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There is substantial interpatient variation in recovery from upper limb impairment after stroke in patients with severe initial impairment. Defining recovery as a change in the upper limb Fugl-Meyer score (ΔFM), we predicted ΔFM with its conditional expectation (i.e., posterior mean) given upper limb Fugl-Meyer initial impairment (FM(ii)) and a putative functional magnetic resonance imaging (fMRI) recovery measure. Patients with first time, ischemic stroke were imaged at 2.5 ± 2.2 days poststroke with 1.5-T fMRI during a hand closure task alternating with rest (fundamental frequency = 0.025 Hz, scan duration = 172 s). Confirming a previous finding, we observed that the prediction of ΔFM by FM(ii) alone is good in patients with nonsevere initial hemiparesis but is not good in patients with severe initial hemiparesis (96% and 16% of the total sum of squares of ΔFM explained, respectively). In patients with severe initial hemiparesis, prediction of ΔFM by the combination of FM(ii) and the putative fMRI recovery measure nonsignificantly increased predictive explanation from 16% to 47% of the total sum of squares of ΔFM explained. The implications of this preliminary negative result are discussed.

There is unexplained variability in the extent to which patients recover after stroke, particularly from the reference point of the first few days after onset. Among studies tracking motor impairment and recovery, only 30–50% of the variance of recovery is explained by the most commonly reported predictors --lesion volume and initial stroke severity 1, 2. We hypothesized that functional imaging early after stroke could provide information over and above initial severity and lesion volume about the degree of subsequent recovery. Several prior functional imaging studies have reported altered brain activation patterns in patients at various stages of motor recovery after stroke3–6. These studies describe brain activation related to concurrent recovered performance at the time of scanning that differs to varying degrees from what is seen in age-matched controls. In this study we used functional imaging to ask a specific and unique question about motor recovery after stroke: can functional imaging in the early period after stroke detect brain activation related to subsequent recovered performance? Should such activation be identified then it could serve as a physiological target for intervention (e.g. non-invasive brain stimulation) in this early time period. To investigate whether brain activation early after stroke can be correlated with subsequent recovery, we scanned patients approximately 48 hours after stroke using fMRI, and defined recovery as the change in motor impairment from the time of scanning to a follow up point 3 months later. We used 3 different statistical tests: 1) a multivariate test, which is most sensitive to spatially diffuse activation, 2) voxel-wise statistical parametric mapping (SPM), which is most sensitive to focal activation, and 3) primary motor cortex (M1) region of interest (ROI) analysis, which is most sensitive to average activation within this region. The ROI analysis was chosen to test existing hypotheses implicating M1 and the corticospinal tract in recovery.7–9 All tests controlled for lesion volume and initial stroke severity, as well as other established clinical variables.

Adaptation of the motor system to sensorimotor perturbations is a type of learning relevant for tool use and coping with an ever-changing body. Memory for motor adaptation can take the form of savings: an increase in the apparent rate constant of readaptation compared with that of initial adaptation. The assessment of savings is simplified if the sensory errors a subject experiences at the beginning of initial adaptation and the beginning of readaptation are the same. This can be accomplished by introducing either 1) a sufficiently small number of counterperturbation trials (counterperturbation paradigm [ CP]) or 2) a sufficiently large number of zero-perturbation trials (washout paradigm [ WO]) between initial adaptation and readaptation. A two-rate, linear time-invariant state-space model (SSMLTI,2) was recently shown to theoretically produce savings for CP. However, we reasoned from superposition that this model would be unable to explain savings for WO. Using the same task (planar reaching) and type of perturbation (visuomotor rotation), we found comparable savings for both CP and WO paradigms. Although SSMLTI,2 explained some degree of savings for CP it failed completely for WO. We conclude that for visuomotor rotation, savings in general is not simply a consequence of LTI dynamics. Instead savings for visuomotor rotation involves metalearning, which we show can be modeled as changes in system parameters across the phases of an adaptation experiment.

