A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial

Cognitive impairment in individuals with multiple sclerosis (MS) is now well recognized. One of the most common cognitive deficits is found in memory functioning, largely due to impaired acquisition. We examined functional brain activity 6 months after memory retraining in individuals with MS. The current report presents long term follow-up results from a randomized clinical trial on a memory rehabilitation protocol known as the modified Story Memory Technique. Behavioral memory performance and brain activity of all participants were evaluated at baseline, immediately after treatment, and 6 months after treatment. Results revealed that previously observed increases in patterns of cerebral activation during learning immediately after memory training were maintained 6 months post training.     

The therapeutic effect of treatment with RehaCom software on verbal performance in patients with multiple sclerosis

Multiple sclerosis (MS) is characterized by central nervous system lesions that lead to neurological dysfunctions including fatigue, depression and anxiety. MS is affecting almost 2.3 million people around the world, with the significant highest prevalence in the North America. MS also affects different cognitive abilities, such as attention, memory and executive functions. Furthermore, a significant impairment in verbal fluency and naming abilities in patients with MS has been reported. RehaCom, is a software that has improvement effects on cognitive functions. The goal of this research is to investigate the effect of treatment with RehaCom on verbal performance in patients with MS. To select the participants, 60 patients with MS who referred to our clinic were chosen randomly and divided into Control (n = 30) and Experimental (n = 30) groups. The participants in the experimental group were treated by RehaCom software for 10 sessions during 5 weeks (2 sessions per week and each session was 1 h). Controlled Oral Word Association Test (COWAT) and California Verbal Learning Test – Second Edition (CVLT-II), were used to assess verbal performance (verbal fluency, and verbal learning and memory) at weeks 0 (baseline), 5 (post-test) and 10 (follow-up). The results showed that, treatment with RehaCom improved verbal performance in patient with MS, at both post-test and follow-up stages. In conclusion, treatment with RehaCom cognitive rehabilitation software can improve verbal fluency, and verbal learning and memory in patient with MS, possibly by affecting the brain regions involved in language performance.     

Efficacy of a cognitive training programme for mild cognitive impairment: Results of a randomised controlled study

This study aimed to determine the efficacy of cognitive training in a 10-week randomised controlled study involving 22 individuals presenting with mild cognitive impairment of the amnestic type (MCI-A). Participants in the experimental group (n = 11) learned face–name associations using a paradigm combining errorless (EL) learning and spaced retrieval (SR) whereas participants in the control group (n = 11) were trained using an errorful (EF) learning paradigm. Psycho-educational sessions on memory were also provided to all participants. After neuropsychological screening and baseline evaluations, the cognitive training took place in 6 sessions over a 3-week period. The post-training and follow-up evaluations, at one and four weeks respectively, were performed by research assistants blind to the participant's study group. The results showed that regardless of the training condition, all participants improved their capacity to learn face–name associations. A significant amelioration was also observed in participant satisfaction regarding their memory functioning and in the frequency with which the participants used strategies to support memory functions in daily life. The absence of difference between groups on all variables might be partly explained by the high variability of scores within the experimental group. Other studies are needed in order to verify the efficacy of EL learning and SR over EF in MCI-A.     

Information processing efficiency in patients with multiple sclerosis

Reduced information processing efficiency, consequent to impaired neural transmission, has been proposed as underlying various cognitive problems in patients with Multiple Sclerosis (MS). This study employed two measures developed from experimental psychology that control for the potential confound of perceptual-motor abnormalities (Salthouse, Babcock, & Shaw, 1991; Sternberg, 1966, 1969) to assess the speed of information processing and working memory capacity in patients with mild to moderate MS. Although patients had significantly more cognitive complaints than neurologically intact matched controls, their performance on standard tests of immediate memory span did not differ from control participants and their word list learning was within normal limits. On the experimental measures, both relapsing-remitting and secondary-progressive patients exhibited significantly slowed information processing speed relative to controls. However, only the secondary-progressive patients had an additional decrement in working memory capacity. Depression, fatigue, or neurologic disability did not account for performance differences on these measures. While speed of information processing may be slowed early in the disease process, deficits in working memory capacity may appear only as there is progression of MS. It is these latter deficits, however, that may underlie the impairment of new learning that patients with MS demonstrate.     

