Neuralsystems Underlying Learning and Representation of Global Motion

Lucia M. Vaina, John W. Belliveau, Eric B.des Roziers, & Thomas A. Zeffiro

INTRODUCTION
Until recently, the predominant view of plasticityof cortical maps and of functional properties of neurons in the early levelsof cortical sensory processing was that they are specific to early development,and are fixed in adulthood. Research over the past fifteen years has amplydemonstrated that this is not the case. It is now clearly established thatcortical maps in the early stages of sensory processing in the adult animalare not fixed, but dynamic throughout life. Lesion studies in differentadult mammalian species, including humans, have demonstrated significantneuronal plasticity. – When a specific cortical area is deprived of itsnormal afferent inputs, it reorganizes so that it becomes responsive toinputs that were initially represented only by the surrounding cortex (fora review (2)). Another important form of neural plasticity, known as perceptuallearning, relies on changes resulting from practicing a stimulus discrimination.These two forms of cortical plasticity are complementary. In the former,there is a peripheral or central reduction of the input, while in the latteran enrichment of the input (3).

Currently, considerable research is aimedtoward understanding the relationship between neuronal activity and performanceon the task, in particular within the framework of perceptual learning.One proposal is that learning largely implies an increased representationof the trained stimulus and thus the effects of learning may be manifestedas recruitment of cortical regions involved in performing the task. Expansionof the cortical territory activated by a trained stimulus has been demonstratedin the somatosensory and auditory modalities in awake behaving monkeys(4-7). However, the reorganization of the cortical maps observed in theselearning task occurred after a long period of training, up to several months.

Recent neurobiological (8, 9) and psychophysicalstudies (for reviews (10-12)) provided robust evidence for learning effectsin the early stages of visual information processing. Interestingly, althoughlearning in the visual system also occurs with training over days or weeks,several psychophysical studies have demonstrated that it can also occurrapidly, within a few trials in a single session.

The remarkable but still poorly understoodphenomenon of rapid perceptual learning has been investigated psychophysicallyin several laboratories, including ours (1,3,13-16). In trying to characterizethe rapid learning of direction discrimination in global motion stimuliwe investigated psychophysically the specificity of perceptual learningwith respect to the stimulus attributes, visual field position, and theeye tested. The global motion stimulus consisted of two-frame stochasticrandom dot cinematograms in which a proportion of the dots (~20%) movedcoherently, in the same direction and with the same speed, while the remindermoved in random directions and with random steps from one frame to thenext, providing masking motion noise. On each trial subjects reported whetherthe motion field moved in one direction or in the opposite direction (e.g.,right or left). Our results demonstrated rapid learning. – Only a few minutesof a single session sufficed for human subjects to improve their performancefrom close to chance to almost perfect score (1). Furthermore, when presentedwith a previously untrained direction discrimination (e.g., up or down),or when the same stimulus was displayed in a different location in thevisual field, subjects’ performance immediately returned to chance levels.The stability and retention of the good performance, together with thetime course of learning and the specificity to the trained direction ofmotion and spatial location of the stimulus, qualify it as perceptual learning.In the study described here, we used functional neuroimaging to determinewhat and where are the neuronal substrates for this short term and stimulusspecific behavioral plasticity.

Electrophysiological studies have demonstratedthat neurons in the middle temporal visual area (MT or V5) in macaque monkeysare particularly sensitive to direction in global motion displays (17).Electrode recordings also show that the directional specificity of theMT and MST neurons improved hand-in-hand with the animal’s progressivelyimproving perceptual performance (18). Furthermore, electrical microstimulationof MT neurons while the monkey performed a psychophysical direction discriminationtask provide evidence for a causal relationship between neuronal activityand the perceptually judged direction of motion. Additional experimentsin various laboratories, including ours, show that lesions of MT, bothin macaque monkeys and in human patients, impair perception of the discriminationof direction in global motion displays (19-21). Functional imaging studieshave reliably identified the location of the human homologue of MT andprovide definitive evidence for its specific involvement in the analysisof global motion (22-24. Collectively, these findings support the hypothesisthat the neuronal circuitry within area MT is a prime candidate for representingglobal motion and changes in its discrimination with practice.

