Implicit prototype learning in patients with memory deficit: Evidence from a study with Alzheimer's disease patients.

OBJECTIVE: In a previous study (Zannino et al., 2012), it was demonstrated that individuals with amnestic mild cognitive impairment (MCI) were unimpaired on a new prototype learning task consisting of morphed faces (face prototype learning task [FPLT]). This paradigm was devised to improve on the classical dot pattern task by ruling out any reliance on residual episodic memory or working memory resources. In the present study, we aimed to demonstrate: first, that people with even more severe episodic memory impairment than MCI are unimpaired on a fully implicit prototype learning task and second, that the dot pattern task, at variance with the FPLT, requires a no negligible contribution from the episodic memory system. METHOD: Twenty-four persons with Alzheimer's disease (AD) and 48 healthy controls took part in this experiment. As in the original study, in addition to the FPLT, they were also administered the classical dot pattern task and an ordinary forced-choice face recognition task. RESULTS: AD performed like normal controls in the FPLT but scored significantly worse on the dot pattern task and the face recognition task. Interestingly, although performance on the face recognition task did not correlate with that on the FPLT, a significant correlation was observed between the face recognition and the dot pattern task. CONCLUSIONS: Results support both of our claims: first, that also severe amnesic people can learn new visual prototypes with a fully implicit paradigm and, second, that the classical dot pattern task requires some degree of episodic resources. Further research is needed to rule out the role of working memory in solving the FPLT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Does Cue Focality Modulate Age-related Performance in Prospective Memory? An fMRI Investigation.

How prospective memory (PM) weakens with increasing age has been largely debated. We hypothesized that automatic and strategic PM processes, respectively mediated by focal and non-focal cues, are differently affected by aging, even starting from 50-60 years of age. We investigated this issue using a 2 × 2 design in which focal and non-focal experimental conditions were created by varying the conjoint nature of the ongoing task (lexical decision vs. syllable matching tasks) and the PM cue (words vs. syllables). In the whole-brain analysis we found that the left inferior frontal gyrus and the middle cingulate cortex were more activated when young compared to older individuals performed a PM task; moreover, the anterior cingulate cortex was selectively activated during non-focal PM when the cues were words. In a region-of-interest analysis we observed that the medial and the lateral portions of the rostral prefrontal cortex were associated with the focal and non-focal conditions respectively, more in young than in older adults. Our findings provide evidence in support of early age-related differences in automatic/strategic PM functioning.

Medio-lateral functional dissociation of the rostral prefrontal cortex with focal/non-focal cues during a prospective memory task.

The rostral prefrontal cortex (rPFC) is crucial in prospective memory (PM) behavior. Several functional magnetic resonance imaging studies showed that its medial (mrPFC) and lateral (lrPFC) portions dissociate during PM tasks. In light of the Multiprocess theory (McDaniel and Einstein 2000), here we tested whether the two portions of the rPFC are dissociable by modulating strategic vs. spontaneous processes during a PM task. We investigated these two processes by means of a 2 × 2 experimental design in which focal vs. non-focal conditions were modulated by varying the conjoint nature of the ongoing task (i.e., lexical decision vs. syllable matching) and the PM cue (words vs. syllables). Using the two portions of the rPFC as regions of interest, we found an effect of the non-focal condition in the lrPFC and, conversely, an effect of the focal condition in the mrPFC. In the whole-brain analysis we found an effect of the non-focal condition in the bilateral intraparietal sulcus, the bilateral middle frontal gyrus, the supplementary motor areas and the vermis of the cerebellum, whereas we found an effect of the focal condition in the ventromedial PFC. Overall, our results show that different brain regions are involved when multiple processes underlying PM behavior are modulated.

A Pilot Study on Brain Plasticity of Functional Connectivity Modulated by Cognitive Training in Mild Alzheimer's Disease and Mild Cognitive Impairment.

Alzheimer's disease (AD) alters the functional connectivity of the default mode network (DMN) but also the topological properties of the functional connectome. Cognitive training (CT) is a tool to slow down AD progression and is likely to impact on functional connectivity. In this pilot study, we aimed at investigating brain functional changes after a period of CT and active control (AC) in a group of 26 subjects with mild AD (mAD), 26 with amnestic mild cognitive impairment (aMCI), and a control group of 29 healthy elderly (HE) people. They all underwent a CT and AC in a counterbalanced order following a crossover design. Resting-state functional MRI and neuropsychological testing were acquired before and after each period. We tested post-CT and post-AC changes of cognitive abilities, of the functional connectivity of the DMN, and of topological network properties derived from graph theory and network-based statistics. Only CT produced functional changes, increasing the functional connectivity of the posterior DMN in all three groups. mAD also showed functional changes in the medial temporal lobe and topological changes in the anterior cingulum, whereas aMCI showed more widespread topological changes involving the frontal lobes, the cerebellum and the thalamus. Our results suggest specific functional connectivity changes after CT for aMCI and mAD.