Information Processing Efficiency in Patients with Multiple Sclerosis

Reduced information processing efficiency, consequent to impaired neural transmission, has been proposed as underlying various cognitive problems in patients with Multiple Sclerosis (MS). This study employed two measures developed from experimental psychology that control for the potential confound of perceptual-motor abnormalities (Salthouse, Babcock, & Shaw, 1991; Sternberg, 1966, 1969) to assess the speed of information processing and working memory capacity in patients with mild to moderate MS. Although patients had significantly more cognitive complaints than neurologically intact matched controls, their performance on standard tests of immediate memory span did not differ from control participants and their word list learning was within normal limits. On the experimental measures, both relapsing-remitting and secondary-progressive patients exhibited significantly slowed information processing speed relative to controls. However, only the secondary-progressive patients had an additional decrement in working memory capacity. Depression, fatigue, or neurologic disability did not account for performance differences on these measures. While speed of information processing may be slowed early in the disease process, deficits in working memory capacity may appear only as there is progression of MS. It is these latter deficits, however, that may underlie the impairment of new learning that patients with MS demonstrate.     

Mnemonic strategy training partially restores hippocampal activity in patients with mild cognitive impairment

Learning and memory deficits typify patients with mild cognitive impairment (MCI) and are generally attributed to medial temporal lobe dysfunction. Although the hippocampus is perhaps the most commonly studied neuroanatomical structure in these patients, there have been few attempts to identify rehabilitative interventions that facilitate its functioning. Here, we present results from a randomized, controlled, single‐blind study in which patients with MCI and healthy elderly controls (HEC) were randomized to either three sessions of mnemonic strategy training (MS) or a matched‐exposure control group (XP). All participants underwent pre‐ and posttraining fMRI scanning as they encoded and retrieved object–location associations. For the current report, fMRI analyses were restricted to the hippocampus, as defined anatomically. Before training, MCI patients showed reduced hippocampal activity during both encoding and retrieval, relative to HEC. Following training, the MCI MS group demonstrated increased activity during both encoding and retrieval. There were significant differences between the MCI MS and MCI XP groups during retrieval, especially within the right hippocampus. Thus, MS facilitated hippocampal functioning in a partially restorative manner. We conclude that cognitive rehabilitation techniques may help mitigate hippocampal dysfunction in MCI patients. © 2012 Wiley Periodicals, Inc.     

Memory impairment in multiple sclerosis is due to a core deficit in initial learning

Persons with multiple sclerosis (MS) suffer memory impairment, but research on the nature of MS-related memory problems is mixed. Some have argued for a core deficit in retrieval, while others have identified deficient initial learning as the core deficit. We used a selective reminding paradigm to determine whether deficient initial learning or delayed retrieval represents the primary memory deficit in 44 persons with MS. Brain atrophy was measured from high-resolution MRIs. Regression analyses examined the impact of brain atrophy on (a) initial learning and delayed retrieval separately, and then (b) delayed retrieval controlling for initial learning. Brain atrophy was negatively associated with both initial learning and delayed retrieval (ps < 0.01), but brain atrophy was unrelated to retrieval when controlling for initial learning (p > 0.05). In addition, brain atrophy was associated with inefficient learning across initial acquisition trials, and brain atrophy was unrelated to delayed recall among MS subjects who successfully acquired the word list (although such learning frequently required many exposures). Taken together, memory deficits in MS are a result of deficits in initial learning; moreover, initial learning mediates the relationship between brain atrophy and subsequent retrieval, thereby supporting the core learning-deficit hypothesis of memory impairment in MS.     

Neuropsychological assessment in MS: clinical, neurophysiological and neuroradiological relationships

We assessed cognitive performance and its relationship with clinical and anatomic disease severity in MS with mild to moderate handicap; 34 definite MS and 18 healthy subjects matched for age and education were submitted to a neuropsychological test battery. Both groups were examined for anxiety. MS patients underwent magnetic resonance imaging examination. MS performed worse than controls on all WAIS-P subtests and had learning, short- and long-term verbal memory impairment. Cognitive deficits were not related to abnormal emotional states, but were found to be associated with attentional process and information-processing speed impairment. Cognitive impairment did not correlate with severity of physical disability. The most severe memory deficits were found in patients with extensive periventricular damage.     

