On a wintery afternoon over 60 years ago, I was browsing the Baker Library stacks at Dartmouth College and stumbled across a small book with an arresting title: What Is Life? [Schrödinger, E. What is Life? The physical aspect of the living cell and mind . Cambridge: Cambridge University Press, 1944]. This small volume contained numerous concepts that would transform the future of the biological sciences, giving rise to new fields, dogmas, approaches, and debates. Here, I present the core concepts of Schrödinger’s book, the influence they have had on biology, and the influence they may continue to have on the cognitive neurosciences.

Several studies report a right hemisphere advantage for visuospatial integration and a left hemisphere advantage for inferring conceptual knowledge from patterns of covariation. The present study examined hemispheric asymmetry in the implicit learning of new visual feature combinations. A split-brain patient and normal control participants viewed multishape scenes presented in either the right or the left visual fields. Unbeknownst to the participants, the scenes were composed from a random combination of fixed pairs of shapes. Subsequent testing found that control participants could discriminate fixed-pair shapes from randomly combined shapes when presented in either visual field. The split-brain patient performed at chance except when both the practice and the test displays were presented in the left visual field (right hemisphere). These results suggest that the statistical learning of new visual features is dominated by visuospatial processing in the right hemisphere and provide a prediction about how fMRI activation patterns might change during unsupervised statistical learning.

The corpus callosum is the largest white matter pathway in the human brain. The most posterior portion, known as the splenium, is critical for interhemispheric communication between visual areas. The current study employed diffusion tensor imaging to delineate the complete cortical projection topography of the human splenium. Homotopic and heterotopic connections were revealed between the splenium and the posterior visual areas, including the occipital and the posterior parietal cortices. In nearly one third of participants, there were homotopic connections between the primary visual cortices, suggesting interindividual differences in splenial connectivity. There were also more instances of connections with the right hemisphere, indicating a hemispheric asymmetry in interhemispheric connectivity within the splenium. Combined, these findings demonstrate unique aspects of human interhemispheric connectivity and provide anatomical bases for hemispheric asymmetries in visual processing and a long-described hemispheric asymmetry in speed of interhemispheric communication for visual information.

In the present study, we combined 2 types of magnetic resonance technology to explore individual differences on a task that required the recognition of objects presented from unusual viewpoints. This task was chosen based on previous work that has established the necessity of information transfer from the right parietal cortex to the left inferior cortex for its successful completion. We used reaction times (RTs) to localize regions of cortical activity in the superior parietal and inferior frontal regions (blood oxygen level-dependent [BOLD] response) that were more active with longer response times. These regions were then sampled, and their signal change used to predict individual differences in structural integrity of white matter in the corpus callosum (using diffusion tensor imaging). Results show that shorter RTs (and associated increases in BOLD response) are associated with increased organization in the splenium of the corpus callosum, whereas longer RTs are associated with increased organization in the genu.

The overwhelming majority of evidence indicates that the left cerebral hemisphere of right-handed humans is dominant both for manual control and the representation of acquired skills, including tool use. It is, however, unclear whether these functions involve common or dissociable mechanisms. Here we demonstrate that the disconnected left hemispheres of both right- and left-handed split-brain patients are specialized for representing acquired tool-use skills. When required to pantomime actions associated with familiar tools (Experiment 2), both patients show a right-hand (left hemisphere) advantage in response to tool names, pictures, and actual objects. Accuracy decreases as stimuli become increasingly symbolic when using the left hand (right hemisphere). Tested in isolation with lateralized pictures (Experiment 3), each patient's left hemisphere demonstrates a significant advantage over the right hemisphere for pantomiming tool-use actions with the contralateral hand. The fact that this asymmetry occurs even in a left-handed patient suggests that the left hemisphere specialization for representing praxis skills can be dissociated from mechanisms involved in hand dominance located in the right hemisphere. This effect is not attributable to differences at the conceptual level, as the left and right hemispheres are equally and highly competent at associating tools with observed pantomimes (Experiment 4).

The localization of brain functions using neuroimaging techniques is commonly dependent on statistical analyses of groups of subjects in order to identify sites of activation, particularly in studies of episodic memory. Exclusive reliance on group analysis may be to the detriment of understanding the true underlying cognitive nature of brain activations. In the present study, we found that the patterns of brain activity associated with episodic retrieval are very distinct for individual subjects from the patterns of brain activity at the group level. These differences go beyond the relatively small variations due to cyctoarchitectonic differences or spatial normalization. We quantify this individual variability by cross-correlating volumes of brain images. We demonstrate that individual patterns of brain activity are reliable over time despite their extensive variability. We suggest that varied but reliable individual patterns of significant brain activity may be indicative of different cognitive strategies used to produce a recognition response. We believe that individual analysis in conjunction with group analysis may be critical to fully understanding the relationship between retrieval processes and underlying brain regions.

