Individual classification of mild cognitive impairment subtypes by support vector machine analysis of white matter DTI.

BACKGROUND AND PURPOSE: MCI was recently subdivided into sd-aMCI, sd-fMCI, and md-aMCI. The current investigation aimed to discriminate between MCI subtypes by using DTI. MATERIALS AND METHODS: Sixty-six prospective participants were included: 18 with sd-aMCI, 13 with sd-fMCI, and 35 with md-aMCI. Statistics included group comparisons using TBSS and individual classification using SVMs. RESULTS: The group-level analysis revealed a decrease in FA in md-aMCI versus sd-aMCI in an extensive bilateral, right-dominant network, and a more pronounced reduction of FA in md-aMCI compared with sd-fMCI in right inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. The comparison between sd-fMCI and sd-aMCI, as well as the analysis of the other diffusion parameters, yielded no significant group differences. The individual-level SVM analysis provided discrimination between the MCI subtypes with accuracies around 97%. The major limitation is the relatively small number of cases of MCI. CONCLUSIONS: Our data show that, at the group level, the md-aMCI subgroup has the most pronounced damage in white matter integrity. Individually, SVM analysis of white matter FA provided highly accurate classification of MCI subtypes.

Aging effects on selective attention-related electroencephalographic patterns during face encoding.

Previous electrophysiological studies revealed that human faces elicit an early visual event-related potential (ERP) within the occipito-temporal cortex, the N170 component. Although face perception has been proposed to rely on automatic processing, the impact of selective attention on N170 remains controversial both in young and elderly individuals. Using early visual ERP and alpha power analysis, we assessed the influence of aging on selective attention to faces during delayed-recognition tasks for face and letter stimuli, examining 36 elderly and 20 young adults with preserved cognition. Face recognition performance worsened with age. Aging induced a latency delay of the N1 component for faces and letters, as well as of the face N170 component. Contrasting with letters, ignored faces elicited larger N1 and N170 components than attended faces in both age groups. This counterintuitive attention effect on face processing persisted when scenes replaced letters. In contrast with young, elderly subjects failed to suppress irrelevant letters when attending faces. Whereas attended stimuli induced a parietal alpha band desynchronization within 300-1000 ms post-stimulus with bilateral-to-right distribution for faces and left lateralization for letters, ignored and passively viewed stimuli elicited a central alpha synchronization larger on the right hemisphere. Aging delayed the latency of this alpha synchronization for both face and letter stimuli, and reduced its amplitude for ignored letters. These results suggest that due to their social relevance, human faces may cause paradoxical attention effects on early visual ERP components, but they still undergo classical top-down control as a function of endogenous selective attention. Aging does not affect the face bottom-up alerting mechanism but reduces the top-down suppression of distracting letters, possibly impinging upon face recognition, and more generally delays the top-down suppression of task-irrelevant information.

Working memory load-related electroencephalographic parameters can differentiate progressive from stable mild cognitive impairment.

Recent studies described several changes of endogenous event-related potentials (ERP) and brain rhythm synchronization during memory activation in patients with Alzheimer's disease (AD). To examine whether memory-related EEG parameters may predict cognitive decline in mild cognitive impairment (MCI), we assessed P200 and N200 latencies as well as beta event-related synchronization (ERS) in 16 elderly controls (EC), 29 MCI cases and 10 patients with AD during the successful performance of a pure attentional detection task as compared with a highly working memory demanding two-back task. At 1 year follow-up, 16 MCI patients showed progressive cognitive decline (PMCI) and 13 remained stable (SMCI). Both P200 and N200 latencies in the two-back task were longer in PMCI and AD cases compared with EC and SMCI cases. During the interval 1000 ms to 1700 ms after stimulus, beta ERS at parietal electrodes was of lower amplitude in PMCI and AD compared with EC and SMCI cases. Univariate models showed that P200, N200 and log% beta values were significantly related to the SMCI/PMCI distinction with areas under the receiver operating characteristic curve of 0.93, 0.78 and 0.72, respectively. The combination of all three EEG hallmarks was the stronger predictor of MCI deterioration with 90% of correctly classified MCI cases. Our data reveal that PMCI and clinically overt AD share the same pattern of working memory-related EEG activation characterized by increased P200-N200 latencies and decreased beta ERS. They also show that P200 latency during the two-back task may be a simple and promising EEG marker of rapid cognitive decline in MCI.

Frontal theta event-related synchronization: comparison of directed attention and working memory load effects.