Prospective memory in multiple sclerosis.

There is considerable evidence that multiple sclerosis (MS) is associated with impaired retrospective memory. However, although preliminary evidence suggests that prospective memory is also affected by the disorder, the degree and nature of the impairment remains to be clarified. Twenty participants with MS were compared with 20 matched controls on Virtual Week, a measure of prospective memory that closely represents the types of prospective memory tasks that actually occur in everyday life, and provides an opportunity to investigate the different sorts of prospective memory failures that occur. The results indicated that irrespective of the specific prospective memory task demands, MS participants' performance was significantly impaired relative to controls. MS deficits could not be attributed to problems with retrospective memory because MS participants in the present study did not differ significantly from controls on measures of long- and short-term memory, and significant impairment was observed on a prospective memory task, which imposed only minimal demands on retrospective memory. These results therefore suggest that individuals with MS may experience general difficulties with prospective memory. The practical and theoretical implications of these findings are discussed.     

Acquisition and Storage Deficits in Multiple Sclerosis

This study examined whether verbal and visual memory impairments in multiple sclerosis (MS) are attributable to deficits in acquisition, storage, or retrieval. Volunteers with MS (n = 40) and healthy controls (n = 20) rehearsed a word list and a checkerboard pattern using a selective reminding procedure until two consecutive error-free trials were attained. Recall and recognition were assessed after 30 min and 90 min (and 1 week for verbal material) delays. The MS group required significantly more trials to attain criterion on both learning tests. Once equated for acquisition, both groups performed similarly on verbal recall and recognition. However the MS group performed significantly worse on measures of visual recall and recognition. The results suggest that the verbal memory impairment in MS is due to deficient acquisition, while the visual memory impairment in MS is attributable to deficits in acquisition and storage.     

Cerebral activation patterns during working memory performance in multiple sclerosis using FMRI

Working memory deficits are common in Multi Sclerosis (MS) and have been identified behaviourally in numerous studies. Despite recent advance in functional magnetic resonance imaging (fMRI), few published studies have examined cerebral activations associated with working memory dysfunction in MS. The present study examines brain activation patterns during performance of a working memory task in individual with clinically definite MS, compared to healthy controls (HC). fMRI was performed using a 1.5 Tesla GE scanner during a modified Paced Auditory Serial Addition Test (mPA-SAT). Participants were 6 individuals with MS with working memory impairment as evidenced on neuropsychological testing, 5 individuals with MS without working memory impairment, and 5 HC. Groups were demographically equivalent. Data were analyzed using Statistical Parametric Mapping (SPM99) software, with a stringent significance level (alpha < .005, voxel extent > or =8). Both MS groups and the HC group were able to perform the task, with comparable performance in terms of numbers of correct responses. Activation patterns within the HC and MS not-impaired groups were noted in similar brain regions, consistent with published observations in healthy samples That is, activations were lateralized to the left hemisphere, involving predominantly frontal regions. In contrast, the MS impaired group showed greater right frontal and right parietal lobe activation, when compared with the HC group. Thus, it appears that working memory dysfunction in MS is associated with altered patterns of cerebral activation that are related to the presence of cognitive impairement, and not solely a function of MS.     

Towards a cognitive stimulation program using an errorless learning paradigm in amnestic mild cognitive impairment

Considering the high risk for amnestic mild cognitive impairment (A-MCI) individuals to progress towards dementia, it is crucial to study the efficacy of innovative treatment strategies such as cognitive stimulation techniques. The present study is a case report of two individuals presenting with A-MCI who were enrolled in a memory training program. After a broad neuropsychological assessment, the two participants were trained with an errorless (EL) learning paradigm on an individual basis, twice a week, over three weeks. Two follow-up sessions took place one and five weeks after the end of the training. Results showed that the program was well tolerated and feasible, and enhanced daily memory abilities. For the second participant only, a re-evaluation of her cognitive profile was completed 23 months after her first assessment and training. In addition, EL was directly compared with a control condition using an errorful (EF) learning paradigm to teach her new names over two sessions (one session for each condition). Her improvement on the trained material supported the preliminary efficacy of EL compared with EF for learning episodic material. These results are compatible with previous work that has preliminarily demonstrated the efficacy of an EL paradigm in patients with dementia.     

