Real-time quantification of T(2)(*) changes using multiecho planar imaging and numerical methods.

Conventional approaches to quantify whole brain T(2)(*) maps use nonlinear regression with intensive computational requirements that therefore likely limit quantitative T(2)(*) mapping for real-time applications. To overcome these limitations an alternative method, NumART(2)(*) (NUMerical Algorithm for Real-time T(2)(*) mapping) that directly calculates T(2)(*) by a linear combination of images obtained at three or more different echo times was developed. NumART(2)(*), linear least-squares, and nonlinear regression techniques were applied to multiecho planar images of the human brain and to simulated data. Although NumART(2)(*) may overestimate T(2)(*), it yields comparable values to regression techniques in cortical and subcortical areas, with only moderate deviations for echo spacings between 18 and 40 ms. NumART(2)(*), like linear regression, requires 2% of the computational time needed for nonlinear regression and compares favorably with linear regression due to its higher precision. The use of NumART(2)(*) for continuous on-line T(2)(*) mapping in real time fMRI studies is shown.

Improved detection of event-related functional MRI signals using probability functions.

Selecting an optimal event distribution for experimental use in event-related fMRI studies can require the generation of large numbers of event sequences with characteristics hard to control. The use of known probability distributions offers the possibility to control event timing and constrain the search space for finding optimal event sequences. We investigated different probability distributions in terms of response estimation (estimation efficiency), detectability (detection power, parameter estimation efficiency, sensitivity to true positives), and false-positive activation. Numerous simulated event sequences were generated selecting interevent intervals (IEI) from the uniform, uniform permuted, Latin square, exponential, binomial, Poisson, chi(2), geometric, and bimodal probability distributions and fixed IEI. Event sequences from the bimodal distribution, like block designs, had the best performance for detection and the poorest for estimation, while high estimation and detectability occurred for the long-decay exponential distribution. The uniform distribution also yielded high estimation efficiency, but probability functions with a long tail toward higher IEI, such as the geometric and the chi(2) distributions, had superior detectability. The distributions with the best detection performance also had a relatively high incidence of false positives, in contrast to the ordered distributions (Latin square and uniform permuted). The predictions of improved sensitivities for distributions with long tails were confirmed with empirical data. Moreover, the Latin square design yielded detection of activated voxels similar to the chi(2) distribution. These results indicate that high detection and suitable behavioral designs have compatibility for application of functional MRI methods to experiments requiring complex designs.

Human brain activation accompanying explicitly directed movement sequence learning.

We examined brain activation patterns occurring during the production and encoding of a motor sequence. Participants performed a variant of the serial reaction-time task under two conditions. The first condition was designed to foster the engagement of explicit mechanisms of knowledge acquisition. The second condition was intended to encourage the engagement of implicit learning mechanisms that would be more typical of the standard serial reaction-time task. In the first condition, the acquisition of explicit knowledge about an 8-element ordered sequence led to a significant and rapid decline in reaction time. By contrast, the second condition, the task in which a sequence was presented unbeknownst to participants, did not yield changes in reaction time. Several brain regions, including prefrontal cortex, superior and inferior parietal lobules, and cerebellum, exhibited explicit learning-related activation. The prefrontal cortex and inferior parietal lobules increased their levels of activation between the beginning and end of the experiment, while primary motor, primary sensory, and cerebellar cortex decreased their levels of activation from the beginning to the end of the experiment. We propose a model in which two processes, a learning-related increase and a habituation process might interact to produce the activation patterns observed during movement sequence acquisition. In short, the prefrontal cortex and inferior parietal lobule together direct and recruit superior parietal lobule and cerebellum to encode and perform the sequence. The increased activation in prefrontal cortex and inferior parietal lobule may represent the activity of a working memory circuit that functions in the acquisition and recall of sequence information.

Combined visual attention and finger movement effects on human brain representations.

