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PubMed2005

Pattern of impaired working memory during major depression.

BACKGROUND: The aim of this study was to assess working memory (WM) in patients with major depressive disorder (MDD), using a robust parametric WM task (the n-back task). METHODS: Twenty patients with MDD and twenty healthy controls completed a visual version of the paradigm, comprising four levels of task difficulty (i.e. 0-, 1-, 2-, and 3-back). Performance accuracy and reaction time (RT) were measured at each difficulty level. RESULTS: In comparison with controls, patients with MDD exhibited slower RTs (F((1,38)) = 25.16, p < 0.001), and reduced accuracy (F((1,38)) = 5.93, p < 0.001). There was no diagnosis-specific effect of task difficulty on performance accuracy. However, the faster response to memory (1-3-back) than to shadowing (0-back) tasks observed in controls was not as pronounced in patients. CONCLUSIONS: These observations support a relatively specific impairment of WM/central executive function in MDD, which may potentially mediate the diverse pattern of cognitive dysfunction noted in MDD. The parametric n-back task is applicable to subjects with MDD and yields results interpretable across the dimensions of task difficulty and performance in controls and patients.

Adult↗
PubMed2005

Examining the association between rumination, negative affectivity, and negative affect induced by a paced auditory serial addition task.

The present study examined the relations among a depressive ruminative response style, a general propensity to experience negative affectivity, and negative affect induced by a paced serial auditory addition task (PASAT). Ninety nonclinical individuals completed a computerized version of the PASAT, which elicits a generalized negative affect response [Lejuez, C. W., Kahler, C. W., & Brown, R. A. (2003). A modified computer version of the paced auditory serial addition task (PASAT) as a laboratory-based stressor: Implications for behavioral assessment. Behavior Therapist, 26, 290-292]. As hypothesized, there was a moderate correlation between depressive rumination and a propensity to experience negative affect, as indexed both by a significant association with a negative affect personality factor and the prediction of negative affect elicited during the provocation. Findings also suggested that dispositional negative affectivity moderated the effects of a depressive ruminative response style on the valence but not arousal dimensions of emotional responding to the challenge. These findings are discussed in terms of improving our understanding of rumination and its potential role in emotional vulnerability processes.

Adolescent↗
PubMed2005

Control of attention in schizophrenia.

The deficits of attention contribute significantly to the clinical picture of functional disability seen in schizophrenia, but there is no consensus as to whether this cognitive function can be fractionated to allow further characterisation of the impairment. We examined fifteen patients with chronic schizophrenia and fifteen controls using paired tasks designed to measure four hypothetical aspects of attentional control: the ability to focus attention, to resist distraction, to shift attention, and to divide attention. The group with schizophrenia showed a significant improvement in accuracy on a digit span repetition task when a simultaneous box-crossing task was added (divided attention condition). Although the patient group showed impaired performance across nearly all of the tasks, they were not disproportionately impaired during the task conditions assumed to demand greater attention. These results suggest that the aspects of attention and executive function under study are not significantly affected by schizophrenia and indicate the need for further characterisation of the impairment usually reported using conventional tests of attention on those with schizophrenia.

Adult↗
PubMed2006

Exploring the short term visual store in schizophrenia using the attentional blink.

Schizophrenia patients exhibit numerous deficits on visual processing tasks, ranging from very early stages of visual processing (e.g., backward masking) to the later working memory stages (e.g., delayed match-to-sample, N-back). However, little is known about deficits in an intermediate stage of visual information processing, namely short term visual memory (STVM). The attentional blink (AB) paradigm is considered to be a valid way to assess the STVM, and recent studies have reported AB deficits in schizophrenia. However, it is not clear whether the reported AB deficit in schizophrenia patients is due to their increased susceptibility to backward masking or increased vulnerability in the STVM. In this study we first found poorer performance in the AB task in 37 schizophrenia patients compared to 26 normal controls. To examine the effects of increasing and decreasing mask strength on AB performance in patients and controls, we next systematically varied the masking effect by varying the length of the distracters immediately following the targets. The manipulation had relatively little effect on the patient--control differences and patients continued to show an enhanced AB effect across conditions. The findings suggest that the enhanced AB effect in schizophrenia reflects an abnormality in their short term visual memory, as opposed to their enhanced susceptibility to visual masking.

