Supramodal representation of emotions

Supramodal representation of emotion and its neural substrates have recently attracted attention as a marker of social cognition. However, the question whether perceptual integration of facial and vocal emotions takes place in primary sensory areas, multimodal cortices, or in affective structures remains unanswered yet. Using novel computer-generated stimuli, we combined emotional faces and voices in congruent and incongruent ways and assessed functional brain data (fMRI) during an emotional classification task. Both congruent and incongruent audiovisual stimuli evoked larger responses in thalamus and superior temporal regions compared with unimodal conditions. Congruent emotions were characterized by activation in amygdala, insula, ventral posterior cingulate (vPCC), temporo-occipital, and auditory cortices; incongruent emotions activated a frontoparietal network and bilateral caudate nucleus, indicating a greater processing load in working memory and emotion-encoding areas. The vPCC alone exhibited differential reactions to congruency and incongruency for all emotion categories and can thus be considered a central structure for supramodal representation of complex emotional information. Moreover, the left amygdala reflected supramodal representation of happy stimuli. These findings document that emotional information does not merge at the perceptual audiovisual integration level in unimodal or multimodal areas, but in vPCC and amygdala.     

Beliefs about human agency influence the neural processing of gaze during joint attention

The current study measured adults’ P350 and N170 ERPs while they interacted with a character in a virtual reality paradigm. Some participants believed the character was controlled by a human (“avatar” condition, n = 19); others believed it was controlled by a computer program (“agent” condition, n = 19). In each trial, participants initiated joint attention in order to direct the character’s gaze toward a target. In 50% of trials, the character gazed toward the target (congruent responses), and in 50% of trials the character gazed to a different location (incongruent response). In the avatar condition, the character’s incongruent gaze responses generated significantly larger P350 peaks at centro-parietal sites than congruent gaze responses. In the agent condition, the P350 effect was strikingly absent. Left occipitotemporal N170 responses were significantly smaller in the agent condition compared to the avatar condition for both congruent and incongruent gaze shifts. These data suggest that beliefs about human agency may recruit mechanisms that discriminate the social outcome of a gaze shift after approximately 350 ms, and that these mechanisms may modulate the early perceptual processing of gaze. These findings also suggest that the ecologically valid measurement of social cognition may depend upon paradigms that simulate genuine social interactions.     

Inactivation of the prelimbic, but not infralimbic, prefrontal cortex impairs the contextual control of response conflict in rats

One fundamental function of the prefrontal cortex (PFC) is to guide context-appropriate behaviour in situations of response conflict. Haddon and Killcross recently developed a task in rats which mimics some aspects of response conflict seen in human cognitive paradigms such as the Stroop task. Using this paradigm they demonstrated that large PFC lesions including the prelimbic (PL), infralimbic (IL) and anterior cingulate cortices (ACC) selectively impaired performance on incongruent trials which required the use of task-setting contextual cues to control responding in the face of ambiguous response information. The current experiment was conducted to determine whether specific PFC regions were responsible for the deficit in incongruent performance. Rats were trained on two instrumental biconditional discriminations, one auditory and one visual, in two different contexts. Following acquisition, rats were implanted with guide cannulae aimed at the PL or the IL cortices of the rat prefrontal cortex. Following retraining, rats received microinfusions of the GABA(A) agonist muscimol or artificial cerebrospinal fluid (aCSF) into either the PL or the IL prior to presentations of novel congruent and incongruent audiovisual compounds of the training stimuli in extinction. Results showed that temporary inactivation of the PL cortex led to a selective deficit on incongruent compound trials, but left congruent, and hence biconditional task performance intact. By contrast, IL inactivation had no effect on the accuracy of responding during either congruent or incongruent trials. These results suggest that the PL cortex is necessary for the use of task-setting contextual cues to control responding to conflicting information.     

Neural basis of the Stroop interference task: response competition or selective attention?

