Johan Eriksson

Longitudinal evidence for diminished frontal cortex function in aging

Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.

Learning by doing versus learning by thinking: An fMRI study of motor and mental training

Previous studies have documented that motor training improves performance on motor skill tasks and related this to altered functional brain activity in cerebellum, striatum, and frontal motor cortical areas. Mental training can also improve the performance on motor tasks, but the neural basis of such facilitation is unclear. The purpose of the present study was to identify neural correlates of training-related changes on a finger-tapping task. Subjects were scanned twice, 1 week apart, with fMRI while they performed two finger-tapping sequences with the left hand. In-between scans, they practiced daily on one of the sequences. Half of the participants received motor training and the other half received mental training (motor imagery). Both training procedures led to significant increases in tapping performance. This was seen for both the trained and the untrained sequence (non-specific effect), although the gain was larger for the trained sequence (sequence-specific effect). The non-specific training effect corresponded to a reduction in the number of activated areas from an extensive set of brain regions prior to training to mainly motor cortex and cerebellum after training. The sequence-specific training effect involved the supplementary motor area and the cerebellum for motor training and visual association cortex for mental training. We conclude that gains following motor and mental training are based on distinct neuroplastic changes in the brain.

Growth of language-related brain areas after foreign language learning

The influence of adult foreign-language acquisition on human brain organization is poorly understood. We studied cortical thickness and hippocampal volumes of conscript interpreters before and after three months of intense language studies. Results revealed increases in hippocampus volume and in cortical thickness of the left middle frontal gyrus, inferior frontal gyrus, and superior temporal gyrus for interpreters relative to controls. The right hippocampus and the left superior temporal gyrus were structurally more malleable in interpreters acquiring higher proficiency in the foreign language. Interpreters struggling relatively more to master the language displayed larger gray matter increases in the middle frontal gyrus. These findings confirm structural changes in brain regions known to serve language functions during foreign-language acquisition.

Neurocognitive Architecture of Working Memory

A crucial role for working memory in temporary information processing and guidance of complex behavior has been recognized for many decades. There is emerging consensus that working-memory maintenance results from the interactions among long-term memory representations and basic processes, including attention, that are instantiated as reentrant loops between frontal and posterior cortical areas, as well as sub-cortical structures. The nature of such interactions can account for capacity limitations, lifespan changes, and restricted transfer after working-memory training. Recent data and models indicate that working memory may also be based on synaptic plasticity and that working memory can operate on non-consciously perceived information.

Looking as if you know: Systematic object inspection precedes object recognition

Sometimes we seem to look at the very object we are searching for, without consciously seeing it. How do we select object relevant information before we become aware of the object? We addressed this question in two recognition experiments involving pictures of fragmented objects. In Experiment 1, participants preferred to look at the target object rather than a control region 25 fixations prior to explicit recognition. Furthermore, participants inspected the target as if they had identified it around 9 fixations prior to explicit recognition. In Experiment 2, we investigated the influence of semantic knowledge in guiding object inspection prior to explicit recognition. Consistently, more specific knowledge about target identity made participants scan the fragmented stimulus more efficiently. For instance, non-target regions were rejected faster when participants knew the target objects name. Both experiments showed that participants were looking at the objects as if they knew them before they became aware of their identity.

Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition☆

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n=287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Functional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study

BACKGROUNDnMany patients with Parkinsons disease have mild cognitive impairment (MCI). Deficits in executive functions and working memory suggest dysfunctional frontostriatal brain circuitry. We aimed to assess brain responses during a working memory task in a cohort of newly diagnosed drug-naive patients with Parkinsons disease with and without MCI.nnnMETHODSnParticipants were recruited within a prospective cohort study of incident patients with idiopathic parkinsonism, including Parkinsons disease. Between Jan 1, 2004, and April 30, 2009, all physicians in the Umeå catchment area were requested to refer all individuals with suspected parkinsonism to the Department of Neurology at Umeå University. Included patients fulfilled the UK Parkinsons Disease Society Brain Bank clinical diagnostic criteria for Parkinsons disease. Control individuals were matched on the basis of age and sex with the first 50 patients included in the study. Participants who scored 1·5 SDs or more below the population mean on at least two cognitive measures were diagnosed with MCI. The primary outcome measures were functional MRI blood-oxygen-level-dependent signal and SPECT presynaptic uptake. Functional MRI was done during a verbal two-back working memory task. Presynaptic dopamine SPECT was done to assess presynaptic striatal dopaminergic system integrity. Event-related transient analyses of functional MRI data were done for the whole brain and for frontostriatal regions of interest, and semi-quantitative SPECT analyses were done for striatal regions of interest.nnnFINDINGSnCompared with controls (n=24), patients with Parkinsons disease (n=77) had under-recruitment in an extensive brain network including bilateral striatal and frontal regions (p<0·001). Within the Parkinsons disease group, patients with Parkinsons disease and MCI (n=30) had additional under-recruitment in the right dorsal caudate nucleus (p=0·005) and the bilateral anterior cingulate cortex (p<0·001) compared with patients with Parkinsons disease without MCI (n=26). In patients with Parkinsons disease and MCI, SPECT uptake in the right caudate was lower than in patients with Parkinsons disease without MCI (p=0·008) and correlated with striatal functional MRI blood-oxygen-level-dependent signal (r=0·32, p=0·031).nnnINTERPRETATIONnThese altered brain responses in patients with Parkinsons disease and MCI suggest that cognitive impairment is linked to frontostriatal dysfunction.nnnFUNDINGnSwedish Medical Research Council, Swedish Parkinson Foundation, Swedish Parkinsons Disease Association, Umeå University, Kempe Foundation, Foundation for Clinical Neuroscience at Umeå University Hospital, Västerbotten County Council (ALF), King Gustaf Vs and Queen Victorias Freemason Foundation, Knut and Alice Wallenberg Foundation, and Swedish Brain Power.