Benefits from an autobiographical memory facilitation programme in relapsing-remitting multiple sclerosis patients: a clinical and neuroimaging study

While the efficacy of mental visual imagery (MVI) to alleviate autobiographical memory (AM) impairment in multiple sclerosis (MS) patients has been documented, nothing is known about the brain changes sustaining that improvement. To explore this issue, 20 relapsing-remitting MS patients showing AM impairment were randomly assigned to two groups, experimental (n?=?10), who underwent the MVI programme, and control (n?=?10), who followed a sham verbal programme. Besides the stringent AM assessment, the patients underwent structural and functional MRI sessions, consisting in retrieving personal memories, within a pre-/post-facilitation study design. Only the experimental group showed a significant AM improvement in post-facilitation, accompanied by changes in brain activation (medial and lateral frontal regions), functional connectivity (posterior brain regions), and grey matter volume (parahippocampal gyrus). Minor activations and functional connectivity changes were observed in the control group. The MVI programme improved AM in MS patients leading to functional and structural changes reflecting (1) an increase reliance on brain regions sustaining a self-referential process; (2) a decrease of those reflecting an effortful research process; and (3) better use of neural resources in brain regions sustaining MVI. Functional changes reported in the control group likely reflected ineffective attempts to use the sham strategy in AM.     

The effect of electroconvulsive therapy (ECT) on implicit memory: skill learning and perceptual priming in patients with major depression

While explicit memory in amnesics is impaired, their implicit memory remains preserved. Memory impairment is one of the side effects of electroconvulsive therapy (ECT). ECT patients are expected to show impairment on explicit but not implicit tasks. The present study examined 17 normal controls and 17 patients with severe major depressive disorder who underwent right unilateral ECT. Patients were tested in three sessions: 24-48 hours prior to, 24-48 hours following the first ECT, and 24-48 hours following the eighth ECT. The controls were tested in three sessions, at time intervals that paralleled those of the patients. Implicit memory was tested by the perceptual priming task - Partial Picture-Identification (PPI). The skill learning task used entailed solving the Tower of Hanoi puzzle (TOHP). Explicit memory was tested by picture recall from the PPI task, verbal recall of information regarding the TOHP, and by the Visual Paired Association (VPA) test. Results showed that explicit questions about the implicit tasks were impaired following ECT treatment. Patients' learning ability, as measured by the VPA task, was only impaired in the first testing session, prior to ECT treatment, reflecting the effect of depression. In addition, groups only differed in the first session on the learning rate of the skill learning task. Perceptual priming was preserved in the patients' group in all sessions, indicating that it is resilient to the effect of depression and ECT. The results are interpreted in terms of the differential effect of depression and ECT on explicit and implicit memory.     

Episodic memory impairment in bipolar disorder and obsessive-compulsive disorder: the role of memory strategies

BACKGROUND: There is evidence that individuals with bipolar disorder exhibit neuropsychological impairments not only during mood episodes but also when they are euthymic. One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is an impairment in verbal episodic memory. Verbal learning and memory depend on individuals' ability to organize verbal information appropriately during learning. The purpose of the present study was (i) to determine whether episodic memory impairment in euthymic individuals with bipolar disorder is mediated by impairments in organization of verbal information during learning and (ii) to compare the characteristics of memory impairment in bipolar disorder with that previously found in obsessive-compulsive disorder (OCD). METHODS: Study participants were 30 individuals with DSM-IV bipolar I disorder (BP-I), 30 individuals with DSM-IV OCD and 30 normal control participants matched for age, gender and education. Participants completed the California Verbal Learning Test (CVLT), a well-established measure of verbal learning and memory that enables assessment of verbal organization strategies during learning. RESULTS: Compared with control subjects, both BP-I and OCD participants showed impaired performance in long-delayed free recall and verbal organization strategies during learning. BP-I participants showed greater long-delay free recall difficulties but not greater verbal organization difficulties during learning than OCD participants. For OCD participants, the long-delay recall impairment was mediated by difficulties using verbal organizational strategies during learning. In contrast, the group difference in long-delayed free recall between BP-I and control participants remained significant even when semantic clustering was introduced as a mediator. This indicated that BP-I participants' long-delayed free recall difficulties were mediated to a lesser extent by difficulties using verbal organizational strategies than for OCD participants. CONCLUSIONS: Verbal episodic memory problems in individuals with bipolar I disorder and OCD are mediated to different degrees by difficulties using semantic clustering encoding strategies compared with control participants.     

