Tracy L. Luks

Evidence for Anterior Cingulate Cortex Involvement in Monitoring Preparatory Attentional Set

An important cognitive function underlying unified, voluntary behavior is attentional control. Two frontal regions, anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), appear to be particularly involved in attentional control and monitoring. In this study, we investigated whether ACC is involved in monitoring the preparatory allocation of attention during task switching, or whether ACC is active only when subjects are processing target stimuli and selecting a response, via a cued-attention design. Event-related BOLD fMRI activity was examined using a cue-target paradigm in which subjects performed task switches that selectively required reallocation of attention when tasks changed. There were three cue conditions: informative switch, informative repeat, and neutral. There were four target conditions: informatively cued switch, informatively cued repeat, neutrally cued switch, and neutrally cued repeat. Significant ACC activity was observed following both informative switch and informative repeat cues, but not after neutral cues. No significant ACC activity was observed following any of the target conditions. Significant DLPFC activity was observed following all three cue conditions and following neutrally cued switch targets. Overall, our results suggest that ACC is involved in monitoring the preparatory allocation of attention for conflict at the level of activation of competing attentional sets. The results also support the role of DLPFC in holding cognitive goals in working memory and allocating attention to the appropriate processing systems to meet those goals.

Deficit in a Neural Correlate of Reality Monitoring in Schizophrenia Patients

Patients who suffer from the devastating psychiatric illness schizophrenia are plagued by hallucinations, bizarre behavior, and delusional ideas, such as believing that they are controlled by malevolent outside forces. A fundamental human cognitive operation that may contribute to these hallmark symptoms is the ability to maintain accurate and coherent self-referential processing over time, such as occurs during reality monitoring (distinguishing self-generated from externally perceived information). However, the neural bases for a disturbance in this operation in schizophrenia have not been fully explored. Using functional magnetic resonance imaging, we asked clinically stable schizophrenia patients to remember whether or not they had generated a target word during an earlier sentence completion task. We found that, during accurate performance of this self-referential source memory task, the schizophrenia subjects manifest a deficit in rostral medial prefrontal cortex (mPFC) activity--a brain region critically implicated in both the instantiation and the retrieval of self-referential information in healthy subjects. Impairment in rostral mPFC function likely plays a key role in the profound subjective disturbances that characterize schizophrenia and that are the aspect of the disorder most troubling to patients and to society at large.

Preparatory allocation of attention and adjustments in conflict processing.

Attentional control involves the ability to allocate preparatory attention to improve subsequent stimulus processing and response selection. There is behavioral evidence to support the hypothesis that increased expectancy of stimulus and response conflict may decrease the subsequent experience of conflict during task performance. We used a cued flanker and event-related fMRI design to separate processes involved in preparation from those involved in resolving conflict and to identify the brain systems involved in these processes as well as the association between preparatory activity levels and activity related to subsequent conflict processing. Our results demonstrate that preparatory attentional allocation following a cue to the upcoming level of conflict is mediated by a network involving Dorsolateral Prefrontal Cortex (DLPFC) and the Intraparietal Sulcus (IPS). Informed preparation for conflict processing was associated with decreased Anterior Cingulate Cortex/pre-Supplementary Motor Area (ACC/pre-SMA) and IPS activity during the flanker target presentation, supporting their roles in conflict processing and visuospatial attention during the flanker task. Ventrolateral Prefrontal Cortex/Orbitofrontal Cortex (VLPFC/OFC) was active when specific strategic task rule and outcome information was available.

Preparatory deployment of attention to motion activates higher-order motion-processing brain regions.

We used event-related fMRI to test the hypothesis that preparatory attention modulations occur in higher-order motion-processing regions when subjects deploy attention to internally driven representations in a complex motion-processing task. Using a cued attention-to-motion task, we found preparatory increases in fMRI activity in visual motion regions in the absence of visual motion stimulation. The cue, a brief enlargement of the fixation cross, directed subjects to prepare for a complex motion discrimination task. This preparation activated higher-order and lower-order motion regions. The motion regions activated included temporal regions consistent with V5/MT+, occipital regions consistent with V3+, parietal-occipital junction regions, ventral and dorsal intraparietal sulcus, superior temporal sulcus (STS), posterior insular cortex (PIC), and a region of BA 39/40 superior to V5/MT+ involving the angular gyrus and supramarginal gyrus (A-SM). Consistent with our hypothesis that these motion sensory activations are under top-down control, we also found activation of an extensive frontal network during the cue period, including anterior cingulate and multiple prefrontal regions. These results support the hypothesis that anticipatory deployment of attention to internally driven representations is achieved via top-down modulation of activity in task-relevant processing areas.