Adult↗
PubMed2006

Fronto-striatal deficit in Parkinson's disease during semantic event sequencing.

Studies of Parkinson's disease (PD) suggest that cognitive deficits accompany the classically recognized motor symptoms, and that these cognitive deficits may result from damage to frontal-basal ganglia circuits. PD patients are impaired on ordering events and action components into coherent sequences. In this study, we examined early-stage, nondemented, medicated PD subjects and matched control subjects during a semantic event sequencing task using functional MRI (fMRI). The task required subjects to examine four pictures of meaningful events, determine the correct temporal relationship between each picture, and re-order the pictures into a coherent sequence. There were two main findings. First, we found abnormal activation within the prefrontal cortex (PFC) and the "default" network in the PD group. Distinct areas of the PFC showed both hypoactivation and hyperactivation, whereas the "default" network showed reduced levels of resting activation in PD. Secondly, we observed left caudate hyperactivation in the PD group. The findings are discussed in relationship to how more activation may be compensatory, but does not necessarily mean efficient and correlated brain function.

Brain Mapping↗
PubMed2004

Brain activation in processing temporal sequence: an fMRI study.

Structured event complexes (SECs) are stored representations of sequential event knowledge, and represent sequences of activities that have been described elsewhere as scripts or schemas. Previous studies have shown that the prefrontal cortex is involved in temporal sequencing. The present study investigates the involvement of the prefrontal cortex in temporal order and membership judgments of script and category items by using functional magnetic resonance imaging. In this experiment, stimuli were either script events or category items. In experimental trials, subjects classified stimuli according to temporal order or membership category. Results show that the script order task and the chronological order task (relative to their respective memberships tasks) were associated with different patterns of PFC activation. Both order tasks activated the middle frontal gyrus bilaterally; however, script order tasks showed additional activation in right inferior frontal gyrus, and the chronological order tasks in left inferior frontal gyrus. These results suggest that while the middle frontal gyri are activated bilaterally in both script and chronological temporal ordering tasks, there are different, though largely overlapping, neural substrates for script and chronological representations during temporal ordering.

Adult↗
PubMed2005

rTMS evidence of different delay and decision processes in a fronto-parietal neuronal network activated during spatial working memory.

The existence of a specific and widely distributed network for spatial working memory (WM) in humans, involving the posterior parietal cortex and the prefrontal cortex, is supported by a number of neuroimaging studies. We used a repetitive transcranial magnetic stimulation (rTMS) approach to investigate the temporal dynamics and the reciprocal interactions of the different areas of the parieto-frontal network in normal subjects performing a spatial WM task, with the aim to compare neural activity of the different areas in the delay and decision phases of the task. Trains of rTMS at 25 Hz were delivered over the posterior parietal cortex (PPC), the premotor cortex (SFG) and the dorsolateral prefrontal cortex (DLPFC) of the right hemisphere alternatively during the two phases. We found a pattern of interference of TMS during the delay phase for both parietal and DLPFC sites of stimulation, with no effect observed for the SFG site. When rTMS trains were applied during the decision phase, an interference was observed selectively for DLPFC. The present study shows the existence of a parallel processing in the parieto-frontal network of spatial WM during the delay phase. Furthermore, it provides new evidence of the critical role of the DLPFC during both the delay and the decision phases. We suggest that in DLPFC, two different networks coexist: A local neural network subserving the decisional processes and a second neural population functionally interconnected with the PPC and activated when a certain spatial information has to be kept in memory, available to use.

Adult↗
PubMed2005

CASL fMRI of subcortico-cortical perfusion changes during memory-guided finger sequences.

Arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) is an attractive alternative to BOLD fMRI. Nevertheless, current ASL fMRI techniques are limited by several factors that hamper more routine applications in humans. One of these factors is restricted brain coverage so that whole-brain ASL fMRI studies have never been reported. The present study tested the ability of a multislice continuous ASL (CASL) fMRI approach using a small surface coil placed on the subject's neck to map changes in regional cerebral blood flow (rCBF) throughout the brain while healthy individuals (N = 15) performed memory-guided sequential finger movements at a mean rate of approximately 0.5 Hz. As predicted by results from a large number of studies, reliable task-related increases in flow were detected across subjects not only in primary and associative cortical areas but also in subcortical brain regions. When normalized to baseline, rCBF increased 31% in the hand representation area (HRA) of left primary motor cortex (M1), 13% in the left supplementary motor area proper (SMA), 10% in the left dorsolateral prefrontal cortex (DLPFC), 10-18% in the bilateral intraparietal sulci, 6% in the HRA of left putamen, 10% in the left thalamus, and 17% in the right anterior cerebellum. In addition to these increases, 6% and 4% decreases in rCBF were detected in the HRA of the right M1 and the bilateral posterior cingulate sulci, respectively. These results demonstrate that perfusion-based fMRI using CASL with a separate labeling coil can now be used to characterize task-related flow changes in most of the brain volume with adequate accuracy and sensitivity.

Adult↗
PubMed2005

Identification of large-scale networks in the brain using fMRI.

Cognition is thought to result from interactions within large-scale networks of brain regions. Here, we propose a method to identify these large-scale networks using functional magnetic resonance imaging (fMRI). Regions belonging to such networks are defined as sets of strongly interacting regions, each of which showing a homogeneous temporal activity. Our method of large-scale network identification (LSNI) proceeds by first detecting functionally homogeneous regions. The networks of functional interconnections are then found by comparing the correlations among these regions against a model of the correlations in the noise. To test the LSNI method, we first evaluated its specificity and sensitivity on synthetic data sets. Then, the method was applied to four real data sets with a block-designed motor task. The LSNI method correctly recovered the regions whose temporal activity was locked to the stimulus. In addition, it detected two other main networks highly reproducible across subjects, whose activity was dominated by slow fluctuations (0-0.1 Hz). One was located in medial and dorsal regions, and mostly overlapped the "default" network of the brain at rest [Greicius, M.D., Krasnow, B., Reiss, A.L., Menon, V., 2003. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the U.S.A. 100, 253-258]; the other was composed of lateral frontal and posterior parietal regions. The LSNI method we propose allows to detect in an exploratory and systematic way all the regions and large-scale networks activated in the working brain.

Adult↗
PubMed2005

Attention modulates hemispheric differences in functional connectivity: evidence from MEG recordings.

The present study examined intrahemispheric functional connectivity during rest and dichotic listening in 8 male and 9 female healthy young adults measured with magnetoencephalography (MEG). Generalized synchronization within the separate hemispheres was estimated by means of the synchronization likelihood that is sensitive to linear as well as non-linear coupling of MEG signals. We found higher functional intrahemispheric connectivity of frontal and temporal areas within the right as compared to the left hemisphere in the lower and higher theta band during rest and in the lower theta band during dichotic listening. In addition, higher synchronization in the lower theta band correlated with better task performance. In the upper alpha band, hemispheric differences in intrahemispheric connectivity of the frontal regions were found to be modulated by focused attention instructions. That is, attention to the right ear exaggerates the pattern of higher synchronization likelihood for the right frontal region, while attention to the left ear has an opposite effect. We found higher intrahemispheric connectivity in males compared to females as shown by higher synchronization in the lower alpha band. Taken together, our results reflect a physiological basis for functional hemispheric laterality and support the general assumption of sex differences in brain organization. Furthermore, in addition to studies that show that controlled attention processes modulate activation of the frontal areas, our study indicates that attention modulates ipsilateral functional connectivity in the frontal areas. This supports the idea of a supervisory role for the frontal cortex in attention processes.

Acoustic Stimulation↗
PubMed2006

Levels of appraisal: a medial prefrontal role in high-level appraisal of emotional material.

Appraisal refers to the evaluation of the meaning of emotional stimuli and is considered causal in the generation of an emotional response. Cognitive neuroscience has paid little attention to a theoretical distinction between low-level appraisal, considered to be automatic and preattentive, and high-level appraisal that requires attentional and working memory resources. To disentangle low-level from high-level appraisal, we varied cognitive load in a concurrent, unrelated working memory task, while anxiety was induced through anticipation of impending pain. Confirming theoretical predictions, we show that anxiety-related activity in dorsal medial prefrontal/rostral anterior cingulate cortex (dorsal MPFC/ACC) is attenuated under high, relative to low, cognitive load. Lateral prefrontal regions previously implicated in reappraisal and cognitive emotion regulation show a similar interaction between anxiety and cognitive load. Critically, there were no changes in physiological and subjective measures of low-level appraisal outcome and emotional response generation as a function of load, allowing us to conclude that MPFC/ACC and lateral PFC activity during anticipatory anxiety reflects high-level appraisal. Our data provide neurobiological evidence for a distinction between low-level and high-level appraisal mechanisms.

