Norihiro Sadato

Functional relevance of cross-modal plasticity in blind humans.

Functional imaging studies of people who were blind from an early age have revealed that their primary visual cortex can be activated by Braille reading and other tactile discrimination tasks. Other studies have also shown that visual cortical areas can be activated by somatosensory input in blind subjects but not those with sight. The significance of this cross-modal plasticity is unclear, however, as it is not known whether the visual cortex can process somatosensory information in a functionally relevant way. To address this issue, we used transcranial magnetic stimulation to disrupt the function of different cortical areas in people who were blind from an early age as they identified Braille or embossed Roman letters. Transient stimulation of the occipital (visual) cortex induced errors in both tasks and distorted the tactile perceptions of blind subjects. In contrast, occipital stimulation had no effect on tactile performance in normal-sighted subjects, whereas similar stimulation is known to disrupt their visual performance. We conclude that blindness from an early age can cause the visual cortex to be recruited to a role in somatosensory processing. We propose that this cross-modal plasticity may account in part for the superior tactile perceptual abilities of blind subjects.

Modeling other minds

Nine normal volunteers performed a ‘theory of mind’ task while their regional brain blood flow pattern was recorded using the PET [15O]H2O technique. Control conditions induced subjects to attend to the visual and semantic attributes of known objects. In a third condition, subjects had to infer the function of an unfamiliar object from its form. In the ‘theory of mind’ condition, subjects had to infer function based on the form of both familiar and unfamiliar objects and in addition, model the knowledge and rationality of another mind about the function of these objects. Performance during the ‘theory of mind’ condition evoked the activation of a distributed set of neural networks with prominent activation of the left medial frontal lobe (Brodmann area 9) and left temporal lobe (Brodmann areas 21, 39/19, 38). This result suggests that when inferential reasoning depends on constructing a mental model about the beliefs and intentions of others, the participation of the prefrontal cortex is required. When access to such knowledge is affected by central nervous system dysfunction, such as that found in autism, modeling other minds may prove difficult.

Neural networks for generation and suppression of alpha rhythm: a PET study.

TO study neuronal activities that influence the generation of the alpha rhythm, we used positron emission tomography and simultaneous recording of the electroencephalogram (EEG) in normal volunteers and under passive conditions. A negative correlation between regional cerebral blood flow and alpha power was found in the occipital cortex, consistent with the visual modality-specific reactivity of the alpha rhythm. A positive correlation was found in the pons, midbrain, hypothalamus, amygdala, the basal prefrontal cortex, insula and the right dorsal premotor cortex. Neuronal activities of the brain stem and limbic system that are positively correlated with alpha power may provide an anatomical basis for studies of the relationship between emotional state and brain rhythm in health and disease.

Visual Image Reconstruction from Human Brain Activity using a Combination of Multiscale Local Image Decoders

Perceptual experience consists of an enormous number of possible states. Previous fMRI studies have predicted a perceptual state by classifying brain activity into prespecified categories. Constraint-free visual image reconstruction is more challenging, as it is impractical to specify brain activity for all possible images. In this study, we reconstructed visual images by combining local image bases of multiple scales, whose contrasts were independently decoded from fMRI activity by automatically selecting relevant voxels and exploiting their correlated patterns. Binary-contrast, 10 x 10-patch images (2(100) possible states) were accurately reconstructed without any image prior on a single trial or volume basis by measuring brain activity only for several hundred random images. Reconstruction was also used to identify the presented image among millions of candidates. The results suggest that our approach provides an effective means to read out complex perceptual states from brain activity while discovering information representation in multivoxel patterns.

Attention to emotion modulates fMRI activity in human right superior temporal sulcus

A parallel neural network has been proposed for processing various types of information conveyed by faces including emotion. Using functional magnetic resonance imaging (fMRI), we tested the effect of the explicit attention to the emotional expression of the faces on the neuronal activity of the face-responsive regions. Delayed match to sample procedure was adopted. Subjects were required to match the visually presented pictures with regard to the contour of the face pictures, facial identity, and emotional expressions by valence (happy and fearful expressions) and arousal (fearful and sad expressions). Contour matching of the non-face scrambled pictures was used as a control condition. The face-responsive regions that responded more to faces than to non-face stimuli were the bilateral lateral fusiform gyrus (LFG), the right superior temporal sulcus (STS), and the bilateral intraparietal sulcus (IPS). In these regions, general attention to the face enhanced the activities of the bilateral LFG, the right STS, and the left IPS compared with attention to the contour of the facial image. Selective attention to facial emotion specifically enhanced the activity of the right STS compared with attention to the face per se. The results suggest that the right STS region plays a special role in facial emotion recognition within distributed face-processing systems. This finding may support the notion that the STS is involved in social perception.

Cerebral processes related to visuomotor imagery and generation of simple finger movements studied with positron emission tomography.

Positron emission tomography was used to compare the functional anatomy of visual imagination and generation of movement. Subjects were asked to generate visual images of their finger movement in response to a preparatory signal. Four conditions were tested: in two, no actual movement was required; in the other two, a second signal prompted the subjects to execute the imagined movement. Which movement to imagine was either specified by the preparatory stimulus or freely selected by the subjects. Compared with a rest condition, tasks involving only imagination activated several cortical regions (inferoparietal cortex, presupplementary motor area, anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex) contralateral to the imagined movement. Tasks involving both imagination and movement additionally increased activity in the ipsilateral cerebellum, thalamus, contralateral anteroparietal, and motor cortex and decreased activity in the inferior frontal cortex. These results support the hypothesis that distinct functional systems are involved in visuomotor imagination and generation of simple finger movements: associative parietofrontal areas are primarily related to visuomotor imagination, with inferior frontal cortex likely engaged in active motor suppression, and primary motor structures contribute mainly to movement execution.

