Elton T.C. Ngan

The eyes have it!: An fMRI investigation

For the past several years it has been thought that cues, such as eye direction, can trigger reflexive shifts in attention because of their biological relevance and their specialized neural architecture. However, very recently, reported that other stimuli, such as arrows, trigger reflexive shifts in attention in a manner that is behaviourally identical to those triggered by eyes. Nevertheless these authors speculated that reflexive orienting to gaze direction may be subserved by a neural system-the superior temporal sulcus (STS)-that is specialized for processing eyes. The present study presents fMRI data that provide direct and compelling empirical support to this proposal. Subjects were presented with fixation stimuli that, based on instruction, could be perceived as eyes or as another type of directional cue. Both produced equivalent shifts in reflexive attention, replicating Ristic et al. However, the neural systems subserving the two forms of orienting were not equivalent-with the STS being engaged exceptionally when the fixation stimulus was perceived as eyes.

Functional connectivity reveals load dependent neural systems underlying encoding and maintenance in verbal working memory

One of the main challenges in working memory research has been to understand the degree of separation and overlap between the neural systems involved in encoding and maintenance. In the current study we used a variable load version of the Sternberg item recognition test (two, four, six, or eight letters) and a functional connectivity method based on constrained principal component analysis to extract load-dependent neural systems underlying encoding and maintenance, and to characterize their anatomical overlap and functional interaction. Based on the pattern of functional connectivity, constrained principal component analysis identified a load-dependent encoding system comprising bilateral occipital (Brodmanns area (BA) 17, 18), bilateral superior parietal (BA 7), bilateral dorsolateral prefrontal (BA 46), and dorsal anterior cingulate (BA 24, 32) regions. For maintenance, in contrast, constrained principal component analysis identified a system that was characterized by both load-dependent increases and decreases in activation. The structures in this system jointly activated by maintenance load involved left posterior parietal (BA 40), left inferior prefrontal (BA 44), left premotor and supplementary motor areas (BA 6), and dorsal cingulate regions (BA 24, 32), while the regions displaying maintenance-load-dependent activity decreases involved bilateral occipital (BA 17, 18), posterior cingulate (BA 23) and rostral anterior cingulate/orbitofrontal (BA 10, 11, 32) regions. The correlation between the encoding and maintenance systems was strong and negative (Pearsons r = -.55), indicting that some regions important for visual processing during encoding displayed reduced activity during maintenance, while subvocal rehearsal and phonological storage regions important for maintenance showed a reduction in activity during encoding. In summary, our analyses suggest that separable and complementary subsystems underlie encoding and maintenance in verbal working memory, and they demonstrate how constrained principal component analysis can be employed to characterize neuronal systems and their functional contributions to higher-level cognition.

Attention orienting dysfunction during salient novel stimulus processing in schizophrenia.

Schizophrenia is characterised by marked disturbances of attention and information processing. Patients experience difficulty focusing on relevant cues and avoiding distraction by irrelevant stimuli. Event-related potential recordings indicate an amplitude reduction in the P3a component elicited by involuntary orienting to task-irrelevant, infrequent novel stimuli presented during auditory oddball detection in patients with schizophrenia. The goal of the present study was to elucidate the functional abnormality underlying the disturbed orienting to novel stimuli in schizophrenia. Twenty-eight stable, partially remitted, medicated patients with schizophrenia and 28 healthy control participants completed a novelty oddball variant during event-related fMRI. Relative to healthy participants, patients with schizophrenia were characterised by underactivity during novel stimulus processing in the right amygdala-hippocampus, within paralimbic cortex in the rostral anterior cingulate and posterior cingulate cortices and the right frontal operculum, and in association cortex at the right temporo-parietal-occipital junction, bilateral intraparietal sulcus, and bilateral dorsal frontal cortex. Subcortically, relative hypoactivation during novelty processing was apparent in the cerebellum, thalamus, and basal ganglia. These results suggest that patients less efficiently reorient processing resources away from the ongoing task of detecting and responding to the task-relevant target stimuli. In addition, trend results suggest that patients experienced increased distraction by novel stimuli.