There is also supporting data for the involvementof MT in learning. Zohary et al., (9), found a 13 percent increase in sensitivityof motion-sensitive cells in MT associated with a 19 percent improvementin the monkey’s ability to discriminate the direction of motion, and thatthe neuronal effects associated with learning transfer from a conditionedpart of the receptive field of an MT neuron to an unconditioned part. Thesefindings indicate that the learning effect is likely to involve corticalregions with receptive fields at least as large as those of MT and notearlier stages in cortical visual processing where neurons have smallerreceptive fields. Although these results suggest that the same neuronalcircuitry mediates both the representation and learning of global motiondiscrimination, electrode and lesion studies have intrinsically limitedspatial sampling and can provide only a partial answer. We therefore usedthe same global motion task as previously described in conjunction withwhole-head fMRI to explore the neural substrate of learning a visual directiondiscrimination. Preliminary reports of this work have appeared (25, 26).

MATERIALS & METHODS
Experimental paradigm
The fMRI experimental paradigm consistedof two visual displays: the task condition, incorporating the global motionstimulus (Fig 1a), and a controlcondition , which contained a static random dot display with the same statisticalcharacteristics as the motion display except the dots were static. In thetask condition subjects performed a direction of motion discriminationtask (i.e., left vs. right), and in the control condition, the centralfixation square transiently (30 msec) turned into a T or an L, and subjectswere asked to perform a letter discrimination task.

During both conditions, subjects were instructedto maintain their gaze on the fixation mark at the center of the displayand to enter their answers by key-press on predetermined keys on a keypadconnected to the Macintosh computer which generated the stimuli and collectedthe subject’s answers trial-by-trial. No feedback was provided.

Prior to the fMRI study all the subjects wereshown examples of the psychophysical stimulus and the tasks, but no practicewas given. All subjects gave informed consent to participate in the studyaccording to the MGH Human Subjects’ Committee requirements.

Each run lasted for 240s, composed of 60smean luminance (baseline fixation), 120s involving discrimination of eithermotion or letters, followed by 60s mean luminance (baseline fixation).Motion and letter discrimination runs were interleaved. For all functionalruns, a time series of 100 images per slice was acquired from twenty slicesthat covered the whole brain.
Each subject underwent about 8 consecutiveruns, with learning motion discrimination runs interleaved with staticcontrol runs, yielding a total of roughly 400 motion discrimination trials,which were amply sufficient for observing the fast learning demonstratedin our previous psychophysical studies.

Data Acquisition and Experimental Set Up
Six subjects (mean age 26.2, range 21-37years) were scanned on a 1.5 Tesla GE Signa MRI system, retrofitted forecho planar imaging (EPI) (Advanced NMR, Inc., Instascan), using a standardr.f. head coil (quadrature birdcage, receive only). An automated fieldshimming procedure was performed to minimize magnetic susceptibility distortions.A co-planar conventional volume was acquired using twenty, 6mm thick contiguousoblique slices (3.125 mm x 3.125 mm in plane) parallel to a line drawnbetween the anterior and posterior commissure (AC-PC), sufficient to coverthe whole brain. A flow series was obtained in the oblique planes selectedfor functional scanning to detect major blood vessels, followed by a T1-weightedsagittal localizer series (TR=25s, TI=70msec, NEX=1, FOV=24 cm, matrix256x192). The scans were used to guide slice selection for the functionalacquisitions. Functional images, sensitive to changes in blood oxygenationstate (BOLD) were obtained using an ASE pulse sequence (TR=2.5s, TE=70ms, tau offset = -25ms, 100 images per slice). For each subject a high-resolutionconventional structural scan (124 slice sagittal volume) was also acquired(SPGR: FOV=24cm, acquisition matrix 256×192, voxel size: 1x1x1.5mm; TE=4msec,TR=25msec).

During the experiment, the room was darkenedto reduce unwanted activation of visual cortex. Before entering the MRIchamber subjects were fitted with earplugs. Subjects lay supine, foam padswere tightly put around the ears to hold the head still and an adjustablebite-bar minimized head motion. During fMRI scanning, visual stimuli wererear-projected onto an acrylic screen (DaTex, Da-Lite Corp.) providingan activated visual field of 40 x 25 degrees. Stimuli subtending 79degsq were projected onto the screen by a Sharp 2000 color LCD projector,through a collimating lens (Buhl Optical).