Sensory and motor systems interact in complex ways; visual attention modifies behavior, neural encoding, and brain activation; and dividing attention with simultaneous tasks may impede performance while producing specific brain activation patterns. We hypothesized that combining voluntary movement with visual attention would yield unique brain representations differing from those occurring for movement or visual attention alone. Hemodynamic signals in humans were obtained with functional magnetic resonance imaging (MRI) while participants performed one of four tasks that required only a repetitive finger movement, only attending to the color of a visual stimulus, simultaneous finger movement and visual attention, or no movement and no visual attention. The movement-alone task yielded brain activation in structures commonly engaged during voluntary movement, including the primary motor cortex, supplementary motor area, and cerebellum. Visual attention alone resulted in sparse cerebral cortical and substantial bilateral cerebellar activation. Simultaneous performance of visual attention and finger movements yielded widespread cerebral cortical, cerebellar, and other subcortical activation, in many of the same sites activated for the movement or attention tasks. However, the movement-related plus attention-related activation extended beyond the movement-alone or attention-alone activation sites, indicating a novel activation pattern related to the combined performance of attention and movement. Additionally, the conjoint effects of visual attention and movement upon brain activation were probably not simple gain effects, since we found activation-related interactions in the left superior parietal lobule, the right fusiform gyrus, and left insula, indicating a potent combinatory role for visual attention and movement for activation patterns in the human brain. In conclusion, performing visual attention and movement tasks simultaneously, even though the tasks had no specific interrelationship, resulted in novel activation patterns not predicted by performing movements or visual attention alone.

Spatial coding of visual and somatic sensory information in body-centred coordinates.

Because sensory systems use different spatial coordinate frames, cross-modal sensory integration and sensory-motor coordinate transformations must occur to build integrated spatial representations. Multimodal neurons using non-retinal body-centred reference frames are found in the posterior parietal and frontal cortices of monkeys. We used functional magnetic resonance imaging to reveal regions of the human brain using body-centred coordinates to code the spatial position of both visual and somatic sensory stimuli. Participants determined whether a visible vertical bar (visual modality) or a location touched by the right index finger (somatic sensory modality) lay to the left or to the right of their body mid-sagittal plane. This task was compared to a spatial control task having the same stimuli and motor responses and comparable difficulty, but not requiring body-centred coding of stimulus position. In both sensory modalities, the body-centred coding task activated a bilateral fronto-parietal network, though more extensively in the right hemisphere, to include posterior parietal regions around the intraparietal sulcus and frontal regions around the precentral and superior frontal sulci, the inferior frontal gyrus and the superior frontal gyrus on the medial wall. The occipito-temporal junction and other extrastriate regions exhibited bilateral activation enhancement related to body-centred coding when driven by visual stimuli. We conclude that posterior parietal and frontal regions of humans, as in monkeys, appear to provide multimodal integrated spatial representations in body-centred coordinates, and these data furnish the first indication of such processing networks in the human brain.

On somatotopic representation centers for finger movements in human primary motor cortex and supplementary motor area.

We used functional magnetic resonance imaging to examine the representation pattern for repetitive voluntary finger movements in the primary motor cortex (M1) and the supplementary motor area (SMA) of humans. Healthy right-handed participants performed repetitive individuated flexion-extension movements of digits 1, 2, and 3 using the dominant hand. Contralateral functional labeling for the group indicated a largely overlapping activation pattern in M1 and SMA for the three digits. Consistent with recent findings, the geographic activation center in M1 for each finger differed, and we found some evidence of a homunculus organization pattern in M1 and SMA, but only for the central location of the representations. However, the statistical power for the homunculus pattern was weak, and the distance separating the digit geographical centers was typically less than 15% of the entire extent of digit representations in M1 or SMA. While separations for digit representations occurred, the entire data set provided more support for the concept of distributed, overlapping representations than for a classic homunculus organization for voluntary finger movements.

Motor cortex rules for learning and memory.

Primary motor cortex has a complex, interconnected anatomical and functional architecture with dynamic properties. Recent evidence suggests that, concomitantly with regulating muscle activity and movements, the motor cortex makes key contributions to learning and remembering motor skills.

Plasticity and primary motor cortex.

One fundamental function of primary motor cortex (MI) is to control voluntary movements. Recent evidence suggests that this role emerges from distributed networks rather than discrete representations and that in adult mammals these networks are capable of modification. Neuronal recordings and activation patterns revealed with neuroimaging methods have shown considerable plasticity of MI representations and cell properties following pathological or traumatic changes and in relation to everyday experience, including motor-skill learning and cognitive motor actions. The intrinsic horizontal neuronal connections in MI are a strong candidate substrate for map reorganization: They interconnect large regions of MI, they show activity-dependent plasticity, and they modify in association with skill learning. These findings suggest that MI cortex is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning and possibly in cognitive events as well.

Gaze direction modulates finger movement activation patterns in human cerebral cortex.

We investigated whether gaze direction modified the pattern of finger movement activation in human cerebral cortex using functional magnetic resonance imaging (MRI). Participants performed a sequential finger-tapping task or made no finger movements while maintaining gaze in the direction of the moving hand (aligned conditions) or away from the location of the moving hand. Functional MR signals, measured in the hemisphere contralateral to the moving hand, revealed finger movement-related activation in primary motor cortex, lateral and medial premotor cortex, and a wide extent of the lateral superior and inferior parietal lobules. In each area, the extent of the finger movement activation increased when static gaze was more aligned with the moving hand compared to when gaze was directed away from the moving hand. These data suggest the existence of large-scale cortical networks related to finger actions and indicate that skeletomotor processing in the cerebral cortex is consistently modified by gaze direction signals.