Intensive cognitive training in schizophrenia enhances working memory and associated prefrontal cortical efficiency in a manner that drives long-term functional gains

We investigated whether intensive computerized cognitive training in schizophrenia could improve working memory performance and increase signal efficiency of associated middle frontal gyri (MFG) circuits in a functionally meaningful manner. Thirty schizophrenia participants and 13 healthy comparison participants underwent fMRI scanning during a letter N-back working memory task. Schizophrenia participants were then randomly assigned to either 80 h (16 weeks) of cognitive training or a computer games control condition. After this intervention, participants completed a second fMRI N-back scanning session. At baseline, during 2-back working memory trials, healthy participants showed the largest and most significant activation in bilateral MFG, which correlated with task performance. Schizophrenia participants showed impaired working memory, hypoactivation in left MFG, and no correlation between bilateral MFG signal and task performance. After training, schizophrenia participants improved their 2-back working memory performance and showed increased activation in left MFG. They also demonstrated a significant association between enhanced task performance and right MFG signal, similar to healthy participants. Both task performance and brain activity in right MFG after training predicted better generalized working memory at 6-month follow-up. Furthermore, task performance and brain activity within bilateral MFG predicted better occupational functioning at 6-month follow-up. No such findings were observed in the computer games control participants. Working memory impairments in schizophrenia and its underlying neural correlates in MFG can be improved by intensive computerized cognitive training; these improvements generalize beyond the trained task and are associated with enduring effects on cognition and functioning 6 months after the intervention.

Brain activation patterns during memory of cognitive agency.

Agency is the awareness that ones own self is the agent or author of an action, a thought, or a feeling. The implicit memory that ones self was the originator of a cognitive event - the sense of cognitive agency - has not yet been fully explored in terms of relevant neural systems. In this functional magnetic resonance imaging (fMRI) study, we examined brain activation patterns differentiating memory for the source of previously self-generated vs. experimenter-presented word items from a sentence completion paradigm designed to be emotionally neutral and semantically constrained in content. Accurate memory for the source of self-generated vs. externally-presented word items resulted in activation of dorsal medial prefrontal cortex (mPFC) bilaterally, supporting an emerging body of work that indicates a key role for this region in self-referential processing. Our data extend the function of mPFC into the domain of memory and the accurate retrieval of the sense of cognitive agency under conditions where agency was encoded implicitly.

Smoking-Related Cue-Induced Brain Activation in Adolescent Light Smokers

PURPOSE To examine using functional magnetic resonance imaging whether adolescents with low levels of nicotine exposure (light smokers) display neural activation in areas shown to be involved with addiction in response to smoking-related stimuli. DESIGN/SETTING/PARTICIPANTS A total of 12 adolescent light smokers (aged 13-17, who smoked 1-5 cigarettes per day) and 12 nonsmokers (ages 13-17, never smoked a cigarette) from the San Francisco Bay Area underwent functional magnetic resonance imaging scanning. During scanning, the adolescents were shown photographic blocks of smoking and control cues. Smoking cues comprised pictures of individuals smoking cigarettes and smoking-related objects such as lighters and ashtrays. Neutral cues comprised images of everyday objects and individuals engaged in daily activities. FINDINGS For smokers, smoking cues elicited greater activation than neutral cues in the mesolimbic reward circuit (left anterior cingulate: t = 7.04, p < .001; right hippocampus: t = 6.37, p < .001). We found activation from smoking cues versus neutral cues within both the left and right frontal medial orbital regions (t = 5.09, p < .001 and t = 3.94, p = .001, respectively). Nonsmokers showed no significant difference in activation between smoking-related cues and neutral cues. CONCLUSION Our finding that smoking cues produced activation in adolescent light smokers in brain regions, similar to that seen in adult and teenage heavy smokers, suggests that adolescents exhibit heightened reactivity to smoking cues even at low levels of smoking. This article adds to the existing published data by suggesting that nicotine dependence may begin with exposure to low levels of nicotine, thus underscoring the need for early intervention among adolescent smokers.

