disruptive behaviour and conduct problems (all p ≤ .01). Carers reported significantly higher rates of emotional problems, hyperactivity and peer problems, and significantly lower prosocial behaviours (all p ≤ .01). Pearson's correlation coefficients showed lower levels of self-esteem were related to higher levels of anxiety (p = .015). High levels of pain were related to parent-rated conduct problems (p = .004). Age of dystonia onset and motor severity did not correlate with any of the psychological or behavioural measures. INTERPRETATION/CONCLUSIONS: Our study suggests high rates of anxiety and behaviours that challenge in children with dystonia. Screening in movement clinics would be helpful in early identification and signposting for support.

Progress in the Management of Paediatric-Onset Multiple Sclerosis.

Considerable progress has been made in the understanding and treatment of paediatric-onset multiple sclerosis (POMS); how this has translated into more effective care is less well understood. Here, we evaluate how recent advances have affected patient management and outcomes with a retrospective review of POMS patients managed at two paediatric neuroimmunology centres. Two cohorts, seen within a decade, were compared to investigate associations between management approaches and outcomes. Demographic, clinical and neurocognitive data were extracted from case notes and analysed. Of 51 patients, 24 were seen during the period 2007-2010 and 27 during the period 2015-2016. Median age at onset was 13.7 years; time from symptom onset to diagnosis was 9 months. Disease-modifying therapies were commenced in 19 earlier-cohort and 24 later-cohort patients. Median time from diagnosis to treatment was 9 months for earlier vs. 3.5 months in later patients (p = 0.013). A wider variety of treatments were used in the later cohort (four medications earlier vs. seven in the later and two clinical trials), with increased quality of life and neurocognitive monitoring (8% vs. 48% completed PedsQL quality of life inventory; 58% vs. 89% completed neurocognitive assessment). In both cohorts, patients were responsive to disease-modifying therapy (mean annualised relapse rate pre-treatment 2.7 vs. 1.7, mean post-treatment 0.74 vs. 0.37 in earlier vs. later cohorts). In conclusion, over the years, POMS patients were treated sooner with a wider variety of medications and monitored more comprehensively. However, this hugely uncontrolled cohort did not allow us to identify key determinants for the improvements observed.

Pre- and postsurgical cognitive trajectories and quantitative MRI changes in Rasmussen syndrome.

OBJECTIVE: To quantify the longitudinal cognitive trajectory, before and after surgery, of Rasmussen syndrome (RS), a rare disease characterized by focal epilepsy and progressive atrophy of one cerebral hemisphere. METHOD: Thirty-two patients (mean age = 6.7 years; 17 male, 16 left hemispheres affected) were identified from hospital records. The changes in intelligence scores during 2 important phases in the patients' journey to treatment were investigated: (1) during the preoperative period (n = 28, mean follow-up 3.4 years) and (2) from before to after surgery (n = 21 patients, mean time to follow-up 1.5 years). A volumetric magnetic resonance imaging (MRI) analysis of longitudinal changes in gray matter volume was conducted in a subsample of 18 patients. RESULTS: (1) IQ during the preoperative period: At baseline assessment (on average 2.4 years after seizure onset), the left RS group had lower verbal than nonverbal intellectual abilities, whereas the right group exhibited more difficulties in nonverbal than verbal intellect. Verbal and nonverbal scores declined during the follow-up in both groups, irrespective of the affected side. Hemispheric gray matter volumes declined over time in both groups in affected as well as unaffected hemispheres. (2) Postoperative IQ change: The left surgery group declined further in verbal and nonverbal intellect. The right group's nonverbal intellect declined after surgery, whereas verbal abilities did not. Patients with higher abilities preoperatively experienced large declines, whereas those with poorer abilities showed little change. Postoperative seizures negatively impacted on cognitive abilities. SIGNIFICANCE: During the chronic phase of the disease, parallel decline of verbal and nonverbal abilities suggest progressive bilateral hemispheric involvement, supported by evidence from MRI morphometry. Postsurgical cognitive losses are predicted by greater presurgical ability and continuing seizures. A shorter duration from seizure onset to surgery could reduce the postoperative cognitive burden by minimizing the decline in functions supported by the unaffected hemisphere.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Disentangling spatial perception and spatial memory in the hippocampus: a univariate and multivariate pattern analysis fMRI study.

Although the role of the hippocampus in spatial cognition is well accepted, it is unclear whether its involvement is restricted to the mnemonic domain or also extends to perception. We used fMRI to scan neurologically healthy participants during a scene oddity judgment task that placed no explicit demand on long-term memory. Crucially, a surprise recognition test was administered after scanning so that each trial could be categorized not only according to oddity accuracy but also according to subsequent memory. Univariate analyses showed significant hippocampal activity in association with correct oddity judgment, whereas greater parahippocampal place area (PPA) activity was observed during incorrect oddity trials, both irrespective of subsequent recognition performance. Consistent with this, multivariate pattern analyses revealed that a linear support vector machine was able to distinguish correct from incorrect oddity trials on the basis of activity in voxels within the hippocampus or PPA. Although no significant regions of activity were identified by univariate analyses in association with memory performance, a classifier was able to predict subsequent memory using voxels in either the hippocampus or PPA. Our findings are consistent with the idea that the hippocampus is important for processes beyond long-term declarative memory and that this structure may also play a role in complex spatial perception.

Can complex visual discrimination deficits in amnesia be attributed to the medial temporal lobe? An investigation into the effects of medial temporal lobe damage on brain connectivity.

