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The apolipoprotein E (APOE) epsilon4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE epsilon4 with better episodic memory compared with APOE epsilon2 and epsilon3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas epsilon2 and epsilon3 carriers increased activity. This smaller neural investment of epsilon4 carriers into learning reappeared during retrieval: epsilon4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE epsilon4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.

Presenilin 1 (PSEN1) mutations cause autosomal dominant familial Alzheimer's disease (FAD). PSEN1 mutation carriers undergo the course of cognitive deterioration, which is typical for sporadic Alzheimer's disease but disease onset is earlier and disease progression is faster. Here, we sought to detect signs of FAD in presymptomatic carriers of the PSEN1 mutation (C410Y) by use of a neuropsychological examination, functional MRI during learning and memory tasks and MRI volumetry. We examined five non-demented members of a FAD family and 21 non-related controls. Two of the five family members were carrying the mutation; one was 20 years old and the other 45 years old. The age of clinical manifestation of FAD in the family studied here is approximately 48 years. Neuropsychological assessments suggested subtle problems with episodic memory in the 20-year-old mutation carrier. The middle-aged mutation carrier fulfilled criteria for amnestic mild cognitive impairment. The 20-year-old mutation carrier exhibited increased, while the middle-aged mutation carrier exhibited decreased brain activity compared to controls within memory-related neural networks during episodic learning and retrieval, but not during a working-memory task. The increased memory-related brain activity in the young mutation carrier might reflect a compensatory effort to overcome preclinical neural dysfunction caused by first pathological changes. The activity reductions in the middle-aged mutation carrier might reflect gross neural dysfunction in a more advanced stage of neuropathology. These data suggest that functional neuroimaging along with tasks that challenge specifically those brain areas which are initial targets of Alzheimer's disease pathology may reveal activity alterations on a single-subject level decades before the clinical manifestation of Alzheimer's disease.

Background: Animal and human studies implicate forebrain neural circuits in maternal behavior. Here, we hypothesized that human brain response to emotional stimuli relevant for social interactions between infants and adults are modulated by sex- and experience-dependent factors., Methods: We used functional magnetic resonance imaging and examined brain response to infant crying and laughing in mothers and fathers of young children and in women and men without children., Results: Women but not men, independent of their parental status, showed neural deactivation in the anterior cingulate cortex, as indexed by decreased blood oxygenation level-dependent signal, in response to both infant crying and laughing. The response pattern changed fundamentally with parental experience: in the amygdala and interconnected limbic regions, parents (independent of sex) showed stronger activation from crying, whereas nonparents showed stronger activation from laughing., Conclusions: Our data show sex- and experience-dependent modulation of brain response to infant vocalizations. Successful recognition and evaluation of infant vocalizations can be critical for bonding mechanisms and for offspring well-being and survival. Thus, the modulation of responses by experience seems to represent an adaptive mechanism that can be related to reproductive fitness.

Temporal integration is a fundamental process that the brain carries out to construct coherent percepts from serial sensory events. This process critically depends on the formation of memory traces reconciling past with present events and is particularly important in the auditory domain where sensory information is received both serially and in parallel. It has been suggested that buffers for transient auditory memory traces reside in the auditory cortex. However, previous studies investigating "echoic memory" did not distinguish between brain response to novel auditory stimulus characteristics on the level of basic sound processing and a higher level involving matching of present with stored information. Here we used functional magnetic resonance imaging in combination with a regular pattern of sounds repeated every 100 ms and deviant interspersed stimuli of 100-ms duration, which were either brief presentations of louder sounds or brief periods of silence, to probe the formation of auditory memory traces. To avoid interaction with scanner noise, the auditory stimulation sequence was implemented into the image acquisition scheme. Compared to increased loudness events, silent periods produced specific neural activation in the right planum temporale and temporoparietal junction. Our findings suggest that this area posterior to the auditory cortex plays a critical role in integrating sequential auditory events and is involved in the formation of short-term auditory memory traces. This function of the planum temporale appears to be fundamental in the segregation of simultaneous sound sources.

Acoustic intensity change, along with interaural, spectral, and reverberation information, is an important cue for the perception of auditory motion. Approaching sound sources produce increases in intensity, and receding sound sources produce corresponding decreases. Human listeners typically overestimate increasing compared to equivalent decreasing sound intensity and underestimate the time to contact of approaching sound sources. These characteristics could provide a selective advantage by increasing the margin of safety for response to looming objects. Here, we used dynamic intensity and functional magnetic resonance imaging to examine the neural underpinnings of the perceptual priority for rising intensity. We found that, consistent with activation by horizontal and vertical auditory apparent motion paradigms, rising and falling intensity activated the right temporal plane more than constant intensity. Rising compared to falling intensity activated a distributed neural network subserving space recognition, auditory motion perception, and attention and comprising the superior temporal sulci and the middle temporal gyri, the right temporoparietal junction, the right motor and premotor cortices, the left cerebellar cortex, and a circumscribed region in the midbrain. This anisotropic processing of acoustic intensity change may reflect the salience of rising intensity produced by looming sources in natural environments.

The principles that the auditory cortex uses to decipher a stream of acoustic information have remained elusive. Neural responses in the animal auditory cortex can be broadly classified into transient and sustained activity. We examined the existence of similar principles in the human brain. Sound-evoked, blood oxygen level-dependent signal response was decomposed temporally into independent transient and sustained constituents, which predominated in different portions-core and belt-of the auditory cortex. Converging with unit recordings, our data suggest that this spatiotemporal pattern in the auditory cortex may represent a fundamental principle of analyzing sound information.