Decreased Efficiency of Task-Positive and Task-Negative Networks During Working Memory in Schizophrenia

Working memory (WM) is one of the most impaired cognitive processes in schizophrenia. Functional magnetic resonance imaging (fMRI) studies in this area have typically found a reduction in information processing efficiency but have focused on the dorsolateral prefrontal cortex. In the current study using the Sternberg Item Recognition Test, we consider networks of regions supporting WM and measure the activation of functionally connected neural networks over different WM load conditions. We used constrained principal component analysis with a finite impulse response basis set to compare the estimated hemodynamic response associated with different WM load condition for 15 healthy control subjects and 15 schizophrenia patients. Three components emerged, reflecting activated (task-positive) and deactivated (task-negative or default-mode) neural networks. Two of the components (with both task-positive and task-negative aspects) were load dependent, were involved in encoding and delay phases (one exclusively encoding and the other both encoding and delay), and both showed evidence for decreased efficiency in patients. The results suggest that WM capacity is reached sooner for schizophrenia patients as the overt levels of WM load increase, to the point that further increases in overt memory load do not increase fMRI activation, and lead to performance impairments. These results are consistent with an account holding that patients show reduced efficiency in task-positive and task-negative networks during WM and also partially support the shifted inverted-U-shaped curve theory of the relationship between WM load and fMRI activation in schizophrenia.

Abnormal function of the brain system supporting motivated attention in medicated patients with schizophrenia : an fMRI study

BACKGROUND Patients with schizophrenia have an impaired ability to generate activity that is appropriate to current circumstances and goals. METHOD We report a study using functional magnetic resonance imaging (fMRI) to examine cerebral activity during a three-tone auditory oddball target detection task in a sample of 28 patients with schizophrenia and 28 healthy controls. RESULTS The patients exhibited significantly less activation in response to target stimuli relative to baseline in an extensive set of sites in association neocortex, paralimbic cortex, limbic structures and subcortical nuclei, yet demonstrated a normal level of activation in the sensorimotor cortex. Comparison of activity elicited by rare target stimuli with that elicited by equally rare novel stimuli makes it possible to distinguish cerebral activity associated with attention to behaviourally salient stimuli from activity associated with attending to other attention-capturing stimuli. This comparison revealed that the patients with schizophrenia also exhibited a deficit in activation of basal forebrain areas that mediate motivation during the processing of behaviourally salient stimuli, including the amygdala, ventral striatum, orbital frontal cortex and rostral anterior cingulate cortex. CONCLUSION Patients with schizophrenia have a deficit in function of the brain system concerned with mediating motivation, in addition to a more general deficit in the cerebral response to attention-captivating stimuli.

Constrained Principal Component Analysis Reveals Functionally Connected Load-Dependent Networks Involved in Multiple Stages of Working Memory

Constrained principal component analysis (CPCA) with a finite impulse response (FIR) basis set was used to reveal functionally connected networks and their temporal progression over a multistage verbal working memory trial in which memory load was varied. Four components were extracted, and all showed statistically significant sensitivity to the memory load manipulation. Additionally, two of the four components sustained this peak activity, both for approximately 3 s (Components 1 and 4). The functional networks that showed sustained activity were characterized by increased activations in the dorsal anterior cingulate cortex, right dorsolateral prefrontal cortex, and left supramarginal gyrus, and decreased activations in the primary auditory cortex and “default network” regions. The functional networks that did not show sustained activity were instead dominated by increased activation in occipital cortex, dorsal anterior cingulate cortex, sensori‐motor cortical regions, and superior parietal cortex. The response shapes suggest that although all four components appear to be invoked at encoding, the two sustained‐peak components are likely to be additionally involved in the delay period. Our investigation provides a unique view of the contributions made by a network of brain regions over the course of a multiple‐stage working memory trial. Hum Brain Mapp, 2011.

Reaction time, symptom profiles and course of illness in schizophrenia

Schizophrenic subjects perform more poorly than normal controls on a wide range of neurocognitive tasks. Some studies suggest that patients with persistent illness may have different patterns of cognitive deficits and different associations between cognitive deficits and symptom profiles compared with patients with fluctuating illness. This study uses simple reaction time, choice reaction time and Stroop tasks to explore the relationship between reaction time and symptom profiles in patients with fluctuating illness (n=24), persistent illness (n=17) and normal controls (n=16). We tested the hypothesis that in patients with persistent illness, psychomotor poverty is associated with impaired initiation of activity, and that disorganization is associated with impaired selection in both persistent and fluctuating illness. There were no differences in the severity of symptoms in the patient groups. In the simple reaction time task, patients with persistent illness performed more poorly than patients with fluctuating illness and controls. Both patient groups performed more poorly than controls in the choice reaction time tasks. Psychomotor poverty was associated with simple reaction time in patients with persistent symptoms. Disorganization was associated with poorer performance on the choice reaction time task in both patient groups. These results suggest the possibility that persistent illness, negative symptoms, and impaired initiation may reflect dysfunction associated with enduring structural abnormalities. In the case of impaired selection processes and disorganization, our data indicate that these abnormalities occur in both persistent and fluctuating illness. This suggests that enduring brain damage might create a predisposition to impaired selection and disorganization, but these clinical features can also arise as a result of transient biochemical imbalance.

