The temporally graded memory impairment seen in many neurobehavioral disorders implies different neuroanatomical pathways and/or cognitive mechanisms involved in storage and retrieval of memories of different ages. A dynamic interaction between medial-temporal and neocortical brain regions has been proposed to account for memory's greater permanence with time. Despite considerable debate concerning its time-dependent role in memory retrieval, medial-temporal lobe activity has been well studied. However, the relative participation of neocortical regions in recent and remote memory retrieval has received much less attention. Using functional magnetic resonance imaging, we demonstrate robust, temporally graded signal differences in posterior cingulate, right middle frontal, right fusiform, and left middle temporal regions in healthy older adults during famous name identification from two disparate time epochs. Importantly, no neocortical regions demonstrated greater response to older than to recent stimuli. Our results suggest a possible role of these neocortical regions in temporally dating items in memory and in establishing and maintaining memory traces throughout the lifespan. Theoretical implications of these findings for the two dominant models of remote memory functioning (Consolidation Theory and Multiple Trace Theory) are discussed.

The hippocampus is critical for encoding and retrieving semantic and episodic memories. Animal studies indicate that the hippocampus is also required for relational learning tasks. A prototypical relational learning task, and the one investigated in this experiment, using event-related functional magnetic resonance imaging, is the transitive inference (TI) task. In the TI task, participants were to choose between A and B (A?B) and learned by trial and error to choose A (A > B). There were four such premise pairs during a training (A > B, B > C, C > D, D > E). These can be acquired distinctly or can be organized into a superordinate hierarchy (A > B > C > D > E), which would efficiently represent all the learned relations and allow inferences (e.g., B > D). At test there was no reinforcement: In addition to premise pairs, untrained pairings were introduced (e.g., A?E, B?D). Correctly inferring that B > D is taken as evidence for the formation of a superordinate hierarchy; several alternatives to the superordinate hierarchy hypothesis are considered. Awareness of the formation of this hierarchy was measured by a postscan questionnaire. Four main findings are reported: (1) Inferential performance and task awareness dissociated behaviorally and at the level of hemodynamic response; (2) As expected, performance on the inferred relation, B > D, corresponded to the ability to simultaneously acquire B > C and C > D premise pairs during training; (3) Interestingly, acquiring these “inner pairs” corresponded to greater hippocampal activation than the “outer pairs” (A > B, D > E) for all participants. However, a distinct pattern of hippocampal activity for these inner pairs differentiated those able to perform the inferential discrimination, B > D, at test. Because these inner premise pairs require contextual discrimination (e.g., C is incorrect in the context of B but correct in the context of D), we argue that the TI task is hippocampal-dependent because the premise pair acquisition necessary for inference is hippocampal-dependent; (4) We found B > D related hippocampal activity at test that is anatomically consistent with preconsolidation recall effects shown in other studies.

This event-related fMRI experiment examined the neural substrates of exogenous visuospatial attention. Exogenous attention produces a biphasic response pattern denoted by facilitation at short cue–target intervals and inhibition of return (IOR) at longer intervals. Whereas the volitional orienting of attention has been well described in the literature, the neural systems that support exogenous facilitation and IOR in humans are relatively unknown. In direct comparisons to valid facilitation trials, valid IOR trials produced unique foci of activation in the right posterior parietal, superior temporal, middle temporal, middle occipital, anterior cingulate, and dorsal medial thalamic areas. Valid IOR trials also resulted in activation of motor exploratory and frontal areas previously associated with inhibition and oculomotor control. In contrast, invalid IOR compared to facilitation trials only activated anterior cortical structures. These results provide support for both attentional and oculomotor theories of IOR and suggest that IOR may be mediated by two networks. One network may mediate the inhibitory bias following an exogenous cue, whereas a separate network may be activated when a response must be made to stimuli that appear in inhibited locations of space.