Previous neuroimaging studies of the Stroop task have postulated that the anterior cingulate cortex (ACC) plays a critical role in resolution of the Stroop interference condition. However, activation of the ACC is not invariably seen and appears to depend on a variety of methodological factors, including the degree of response conflict and response expectancies. The present functional MRI study was designed to identify those brain areas critically involved in the interference condition. Healthy subjects underwent a blocked-trial design fMRI experiment while responding to 1 of 3 stimulus conditions: (1) incongruent color words, (2) congruent color words, and (3) color-neutral words. Subjects responded to the printed color of the word via a manual response. Compared to the congruent and neutral conditions, the incongruent condition produced significant activation within the left inferior precentral sulcus (IpreCS) located on the border between the inferior frontal gyrus, pars opercularis (BA 44) and the ventral premotor region (BA 6). Significant deactivations in the rostral component of the ACC and the posterior cingulate gyrus were also observed. Selective activation of the left IpreCS is compatible with findings from previous neuroimaging, lesion, electrophysiological, and behavioral studies and is presumably related to the mediation of competing articulatory demands during the interference condition.     

Individual differences in science competence among students are associated with ventrolateral prefrontal cortex activation

Functional neuroimaging studies have revealed that, compared with novices, science experts show increased activation in dorsolateral and ventrolateral prefrontal brain areas associated with inhibitory control mechanisms when providing scientifically valid responses in tasks related to electricity and mechanics. However, no study thus far has explored the relationship between activation of the key brain regions involved in inhibitory control mechanisms, namely the ventrolateral prefrontal cortex (VLPC) and dorsolateral prefrontal cortex (DLPC), and individual differences in conceptual science competence, while controlling for scientific training. In the present study, 24 secondary school students (11 female participants, 13 male participants) were selected from a larger pool based on their performance on a conceptual science questionnaire and were divided into groups with low and high conceptual science competence. In an fMRI block design, participants had to verify the correctness (true or false) of congruent and incongruent statements. In congruent statements, both spontaneous and scientific conceptions about given natural phenomena lead to a scientifically appropriate judgment. However, in incongruent statements, commonly held spontaneous conceptions about natural phenomena lead to a scientifically inappropriate judgment. The interaction effect reveals that students with higher conceptual science competence display stronger activation of the left VLPC and DLPC in incongruent trials than in congruent trials. These findings show that activation of the VLPC and DLPC when reasoning in incongruent situations underlies individual differences in conceptual science competence, and suggests stronger recruitment of inhibitory control mechanisms in more competent individuals.     

Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder

OBJECTIVE: While adolescent anxiety disorders represent prevalent, debilitating conditions, few studies have explored their brain physiology. Using event-related functional magnetic resonance imaging (fMRI) and a behavioral measure of attention to angry faces, the authors evaluated differences in response between healthy adolescents and adolescents with generalized anxiety disorder. METHOD: In the primary trials of interest, 18 adolescents with generalized anxiety disorder and 15 comparison subjects of equivalent age/gender/IQ viewed angry/neutral face pairs during fMRI acquisition. Following the presentation of each face pair, subjects pressed a button to indicate whether a subsequent asterisk appeared on the same (congruent) or opposite (incongruent) side as the angry face. Reaction time differences between congruent and incongruent face trials provided a measure of attention bias to angry faces. RESULTS: Relative to the comparison subjects, patients with generalized anxiety disorder manifested greater right ventrolateral prefrontal cortex activation to trials containing angry faces. Patients with generalized anxiety disorder also showed greater attention bias away from angry faces. Ventrolateral prefrontal cortex activation differences remained evident when differences in attention bias were covaried. Finally, in an examination among patients of the association between degree of anxiety and brain activation, the authors found that as ventrolateral prefrontal cortex activation increased, severity of anxiety symptoms diminished. CONCLUSIONS: Adolescents with generalized anxiety disorder show greater right ventrolateral prefrontal cortex activation and attentional bias away from angry faces than healthy adolescents. Among patients, increased ventrolateral prefrontal cortex activation is associated with less severe anxiety, suggesting that this activation may serve as a compensatory response.     

Neural evidence of motivational conflict between social values

Motivational interdependence is an organizing principle in Schwartz’s circumplex model of social values, which has received abundant cross-cultural support. We used fMRI to test whether motivational relations between social values predict different brain responses in a situation of choice between values. We hypothesized that differences in brain responses would become evident when the more important value had to be selected in pairs of congruent (e.g., wealth and success) as opposed to incongruent (e.g., curiosity and stability) values as they are described in Schwartz’s model, because the former serve mutually facilitating motives, whereas the latter serve mutually inhibiting motives. Consistent with the model, choosing between congruent values led to longer response times and more activation in conflict-related brain regions (e.g., the supplementary motor area, dorsolateral prefrontal cortex) than selecting between incongruent values. These results provide novel neural evidence supporting the circumplex model’s predictions about motivational interdependence between social values. In particular, our results show that the neural networks underlying social values are organized in a way that allows activation patterns related to motivational similarity between congruent values to be dissociated from those related to incongruent values.     