Early studies showed that long-term encoding and retrieval of new information is associated with modulation of the theta rhythm. More recently, changes in theta power amplitude over frontal electrode sites were reported during working memory, yet their relative significance in regard to attentional and memory processes remains unclear. Event-related synchronisation responses in the 4-7.5 Hz theta EEG frequency band was studied in 12 normal subjects performing four different tasks: two working memory tasks in which load varied from one (1-back task) to two (2-back task) items, an oddball detection (attention) task and a passive fixation task. A phasic theta increase was observed following stimulus apparition on all electrode sites within each task, with longer culmination peak and maximal amplitude over frontal electrodes. Frontal theta event-related synchronization (ERS) was of higher amplitude in the 1-back, 2-back and detection tasks as compared to the passive fixation task. Additionally, the detection task elicited a larger frontal and central theta ERS than the 2-back task. By analyzing theta ERS characteristics in various experimental conditions, the present study reveals that early phasic theta response over frontal regions primarily reflects the activation of neural networks involved in allocation of attention related to target stimuli rather than working memory processes.

Alpha band power changes in unimanual and bimanual sequential movements, and during motor transitions.

OBJECTIVE: To investigate the cortical activation during execution of unimanual and bimanual synchronous and asynchronous finger sequences, as well as during transitions between those sequences. METHODS: Task-related power (TRPow) analysis of multichannel surface EEG was used to examine the regional oscillatory brain activity in the lower (7.8-9.8 Hz) and upper (10.8-11.8 Hz) alpha band. Unimanual to bimanual, bimanual to unimanual, and unimanual to unimanual transitions, prompted by visual cues, were studied in 10 right handed subjects. RESULTS: (1) Execution of unimanual and bimanual movements was accompanied by a bilateral activation over the central regions. (2) The 7.8-9.8 Hz TRPow decrease was more prominent for left and bimanual movements, suggesting sensitivity of the lower alpha band to task difficulty. (3) No difference in alpha oscillatory activity was found between bimanual synchronous and asynchronous sequences. (4) Transitions between motor sequences were invariably accompanied by a mesioparietal TRPow decrease in the lower alpha band. (5) This mesioparietal activation was contingent to the change of motor program, and could not be accounted for by the change of visual cue, or related attentional processes. CONCLUSION: The 7.8-9.8 Hz mesioparietal activation most likely reflects a posterior parietal motor command initiating transition between motor programs.

Correlations between reaction time and cerebral blood flow during motor preparation.

We show using positron emission tomography in normal volunteers that for four tasks involving motor preparation, regional cerebral blood flow in the ipsilateral cerebellum is negatively correlated with reaction time. Each of the tasks presented subjects with different amounts of advanced information (from none to partial to full information) prior to a signal to move one of two possible fingers in one of two possible directions. The cerebellum was the only brain area that was correlated with reaction time in all the conditions. These results are compatible with the idea that the cerebellum plays an important role in the preparation and initiation of motion.

Gender difference in premotor activity during active tactile discrimination.

To investigate possible gender differences in tactile discrimination tasks, we measured cerebral blood flow of seven men and seven women using positron emission tomography and (15)O water during tactile tasks performed with the right index finger. A nondiscrimination, somatosensory control task activated the left primary sensorimotor cortex and the left parietal operculum extending to the posterior insula without any gender difference. Compared with the control task, discrimination tasks activated the superior and inferior parietal lobules bilaterally, right dorsal premotor cortex, and dorsolateral prefrontal cortex in both genders, consistent with the notion of right hemisphere involvement during exploratory attentional movements. In both genders, symmetric activation of the superior and inferior parietal lobules and asymmetric activation of the right dorsolateral prefrontal cortex were confirmed. The former is consistent with the spatial representation of the tactile input and the latter with the spatial working memory. However, activation of the dorsal premotor cortex was asymmetric in men, whereas it was symmetric in women, the gender difference being statistically significant. This may suggest gender differences in motor programs for exploration in manipulospatial tasks such as tactile discrimination with active touch, possibly by greater interhemispheric interaction through the dorsal premotor cortices in women than in men.

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.

Mesial motor areas in self-initiated versus externally triggered movements examined with fMRI: effect of movement type and rate.

