Roger Sperry, the maverick brain scientist who was haunted by psyche.

This paper describes the scientific figure of Roger Sperry as a maverick researcher, an original thinker who arrived at definitive notions about the working of the brain mostly by distancing himself from the prevalent views of his peers. After solving the riddle of the functions of the corpus callosum, he won a Nobel prize in physiology or medicine for identifying the different cognitive abilities of the disconnected right and left hemispheres of the human brain. He could have won another Nobel prize for his work on the prenatal formation of behavioral neuronal networks and their growth and development after birth. In the last part of his life, he fought a courageous but inconclusive battle for demonstrating that mental and spiritual factors can direct brain activity and behavior without violating the laws of orthodox neurophysiology. Some nodal points in his scientific career and some sources of inspirations for his thinking are identified and discussed within the historical background of the neurosciences of the twentieth century.

Neural Correlates of Visuospatial Attention to Unseen Stimuli in Hemianopic Patients. A Steady-State Visual Evoked Potential Study.

The relationship between attention and awareness is a topic of great interest in cognitive neuroscience. Some studies in healthy participants and hemianopic patients have shown dissociation between these two processes. In contrast, others confirmed the classic notion that the two processes are mutually exclusive. To try and cast further light on this fascinating dilemma, in the present study we have investigated the neural mechanisms of visual spatial attention when perceptual awareness is totally lacking. To do that, we monitored with steady-state visual evoked potentials (SSVEPs) the neurophysiological correlates of endogenous spatial attention to unseen stimuli presented to the blind field of hemianopic patients. Behaviourally, stimulus detection (a brief change in the orientation of a gabor grating) was absent in the blind hemifield while in the sighted field there was a lower, but non-significant, performance in hit rate with respect to a healthy control group. Importantly, however, in both blind and sighted hemifield of hemianopics (as well as in healthy participants) SSVEP recordings showed an attentional effect with higher frequency power in the attended than unattended condition. The scalp distribution of this effect was broadly in keeping with the location of the dorsal system of endogenous spatial attention. In conclusion, the present results provide evidence that the neural correlates of spatial attention are present regardless of visual awareness and this is in accord with the general hypothesis of a possible dissociation between attention and awareness.

Neuropsychology of Consciousness: Some History and a Few New Trends.

Consciousness is a global activity of the nervous system. Its physiological and pathological mechanisms have been studied in relation to the natural sleep-wake cycle and various forms of normal or morbid unconsciousness, mainly in neurophysiology and clinical neurology. Neuropsychology has been more interested in specific higher brain functions, such as perception and memory and their disorders, rather than in consciousness per se. However, neuropsychology has been at the forefront in the identification of conscious and unconscious components in the processing of sensory and mnestic information. The present review describes some historical steps in the formulation of consciousness as a global brain function with arousal and content as principal ingredients, respectively, instantiated in the subcortex and the neocortex. It then reports a few fresh developments in neuropsychology and cognitive neuroscience which emphasize the importance of the hippocampus for thinking and dreaming. Non-neocortical structures may contribute to the contents of consciousness more than previously believed.

Unconscious priming by illusory figures: the role of the salient region.

In this study we provide evidence that unconscious priming can be obtained as a result of the processing of the salient region (SR) of illusory figures and without that of illusory contours (ICs). We used a metacontrast masking paradigm where illusory figures were masked by real figures. In Experiment 1 we found a clear priming effect when participants were asked to discriminate between square and diamond masks preceded by congruent or incongruent illusory square or diamond primes. It is likely that metacontrast impairs the processing of ICs but not of the SR; therefore the above result strongly suggests that the priming effect was specifically related to the processing of the SR. In Experiment 2 participants were tested in the same task as in Experiment 1 with additional primes in which the inducers were presented in the same locations but their shapes were changed so as to modify the global configuration. We termed these primes High, Low, and No Salient Region (HSR, LSR, and NSR, respectively). The HSR condition replicated Experiment 1, whereas in the LSR and NSR conditions the priming effect got progressively smaller. The results of Experiment 1 were replicated with the priming effect significantly larger in the HSR than in all other conditions. It was also larger in the HSR than in LSR condition and smallest but still present in the NSR condition. Taken together, these results indicate that the unconscious processing of only the SR yields a priming effect and that a reduction of the saliency of the SR leads to a reduction of the priming effect, while its elimination does not abolish it.

Interhemispheric transfer of spatial and semantic information: electrophysiological evidence.

The goal of this study was to cast light on the existence of functional callosal channels for the interhemispheric transfer (IHT) of spatial and semantic information. To do so, we recorded event-related potentials in healthy humans while performing a primed odd-even discrimination task. Targets were visually presented numbers preceded by single-letter primes signaling the probable presentation of an odd or an even number. Primes and targets could appear either in the same or in different visual fields, thus requiring an IHT in the latter case. The P1 and N2 components were influenced by IHT of spatial information only, whereas the later N400 was influenced by IHT of both spatial and semantic information. This was not the case for the P3b, which was modulated by semantic validity only. These results provide novel evidence of the existence of a temporally separated interhemispheric exchange of spatial and semantic information.

