Biology subjects

Cabeza, R.

Publications and source records attributed to Cabeza, R..

25 records · Page 2Linked to original sources

bioRxiv2019

Application of long-interval paired-pulse transcranial magnetic stimulation to motion-sensitive visual cortex does not lead to changes in motion perception

The perception of visual motion is dependent on a set of occipitotemporal regions which are readily accessible to neuromodulation. Previous studies using paired-pulse Transcranial Magnetic Stimulation (ppTMS) have provided evidence of the capacity of this type of protocols to modulate cognitive processes. To test whether such cortical modulation can be observed in the visual system, particularly during motion perception, ppTMS was applied to the occipital cortex using both scalp-based and meta-analytic targeting coordinates. In this within-subject, sham-controlled study, fifteen subjects completed two sessions in two consecutive weeks. On the first visit, subject-specific resting motor threshold (RMT) was determined and participants performed an adaptive motion discrimination task to determine individual motion sensitivity. During the second visit, subjects performed the same task with three individualized difficulty levels as two TMS pulses were delivered respectively -150 and -50 ms prior to motion stimulus onset at 120% RMT, under the logic that the cumulative inhibitory effect of these two pulses would alter motion sensitivity as measured by the individually calibrated task. The ppTMS was delivered at one of two locations: 3 cm dorsal and 5 cm lateral to inion (scalp-based coordinate), or at the site of peak activation for \"motion\" according to the NeuroSynth fMRI database (meta-analytic coordinate). Sham stimulation was delivered on one-third of trials and evenly between the two targets. Analyses showed no significant active-versus-sham effects of ppTMS when stimulation was delivered to the meta-analytic (p = 0.15) or scalp-based coordinates (p = 0.17), which were separated by 29 mm on average. Additionally, there was no was significant interaction between ppTMS at either location and task difficulty level (p = 0.12 and p = 0.33, respectively). These findings fail to support the hypothesis that long-interval ppTMS recruits inhibitory processes in motion-sensitive cortex, but must be considered within the limits of the current design choices.\n\nHIGHLIGHTSO_LILong-interval paired-pulse TMS was applied to visual cortex during a motion task\nC_LIO_LIThe ppTMS was delivered according to scalp and meta-analytic coordinates, as well as sham\nC_LIO_LINo effects of active-versus-sham stimulation were observed on motion task performance\nC_LI

neuroscience↗

bioRxiv2019

Older adults benefit from more widespread brain network integration during working memory

Neuroimaging evidence suggests that the aging brain relies on a more distributed set of cortical regions than younger adults in order to maintain successful levels of performance during demanding cognitive tasks. However, it remains unclear how task demands give rise to this age-related expansion in cortical networks. To investigate this issue, we used functional magnetic resonance imaging to measure univariate activity, network connectivity, and cognitive performance in younger and older adults during a working memory (WM) task. In the WM task investigated, participants hold letters online (maintenance) while reordering them alphabetically (manipulation). WM load was titrated to obtain four individualized difficulty levels. Network integration--defined as the ratio of within-versus between-network connectivity--was linked to individual differences in WM capacity. The study yielded three main findings. First, as task difficulty increased, network integration decreased in younger adults, whereas it increased in older adults. Second, age-related increases in network integration were driven by increases in right hemispheric connectivity to both left and right cortical regions, a finding that helps to reconcile extant theories of compensatory recruitment in aging to address the multivariate dynamics of global network functioning. Lastly, older adults with higher WM capacity demonstrated higher levels of network integration in the most difficult condition. These results shed light on the mechanisms of age-related network reorganization by suggesting that changes in network connectivity may act as an adaptive form of compensation, with older adults recruiting a more distributed cortical network as task demands increase.\n\nSignificance statementOlder adults often activate brain regions not engaged by younger adults, but the circumstances under which this widespread network emerges are unclear. Here, we examined the effects of aging on network connectivity between task regions recruited during a working memory (WM) manipulation task, and the rest of the brain. We found an age-related increase in the more global network integration in older adults, and an association between this integration and working memory capacity in older adults. The findings are generally consistent with the compensatory interpretation of these effects.

neuroscience↗

bioRxiv2019

Site-specific effects of online rTMS during a working memory task in healthy older adults.