Previous neuroimaging studies have claimed a left hemisphere specialization for episodic “encoding” and a right hemisphere specialization for episodic “retrieval.” Yet studies of split-brain patients indicate relatively minor memory impairment after disconnection of the two hemispheres. This suggests that both hemispheres are capable of encoding and retrieval. In the present experiment, we examined the possible limits on encoding capacity of each hemisphere by manipulating the “depth” of processing during the encoding of unfamiliar faces and familiar words in the left and right hemispheres of two split-brain patients. Results showed that only the left hemisphere benefited from deeper (more elaborate) encoding of familiar words, and only the right hemisphere benefited from deeper encoding of unfamiliar faces. Our findings are consistent with the view that hemispheric asymmetries in episodic encoding are related to hemisphere-specific processing of particular stimuli. Convergent with recent neuroimaging studies, these results with split-brain patients also suggest that these hemispheric differences are not due to unique specializations in each half brain for encoding memories, but rather, are due to preferential recruitment of the synaptically closer prefrontal cortex to posterior regions processing material-specific information.

We present a longitudinal neuropsychological study (31 examinations over a period of 18 months) of patient DF. DF demonstrated bilateral atrophy of the hippocampal formation and globus pallidus resulting from carbon monoxide poisoning. Eighteen months after the event, the volume of the hippocampal formation was reduced by 42% on the left side and 28% on the right. The patient initially presented with a severe global amnesia. Then, he showed a gradual, yet selective recovery of episodic memory function. Verbal free recall and spatial memory performance remained reduced, whereas immediate word recall and recognition memory, as well as picture learning and memory, improved to levels at the lower range of normal performance. Interestingly, nonspatial associative learning was never much impaired and recovered completely by the end of testing. These data are taken as evidence that the human hippocampal formation does not equally support different forms of episodic memory.

A fundamental problem in form perception is how the visual system can link together spatially separated contour fragments to form the percept of a unitary shape. Illusory contours and amodal completion are two phenomena that demonstrate this linking process. In the present study we investigate these phenomena in the divided hemispheres of two callosotomy (“split-brain”) patients. The data suggest that dissociable neural mechanisms are responsible for the generation of illusory contours and amodal completion. Although both cerebral hemispheres appear to be equally capable of perceiving illusory contours, amodal completion is more readily utilized by the right hemisphere. These results suggest that illusory contours may be attributable to low-level visual processes common to both hemispheres, whereas amodal completion reflects a higher-level, lateralized process.

Following damage to primary visual cortex, some patients our initial findings. The data reveal a patchy distribution of redemonstrate a limited ability to respond to stimuli they do not sidual visual abilities in the absence of acknowledged awareness. acknowledge seeing. This residual vision, which has been referred to as “blindsight,” has been attributed to secondary visual pathways. We previously reported an isolated island of blindsight in one patient and argued it was a likely consequence of cortical sparing in V1. We now report an extension of our initial findings. The data reveal a patchy distribution of residual visual abilities in the absence of acknowledged awareness. Variable patterns of cortical sparing appear to be the most parsimonious way to account for this outcome, suggesting that blindsight is generally mediated by the primary visual pathway.

Three patients with complete resection of the corpus callosum were tested in a series of memory tasks to determine the effects of callosotomy on the encoding and retrieval of information in memory. Verbal and pictorial conjunction tests were administered to measure patients' ability to consolidate the elements of a stimulus into an accurate composite memory. Patients were also tested in a paired-associate learning task to determine the consequences of callosotomy on the encoding and retrieval of associations between stimuli. Although callosotomy patients were unimpaired in the verbal conjunction task, results from both the pictorial conjunction task and the paired-associate learning task suggest that the absence of callosal cross-talk impairs encoding in these patients. In addition, the pattern of results in the paired-associate learning task suggests that callosotomy impairs retrieval processes. The role of the callosum in the formation of memory traces for nonverbal material and associations between verbal stimuli is discussed.