Reducing Fall Risk with Combined Motor and Cognitive Training in Elderly Fallers.

BACKGROUND: Falling is a major clinical problem in elderly people, demanding effective solutions. At present, the only effective intervention is motor training of balance and strength. Executive function-based training (EFt) might be effective at preventing falls according to evidence showing a relationship between executive functions and gait abnormalities. The aim was to assess the effectiveness of a motor and a cognitive treatment developed within the EU co-funded project I-DONT-FALL. METHODS: In a sample of 481 elderly people at risk of falls recruited in this multicenter randomised controlled trial, the effectiveness of a motor treatment (pure motor or mixed with EFt) of 24 one-hour sessions delivered through an i-Walker with a non-motor treatment (pure EFt or control condition) was evaluated. Similarly, a 24 one-hour session cognitive treatment (pure EFt or mixed with motor training), delivered through a touch-screen computer was compared with a non-cognitive treatment (pure motor or control condition). RESULTS: Motor treatment, particularly when mixed with EFt, reduced significantly fear of falling (F(1,478) = 6.786, p = 0.009) although to a limited extent (ES -0.25) restricted to the period after intervention. CONCLUSIONS: This study suggests the effectiveness of motor treatment empowered by EFt in reducing fear of falling.

Exploring classical conditioning for strengthening the links between semantic and lexical representations in pure anomia: Preliminary findings from a single case study.

The same language symptom might arise at different functional loci in people with aphasia. Therefore, it is plausible that different therapeutic interventions should be adopted to approach the same difficulties in different patients. Although this point of view is still widely accepted, recently the focus has shifted from the functional locus of a rehabilitative intervention to the mechanisms of action underlying the relearning process. We maintain that both aspects should be taken into account when programming a rehabilitative intervention; furthermore, investigating relearning mechanisms might shed new light on the functional architecture of the disrupted processes. Here, we investigated, in a single case study, whether classical conditioning was a suitable relearning paradigm for targeting word-finding difficulties in pure anomia, that is in a patient with an impairment in accessing intact output lexical representations from a spared semantic system. Using a word-repetition task on picture presentation, we contrasted a condition in which the stimulus onset asynchrony between word and picture stimuli was well suited to produce classical conditioning with a condition in which repetition training could not benefit from this learning mechanism. Only classical conditioning training exerted a significant, long-lasting effect on our patient's naming skill. Tentative implications of our results for the functional architecture of single-word processing are discussed.

Protecting cognition from aging and Alzheimer's disease: a computerized cognitive training combined with reminiscence therapy.

OBJECTIVE: The aim of this paper was to assess the efficacy of process-based cognitive training (pb-CT) combined with reminiscence therapy (RT) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and in healthy elderly (HE) subjects. METHODS: This multicenter, randomized, controlled trial involved 348 participants with mAD, MCI, and HE from four European countries. Participants were randomly assigned to two arms of a crossover design: those in arm A underwent 3 months of computerized pb-CT for memory and executive functions combined with RT and 3 months of rest; those in arm B underwent the reverse. The primary outcome was the effect of the training on memory and executive functions performance. The secondary outcome was the effect of the training on functional abilities in mAD assessed with the instrumental activities of daily living. RESULTS: We found a significant effect of the training for memory in all three groups on delayed recall of the Rey Auditory Verbal Learning Test and for executive functions in HE on the phonological fluency test. MCI and HE participants maintained these effects at follow-up. MCI and mAD participants also showed a significant effect of the training on the Mini-mental state examination scale. Participants with mAD showed more stable instrumental activities of daily living during the training versus the rest period. CONCLUSIONS: Our results corroborate the positive effect of pb-CT and its maintenance primarily on memory in HE and MCI participants that did not seem to be potentiated by RT. Moreover, our results are very promising for the mAD participants.

A pilot study on the effect of cognitive training on BDNF serum levels in individuals with Parkinson's disease.

