Theodore P. Zanto

Causal role of the prefrontal cortex in top-down modulation of visual processing and working memory

Selective attention filters information to limit what is encoded and maintained in working memory. Although the prefrontal cortex (PFC) is central to both selective attention and working memory, the underlying neural processes that link these cognitive abilities remain elusive. Using functional magnetic resonance imaging to guide repetitive transcranial magnetic stimulation with electroencephalographic recordings in humans, we perturbed PFC function at the inferior frontal junction in participants before they performed a selective-attention, delayed-recognition task. This resulted in diminished top-down modulation of activity in posterior cortex during early encoding stages, which predicted a subsequent decrement in working memory accuracy. Participants with stronger fronto-posterior functional connectivity displayed greater disruptive effects. Our data further suggests that broad alpha-band (7–14 Hz) phase coherence subserved this long-distance top-down modulation. These results suggest that top-down modulation mediated by the prefrontal cortex is a causal link between early attentional processes and subsequent memory performance.

Neural Suppression of Irrelevant Information Underlies Optimal Working Memory Performance

Our ability to focus attention on task-relevant information and ignore distractions is reflected by differential enhancement and suppression of neural activity in sensory cortex (i.e., top-down modulation). Such selective, goal-directed modulation of activity may be intimately related to memory, such that the focus of attention biases the likelihood of successfully maintaining relevant information by limiting interference from irrelevant stimuli. Despite recent studies elucidating the mechanistic overlap between attention and memory, the relationship between top-down modulation of visual processing during working memory (WM) encoding, and subsequent recognition performance has not yet been established. Here, we provide neurophysiological evidence in healthy, young adults that top-down modulation of early visual processing (< 200 ms from stimulus onset) is intimately related to subsequent WM performance, such that the likelihood of successfully remembering relevant information is associated with limiting interference from irrelevant stimuli. The consequences of a failure to ignore distractors on recognition performance was replicated for two types of feature-based memory, motion direction and color. Moreover, attention to irrelevant stimuli was reflected neurally during the WM maintenance period as an increased memory load. These results suggest that neural enhancement of relevant information is not the primary determinant of high-level performance, but rather optimal WM performance is dependent on effectively filtering irrelevant information through neural suppression to prevent overloading a limited memory capacity.

The Influence of Perceptual Training on Working Memory in Older Adults

Normal aging is associated with a degradation of perceptual abilities and a decline in higher-level cognitive functions, notably working memory. To remediate age-related deficits, cognitive training programs are increasingly being developed. However, it is not yet definitively established if, and by what mechanisms, training ameliorates effects of cognitive aging. Furthermore, a major factor impeding the success of training programs is a frequent failure of training to transfer benefits to untrained abilities. Here, we offer the first evidence of direct transfer-of-benefits from perceptual discrimination training to working memory performance in older adults. Moreover, using electroencephalography to evaluate participants before and after training, we reveal neural evidence of functional plasticity in older adult brains, such that training-induced modifications in early visual processing during stimulus encoding predict working memory accuracy improvements. These findings demonstrate the strength of the perceptual discrimination training approach by offering clear psychophysical evidence of transfer-of-benefit and a neural mechanism underlying cognitive improvement.

Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer's disease: a systematic review and meta-analysis

The study aimed to evaluate the effects of noninvasive brain stimulation on cognitive function in healthy older adults and patients with Alzheimers disease. A comprehensive literature search was performed on noninvasive stimulation studies published from January 1990 to November 2014 in Pubmed and Web of Science. Fourteen articles with a total of 331 participants were identified as studies with healthy older adults, and the mean effect size and 95% confidence interval were estimated. A significant effect size of 0.42 was found for the cognitive outcome. Further subgroup analyses demonstrated more prominent effects for studies delivering the stimulation before the execution of the task and studies applying multiple sessions of stimulation. To assess the effects of stimulation on Alzheimers disease patients, 11 studies with a total of 200 patients were included in the analysis. A significant effect size of 1.35 was found for the cognitive outcomes. Subgroup analyses indicated more pronounced effects for studies applying the stimulation during the execution of the task compared with studies delivering the stimulation before the execution of the task. Noninvasive brain stimulation has a positive effect on cognitive function in physiological and pathological aging.

Top-down modulation of visual feature processing: The role of the inferior frontal junction

Distinct areas within the visual association cortex are specialized for representing specific stimulus features, such as V4 for color and V5/hMT+ for motion. Recent studies have demonstrated that areas associated with attended features exhibit enhanced cortical activity, whereas those associated with ignored features elicit reduced activity. However, the source of this attentional (or top-down) modulation remains uncertain. A network of fronto-parietal cortical regions has been proposed as the prime candidate underlying this top-down modulation. Here, we evaluate whether there are distinct or overlapping top-down network regions for attention to different stimulus features. To this end, we explored functional magnetic resonance imaging (fMRI) functional connectivity data, electroencephalographic (EEG) source localization, and phase coherence that were obtained while participants attended or ignored motion and color stimuli. Functional connectivity analysis indicated that attention to color relies strongly on prefrontal regions, whereas attention to motion recruits both prefrontal and parietal areas. Although these networks are generally topologically segregated, both color and motion processes recruit right inferior frontal junction (IFJ). However, the IFJ may be more critical for color processing, as only connectivity with V4 predicted the degree of attentional modulation. Source localization at the time range of attentional modulation of the event related potential corroborated the role of the right IFJ and indicated that feature-based, top-down modulation occurs early during processing (< 200ms post-stimulus onset). Furthermore, long-distance alpha (8-12Hz) phase coherence between the IFJ and visual cortices may serve as a mechanism underlying anticipatory, top-down modulation of color feature processing.

