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Background: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system. More than 90,000 Canadians are affected; a cure is yet to be found. Available treatments to manage the disease course are only partially effective. For many years, persons with MS (PwMS) have used cannabis to relax, to reduce pain and spasticity, or to improve sleep and daily functioning, despite the lack of scientific evidence on the efficacy of specific cannabinoids [i.e., tetrahydrocannabinol (THC) and cannabidiol (CBD)] on these MS symptoms. The purpose of this clinical trial is to assess the effectiveness of different doses of these cannabinoids, alone or combined, on spasticity relief, compared to placebo. Moreover, we aim to determine which treatment is best effective to address other key MS conditions. Methods: A double-blinded, randomized, factorial, placebo-controlled trial will be performed. We intend to include up to 250 PwMS aged over 21 recruited from the Centre hospitalier de l’Université de Montréal MS Clinic. PwMS will be randomly assigned on a 1:1:1:1 ratio to one of the trial arms: THC alone, CBD alone, THC/CBD combination, or placebo, using stratified blocked randomization, with random blocks within each stratum. The primary outcome is a self-assessment of spasticity using the mean Numeric Rating Scale score over 7  days. The main outcome will be the difference in this score at 4  weeks compared to baseline. Secondary outcomes include assessments of spasticity as measured by a clinician, pain, fatigue, sleep, bowel, bladder, and sexual dysfunction, restless legs syndrome, mental health, quality of life, mobility, cognitive functioning, and adverse events. Treatment responders are eligible for a 12-week extension phase, using the same treatment allocation and assessments. Discussion: Previous clinical studies examined the efficacy of cannabis-based medicines in PwMS, mostly using products with 1:1 THC/CBD ratio. The major barrier to effectively use cannabis in real-world clinical settings is the lack of evidence on benefits of specific cannabinoids and information on possible related risks. The CANSEP study will contribute to overcome these limitations and identify the risks and benefits of cannabis-based treatments in PwMS. [ABSTRACT FROM AUTHOR]

The insula is often considered the fifth lobe of the brain and is increasingly recognized as one of the most connected regions in the brain, with widespread connections to cortical and subcortical structures. As a follow-up to our previous tractography work, we investigated the resting-state functional connectivity (rsFC) profiles of insular subregions and assessed their concordance with structural connectivity. We used the CONN toolbox to analyze the rsFC of the same 19 insular regions of interest (ROIs) we used in our prior tractography work and regrouped them into six subregions based on their connectivity pattern similarity. Our analysis of 50 healthy participants confirms the known broad connectivity of the insula and shows novel and specific whole-brain and intra-connectivity patterns of insular subregions. By examining such subregions, our findings provide a more detailed pattern of connectivity than prior studies that may prove useful for comparison between patients. [ABSTRACT FROM AUTHOR]

The role of the anterior temporal lobe (ATL) in semantic memory is now firmly established. There is still controversy, however, regarding the specific role of this region in processing various types of concepts. There have been reports of patients suffering from semantic dementia (SD), a neurodegenerative condition in which the ATL is damaged bilaterally, who present with greater semantic impairment for concrete concepts than for abstract concepts, an effect known as reversal of the concreteness effect. This effect has previously been interpreted as reflecting degraded visual-perceptual features of objects due to damage to the inferior temporal lobes such as is observed in SD. Temporal lobe atrophy in SD, however, is bilateral even if it usually predominates to the left ATL, and it has been found to extend beyond the ATL, throughout the temporal lobes including medial and posterior temporal lobe regions. The question therefore remains whether greater impairment for concrete concepts results from damage to the ATL or from damage to the visual association cortex, and if unilateral damage can produce such a deficit. The aim of the present study was to investigate the processing of concrete and abstract words in rare patients who underwent a selective ATL surgical resection, and to compare their performance with that of patients with selective medial temporal lobe damage sparing the ATL region. Seven patients with a selective unilateral anterior temporal resection (ATL), 15 patients with a selective unilateral amygdalo-hippocampectomy (SeAH), and 15 healthy age- and education-matched controls underwent detailed neuropsychological assessment and carried out a semantic similarity judgment task evaluating their comprehension of concrete and abstract words. Results showed that both ATL and SeAH groups were significantly impaired on the semantic task relative to the control group. Within the patient groups, however, comprehension of concrete words was significantly more impaired than that of abstract words in the ATL group, while comprehension of abstract and concrete words was equally affected in the SeAH group. Results of this study suggest that the ATL region may play a critical role in processing concrete concepts, and that the reversal of the concreteness effect observed in ATL patients may result from damage to a categorical organization underlying the representation of concrete concepts. (Contains 3 figures and 3 tables.)

Objective: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that frequently affects cognition. Persons with MS (PwMS) complain of difficulties with prospective memory (PM), the capacity to remember to perform an intended action at the appropriate moment in the future. The objective of this study was to assess the clinical utility of the Miami Prospective Memory Test (MPMT) in detecting PM deficits in MS. The test is brief, easy to administer and accessible, and allows direct comparison between scores on event- and time-based conditions. A secondary objective was to examine the relationship between PM performance and cognitive functioning. Method: Eighty-four PwMS between 27 and 78 years old were compared to 50 age-, sex- and education-matched healthy adults on the MPMT. Results: Time-based (TB) scores, but not event-based (EB) scores, were significantly lower in PwMS than in healthy adults. The MPMT showed good internal consistency, and correlations were found with disability assessed by the Expanded Disability Status Scale (EDSS). PM was also correlated with memory and executive/attention functioning. Conclusions: This study supports the clinical utility of the MPMT in assessing the presence of PM deficits in PwMS especially under TB constraints. [ABSTRACT FROM AUTHOR]

Prospective memory (PM) problems in aging and, to a greater extent, in mild cognitive impairment (MCI), compromise functional independence. This study examined the effectiveness of a cognitive training program based on visual imagery to improve PM among older adults with and without MCI. Participants were older adults, 24 with MCI and 24 cognitively healthy (HOA). Half of them (12 MCI and 12 HOA) were randomly assigned to the PM training program, the other half to the no-training control group. All participants also completed a pre- and post-test evaluation, including neuropsychological tests, questionnaires, and the Ecological Test of Prospective Memory (TEMP). There was no significant effect of the intervention on the TEMP total, event-based or time-based scores for either the MCI or HOA groups. However, the trained MCI group committed fewer false alarms (i.e., more efficient identification of prospective cues) in the event-based condition of the TEMP at post-test. On the other hand, all trained participants performed better than control participants on retrospective memory tests, which suggests that visual imagery-based training is more effective to improve retrospective memory than PM. Possible explanations for these results are explored. [ABSTRACT FROM AUTHOR]