The human frontomesial cortex reportedly contains at least four cortical areas that are involved in motor control: the anterior supplementary motor area (pre-SMA), the posterior SMA (SMA proper, or SMA), and, in the anterior cingulate cortex, the rostral cingulate zone (RCZ) and the caudal cingulate zone (CCZ). We used functional magnetic resonance imaging (fMRI) to examine the role of each of these mesial motor areas in self-initiated and visually triggered movements. Healthy subjects performed self-initiated movements of the right fingers (self-initiated task, SI). Each movement elicited a visual signal that was recorded. The recorded sequence of visual signals was played back, and the subjects moved the right fingers in response to each signal (visually triggered task, VT). There were two types of movements: repetitive (FIXED) or sequential (SEQUENCE), performed at two different rates: SLOW or FAST. The four regions of interest (pre-SMA, SMA, RCZ, CCZ) were traced on a high-resolution MRI of each subject's brain. Descriptive analysis, consisting of individual assessment of significant activation, revealed a bilateral activation in the four mesial structures for all movement conditions, but SI movements were more efficient than VT movements. The more complex and more rapid the movements, the smaller the difference in activation efficiency between the SI and the VT tasks, which indicated an additional processing role of the mesial motor areas involving both the type and rate of movements. Quantitative analysis was performed on the spatial extent of the area activated and the percentage of change in signal amplitude. In the pre-SMA, activation was more extensive for SI than for VT movements, and for fast than for slow movements; the extent of activation was larger in the ipsilateral pre-SMA. In the SMA, the difference was not significant in the extent and magnitude of activation between SI and VT movements, but activation was more extensive for sequential than for fixed movements. In the RCZ and CCZ, both the extent and magnitude of activation were larger for SI than for VT movements. In the CCZ, both indices of activation were also larger for sequential than for fixed movements, and for fast than for slow movements. These data suggest functional specificities of the frontomesial motor areas with respect not only to the mode of movement initiation (self-initiated or externally triggered) but also to the movement type and rate.

Cortical areas with enhanced activation during object-centred spatial information processing. A PET study.

The phenomenon of object-centred unilateral neglect suggests that some neural networks process spatial information relative to reference objects. To examine object-centred information processing, we measured regional cerebral blood flow in 11 normal subjects with PET. During each PET scan, a subject viewed a sample stimulus followed by a cue on a video screen. The sample consisted of two polygons, termed 'objects', each located in a corner of the screen. A small target spot appeared in a corner of each polygon. There were two tasks: the visuomotor task and the matching-to-sample task. In the visuomotor task, the subject moved a joystick in a direction indicated by either the location of the target spot inside the object (if object-centred coordinates were operative) or the location of the object relative to the video screen (if screen-centred coordinates were operative). In the matching-to-sample task, the subject moved the joystick to report whether the relevant spatial information (object- or screen-centred) in the cue matched the sample. In both the visuomotor and the matching-to-sample task, use of object-centred (versus screen- or viewer-centred) information caused augmented activation in the inferior occipitotemporal cortex, bilaterally, in the left superior occipital gyrus, and in both the thalamus and the brainstem. In addition, in the visuomotor task such activation occurred in the right posterior parietal cortex and in the left ventral premotor, dorsolateral prefrontal and anterior supplementary motor areas. These findings suggest the involvement of the occipitotemporal cortex and a broad frontoparietal network when, as in the visuomotor task, object-centred information guides movement. When the same data underlie declarative reports, as in the matching-to-sample task, the occipitotemporal cortex remains engaged but the frontoparietal network diminishes in importance.

Dynamic cortical involvement in implicit and explicit motor sequence learning. A PET study.

We examined the dynamic involvement of different brain regions in implicit and explicit motor sequence learning using PET. In a serial reaction time task, subjects pressed each of four buttons with a different finger of the right hand in response to a visually presented number. Test sessions consisted of 10 cycles of the same 10-item sequence. The effects of explicit and implicit learning were assessed separately using a different behavioural parameter for each type of learning: correct recall of the test sequence for explicit learning and improvement of reaction time before the successful recall of any component of the test sequence for implicit learning. Regional cerebral blood flow was measured repeatedly during the task, and a parametric analysis was performed to identify brain regions in which activity was significantly correlated with subjects' performances: i.e. with correct recall of the test sequence or with reaction time. Explicit learning, shown as a positive correlation with the correct recall of the sequence, was associated with increased activity in the posterior parietal cortex, precuneus and premotor cortex bilaterally, also in the supplementary motor area (SMA) predominantly in the left anterior part, left thalamus, and right dorsolateral prefrontal cortex. In contrast, the reaction time showed a different pattern of correlation during different learning phases. During the implicit learning phase, when the subjects were not aware of the sequence, improvement of the reaction time was associated with increased activity in the contralateral primary sensorimotor cortex (SM1). During the explicit learning phase, the reaction time was significantly correlated with activity in a part of the frontoparietal network. During the post-learning phase, when the subjects achieved all components of the sequence explicitly, the reaction time was correlated with the activity in the ipsilateral SM1 and posterior part of the SMA. These results show that different sets of cortical regions are dynamically involved in implicit and explicit motor sequence learning.