It has been suggested that complex visual discrimination deficits in patients with medial temporal lobe (MTL) damage may be explained by damage or dysfunction beyond the MTL. We examined the resting functional networks and white matter connectivity of two amnesic patients who have consistently demonstrated discrimination impairments for complex object and/or spatial stimuli across a number of studies. Although exploratory analyses revealed some significant differences in comparison with neurologically healthy controls (more specifically in the patient with a larger MTL lesion), there were no obvious findings involving posterior occipital or posterior temporal regions, which can account entirely for their discrimination deficits. These findings converge with previous work to support the suggestion that the MTL does not subserve long-term declarative memory exclusively.

A potential spatial working memory training task to improve both episodic memory and fluid intelligence.

One current challenge in cognitive training is to create a training regime that benefits multiple cognitive domains, including episodic memory, without relying on a large battery of tasks, which can be time-consuming and difficult to learn. By giving careful consideration to the neural correlates underlying episodic and working memory, we devised a computerized working memory training task in which neurologically healthy participants were required to monitor and detect repetitions in two streams of spatial information (spatial location and scene identity) presented simultaneously (i.e. a dual n-back paradigm). Participants' episodic memory abilities were assessed before and after training using two object and scene recognition memory tasks incorporating memory confidence judgments. Furthermore, to determine the generalizability of the effects of training, we also assessed fluid intelligence using a matrix reasoning task. By examining the difference between pre- and post-training performance (i.e. gain scores), we found that the trainers, compared to non-trainers, exhibited a significant improvement in fluid intelligence after 20 days. Interestingly, pre-training fluid intelligence performance, but not training task improvement, was a significant predictor of post-training fluid intelligence improvement, with lower pre-training fluid intelligence associated with greater post-training gain. Crucially, trainers who improved the most on the training task also showed an improvement in recognition memory as captured by d-prime scores and estimates of recollection and familiarity memory. Training task improvement was a significant predictor of gains in recognition and familiarity memory performance, with greater training improvement leading to more marked gains. In contrast, lower pre-training recollection memory scores, and not training task improvement, led to greater recollection memory performance after training. Our findings demonstrate that practice on a single working memory task can potentially improve aspects of both episodic memory and fluid intelligence, and that an extensive training regime with multiple tasks may not be necessary.

Human medial temporal lobe damage can disrupt the perception of single objects.

The idea that the medial temporal lobe (MTL), traditionally viewed as an exclusive memory system, may also subserve higher-order perception has been debated fiercely. To support this suggestion, monkey and human lesion studies have demonstrated that perirhinal cortex damage impairs complex object discrimination. The interpretation of these findings has, however, been disputed because these impairments may reflect a primary deficit in MTL-mediated working memory processes or, in the case of human patients, undetected damage to visual processing regions beyond the MTL. To address these issues, this study investigated object perception in two human amnesic patients who were chosen on the basis of their lesion locations and suitability for detailed neuroimaging investigation. A neuropsychological task with minimal working memory demands was administered in which participants assessed the structural coherency of single novel objects. Critically, only the patient with perirhinal atrophy was impaired. Moreover, volumetric and functional neuroimaging data demonstrated that this deficit cannot be attributed to the dysfunction of visual cortical areas. Additional analyses of eye-movement patterns during the perceptual task revealed an inability of this patient to detect structural incoherency consistently. This study uses a combination of techniques to provide strong evidence that the perirhinal cortex subserves perception and suggests that the MTL perceptual-mnemonic debate cannot be dismissed on the basis of anatomy or a working memory impairment.

Investigating the interaction between spatial perception and working memory in the human medial temporal lobe.

There has been considerable debate surrounding the functions of the medial temporal lobe (MTL). Although this region has been traditionally thought to subserve long-term declarative memory only, recent evidence suggests a role in short-term working memory and even higher order perception. To investigate this issue, functional neuroimaging was used to investigate the involvement of the MTL in spatial scene perception and working memory. Healthy participants were scanned during a working memory task incorporating two factors of working memory (high vs. low demand) and spatial processing (complex vs. simple). It was found that an increase in spatial processing demand produced significantly greater activity in the posterior hippocampus and parahippocampal cortex irrespective of whether working memory demand was high or low. In contrast, there was no region within the MTL that increased significantly in activity during both the complex and the simple spatial processing conditions when working memory demand was increased. There was, however, a significant interaction effect between spatial processing and working memory in the right posterior hippocampus and parahippocampal cortex bilaterally: An increase in working memory demand produced a significant increase in activity in these areas during the complex, but not simple, spatial processing conditions. These findings suggest that although there may be a role for the MTL in both stimulus processing and working memory, increasing the latter does not necessarily increase posterior MTL involvement. We suggest that these structures may play a critical role in processing complex spatial representations, which, in turn, may form the basis of short- and long-term mnemonic processes.

Fornix microstructure correlates with recollection but not familiarity memory.

The fornix is the main tract between the medial temporal lobe (MTL) and medial diencephalon, both of which are critical for episodic memory. The precise involvement of the fornix in memory, however, has been difficult to ascertain since damage to this tract in human amnesics is invariably accompanied by atrophy to surrounding structures. We used diffusion-weighted imaging to investigate whether individual differences in fornix white matter microstructure in neurologically healthy participants were related to differences in memory as assessed by two recognition tasks. Higher microstructural integrity in the fornix tail was found to be associated with significantly better recollection memory. In contrast, there was no significant correlation between fornix microstructure and familiarity memory or performance on two non-mnemonic tasks. Our findings support the idea that there are distinct MTL-diencephalon pathways that subserve differing memory processes.