Studies in brain damaged patients conclude that the left hemisphere is dominant for controlling heterogeneous sequences performed by either hand, presumably due to the cognitive resources involved in planning complex sequential movements. To determine if this lateralized effect is due to asymmetries in primary sensorimotor or association cortex, whole-brain functional magnetic resonance imaging was used to measure differences in volume of activation while healthy right-handed subjects performed repetitive (simple) or heterogeneous (complex) finger sequences using the right or left hand. Advanced planning, as evidenced by reaction time to the first key press, was greater for the complex than simple sequences and for the left than right hand. In addition to the expected greater contralateral activation in the sensorimotor cortex (SMC), greater left hemisphere activation was observed for left, relative to right, hand movements in the ipsilateral left superior parietal area and for complex, relative to simple, sequences in the left premotor and parietal cortex, left thalamus, and bilateral cerebellum. No such volumetric asymmetries were observed in the SMC. Whereas the overall MR signal intensity was greater in the left than right SMC, the extent of this asymmetry did not vary with hand or complexity level. In contrast, signal intensity in the parietal and premotor cortex was greater in the left than right hemisphere and for the complex than simple sequences. Signal intensity in the caudal anterior cerebellum was greater bilaterally for the complex than simple sequences. These findings suggest that activity in the SMC is associated with execution requirements shared by the simple and complex sequences independent of their differential cognitive requirements. In contrast, consistent with data in brain damaged patients, the left dorsal premotor and parietal areas are engaged when advanced planning is required to perform complex motor sequences that require selection of different effectors and abstract organization of the sequence, regardless of the performing hand.

Objects play an important role in guiding spatial attention through a cluttered visual environment. We used event-related functional magnetic resonance imaging (ER-fMRI) to measure brain activity during cued discrimination tasks requiring subjects to orient attention either to a region bounded by an object (object-based spatial attention) or to an unbounded region of space (location-based spatial attention) in anticipation of an upcoming target. Comparison between the two tasks revealed greater activation when attention selected a region bounded by an object. This activation was strongly lateralized to the left hemisphere and formed a widely distributed network including (a) attentional structures in parietal and temporal cortex and thalamus, (b) ventral-stream object processing structures in occipital, inferior-temporal, and parahippocampal cortex, and (c) control structures in medial-and dorsolateral-prefrontal cortex. These results suggest that object-based spatial selection is achieved by imposing additional constraints over and above those processes already operating to achieve selection of an unbounded region. In addition, ER-fMRI methodology allowed a comparison of validly versus invalidly cued trials, thereby delineating brain structures involved in the reorientation of attention after its initial deployment proved incorrect. All areas of activation that differentiated between these two trial types resulted from greater activity during the invalid trials. This outcome suggests that all brain areas involved in attentional orienting and task performance in response to valid cues are also involved on invalid trials. During invalid trials, additional brain regions are recruited when a perceiver recovers from invalid cueing and reorients attention to a target appearing at an uncued location. Activated brain areas specific to attentional reorientation were strongly right-lateralized and included posterior temporal and inferior parietal regions previously implicated in visual attention processes, as well as prefrontal regions that likely subserve control processes, particularly related to inhibition of inappropriate responding.

The ease by which movements are combined into skilled actions depends on many factors, including the complexity of movement sequences. Complexity can be defined by the surface structure of a sequence, including motoric properties such as the types of effectors, and by the abstract or sequence-specific structure, which is apparent in the relations amongst movements, such as repetitions. It is not known whether different neural systems support the cognitive and the sensorimotor processes underlying different structural properties of sequential actions. We investigated this question using whole-brain functional magnetic resonance imaging (fMRI) in healthy adults as they performed sequences of five key presses involving up to three fingers. The structure of sequences was defined by two factors that independently lengthen the time to plan sequences before movement: the number of different fingers (1-3; surface structure) and the number of finger transitions (0-4; sequence-specific structure). The results showed that systems involved in visual processing (extrastriate cortex) and the preparation of sensory aspects of movement (rostral inferior parietal and ventral premotor cortex (PMv)) correlated with both properties of sequence structure. The number of different fingers positively correlated with activation intensity in the cerebellum and superior parietal cortex (anterior), systems associated with sensorimotor, and kinematic representations of movement, respectively. The number of finger transitions correlated with activation in systems previously associated with sequence-specific processing, including the inferior parietal and the dorsal premotor cortex (PMd), and in interconnecting superior temporal-middle frontal gyrus networks. Different patterns of activation in the left and right inferior parietal cortex were associated with different sequences, consistent with the speculation that sequences are encoded using different mnemonics, depending on the sequence-specific structure. In contrast, PMd activation correlated positively with increases in the number of transitions, consistent with the role of this area in the retrieval or preparation of abstract action plans. These findings suggest that the surface and the sequence-specific structure of sequential movements can be distinguished by distinct distributed systems that support their underlying mental operations.

Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80% of the time), exogenous (peripheral target preceded by a noninformative peripheral cue), and control (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.