Alterations of resting-state fMRI measurements in individuals with cervical dystonia.

Cervical dystonia (CD) is a neurological disorder with typical symptoms of involuntary and abnormal movements and postures of the head. CD-associated alterations of functional brain networks have not been well characterized. Previous studies of CD using resting-state functional MRI (rfMRI) are limited in two aspects: (i) the analyses were not directly focused on the functional brain network related to head movement and (ii) rfMRI measurements other than functional connectivity (FC) were not investigated. The present study examined alterations of FC in CD by capitalizing on newly identified brain regions supporting isometric head rotation (Prudente et al.: J Neurosci 35 (2015) 9163-9172). In addition to FC, which only reflects inter-regional signal synchronization, local, or intraregional alterations were also examined using rfMRI measurements of the fractional amplitude of low-frequency fluctuations and regional homogeneity (ReHo). Finally, with alterations of different rfMRI measures identified, a support vector machine (SVM) learning algorithm was implemented for group classification. The results revealed both inter- (FC) and intra-regional (ReHo) alterations extensively distributed in both cortical and subcortical structures; and common alterations of these measures were identified bilaterally in the postcentral gyrus as well as in the basal ganglia and thalamus. Of the rfMRI features examined, seven of them (four FC and three ReHo measures) survived the SVM procedure of recursive feature elimination and together provided the highest group classification accuracy of 90.6%. The present findings extend previous studies of rfMRI in CD and offer insight into the underlying pathophysiology of the disorder in relation to network dysfunction and somatosensory disturbances. Hum Brain Mapp 38:4098-4108, 2017. © 2017 Wiley Periodicals, Inc.

Neural Substrates for Head Movements in Humans: A Functional Magnetic Resonance Imaging Study.

The neural systems controlling head movements are not well delineated in humans. It is not clear whether the ipsilateral or contralateral primary motor cortex is involved in turning the head right or left. Furthermore, the exact location of the neck motor area in the somatotopic organization of the motor homunculus is still debated and evidence for contributions from other brain regions in humans is scarce. Because currently available neuroimaging methods are not generally suitable for mapping brain activation patterns during head movements, we conducted fMRI scans during isometric tasks of the head. During isometric tasks, muscle contractions occur without an actual movement and they have been used to delineate patterns of brain activity related to movements of other body parts such as the hands. Healthy individuals were scanned during isometric head rotation or wrist extension. Isometric wrist extension was examined as a positive control and to establish the relative locations of head and hand regions in the motor cortex. Electromyographic recordings of neck and hand muscles during scanning ensured compliance with the tasks. Increased brain activity during isometric head rotation was observed bilaterally in the precentral gyrus, both medial and lateral to the hand area, as well the supplementary motor area, insula, putamen, and cerebellum. These findings clarify the location of the neck region in the motor homunculus and help to reconcile some of the conflicting results obtained in earlier studies.

Neural changes with tactile learning reflect decision-level reweighting of perceptual readout.

Despite considerable work, the neural basis of perceptual learning remains uncertain. For visual learning, although some studies suggested that changes in early sensory representations are responsible, other studies point to decision-level reweighting of perceptual readout. These competing possibilities have not been examined in other sensory systems, investigating which could help resolve the issue. Here we report a study of human tactile microspatial learning in which participants achieved >six-fold decline in acuity threshold after multiple training sessions. Functional magnetic resonance imaging was performed during performance of the tactile microspatial task and a control, tactile temporal task. Effective connectivity between relevant brain regions was estimated using multivariate, autoregressive models of hidden neuronal variables obtained by deconvolution of the hemodynamic response. Training-specific increases in task-selective activation assessed using the task × session interaction and associated changes in effective connectivity primarily involved subcortical and anterior neocortical regions implicated in motor and/or decision processes, rather than somatosensory cortical regions. A control group of participants tested twice, without intervening training, exhibited neither threshold improvement nor increases in task-selective activation. Our observations argue that neuroplasticity mediating perceptual learning occurs at the stage of perceptual readout by decision networks. This is consonant with the growing shift away from strictly modular conceptualization of the brain toward the idea that complex network interactions underlie even simple tasks. The convergence of our findings on tactile learning with recent studies of visual learning reconciles earlier discrepancies in the literature on perceptual learning.

Mnemonic strategy training partially restores hippocampal activity in patients with mild cognitive impairment.

