Hand rehabilitation with sonification techniques in the subacute stage of stroke.

After a stroke event, most survivors suffer from arm paresis, poor motor control and other disabilities that make activities of daily living difficult, severely affecting quality of life and personal independence. This randomized controlled trial aimed at evaluating the efficacy of a music-based sonification approach on upper limbs motor functions, quality of life and pain perceived during rehabilitation. The study involved 65 subacute stroke individuals during inpatient rehabilitation allocated into 2 groups which underwent usual care dayweek) respectively of standard upper extremity motor rehabilitation or upper extremity treatment with sonification techniques. The Fugl-Meyer Upper Extremity Scale, Box and Block Test and the Modified Ashworth Scale were used to perform motor assessment and the McGill Quality of Life-it and the Numerical Pain Rating Scale to assess quality of life and pain. The assessment was performed at baseline, after 2 weeks, at the end of treatment and at follow-up (1 month after the end of treatment). Total scores of the Fugl-Meyer Upper Extremity Scale (primary outcome measure) and hand and wrist sub scores, manual dexterity scores of the affected and unaffected limb in the Box and Block Test, pain scores of the Numerical Pain Rating Scale (secondary outcomes measures) significantly improved in the sonification group compared to the standard of care group (time*group interaction < 0.05). Our findings suggest that music-based sonification sessions can be considered an effective standardized intervention for the upper limb in subacute stroke rehabilitation.

Brain Connectivity Changes after Osteopathic Manipulative Treatment: A Randomized Manual Placebo-Controlled Trial.

The effects of osteopathic manipulative treatment (OMT) on functional brain connectivity in healthy adults is missing in the literature. To make up for this lack, we applied advanced network analysis methods to analyze resting state functional magnetic resonance imaging (fMRI) data, after OMT and Placebo treatment (P) in 30 healthy asymptomatic young participants randomized into OMT and placebo groups (OMTg; Pg). fMRI brain activity measures, performed before (T0), immediately after (T1) and three days after (T2) OMT or P were used for inferring treatment effects on brain circuit functional organization. Repeated measures ANOVA and post-hoc analysis demonstrated that Right Precentral Gyrus (F (2, 32) = 5.995, p < 0.005) was more influential over the information flow immediately after the OMT, while decreased betweenness centrality in Left Caudate (F (2, 32) = 6.496, p < 0.005) was observable three days after. Clustering coefficient showed a distinct time-point and group effect. At T1, reduced neighborhood connectivity was observed after OMT in the Left Amygdala (L-Amyg) (F (2, 32) = 7.269, p < 0.005) and Left Middle Temporal Gyrus (F (2, 32) = 6.452, p < 0.005), whereas at T2 the L-Amyg and Vermis-III (F (2, 32) = 6.772, p < 0.005) increased functional interactions. Data demonstrated functional connectivity re-arrangement after OMT.

Te.M.P.O., an app for using temporal musical mismatch in post-stroke neurorehabilitation: A preliminary randomized controlled study.

BACKGROUND: Recently, the potential rehabilitation value of music has been examined and music-based interventions and techniques such as the Negative Mismatch (MMN) have been increasingly investigated in the neurological rehabilitation context. OBJECTIVE: The aim of this study was to investigate the effectiveness of a negative mismatch-based therapy on the disability and quality of life in patients with stroke in sub-acute phase. METHODS: Thirty patients with a stroke diagnosis in sub-acute phase were randomly assigned to one of two groups: Mismatch (Mg) or Control (CTRLg) group. Both groups used an innovative Android application: Temporal Musical Patterns Organisation (Te.M.P.O). The Disability Rating Scale (DRS), the Modified Barthel Index (MBI) and the Stroke Specific Quality of Life scale (SSQoL) were used at the baseline (T0) and after four weeks of training (T1), in order to assess changes over time. RESULTS: Statistical analysis was performed using the data of 24 (Mg = 12, CTRLg = 12) subjects. The results show a major improvement of the Mg with respect to the CTRLg in all clinical scales score. CONCLUSION: The temporal negative mismatch-based therapy performed with the Te.M.P.O. application could be useful in improving the disability and the quality of life in stroke survivors in a sub-acute phase.

Stairways to the brain: Transcutaneous spinal direct current stimulation (tsDCS) modulates a cerebellar-cortical network enhancing verb recovery.