Mapping reflexive shifts of attention in eye-centered and hand-centered coordinate systems

Behavioral studies indicate that directional gaze and hand pointing are fundamental social signals that may capture spatial attention more powerfully than directional arrows. By using fMRI, we explored whether reflexive shifts of attention triggered by different distracters were influenced by the motor effector used for performing an overt response. In separate blocks, healthy participants performed a directional saccadic or a hand pointing movement. Color changes of a central black fixation point constituted the imperative instruction signal to make a leftward (red color) or a rightward (blue color) movement while ignoring distracting leftward or rightward oriented gaze, hand pointing, or arrow. Distracters that were directionally incongruent with the instruction cue impaired the saccadic and pointing-release RTs. The comparison of incongruent vs. congruent conditions showed an increase of BOLD signal in the frontal eye field (FEF), the intraparietal sulcus (IPS), and the posterior parietal cortex (PPC) bilaterally. Importantly, a specific relationship between distracter and effector used for the response was found in these frontal and parietal regions. In particular, higher activity in the FEF, for distracting gaze was found mainly during the saccadic response task. In the same vein, higher activity in the left and right IPS regions was found for the distracting hand mainly in the hand pointing task. The results suggest that reflexive shifts of attention triggered by social signals are coded in the fronto-parietal cortex according to effector-specific mapping rules.     

A functional MRI study of multimodal selective attention following mild traumatic brain injury

Previous work suggests that the ability to selectively attend to and resolve conflicting information may be the most enduring cognitive deficit following mild traumatic brain injury (mTBI). The current study used fMRI to evaluate potential differences in hemodynamic activation in 22 mTBI patients and 22 carefully matched healthy controls (HC) during a multimodal selective attention task (numeric Stroop). Behavioral data indicated faster reaction times for congruent versus incongruent trials and for stimuli presented at 0.66 compared to 0.33 Hz across both groups, with minimal differences in behavioral performance across the groups. Similarly, there were no group-wise differences in functional activation within lateral and medial prefrontal cortex during the execution of cognitive control (incongruent versus congruent trials). In contrast, within-group comparisons indicated robust patterns of attention-related modulations (ARM) within the bilateral dorsolateral prefrontal cortex and bilateral visual streams for HC but not mTBI patients. In addition, mTBI patients failed to exhibit task-induced deactivation within the default-mode network (DMN) under conditions of higher attentional load. In summary, in spite of near normal behavioral performance, current results suggest within-group abnormalities during both the top-down allocation of visual attention and in regulating the DMN during the semi-acute stage of mTBI.     

Neural responses to rigidly moving faces displaying shifts in social attention investigated with fMRI and MEG

A widely adopted neural model of face perception (Haxby, Hoffman, & Gobbini, 2000) proposes that the posterior superior temporal sulcus (STS) represents the changeable features of a face, while the face-responsive fusiform gyrus (FFA) encodes invariant aspects of facial structure. ‘Changeable features’ of a face can include rigid and non-rigid movements. The current study investigated neural responses to rigid, moving faces displaying shifts in social attention. Both functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were used to investigate neural responses elicited when participants viewed video clips in which actors made a rigid shift of attention, signalled congruently from both the eyes and head. These responses were compared to those elicited by viewing static faces displaying stationary social attention information or a scrambled video displaying directional motion. Both the fMRI and MEG analyses demonstrated heightened responses along the STS to turning heads compared to static faces or scrambled movement conditions. The FFA responded to both turning heads and static faces, showing only a slight increase in response to the dynamic stimuli. These results establish the applicability of the Haxby model to the perception of rigid face motions expressing changes in social attention direction. Furthermore, the MEG beamforming analyses found an STS response in an upper frequency band (30-80 Hz) which peaked in the right anterior region. These findings, derived from two complementary neuroimaging techniques, clarify the contribution of the STS during the encoding of rigid facial action patterns of social attention, emphasising the role of anterior sulcal regions alongside previously observed posterior areas.     