Learning and memory deficits typify patients with mild cognitive impairment (MCI) and are generally attributed to medial temporal lobe dysfunction. Although the hippocampus is perhaps the most commonly studied neuroanatomical structure in these patients, there have been few attempts to identify rehabilitative interventions that facilitate its functioning. Here, we present results from a randomized, controlled, single-blind study in which patients with MCI and healthy elderly controls (HEC) were randomized to either three sessions of mnemonic strategy training (MS) or a matched-exposure control group (XP). All participants underwent pre- and posttraining fMRI scanning as they encoded and retrieved object-location associations. For the current report, fMRI analyses were restricted to the hippocampus, as defined anatomically. Before training, MCI patients showed reduced hippocampal activity during both encoding and retrieval, relative to HEC. Following training, the MCI MS group demonstrated increased activity during both encoding and retrieval. There were significant differences between the MCI MS and MCI XP groups during retrieval, especially within the right hippocampus. Thus, MS facilitated hippocampal functioning in a partially restorative manner. We conclude that cognitive rehabilitation techniques may help mitigate hippocampal dysfunction in MCI patients.

Art for reward's sake: visual art recruits the ventral striatum.

A recent study showed that people evaluate products more positively when they are physically associated with art images than similar non-art images. Neuroimaging studies of visual art have investigated artistic style and esthetic preference but not brain responses attributable specifically to the artistic status of images. Here we tested the hypothesis that the artistic status of images engages reward circuitry, using event-related functional magnetic resonance imaging (fMRI) during viewing of art and non-art images matched for content. Subjects made animacy judgments in response to each image. Relative to non-art images, art images activated, on both subject- and item-wise analyses, reward-related regions: the ventral striatum, hypothalamus and orbitofrontal cortex. Neither response times nor ratings of familiarity or esthetic preference for art images correlated significantly with activity that was selective for art images, suggesting that these variables were not responsible for the art-selective activations. Investigation of effective connectivity, using time-varying, wavelet-based, correlation-purged Granger causality analyses, further showed that the ventral striatum was driven by visual cortical regions when viewing art images but not non-art images, and was not driven by regions that correlated with esthetic preference for either art or non-art images. These findings are consistent with our hypothesis, leading us to propose that the appeal of visual art involves activation of reward circuitry based on artistic status alone and independently of its hedonic value.

Dual pathways for haptic and visual perception of spatial and texture information.

Segregation of information flow along a dorsally directed pathway for processing object location and a ventrally directed pathway for processing object identity is well established in the visual and auditory systems, but is less clear in the somatosensory system. We hypothesized that segregation of location vs. identity information in touch would be evident if texture is the relevant property for stimulus identity, given the salience of texture for touch. Here, we used functional magnetic resonance imaging (fMRI) to investigate whether the pathways for haptic and visual processing of location and texture are segregated, and the extent of bisensory convergence. Haptic texture-selectivity was found in the parietal operculum and posterior visual cortex bilaterally, and in parts of left inferior frontal cortex. There was bisensory texture-selectivity at some of these sites in posterior visual and left inferior frontal cortex. Connectivity analyses demonstrated, in each modality, flow of information from unisensory non-selective areas to modality-specific texture-selective areas and further to bisensory texture-selective areas. Location-selectivity was mostly bisensory, occurring in dorsal areas, including the frontal eye fields and multiple regions around the intraparietal sulcus bilaterally. Many of these regions received input from unisensory areas in both modalities. Together with earlier studies, the activation and connectivity analyses of the present study establish that somatosensory processing flows into segregated pathways for location and object identity information. The location-selective somatosensory pathway converges with its visual counterpart in dorsal frontoparietal cortex, while the texture-selective somatosensory pathway runs through the parietal operculum before converging with its visual counterpart in visual and frontal cortex. Both segregation of sensory processing according to object property and multisensory convergence appear to be universal organizing principles.

Neural Basis of the Sound-Symbolic Crossmodal Correspondence Between Auditory Pseudowords and Visual Shapes.

