Brain aerobic glycolysis and motor adaptation learning.

Ten percent to 15% of glucose used by the brain is metabolized nonoxidatively despite adequate tissue oxygenation, a process termed aerobic glycolysis (AG). Because of the known role of glycolysis in biosynthesis, we tested whether learning-induced synaptic plasticity would lead to regionally appropriate, learning-dependent changes in AG. Functional MRI (fMRI) before, during, and after performance of a visual-motor adaptation task demonstrated that left Brodmann area 44 (BA44) played a key role in adaptation, with learning-related changes to activity during the task and altered resting-state, functional connectivity after the task. PET scans before and after task performance indicated a sustained increase in AG in left BA 44 accompanied by decreased oxygen consumption. Intersubject variability in behavioral adaptation rate correlated strongly with changes in AG in this region, as well as functional connectivity, which is consistent with a role for AG in synaptic plasticity.

Premotor functional connectivity predicts impulsivity in juvenile offenders.

Teenagers are often impulsive. In some cases this is a phase of normal development; in other cases impulsivity contributes to criminal behavior. Using functional magnetic resonance imaging, we examined resting-state functional connectivity among brain systems and behavioral measures of impulsivity in 107 juveniles incarcerated in a high-security facility. In less-impulsive juveniles and normal controls, motor planning regions were correlated with brain networks associated with spatial attention and executive control. In more-impulsive juveniles, these same regions correlated with the default-mode network, a constellation of brain areas associated with spontaneous, unconstrained, self-referential cognition. The strength of these brain-behavior relationships was sufficient to predict impulsivity scores at the individual level. Our data suggest that increased functional connectivity of motor-planning regions with networks subserving unconstrained, self-referential cognition, rather than those subserving executive control, heightens the predisposition to impulsive behavior in juvenile offenders. To further explore the relationship between impulsivity and neural development, we studied functional connectivity in the same motor-planning regions in 95 typically developing individuals across a wide age span. The change in functional connectivity with age mirrored that of impulsivity: younger subjects tended to exhibit functional connectivity similar to the more-impulsive incarcerated juveniles, whereas older subjects exhibited a less-impulsive pattern. This observation suggests that impulsivity in the offender population is a consequence of a delay in typical development, rather than a distinct abnormality.

Spatial correlation between brain aerobic glycolysis and amyloid-ß (Aß ) deposition.

Amyloid-ß (Aß) plaque deposition can precede the clinical manifestations of dementia of the Alzheimer type (DAT) by many years and can be associated with changes in brain metabolism. Both the Aß plaque deposition and the changes in metabolism appear to be concentrated in the brain's default-mode network. In contrast to prior studies of brain metabolism which viewed brain metabolism from a unitary perspective that equated glucose utilization with oxygen consumption, we here report on regional glucose use apart from that entering oxidative phosphorylation (so-called "aerobic glycolysis"). Using PET, we found that the spatial distribution of aerobic glycolysis in normal young adults correlates spatially with Aß deposition in individuals with DAT and cognitively normal participants with elevated Aß, suggesting a possible link between regional aerobic glycolysis in young adulthood and later development of Alzheimer pathology.

Coherent spontaneous activity identifies a hippocampal-parietal memory network.

Despite traditional theories emphasizing parietal contributions to spatial attention and sensory-motor integration, functional MRI (fMRI) experiments in normal subjects suggest that specific regions within parietal cortex may also participate in episodic memory. Here we examined correlations in spontaneous blood-oxygenation-level-dependent (BOLD) signal fluctuations in a resting state to identify the network associated with the hippocampal formation (HF) and determine whether parietal regions were elements of that network. In the absence of task, stimuli, or explicit mnemonic demands, robust correlations were observed between activity in the HF and several parietal regions (including precuneus, posterior cingulate, retrosplenial cortex, and bilateral inferior parietal lobule). These HF-correlated regions in parietal cortex were spatially distinct from those correlated with the motion-sensitive MT+ complex. Reanalysis of event-related fMRI studies of recognition memory showed that the regions spontaneously correlated with the HF (but not MT+) were also modulated during directed recollection. These regions showed greater activity to successfully recollected items as compared with other trial types. Together, these results associate specific regions of parietal cortex that are sensitive to successful recollection with the HF.

Parietal lobe contributions to episodic memory retrieval.

Although the parietal lobe is not traditionally thought to support declarative memory, recent event-related fMRI studies of episodic retrieval have consistently revealed a range of memory-related influences on activation in lateral posterior parietal cortex (PPC) and precuneus extending into posterior cingulate and retrosplenial cortex. This article surveys the fMRI literature on PPC activation during remembering, a literature that complements earlier electroencephalography data. We consider these recent memory-related fMRI responses within the context of classical ideas about parietal function that emphasize space-based attention and motor intention. We conclude by proposing three hypotheses concerning how parietal cortex might contribute to memory.

Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory.

Alzheimer's disease (AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. In total, data from 764 participants were compared across five in vivo imaging methods. Convergence of effects was seen in posterior cortical regions, including posterior cingulate, retrosplenial, and lateral parietal cortex. These regions were active in default states in young adults and also showed amyloid deposition in older adults with AD. At early stages of AD progression, prominent atrophy and metabolic abnormalities emerged in these posterior cortical regions; atrophy in medial temporal regions was also observed. Event-related functional magnetic resonance imaging studies further revealed that these cortical regions are active during successful memory retrieval in young adults. One possibility is that lifetime cerebral metabolism associated with regionally specific default activity predisposes cortical regions to AD-related changes, including amyloid deposition, metabolic disruption, and atrophy. These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment.

Functional-anatomic correlates of memory retrieval that suggest nontraditional processing roles for multiple distinct regions within posterior parietal cortex.

Current theories of posterior parietal cortex (PPC) function emphasize space-based attention and motor intention. Imaging studies of long-term memory have demonstrated PPC activation during successful memory retrieval. Here, we explored the relationship between memory processes and classical notions of PPC function. Study 1 investigated old-new recognition using picture and sound stimuli to test whether PPC memory effects were dependent on visuospatial attention. A region lateral to the intraparietal sulcus [inferior parietal lobule complex (IPLC)] and two regions in the medial PPC [precuneus complex (PCC) and posterior cingulate/retrosplenial cortex (pC/Rsp)] showed strong retrieval success effects for both picture and sound stimuli. Study 2 explored a recognition task with varied response contingencies to investigate whether these retrieval success effects are dependent on motor intentions. In one condition, subjects responded to both old and new items. In two other conditions, subjects responded only to old or only to new items. IPLC, PCC, and pC/Rsp continued to show retrieval success effects with similar magnitudes for all response contingencies, including a condition in which no responses were made to old items. In a third study, IPLC and PCC activity was modulated at retrieval based on levels of processing at study, suggesting sensitivity to memory demands. These studies demonstrate that retrieval success effects in lateral and medial PPC regions are not affected by manipulations predicted by classical theories of PPC function but can be modulated by memory-related manipulations. PPC regions thus have prominent response properties associated with memory, which may arise through interactions with medial temporal cortex.