Interaction in isolation: 50 years of insights from split-brain research

Transcription

1 doi: /brain/awx139 BRAIN 2017: 140; DORSAL COLUMN Grey Matter Interaction in isolation: 50 years of insights from split-brain research Lukas J. Volz and Michael S. Gazzaniga SAGE Center for the Study of the Mind, University of California, Santa Barbara, USA Introduction Fifty years ago, one of the first studies that showed the neuropsychological consequences of sectioning the corpus callosum, that great bundle of fibres that connects the two cerebral hemispheres, was published in Brain (Gazzaniga and Sperry, 1967). With the help of several patients who have undergone this procedure and generously given of their time as willing participants in research, a gold mine of information about the way brains function has been ferreted out. Research studies in the ensuing years have both confirmed and extended the findings, not only in the original patient group, but other groups as well. The insights gained from testing these so called split-brain patients have contributed to the evolving field of cognitive neuroscience and have helped establish information processing models for how the brain governs behaviour and cognition. The original split-brain patients tested in California had undergone a complete transection of the corpus callosum and the anterior and hippocampal commissures (with some minor variance occurring between subjects) to alleviate intractable, severe epilepsy, which it did. Twenty years before, testing of another group of similar split-brain patients in Rochester, New York (cf. Akelaitis, 1941) had not revealed any discernible differences between pre- and post-surgical behaviour, suggesting that not much would be learned from this new group. Using a behavioural testing device (which had not been used in New York) that allowed information to be fed to either hemisphere independent of the other, however, revealed that these patients were to provide a unique opportunity to investigate the separate functions of the two cerebral hemispheres (Fig. 1). From the start, the very earliest studies suggested that the separate hemispheres were perceiving, predicting and interacting with the world independently and differently. Although the 1967 paper s title puts the focus on language processing, its abstract addresses implications far beyond language processing: In general the post-surgical studies indicate a striking functional independence of the gnostic activities of the two hemispheres. Perceptual, cognitive, mnemonic, learned and volitional activities persist in each hemisphere, but can proceed separately in each case outside the realm of awareness of the other hemisphere. These findings provoked the authors to imagine the previously unimaginable: the eerie idea that both of these half brains, lodged in a single head and body, were separately conscious. Was the patient now two patients? The broad conclusions made in the article were based on meticulous observations and careful behavioural testing of these special neurological patients. As anyone with experience in examining and testing neurological patients can confirm, however, the seeming simplicity of behavioural testing can be highly misleading, and the interpretation of subtle variations in behaviour can become extremely challenging. The goal of this article is to outline some of the challenges in interpreting the experience of interacting with split-brain patients. After briefly summarizing some elementary and uncontroversial findings derived from split-brain patients, we will focus on more controversial points that remain the topic of ongoing debate. In particular, we will review the concept of cross-cueing, which is a crucial and tangible reality when interpreting splitbrain results. This may resonate with any reader who Received April 23, Accepted April 24, ß The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please journals.permissions@oup.com

2 2052 BRAIN 2017: 140; L. J. Volz and M. S. Gazzaniga Figure 1 Tachistoscope. Presenting visual stimuli with a tachistoscope allows selective presentation of visual information to one hemisphere at a time. Patients were asked to fix their gaze on the centre of the translucent screen, upon which the examiner projects visual stimuli for 0.1 s. Information projected onto the left half of the screen is subsequently processed by the right hemisphere, whereas stimuli presented in the right visual field are processed by the left hemisphere. The short presentation interval prevents visual information on one side of the screen from being processed by both hemispheres due to eye movements. Modified from Gazzaniga (2000), with permission. has had the experience of working with neurological patients. Separated information processing in both hemispheres The starting point for many split-brain experiments is to provide information to one hemisphere at a time (Fig. 1). Figure 2 Neuroanatomical basis for processing of visual information. When fixating the centre of the screen (cross), visual information presented on the left half of the screen (blue square) is processed by neurons located in the nasal half of the retina in the left eye and lateral half of the retina in the right eye. While