Hemispheric lateralization of cerebral blood-flow changes during selective listening to dichotically presented continuous speech

Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) while subjects were selectively listening to continuous speech delivered to one ear and ignoring concurrent speech delivered to the opposite ear, as well as concurrent text or letter strings running on a screen. rCBF patterns associated with selective listening either to the left-ear or right-ear speech message were compared with each other and with rCBF patterns in two visual-attention conditions in which the subjects ignored both speech messages and either read the text or discriminated the meaningless letter strings moving on the screen. Attention to either speech message was associated with enhanced activity in the superior temporal cortex of the language-dominant left hemisphere, as well as in the superior and middle temporal cortex of the right hemisphere suggesting enhanced processing of prosodic features in the attended speech. Moreover, enhanced activity during attention to either speech message was observed in the right parietal areas known to have an important role in directing spatial attention. Evidence was also found for attentional tuning of the left and right auditory cortices to select information from the contralateral auditory hemispace.     

The Neural Correlates of the Noradrenergic Modulation of Human Attention, Arousal and Learning

The prefrontal cortex has been suggested as a site of action for the noradrenergic modulation of cognition. In healthy volunteers attentional deficits can be induced by the α2 adrenoceptor agonist clonidine, without impairment of more explicit tests of frontal lobe function. It is therefore possible that the effects of noradrenaline cannot be localized to a specific brain area such as the prefrontal cortex, but instead involve structures in a more widespread attentional network. A 1.5 μg/kg dose of clonidine or placebo was administered to 13 healthy male volunteers performing the rapid visual information processing task, which places demands on both sustained attention and working memory. Twelve positron emission tomography measurements of regional cerebral blood flow (rCBF) were collected during performance of this task and also during a rest state. A second experiment in 12 healthy volunteers examined the effects of a 1.3 μg/kg dose of clonidine on the rCBF changes associated with performance of a paired associates learning task compared with passive listening to word pairs. Comparison of each of the experimental tasks with its respective control replicated previous findings. A significant drug × task interaction, common to the two studies, was found in the right thalamus. Inspection of the adjusted rCBF values showed that the effect was due to attenuation of thalamic rCBF during the control states rather than to any effects of clonidine during performance of the cognitive tasks, although the effect was stronger in the rapid visual information processing study than in the paired associates learning study. The significant effect of clonidine during the control as opposed to the ‘cognitive’ activation state is consistent with previous findings in animals and humans demonstrating greater effects of clonidine during states of relatively low arousal. The results suggest neuroanatomical dissociation of the noradrenergic modulation of arousal (via the thalamus) and attention.     

Decreases in frontal and parietal lobe regional cerebral blood flow related to habituation.

We previously reported decreased mean CBF between consecutive resting conditions, ascribed to habituation. Here we address the regional specificity of habituation over three consecutive flow studies. Regional CBF (rCBF) was measured in 55 adults (12 right-handed men, 12 right-handed women, 14 left-handed men, 17 left-handed women), with the 133Xe inhalation technique, during three conditions: resting, verbal tasks (analogies), and spatial tasks (line orientation). Changes in rCBF attributable to the cognitive tasks were eliminated by correcting these values to a resting equivalent. There was a progressive decrease in mean rCBF over time, reflecting habituation. This effect differed by region, with specificity at frontal (prefrontal, inferior frontal, midfrontal, superior frontal) and inferior parietal regions. In the inferior parietal region, habituation was more marked in the left than the right hemisphere. Right-handers showed greater habituation than did left-handers. There was no sex difference in global habituation, but males showed greater left whereas females showed greater right hemispheric habituation. The results suggest that habituation to the experimental setting has measurable effects on rCBF, which are differently lateralized for men and women. These effects are superimposed on task activation and are most pronounced in regions that have been implicated in attentional processes. Thus, regional decrement in brain activity related to habituation seems to complement attentional effects, suggesting a neural network for habituation reciprocating that for attention.     

Distinct neural substrates for visual search amongst spatial versus temporal distractors

Whether the contribution of the superior parietal cortex (BA7) to attention-demanding tasks is strictly spatial in nature remains unresolved. We used functional magnetic resonance imaging to explore the behavioural and neuroanatomical correlates of non-spatial search for a conjunction of features within a stream of temporally-distracting stimuli. In addition, we compared these data to those from a conventional visuo-spatial search task, performed by the same subjects, in order to determine the specificity of right BA7 activation. Mode of stimulus-distribution (spatial versus temporal) and search type (target defined by a single feature or a conjunction of features) were manipulated in a 2 x 2 factorial design. Behaviourally, the temporal conjunction task was shown to index temporal selective attention. Accuracy of detecting a second target varied with the temporal proximity of two successive targets when subjects searched for a conjunction of features, but not a single feature. The temporal conjunction task activated a network of areas including right superior parietal cortex and bilateral regions of intraparietal sulcus, frontal operculum and putamen. The two latter regions were selectively activated by the attentional demands of the temporal conjunction task when compared directly to the attentional demands of the spatial conjunction task, implicating these regions specifically in selective attention among temporally-distracting stimuli. By comparison, only a very medial region of right BA7 was selectively activated by the spatial conjunction task. The more lateral region of BA7 previously reported by other groups was engaged to a similar degree by both spatial and temporal versions of the conjunction search task.     