Parkinson's disease (PD) patients, besides motor dysfunctions, may also display mild cognitive deficits (MCI) which increase with disease progression. The neurotrophin brain-derived neurotrophic factor (BDNF) plays a role in the survival of dopaminergic neurons and in the regulation of synaptic connectivity. Moreover, the brain and peripheral level of this protein may be significantly reduced in PD patients. These data suggest that a cognitive rehabilitation protocol aimed at restoring cognitive deficits in PD patients may also involve changes in this neurotrophin. Thus, in this pilot study we evaluated the effect of a cognitive rehabilitation protocol focused on the training of executive functioning and measured BDNF serum levels in a group of PD patients with mild cognitive impairment, as compared to the effect of a placebo treatment (n = 7/8 group). The results showed that PD patients undergoing the cognitive rehabilitation, besides improving their cognitive performance as measured with the Zoo Map Test, also displayed increased serum BDNF levels as compared to the placebo group. These findings suggest that BDNF serum levels may represent a biomarker of the effects of cognitive rehabilitation in PD patients affected by MCI. However, the functional significance of this increase in PD as well as other neuropathological conditions remains to be determined.

Prospective memory performance in individuals with Parkinson's disease who have mild cognitive impairment.

OBJECTIVE: Prospective memory (PM) is the ability to keep in memory and realize future intentions. We aimed at investigating whether in Parkinson's disease (PD) PM deficits are related to mild cognitive impairment (MCI). Other aims were to investigate the cognitive abilities underlying PM performance, and the association between PM performance and measures of daily living functioning. METHOD: The study included 15 PD patients with single domain MCI, 15 with multiple domain MCI, 17 PD patients without cognitive disorders (PDNC) and 25 healthy controls (HCs). All subjects were administered a PM procedure that included focal (PM cue is processed in the ongoing task) and nonfocal (PM cue is not processed in the ongoing task) conditions. PD patients were administered an extensive neuropsychological battery and scales to assess daily living abilities. RESULTS: PD patients with MCI (both single and multiple domains) showed lower accuracy on all PM conditions than both HC and PDNC patients. This was predicted by their scores on shifting indices. Conversely, PM accuracy of PDNC patients was comparable to HCs. Regression analyses revealed that PD patients' PM performance significantly predicted scores on daily living scales Conclusions: Results suggest that PM efficiency is not tout-court reduced in PD patients, but it specifically depends on the presence of MCI. Moreover, decreased executive functioning, but not episodic memory failure, accounts for a significant proportion of variance in PM performance. Finally, PM accuracy indices were found to be associated with measures of global daily living functioning and management of medication.

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.

Prospective memory performance of patients with Parkinson's disease depends on shifting aptitude: evidence from cognitive rehabilitation.

This study investigated the effect of cognitive training aimed at improving shifting ability on Parkinson's disease (PD) patients' performance of prospective memory (PM) tasks. Using a double-blind protocol, 17 PD patients were randomly assigned to two experimental arms. In the first arm (n=9) shifting training was administered, and in the second (placebo) arm (n=8), language and respiratory exercises. Both treatments consisted of 12 sessions executed over 4 weeks. PM and shifting measures (i.e., Trail Making Test and Alternate Fluency Test) were administered at T0 (before treatment) and T1 (immediately after treatment). A mixed analysis of variance was applied to the data. To evaluate the effects of treatment, the key effect was the interaction between Group (experimental vs. placebo) and Time of Assessment (T0 vs. T1). This interaction was significant for the accuracy indices of the PM procedure (p<.05) and for the performance parameters of the shifting tasks (p ≤.05). Tukey's HSD tests showed that in all cases passing from T0 to T1 performance significantly improved in the experimental group (in all cases p ≤.02) but remained unchanged in the placebo group (all p consistently>.10). The performance change passing from T0 to T1 on the Alternate Fluency test and the PM procedure was significantly correlated (p<.05). Results show that the cognitive training significantly improved PD patients' event-based PM performance and suggest that their poor PM functioning might be related to reduced shifting abilities.

Functional interplay between stimulus-oriented and stimulus-independent attending during a prospective memory task.

Recent studies have suggested that medial (medBA10) and lateral (latBA10) portions of the Brodmann area 10 subserve respectively stimulus-oriented (SO) and stimulus-independent (SI) attending during prospective memory (PM) tasks. We investigated this dissociation by manipulating the saliency (SO) and the memory load (SI) of PM cues. Sixteen healthy subjects participated to a functional imaging protocol with a 2×2×2 experimental design, including the factors: task (ongoing target vs. PM cue), Saliency (high vs. low; with targets/cues either embedded or standing out from distracters), and memory load (high vs. low; with 1 or 4 possible PM targets). We localized the medBA10 and latBA10 by means of a localizer task. In medBA10 we found a significant main effects of high Saliency and low memory load; whereas in the left latBA10, we found a significant task×load interaction, with maximal activation for PM cues presented in the high load condition. These results are in agreement with the gateway hypothesis: during a PM task medBA10 biases attention toward external salient stimuli, SO attending, while latBA10 biases attention toward internal mnemonic representations, SI attending. Additional whole-brain analyses highlighted activation of other areas besides BA10, consistent with recent proposals that emphasise the role of distributed networks during PM performance.