the latter directly project into the right hemisphere, axons of retinal neurons in the nasal half of the left eye (blue) cross from the left to the right hemisphere in the optic chiasm. As a result, visual stimuli presented to the left visual field are processed by the right hemisphere, while stimuli presented to the right visual field (red circle) are processed by the left hemisphere. This is most easily accomplished through the visual system, thanks to its tidy anatomy (Fig. 2). If you stare straight ahead at a spot, information on the right side of space perceived by both eyes will end up in the left hemisphere and information on the left side of space will end up in the right hemisphere. This is true for all of us, including our split-brain patients. Since our hemispheres are connected, it is natural for our brains to stitch the two sides together and create a unified visual world (Gazzaniga et al., 1965). Yet,

3 Interaction in isolation BRAIN 2017: 140; Figure 3 Separated information processing. (A) When two different letters are presented in each visual field, the patient will report the letter projected onto the right half of the screen ( R, processed by the verbally dominant left hemisphere). The letter presented on the left half of the screen ( B, processed by the right hemisphere) is not verbally reported, but can be identified via tactile information using the left hand (controlled by the right hemisphere). (B) If visual stimuli are exclusively presented in the left visual field (processed by the right hemisphere), they can again be identified by the patient via tactile information from the left hand (also processed by the right hemisphere). Intriguingly, the patient will verbally report that he did not see any stimulus, due to the lack of information in the verbal left hemisphere. Modified from Sperry et al. (1969), with permission. for the split-brain patient with no such connection, each hemisphere sees only the opposite half of the space. This neat separation of visual input makes it possible to provide visual information to one hemisphere of split-brain patients without the knowledge of the other hemisphere. For example, when an object is shown in the right visual field, the visual information travels to the left hemisphere and the patient is effortlessly able to name it (Fig. 3A). When shown to the left visual field, however, the information travels to the right hemisphere, and when asked, the patient will typically answer that no object was seen (Fig. 3B). This phenomenon is easily explained by the fact that most people s speech centre is located in their left hemisphere. When the hemispheres are separated, the left will be capable of naming an object, while the right hemisphere stays mute. Moreover, the left hemisphere will also eagerly answer the question intended for the right hemisphere. When it hears the question directed to the right hemisphere asking what the object was, the left hemisphere correctly and honestly reports that it did not see anything at all. Now picture yourself listening to the completely normal looking person sitting in front of you saying that he did not see the object. He sounds absolutely sure about this. One might jump to the conclusion that the right hemisphere did not perceive the stimulus. Yet this interpretation drastically changes when the right hemisphere is asked to communicate non-verbally. For example, when instructed to point out the object from a group of objects with the left hand, patients reliably identify the object that had been presented to the right hemisphere. Not just better than chance. Every time. From an anatomical perspective, this hardly seems surprising: the right hemisphere perceives and processes the visual input and then uses its loyal henchman, the left hand, to point it out. The left hand does this because it receives its neuronal input from corticospinal fibres that originate from the right hemisphere. Phenomenologically for the onlooker, however, the observation is far more challenging: the left hand is now confidently pointing out the object that the person just categorically and confidently denied seeing. This is where things get really interesting. Ask the person why he is pointing to that object. Since the left hemisphere and its speech centre do not know what the right hemisphere saw and do not know why the left hand is pointing to a particular object, one might think that the person would once again answer correctly and honestly by admitting ignorance with a simple I don t know. This never happens. The left hemisphere always comes up with a story about why the left hand is doing what it is doing, It is pointing to the apple because I like red. The results of this very simple experiment led to numerous questions and more testing of the split-brain patients, resulting in more intriguing answers and inferences which are well summarized by the notion of the left hemisphere interpreter (Fig. 4; for a detailed account see Gazzaniga and LeDoux, 1978; Gazzaniga, 2000). On the one hand, the strict separation of information processing seems to be a logical consequence of well understood basic neuroanatomy. At the same time, however, interpreting the consequences of two independent information processing systems housed in the same body challenges our intuitive understanding of fundamental aspects of psychology, such as conscious awareness of perception (when one hemisphere reports, I didn t see anything ) or agency (yet the other chooses the correct object) and causation ( because I like red ), which ultimately led to the question how these independent systems can coexist and coordinate a single physical body despite

