Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono-and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto-and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the ¢rst large scale opportunity to gain meaningful insights into the concordance or discordance in micro-and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the ¢rst assessment of cerebral genotype^phenotype^behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Alpha-band (8-14 Hz) oscillatory EEG activity was examined with high-density scalp electrical recording during the cue-stimulus interval of an endogenous spatial cueing paradigm. In different blocks, cued spatial locations (left or right) were in either the upper or lower visual field, and attended stimuli were either oriented Ts or moving dots. Distractor stimuli were equally likely in the uncued hemifield. Sustained focal increases of alpha-band activity were seen over occipital cortex contralateral to the direction of the to-be-ignored location (ipsilateral to the cued direction of attention) before onset of the to-be-attended stimulus. The focus of alpha-band activity also moved depending on whether cued locations were in the upper or lower field. Results are consistent with active gating of uncued spatial locations.

High-density eeg recordings revealed sensory specific modulation of anticipatory parieto-occipital approximately 10 Hz oscillatory activity when visually presented word cues instructed subjects in an intermodal selective attention paradigm. Cueing attention to the auditory features of imminent compound audio-visual stimuli resulted in significantly higher approximately 10 Hz amplitude in the period preceding onset of this stimulus than when attention was cued to the visual features. We propose that this parieto-occipital approximately 10 Hz activity reflects a disengaged visual attentional system in preparation for anticipated auditory input that is attentionally more relevant. Conversely, lower approximately 10 Hz activity during the attend-visual condition may reflect active engagement of parieto-occipital areas in the anticipatory period. These results support models implicating parieto-occipital areas in the directing and maintenance of visual attention.

SUMMARY Schizophrenia patients suffer from severe cognitive deficits, such as impaired reality monitoring. Reality monitoring is the ability to distinguish the source of internal experiences from outside reality. During reality monitoring tasks, schizophrenia patients make errors identifying “I made it up” items, and even during accurate performance, they show abnormally low activation of the medial prefrontal cortex (mPFC), a region that supports self-referential cognition. We administered 80 hours of computerized training of cognitive processes to schizophrenia patients and found improvement in reality monitoring that correlated with increased mPFC activity. In contrast, patients in a computer games control condition did not show any behavioral or neural improvements. Notably, recovery in mPFC activity after training was associated with improved social functioning six months later. These findings demonstrate that a serious behavioral deficit in schizophrenia, and its underlying neural dysfunction, can be improved by well-designed computerized cognitive training, resulting in better quality of life.

Working memory has been linked to elevated single neuron discharge in monkeys and to oscillatory changes in the human EEG, but the relation between these effects has remained largely unexplored. We addressed this question by measuring local field potentials and single unit activity simultaneously from multiple electrodes placed in extrastriate visual cortex while monkeys were performing a working memory task. We describe a significant enhancement in theta band energy during the delay period. Theta oscillations had a systematic effect on single neuron activity, with neurons emitting more action potentials near their preferred angle of each theta cycle. Sample-selective delay activity was enhanced if only action potentials emitted near the preferred theta angle were considered. Our results suggest that extrastriate visual cortex is involved in short-term maintenance of information and that theta oscillations provide a mechanism for structuring the recurrent interaction between neurons in different brain regions that underlie working memory.