Letters persistence after physical offset: visual word form area and left planum temporale. An fMRI study.

Iconic memory is a high-capacity low-duration visual memory store that allows the persistence of a visual stimulus after its offset. The categorical nature of this store has been extensively debated. This study provides functional magnetic resonance imaging evidence for brain regions underlying the persistence of postcategorical representations of visual stimuli. In a partial report paradigm, subjects matched a cued row of a 3 × 3 array of letters (postcategorical stimuli) or false fonts (precategorical stimuli) with a subsequent triplet of stimuli. The cued row was indicated by two visual flankers presented at the onset (physical stimulus readout) or after the offset of the array (iconic memory readout). The left planum temporale showed a greater modulation of the source of readout (iconic memory vs. physical stimulus) when letters were presented compared to false fonts. This is a multimodal brain region responsible for matching incoming acoustic and visual patterns with acoustic pattern templates. These findings suggest that letters persist after their physical offset in an abstract postcategorical representation. A targeted region of interest analysis revealed a similar pattern of activation in the Visual Word Form Area. These results suggest that multiple higher-order visual areas mediate iconic memory for postcategorical stimuli.

The right frontopolar cortex is involved in visual-spatial prospective memory.

The involvement of frontopolar cortex in mediating prospective memory processes has been evidenced by various studies, mainly by means of neuroimaging techniques. Recently, one transcranial magnetic stimulation study documented that transient inhibition of left Brodmann Area (BA) 10 impaired verbal prospective memory. This result raises the issue of whether the BA 10 involvement in prospective memory functioning may be modulated by the physical characteristics of the stimuli used. The present study aimed to investigate the role of the frontopolar cortex in visual-spatial PM by means of the application of inhibitory theta-burst stimulation. Twelve volunteers were evaluated after inhibitory theta-burst stimulation over left BA 10, right BA10 and CZ (control condition). In the prospective memory procedure, sequences of four spatial positions (black squares) each were presented. During the inter-sequence delay, subjects had to reproduce the sequence in the observed order (ongoing task forward) or the reverse order (backward). At the occurrence of a target position, subjects had to press a key on the keyboard (prospective memory score). Recall and recognition of the target positions were also tested. We found that prospective memory accuracy was lower after theta-burst stimulation over right BA10 than CZ (p<0.01), whereas it was comparable in left BA10 and CZ conditions. No significant difference was found among the three conditions on recall and recognition of target positions and on ongoing task performance. Our findings provide a novel strong evidence for a specific involvement of right frontopolar cortex in visual-spatial prospective memory. In the context of previous data providing evidence for left BA 10 involvement in verbal prospective memory, our results also suggest material-specific lateralization of prospective memory processes in BA 10.

Functional brain activity within the medial and lateral portion of BA10 during a prospective memory task.

In this study we tested the gateway hypothesis of Broadmann area 10 (BA10). With a functional magnetic resonance imaging (fMRI) protocol we manipulated the saliency--stimulus-oriented (SO) attending--and the memory load--stimulus-independent (SI) attending--during a prospective memory (PM) task. We found a significant main effect of the SO manipulation within the medial BA10 and a significant interaction between SI attending and PM task within the left lateral BA10. Our results give experimental support to the gateway hypothesis.

Slowing of information processing in Alzheimer disease: motor as well as cognitive factors.

OBJECTIVE: To use Sternberg's Additive Factor Method to determine whether patients with mild Alzheimer disease (AD) are slow in information processing and/or response execution. METHODS: We gave an odd-even categorization task to 16 patients with probable mild AD and 17 age-matched healthy controls. We recorded reaction and movement times to stimuli varying for noise, target set size, stimulus-response compatibility, and fore-period interval, to probe the cognitive and motor stages of information processing. RESULTS: Both groups performed the task accurately, indicating good preservation of odd-even categorization in mild AD. The AD group's reaction times were similar to the controls' across conditions, and not selectively affected in any of the cognitive stages of the Additive Factor Method. However, the AD group's movement times were slower than the controls' across conditions. CONCLUSIONS: AD patients' performance on a task requiring categorization ability was slowed more by motor than cognitive components of information processing. When evaluating the performance of patients with AD in reaction-time paradigms, we should not attribute group differences solely to differences in cognitive processing. Execution components should also be considered.