We measured the surEdce area of the cerebral cortex and its gross morphological subdivisions in 10 pairs of monozygotic twins. Cortical surface area was estimated in vivo using magnetic resonance imaging and threedimensional computer models of the intra- and extrasulcal pial surface. The means and standard deviations of regional (e.g., gyral), lobar, hemisphere, and total cortical surface area were tabulated for the entire population of 20 young, right-handed adults (10 females, 10 males). To determine whether genotypic differences were associated with morphometric differences, analyses of variance were carried out on each measure across unrelated twin pairs (genotype factor) and within co-twins (birth order factor). Across unrelated pairs, there was wide variation in regional cortical surface area for the left hemisphere (normalized by total cortical surface area, p ≤ 0.0001) but not for the right hemisphere (normalized, p = 0.12). More variation in lobar surface area was also observed for the left hemisphere (normalized, p = 0.05) than for the right (normalized, p = 0.48). Within co-twins, no signifcant variation in regional surface area or lobar surface area was found for the left or right hemisphere. Although normalized regional and lobar surface area in the left hemisphere differed across unrelated pairs, overall left hemisphere surface area normalized by total cortical surface area did not (p = 0.73). Total cortical surface area normallzed by body weight varied across unrelated pairs (p = 0.001) but not within co-twins (p = 0.39). The effects observed across unrelated pairs were not attributable to sex differences. These results suggest: 1) both the total area and folding of the cortical surface are heavily influenced by genetic factors in humans; and 2) the cerebral hemispheres may be differentially affected by genetic influences on cortical morphogenesis, with the languagedominant left cerebral cortex under stronger genetic control than the right.

Previous studies of visuospatial attention indicated that the isolated cerebral hemispheres of split-brain patients maintain an integrated, unitary focus of attention, presumably due to subcortical attentional mechanisms. The present study examined whether a unitary attentional focus would also be observed during a visual search task in which subjects scanned stimulus arrays for a target item. In a group of four commis-surotomy patients, the search rate for bilateral stimulus arrays was found to be approximately twice as fast as the search rate for unilateral arrays, indicating that the separated hemispheres were able to scan their respective hemifields independently. In contrast, the search rates for unilateral and bilateral arrays were approximately equal in a group of six normal control subjects, suggesting that the intact corpus callosum in these subjects is responsible for maintaining a unitary attentional focus during visual search.

The lateral distribution of the P300 component of the event-related brain potential (ERP) was studied in five epileptic patients whose corpus callosum had been surgically sectioned and in seven neurologically intact controls. The P300 was elicited in an auditory “oddball” task using high- and low-pitched tones and in a visual oddball task in which target words were presented either to the left or right visual fields, or to both fields simultaneously. Commissurotomy altered the normal pattern of bilaterally symmetrical P300 waves over the left and right hemispheres, but in a different manner for auditory and visual stimuli. The auditory P3 to binaural tones was larger in amplitude over the right than the left hemisphere for the patients. In the visual task, the laterality of the P300 varied with the visual field of the target presentation. Left field targets elicited much larger P300 amplitudes over the right than the left hemisphere, as did bilateral targets. In contrast, right field targets triggered P300 waves of about the same amplitude over the two hemispheres. The overall amplitude of the P300 to simultaneous bilateral targets was less than the sum of the individual P300 amplitudes produced in response to the unilateral right and left field targets. These shifts in P300 laterality argue against the view that the P300 is an index of diffuse arousal or activation that is triggered in both hemispheres simultaneously irrespective of which hemisphere processes the target information. The results further demonstrate that the P300 does not depend for its production on interhemispheric comparisons of information mediated by the corpus callosum, as suggested recently by Knight et al. (1989).

The capacity of each disconnected cerebral hemisphere to control a variety of facial postures was examined in three split-brain patients. The dynamics of facial posturing were analyzed in 30-msec optical disc frames that were generated off videotape recordings of each patient's response to lateralized stimuli. The results revealed that commands presented to the left hemisphere effecting postures of the lower facial muscles showed a marked asymmetry, with the right side of the face sometimes responding up to 180 msec before the left side of the face. Commands presented to the right hemisphere elicited a response only if the posture involved moving the upper facial muscles. Spontaneous postures filmed during free conversation were symmetrical. The results suggest that while either hemisphere can generate spontaneous facial expressions only the left hemisphere is efficient at generating voluntaly expressions. This contrasts sharply with the fact that both hemispheres can carry out a wide variety of other voluntary movements with the hand and foot.