4 2054 BRAIN 2017: 140; L. J. Volz and M. S. Gazzaniga Figure 4 Example of the left hemisphere interpreter. In a classic test, a chicken claw was shown to the (speaking) left hemisphere and a snow scene was shown to the (silent) right hemisphere. Patient P.S. easily picked out related pictures from a set of eight options. His left hand chose a snow shovel and his right hand chose a chicken. When asked why he had picked those particular pictures, P.S. said, Oh, that s simple. The chicken claw goes with the chicken, and you need a shovel to clean out the chicken shed. Modified from Gazzaniga (2000), with permission. the lack of direct, neural interaction. And there was the other nagging notion: can a flick of a knife really produce two separate-consciousness autonomous brains? If so, what exactly does that mean for, say, personal identity? Lateralization of function The fact that the left hemisphere jumps in to offer an explanation whenever asked, even if it does not know what its counterpart to the right is up to, may suggest that the right hemisphere is unable to process language at all. While, indeed, the right hemisphere is typically, at first, not capable of speech production, it does, however, understand both spoken and written language. Since auditory stimuli are typically processed bilaterally, the experimental design had to be adjusted to test lateralization of phoneme processing. For example, after verbally presenting a target word (perceived by both hemispheres) such as chair, a series of words was visually presented to the right hemisphere only. The left hand then successfully indicated that it recognized the target word by pointing to it (Gazzaniga and Sperry, 1967). To accomplish this, the spoken word had to be interpreted by the right hemisphere in order to produce the correct response from the left hand, since only the right hemisphere could see the list of words from which to choose. In a similar fashion, the right hemisphere can also process the semantic meaning of short sentences. For example, changing the initial verbal target from a single word to a description ( Used to tell the time ), also leads to a correct response with the left hand pointing to clock from a list of words. Despite the obvious dominance of the left hemisphere, various follow-up experiments have established and further characterized that both hemispheres possess the ability to process language independently. In a complementary fashion, the right hemisphere shows superior specialization for visuospatial processing, as observed in tasks involving partwhole relations, spatial relationships, apparent motion detection, mental rotation, spatial matching and mirror image discrimination (for further details see Gazzaniga, 2005). More recent findings suggest that in the split-brain, the right hemisphere may be specialized to infer causality from physical interactions, whereas the left hemisphere may be involved in more abstract inference of causality (Roser et al., 2005). The right hemisphere is also better at recognizing familiar faces and human faces. The clinical observation that prosopagnosia typically occurs after lesions to

5 Interaction in isolation BRAIN 2017: 140; the right hemisphere converges with results from split-brain research (Turk et al., 2002), as well as neuroimaging findings in both healthy subjects and neurological patients alike (Rossion et al., 2011). It also appears that the right hemisphere plays a major role in our ability to determine what the intentions of another person might be (Young and Saxe, 2009). Even more startling the right hemisphere can develop speech following callosal section (Gazzaniga et al., 1979, 1984; Baynes et al., 1995). Non-neural interhemispheric integration? The concept of cross-cueing The fact that the split-brain separately processes information in each hemisphere has been replicated numerous times for various domains and, by itself, constitutes an uncontroversial and accepted concept. The degree of hemispheric separation, however, is a topic of ongoing debate. Does surgically disconnecting (most) cortical interhemispheric fibres result in two distinct conscious systems? Are the two hemispheres each perceiving the world and processing information in a slightly different fashion, leading to two independent minds constructing and following their own respective goals? A first objection might be that two completely separated neural systems should have trouble coordinating one body, given that each of these systems governs the motor function of half of the body. Indeed, some split-brain patients transiently experienced symptoms of an alien hand syndrome, where typically the left hand is perceived to be moving as if following its own goals with a reduced experience of agency over those movements (Gazzaniga, 2015). Moreover, for