Does subliminal visual perception have an error-monitoring system?

There is substantial evidence that subliminal stimuli, i.e. stimuli that cannot be perceived consciously, may influence visually guided human behaviour. Two important points require further investigation, namely, the neural bases and the functional capability of unconscious stimulus processing. In this study we aimed at studying one specific aspect of the latter question, i.e. whether unconscious vision can feed into an error-monitoring system in much the same way as conscious vision. We therefore tested whether the event-related potential component known as error-related negativity, which represents the electrophysiological correlate of an error-monitoring system, is produced by unconscious errors. We found an error-related negativity not only for errors committed in a discrimination task with visible stimuli but also for those committed with subthreshold stimuli. Moreover, behavioural analysis showed post-error slowing of reaction time for correct responses following unconscious as well as conscious errors. Thus, the present results provide both electrophysiological and behavioural evidence of an error-monitoring system operating even when stimuli cannot access consciousness.

Visual trajectory perception in humans: is it lateralized? Clues from online rTMS of the middle-temporal complex (MT/V5).

Inconsistent observations have been reported in the literature regarding the asymmetrical contribution of higher visual areas of the left and right hemispheres to visual motion processing. In the present experiment, we tested for hemispheric asymmetry of the middle-temporal complex (V5/MT), which is a key-component of the visual motion network, by using rTMS applied over left or right V5/MT during a visual trajectory perception task. The results showed that the effect of rTMS was to enhance individual hemispheric asymmetries present when the test was performed without rTMS. The more general meaning of these results is that there are robust individual hemispheric asymmetries in motion perception but no general pattern of hemispheric differences.

FMRI correlates of visuo-spatial reorienting investigated with an attention shifting double-cue paradigm.

The control of visuo-spatial attention entails the joint contribution of goal-directed (endogenous) and stimulus-driven (exogenous) factors. However, little is known about the neural bases of the interplay between these two mechanisms. To address this issue, we presented endogenous (spatially informative) and exogenous (noninformative) visual cues sequentially within the same trial (double-cue paradigm) during fMRI, crossing factorially the validity of the two cues. We found that both endogenous and exogenous cues affected behavioral performance, speeding-up or slowing-down target discrimination when valid and invalid, respectively. Despite the double-cue paradigm maximizes the interplay between endogenous and exogenous factors, the two types of cue affected responses in an independent manner without any significant effect of congruence. The imaging data revealed increased activation in separate cortical areas following invalid endogenous and invalid exogenous cues. A fronto-parietal system was activated during invalid endogenous trials, whereas a region at the temporo-occipital junction was activated during invalid exogenous trials. Within both circuits, activity was unaffected by the validity of the other cue. These results indicate the existence of separate, noninteracting neural circuits for endogenous and exogenous reorienting of visuo-spatial attention.

Interhemispheric transfer following callosotomy in humans: role of the superior colliculus.

It is now common knowledge that the total surgical section of the corpus callosum (CC) and of the other forebrain commissures prevents interhemispheric transfer (IT) of a host of mental functions. By contrast, IT of simple sensorimotor functions, although severely delayed, is not abolished, and an important question concerns the pathways subserving this residual IT. To answer this question we assessed visuomotor IT in split-brain patients using the Poffenberger paradigm (PP), that is, a behavioral paradigm in which simple reaction time (RT) to visual stimuli presented to the hemifield ipsilateral to the responding hand is compared to stimuli presented to the contralateral hemifield, a condition requiring an IT. We tested the possibility that the residual IT is mediated by the collicular commissure interconnecting the two sides of the superior colliculus (SC). To this purpose, we used short-wavelength visual stimuli, which in neurophysiological studies in non-human primates have been shown to be undetectable by collicular neurons. We found that, in both totally and partially callosotomised patients, IT was considerably longer with S-cone input than with L-cone input or with achromatic stimuli. This was not the case in healthy participants in whom IT was not affected by color. These data clearly show that the SC plays an important role in IT of sensorimotor information in the absence of the corpus callosum.

Lateralized readiness potential elicited by undetected visual stimuli.

Visual stimuli undetected by normal subjects as a result of masking procedures can nonetheless activate response preparation in motor areas and yield a motor response. An unanswered question is whether the same holds for undetected subliminal stimuli that are not responded to. To answer this question, in this study normal subjects were tested on a simple visual reaction time task with stimuli above, at, or below the psychophysical threshold while the lateralized readiness potential (LRP), i.e. an electrophysiological correlate of premotor activation in the primary motor cortex, was computed. We found a reliable LRP not only for suprathreshold stimuli but also for subthreshold stimuli to which subjects did not respond. The main thrust of this study is that it provides evidence that activation of the motor cortex occurs even with subthreshold visual stimuli and without an overt response.