Decreased encoding efficiency in schizophrenia.

BACKGROUND Working memory deficits are a cardinal feature of schizophrenia that contribute to social and occupational dysfunction. METHODS We used functional magnetic resonance imaging to compare the response to varying task demands during the performance of an item recognition task. Study design and analysis procedures were optimized for the detection of load dependent activity during the encoding phase of working memory. RESULTS At the lowest load conditions the schizophrenia group performed as well as controls, however to achieve this equivalent performance the schizophrenia group had a significantly higher magnitude of activation compared to the controls. At the higher load conditions, the magnitude of activation between groups became more similar and we began to see performance deficits in the schizophrenic group. CONCLUSIONS These results suggest that patients with schizophrenia have decreased efficiency in the cognitive processes that underlie the early encoding phase of this task. For lower demand tasks, patients with schizophrenia can compensate for decreased efficiency by working harder to achieve equivalent performance. Encoding utilizes attentional and perceptual cognitive operations that are likely common to many other cognitive tasks; therefore, inefficiency may underlie the deficits observed in a wide range of cognitive tasks in schizophrenia compared to healthy controls.

Abnormal processing of speech during oddball target detection in schizophrenia

Healthy subjects show increased activation in left temporal lobe regions in response to speech sounds compared to complex nonspeech sounds. Abnormal lateralization of speech-processing regions in the temporal lobes has been posited to be a cardinal feature of schizophrenia. Event-related fMRI was used to test the hypothesis that schizophrenic patients would show an abnormal pattern of hemispheric lateralization when detecting speech compared with complex nonspeech sounds in an auditory oddball target-detection task. We predicted that differential activation for speech in the vicinity of the superior temporal sulcus would be greater in schizophrenic patients than in healthy subjects in the right hemisphere, but less in patients than in healthy subjects in the left hemisphere. Fourteen patients with schizophrenia (selected from an outpatient population, 2 females, 12 males, mean age 35.1 years) and 29 healthy subjects (8 females, 21 males, mean age 29.3 years) were scanned while they performed an auditory oddball task in which the oddball stimuli were either speech sounds or complex nonspeech sounds. Compared to controls, individuals with schizophrenia showed greater differential activation between speech and nonspeech in right temporal cortex, left superior frontal cortex, and the left temporal-parietal junction. The magnitude of the difference in the left temporal parietal junction was significantly correlated with severity of disorganized thinking. This study supports the hypothesis that aberrant functional lateralization of speech processing is an underlying feature of schizophrenia and suggests the magnitude of the disturbance in speech-processing circuits may be associated with severity of disorganized thinking.

Short- and long-term changes in anterior cingulate activation during resolution of task-set competition

Alternating between task sets involves detection that the current task set is unfavorable, initiation of a change in set, and application of the new task set while fine-tuning to optimally adjust to the demands of the environment. Functional magnetic resonance imaging (fMRI) studies of cognitive flexibility consistently report activation of the anterior cingulate cortex and/or adjacent pre-supplementary motor regions (ACC/pre-SMA, medial Brodmanns areas 24/32/6), suggesting that these cortical regions are involved in switching task set. In the current study, our objective was to probe whether ACC/pre-SMA activation would decrease for a number of trials following a switch in task set, implying longer-term involvement in fine-tuning adjustments. By measuring activation when switching between word reading and color naming in response to Stroop stimuli, ACC/pre-SMA activation was observed when actively countering the influence of the irrelevant task set, and this activation decreased as a function of the number of trials since a task switch. Basal ganglia and thalamic regions also displayed a decreased response over successive trials after task switches. These findings suggest that the ACC/pre-SMA are not only involved in generating a new course of action, but are also involved (along with subcortical regions) in fine-tuning operations that resolve competition between task sets over subsequent repetitions of the same task.