The neural response to emotional prosody,as revealed by functional magnetic resonance imaging

Prosody is an important feature of language, comprising intonation, loudness, and tempo. Emotional prosodic processing forms an integral part of our social interactions. The main aim of this study was to use bold contrast fMRI to clarify the normal functional neuroanatomy of emotional prosody, in passive and active contexts. Subjects performed six separate scanning studies, within which two different conditions were contrasted: (1) "pure" emotional prosody versus rest; (2) congruent emotional prosody versus 'neutral' sentences; (3) congruent emotional prosody versus rest; (4) incongruent emotional prosody versus rest; (5) congruent versus incongruent emotional prosody; and (6) an active experiment in which subjects were instructed to either attend to the emotion conveyed by semantic content or that conveyed by tone of voice. Data resulting from these contrasts were analysed using SPM99. Passive listening to emotional prosody consistently activated the lateral temporal lobe (superior and/or middle temporal gyri). This temporal lobe response was relatively right-lateralised with or without semantic information. Both the separate and direct comparisons of congruent and incongruent emotional prosody revealed that subjects used fewer brain regions to process incongruent emotional prosody than congruent. The neural response to attention to semantics, was left lateralised, and recruited an extensive network not activated by attention to emotional prosody. Attention to emotional prosody modulated the response to speech, and induced right-lateralised activity, including the middle temporal gyrus. In confirming the results of lesion and neuropsychological studies, the current study emphasises the importance of the right hemisphere in the processing of emotional prosody, specifically the lateral temporal lobes.     

Primary and multisensory cortical activity is correlated with audiovisual percepts

Incongruent auditory and visual stimuli can elicit audiovisual illusions such as the McGurk effect where visual /ka/ and auditory /pa/ fuse into another percept such as/ta/. In the present study, human brain activity was measured with adaptation functional magnetic resonance imaging to investigate which brain areas support such audiovisual illusions. Subjects viewed trains of four movies beginning with three congruent /pa/ stimuli to induce adaptation. The fourth stimulus could be (i) another congruent /pa/, (ii) a congruent /ka/, (iii) an incongruent stimulus that evokes the McGurk effect in susceptible individuals (lips /ka/ voice /pa/), or (iv) the converse combination that does not cause the McGurk effect (lips /pa/ voice/ ka/). This paradigm was predicted to show increased release from adaptation (i.e. stronger brain activation) when the fourth movie and the related percept was increasingly different from the three previous movies. A stimulus change in either the auditory or the visual stimulus from /pa/ to /ka/ (iii, iv) produced within‐modality and cross‐modal responses in primary auditory and visual areas. A greater release from adaptation was observed for incongruent non‐McGurk (iv) compared to incongruent McGurk (iii) trials. A network including the primary auditory and visual cortices, nonprimary auditory cortex, and several multisensory areas (superior temporal sulcus, intraparietal sulcus, insula, and pre‐central cortex) showed a correlation between perceiving the McGurk effect and the fMRI signal, suggesting that these areas support the audiovisual illusion. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Activation of the caudal anterior cingulate cortex due to task‐related interference in an auditory Stroop paradigm

Successful information processing requires the focusing of attention on a certain stimulus property and the simultaneous suppression of irrelevant information. The Stroop task is a useful paradigm to study such attentional top‐down control in the presence of interference. Here, we investigated the neural correlates of an auditory Stroop task using fMRI. Subjects focused either on tone pitch (relatively high or low; phonetic task) or on the meaning of a spoken word (high/low/good; semantic task), while ignoring the other stimulus feature. We differentiated between task‐related (phonetic incongruent vs. semantic incongruent) and sensory‐level interference (phonetic incongruent vs. phonetic congruent). Task‐related interference activated similar regions as in visual Stroop tasks, including the anterior cingulate cortex (ACC) and the presupplementary motor‐area (pre‐SMA). More specifically, we observed that the very caudal/posterior part of the ACC was activated and not the dorsal/anterior region. Because identical stimuli but different task demands are compared in this contrast, it reflects conflict at a relatively high processing level. A more conventional contrast between incongruent and congruent phonetic trials was associated with a different cluster in the pre‐SMA/ACC which was observed in a large number of previous studies. Finally, functional connectivity analysis revealed that activity within the regions activated in the phonetic incongruent vs. semantic incongruent contrast was more strongly interrelated during semantically vs. phonetically incongruent trials. Taken together, we found (besides activation of regions well‐known from visual Stroop tasks) activation of the very caudal and posterior part of the ACC due to task‐related interference in an auditory Stroop task. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Activation in the angular gyrus and in the pSTS is modulated by face primes during voice recognition

