Neuronal Correlates of Perception, Imagery, and Memory for Familiar Tunes

We used fMRI to investigate the neuronal correlates of encoding and recognizing heard and imagined melodies. Ten participants were shown lyrics of familiar verbal tunes; they either heard the tune along with the lyrics, or they had to imagine it. In a subsequent surprise recognition test, they had to identify the titles of tunes that they had heard or imagined earlier. The functional data showed substantial overlap during melody perception and imagery, including secondary auditory areas. During imagery compared with perception, an extended network including pFC, SMA, intraparietal sulcus, and cerebellum showed increased activity, in line with the increased processing demands of imagery. Functional connectivity of anterior right temporal cortex with frontal areas was increased during imagery compared with perception, indicating that these areas form an imagery-related network. Activity in right superior temporal gyrus and pFC was correlated with the subjective rating of imagery vividness. Similar to the encoding phase, the recognition task recruited overlapping areas, including inferior frontal cortex associated with memory retrieval, as well as left middle temporal gyrus. The results present new evidence for the cortical network underlying goal-directed auditory imagery, with a prominent role of the right pFC both for the subjective impression of imagery vividness and for on-line mental monitoring of imagery-related activity in auditory areas.

Cognitive functioning in the schizophrenia prodrome

In the last decade, there has been an increasing interest in cognitive alterations during the early course of schizophrenia. From a clinical perspective, a better understanding of cognitive functioning in putative at-risk states for schizophrenia is essential for developing optimal early intervention models. Two approaches have more recently been combined to assess the entire course of the initial schizophrenia prodrome: the predictive "basic symptom at-risk" (BS) and the ultra high-risk (UHR) criteria. Basic symptoms are considered to be present during the entire disease progression, including the initial prodrome, while the onset of symptoms captured by the UHR criteria expresses further disease progression toward frank psychosis. The present study investigated the cognitive functioning in 93 subjects who met either BS or UHR criteria and thus were assumed to be at different points on the putative trajectory to psychosis. We compared them with 43 patients with a first episode of psychosis and to 49 help-seeking patient controls. All groups performed significantly below normative values. Both at-risk groups performed at intermediate levels between the first-episode (FE) group and normative values. The UHR group demonstrated intermediate performance between the FE and BS groups. Overall, auditory working memory, verbal fluency/processing speed, and declarative verbal memory were impaired the most. Our results suggest that cognitive impairments may still be modest in the early stages of the initial schizophrenia prodrome and thus support current efforts to intervene in the early course of impending schizophrenia because early intervention may prevent or delay the onset of frank psychosis and thus prevent further cognitive damage.

Better Memory and Neural Efficiency in Young Apolipoprotein E 4 Carriers

The apolipoprotein E (APOE) epsilon4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE epsilon4 with better episodic memory compared with APOE epsilon2 and epsilon3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas epsilon2 and epsilon3 carriers increased activity. This smaller neural investment of epsilon4 carriers into learning reappeared during retrieval: epsilon4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE epsilon4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.

Information processing in long delay memory-guided saccades: further insights from TMS

The performance of memory-guided saccades with two different delays (3 s and 30 s of memorisation) was studied in eight subjects. Single pulse transcranial magnetic stimulation (TMS) was applied simultaneously over the left and right dorsolateral prefrontal cortex (DLPFC) 1 s after target presentation. In both delays, stimulation significantly increased the percentage of error in amplitude of memory-guided saccades. Furthermore, the interfering effect of TMS was significantly higher in the short delay compared to that of the long delay paradigm. The results are discussed in the context of a mixed model of spatial working memory control including two components: First, serial information processing with a predominant role of the DLPFC during the early period of memorisation and, second, parallel information processing, which is independent from the DLPFC, operating during longer delays.