some patients an intermanual conflict was observed. For example, when trying to arrange a set of blocks with both hands, one hand often undoes what the other has just arranged rather than cooperating to optimize task performance (Gazzaniga, 2015). It is no surprise that the right hemisphere, with its specialized skills for visuospatial reasoning, runs circles around the left hemisphere outperforming it hands down in this task. Yet very quickly after surgery, patients are able to walk and run while avoiding obstacles (Holtzman et al., 1981), even swim (Gazzaniga, 2015), dance and play the piano (Akelaitis, 1941). Such behaviours critically rely on the coordinated interactions between the hemispheres and the movements they control. It seems almost impossible that two separated hemispheres should be able to swim or play piano, naturally leading to the question of whether the split-brain uses some alternative mysterious non-callosal pathway to transfer information. Could visual information from both hemifields be transferred via non-callosal fibres and used to adjust motor controls to avoid bumping into objects while walking or running? While in monkeys, visual information can indeed be exchanged between hemispheres via the anterior commissure, a similar mechanism has been ruled out in humans (Gazzaniga, 2005). A more likely explanation lies in behavioural crosscueing between hemispheres. A popular analogy illustrating the concept of cross-cueing lies in the coordinated behaviour displayed by conjoined twins. If two unquestionably independent brains control one body, as is the case if the conjunction is sufficiently high, we see a wonderful example of two distinct neural systems integrating information without direct pathways linking the two. Abby and Brittany Hensel are such a pair, each with different desires, likes and dislikes, and personalities. They are conjoined at the chest and torso with a single pair of arms and legs. Even though Abby controls one arm and leg and Brittany the other, they are athletically coordinated. By picking up on behavioural cues, for example when Brittany perceives a movement initiated by Abby (and vice versa), they are able to unconsciously and effortlessly coordinate their movements to a degree that allows them to do such things as play softball. Split-brain patients might be in a related situation in some instances only one hemisphere may have access to crucial information needed to perform a certain task. With the abundant amount of constant practice starting right after the surgery, it seems logical that split-brain patients quickly develop nuanced ways to integrate such crucial pieces of information, even in the absence of fibre bundles carrying it from one hemispheres to the other. Since patients are used to constantly relying on crosscueing, these subtle behavioural cues, which allow them to accomplish complex behaviour, can turn into a profound problem for an experimenter who is trying to test the hemispheres in isolation. In a manner similar to a patient with early dementia, who creatively dodges questions that would reveal his inability to recall recent events, a split-brain patient will use cueing mechanisms when faced with a task that requires integration of information between hemispheres. Neither of these patients, however, intend to trick the examiner. Their intent, like anyone s, is simply to perform as well as they can when faced with a challenge. Over the decades, various findings seemed to support the notion of information integration across hemispheres in split-brain patients at first glance. Yet this support dissolved when meticulous reexamination prevented any possibility of cross-cueing (Gazzaniga and Hillyard, 1971). Depending on the experimental design, this can be highly challenging or even impossible (Seymour et al., 1994). Recently, Pinto et al. (2017) investigated the degree to which processing of visual information is segregated between hemispheres in two split-brain patients. In line with the canonical interpretation of independent visual processing, they observed that visual stimuli could not be compared across visual half-fields. The authors, however, also observed that some features, such as the presence or location of visual stimuli, were correctly reported throughout

6 2056 BRAIN 2017: 140; L. J. Volz and M. S. Gazzaniga the entire visual field for responses obtained verbally or with either hand (Pinto et al., 2017). This seems at odds with two separated perceptual streams of information. For example, how can the patients verbally report or indicate with their right hand (both controlled by the left hemisphere) whether a visual stimulus was presented to the left visual half-field (i.e. the right hemisphere)? The authors conclude that a certain degree of information exchange has to occur between hemispheres through non-callosal fibres. They suggest that although the information is not sufficient to inform the other hemisphere about its details, there is enough to let it know if and where a stimulus was presented. These findings can easily be explained by cross-cueing, even though the authors quickly discarded this explanation in their discussion. By characterizing cross-cueing as behavioural tricks, such