It has long been assumed that the language function is hierarchically organized into specific cortical areas. Here, for the first time, we present direct evidence that the spinal cord takes part in language processing. In a randomized-double blind design, sixteen aphasics underwent a language treatment combined with transcutaneous spinal direct current stimulation (tsDCS). During the treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (IX-X vertebrae) in two different conditions: (1) anodal, and (2) sham while performing a verb naming task. Each experimental condition was run in five consecutive daily sessions over two weeks. Before and after each condition, all patients underwent a resting state functional magnetic resonance imaging (rs-fMRI). After anodal tsDCS, significant functional connectivity changes were found in a cerebellar-cortical network recruiting regions such as the left cerebellum, the right parietal and premotor cortex known to be also involved in action-related verb processing. Indeed, this increase of connectivity significantly correlated with the greatest amount of improvement found in verb naming. In line with our experimental data, we also found a greater improvement after anodal tsDCS also on untreated items of the language test but only on tasks which required the use of verbs, such as verb naming and picture description. No significant changes were found in noun naming. Thus, this evidence emphasizes, for the first time, that the neural response due to tsDCS combined with language treatment changes during the course of recovery by enhancing activity into cortical regions which influence verb processing.

Osteopathic Manipulative Therapy Potentiates Motor Cortical Plasticity.

CONTEXT: Osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) is effective in managing pain caused by a variety of clinical conditions. Nevertheless, the physiologic mechanisms at the basis of the clinical improvement are poorly understood. OBJECTIVE: To investigate the effects of OMTh, muscle stretching, and soft touch interventions on motor cortical excitability through a rapid-rate paired associative stimulation (PAS) protocol. METHODS: In this crossover study, participants underwent OMTh, muscle stretching, and soft touch interventions. A rapid-rate PAS transcranial magnetic stimulation protocol was performed immediately after each intervention session, which consisted of 600 pairs of stimuli continuously delivered to the left primary motor cortex and to the right median nerve at a rate of 5 Hz for 2 minutes. The interstimulus intervals between the peripheral stimulus and the transcranial magnetic stimulation was set at 25 milliseconds. Before and after rapid-rate PAS (immediately after and 15 minutes after), changes in the amplitude of the motor evoked potentials were measured in the right abductor pollicis brevis and the right first dorsal interosseous. RESULTS: Of the potential 15 participants initially recruited, 12 fit the inclusion criteria. Two of the 12 participants were excluded from the final analysis because of excessive artifact movements. Rapid-rate PAS induced a more pronounced, longer-lasting increase in cortical excitability in the abductor pollicis brevis muscle in patients 15 minutes after the OMTh intervention than after the muscle stretching or sham interventions (P=.016). CONCLUSION: Results of the current study provide support for the effects of OMTh on cortical plasticity.

Bromelain Degrades Aß1-42 Monomers and Soluble Aggregates: An In Vitro Study in Cerebrospinal Fluid of Alzheimer's Disease Patients.

BACKGROUND: Therapeutic approaches targeting amyloid ß42 (Aß42) oligomers may represent a promising neuroprotective strategy for the prevention and treatment of Alzheimer's disease (AD). OBJECTIVE: In this study we evaluated the ability of bromelain, a plant cysteine protease derived from pineapple stems, to interact with synthetic Aß42 monomers and oligomers. We also examined the ability of bromelain to interfere in vitro with synthetic Aß42 aggregates in the cerebrospinal fluid (CSF) of Alzheimer's disease as well as of control patients affected by other neurological diseases. METHOD: Both synthetic monomers and aggregates of Aß42 were incubated in CSF with varying concentrations of bromelain. The effects of digestion were evaluated by Western Blot analysis using the specific monoclonal antibody 4G8 to identify the patterns of residual content of Aß42. We further used rat primary cortical culture neurons (CN) to examine the cytotoxic action of this natural compound. RESULTS: We found that bromelain successfully degraded Aß42 monomers and low and high molecular weight oligomers. Indeed, when bromelain preparations of 3 and 6 mU were added to the CSF, the residual amount of Aß42 monomers and oligomers were significantly reduced when compared to the same standard Aß42 preparations incubated in CSF without bromelain. Moreover, bromelain incubations of 0.1, 0.5, and 1 mU/ml were not toxic to CN, as compared to vehicle treated cells. CONCLUSION: Overall, these results represent an important insight into the action of bromelain on Aß42 oligomers, suggesting its potential use in the therapy of AD.