Sound symbolism refers to the association between the sounds of words and their meanings, often studied using the crossmodal correspondence between auditory pseudowords, e.g., 'takete' or 'maluma', and pointed or rounded visual shapes, respectively. In a functional magnetic resonance imaging study, participants were presented with pseudoword-shape pairs that were sound-symbolically congruent or incongruent. We found no significant congruency effects in the blood oxygenation level-dependent (BOLD) signal when participants were attending to visual shapes. During attention to auditory pseudowords, however, we observed greater BOLD activity for incongruent compared to congruent audiovisual pairs bilaterally in the intraparietal sulcus and supramarginal gyrus, and in the left middle frontal gyrus. We compared this activity to independent functional contrasts designed to test competing explanations of sound symbolism, but found no evidence for mediation via language, and only limited evidence for accounts based on multisensory integration and a general magnitude system. Instead, we suggest that the observed incongruency effects are likely to reflect phonological processing and/or multisensory attention. These findings advance our understanding of sound-to-meaning mapping in the brain.

Object familiarity modulates effective connectivity during haptic shape perception.

In the preceding paper (Lacey, S., Flueckiger, P., Stilla, R., Lava, M., Sathian, K., 2009a. Object familiarity modulates involvement of visual imagery in haptic shape perception), we showed that the activations evoked by visual imagery overlapped more extensively, and their magnitudes were more correlated, with those evoked during haptic shape perception of familiar, compared to unfamiliar, objects. Here we used task-specific analyses of functional and effective connectivity to provide convergent evidence. These analyses showed that the visual imagery and familiar haptic shape tasks activated similar networks, whereas the unfamiliar haptic shape task activated a different network. Multivariate Granger causality analyses of effective connectivity, in both a conventional form and one purged of zero-lag correlations, showed that the visual imagery and familiar haptic shape networks involved top-down paths from prefrontal cortex into the lateral occipital complex (LOC), whereas the unfamiliar haptic shape network was characterized by bottom-up, somatosensory inputs into the LOC. We conclude that shape representations in the LOC are flexibly accessible, either top-down or bottom-up, according to task demands, and that visual imagery is more involved in LOC activation during haptic shape perception when objects are familiar, compared to unfamiliar.

Object familiarity modulates the relationship between visual object imagery and haptic shape perception.

Although visual cortical engagement in haptic shape perception is well established, its relationship with visual imagery remains controversial. We addressed this using functional magnetic resonance imaging during separate visual object imagery and haptic shape perception tasks. Two experiments were conducted. In the first experiment, the haptic shape task employed unfamiliar, meaningless objects, whereas familiar objects were used in the second experiment. The activations evoked by visual object imagery overlapped more extensively, and their magnitudes were more correlated, with those evoked during haptic shape perception of familiar, compared to unfamiliar, objects. In the companion paper (Deshpande et al., this issue), we used task-specific functional and effective connectivity analyses to provide convergent evidence: these analyses showed that the neural networks underlying visual imagery were similar to those underlying haptic shape perception of familiar, but not unfamiliar, objects. We conclude that visual object imagery is more closely linked to haptic shape perception when objects are familiar, compared to when they are unfamiliar.

Mnemonic strategy training increases neocortical activation in healthy older adults and patients with mild cognitive impairment.

Learning and memory deficits characterize the diagnosis of amnestic mild cognitive impairment (aMCI), which is widely viewed as a clinical precursor to Alzheimer's type dementia. There is a growing interest in non-pharmacologic interventions, such as mnemonic strategies, for improving learning and memory in patients with aMCI as well as for maintaining functioning in healthy older adults. Using an ecologically relevant object-location association paradigm, we conducted a randomized, controlled, single-blind study in which healthy older adults and patients with aMCI were randomized to either mnemonic strategy training or a control group that was matched for stimulus exposure. We previously reported that mnemonic strategy training resulted in significantly greater learning and memory improvements compared to the matched exposure condition, in both aMCI patients and healthy controls. The current study examined changes in neocortical activation during encoding in a subset of participants who underwent functional magnetic resonance imaging (fMRI) scanning both before and after training. To minimize potential confounds in between-group comparisons, we employed non-linear cortex based alignment and included only correctly encoded stimuli in our analyses. When re-encoding stimuli learned during training (i.e., trained stimuli), we found a general enhancement of activation in right prefrontal and parietal regions, possibly reflecting practice-related improvement in coordinate spatial processing in all but the aMCI exposure group. Left hemisphere activation was typically only evident in the mnemonic strategy trained participants, regardless of diagnostic status, with the ventrolateral prefrontal cortex appearing especially important for strategy use. While encoding relatively novel stimuli, both mnemonic strategy groups (aMCI patients and healthy controls) demonstrated increased activation in a subset of regions showing change for the trained stimuli, indicating a mnemonic strategy-induced change in the processing of new information. These findings could not be explained by repeated exposure since there was little to no activation overlap in the respective exposure control groups. The current results reinforce the potential benefits of cognitive interventions in these growing populations and indicate that neuroplastic change in key rostral and lateral prefrontal regions mediate this behavioral change.