Learning and memory impairment in cocaine-dependent and comorbid schizophrenic patients

Impairments in verbal learning and memory functioning have been found to be cardinal features among individuals with schizophrenia as well as among non-schizophrenic cocaine abusers. Cognitive deficits in these areas, moreover, have been associated with poor treatment response and short-term outcome. Little is known, however, about the acute effects of cocaine abuse on schizophrenic patients' learning and memory functioning. Consequently, a potentially reversible and treatable source of cognitive impairment has been virtually ignored. The present study examined the extent of verbal learning and memory impairment in a group of cocaine-dependent schizophrenic patients (n=42) and a group of non-schizophrenic cocaine-dependent patients (n=21) within 72 h of the last cocaine use using the California Verbal Learning Test (CVLT). Schizophrenic patients (n=34) without any substance-use disorders were also tested in an identical time frame and served as a comparison group. Results revealed that all groups demonstrated significant learning and memory impairment relative to CVLT published age and gender corrected norms. Both cocaine-dependent and non-substance abusing schizophrenic groups presented a very similar pattern of impaired learning and recall performance across all CVLT task domains. Comorbid patients, in contrast, presented with marked deficits in their ability to learn and recall verbal information relative to either schizophrenic or cocaine-only groups. Moreover, the cocaine-abusing schizophrenic patients showed significant forgetfulness of the information that they did acquire during delayed recall conditions. The performance deficits exhibited by cocaine-abusing schizophrenic patients differed not only in relative severity of impairment, but also qualitatively in their increased rates of forgetfulness of acquired information. These results are interpreted in terms of the neurobiological substrates of learning and memory and the neurobiological impact of cocaine on schizophrenic patients' cognition during the early phase of inpatient hospitalization. These results suggest that comorbid patients should be targeted for specialized remediation efforts at the beginning phases of inpatient treatment.     

The relative contributions of processing speed and cognitive load to working memory accuracy in multiple sclerosis

Cognitive symptoms of multiple sclerosis (MS) include processing-speed deficits and working memory impairment. The precise manner in which these deficits interact in individuals with MS remains to be explicated. We hypothesized that providing more time on a complex working memory task would result in performance benefits for individuals with MS relative to healthy controls. Fifty-three individuals with clinically definite MS and 36 matched healthy controls performed a computerized task that systematically manipulated cognitive load. The interval between stimuli presentations was manipulated to provide increasing processing time. The results confirmed that individuals with MS who have processing-speed deficits significantly improve in performance accuracy when given additional time to process the information in working memory. Implications of these findings for developing appropriate cognitive rehabilitation interventions are discussed.     

Reduced mismatch negativity in mild cognitive impairment: associations with neuropsychological performance

Mild cognitive impairment (MCI) refers to a transitory state between healthy aging and dementia. Biomarkers are needed to facilitate early identification of MCI and predict progression to dementia. One potential neurophysiological biomarker, mismatch negativity (MMN), is an event-related potential reflecting fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging and dementia and in neuropsychiatric samples and is associated with verbal memory deficits and poor executive functioning. This study aimed to investigate auditory MMN and its relationship to neuropsychological performance in MCI. Twenty-eight MCI participants and fourteen controls, aged ≥50 years, underwent neurophysiological and neuropsychological assessment, and completed questionnaires pertaining to disability. Relative to controls, the MCI group demonstrated reduced temporal MMN amplitude (p < 0.01). Reduced right temporal MMN was significantly associated with poorer verbal learning (r = 0.496; p < 0.01) and reduced left temporal MMN was significantly associated with increased self-reported disability (r = -0.419; p < 0.05). These results indicate that patients with MCI exhibit altered pre-attentive information processing, which in turn is associated with memory and psychosocial deficits. These findings overall suggest that MMN may be a viable neurophysiological biomarker of underlying disease in this 'at risk' group.     

