Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition.

Studies with experimental animals have revealed a mood-regulating neural pathway linking intrinsically photosensitive retinal ganglion cells (ipRGCs) and the prefrontal cortex (PFC), involved in the pathophysiology of mood disorders. Since humans also have light-intensity-encoding ipRGCs, we asked whether a similar pathway exists in humans. Here, functional MRI was used to identify PFC regions and other areas exhibiting light-intensity-dependent signals. We report 26 human brain regions having activation that either monotonically decreases or monotonically increases with light intensity. Luxotonic-related activation occurred across the cerebral cortex, in diverse subcortical structures, and in the cerebellum, encompassing regions with functions related to visual image formation, motor control, cognition, and emotion. Light suppressed PFC activation, which monotonically decreased with increasing light intensity. The sustained time course of light-evoked PFC responses and their susceptibility to prior light exposure resembled those of ipRGCs. These findings offer a functional link between light exposure and PFC-mediated cognitive and affective phenomena.

Visual perceptual learning of a primitive feature in human V1/V2 as a result of unconscious processing, revealed by decoded functional MRI neurofeedback (DecNef).

Although numerous studies have shown that visual perceptual learning (VPL) occurs as a result of exposure to a visual feature in a task-irrelevant manner, the underlying neural mechanism is poorly understood. In a previous psychophysical study (Watanabe et al., 2002), subjects were repeatedly exposed to a task-irrelevant Sekuler motion display that induced the perception of not only the local motions, but also a global motionmoving in the direction of the spatiotemporal average of the local motion vectors. As a result of this exposure, subjects enhanced their sensitivity only to the local moving directions, suggesting that early visual areas (V1/V2) that process local motions are involved in task-irrelevant VPL. However, this hypothesis has never been tested directly using neuronal recordings. Here, we employed a decoded neurofeedback technique (DecNef) using functional magnetic resonance imaging in human subjects to examine the involvement of early visual areas (V1/V2) in task-irrelevant VPL of local motion within a Sekuler motion display. During the DecNef training, subjects were trained to induce the activity patterns in V1/V2 that were similar to those evoked by the actual presentation of the Sekuler motion display. The DecNef training was conducted with neither the actual presentation of the display nor the subjects' awareness of the purpose of the experiment. After the experiment, subjects reported that they neither perceived nor imagined the trained motion during the DecNef training. As a result of DecNef training, subjects increased their sensitivity to the local motion directions, but not specifically to the global motion direction. Neuronal changes related to DecNef training were confined to V1/V2. These results suggest that V1/V2 are involved in exposure-based task-irrelevant VPL of local motion.

Not all attention orienting is created equal: recognition memory is enhanced when attention orienting involves distractor suppression.

Learning through visual exploration often requires orienting of attention to meaningful information in a cluttered world. Previous work has shown that attention modulates visual cortex activity, with enhanced activity for attended targets and suppressed activity for competing inputs, thus enhancing the visual experience. Here we examined the idea that learning may be engaged differentially with variations in attention orienting mechanisms that drive eye movements during visual search and exploration. We hypothesized that attention orienting mechanisms that engaged suppression of a previously attended location would boost memory encoding of the currently attended target objects to a greater extent than those that involve target enhancement alone. To test this hypothesis we capitalized on the classic spatial cueing task and the inhibition of return (IOR) mechanism (Posner, 1980; Posner, Rafal, & Choate, 1985) to demonstrate that object images encoded in the context of concurrent suppression at a previously attended location were encoded more effectively and remembered better than those encoded without concurrent suppression. Furthermore, fMRI analyses revealed that this memory benefit was driven by attention modulation of visual cortex activity, as increased suppression of the previously attended location in visual cortex during target object encoding predicted better subsequent recognition memory performance. These results suggest that not all attention orienting impacts learning and memory equally.

Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months.