Posteromedial parietal cortical activity and inputs predict tactile spatial acuity.

We used functional magnetic resonance imaging (fMRI) to investigate the neural circuitry underlying tactile spatial acuity at the human finger pad. Stimuli were linear, three-dot arrays, applied to the immobilized right index finger pad using a computer-controlled, MRI-compatible, pneumatic stimulator. Activity specific for spatial processing was isolated by contrasting discrimination of left-right offsets of the central dot in the array with discrimination of the duration of stimulation by an array without a spatial offset. This contrast revealed activity in a distributed frontoparietal cortical network, within which the levels of activity in right posteromedial parietal cortical foci [right posterior intraparietal sulcus (pIPS) and right precuneus] significantly predicted individual acuity thresholds. Connectivity patterns were assessed using both bivariate analysis of Granger causality with the right pIPS as a reference region and multivariate analysis of Granger causality for a selected set of regions. The strength of inputs into the right pIPS was significantly greater in subjects with better acuity than those with poorer acuity. In the better group, the paths predicting acuity converged from the left postcentral sulcus and right frontal eye field onto the right pIPS and were selective for the spatial task, and their weights predicted the level of right pIPS activity. We propose that the optimal strategy for fine tactile spatial discrimination involves interaction in the pIPS of a top-down control signal, possibly attentional, with somatosensory cortical inputs, reflecting either visualization of the spatial configurations of tactile stimuli or engagement of modality-independent circuits specialized for fine spatial processing.

Selective visuo-haptic processing of shape and texture.

Previous functional neuroimaging studies have described shape-selectivity for haptic stimuli in many cerebral cortical regions, of which some are also visually shape-selective. However, the literature is equivocal on the existence of haptic or visuo-haptic texture-selectivity. We report here on a human functional magnetic resonance imaging (fMRI) study in which shape and texture perception were contrasted using haptic stimuli presented to the right hand, and visual stimuli presented centrally. Bilateral selectivity for shape, with overlap between modalities, was found in a dorsal set of parietal areas: the postcentral sulcus and anterior, posterior and ventral parts of the intraparietal sulcus (IPS); as well as ventrally in the lateral occipital complex. The magnitude of visually- and haptically-evoked activity was significantly correlated across subjects in the left posterior IPS and right lateral occipital complex, suggesting that these areas specifically house representations of object shape. Haptic shape-selectivity was also found in the left postcentral gyrus, the left lingual gyrus, and a number of frontal cortical sites. Haptic texture-selectivity was found in ventral somatosensory areas: the parietal operculum and posterior insula bilaterally, as well as in the right medial occipital cortex, overlapping with a medial occipital cortical region, which was texture-selective for visual stimuli. The present report corroborates and elaborates previous suggestions of specialized visuo-haptic processing of texture and shape.

Neural processing underlying tactile microspatial discrimination in the blind: a functional magnetic resonance imaging study.

Although blindness alters neocortical processing of non-visual tasks, previous studies do not allow clear conclusions about purely perceptual tasks. We used functional magnetic resonance imaging (fMRI) to examine the neural processing underlying tactile microspatial discrimination in the blind. Activity during the tactile microspatial task was contrasted against that during a tactile temporal discrimination task. The spatially selective network included frontoparietal and visual cortical regions. Activation magnitudes in left primary somatosensory cortex and in visual cortical foci predicted acuity thresholds. Effective connectivity was investigated using multivariate Granger causality analyses. Bilateral primary somatosensory cortical foci and a left inferior temporal focus were important sources of connections. Visual cortical regions interacted mainly with one another and with somatosensory cortical regions. Among a set of distributed cortical regions exhibiting greater spatial selectivity in early blind compared to late blind individuals, the age of complete blindness was predicted by activity in a subset of frontoparietal regions and by the weight of a path from the right lateral occipital complex to right occipitopolar cortex. Thus, many aspects of neural processing during tactile microspatial discrimination differ between the blind and sighted, with some of the key differences reflecting visual cortical engagement in the blind.