Theory of mind in individuals with Alzheimer-type dementia

Abstract

Background: Theory of Mind (ToM) ability allows attribution of mental states to oneself and others. Recent studies suggest that impairment of ToM may be a partial cause of social-communication impairment in adults with right hemisphere disorder, frontal lobe damage, and the frontal variant of frontotemporal dementia. Initial evidence has also been presented for a ToM impairment in individuals with Alzheimer's disease (AD), but extant investigations have inadequately controlled for other cognitive impairments.

Aims: The purpose of this study was to determine whether individuals with AD exhibit a ToM impairment that is distinguishable from cognitive and executive function deficits, and to investigate whether memory support affects their ToM performance.

Methods & Procedures: Ten participants with mild to moderate AD completed first‐order and second-order false belief tasks with and without memory support, and their performances on ToM testing were compared to those of elderly controls. All ToM testing was controlled with memory, comprehension, and general inferencing questions. AD participants completed neuropsychological testing to concurrently assess general cognitive functioning, memory, and executive functioning. Independent and paired t‐tests compared experimental and control group ToM performances. Correlations assessed relations between ToM and neurocognitive test performances.

Outcomes & Results: Results indicated that, in the absence of memory support, AD participants did not exhibit a specific ToM difficulty as compared to control participants. However, significant group differences for specific ToM impairment that appeared to be separable from comprehension, memory, and general inferencing difficulties emerged during ToM testing when memory support was provided. Correlations between ToM performance and neurocognitive test performances were not significant; however, four of the eight AD participants who exhibited specific, ToM difficulty also had difficulty with executive function testing.

Conclusions: These results indicate that individuals with mild to moderate AD may possess an underlying, mild, specific ToM impairment, which becomes apparent during supported memory testing. Such mild ToM impairment in moderate AD individuals must be further investigated, and possible contributions of executive function impairments to apparent ToM difficulty further explored before the current results can be confidently generalised to a larger AD population.     

Memory rehabilitation for the working memory of patients with multiple sclerosis (MS)

Objective: The main cognitive impairments in multiple sclerosis (MS) affect the working memory, processing speed, and performances that are in close interaction with one another. Cognitive problems in MS are influenced to a lesser degree by disease recovery medications or treatments,but cognitive rehabilitation is considered one of the promising methods for cure. There is evidence regarding the effectiveness of cognitive rehabilitation for MS patients in various stages of the disease. Since the impairment in working memory is one of the main MS deficits, a particular training that affects this cognitive domain can be of a great value. This study aims to determine the effectiveness of memory rehabilitation on the working memory performance of MS patients.

Method: Sixty MS patients with cognitive impairment and similar in terms of demographic characteristics, duration of disease, neurological problems, and mental health were randomly assigned to three groups: namely, experimental, placebo, and control. Patients’ cognitive evaluation incorporated baseline assessments immediately post-intervention and 5 weeks post-intervention. The experimental group received a cognitive rehabilitation program in one-hour sessions on a weekly basis for 8 weeks. The placebo group received relaxation techniques on a weekly basis; the control group received no intervention.

Results: The results of this study showed that the cognitive rehabilitation program had a positive effect on the working memory performance of patients with MS in the experimental group. These results were achieved in immediate evaluation (post-test) and follow-up 5 weeks after intervention. There was no significant difference in working memory performance between the placebo group and the control group.

Conclusions: According to the study, there is evidence for the effectiveness of a memory rehabilitation program for the working memory of patients with MS. Cognitive rehabilitation can improve working memory disorders and have a positive effect on the working memory performance of these patients.