Structural magnetic resonance imaging (MRI) studies have shown dramatic age-associated changes in grey and white matter volume, but typically use univariate analyses that do not explicitly test the interrelationship among brain regions. The current study used a multivariate approach to identify covariance patterns of grey and white matter tissue density to distinguish older from younger adults. A second aim was to examine whether the expression of the age-associated covariance topographies is related to performance on cognitive tests affected by normal aging. Eighty-four young (mean age = 24.0) and 29 older (mean age = 73.1) participants were scanned with a 1.5 T MRI machine and assessed with a cognitive battery. Images were spatially normalized and segmented to produce grey and white matter density maps. A multivariate technique, based on the subprofile scaling model, was used to capture sources of between- and within-group variation to produce a linear combination of principal components that represented a “pattern” or “network” that best discriminated between the two age groups. Univariate analyses were also conducted with statistical parametric maps. Grey and white matter covariance patterns were identified that reliably discriminated between the groups with greater than 0.90 sensitivity and specificity. The identified patterns were similar for the univariate and multivariate techniques, and involved widespread regions of the cortex and subcortex. Age and the expression of both patterns were significantly associated with performance on tests of attention, language, memory, and executive functioning. The results suggest that identifiable networks of grey and white matter regions systematically decline with age and that pattern expression is linked to age-related cognitive decline.

To specifically investigate the effect that large-vessel disease may have on cortical reorganization, we used functional magnetic resonance imaging to study patients with unilateral hemispheric hypoperfusion and impaired vasomotor reactivity from critical internal carotid or middle cerebral artery disease but without stroke. We hypothesized that when these patients used the hand contralateral to the hypoperfused hemisphere they would show unique activation in motor-related areas of the normally perfused hemisphere, that is, ipsilateral activation. We found that normal performance of two motor tasks was associated with increased ipsilateral hemispheric activation in the patients compared with age-matched controls. In addition, although task difficulty had an effect on ipsilateral activation, the increased ipsilateral activation seen in patients was not dependent on task difficulty. Our findings demonstrate that hemodynamic compromise alone is sufficient to cause atypical ipsilateral activation. This activation may serve to maintain normal motor performance.

We examined neural activations during decision-making using fMRI paired with the wheel of fortune task, a newly developed two-choice decision-making task with probabilistic monetary gains. In particular, we assessed the impact of high-reward/risk events relative to low-reward/risk events on neural activations during choice selection and during reward anticipation. Seventeen healthy adults completed the study. We found, in line with predictions, that (i) the selection phase predominantly recruited regions involved in visuo-spatial attention (occipito-parietal pathway), conflict (anterior cingulate), manipulation of quantities (parietal cortex), and preparation for action (premotor area), whereas the anticipation phase prominently recruited regions engaged in reward processes (ventral striatum); and (ii) high-reward/risk conditions relative to low-reward/risk conditions were associated with a greater neural response in ventral striatum during selection, though not during anticipation. Following an a priori ROI analysis focused on orbitofrontal cortex, we observed orbitofrontal cortex activation (BA 11 and 47) during selection (particularly to high-risk/reward options), and to a more limited degree, during anticipation. These findings support the notion that (1) distinct, although overlapping, pathways subserve the processes of selection and anticipation in a two-choice task of probabilistic monetary reward; (2) taking a risk and awaiting the consequence of a risky decision seem to affect neural activity differently in selection and anticipation; and thus (3) common structures, including the ventral striatum, are modulated differently by risk/reward during selection and anticipation.