Using transcranial magnetic stimulation to probe decision-making and memory

Decision-making and memory are fundamental processes for successful human behaviour. For eye movements, the frontal eye fields (FEF), the supplementary eye fields (SEF), the dorsolateral prefrontal cortex (DLPFC), the ventrolateral frontal cortex and the anterior cingulum are important for these cognitive processes. The online approach of transcranial magnetic stimulation (TMS), i.e., the application of magnetic pulses during planning and performance of saccades, allows interfering specifically with information processing of the stimulated region at a very specific time interval (chronometry of cortical processing). The paper presents studies, which showed the different roles of the FEF and DLPFC in antisaccade control. The critical time interval of DLPFC control seems to be before target onset since TMS significantly increased the percentage of antisaccade errors at that time interval. The FEF seems to be important for the triggering of correct antisaccades. Bilateral stimulation of the DLPFC could demonstrate parallel information-processing transfer in spatial working memory during memory-guided saccades.

The Role of Consciousness in Memory

Conscious events interact with memory systems in learning, rehearsal and retrieval (Ebbinghaus 1885/1964; Tulving 1985). Here we present hypotheses that arise from the IDA computional model (Franklin, Kelemen and McCauley 1998; Franklin 2001b) of global workspace theory (Baars 1988, 2002). Our primary tool for this exploration is a flexible cognitive cycle employed by the IDA computational model and hypothesized to be a basic element of human cognitive processing. Since cognitive cycles are hypothesized to occur five to ten times a second and include interaction between conscious contents and several of the memory systems, they provide the means for an exceptionally fine-grained analysis of various cognitive tasks. We apply this tool to the small effect size of subliminal learning compared to supraliminal learning, to process dissociation, to implicit learning, to recognition vs. recall, and to the availability heuristic in recall. The IDA model elucidates the role of consciousness in the updating of perceptual memory, transient episodic memory, and procedural memory. In most cases, memory is hypothesized to interact with conscious events for its normal functioning. The methodology of the paper is unusual in that the hypotheses and explanations presented are derived from an empirically based, but broad and qualitative computational model of human cognition.

Ecological validity of virtual reality daily living activities screening for early dementia: longitudinal study

Background: Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. Objective: The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer’s-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. Methods: The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and while performing VR-DOTs in order to correlate performance in these measures with VR-DOTs because performance while navigating a virtual environment is a valid and reliable indicator of cognitive decline in elderly persons. Results: The mild AD group was more impaired than the amnestic MCI group, and both were more impaired than healthy controls. The novel VR-DOT functional index correlated strongly with standard cognitive and functional measurements, such as mini-mental state examination (MMSE; rho=0.26, P=.01) and Bristol Activities of Daily Living (ADL) scale scores (rho=0.32, P=.001). Conclusions: Functional impairment is a defining characteristic of predementia and is partly dependent on the degree of cognitive impairment. The novel virtual reality measures of functional ability seem more sensitive to functional impairment than qualitative measures in predementia, thus accurately differentiating from healthy controls. We conclude that VR-DOT is an effective tool for discriminating predementia and mild AD from controls by detecting differences in terms of errors, omissions, and perseverations while measuring ADL functional ability.

Orthostatic hypotension in Parkinson's disease: association with cognitive decline?

BACKGROUND Orthostatic hypotension is common in Lewy body disorders and may be related to disease progression and the spread of Lewy body pathology. We therefore hypothesize that PD patients with orthostatic hypotension (OH) have a different cognitive profile compared to PD patients without OH. METHODS This cross-sectional study included 175 PD patients. Blood pressure (BP) was measured with a validated digital blood pressure monitor and patients with a systolic BP drop of > or =20 mmHg or a systolic pressure of <90 mm Hg after standing were considered to have OH. Cognition was assessed using MMSE extended by a selection of computerized cognitive tests focusing on reaction time, sustained attention, working memory and episodic verbal and visual memory. RESULTS Eighty-seven (49.7%) of the PD patients had OH. These patients were significantly more impaired in sustained attention and visual episodic memory compared to PD patients without OH. CONCLUSION We conclude that there are differences in the neuropsychological performance of patients with PD and OH, supporting the hypothesis that OH might be a marker for disease progression and cognitive decline in PD.