The aim of the present study was to better understand the interaction of face and voice processing when identifying people. In a S1‐S2 crossmodal priming fMRI experiment, the target (S2) was a disyllabic voice stimulus, whereas the modality of the prime (S1) was manipulated blockwise and consisted of the silent video of a speaking face in the crossmodal condition or of a voice stimulus in the unimodal condition. Primes and targets were from the same speaker (person‐congruent) or from two different speakers (person‐incongruent). Participants had to classify the S2 as either an old or a young person. Response times were shorter after a congruent than after an incongruent face prime. The right posterior superior temporal sulcus (pSTS) and the right angular gyrus showed a significant person identity effect (person‐incongruent > person‐congruent) in the crossmodal condition but not in the unimodal condition. In the unimodal condition, a person identity effect was observed in the bilateral inferior frontal gyrus. Our data suggest that both the priming with a voice and with a face result in a preactivated voice representation of the respective person, which eventually facilitates (person‐congruent trials) or hampers (person‐incongruent trials) the processing of the identity of a subsequent voice. This process involves activation in the right pSTS and in the right angular gyrus for voices primed by faces, but not for voices primed by voices. Hum Brain Mapp 38:2553–2565, 2017. © 2017 Wiley Periodicals, Inc.     

Spatial attention can modulate audiovisual integration at multiple cortical and subcortical sites

The role of attention in multisensory integration (MI) is presently uncertain, with some studies supporting an automatic, pre-attentive process and others suggesting possible modulation through selective attention. The goal of this functional magnetic resonance imaging study was to investigate the role of spatial attention on the processing of congruent audiovisual speech stimuli (here indexing MI). Subjects were presented with two simultaneous visual streams (speaking lips in the left and right visual hemifields) plus a single central audio stream (spoken words). In the selective attention conditions, the auditory stream was congruent with one of the two visual streams. Subjects attended to either the congruent or the incongruent visual stream, allowing the comparison of brain activity for attended vs. unattended MI while the amount of multisensory information in the environment and the overall attentional requirements were held constant. Meridian mapping and a lateralized 'speaking-lips' localizer were used to identify early visual areas and to localize regions responding to contralateral visual stimulations. Results showed that attention to the congruent audiovisual stimulus resulted in increased activation in the superior temporal sulcus, striate and extrastriate retinotopic visual cortex, and superior colliculus. These findings demonstrate that audiovisual integration and spatial attention jointly interact to influence activity in an extensive network of brain areas, including associative regions, early sensory-specific visual cortex and subcortical structures that together contribute to the perception of a fused audiovisual percept.     

Neural Networks of Motor and Cognitive Inhibition are Dissociated Between Brain Hemispheres: An fMRI Study

Paradigms exploring cognitive inhibition involve motor responses, which may confound the results. We compare cognitive inhibition activation obtained without motor involvement, to motor inhibition alone, in a group of young right-handed volunteers, utilizing a classical color Stroop task (CST), and a Stop Task. Comparison of fMRI activation was performed contrasting lateralization indexes of different Regions of Interest (ROI). Cognitive inhibition showed left brain lateralization, while motor inhibition showed right brain lateralization. Homologue brain areas involved the inferior frontal gyrus, inferior parietal lobule, middle temporal gyrus, and anterior cingulate gyrus. These circuitries appear to support that inhibition is a complicated function involving working memory, attention, semantic decision, and motivation modules.     