Period of susceptibility for cross-modal plasticity in the blind

Cross‐modal plasticity in blind subjects contributes to sensory compensation when vision is lost early in life, but it is not known if it does so when visual loss occurs at an older age. We used H215O positron emission tomography to identify cerebral regions activated in association with Braille reading, and repetitive transcranial magnetic stimulation to induce focal transient disruption of function during Braille reading, in 8 subjects who became blind after age 14 years (late‐onset blind), after a lengthy period of normal vision. Results were compared with those previously reported obtained from congenitally and early‐onset blind subjects. As shown by H215O positron emission tomographic scanning, the occipital cortex was strongly activated in the congenitally blind and early‐onset blind groups but not in the late‐onset blind group. Occipital repetitive transcranial magnetic stimulation disrupted the Braille reading task in congenitally blind and early‐onset blind subjects but not in late‐onset blind subjects. These results indicate that the susceptible period for this form of functionally relevant cross‐modal plasticity does not extend beyond 14 years. Ann Neurol 1999;45:451–460

Internally Simulated Movement Sensations during Motor Imagery Activate Cortical Motor Areas and the Cerebellum

It has been proposed that motor imagery contains an element of sensory experiences (kinesthetic sensations), which is a substitute for the sensory feedback that would normally arise from the overt action. No evidence has been provided about whether kinesthetic sensation is centrally simulated during motor imagery. We psychophysically tested whether motor imagery of palmar flexion or dorsiflexion of the right wrist would influence the sensation of illusory palmar flexion elicited by tendon vibration. We also tested whether motor imagery of wrist movement shared the same neural substrates involving the illusory sensation elicited by the peripheral stimuli. Regional cerebral blood flow was measured with H215O and positron emission tomography in 10 right-handed subjects. The right tendon of the wrist extensor was vibrated at 83 Hz (“illusion”) or at 12.5 Hz with no illusion (“vibration”). Subjects imagined doing wrist movements of alternating palmar and dorsiflexion at the same speed with the experienced illusory movements (“imagery”). A “rest” condition with eyes closed was included. We identified common active fields between the contrasts of imagery versus rest and illusion versus vibration. Motor imagery of palmar flexion psychophysically enhanced the experienced illusory angles of plamar flexion, whereas dorsiflexion imagery reduced it in the absence of overt movement. Motor imagery and the illusory sensation commonly activated the contralateral cingulate motor areas, supplementary motor area, dorsal premotor cortex, and ipsilateral cerebellum. We conclude that kinesthetic sensation associated with imagined movement is internally simulated during motor imagery by recruiting multiple motor areas.

Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells

To reveal the metabolic fate of acetate in neoplasms that may characterize the accumulation patterns of [1-(11)C]acetate in tumors depicted by positron emission tomography. Four tumor cell lines (LS174T, RPMI2650, A2780, and A375) and fibroblasts in growing and resting states were used. In uptake experiments, cells were incubated with[1-(14)C]acetate for 40 min. [(14)C]CO(2) was measured in the tight-air chamber, and the metabolites in cells were identified by thin layer chromatography and paper chromatography. The glucose metabolic rate of each cell line was measured with [2,6-(3)H]2-deoxy-glucose (DG), and the growth activity of each cell line was estimated by measuring the incorporation of [(3)H]methyl thymidine into DNA. Compared with resting fibroblasts, all four tumor cell lines showed higher accumulation of (14)C activity from [1-(14)C]acetate. These tumor-to-normal ratios of [1-(14)C]acetate were larger than those of DG. Tumor cells incorporated (14)C activity into the lipid-soluble fraction, mostly of phosphatidylcholine and neutral lipids, more prominently than did fibroblasts. The lipid-soluble fraction of (14)C accumulation in cells showed a positive correlation with growth activity, whereas the water-soluble and CO(2) fractions did not. These findings suggest that the high tumor-to-normal ratio of [1-(14)C]acetate is mainly due to the enhanced lipid synthesis, which reflects the high growth activity of neoplasms. This in vitro study suggests that [1-(11)C]acetate is appropriate for estimating the growth activity of tumor cells.

Deficient activation of the motor cortical network in patients with writer's cramp

Objective: To study regional cerebral blood flow (rCBF) in patients with simple writer’s cramp using PET to identify regions that malfunction. Background: Several lines of evidence indicate impaired cortical function in patients with focal dystonia, but the precise pathophysiology is still unknown. Methods: Seven patients with writer’s cramp were compared with seven age- and sex-matched control subjects. Control subjects and patients were scanned during sustained contraction, tapping, and writing with the right hand. After realignment and stereotactic normalization of the scans, all tasks were compared with a rest condition. For each task, an intra- and intergroup comparison was performed using statistical parametric mapping. For each condition and within groups, rCBF correlation analysis was performed between some selected regions that were activated during movement. Results: In control subjects and patients, significant increases of rCBF were observed for each task in areas already known to be activated in motor paradigms. The intergroup comparison disclosed less activation in writer’s cramp patients for several areas for all three tasks. This decrease reached significance for the sensorimotor cortex during the sustained contraction task and for the premotor cortex during writing. rCBF correlation analysis showed different patterns between control subjects and patients. At rest and during writing, the correlations between the putamen and premotor cortical regions and between the premotor cortical regions themselves were stronger in control subjects. Conclusions: Deficient activation of premotor cortex and decreased correlation between premotor cortical regions and putamen suggest a dysfunction of the premotor cortical network in patients with writer’s cramp possibly arising in the basal ganglia. The dysfunction is compatible with a loss of inhibition during the generation of motor commands, which in turn could be responsible for the dystonic movements.