Evidence for mental ability related individual differences in the attentional blink obtained by an analysis of the P300 component

Attentional blink (AB) refers to impaired identification of a target (T2) when this target follows a preceding target (T1) after about 150-450 ms within a stream of rapidly presented stimuli. Previous research on a possible relation between AB and mental ability (MA) turned out to be highly ambiguous. The present study investigated MA-related individual differences in consolidation of T2 in working memory during the AB as indicated by the P300 component of the event-related potential. Thirty high (HA) and 30 low MA (LA) female participants performed an AB task while their brain activity was recorded. The AB did not differ between the two groups. HA individuals exhibited a larger P300 amplitude and longer P300 latencies during the AB suggesting higher mental effort. This higher mental effort, however, did not result in better performance presumably because of more competition between target and distractor stimuli in HA than LA individuals.

Memory and attention problems in children with brain tumors at diagnosis

Purpose: Results from previous studies indicate that children with brain tumors (BT) might present with cognitive problems at diagnosis and thus before the start of any medical treatment. The question remains whether these problems are due to the underlying tumor itself or due to the high level of emotional and physical stress which is involved at diagnosis of a malignant disorder. All children with a de novo oncological diagnosis not involving the central nervous systems (CNS) are usually exposed to a comparable level of distress. However, patients with cancer not involving the CNS are not expected to show disease-related cognitive problems. Thus they serve as a well-balanced control group (CG) to help distinguish between the probable causes of the effect. Method: In a pilot study we analyzed an array of cognitive functions in 16 children with BT and 17 control patients. In both groups, tests were administered in-patient at diagnosis before any therapeutic intervention such as surgery, chemotherapy od irradiation. Results: Performance of children with BT was comparable to that of CG patients in the areas of intelligence, perceptual reasoning, verbal comprehension, working memory, and processing speed. In contrast, however, BT patients performded significantly worse in verbal memory and attention. Conclusion: Memory and attention seem to be the most vulnerable funstions affected by BT, with other functions being preserved at the time of diagnosis. It ist to be expected that this vulnerability might exacerbate the cognitive decline after chemotherapy and radiation treatment - known to impair intellectual performance. The findings highlight the need of early cognitive assessments in children with BT in order to introduce cognitive training as early as possible to minimize or even prevent cognitive long-term sequelae. This might improve long-term academic and professional outcome of these children, but especially helps their return to school after hospitalization.

Improving children’s cognitive performance – Effect of a memory strategy training in children born very preterm

Aims: To examine the effect of memory strategy training on different aspects of memory in children born very preterm and to determine whether there is a generalization of the training effect to non-trained functions. The influence of individual factors such as age and performance level on the training success will be determined. Methods: In a randomized, controlled and blinded clinical trial, 46 children born very preterm (aged 7-12 years) were allocated to a memory strategy training (MEMO-Training, n=23) or a control group (n=23). Neuropsychological assessment was performed before, immediately after the training and at a 6-month follow-up. In the MEMO-Training, five different memory strategies were introduced and practiced in a one-to-one setting (4 hour-long training sessions over 4 weeks, 20 homework sessions). Results: A significant training-related improvement occurred in trained aspects of memory (verbal and visual learning and recall, verbal working memory) and in non-trained functions (inhibition, mental arithmetic). No performance increase was observed in the control group. At six months follow-up, there was a significant training-related improvement of visual working memory. Age and performance level before the training predicted the training success significantly. Conclusion: Teaching memory strategies is an effective way to improve different aspects of memory but also non-trained functions such as inhibition and mental arithmetic in children born very preterm. Age and performance level influence the success of memory strategy training. These results highlight the importance of teaching children memory strategies to reduce scholastic problems.