A longitudinal study of ventricular volume in early relapsing-remitting multiple sclerosis

The specific aim of this study was to determine whether progressive brain atrophy could be detected within 18 months of establishing a diagnosis of relapsing-remitting multiple sclerosis (RRMS). Fifteen patients with clinically definite RRMS (mean disease duration from first symptom=6 months, mean EDSS=1.2) completed 6-14 monthly quantitative MRI sessions. The volume of the lateral ventricles was determined each month using a semi-automated thresholding technique from T1-weighted axial images. The number of new monthly gadolinium-enhancing (Gd+) lesions and EDSS scores were also recorded. Lateral ventricular volumes increased significantly during this study. When individual data were examined, statistically significant changes were observed in six of 15 patients. Monthly change in ventricular volume was related to baseline EDSS and total number of new Gd+ lesions. These observations indicate brain atrophy, a putative imaging marker of diffuse demyelination and axonal loss, can occur as early as 18 months after first symptons of RRMS, and is related to the baseline level of disability and to the number of new Gd+ lesions.

Timing is everything: Neural response dynamics during syllable processing and its relation to higher-order cognition in schizophrenia and healthy comparison subjects

Successful linguistic processing requires efficient encoding of successively-occurring auditory input in a time-constrained manner, especially under noisy conditions. In this study we examined the early neural response dynamics to rapidly-presented successive syllables in schizophrenia participants and healthy comparison subjects, and investigated the effects of noise on these responses. We used magnetoencephalography (MEG) to reveal the time-course of stimulus-locked activity over bilateral auditory cortices during discrimination of syllable pairs that differed either in voice onset time (VOT) or place of articulation (POA), in the presence or absence of noise. We also examined the association of these early neural response patterns to higher-order cognitive functions. The M100 response, arising from auditory cortex and its immediate environs, showed less attenuation to the second syllable in patients with schizophrenia than healthy comparison subjects during VOT-based discrimination in noise. M100 response amplitudes were similar between groups for the first syllable during all three discrimination conditions, and for the second syllable during VOT-based discrimination in quiet and POA-based discrimination in noise. Across subjects, the lack of M100 attenuation to the second syllable during VOT-based discrimination in noise was associated with poorer task accuracy, lower education and IQ, and lower scores on measures of Verbal Learning and Memory and Global Cognition. Because the neural response to the first syllable was not significantly different between groups, nor was a schizophrenia-related difference obtained in all discrimination tasks, early linguistic processing dysfunction in schizophrenia does not appear to be due to general sensory input problems. Rather, data suggest that faulty temporal integration occurs during successive syllable processing when the signal-to-noise ratio is low. Further, the neural mechanism by which the second syllable is suppressed during noise-challenged VOT discrimination appears to be important for higher-order cognition and provides a promising target for neuroscience-guided cognitive training approaches to schizophrenia.

Dynamic Activation of Frontal, Parietal, and Sensory Regions Underlying Anticipatory Visual Spatial Attention

Although it is well established that multiple frontal, parietal, and occipital regions in humans are involved in anticipatory deployment of visual spatial attention, less is known about the electrophysiological signals in each region across multiple subsecond periods of attentional deployment. We used MEG measures of cortical stimulus-locked, signal-averaged (event-related field) activity during a task in which a symbolic cue directed covert attention to the relevant location on each trial. Direction-specific attention effects occurred in different cortical regions for each of multiple time periods during the delay between the cue and imperative stimulus. A sequence of activation from V1/V2 to extrastriate, parietal, and frontal regions occurred within 110 ms after cue, possibly related to extraction of cue meaning. Direction-specific activations ∼300 ms after cue in frontal eye field (FEF), lateral intraparietal area (LIP), and cuneus support early covert targeting of the cued location. This was followed by coactivation of a frontal–parietal system [superior frontal gyrus (SFG), middle frontal gyrus (MFG), LIP, anterior intraparietal sulcus (IPSa)] that may coordinate the transition from targeting the cued location to sustained deployment of attention to both space and feature in the last period. The last period involved direction-specific activity in parietal regions and both dorsal and ventral sensory regions [LIP, IPSa, ventral IPS, lateral occipital region, and fusiform gyrus], which was accompanied by activation that was not direction specific in right hemisphere frontal regions (FEF, SFG, MFG). Behavioral performance corresponded with the magnitude of attention-related activity in different brain regions at each time period during deployment. The results add to the emerging electrophysiological characterization of different cortical networks that operate during anticipatory deployment of visual spatial attention.