Fronto-parietal network: flexible hub of cognitive control

A recent study shows that the fronto-parietal network (FPN), and subregions therein, alters its functional connectivity with nodes of other networks based on task goals. Moreover, FPN patterns of connectivity not only reflect engagement of specific tasks, but also serve as a code that can be transferred to facilitate learning novel tasks.

Age-Related Changes in Orienting Attention in Time

Temporal cues guide attentional resources toward relevant points in time, resulting in optimized behavioral performance. Although deficits in aspects of attention have been documented in older adults, it remains unknown whether the critical ability to orient attention in time is affected by normal aging. To address this, younger and older adults participated in a temporally cued target–response experiment while electroencephalographic data were recorded. Three conditions (one detection and two discrimination tasks) were used to manipulate task complexity. Response times show that younger adults, but not older adults, used temporal cues to enhance performance regardless of task complexity. Similarly, alpha band activity (8–12 Hz) and the contingent negative variation preceding targets indicated that only younger adults engaged prestimulus, anticipatory neural mechanisms associated with temporal cues. Overall, these results provide novel evidence that older adults do not use temporal cues to orient attention in time and support an expectation deficit in normal aging.

Expectation-Driven Changes in Cortical Functional Connectivity Influence Working Memory and Long-Term Memory Performance

Expectations generated by predictive cues increase the efficiency of perceptual processing for complex stimuli (e.g., faces, scenes); however, the impact this has on working memory (WM) and long-term memory (LTM) has not yet been investigated. Here, healthy young adults performed delayed-recognition tasks that differed only in stimulus category expectations, while behavioral and functional magnetic resonance imaging data were collected. Univariate and functional-connectivity analyses were used to examine expectation-driven, prestimulus neural modulation, networks that regulate this modulation, and subsequent memory performance. Results revealed that predictive category cueing was associated with both enhanced WM and LTM for faces, as well as baseline activity shifts in a face-selective region of the visual association cortex [i.e., fusiform face area (FFA)]. In addition, the degree of functional connectivity between FFA and right inferior frontal junction (IFJ), middle frontal gyrus (MFG), inferior frontal gyrus, and intraparietal sulcus correlated with the magnitude of prestimulus activity modulation in the FFA. In an opposing manner, prestimulus connectivity between FFA and posterior cingulate cortex, a region of the default network, negatively correlated with FFA activity modulation. Moreover, whereas FFA connectivity with IFJ and the precuneus predicted enhanced expectation-related WM performance, FFA connectivity with MFG predicted LTM improvements. These findings suggest a model of expectancy-mediated neural biasing, in which a single node (e.g., FFA) can be dynamically linked or disconnected from different brain regions depending on prestimulus expectations, and the strength of distinct connections is associated with WM or LTM benefits.

Delays in neural processing during working memory encoding in normal aging.

Declines in neural processing speed have been proposed to underlie a broad range of cognitive deficits in older adults. However, the impact of delays in neural processing during stimulus encoding on working memory (WM) performance is not well understood. In the current study, we assessed the influence of aging on the relationship between neural measures of processing speed and WM performance during a selective delayed-recognition task for color and motion stimuli, while electroencephalography (EEG) was recorded in young and older adults. A latency delay was observed for the selection negativity (SN) and alpha band activity (measures of attentional allocation) in older adults during WM encoding of both motion and color stimuli, with the latency and magnitude of the SN predicting subsequent recognition performance. Furthermore, an age-related delay in the N1 latency occurred specifically during the encoding of color stimuli. These results suggest that the presence of both generalized feature-based and feature-specific deficits in the speed of selective encoding of information contributes to WM performance deficits in older adults.

Neural responses to complex auditory rhythms: the role of attending.

The aim of this study was to explore the role of attention in pulse and meter perception using complex rhythms. We used a selective attention paradigm in which participants attended to either a complex auditory rhythm or a visually presented word list. Performance on a reproduction task was used to gauge whether participants were attending to the appropriate stimulus. We hypothesized that attention to complex rhythms – which contain no energy at the pulse frequency – would lead to activations in motor areas involved in pulse perception. Moreover, because multiple repetitions of a complex rhythm are needed to perceive a pulse, activations in pulse-related areas would be seen only after sufficient time had elapsed for pulse perception to develop. Selective attention was also expected to modulate activity in sensory areas specific to the modality. We found that selective attention to rhythms led to increased BOLD responses in basal ganglia, and basal ganglia activity was observed only after the rhythms had cycled enough times for a stable pulse percept to develop. These observations suggest that attention is needed to recruit motor activations associated with the perception of pulse in complex rhythms. Moreover, attention to the auditory stimulus enhanced activity in an attentional sensory network including primary auditory cortex, insula, anterior cingulate, and prefrontal cortex, and suppressed activity in sensory areas associated with attending to the visual stimulus.