Adolescent↗
PubMed2006

Improvement-related functional plasticity following pitch memory training.

Functional activation patterns of an auditory working memory task were examined prior to and after 5 days of training (1 h/day). A control group with no training was scanned twice at the same intervals to assess test-retest effects. Based on behavioral improvement scores, the training group (n = 14) was divided into "Strong-Learners (SL)" and "Weak-Learners (WL)". No significant functional or structural brain differences were seen between the SL and WL groups prior to training. Imaging contrasts comparing post- with pre-training sessions showed a significant signal increase in the left Heschl's gyrus (HG) as well as in the left posterior superior temporal and supramarginal gyrus for the SL group, while the WL group showed significant signal increases in the left HG and anterior insular cortex as well as in a lingual-orbitofrontal-parahippocampal network. The test-retest analysis in the control group revealed only minimal signal increases in a right dorsolateral prefrontal region. A random effects analysis comparing the SL group with the WL group using the post- and pre-training contrast images showed increased activation only in the left supramarginal gyrus but not in HG. The importance of HG in pitch discrimination has been established in previous studies. The pitch memory component differentiated our task from a straight pitch discrimination task. It is most likely that the activation of the SMG reflects its importance in the short-term storage of auditory material, and it was this activation that best differentiated between subjects' levels of performance.

Adult↗
PubMed2006

From preparation to online control: reappraisal of neural circuitry mediating internally generated and externally guided actions.

Action plans internally generated (IG) from memory are thought to be regulated by the supplementary motor area (SMA), whereas plans externally guided (EG) online using sensory cues are believed to be controlled by the premotor cortex. This theory was investigated in an event-related fMRI study that separated the time course of activation before and during movement to distinguish advance planning from online control. In contrast to prevailing theory, the SMA was not more important for online control of IG actions. EG movement was distinguished from IG movement by greater activation in a more distributed right hemisphere parietal-frontal network than previously reported. Comparisons between premovement and movement periods showed that frontostriatal networks are central for preparing actions before movement onset. However, unlike cortical and cerebellar regions, the basal ganglia exhibited planning-related activity before, but not during, movement. These findings indicate that the basal ganglia mediate planning and online control processes in different ways and suggest a specific role for the striatum in internally planning sequences of actions before they are implemented.

Adult↗
PubMed2006

EEG oscillations and recognition memory: theta correlates of memory retrieval and decision making.

Studies of memory retrieval have identified electroencephalographic (EEG) correlates of a test item's old-new status, reaction time, and memory load. In the current study, we used a multivariate analysis to disentangle the effects of these correlated variables. During retrieval, power of left-parietal theta (4-8 Hz) oscillations increased in proportion to how well a test item was remembered, and theta in central regions correlated with decision making. We also studied how these oscillatory dynamics complemented event-related potentials. These findings are the first to demonstrate that distinct patterns of theta oscillations can simultaneously relate to different aspects of behavior.

Adult↗
PubMed2006

The left intraparietal sulcus and verbal short-term memory: focus of attention or serial order?

One of the most consistently activated regions during verbal short-term memory (STM) tasks is the left intraparietal sulcus (IPS). However, its precise role remains a matter of debate. While some authors consider the IPS to be a specific store for serial order information, other data suggest that it serves a more general function of attentional focalization. In the current fMRI experiment, we investigated these two hypotheses by presenting different verbal STM conditions that probed recognition for word identity or word order and by assessing functional connectivity of the left IPS with distant brain areas. If the IPS has a role of attentional focalization, then it should be involved in both order and item conditions, but it should be connected to different brain regions, depending on the neural substrates involved in processing the different types of information (order versus phonological/orthographic) to be remembered in the item and order STM conditions. We observed that the left IPS was activated in both order and item STM conditions but for different reasons: during order STM, the left IPS was functionally connected to serial/temporal order processing areas in the right IPS, premotor and cerebellar cortices, while during item STM, the left IPS was connected to phonological and orthographic processing areas in the superior temporal and fusiform gyri. Our data support a position considering that the left IPS acts as an attentional modulator of distant neural networks which themselves are specialized in processing order or language representations. More generally, they strengthen attention-based accounts of verbal STM.