Neural networks for Braille reading by the blind.

To explore the neural networks used for Braille reading, we measured regional cerebral blood flow with PET during tactile tasks performed both by Braille readers blinded early in life and by sighted subjects. Eight proficient Braille readers were studied during Braille reading with both right and left index fingers. Eight-character, non-contracted Braille-letter strings were used, and subjects were asked to discriminate between words and non-words. To compare the behaviour of the brain of the blind and the sighted directly, non-Braille tactile tasks were performed by six different blind subjects and 10 sighted control subjects using the right index finger. The tasks included a non-discrimination task and three discrimination tasks (angle, width and character). Irrespective of reading finger (right or left), Braille reading by the blind activated the inferior parietal lobule, primary visual cortex, superior occipital gyri, fusiform gyri, ventral premotor area, superior parietal lobule, cerebellum and primary sensorimotor area bilaterally, also the right dorsal premotor cortex, right middle occipital gyrus and right prefrontal area. During non-Braille discrimination tasks, in blind subjects, the ventral occipital regions, including the primary visual cortex and fusiform gyri bilaterally were activated while the secondary somatosensory area was deactivated. The reverse pattern was found in sighted subjects where the secondary somatosensory area was activated while the ventral occipital regions were suppressed. These findings suggest that the tactile processing pathways usually linked in the secondary somatosensory area are rerouted in blind subjects to the ventral occipital cortical regions originally reserved for visual shape discrimination.

The preparation, execution and suppression of copied movements in the human brain.

We used positron emission tomography (PET) to measure movement set-related changes in regional cerebral blood flow (rCBF) when human subjects were asked to copy hand movements. Movement set-related activity in the brain is thought to reflect the processes of movement selection, preparation and inhibition. Four conditions were used. In the first condition, prepare and execute (PE), the hand stimulus to be copied was shown to subjects 3 s before an auditory "go"-cue instructed subjects to execute the movement; a large part of the scanning time was therefore spent in preparing to move. In the immediate execution condition (E), the hand stimulus and the go cue were presented simultaneously. The prepare-only condition (P) was similar to PE, except subjects only prepared to make the movement and did not actually execute any movement when they heard the auditory go-cue. The same stimuli were presented in a baseline condition (B), but the subjects were instructed to neither prepare nor execute movements. There were 5 principle findings: (1) In contrast to a previous study of human set-related activity in which movements were instructed by an arbitrary pattern of LEDs, preparing to make a copied movement causes rCBF changes in area 44 in posterior Broca's area; (2) set-related activity can be recorded in the cerebellar hemispheres and midline; (3) we confirmed that the supramarginal gyrus has a general role in preparing movements - there was more rCBF in the P than the E condition; (4) the cerebellar nuclei and the basal ganglia may be particularly involved in the initiation and execution of a planned movement; these regions were more active in the PE condition than the P condition; (5) the ventrolateral prefrontal cortex and a left anterior cingulate area are part of a distributed system involved in the suppression of a motor response; these areas were significantly more active in the P than the PE condition.

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.

Frontal and parietal networks for conditional motor learning: a positron emission tomography study.

Studies on nonhuman primates show that the premotor (PM) and prefrontal (PF) areas are necessary for the arbitrary mapping of a set of stimuli onto a set of responses. However, positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) in human subjects have failed to reveal the predicted rCBF changes during such behavior. We therefore studied rCBF while subjects learned two arbitrary mapping tasks. In the conditional motor task, visual stimuli instructed which of four directions to move a joystick (with the right, dominant hand). In the evaluation task, subjects moved the joystick in a predetermined direction to report whether an arrow pointed in the direction associated with a given stimulus. For both tasks there were three rules: for the nonspatial rule, the pattern within each stimulus determined the correct direction; for the spatial rule, the location of the stimulus did so; and for the fixed-response rule, movement direction was constant regardless of the pattern or its location. For the nonspatial rule, performance of the evaluation task led to a learning-related increase in rCBF in a caudal and ventral part of the premotor cortex (PMvc, area 6), bilaterally, as well as in the putamen and a cingulate motor area (CM, area 24) of the left hemisphere. Decreases in rCBF were observed in several areas: the left ventro-orbital prefrontal cortex (PFv, area 47/12), the left lateral cerebellar hemisphere, and, in the right hemisphere, a dorsal and rostral aspect of PM (PMdr, area 6), dorsal PF (PFd, area 9), and the posterior parietal cortex (area 39/40). During performance of the conditional motor task, there was only a decrease in the parietal area. For the spatial rule, no rCBF change reached significance for the evaluation task, but in the conditional motor task, a ventral and rostral premotor region (PMvr, area 6), the dorsolateral prefrontal cortex (PFdl, area 46), and the posterior parietal cortex (area 39/40) showed decreasing rCBF during learning, all in the right hemisphere. These data confirm the predicted rCBF changes in premotor and prefrontal areas during arbitrary mapping tasks and suggest that a broad frontoparietal network may show decreased synaptic activity as arbitrary rules become more familiar.