as touching the left hand with the right hand the authors reveal that they underestimate the potential range and subtlety of cueing behaviour, which has been flushed out over decades. In fact, their data and observations fall nicely in line with previous observations of non-neural communication occurring via cross-cueing. As noted by the authors, the amount of information transferred from one hemisphere to the other by cross-cueing is limited. Accordingly, the patients answered the simple question of whether a visual stimulus was presented or not (almost) perfectly. With the more difficult question of the stimulus s localization, the answers were not so perfect: though reported above chance level, there was a higher errorrate(seefigure2inpintoet al., 2017). Thus, cueing binary information (stimulus/no stimulus) is easy for two separated hemispheres, even without a highly obvious manoeuvre such as touching hands. Informing the other hemisphere about the location of the stimulus is more difficult, however, as readily reflected in the increased error rates. The fact that patients localized stimuli above chance level, even in the crossed case (e.g. stimulus presented to the left hemisphere and response with left hand), can be explained by the experimental design: while an eye-tracking device made sure that a patient fixated on the centre of the screen during the presentation of the visual stimulus, the patients did not have to focus their gaze on the centre of the screen while consecutively indicating the stimulus location. Because splitbrain patients have the capacity to cross-cue the location of visual stimuli by eye movements (a glance to the upper-left or right would be cue enough), this allowed them to cue the opposite hemisphere (Gazzaniga, 1969). Even without the cue of eye movements, intriguing previous data suggest that attentional capacities can be controlled by either hemisphere in split-brain patients, hence giving yet another alternative explanation for the above chance localization of visual stimuli (Fig. 5; Holtzman et al., 1981). For example, after a visual stimulus was exclusively perceived by the right hemisphere, it can direct the attention of the left hemisphere to the given spot in the consecutive relocation condition, by using eye movements or neural connections via collicular-cortical projections or the intact anterior commissure (Holtzman et al., 1981). In summary, cross-cueing directing hemispheric attention may well explain the findings, rendering the concluded direct inter-hemispheric transfer of visual information unnecessary. This explanation is also in perfect agreement with the observation that two stimuli simultaneously presented in different visual half-fields, could not be compared by the patients (in line with the canonical view of two independent processing systems). Cross-cueing mechanism and mirror neurons If cross-cueing indeed plays a prominent role in integrating information between hemispheres lacking direct neural connections, how does one hemisphere express content in a way that allows the other hemisphere to understand it? As mentioned above, an obvious possibility lies in initiating a motor action that is perceived by the other hemisphere, for example touching the right hand with the left or tapping a finger. But many more subtle possibilities exist. For example, some of the facial musculature is innervated bilaterally. Thus, a contraction instigated by one hemisphere can attract the other hemisphere s attention. As discussed above, eye movements and direction of attention via subcortical pathways may be particularly suitable ways to convey the location of a stimulus. The success of cross-cueing critically relies on the capacity of the recipient hemisphere to decipher the meaning of a given cue. This leads to the question of whether specific mechanisms are involved in the perception and interpretation of cues. Does each hemisphere possess neural circuitry that specializes in picking up, deciphering and potentially even anticipating actions initiated by the other hemisphere? A suitable candidate for this job may be mirror neurons, a set of neurons in the cortical motor system that are active each time an individual performs an action or observes another individual performing the same action (Rizzolatti et al., 1996). While the initial studies described the mirror mechanism for hand movements with neuronal representations in the ventral premotor cortex, similar neurons have been reported throughout a parieto-frontal network, reacting to a range of different actions, including movements of the mouth and face (Rizzolatti and Sinigaglia, 2010). Could these specialized neurons also be activated in one hemisphere of a splitbrain when it detects an action initiated by the other hemisphere? Indeed, when healthy subjects imitate actions, mirror neurons in the hemisphere not controlling the motor output show stronger activation than in the contralateral hemisphere s network that performs the actual movement (Aziz-zadeh et al., 2006). Moreover, mirror neurons in the parietal cortex have been characterized as encoding the goal of a perceived action (Rizzolatti and Sinigaglia, 2010), thus making them prominent candidates to decode action cues.