Neural basis of the crossmodal correspondence between auditory pitch and visuospatial elevation.

Crossmodal correspondences refer to associations between otherwise unrelated stimulus features in different sensory modalities. For example, high and low auditory pitches are associated with high and low visuospatial elevation, respectively. The neural mechanisms underlying crossmodal correspondences are currently unknown. Here, we used functional magnetic resonance imaging (fMRI) to investigate the neural basis of the pitch-elevation correspondence. Pitch-elevation congruency effects were observed bilaterally in the inferior frontal and insular cortex, the right frontal eye field and right inferior parietal cortex. Independent functional localizers failed to provide strong evidence for any of three proposed mechanisms for crossmodal correspondences: semantic mediation, magnitude estimation, and multisensory integration. Instead, pitch-elevation congruency effects overlapped with areas selective for visually presented non-word strings relative to sentences, and with regions sensitive to audiovisual asynchrony. Taken together with the prior literature, the observed congruency effects are most consistent with mediation by multisensory attention.

Activity and effective connectivity of parietal and occipital cortical regions during haptic shape perception.

It is now widely accepted that visual cortical areas are active during normal tactile perception, but the underlying mechanisms are still not clear. The goal of the present study was to use functional magnetic resonance imaging (fMRI) to investigate the activity and effective connectivity of parietal and occipital cortical areas during haptic shape perception, with a view to potentially clarifying the role of top-down and bottom-up inputs into visual areas. Subjects underwent fMRI scanning while engaging in discrimination of haptic shape or texture, and in separate runs, visual shape or texture. Accuracy did not differ significantly between tasks. Haptic shape-selective regions, identified on a contrast between the haptic shape and texture conditions in individual subjects, were found bilaterally in the postcentral sulcus (PCS), multiple parts of the intraparietal sulcus (IPS) and the lateral occipital complex (LOC). The IPS and LOC foci tended to be shape-selective in the visual modality as well. Structural equation modelling was used to study the effective connectivity among the haptic shape-selective regions in the left hemisphere, contralateral to the stimulated hand. All possible models were tested for their fit to the correlations among the observed time-courses of activity. Two equivalent models emerged as the winners. These models, which were quite similar, were characterized by both bottom-up paths from the PCS to parts of the IPS, and top-down paths from the LOC and parts of the IPS to the PCS. We conclude that interactions between unisensory and multisensory cortical areas involve bidirectional information flow.

Engagement of the left extrastriate body area during body-part metaphor comprehension.

Grounded cognition explanations of metaphor comprehension predict activation of sensorimotor cortices relevant to the metaphor's source domain. We tested this prediction for body-part metaphors using functional magnetic resonance imaging while participants heard sentences containing metaphorical or literal references to body parts, and comparable control sentences. Localizer scans identified body-part-specific motor, somatosensory and visual cortical regions. Both subject- and item-wise analyses showed that, relative to control sentences, metaphorical but not literal sentences evoked limb metaphor-specific activity in the left extrastriate body area (EBA), paralleling the EBA's known visual limb-selectivity. The EBA focus exhibited resting-state functional connectivity with ipsilateral semantic processing regions. In some of these regions, the strength of resting-state connectivity correlated with individual preference for verbal processing. Effective connectivity analyses showed that, during metaphor comprehension, activity in some semantic regions drove that in the EBA. These results provide converging evidence for grounding of metaphor processing in domain-specific sensorimotor cortical activity.

A Functional Magnetic Resonance Imaging Study of Head Movements in Cervical Dystonia.

Cervical dystonia (CD) is a neurological disorder characterized by abnormal movements and postures of the head. The brain regions responsible for these abnormal movements are not well understood, because most imaging techniques for assessing regional brain activity cannot be used when the head is moving. Recently, we mapped brain activation in healthy individuals using functional magnetic resonance imaging during isometric head rotation, when muscle contractions occur without actual head movements. In the current study, we used the same methods to explore the neural substrates for head movements in subjects with CD who had predominantly rotational abnormalities (torticollis). Isometric wrist extension was examined for comparison. Electromyography of neck and hand muscles ensured compliance with tasks during scanning, and any head motion was measured and corrected. Data were analyzed in three steps. First, we conducted within-group analyses to examine task-related activation patterns separately in subjects with CD and in healthy controls. Next, we directly compared task-related activation patterns between participants with CD and controls. Finally, considering that the abnormal head movements in CD occur in a consistently patterned direction for each individual, we conducted exploratory analyses that involved normalizing data according to the direction of rotational CD. The between-group comparisons failed to reveal any significant differences, but the normalization procedure in subjects with CD revealed that isometric head rotation in the direction of dystonic head rotation was associated with more activation in the ipsilateral anterior cerebellum, whereas isometric head rotation in the opposite direction was associated with more activity in sensorimotor cortex. These findings suggest that the cerebellum contributes to abnormal head rotation in CD, whereas regions in the cerebral cortex are involved in opposing the involuntary movements.