Dissociating arbitrary stimulus-response mapping from movement planning during preparatory period: evidence from event-related functional magnetic resonance imaging.

In the present study, we aimed to dissociate the neural correlates of two subprocesses involved in the preparatory period in the context of arbitrary, prelearned stimulus-response (S-R) associations, namely, S-R mapping and movement planning (MP). We teased apart these two subprocesses by comparing three tasks in which the complexity of both S-R mapping and MP were independently manipulated: simple reaction time (SRT) task, go/no-go reaction time (GNGRT) task, and choice reaction time (CRT) task. We found that a more complex S-R mapping, which is the common element differentiating CRT and GNGRT from SRT, was associated with higher brain activation in the left superior parietal lobe (SPL). Conversely, a greater number of planned finger movements, which is the common difference between CRT and both SRT and GNGRT, was associated with higher brain activation in a number of frontal areas, including the left supplementary motor area (SMA), left dorsal premotor cortex (dPM), and left anterior cingulate cortex (ACC). The left-hemisphere dominance for S-R mapping could be related to the fact that arbitrary S-R mapping is often verbally mediated in humans. Overall, these results suggest a clear dissociation in the preparatory-set period between the more abstract role of left SPL in activating the appropriate S-R associations and the more concrete role played by the SMA, dPM, and ACC in preparing the required motor programs.

Abnormal somatotopic arrangement of sensorimotor interactions in dystonic patients.

The aim of the study was to detect abnormalities of sensorimotor interactions and their topographic distribution in the hand muscles of dystonic patients. We investigated the effect of electrical stimulation of the second (D2) and fifth (D5) fingers on the amplitude of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) in the relaxed first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles on both sides of eight patients with unilateral hand dystonia (HD) and in four patients with cervical dystonia (CD). Six Parkinson's disease patients were used as the disease control group and 10 healthy subjects served as normal controls. For each muscle, the digital stimulation was applied to a contiguous finger (CF) and to a non-contiguous finger (NCF). The digital stimulation was set at three times the sensory threshold and preceded TMS or TES at intervals ranging from 10 to 100 ms. In normal subjects, a somatotopic inhibitory effect was detected, since the CF stimulation was significantly more powerful in determining the reduction of MEPs in response to TMS at intervals ranging from 20 to 50 ms. In dystonic patients, on the contrary, the somatopic effect was not present, because both CF and NCF stimulation evoked a consistent MEP inhibition and no significant difference was detected between the conditioning effect of CF and NCF stimulation. These abnormalities were present in the muscles of both the affected and unaffected hands of HD patients, as well as in CD patients. TES conditioning provoked MEP inhibition only at interstimulus intervals (ISIs) <40 ms. Significant MEP potentiation was found at ISIs of 20-40 ms to CF stimulation in Parkinson's disease patients, while there was no effect after NCF stimulation. These data suggest that MEP suppression in response to digital stimulation is preserved in dystonia, but the somatotopically distributed input-output organization of the sensorimotor interactions is lost in dystonic patients' hands. The comparison between TMS and TES experiments indicates that abnormalities may be present at both the spinal and the cortical level, at least in some patients. These findings suggest that a mechanism that normally operates in order to focus the effect of somatosensory afferences on the motor system may be impaired in dystonia. This abnormality seems specific to dystonia.

Interhemispheric transfer and laterality effects in simple visual reaction time in schizophrenics.

INTRODUCTION: There is evidence that schizophrenics have an abnormal corpus callosum and an abnormal pattern of cerebral asymmetries. We investigated whether there are corresponding functional abnormalities in interhemispheric transfer (IT) and laterality effects. METHODS: Medicated schizophrenic patients and matched controls were tested in the Poffenberger paradigm, that is, a simple manual reaction time (RT) paradigm with laterally presented visual stimuli designed to provide a behavioural estimate of IT. By subtracting RT averaged across the uncrossed hand-hemifield conditions, from RT averaged across the crossed hand-hemifield conditions, one can obtain an estimate of IT time. RESULTS: In schizophrenic patients the difference between crossed and uncrossed conditions was 0 because of an unusually prolonged RT in the uncrossed condition right hand/ right field. A broadly similar result has been obtained previously in the tactile modality (Ditchfield & Hemsley, 1990) and is consistent with a left hemisphere impairment. This effect was still present when the patients were retested about 2 years later. CONCLUSIONS: These results demonstrate the existence in schizophrenic patients of a consistent slowing down of simple visuomotor responses subserved by the left hemisphere.