BACKGROUND: Amyloid accumulation in the brain parenchyma is a hallmark of Alzheimer's disease (AD) and is seen in normal aging. Alterations in cerebrospinal fluid (CSF) dynamics are also associated with normal aging and AD. This study analyzed CSF volume, production and turnover rate in relation to amyloid-beta peptide (Aß) accumulation in the aging rat brain. METHODS: Aging Fischer 344/Brown-Norway hybrid rats at 3, 12, 20, and 30 months were studied. CSF production was measured by ventriculo-cisternal perfusion with blue dextran in artificial CSF; CSF volume by MRI; and CSF turnover rate by dividing the CSF production rate by the volume of the CSF space. Aß40 and Aß42 concentrations in the cortex and hippocampus were measured by ELISA. RESULTS: There was a significant linear increase in total cranial CSF volume with age: 3-20 months (p < 0.01); 3-30 months (p < 0.001). CSF production rate increased from 3-12 months (p < 0.01) and decreased from 12-30 months (p < 0.05). CSF turnover showed an initial increase from 3 months (9.40 day-1) to 12 months (11.30 day-1) and then a decrease to 20 months (10.23 day-1) and 30 months (6.62 day-1). Aß40 and Aß42 concentrations in brain increased from 3-30 months (p < 0.001). Both Aß42 and Aß40 concentrations approached a steady state level by 30 months. CONCLUSIONS: In young rats there is no correlation between CSF turnover and Aß brain concentrations. After 12 months, CSF turnover decreases as brain Aß continues to accumulate. This decrease in CSF turnover rate may be one of several clearance pathway alterations that influence age-related accumulation of brain amyloid.

Neural systems underlying lexical competition: an eye tracking and fMRI study.

The present study investigated the neural bases of phonological onset competition using an eye tracking paradigm coupled with fMRI. Eighteen subjects were presented with an auditory target (e.g., beaker) and a visual display containing a pictorial representation of the target (e.g., beaker), an onset competitor (e.g., beetle), and two phonologically and semantically unrelated objects (e.g., shoe, hammer). Behavioral results replicated earlier research showing increased looks to the onset competitor compared to the unrelated items. fMRI results showed that lexical competition induced by shared phonological onsets recruits both frontal structures and posterior structures. Specifically, comparison between competitor and no-competitor trials elicited activation in two nonoverlapping clusters in the left IFG, one located primarily within BA 44 and the other primarily located within BA 45, and one cluster in the left supramarginal gyrus (SMG) extending into the posterior superior temporal gyrus. These results indicate that the left IFG is sensitive to competition driven by phonological similarity and not only to competition among semantic/conceptual factors. Moreover, they indicate that the SMG is not only recruited in tasks requiring access to lexical form but is also recruited in tasks that require access to the conceptual representation of a word.

ERP correlates of anticipatory attention: spatial and non-spatial specificity and relation to subsequent selective attention.

Brain-based models of visual attention hypothesize that attention-related benefits afforded to imperative stimuli occur via enhancement of neural activity associated with relevant spatial and non-spatial features. When relevant information is available in advance of a stimulus, anticipatory deployment processes are likely to facilitate allocation of attention to stimulus properties prior to its arrival. The current study recorded EEG from humans during a centrally-cued covert attention task. Cues indicated relevance of left or right visual field locations for an upcoming motion or orientation discrimination. During a 1 s delay between cue and S2, multiple attention-related events occurred at frontal, parietal and occipital electrode sites. Differences in anticipatory activity associated with the non-spatial task properties were found late in the delay, while spatially-specific modulation of activity occurred during both early and late periods and continued during S2 processing. The magnitude of anticipatory activity preceding the S2 at frontal scalp sites (and not occipital) was predictive of the magnitude of subsequent selective attention effects on the S2 event-related potentials observed at occipital electrodes. Results support the existence of multiple anticipatory attention-related processes, some with differing specificity for spatial and non-spatial task properties, and the hypothesis that levels of activity in anterior areas are important for effective control of subsequent S2 selective attention.

The relation of brain oscillations to attentional networks.

Previous studies have suggested the relation of particular frequency bands such as theta (4-8 Hz), alpha (8-14 Hz), beta (14-30 Hz), or gamma (>30 Hz) to cognitive functions. However, there has been controversy over which bands are specifically related to attention. We used the attention network test to separate three anatomically defined brain networks that carry out the functions of alerting, orienting, and executive control of attention. High-density scalp electrical recording was performed to record synchronous oscillatory activity and power spectrum analyses based on functional magnetic resonance imaging constrained dipole modeling were conducted for each attentional network. We found that each attentional network has a distinct set of oscillations related to its activity. The alerting network showed a specific decrease in theta-, alpha-, and beta-band activity 200-450 ms after a warning signal. The orienting network showed an increase in gamma-band activity at approximately 200 ms after a spatial cue, indicating the location of a target. The executive control network revealed a complex pattern when a target was surrounded with incongruent flankers compared with congruent flankers. There was an early (<400 ms) increase in gamma-band activity, a later (>400 ms) decrease in beta- and low gamma-band activity after the target onset, and a decrease of all frequency bands before response followed by an increase after the response. These data demonstrate that attention is not related to any single frequency band but that each network has a distinct oscillatory activity and time course.