Adult↗
PubMed2006

Neural correlates of artificial syntactic structure classification.

The human brain supports acquisition mechanisms that extract structural regularities implicitly from experience without the induction of an explicit model. It has been argued that the capacity to generalize to new input is based on the acquisition of abstract representations, which reflect underlying structural regularities in the input ensemble. In this study, we explored the outcome of this acquisition mechanism, and to this end, we investigated the neural correlates of artificial syntactic classification using event-related functional magnetic resonance imaging. The participants engaged once a day during an 8-day period in a short-term memory acquisition task in which consonant-strings generated from an artificial grammar were presented in a sequential fashion without performance feedback. They performed reliably above chance on the grammaticality classification tasks on days 1 and 8 which correlated with a corticostriatal processing network, including frontal, cingulate, inferior parietal, and middle occipital/occipitotemporal regions as well as the caudate nucleus. Part of the left inferior frontal region (BA 45) was specifically related to syntactic violations and showed no sensitivity to local substring familiarity. In addition, the head of the caudate nucleus correlated positively with syntactic correctness on day 8 but not day 1, suggesting that this region contributes to an increase in cognitive processing fluency.

Adult↗
PubMed2005

An fMRI study of the Trail Making Test.

This study investigated the cerebral correlates of the Trail Making Test (TMT), used commonly as a measure of frontal lobe function. Such work sheds additional light on the known shortcomings of the TMT as a localizing instrument, as indicated, for example, by studies of patients with focal brain lesions. Functional magnetic resonance imaging (fMRI) was used to record brain activity while participants performed the TMT using a custom-built, fiber-optic fMRI-compatible writing device, the "virtual stylus". Unlike in a previous fMRI study that used a verbal adaptation of the TMT, the virtual stylus enabled a closer depiction of the brain regions engaged by the actual paper-and-pencil task. Twelve, right-handed healthy young adults participated. In Part A of the task, participants were required to link in ascending order numbers (1-2-3 ...) that were randomly distributed on a computer screen. In Part B, participants were required to link alternately between numbers and letters (1-A-2-B ...). Although behavioral performance was somewhat less than typically obtained with the TMT due to use of the virtual stylus, distinct left-sided dorsolateral and medial frontal activity was revealed when comparing Part B versus Part A. These findings agree with existing literature showing sensitivity of the TMT to frontal regions in the left hemisphere. However, other activity was also observed (left middle and superior temporal gyrus) reinforcing that the brain-behavior correlations for the TMT are multifaceted and not restricted to the frontal lobe.

Adult↗
PubMed2005

Mnemonic anosognosia in Alzheimer's disease: a test of Agnew and Morris (1998).

Agnew and Morris [Agnew, S. K. & Morris, R. G. (1998). The heterogeneity of anosognosia for memory impairment in Alzheimer's disease: A review of the literature and a proposed model. Aging and Mental Health, 2, 9-15] model of awareness for memory functioning has attempted to account for the variance of anosognosia exhibited within the Alzheimer's disease (AD) population. There has been tentative evidence to suggest that the mnemonic anosognosia sub-type, proposed by this model, is common within the early stages of AD. However, this study is the first directly to test the model. Eighteen older adults with early AD and 18 healthy older adults were recruited. Awareness of memory functioning was monitored using patient-performance measures of "task specific" awareness; a measure of global memory awareness; and a patient-informant measure. The stability of participants' awareness was measured across three word recall lists and after a 20-min delay. Results suggested that, whilst the participants with early AD were less aware of their memory ability than the healthy older adults, they were able to improve their awareness following exposure to a memory task. Furthermore, the improvements in awareness were largely retained after the delay period. These findings are discussed in relation to Agnew and Morris [Agnew, S. K. & Morris, R. G. (1998). The heterogeneity of anosognosia for memory impairment in Alzheimer's disease: A review of the literature and a proposed model. Aging and Mental Health, 2, 9-15] model of mnemonic anosognosia and to current thinking about autobiographical memory.

Aged↗