Frequency-dependent changes of regional cerebral blood flow during finger movements: functional MRI compared to PET.

To evaluate the effect of the repetition rate of a simple movement on the magnitude of neuronal recruitment in the primary sensorimotor cortex, we used a blood flow-sensitive, echo planar functional magnetic resonance imaging (fMRI) sequence in six normal volunteers. Three of the volunteers also had [15O]water positron emission tomography (PET) studies using the same paradigm. Previous PET studies had shown an increase in regional CBF (rCBF) with movement frequencies up to 2 Hz and then a plateau of regional cerebral blood flow (rCBF) at faster frequencies. To evaluate the extent of the activation, the correlation coefficient (cc) of the Fourier-transformed time-signal intensity change with the Fourier-transformed reference function was calculated pixel by pixel. The degree of activation was measured as the signal percent change of each region of interest with a cc > 0.5. The left primary sensorimotor cortex was constantly activated at 1, 1.5, 2, and 4 Hz, while there was only inconsistent activation at 0.25 and 0.5 Hz. Percent change in signal intensity linearly increased from 1 to 4 Hz. Area of activation increased up to 2 Hz and showed a tendency to decrease at higher frequencies. Individual analysis of PET data showed activation in the same location as that revealed by fMRI. The combination of progressively increasing signal intensity with an area that increases to 2 Hz and declines at faster frequencies explains the PET finding of plateau of rCBF at the faster frequencies. Functional magnetic resonance imaging shows similar results to PET, but is better able to dissociate area and magnitude of change.

Activation of the primary visual cortex by Braille reading in blind subjects.

Primary visual cortex receives visual input from the eyes through the lateral geniculate nuclei, but is not known to receive input from other sensory modalities. Its level of activity, both at rest and during auditory or tactile tasks, is higher in blind subjects than in normal controls, suggesting that it can subserve nonvisual functions; however, a direct effect of non-visual tasks on activation has not been demonstrated. To determine whether the visual cortex receives input from the somatosensory system we used positron emission tomography (PET) to measure activation during tactile discrimination tasks in normal subjects and in Braille readers blinded in early life. Blind subjects showed activation of primary and secondary visual cortical areas during tactile tasks, whereas normal controls showed deactivation. A simple tactile stimulus that did not require discrimination produced no activation of visual areas in either group. Thus in blind subjects, cortical areas normally reserved for vision may be activated by other sensory modalities.

A controlled positron emission tomography study of obsessive and neutral auditory stimulation in obsessive-compulsive disorder with checking rituals.

Ten nondepressed patients with obsessive-compulsive disorder (OCD) who were characterized by predominant checking rituals were compared with 10 age- and sex-matched control subjects. Hemispheric and regional cerebral blood flow levels (rCBF) were measured with positron emission tomography (H2 15O) across four conditions: rest, auditory stimulation with idiosyncratic normal or abnormal obsession, auditory stimulation with neutral verbal stimuli, and rest. Order of neutral and obsessive stimulation was randomized. Higher subjective responses to obsessive than to neutral stimulation were found in both groups; subjective response was higher in OCD patients when obsessive stimulation was presented first. A four-way analysis of variance (group x stimulation order x hemisphere x condition [neutral or obsessive stimulation]) was performed on stimulation minus rest normalized rCBF values. Control subjects had significantly higher rCBF in the thalamus and putamen. A trend toward higher rCBF in OCD patients was found in the superior temporal regions. When neutral stimulation was presented first, rCBF was significantly higher in the caudate region of control subjects. Obsessive stimulation was associated with higher rCBF than neutral stimulation in orbitofrontal regions in both groups of subjects. Under obsessive stimulation, superior temporal and orbitofrontal activities were correlated in OCD patients but not in control subjects. Our study suggests specific abnormalities of information processing in the basal ganglia and temporal structures of compulsive checkers.