The process of manipulating information within working memory (WM) is central to many cognitive functions, but also declines rapidly in old age. Given the importance of WM manipulation for maintaining healthy cognition, improving this process could markedly enhance health-span in older adults. The current pre-registered study tested the potential of online repetitive transcranial magnetic stimulation (rTMS) to enhance WM manipulation in healthy elderly adults. Online 5Hz rTMS was applied over the left lateral parietal cortex of 15 subjects to test the hypothesis that active rTMS would significantly improve performance compared to sham stimulation, and that these effects would be most pronounced in conditions with the highest cognitive demand. rTMS was applied while participants performed a delayed-response alphabetization task with two individually-titrated levels of difficulty. Sham stimulation was applied using an electrical sham coil that produced similar clicking sounds and somatosensory sensation as active stimulation but induced negligible effects on the brain. A stimulation site in left lateral parietal cortex was identified from fMRI activation maps and was targeted using individualized electric field modeling, stereotactic neuronavigation, and real-time robotic positioning, allowing optimal coil placement during the stimulation. Contrary to the a priori hypothesis, active rTMS significantly decreased accuracy relative to sham, and only in the hardest difficulty level. These results, therefore, demonstrate engagement of cortical WM processing, but not the anticipated facilitation, and provide a prescription for future studies that may attempt to enhance memory through application of different stimulation parameters.\n\nHighlightsO_LIThis study is one of the first attempts to enhance WM manipulation with online rTMS\nC_LIO_LIOnline 5Hz rTMS and sham were applied over the left parietal cortex of older adults\nC_LIO_LIIndividualized fMRI and electric field modeling were used to optimize targeting\nC_LIO_LIContrary to expectations, rTMS disrupted working memory manipulation abilities\nC_LIO_LIThis demonstrates that parietal cortex is involved in WM and modifiable with rTMS\nC_LI

neuroscience↗

bioRxiv2018

Complementary topology of maintenance and manipulation brain networks in working memory

Working memory (WM) is assumed to consist of a process that sustains memory representations in an active state (maintenance) and a process that operates on these activated representations (manipulation). Prior fMRI studies have examined maintenance and manipulation in separate task conditions, whereas in real life these processes operate simultaneously. In the current study, the neural mechanisms of maintenance and manipulation were disentangled during the same task by parametrically varying these processes. During fMRI, participants maintained consonant letters in WM while sorting them in alphabetical order. Maintenance was investigated by varying the number of letters held in WM and manipulation by varying the number of moves required to sort the list alphabetically. The study yielded three main findings. First, the degree of both maintenance and manipulation demand had significant effects on behavior that were associated with different cortical regions: maintenance was associated with bilateral prefrontal and left parietal cortex, and manipulation with right parietal activity, a link that is consistent with the role of parietal cortex in symbolic computations. Second, univariate fMRI and tractography based on diffusion-weighted imaging showed that maintenance and manipulation regions are supported by two dissociable structural networks. Finally, maintenance and manipulation functional networks became increasingly segregated with increasing demand, possibly reflecting the protection of information held in WM from interference generated by manipulation operations. These results represent a novel approach to study the brain as an adaptive system that coordinates multiple ongoing cognitive processes.\n\nSignificance StatementDespite the importance of working memory (WM) in everyday life, little is known about how the brain is able to simultaneously maintain and manipulate information stored in short-term memory buffers. We examined evidence for two distinct, concurrent cognitive functions supporting maintenance and manipulation abilities by testing brain activity as participants performed a WM alphabetization task. We found behavioral and neural evidence in support of dissociable cognitive functions associated with these two operations. Furthermore, we found that connectivity between these networks was increasingly segregated as difficulty increased, and that this effect was positively related to individual WM ability. These results provide evidence that network segregation may act as a protective mechanism to enable successful performance under increasing WM demand.