Opposing Effects of Aging on Large-Scale Brain Systems for Memory Encoding and Cognitive Control

Episodic memory declines with advancing age. Neuroimaging studies have associated such decline to age-related changes in general cognitive-control networks as well as to changes in process-specific encoding or retrieval networks. To assess the specific influence of aging on encoding and retrieval processes and associated brain systems, it is vital to dissociate encoding and retrieval from each other and from shared cognitive-control processes. We used multivariate partial-least-squares to analyze functional magnetic resonance imaging data from a large population-based sample (n = 292, 25–80 years). The participants performed a face-name paired-associates task and an active baseline task. The analysis revealed two significant network patterns. The first reflected a process-general encoding-retrieval network that included frontoparietal cortices and posterior hippocampus. The second pattern dissociated encoding and retrieval networks. The anterior hippocampus was differentially engaged during encoding. Brain scores, representing whole-brain integrated measures of how strongly an individual recruited a brain network, were correlated with cognitive performance and chronological age. The scores from the general cognitive-control network correlated negatively with episodic memory performance and positively with age. The encoding brain scores, which strongly reflected hippocampal functioning, correlated positively with episodic memory performance and negatively with age. Univariate analyses confirmed that bilateral hippocampus showed the most pronounced activity reduction in older age, and brain structure analyses found that the activity reduction partly related to hippocampus atrophy. Collectively, these findings suggest that age-related structural brain changes underlie age-related reductions in the efficient recruitment of a process-specific encoding network, which cascades into upregulated recruitment of a general cognitive-control network.

The claustrum/insula region integrates conceptually related sounds and pictures.

The brain is able to create coherent percepts from multisensory input. This phenomenon, known as multisensory integration (MSI), is a ubiquitous feature of everyday life and has been found to be essential for a reliable interaction with the environment. Recent functional neuroimaging studies suggest that several different networks are engaged in various forms of MSI depending on the nature of information being integrated. However, little is known about the neural basis of a fundamental form of MSI in natural conditions; integration of common auditory and visual objects which are conceptually related, such as when we look at a cat and hear a meowing sound. Here we used event-related fMRI to compare the brain response to conceptually related and unrelated pairs of audio-visual stimuli denoting common objects. Our protocol was designed to preclude contamination of the results by cognitive processes additional to those needed for MSI. The results indicate that higher-order temporal and occipital areas respond to coincident sounds and pictures regardless of their semantic relationship; whereas, the right claustrum/insula region is differentially activated in association with multisensory integration of conceptually related common objects. This observation has important implications for understanding how multimodal information about common objects is represented in the brain.

Neurocognitive Systems Related to Real-World Prospective Memory

Background Prospective memory (PM) denotes the ability to remember to perform actions in the future. It has been argued that standard laboratory paradigms fail to capture core aspects of PM. Methodology/Principal Findings We combined functional MRI, virtual reality, eye-tracking and verbal reports to explore the dynamic allocation of neurocognitive processes during a naturalistic PM task where individuals performed errands in a realistic model of their residential town. Based on eye movement data and verbal reports, we modeled PM as an iterative loop of five sustained and transient phases: intention maintenance before target detection (TD), TD, intention maintenance after TD, action, and switching, the latter representing the activation of a new intention in mind. The fMRI analyses revealed continuous engagement of a top-down fronto-parietal network throughout the entire task, likely subserving goal maintenance in mind. In addition, a shift was observed from a perceptual (occipital) system while searching for places to go, to a mnemonic (temporo-parietal, fronto-hippocampal) system for remembering what actions to perform after TD. Updating of the top-down fronto-parietal network occurred at both TD and switching, the latter likely also being characterized by frontopolar activity. Conclusion/Significance Taken together, these findings show how brain systems complementary interact during real-world PM, and support a more complete model of PM that can be applied to naturalistic PM tasks and that we named PROspective MEmory DYnamic (PROMEDY) model because of its dynamics on both multi-phase iteration and the interactions of distinct neurocognitive networks.