Anterior cingulate cortex: an fMRI analysis of conflict specificity and functional differentiation

In this event-related functional magnetic resonance imaging (fMRI) study, we provide evidence that the role of the anterior cingulate cortex (ACC) in cognitive control may not be unitary, as the responses of different ACC subregions vary depending upon the nature of task-irrelevant information. More specifically, using the color-word Stroop task (congruent, incongruent, and neutral trial types), we examined the degree to which increases in neural activity within ACC are specific to conditions of conflict, as posited by the conflict monitoring theory (Botvinick et al. [1999]: Rev Neurosci 10:49-57; Carter et al. [1998]: Science 280:747-749). Although incongruent and congruent trials both involve two competing sources of color information (color word and ink color), only incongruent trials involve a direct conflict between task-relevant and task-irrelevant information. Although the anterior division of the ACC rostral zone exhibited conflict specific increases in neural activity (i.e., incongruent > congruent = neutral), the posterior division exhibited a more generalized pattern, increasing whenever the task-irrelevant information was color related, regardless of whether it was conflicting (i.e., incongruent and congruent > neutral). Our data thus suggest a possible functional differentiation within the ACC. As such, it is unlikely that the role of the ACC in cognitive control will be able to be accommodated by a single unifying theory.     

Eyes on me: an fMRI study of the effects of social gaze on action control

Previous evidence suggests that ‘social gaze’ can not only cause shifts in attention, but also can change the perception of objects located in the direction of gaze and how these objects will be manipulated by an observer. These findings implicate differences in the neural networks sub-serving action control driven by social cues as compared with nonsocial cues. Here, we sought to explore this hypothesis by using functional magnetic resonance imaging and a stimulus–response compatibility paradigm in which participants were asked to generate spatially congruent or incongruent motor responses to both social and nonsocial stimuli. Data analysis revealed recruitment of a dorsal frontoparietal network and the locus coeruleus for the generation of incongruent motor responses, areas previously implicated in controlling attention. As a correlate for the effect of ‘social gaze’ on action control, an interaction effect was observed for incongruent responses to social stimuli in sub-cortical structures, anterior cingulate and inferior frontal cortex. Our results, therefore, suggest that performing actions in a—albeit minimal—social context significantly changes the neural underpinnings of action control and recruits brain regions previously implicated in action monitoring, the reorienting of attention and social cognition.     

Neural correlates of covert orienting of visual spatial attention along vertical and horizontal dimensions

Covert orienting of spatial attention along the horizontal meridian of the visual field is mediated by a fronto-parietal neural network. The neural substrates underlying covert orienting of attention along the vertical meridian, however, are less understood. We recorded hemodynamic responses using functional magnetic resonance imaging (fMRI) from healthy volunteers in covert visual orienting tasks that required to detect targets either at the fixation or at peripheral attended locations on the horizontal or vertical meridian in the left (LVF), right (RVF), upper (UVF), and lower (LoVF) visual fields. We found that, relative to when attention was at the fixation, covert orienting of attention along the horizontal and vertical meridia induced enhanced activities in the superior parietal and frontal lobes bilaterally and the cerebellum. In addition, attention to the LoVF and UVF generated stronger activation in the medial frontal cortex, anterior cingulate, precuneus, and the cerebellum relative to attention along the horizontal meridian. The reversed contrast, however, produced stronger activation in the right lingual gyrus and right premotor cortex. The fMRI results suggest that, while a common neural network is engaged in guiding visual spatial attention along the vertical and horizontal dimensions, unique neural correlates are associated with covert attentional orienting along the vertical and horizontal meridia of the visual field.     

Increased cortical recruitment in Huntington's disease using a Simon task

Cognitive deficits in Huntington's disease (HD) have been attributed to neuronal degeneration within the striatum; however, postmortem and structural imaging studies have revealed more widespread morphological changes. To examine the impact of HD-related changes in regions outside the striatum, we used functional magnetic resonance imaging (fMRI) in HD to examine brain activation patterns using a Simon task that required a button press response to either congruent or incongruent arrow stimuli. Twenty mild to moderate stage HD patients and 17 healthy controls were scanned using a 3T GE scanner. Data analysis involved the use of statistical parametric mapping software with a random effects analysis model to investigate group differences brain activation patterns compared to baseline. HD patients recruited frontal and parietal cortical regions to perform the task, and also showed significantly greater activation, compared to controls, in the caudal anterior cingulate, insula, inferior parietal lobules, superior temporal gyrus bilaterally, right inferior frontal gyrus, right precuneus/superior parietal lobule, left precentral gyrus, and left dorsal premotor cortex. The significantly increased activation in anterior cingulate-frontal-motor-parietal cortex in HD may represent a primary dysfunction due to direct cell loss or damage in cortical regions, and/or a secondary compensatory mechanism of increased cortical recruitment due to primary striatal deficits.