Background: Prior studies document strong interactions between emotional and mnemonic processes. These interactions have been shown to vary across development and psychopathology, particularly mood and anxiety disorders. Methods: The present study used functional neuroimaging to assess the degree to which adolescents and adults differ in patterns of neuronal engagement during implicit encoding of affective stimuli. Subjects underwent rapid event-related fMRI while viewing faces with angry, fearful, happy, and neutral expressions. A surprise post-scan memory test was administered. Results: Consistent with previous findings, both adolescents and adults displayed engagement of left ventrolateral prefrontal cortex when viewing subsequently recognized stimuli. Age differences emerged in patterns of neuronal activation associated with subsequent recognition of specific face-emotion types. Relative to adults, adolescents displayed more activity in the anterior cingulate when viewing subsequently remembered angry faces, and more activity in the right temporal pole when viewing subsequently remembered fear faces. Conversely, adults displayed more activity in the subgenual anterior cingulate when viewing subsequently remembered happy faces and more activity in the right posterior hippocampus when viewing subsequently remembered neutral faces. These age-related differences emerged in the absence of differences in behavioral performance. Conclusions: These findings document developmental differences in the degree to which engagement of affective circuitry contributes to memory formation.

Objective: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). Background: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. Methods: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. Results: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. Conclusions: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.

Animal and human lesion studies have consistently shown that damage to the prefrontal lobe disrupts performance on tasks requiring memory for temporal context. In this study, functional magnetic resonance imaging (fMRI) was used to explore the brain regions associated with judgements of relative recency in healthy humans. Bilateral dorsolateral prefrontal cortex (Brodmann's area [BA] 9) was more active during a verbal recency judgment task than during a non-mnemonic control task. Activation related to temporal context recognition was also observed in midline supplementary motor area (BA 6) and left precuneus (BA 7). This study provides further evidence that memory for temporal context requires the prefrontal cortex and is the first to demonstrate this association in healthy humans. The current findings also suggest the possibility that recognition of context and recognition of episodic content may involve similar brain systems.

Prior studies document strong interactions between emotional and mnemonic processes. These interactions have been shown to vary across development and psychopathology, particularly mood and anxiety disorders.The present study used functional neuroimaging to assess the degree to which adolescents and adults differ in patterns of neuronal engagement during implicit encoding of affective stimuli. Subjects underwent rapid event-related fMRI while viewing faces with angry, fearful, happy, and neutral expressions. A surprise post-scan memory test was administered.Consistent with previous findings, both adolescents and adults displayed engagement of left ventrolateral prefrontal cortex when viewing subsequently recognized stimuli. Age differences emerged in patterns of neuronal activation associated with subsequent recognition of specific face-emotion types. Relative to adults, adolescents displayed more activity in the anterior cingulate when viewing subsequently remembered angry faces, and more activity in the right temporal pole when viewing subsequently remembered fear faces. Conversely, adults displayed more activity in the subgenual anterior cingulate when viewing subsequently remembered happy faces and more activity in the right posterior hippocampus when viewing subsequently remembered neutral faces. These age-related differences emerged in the absence of differences in behavioral performance.These findings document developmental differences in the degree to which engagement of affective circuitry contributes to memory formation.

There is epidemiologic and imaging evidence for the presence of cognitive reserve, but the neurophysiologic substrate of CR has not been established. In order to test the hypothesis that CR is related to aspects of neural processing, we used fMRI to image 19 healthy young adults while they performed a nonverbal recognition test. There were two task conditions. A low demand condition required encoding and recognition of single items and a titrated demand condition required the subject to encode and then recognize a larger list of items, with the study list size for each subject adjusted prior to scanning such that recognition accuracy was 75%. We hypothesized that individual differences in cognitive reserve are related to changes in neural activity as subjects moved from the low to the titrated demand task. To test this, we examined the correlation between subjects' fMRI activation and NART scores. This analysis was implemented voxel-wise in a whole brain fMRI dataset. During both the study and test phases of the recognition memory task we noted areas where, across subjects, there were significant positive and negative correlations between change in activation from low to titrated demand and the NART score. These correlations support our hypothesis that neural processing differs across individuals as a function of CR. This differential processing may help explain individual differences in capacity, and may underlie reserve against age-related or other pathologic changes.