Nonverbal social communication and gesture control in schizophrenia

Schizophrenia patients are severely impaired in nonverbal communication, including social perception and gesture production. However, the impact of nonverbal social perception on gestural behavior remains unknown, as is the contribution of negative symptoms, working memory, and abnormal motor behavior. Thus, the study tested whether poor nonverbal social perception was related to impaired gesture performance, gestural knowledge, or motor abnormalities. Forty-six patients with schizophrenia (80%), schizophreniform (15%), or schizoaffective disorder (5%) and 44 healthy controls matched for age, gender, and education were included. Participants completed 4 tasks on nonverbal communication including nonverbal social perception, gesture performance, gesture recognition, and tool use. In addition, they underwent comprehensive clinical and motor assessments. Patients presented impaired nonverbal communication in all tasks compared with controls. Furthermore, in contrast to controls, performance in patients was highly correlated between tasks, not explained by supramodal cognitive deficits such as working memory. Schizophrenia patients with impaired gesture performance also demonstrated poor nonverbal social perception, gestural knowledge, and tool use. Importantly, motor/frontal abnormalities negatively mediated the strong association between nonverbal social perception and gesture performance. The factors negative symptoms and antipsychotic dosage were unrelated to the nonverbal tasks. The study confirmed a generalized nonverbal communication deficit in schizophrenia. Specifically, the findings suggested that nonverbal social perception in schizophrenia has a relevant impact on gestural impairment beyond the negative influence of motor/frontal abnormalities.

Neural change following different memory training approaches in very preterm born children - A pilot study.

OBJECTIVE There is mixed evidence regarding neural change following cognitive training. Brain activation increase, decrease, or a combination of both may occur. We investigated training-induced neural change using two different memory training approaches. METHODS Very preterm born children (aged 7-12 years) were randomly allocated to a memory strategy training, an intensive working memory practice or a waiting control group. Before and immediately after the trainings and the waiting period, brain activation during a visual working memory task was measured using fMRI and cognitive performance was assessed. RESULTS Following both memory trainings, there was a significant decrease of fronto-parietal brain activation and a significant increase of memory performance. In the control group, no neural or performance change occurred after the waiting period. CONCLUSION These pilot data point towards a training-related decrease of brain activation, independent of the training approach. Our data highlight the high training-induced plasticity of the child's brain during development.

Effects of two different memory training approaches in very preterm-born children

Background: Little research has been conducted to assess the effect of using memory training with school-aged children who were born very preterm. This study aimed to determine whether two types of memory training approaches resulted in an improvement of trained functions and/or a generalization of the training effect to non-trained cognitive domains. Methods: Sixty-eight children born very preterm (7¬-12 years) were randomly allocated to a group undertaking memory strategy training (n=23), working memory training (n=22), or a waiting control group (n=23). Neuropsychological assessment was performed before and immediately after the training or waiting period, and at a six-month follow-up. Results: In both training groups, significant improvement of different memory domains occurred immediately after training (near transfer). Improvement of non-trained arithmetic performance was observed after strategy training (far transfer). At a six-month follow-up assessment, children in both training groups demonstrated better working memory, and their parents rated their memory functions to be better than controls. Performance level before the training was negatively associated with the training gain. Conclusions: These results highlight the importance of cognitive interventions, in particular the teaching of memory strategies, in very preterm-born children at early school age to strengthen cognitive performance and prevent problems at school.

Effects of two different memory training approaches in very pretermborn children

Background: Little research has been conducted to assess the effect of using memory training with school aged children who were born very preterm. This study aimed to determine whether two types of memory training approaches resulted in an improvement of trained functions and/or a generalization of the training effect to non-trained cognitive domains. Methods: Sixty-eight children born very preterm (7-12 years) were randomly allocated to a group undertaking memory strategy training (n=23), working memory training (n=22), or a waiting control group (n=23). Neuropsychological assessment was performed before and immediately after the training or waiting period, and at a six-month follow-up. Results: In both training groups, significant improvement of different memory domains occurred immediately after training (near transfer). Improvement of non-trained arithmetic performance was observed after strategy training (far transfer). At a six-month follow-up assessment, children in both training groups demonstrated better working memory, and their parents rated their memory functions to be better than controls. Performance level before the training was negatively associated with the training gain. Conclusions: These results highlight the importance of cognitive interventions, in particular the teaching of memory strategies, in very preterm-born children at early school age to strengthen cognitive performance and prevent problems at school.