Neuronal interactions improve cortical population coding of movement direction.

Interactions among groups of neurons in primary motor cortex (MI) may convey information about motor behavior. We investigated the information carried by interactions in MI of macaque monkeys using a novel multielectrode array to record simultaneously from 12-16 neurons during an arm-reaching task. Pairs of simultaneously recorded cells revealed significant correlations in their trial-to-trial firing rate variation when estimated over broad (600 msec) time intervals. This covariation was only weakly related to the preferred directions of the individual MI neurons estimated from the firing rate and did not vary significantly with interelectrode distance. Most significantly, in a portion of cell pairs, correlation strength varied with the direction of the arm movement. We evaluated to what extent correlated activity provided additional information about movement direction beyond that available in single neuron firing rate. A multivariate statistical model successfully classified direction from single trials of neural data. However, classification was consistently better when correlations were incorporated into the model as compared to one in which neurons were treated as independent encoders. Information-theoretic analysis demonstrated that interactions caused by correlated activity carry additional information about movement direction beyond that based on the firing rates of independently acting neurons. These results also show that cortical representations incorporating higher order features of population activity would be richer than codes based solely on firing rate, if such information can exploited by the nervous system.

Cognitive channels computing action distance and direction.

Visually guided, goal-directed reaching requires encoding action distance and direction from attributes of visual landmarks. We identified a cognitive mechanism that seemingly performs visual motor extension before action initiation and replicated and extended previous results that identified a mechanism for visual motor mental rotation. We find that humans systematically delay action onset while newly planning increasingly distant arm movements beyond a visual landmark, consistent with an internal representation for visual motor extension. Onset times also changed systematically during concurrent mental rotation and visual motor extension computations required to process new directions and distances. Visual motor extension associated with reaching slowed when participants needed to plan action direction within the same time frame, whereas mental rotation efficiency was unaffected by concurrent needs to prepare action distance. In contrast to parallel direction and distance computations needed for direct aiming to a visual target, the planning of new directions and distances likely occurs at distinct times. When considered with previous findings, the current results suggest the existence of an intermediate component of motor preparation that engages a covert mechanism of cognitive motor planning.

Transcranial magnetic stimulation selectively impairs interhemispheric transfer of visuo-motor information in humans.

We investigated the cerebral cortical route by which visual information reaches motor cortex when visual signals are used for manual responses. Subjects responded unimanually to photic stimuli delivered to the hemifield ipsilateral or contralateral to the moving hand. On some trials, trans-cranial magnetic stimulation (TMS) was applied unilaterally over the occiput, with the aim of stimulating extrastriate visual areas and thereby modifying transmission of visual input. In association with the side of a visual stimulus and a motor response, TMS could change inter- or intra-hemispheric transmission needed to convey visual information to motor areas. Reaction time differences following TMS suggested that TMS exerted an inhibitory effect only when visuo-motor information had to be transferred interhemispherically. This result reinforces evidence for an extrastriate pathway of interhemispheric transfer of visuomotor information.

Neural discharge and local field potential oscillations in primate motor cortex during voluntary movements.

The role of "fast," or gamma band (20-80 Hz), local field potential (LFP) oscillations in representing neuronal activity and in encoding motor behavior was examined in motor cortex of two alert monkeys. Using chronically implanted microwires, we simultaneously recorded LFPs and single or multiple unit (MU) discharge at a group of sites in the precentral gyrus during trained finger force or reaching movements, during natural reaching and grasping, and during quiet sitting. We evaluated the coupling of oscillations with task-related firing at the same site, the timing of oscillations with respect to the execution of trained and untrained movement, and the temporal synchrony of oscillations across motor cortical sites. LFPs and neural discharge were examined from a total of 16 arm sites (7 sites in 1 monkey and 9 in the other), each showing movement-related discharge modulation and arm microstimulation effects. In the trained tasks, fast LFP and MU oscillations occurred most often during a premovement delay period, ceasing around movement onset. The decrease in oscillation roughly coincided with the appearance of firing rate modulation coupled to the motor action. During this delay, LFP oscillations exhibited either "overlapping" or "mixed" relationships with the simultaneously recorded neural discharge at that site. Overlap was characterized by coincident epochs of increased neural discharge and LFP oscillations. For the mixed pattern, episodes of LFP oscillation typically coincided with periods of diminished firing but overlap also sometimes appeared. Both patterns occurred concurrently across motor cortex during preparation; LFP suppression with motor action was ubiquitous. Fast oscillations reappeared quickly upon transition from quiet sitting to resumption of task performance, indicating an association with task engagement, rather than the general motor inaction of the delay period. In contrast to trained movements, fast oscillations often appeared along with movement during untrained reaching, but oscillations occurred erratically and were not reliably correlated with elevated neural discharge. Synchronous oscillations occurred at sites as much as 5 mm apart, suggesting widespread coupling of neurons and LFP signals in motor cortex. Widespread coupling of oscillatory signals is consistent with the concept that temporal coding processes operate in motor cortex. However, because the relationship between neuronal discharge and the appearance of fast oscillations may be altered by behavioral condition, they must reflect a global process active in conjunction with motor planning or preparatory functions, but not details of motor action encoded in neuronal firing rate.