Outpatient Satisfaction With Osteopathic Manipulative Treatment in a Hospital Center: A Survey.

Context: Although osteopathy is not yet certified as a health profession in Italy, many people choose osteopathic manipulative treatment (OMT) for pain relief. Nevertheless, no study evaluating patients' degree of satisfaction after OMT and the perceived quality of the treatment has occurred in Italy. Objectives: The study intended to assess outpatients' satisfaction with OMT carried out at a hospital. Design: The research team conducted a survey from January 2015 to January 2016 using 3 questionnaires. Setting: The study took place the Fondazione Santa Lucia Hospital (Rome, Italy), an institute for research and health care. Participants: Participants were 101 patients with musculoskeletal (MSK) disorders undergoing OMT at the hospital. Interventions: The OMT was performed by 3 osteopathic practitioners who had completed the 6-y, part-time training program recognized by the Italian Register of Osteopaths. Outcome Measures: To measure the level of their satisfaction, the research team had patients complete the modified patient satisfaction questionnaire (mPSQ), the patient satisfaction with outpatient physical therapy (PSOPT) instrument, and the visual analog scale for satisfaction (VASS). Parametric and nonparametric analyses were performed to correlate the questionnaires and the demographic variables using the Pearson and Spearman tests. Results: Data were obtained from 97 patients, with mean age of 42.48 ± 16.1 y, 50 of whom were female. The data showed high, average general satisfaction after OMT: (1) VASS-9.36 ± 1.00 and (2) PSOPT-43.27 ± 3.65. A significant negative correlation was found between access to care (D1-TOT) on the mPSQ and at ages older than 65 y-r = -0.24 and P < .05. A significant positive correlation was found between the VASS and female gender-r = 0.23 and P < .05. A significant positive correlation was also found between continuity of care (D3-TOT) and continuity of care-family (D3-1) on the mPSQ and education level-r = .20 and P < .05 and r = 0.24, P < .05, respectively, and with other dimensions explored by the questionnaires. Conclusions: The data show a high level of general satisfaction in patients with MSK disorders who underwent OMT in an Italian hospital setting. The overall satisfaction rate was mainly influenced by the patient's perception of the practitioner's technical quality, the continuity of the treatment, and the cost of the service. Some differences emerged for age, gender, and educational level. The information from the current study may be useful for improving the therapeutic assistance provided with OMT and to promote alternative therapies in health and medicine.

Impaired intracortical transmission in G2019S leucine rich-repeat kinase Parkinson patients.

OBJECTIVES: A mutation in leucine-rich repeat kinase 2 is the most common cause of hereditary Parkinson's disease (PD), yet the neural mechanisms and the circuitry potentially involved are poorly understood. METHODS: We used different transcranial magnetic stimulation protocols to explore in the primary motor cortex the activity of intracortical circuits and cortical plasticity (long-term potentiation) in patients with the G2019S leucine-rich repeat kinase 2 gene mutation when compared with idiopathic PD patients and age-matched healthy subjects. Paired pulse transcranial magnetic stimulation was used to investigate short intracortical inhibition and facilitation and short afferent inhibition. Intermittent theta burst stimulation, a form of repetitive transcranial magnetic stimulation, was used to test long-term potentiation-like cortical plasticity. Leucine-rich repeat kinase 2 and idiopathic PD were tested both in ON and in OFF l-dopa therapy. RESULTS: When compared with idiopathic PD and healthy subjects, leucine-rich repeat kinase 2 PD patients showed a remarkable reduction of short intracortical inhibition in both ON and in OFF l-dopa therapy. This reduction was paralleled by an increase of intracortical facilitation in OFF l-dopa therapy. Leucine-rich repeat kinase 2 PD showed abnormal long-term potentiation-like cortical plasticity in ON l-dopa therapy. DISCUSSION: The motor cortex in leucine-rich repeat kinase 2 mutated PD patients is strongly disinhibited and hyperexcitable. These abnormalities could be a result of an impairment of inhibitory (gamma-Aminobutyric acid) transmission eventually related to altered neurotransmitter release. © 2017 International Parkinson and Movement Disorder Society.

Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

Gray and white matter trajectories in patients with bipolar disorder.

OBJECTIVES: Findings on brain structural abnormalities in patients with bipolar disorder (BP) are inconsistent and little is known about age-related evolution of these changes. We employed a cross-sectional, case-control study to compare structural age-related brain trajectories in patients with BP and healthy control subjects (HC) over a period of approximately 50 years. The primary aim was to understand whether white (WM) and gray matter (GM) abnormalities are present from the beginning of the illness and how they change over time. METHODS: Seventy-eight patients with BP and 78 HC matched for age, gender, and educational level underwent a high-resolution structural magnetic resonance imaging protocol. A voxel-based morphometry (VBM) analysis was used to capture GM and WM differences between subjects with BP and HC. Factorial analysis of covariance was used to compare brain volume alterations at different ages between the groups. RESULTS: We found an age-related atrophy in GM and WM volumes both in patients with BP and HC. A main effect of diagnosis emerged in the posterior cingulate cortex bilaterally, in the right thalamus, in the cerebellum bilaterally, and in the left posterior limb of the internal capsule. No interaction between diagnosis and age emerged, indicating that the volumes of these areas were permanently reduced in subjects with BP throughout the entire age range under investigation. CONCLUSIONS: Brain alterations in patients with BP are present from the beginning of the illness and remain stable over time. All the affected areas are involved in mood and psychomotor control process. This suggests a possible neurodevelopmental involvement in the mechanism of BP.

Strategic lesions in the anterior thalamic radiation and apathy in early Alzheimer's disease.

BACKGROUND: Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer's disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI). METHODS: Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients' behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD. RESULTS: Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD. CONCLUSIONS: This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia.

Recollection and familiarity in the human thalamus.

Recollection and familiarity are two distinct forms of recognition memory that differ in terms of the associative richness of the memory experience. In recollection, exposure to a previously encountered item cues the recollection of a number of contextual, temporal and other associative information. In the case of familiarity, instead, the item is recognized as previously encountered, but it does not cue any associative information. According to the dual-process theory, the memory processes that underlie recollection and familiarity are qualitatively different and this distinction is reflected in the existence of different neural substrates underlying the two processes. Thus far, research has primarily focused on distinct regions of the medial temporal lobe as implicated mostly in recollection (hippocampus) or familiarity (perirhinal cortex). Aggleton and Brown (1999) suggested extending the neuroanatomical distinction to other cortical and subcortical areas of the brain, including the thalamus. In particular, they proposed the existence of two reciprocally independent neural circuits for recollection and familiarity. The former would include the hippocampus, the fornix, the mammillary bodies and the anterior thalamic nuclei. The second would involve the mesial magnocellular portion of the mediodorsal nucleus connected to the perirhinal cortex through the ventroamygdalofugal pathway. Here we review neuropsychological evidence in experimental animals and brain-damaged individuals and functional neuroimaging evidence in healthy humans that supports Aggleton and Brown's model at the level of the thalamus. The evidence substantially supports the functional relationship between recollection processes and integrity of the thalamic anterior nuclei. Additional evidence, not predicted by the model, has been provided in favour of the reliance of recollection on the integrity of the lateral portion (parvocellular) of the mediodoral nucleus. Finally, there is sparse and controversial evidence in support of the reliance of familiarity on the integrity of the mesial portion of the mediodorsal nucleus, possibly due to neuroimaging methodological limits which did not satisfactorily distinguish between the medial and lateral portions of the mediodorsal nucleus.

n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice.

As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA) exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations) found in n-3 PUFA supplemented mice also pointed toward an effective neuroprotection. On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.

Effects of two weeks of cerebellar theta burst stimulation in cervical dystonia patients.

Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.

Bihemispheric tDCS enhances language recovery but does not alter BDNF levels in chronic aphasic patients.