Keeping memory for intentions: a cTBS investigation of the frontopolar cortex.

The present study aimed to investigate the role of frontopolar cortex in prospective memory (PM) by means of inhibitory theta-burst stimulation (cTBS). "Experiment 1"-8 volunteers were evaluated after inhibitory cTBS over left Brodmann area (BA) 10, right BA10, and Cz. In the PM procedure, sequences of 4 words each were presented. During the intersequence delay, subjects had to repeat the sequence in the observed order (ongoing task forward) or in the reverse order (backward). At the occurrence of a target word, subjects had to press a key on the keyboard (PM task). Recall and recognition of the target words were also tested. PM accuracy was lower after cTBS over left BA10 compared with Cz (P = 0.012), whereas it was comparable in right BA10 and Cz conditions. No other significant differences between the 3 conditions were found. "Experiment 2"-8 subjects were administered the same experimental PM procedure as above after inhibitory cTBS over left BA46 and Cz. In this case, none of the tested effects were significant. Our findings corroborate the hypothesis that within the prefrontal cortex, the left BA10 is specifically involved in the mediation of processes related to the execution of delayed intentions.

Event-based prospective memory failure in amnestic mild cognitive impairment.

Prospective memory (PM) deficits have recently been documented in individuals with amnestic mild cognitive impairment (aMCI). In this paper, we investigated whether these deficits are due to the failure of retrospective memory processes. We also examined the role played by attentional/executive processes in PM functioning. We enrolled 24 individuals with aMCI and 24 healthy controls (NCs). In the PM procedure, we manipulated both the memory load of the retrospective component of the PM task and the complexity of the ongoing task in a 2 × 2 experimental design. Sequences of four words were presented. Participants had to repeat the sequence in the same order (low attentional demand condition) or in the reverse order (high attentional demand condition). When a target word appeared in the sequence, participants had to press a button on the keyboard (PM task). Target words could be one (low memory load condition) or four (high memory load condition) in different blocks. MCI participants obtained lower PM scores than NCs in all four experimental conditions. However, they recalled the target words less accurately than NCs only in one four-word condition. Finally, the executive demand of the ongoing task did not significantly affect the PM performance of aMCI individuals. Our findings confirm that PM is severely impaired in individuals with aMCI. Moreover, a failure of retrospective memory processes does not seem to fully account for the poor PM performance in aMCI individuals. Finally, the finding that in these individuals, a deficit in executive control cannot be claimed as the main responsible for the observed PM impairment could suggest the involvement of automatic-reflexive processes.

The neural correlates of object familiarity and domain specificity in the human visual cortex: an FMRI study.

Ventral occipito-temporal cortex is known to play a major role in visual object recognition. Still unknown is whether object familiarity and semantic domain are critical factors in its functional organization. Most models assume a functional locus where exemplars of familiar categories are represented: the structural description system. On the assumption that familiarity should modulate the effect of visual noise on form recognition, we attempted to individualize the structural description system by scanning healthy subjects while they looked at familiar (living and nonliving things) and novel 3-D objects, either with increasing or decreasing visual noise. Familiarity modulated the visual noise effect (particularly when familiar items were living things), revealing a substrate for the structural description system in right occipito-temporal cortex. These regions also responded preferentially to living as compared to nonliving items. Overall, these results suggest that living items are particularly reliant on the structural description system.

Prospective memory functioning in mild cognitive impairment.

OBJECTIVE: The present study aimed to investigate prospective memory (PM) in persons with mild cognitive impairment (MCI). METHOD: Twenty individuals with MCI (10 with an amnestic profile and 10 with a dysexecutive profile of cognitive impairment) and 20 control subjects (CS) were recruited. In the PM tasks, subjects had to execute three actions after 20 min had elapsed (time-based condition) or after a timer rang (event-based condition). Separate scores were computed for correct recall of the intention to perform the actions (prospective component) and for correct execution of the actions (retrospective component). RESULTS: Although individuals with MCI were less accurate than CS in both prospective (Cohen's d ranged from 1.04 to 2.23) and retrospective (Cohen's d ranged from 0.81 to 1.06) components of the experimental task, they were significantly more impaired in the former than the latter component (Cohen's d = 0.42). Moreover, the deficit in the prospective component of the time-based task was particularly evident in MCI participants presenting with a dysexecutive impairment in respect to amnestic MCI individuals (Cohen's d = 0.99). CONCLUSIONS: Results of the present study show that the ability of subjects with MCI to comply effectively with a planned delayed intention is impaired and suggest that dysexecutive disorders are likely responsible for this deficit.