Context modulates early stimulus processing when resolving stimulus-response conflict.

When responding to stimuli in our environment, the presence of multiple items associated with task-relevant responses affects both ongoing response selection and subsequent behavior. Computational modeling of conflict monitoring and neuroimaging data predict that the recent context of response competition will bias the selection of certain stimuli over others very early in the processing stream through increased focal spatial attention. We used high-density EEG to test this hypothesis and to investigate the contextual effects on nonspatial, early stimulus processing in a modified flanker task. Subjects were required to respond to a central arrow and to ignore potentially conflicting information from flanking arrows in trials preceded by a series of either compatible or incompatible trials. On some trials, we presented the flanking arrows in the absence of the central target. The visual P1 component was selectively enhanced only for incompatible trials when preceded by incompatible ones, suggesting that contextual effects depend on feature-based processing, and not only simple enhancement of the target location. Context effects also occurred on no-target trials as evidenced by an enhanced early-evoked response when they followed compatible compared to incompatible trials, suggesting that spatial attention was also modulated by recent context. These results support a multi-componential account of spatial and nonspatial attention and they suggest that contextually driven cognitive control mechanisms can operate on specific stimulus features at extremely early stages of processing within stimulus-response conflict tasks.

Inattentional amnesia to words in a high attentional load task.

We investigated the dependence of visual word processes on attention by examining event-related potential (ERP) responses as subjects viewed words while their attention was engaged by a concurrent highly demanding task. We used a paradigm from a previous functional magnetic resonance imaging (fMRI) experiment [Rees, G., Russel, C., Frith, C. D., & Driver, J. Inattentional blindness vs. inattentional amnesia for fixated but ignored words. Science, 286, 2504-2506, 1999] in which participants attended either to drawings or to overlapping letters (words or nonwords) presented at a fast rate. Although previous fMRI results supported the notion that word processing was obliterated by attention withdrawal, the current electrophysiological results demonstrated that visual words are processed even under conditions in which attentional resources are engaged in a different task that does not involve reading. In two experiments, ERPs for attended words versus nonwords differed in the left frontal, left posterior, and medial scalp locations. However, in contrast to the previous fMRI results, ERPs responded differentially to ignored words and consonant strings in several regions. These results suggest that fMRI and ERPs may have differential sensitivity to some forms of neural activation. Moreover, they provide evidence to restore the notion that the brain analyzes words even when attention is tied to another dimension.

Evidence of developmental differences in implicit sequence learning: an fMRI study of children and adults.

Prevailing theories of implicit or unaware learning propose a developmental invariance model, with implicit function maturing early in infancy or childhood despite prolonged improvements in explicit or intentional learning and memory systems across childhood. Neuroimaging studies of adult visuomotor sequence learning have associated fronto-striatal brain regions with implicit learning of spatial sequences. Given evidence of continued development in these brain regions during childhood, we compare implicit sequence learning in adults and 7- to 11-year-old children to examine potential developmental differences in the recruitment of fronto-striatal circuitry during implicit learning. Participants performed a standard serial reaction time task. Stimuli alternately followed a fixed 10-step sequence of locations or were presented in a pseudorandom order of locations. Adults outperformed children, achieving a significantly larger sequence learning effect and showing learning more quickly than children. Age-related differences in activity were observed in the premotor cortex, putamen, hippocampus, inferotemporal cortex, and parietal cortex. We observed differential recruitment of cortical and subcortical motor systems between groups, presumably reflecting age differences in motor response execution. Adults showed greater hippocampal activity for sequence trials, whereas children demonstrated greater signal during random trials. Activity in the right caudate correlated significantly with behavioral measures of implicit learning for both age groups, although adults showed greater signal change than children overall, as would be expected given developmental differences in sequence learning magnitude. These results challenge the idea of developmental invariance in implicit learning and instead support a view of parallel developments in implicit and explicit learning systems.