Data analysis
To determine the areas of brain activationspecific to the training on the motion-discrimination condition, imageanalysis and visualization was performed with MEDx 2.1 image analysis software(Sensor Systems, Inc., Sterling, VA). The image data were motion correctedand ratio-normalized. For neuroanatomical localization, each functionalvolume was registered onto the high resolution 3-D images translated intoTalairach space. Planned contrasts between the motion learning and fixationconditions were computed using the t-statistic and converted into Z-scores.The time series for each significant peak was examined to verify the presenceof task-related signal intensity modulation. To isolate the activationspecific to the motion task, the activation elicited by the static stimuluscompared to the baseline of mean luminance was subtracted from the activationin the motion task compared with the mean luminance.
A standard correlation analysis between psychophysicalperformance and activation was performed for each subject.

RESULTS
As in our previous psychophysical study,in the first block of trials subjects scored close to chance and then showedrapid improved in the subsequent runs. Fig1b shows averaged data of the motion runs from the four subjects. Eachdata point corresponds to approximately 100 trials (for each subject) obtainedduring a motion run (120sec).

Fig1c shows that when subjects were asked to discriminate an untraineddirection of motion (up-down), performance fell to close to chance again(as expected from our previous studies), indicating the directional specificityof the learning. On the letter discrimination task all subjects scoredalmost 100% correct, demonstrating that they were able to maintain attentionto tasks throughout the imaging session.
Because the psychophysical stimulus usedfor training incorporated global motion, we expected that the pattern oflearning related activity in the cerebral cortex would be centered on theMT-complex. Figure 2B and C illustratethe average activity in four subjects at the location of peak intensityin MT in the first run (B), before subjects practiced with the task, andin the fourth run (C), after subjects’ psychophysical performance indicatethat they have learnt the task and performance was stable. The resultsof correlation analysis indicated that the extent of the most activatedcortical region, corresponding to MT, was directly correlated with learning(r=0.8), increasing by 5 fold between the two comparisons. Consistent withFigure2B, in the early runs there was additional and more distributed activation,including higher level extrastriate areas in the dorsal motion processingpathway, including foic of activity in the posterior and medial parietallobes (Table 1).

Concurrently with the expansion of the areaof cortical activation in the MT complex in the late runs, there was asignificant reduction of activity in the other extrastriate areas. Thissuggests that one effect of learning is the development of a more “focused”representation of the motion stimulus and/or the elimination of activitythat is irrelevant to performance of the task.

The activation in the superior colliculus(SC) observed in the first run (Figure2B; slice 31) was totally absent from the late runs (3 and 4) wheresubjects’ psychophysical performance (close to perfect score) indicatedthat they learnt the global motion discrimination task. Although SC hasbeen implicated in oculomotor control (for a review (27)), it is quitecertain that changes in eye movements do not provide a plausible explanationfor our findings. First, although the activation was specific only to thedirection discrimination task, the motion stimulus was on only for 90 msecwhich is not sufficient for the initiation of smooth pursuits. Moreover,the activation in the SC was present only during learning, not after thesubjects learnt the task, or during the control task (letter discrimination).The superior colliculus is strongly connected with the area MT, and itscontribution via the subcortical (retinotectal) motion pathway to the motionspecific neural sensitivity of MT is well established (28, 29). It is thusplausible that SC may be involved in modulating the activity of MT neuronsduring learning.

Another region selectively activated duringthe learning task, and only when subjects’ performance was still improvingwith training, is the anterior cingulate. The role of this region in specificaspects of attention is well established.

By far, in all subjects the most dramaticlearning-related activation was observed in the cerebellum. The involvementof the cerebellum in learning the motion discrimination task is illustratedin Figure 3 through 12 coronalslices. Correlation analysis between the regional extent of significantfMRI signal and psychophysical performance showed a strong inverse correlation(r=0.9); the extensive activation of the cerebellum in the first run (Figure4B) decreased by 12 fold in activation area after learning occurred(Figure 4C). Most intriguing,when subjects are presented with a novel (non-trained) direction discrimination(up-down), performance returns to chance and the strong fMRI signal inthe cerebellum is reinstated (Figure4D). The role of the cerebellar activity in learning the task is alsoindicated by the absence of activation during the control task of letterdiscrimination which clearly did not involve learning (Figure4E).

DISCUSSION
Two major learning-related changes in activationwere detected in all subjects participating in this study: the changesoccurred over a few minutes (300 trials or less) within a single session,and were stimulus-attribute specific.