Spatial imagery in haptic shape perception.

We have proposed that haptic activation of the shape-selective lateral occipital complex (LOC) reflects a model of multisensory object representation in which the role of visual imagery is modulated by object familiarity. Supporting this, a previous functional magnetic resonance imaging (fMRI) study from our laboratory used inter-task correlations of blood oxygenation level-dependent (BOLD) signal magnitude and effective connectivity (EC) patterns based on the BOLD signals to show that the neural processes underlying visual object imagery (objIMG) are more similar to those mediating haptic perception of familiar (fHS) than unfamiliar (uHS) shapes. Here we employed fMRI to test a further hypothesis derived from our model, that spatial imagery (spIMG) would evoke activation and effective connectivity patterns more related to uHS than fHS. We found that few of the regions conjointly activated by spIMG and either fHS or uHS showed inter-task correlations of BOLD signal magnitudes, with parietal foci featuring in both sets of correlations. This may indicate some involvement of spIMG in HS regardless of object familiarity, contrary to our hypothesis, although we cannot rule out alternative explanations for the commonalities between the networks, such as generic imagery or spatial processes. EC analyses, based on inferred neuronal time series obtained by deconvolution of the hemodynamic response function from the measured BOLD time series, showed that spIMG shared more common paths with uHS than fHS. Re-analysis of our previous data, using the same EC methods as those used here, showed that, by contrast, objIMG shared more common paths with fHS than uHS. Thus, although our model requires some refinement, its basic architecture is supported: a stronger relationship between spIMG and uHS compared to fHS, and a stronger relationship between objIMG and fHS compared to uHS.

Metaphorically feeling: comprehending textural metaphors activates somatosensory cortex.

Conceptual metaphor theory suggests that knowledge is structured around metaphorical mappings derived from physical experience. Segregated processing of object properties in sensory cortex allows testing of the hypothesis that metaphor processing recruits activity in domain-specific sensory cortex. Using functional magnetic resonance imaging (fMRI) we show that texture-selective somatosensory cortex in the parietal operculum is activated when processing sentences containing textural metaphors, compared to literal sentences matched for meaning. This finding supports the idea that comprehension of metaphors is perceptually grounded.

Where did I put that? Patients with amnestic mild cognitive impairment demonstrate widespread reductions in activity during the encoding of ecologically relevant object-location associations.

Remembering the location of objects in the environment is both important in everyday life and difficult for patients with amnestic mild cognitive impairment (aMCI), a clinical precursor to Alzheimer's disease. To test the hypothesis that memory impairment for object location in aMCI reflects hippocampal dysfunction, we used an event-related functional magnetic resonance imaging paradigm to compare patients with aMCI and healthy elderly controls (HEC) as they encoded 90 ecologically relevant object-location associations (OLAs). Two additional OLAs, repeated a total of 45 times, served as control stimuli. Memory for these OLAs was assessed following a 1-h delay. The groups were well matched on demographics and brain volumetrics. Behaviorally, HEC remembered significantly more OLAs than did aMCI patients. Activity differences were assessed by contrasting activation for successfully encoded Novel stimuli vs. Repeated stimuli. The HEC demonstrated activity within object-related (ventral visual stream), spatial location-related (dorsal visual stream), and feature binding-related cortical regions (hippocampus and other memory-related regions) as well as in frontal cortex and associated subcortical structures. Activity in most of these regions correlated with memory test performance. Although the aMCI patients demonstrated a similar activation pattern, the HEC showed significantly greater activity within each of these regions. Memory test performance in aMCI patients, in contrast to the HEC, was correlated with activity in regions involved in sensorimotor processing. We conclude that aMCI patients demonstrate widespread cerebral dysfunction, not limited to the hippocampus, and rely on encoding-related mechanisms that differ substantially from healthy individuals.