Motor skill learning in Parkinson's disease.

The motor performance of patients with Parkinson's disease is degraded, but it is unclear whether their motor learning (adaptation learning and skill learning) ability is impaired. To assess the ability of these patients to learn motor tasks, we studied nine Parkinson's disease patients and eight age-matched normal (control) subjects who repetitively traced, as rapidly and accurately as possible, irregular geometric patterns with normal and mirror-reversed vision. The outcome was measured by statistical analysis and graphic plotting of values for actual and standardized performance variables and correlation of data from initial and final performance variables with indicators of disease severity. The results showed that, with normal vision, total movement time was reduced in both patients and normal subjects, but movement errors increased with repetition, apparently reflecting a speed-accuracy trade-off and adaptation learning. With mirror-reversed vision, total movement time and movement errors were reduced equally with repetition in both groups. These concomitant improvements in time and accuracy violate the rule of speed-accuracy trade-off and suggest that this behavior reflects true motor skill learning. We conclude that patients with Parkinson's disease do not differ from normal subjects in the processes of motor adaptation and motor skill learning.

Gamma knife pallidotomy in advanced Parkinson's disease.

Posteroventral pallidotomy as a treatment for Parkinson's disease (PD) has been the subject of increasing interest. We treated 4 nondemented patients with advanced PD, 2 with severe bradykinesia and a declining response to medication, and 2 with marked clinical fluctuations. All patients received 180 Gy delivered in one sitting to the right posteroventral pallidum site, used by Laitinen and colleagues, adjusted as needed, to avoid the optic tract. Only 1 patient changed significantly. Dyskinesia completely resolved on the side contralateral to the lesion in this patient. This same patient also became transiently demented and psychotic. The other 3 patients suffered no clearly identifiable beneficial or harmful effects. Follow-up magnetic resonance imaging scans of the brain at 1 year revealed lesions exactly where targeted although of unequal sizes. Our negative experience forces us to conclude that either larger volumes of tissue must be ablated, that physiologic monitoring is required for placing a lesion, that our subjects were poor candidates for the procedure, or that surgical ablation and radiation cause tissue damage of different types with different results.

Cerebral activation covaries with movement rate.

An important aspect in brain activation studies is the relationship between neuronal activity and measurable indices of function. We applied functional magnetic resonance imaging (fMRI) to investigate blood flow-related MR signal changes in response to different rates of repetitive movements of the index finger. The contralateral precentral gyrus and the posterior frontomesial cortex revealed a significant increase in MR signal over baseline for 1, 2 and 3 Hz finger movements, with a linear effect of rate in the precentral gyrus. Increased firing of neuronal aggregates or recruitment of additional neuronal units within the primary motor cortex necessary for increased output to target neurons and maintaining posture of nearby distal and proximal joints may contribute to the activation pattern.

Shared neural substrates controlling hand movements in human motor cortex.

Voluntary hand movements in humans involve the primary motor cortex (M1). A functional magnetic resonance imaging method that measures relative cerebral blood flow was used to identify a distributed, overlapping pattern of hand movement representation within the posterior precentral gyrus, which contains M1. The observed pattern resembles those reported in nonhuman primates and differs from a somatotopically organized plan typically used to portray human motor cortex organization. Finger and wrist movements activated a wide expanse of the posterior precentral gyrus, and representations for different finger movements overlapped each other and the wrist representation. Multiple sites of activation occurred in the precentral gyrus for all movements. The overlapping representations may mediate motor and cognitive functions requiring coordinated neural processing for finger and wrist actions rather than discrete control implied by somatotopic maps.