First, the five-fold increase in the activatedarea centered on the MT-complex, a cortical region particularly well suitedfor representing the global motion stimulus we used, suggests a learning-inducedcortical recruitment. In humans, training-dependent cortical plasticity,specifically cortical recruitment, has been reported previously in functionalimaging studies of motor learning tasks (30) which also revealed an increasein the region of activation. Similarly, magnetoencephalography (MEG) studiesof Braille readers (31) and of string players (32) have shown an increasein the somatosensory representation of the particular finger of the handused in these tasks as compared with the representation for the correspondingfingers of the other hand or of different fingers of the same hand in controlsubjects. Taken together with previously reported training dependent changesin the somatosensory and auditory cortical map organization in behavinganimals, these results support the view that training induced corticalplasticity in adult animals is critical for some forms of perceptual learning.

We observed constriction in the extent ofspatial distribution of cortical activation in several higher extrastriateareas as a result of learning the motion discrimination tasks. This suggeststhat a plausible important effect of perceptual learning may be a spatiallymore compact and efficient representation of the practiced stimulus.

A second important result of this study isa very significant decrease (12 fold) in the cerebellar activation withlearning. This pattern of cerebellar activity is consistent with recentfunctional neuroimaging studies of motor and non-motor learning tasks (33-35).For example, in a language learning task Raichle and colleagues (33) foundthat in novel trials specific activation was seen in several cortical areasand the lateral cerebellum, but in less than 15 minutes of practice theseareas became inactive, and other areas previously inactive became activated.

Immediately relevant to our findings is arecent study by Allen, et al. (36). Using fMRI to examine the differentialinvolvement of the cerebellum in a motor task and in a visual attentiontask that had no motor component, they found a double dissociation of functionbetween different areas of the cerebellum. During the visual attentiontask the most common site of activation was in the left superior portionof the cerebellum (the posterior quadrangular globule (QuP) and the superiorsemilunar lobule (SeS)). However, in the motor task the most common sitewas in a different, non-overlapping region in the right anterior cerebellum(the anterior vermis (AVe), the central lobule, and the anterior portionof the quadrangular lobule). The region of the cerebellum that we observeto be most strongly modulated during perceptual learning corresponds tothe area that Allen, et al., report to be involved in modulation of visualattention. Unlike Allen, et al., we observed bilateral cerebellar modulation.

The role of attention during learning is alsosupported by the training related activation in the superior colliculusand the anterior cingulate cortex. Both were significantly active in theearly, but not the late stage of performing direction discrimination inthe global motion task. It is therefore plausible that activation of thesuperior colliculus and anterior cingulate during learning has a modulatoryrole. A recent combined fMRI and psychophysical study elegantly demonstratedthe involvement of the SC in modulation of motion-related activity by attentionalload (37). As we noted earlier, it is likely that the superior colliculusis also involved in modulation of visual attention. The role of the anteriorcingulate in attention, specifically in the selection among competing,complex contingencies has been confirmed in both functional neuroimagingstudies (33,38) and single-unit recording work in monkeys (39). We suggestthat the learning dependent activation in the cerebellum, the superiorcolliculus and cingulate provides an attentional neuronal network thatis active during learning, when allocation of attention to the stimulusis necessary. When the task becomes “automatic” (or learnt) there is nolonger a role for this modulatory attentional network and as a consequencewe saw that the neuronal activity in these areas almost disappeared.

This hypothesis that attention modulates theperformance of the neuronal network involved in the stimulus processingis consistent with recent results from psychophysical studies of the natureof visual perceptual learning. These studies (40-44) converge on the viewthat this learning involves plastic changes to early neural processinglevels which are stimulus related and are dependent for their inductionand consolidation on “the general behavioral state of the subject”, suchas attention (10).
The results from the fMRI study reportedhere suggest in addition that the central role of the attentional mechanismsdiminishes significantly once the task is learnt. After learning occursthe “scaffolding” is not required (45), and what remains is the representationspecific to the task. Whether the restricted pattern of activations remainstightly correlated with efficient performance on a particular perceptualtask after several other versions of the task have been mastered or evenafter the passage of much longer time periods , is currently unknown.

Acknowledgments: This work was supported inpart by NIH Grant 2EY07861-8 and and NSF POWRE Grant SBR-9753009 to LMV,and conducted during the tenure of an AHA Established Investigatorshipof JWB.

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