7 Interaction in isolation BRAIN 2017: 140; Figure 5 Interhemispheric transfer of spatial location. In this experiment, patients were instructed to locate target stimuli by fixating them with their right eye, while the left eye was occluded. In the first condition, the target stimulus location was highlighted (A and B). Unsurprisingly, subjects correctly moved their right eye to the target location when the target was presented in the left visual field, processed by the right hemisphere (within-field trial). In the second between-field condition (B), the subject was required to move the eyes to the relative point in the right visual field (not processed by the right hemisphere). Split-brain subjects were able to do this, suggesting cross-integration of spatial information between hemispheres. In the second part of the experiment, information on the identity of the target was presented, either within the left visual field (processed by the right hemisphere, C) or in the right visual field (not processed by the right hemisphere, D). While patients had no problems correctly identifying the indicated target stimulus in within-field trials (C), they had to guess the target-identity in between-field trials (D), as reflected by chance-level accuracy. Hence, while crude information on the spatial localization of a stimulus can be cross-integrated between hemispheres (B), more complex information such as stimulus identity (D) is not integrated in split-brain patients. Modified from Gazzaniga (1995), with permission. The sports world illuminates just how specialized the prediction of movements can be. For example, standing at bat, a skilled baseball player, unconsciously predicting a fastball s trajectory from the pitcher s movement, initiates his swing before the ball even leaves the pitcher s hands. Similarly, the split-brain may rely on the mirror neuron network to become more and more efficient at interpreting and, in the case of sequences of cues, even anticipating such cues thrown to it by the other hemisphere. While this hypothesis remains pure speculation, it may explain how splitbrain patients become more adept at using cross-cueing over time and some have even gained the capacity to produce simple speech, such as one-word utterances, from the formerly mute right hemisphere (cf. Gazzaniga, 2000). How could that formerly mute right hemisphere possibly learn to speak? This skill can emerge years after surgery in some patients and may partially rely on neural plasticity in the right hemisphere. As discussed above, the right hemisphere understands words and hence readily represents their semantic meaning. What could be holding back the right hemisphere s verbal floodgates may be that it lacks the capacity to coordinate muscle activation in order to produce intelligible speech. Over those intervening years, every time a split-brain patient uses the left hemisphere to

8 2058 BRAIN 2017: 140; L. J. Volz and M. S. Gazzaniga speak, the right hemisphere will perceive both intonationrelated movements in the thorax, neck and face, and the auditory result. Using the capacity of the mirror neuron system, the right hemisphere might be able to emulate movements to produce speech-related motor output itself. Support for this hypothesis stems from the observation that some audiovisual mirror neurons discharge both when seeing or hearing an action, such as when ripping paper or snapping a stick in two (Kohler et al., 2002). Such neurons may help to evolve the skill to generate motor commands that result in production of simple speech. How difficult it must be to accomplish this complex task is clear to anyone who has tried to speak a foreign language with a perfect accent, a major challenge even with both hemispheres on the job. The split-brain and concepts of neurological lesions Beyond the insights into the functional specialization of the hemispheres and how much hemispheric integration is necessary to produce behaviour, the split-brain also offers a unique perspective on our understanding of brain lesions. In 1965, Norman Geschwind published his seminal paper entitled Disconnexion syndromes in animals and man (Geschwind, 1965), which reinvigorated the much older idea that the disconnection of communication pathways may lead to specific patterns of functional impairment, introduced by Karl Wernicke (1874). The prototypical example for a disconnection syndrome is conduction aphasia, where a person understands what they hear, can speak fluently, but may use the wrong words or parts of words and has difficulty or is unable to repeat spoken phrases. This condition is produced by lesions to the bundle of neural fibres connecting Broca s area, which is responsible for the motor component of language and Wernicke s area, responsible for the sensory component of language. Thus, the clinical observation linking lesions in communication pathways to specific deficits presented neuroscience a path worth pursuing, paving the way for the concept of distributed functional networks, a hot topic in contemporary neuroscience (for a review see Catani and ffytche, 2005). While the split-brain is clearly an example of a disconnexion syndrome, it provides an opportunity that other examples of disconnection syndromes do not. This is the opportunity to study the presence of mental capacities, not the absence of mental capacity caused by lesions (Gazzaniga, 2015). For example, in some patients, the corpus callosum was surgically sectioned in stages over a period of months, in the hope that the patient s seizures could be controlled without sectioning the entire structure. Figure 6 Imaging the corpus callosum. The necessity to determine the extent of the callosotomy in split-brain patients motivated the advancement of neuroimaging methodology to investigate if the corpus callosum was entirely resected or if residual fibres allow information transfer between hemispheres. The first assessment of a split-brain patient via MRI in 1985 suggested two remaining interhemispheric connections in the anterior and posterior end of the corpus callosum (bright spots in white boxes). Reassessment of the same patient with advanced imaging technology (higher spatial resolution and 3D acquisition) in 2001 confirmed the remaining anterior connection, while showing that the posterior fibres were clearly severed. Modern imaging techniques allow reconstruction of callosal fibres from diffusion imaging data [diffusion spectrum imaging (DSI)] and hence a more direct assessment of corpus callosum integrity. Modified from Corballis et al. (2001), with permission.