neuroscience↗

bioRxiv2018

Excitatory TMS Boosts Memory Representations

Brain stimulation technologies have seen increasing application in basic science investigations, specifically towards the goal of improving memory functioning. However, proposals concerning the neural mechanisms underlying cognitive enhancement often rely on simplified notions of excitation and, most applications examining the effects of transcranial magnetic stimulation (TMS) on functional neuroimaging measures have been limited to univariate analyses of brain activity. We present here analyses using representational similarity analysis (RSA) and encoding-retrieval similarity (ERS) analysis in order to quantify the effect of TMS on memory representations. To test whether an increase in local excitability in PFC can have measurable influences on upstream representations in earlier temporal memory regions, we compared 1Hz and 5Hz stimulation to the left dorsolateral PFC. We found that 10 minutes of 5Hz rTMS, relative to 1Hz, had multiple effects on neural representations: 1) greater RSA during both encoding and retrieval, 2) greater ERS across all items, and, critically, 3) increasing ERS in MTL with increasing univariate activity in DLPFC, and greater functional connectivity for hits than misses between these regions. These results provide the first evidence of rTMS enhancing semantic representations and strengthen the idea that rTMS may affect the reinstatement of previously experienced events in upstream regions.

neuroscience↗

bioRxiv2018

A systematic study of repetitive transcranial magnetic stimulation to enhance working memory manipulation abilities

A core element of human working memory (WM) is the ability to perform mental operations on information that is stored in a flexible, limited capacity buffer. Given the profound importance of such WM manipulation (WM-M) abilities, there is a concerted effort aimed at developing approaches to improve them. Past research has identified neural substrates of WM-M centered in the dorsolateral prefrontal cortex (DLPFC), thereby providing a plausible and accessible target for noninvasive neuromodulatory stimulation that can be used to alter cortical excitability and potentially lead to facilitation of WM-M. In the current study, 5Hz online repetitive transcranial magnetic stimulation (rTMS), applied over the left DLPFC, was used to test the hypothesis that active rTMS would lead to significant improvements in memory recall accuracy compared to sham stimulation, and that these effects would be most pronounced in the WM-M conditions with the highest cognitive demand (registered Clinical Trial: #NCT02767323). Participants performed a delayed response alphabetization task with three individually-titrated levels of difficulty during active and sham rTMS. Analyses revealed that active rTMS led to numerically greater accuracy relative to sham stimulation for the hardest condition; however, this effect did not survive Bonferroni correction over all task conditions. Despite the lack of robust, study-wise significant effects, when considered in isolation, the magnitude of behavioral improvement in the hardest condition was negatively correlated with parametric difficulty-related fMRI activity in the targeted brain region, suggesting that individuals with less activation benefit more from rTMS. The present findings therefore suggest evidence towards the hypothesis that active rTMS can enhance performance during difficult memory manipulation conditions; however, firm conclusions cannot be drawn given the lack of overall significant effects. These findings are discussed in the context of individualized targeting and other factors that might moderate rTMS effects.

neuroscience↗

bioRxiv2017

Cooperative Contributions of Structural and Functional Connectivity to Successful Memory and Aging

Understanding the precise relation between functional connectivity and structural (white-matter) connectivity and how these relationships account for cognitive changes in older adults are major challenges for neuroscience. We investigate these issues using a new approach in which structural equation modeling (SEM) is employed to integrate functional and structural connectivity data analyzed with a common framework based on regions connected by canonical tract groups (CTGs). CTGs (e.g., uncinate fasciculus, cingulum, etc.) serve as a common currency between functional and structural connectivity matrices, and ensures that the same amount of data contributing to brain-behavior relationships. We used this approach to investigate the neural mechanisms supporting memory for items and memory for associations, and how they are affected by healthy aging. Our results are threefold. Firstly, structural and functional CTGs made independent contributions to associative memory performance, suggesting that both forms of connectivity underlie age-related changes in associative memory. Secondly, distinct groups of CTGs supported associative versus item memory. Lastly, the relationship between functional and structural connectivity was best explained by the relationship between latent variables describing functional and structural CTGs based on a constrained set of tracts--but no one specific CTG group--suggesting that age effects in connectivity are constrained to specific pathways. These results provide further insights into the interplay between structural and functional connectivity patterns, and help to elucidate their relative contribution to age-related changes in associative memory performance.

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