Frequency-dependent changes of regional cerebral blood flow during finger movements.

To study the effect of the repetition rate of a simple movement on the distribution and magnitude of neuronal recruitment, we measured regional CBF (rCBF) in eight normal volunteers, using positron emission tomography and 15O-labeled water. An auditory-cued, repetitive flexion movement of the right index finger against the thumb was performed at very slow (0.25 and 0.5 Hz), slow (0.75 and 1 Hz), fast (2 and 2.5 Hz), and very fast (3 and 4 Hz) rates. The increase of rCBF during movement relative to the resting condition was calculated for each pair of movement conditions. Left primary sensorimotor cortex showed no significant activation at the very slow rates. There was a rapid rise of rCBF between the slow and the fast rates, but no further increase at the very fast rates. The right cerebellum showed similar changes. Changes in the left primary sensorimotor cortex and the cerebellum likely reflect the effect of the movement rate. The posterior supplementary motor area (SMA) showed its highest activation at the very slow rates but no significant activation at the very fast rates. Changes correlating with those in the SMA were found in the anterior cingulate gyrus, right prefrontal area, and right thalamus. The decreases in CBF may reflect a progressive change in performance from reactive to predictive.

Cerebral structures participating in motor preparation in humans: a positron emission tomography study.

1. Using positron emission tomography and measurement of regional cerebral blood flow (rCBF) as an index of cerebral activity we investigated the central processing of motor preparation in 13 healthy volunteers. 2. We used a motor reaction time paradigm with visual cues as preparatory and response signals. A preparatory stimulus (PS) provided either full, partial, or no information regarding two variables of a forthcoming right finger movement: finger type (index or little finger) and movement direction (abduction or elevation). After a variable delay period, a response stimulus (RS) prompted the movement. A condition was also tested in which the subject could freely select any of the four possible movements during the preparation period ("free" condition). The timing of events was designed to emphasize the motor preparation phase over the motor execution component during the scanning time of 1 min. 3. Distinct preparatory processes, which depended on the information contained in the PS, were demonstrated by significant differences in reaction time between conditions. The reaction time was shorter in the "full" and free conditions, intermediate in the two partial information conditions ("finger" and "direction"), and longer when no preparatory information was available ("none" condition). Conversely, movement time and movement amplitude were similar between conditions, establishing the constancy of the motor executive output. 4. In comparison with a "rest" condition, which had matched visual inputs, the different conditions of motor preparation were associated with increased rCBF in a common set of cerebral regions: the contralateral frontal cortex (sensorimotor, premotor, cingulate, and supplementary motor cortex), the contralateral parietal association cortex (anterior and posterior regions), the ipsilateral cerebellum, the contralateral basal ganglia, and the thalamus. This observation substantiates the participation of those cerebral structures in the preparation for movement. Furthermore, the similarity of the activated areas among the different conditions compared with the rest condition suggests a single anatomic substrate for motor preparation, independent of the movement information context. 5. Differing amounts of movement information contained in the PS affected rCBF changes in some cerebral regions. In particular, the rCBF in the anterior parietal cortex (Brodmann's area 40) was significantly larger in each of the full, finger, and direction conditions, individually, compared with the none condition. This observation supports the hypothesis that the anterior parietal association cortex plays a major role in the use of visual instructions contained in the PS for partial or complete preparation to perform a motor act. On the other hand, the posterior parietal association cortex (Brodmann's area 7) was more activated in the finger, direction, and none conditions than in the full condition. This increased activity with restricted advance information suggests that the posterior region of the parietal cortex is concerned with correct movement selection on the basis of enhanced spatial attention to the RS. 6. In contrast with the parietal cortex, the secondary motor areas (i.e, premotor cortex, cingulate cortex, and supplementary motor area) showed similar activity regardless of the degree of preparation allowed by the advance visual information. Thus the parietal cortex may play a more crucial role than the secondary motor areas in integrating visual information in preparation for movement. 7. The effect on brain activity of the internal (self-generated) versus the external (cued) mode of movement selection was assessed by comparing the free and full conditions, the preparatory component being matched in the two conditions. The anterior part of the supplementary motor area was the main area preferentially involved in the internal selection of movement, independently of motor preparation processes.