9 Interaction in isolation BRAIN 2017: 140; Testing patients throughout this process revealed the functional organization of the corpus callosum: the more posterior regions transfer basic sensory information that relates to vision, audition and somatosensory information, while anterior regions are involved in the transfer of attentional resources and higher cognitive information (cf. Gazzaniga, 2005). Moreover, split-brain research led to the development of several methodological advances that derived from questions specifically occurring in split-brain patients. One such question lies in accurately assessing the surgical result of the sectioning, that is, the actual extent of the corpus callosum sectioning. This led to the development of a specific neuroimaging approach that allows one to assess the extent of callosal disconnection in split-brain patients (Gazzaniga et al., 1985; Corballis et al., 2001) and callosal lesions due to all kinds of pathologies (Fig. 6). Implications for understanding consciousness Besides the various insights on aspects of functional specialization of the hemispheres or the functional anatomy of the corpus callosum that were obtained from split-brain work, these extraordinary cases of separated hemispheres raise an even more general question: how much integration of information between specialized brain modules is necessary to give rise to our skilled behaviour and to create our unique experience of the world around us? It seems puzzling that the verbal IQ and problem solving capacities of split-brain patients are typically unaffected by the surgery. Moreover, patients do not report any difference in the nature of their personal experience despite the fact that their hemispheres are separated, they report that they experience a single consciousness (cf. Gazzaniga, 2000). Not surprisingly, theoretical frameworks of consciousness often include the split-brain as a test-case for their respective theory. Yet claims of support are made regardless of whether conscious experience is interpreted to result from the integration of regional resources, as in the Global Workspace Theory (cf. Baars, 1997) or the Information Integration Theory (cf. Tononi and Koch, 2015) or, in contrast, is hypothesized to stem from focal activity, as suggested by the local recurrent processing theory of consciousness for example (cf. Lamme, 2006). A set of observations from split-brain experiments may be particularly suitable to inform such theoretical frameworks of consciousness. In several domains of problem-solving, the left hemisphere shows fundamentally different strategic tendencies compared to the right hemisphere. For example, the right hemisphere adheres to factual knowledge when asked to identify previously presented stimuli and thus outperforms the left hemisphere, which falsely recognizes similar yet unseen objects (Phelps and Gazzaniga, 1992). This observation is in line with the notion that the left hemisphere gets the gist and tends to integrate information into theories, which can help to predict future events and offer a coherent interpretative framework. Interpretive qualities unique to the left hemisphere were also observed in a probability-guessing paradigm (Wolford et al., 2000) where it tries to find patterns, i.e. a theory in random events. The left hemisphere is not shy to interpret the behaviour of or physiological responses evoked by emotional stimuli presented to the right hemisphere, even when it is bound to fail to come up with a veridical story due to the lack of critical information exclusively present in the right hemisphere. Why would the left hemisphere interpreter bother to do so? By constantly offering explanations for what it perceives, the left hemisphere interpreter may generate a feeling in all of us that we are integrated and unified (Gazzaniga, 2000). 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