PURPOSE: Several studies have shown that transcranial direct current stimulation (tDCS) is a useful tool to enhance language recovery in aphasia. It has also been suggested that modulation of the neurotrophin brain-derived neurotrophic factor (BDNF) might be part of the mechanisms involved in tDCS effects on synaptic connectivity. However, all language studies have previously investigated the effects using unihemispheric stimulation. The purpose of the present study is to investigate the role of bihemispheric tDCS on language recovery and BDNF serum levels. METHODS: Seven aphasic persons underwent an intensive language therapy in two different conditions: real bihemispheric stimulation over the left and right Broca's areas and a sham condition. RESULTS: After the stimulation, patients exibited a significant recovery in three language tasks (picture description, noun and verb naming) compared to the sham condition which persisted in the follow-up session. No significant differences were found in BDNF serum levels after tDCS stimulation and in the follow-up session. However, a significant positive correlation was present for the real stimulation condition between percent changes in BDNF levels and in the verb naming task. CONCLUSIONS: The data suggest that this novel approach may potentiate the recovery of language in chronic aphasia. They also emphasize the importance to further investigate the role of possible biomarkers associated with tDCS treatment response in language recovery.

Something to talk about: enhancement of linguistic cohesion through tdCS in chronic non fluent aphasia.

Several studies have shown that the modulation of cortical activity through transcranial direct current stimulation (tDCS) enhances naming performance in persons with aphasia. In this study, we investigated the potential effects of tDCS in improving spontaneous speech and the ability to use connective words to establish cohesion among adjacent utterances in a group of eight participants with chronic non fluent aphasia. They were administered five short videoclips representing everyday life contexts and two picture description tasks. Three videoclips were used to elicit spontaneous conversation during the treatment, while the remaining tasks were presented to the patients only before and after the therapy. Patients were required to talk about each videoclip, with the help of a therapist, while they were treated with tDCS (20 min, 1 mA) over the left hemisphere in three different conditions: anodic tDCS over the Broca's area, anodic tDCS over the Wernicke's area and a sham condition. Each experimental condition was performed for ten consecutive daily sessions with 14 days of intersession interval. Only after Broca's stimulation, patients showed a greater improvement in producing words that enhanced the cohesion of their speech samples (i.e., pronouns, ellipses, word repetitions, conjunctions). Beneficial effects of the stimulation were generalized also to contexts presented to the patients at the beginning and at the end of the therapy sessions. Our data further confirm the key role of the left inferior frontal gyrus in binding words into a coherent speech. We believe that positive tDCS effects may be further extended to different linguistic domains, useful to promote language recovery.

Options to enhance recovery from aphasia by means of non-invasive brain stimulation and action observation therapy.

Aphasia is a highly disabling language disorder usually caused by a left-lateralized brain damage. Even if traditional linguistic-based therapies have been proved to induce an adequate clinical improvement, a large percentage of patients are left with some degree of language impairments. Therefore, new approaches to common speech therapies are urgently needed in order to maximize the recovery from aphasia. The recent application of non-invasive neurostimulation techniques to language rehabilitation has already provided promising results particularly for the recovery of word-retrieval deficits in chronic stroke aphasic patients. Positive outcomes also come from action observation therapy. Indeed, some very recent studies have shown that the observation and/or execution of gestures positively influences language recovery especially for words related to human actions. This article gives an overview of the most important results achieved using these two approaches and discusses how the application of these treatments might potentiate aphasia recovery.

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct.

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns.

Normative data for measuring performance change on parallel forms of a 15-word list recall test.

Declarative memory evaluation is an essential step in the clinical and neuropsychological assessment of a variety of neurological disorders. It typically addresses the issue of normality/abnormality of an individual's performance. Another clinical application of the neuropsychological assessment of declarative memory is the longitudinal evaluation of an individual's performance change. In fact, in a variety of neurological conditions repeated assessments are needed to evaluate the modifications of a memory disorder as a function of time or in response to a pharmacological or rehabilitation treatment. This study was aimed at collecting data for measuring and interpreting performance change on a memory test for verbal material. For this purpose, we administered to 100 healthy subjects (age range 20-80 years; years of formal education range 8-17 years) three parallel forms of a test requiring the immediate and delayed recall of a 15-word list. The subjects performed the recall test three times (each time with a different list) at least 1 week apart. The order of the lists was randomized across subjects. Results revealed that performance on the three lists was highly correlated and did not vary as a function of the order of presentation. However, accuracy of recall was slightly better on a list compared to the others. Based on a method devised by Payne and Jones (J Clin Psychol 13:115-121, 1957), we provide normative data for establishing whether a discrepancy in recall accuracy on two versions of the test exceeds the discrepancy expected based on the performance of normal controls.