Cerebral blood flow in corticobasal degeneration and progressive supranuclear palsy

To compare brain perfusion between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), we investigated regional cerebral blood flow (rCBF) semiquantitatively with single-photon emission computed tomography and [123I]iodoamphetamine in six patients with CBD and five with PSP. Compared with 12 age-matched control subjects, the average of the left and right rCBF values for the CBD patients was significantly reduced in the inferior prefrontal, anterior cingulate, medial premotor, sensorimotor, posterior parietal, and superior temporal cortices as well as in the basal ganglia and thalamus, whereas only the medial premotor cortex was significantly hypoperfused in the PSP patients. Compared with the PSP patients, the CBD patients showed significantly decreased rCBF in the inferior prefrontal, sensorimotor, and posterior parietal cortices, but not in the subcortical regions. Compared with the controls, interhemispheric differences of rCBF were significant in the inferior prefrontal, sensorimotor, and posterior parietal cortices of the CBD patients but in only the medial prefrontal cortex of the PSP patients. These results indicate that rCBF reductions are more extensive and asymmetric in CBD than in PSP, although the two diseases share medial frontal involvement.     

Functional neuroanatomy of sustained attention in schizophrenia: contribution of parietal cortices

Deficits in sustained attention have been frequently described in schizophrenia. The neuroanatomical basis reported previously have included altered levels of activation in cingulate and prefrontal cortex, but the contribution of further regions remains unclear. We explored the full neuroanatomy underlying the sustained attentional deficits observed in naïve schizophrenics compared with controls. Participants included 10 controls and 11 patients. The experimental design included rest, auditory stimulation using clicks, and two counting tasks. Subjects were instructed to mentally count the clicks, and then to count forward at the same frequency they heard previously when listening to the clicks. Relative cerebral blood flow (relCBF) was measured by means of PET ¹⁵O‐water. Differences were observed between both groups at superior temporal cortex, superior parietal gyrus, and cerebellum during tasks requiring listening. During all counting conditions, additionally to supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPCF), precentral gyrus, cingulate, cerebellum, and inferior parietal (IP) gyrus, patients engaged other frontal structures including inferior, medial, and superior frontal areas. When counting with no auditory stimulation (C; requires components of working memory and time estimation), significant differences were observed in the level of activation of frontal and IP regions. Our naïve patients presented abnormal activation of auditory associative pathways. They failed to activate prefrontal and parietal regions at a similar level during tasks requiring increased cognitive effort, and they required a higher activation of inferior frontal regions to properly respond to cognitive demands. Hum. Brain Mapping 17:116–130, 2002. © 2002 Wiley‐Liss, Inc.     

Regional cerebral blood flow deficits in mild Alzheimer's disease using high resolution single photon emission computerized tomography

In spite of its wide availability, single photon emission computerized tomography (SPECT) scanning is uncommonly used in the assessment of Alzheimer's disease (AD) and related dementias. In light of recent advances in scanning protocols and image analysis, SPECT needs to be re-examined as a tool in the diagnosis of dementia. A total of 18 subjects with early AD and 10 healthy elderly control subjects were examined with high resolution SPECT during the performance of a simple word discrimination task. SPECT images were coregistered with individual magnetic resonance imaging scans, allowing delineation of predetermined neuroanatomical Regions of Interest (ROI). There was a gradation of regional cerebral blood flow (rCBF) values in both groups, with the lowest values being in the hippocampus and the highest in the striatum, thalamus and cerebellum. Compared to healthy controls, AD subjects demonstrated lower relative rCBF in parietal and prefrontal cortices. Analysis of individual ROI demonstrated bilateral reduction of rCBF in prefrontal poles, posterior temporal and anterior parietal cortex, and unilateral reduction of rCBF in left dorsolateral prefrontal cortex, right posterior parietal cortex and the left cingulate body. There were no significant differences for hippocampal, occipital or basal ganglia rCBF. Discriminant function analysis indicated that rCBF in the prefrontal polar regions achieved the best classification of cases. SPECT has utility in the diagnostic assessment of AD if standardized and semiquantitative techniques are used.     

Selective tuning of the left and right auditory cortices during spatially directed attention

Effects of spatially directed auditory attention on human brain activity, as indicated by changes in regional cerebral blood flow (rCBF), were measured with positron emission tomography (PET). Subjects attended to left-ear tones, right-ear tones, or foveal visual stimuli presented at rapid rates in three concurrent stimulus sequences. It was found that attending selectively to the right-ear input activated the auditory cortex predominantly in the left hemisphere and vice versa. This selective tuning of the left and right auditory cortices according to the direction of attention was presumably controlled by executive attention mechanisms of the frontal cortex, where enhanced activation during auditory attention was also observed.     

Pharmacological modulation of prefrontal cortical activity during a working memory task in young and older humans: a PET study with physostigmine

OBJECTIVE: Age-associated cholinergic dysfunction may contribute to the cognitive decline observed during aging, including a decline in working memory. The current study was designed to determine how healthy aging influences the neural response to working memory before and during pharmacological potentiation of the cholinergic system. METHOD: In 13 young and 13 older healthy volunteers, regional cerebral blood flow (rCBF) was measured by using [15O]H2O and positron emission tomography across 10 scans that alternated between a working-memory-for-faces task and rest. In all subjects, the first two scans were obtained during intravenous saline infusion. Seven young and eight older subjects then received intravenous infusion of physostigmine, a cholinesterase inhibitor, and the remaining six young and five older subjects continued to receive saline. RESULTS: In the placebo condition, task-specific rCBF increases in prefrontal regions were observed in the right middle and inferior frontal cortices in young subjects and in more anterior and ventral prefrontal regions in older individuals. Physostigmine during the working memory task significantly improved performance in both age groups. The right prefrontal regions that were selectively recruited in each age group during the placebo condition showed significantly lower rCBF during physostigmine administration. CONCLUSIONS: Cholinergic enhancement does not affect structurally defined cortical regions but rather modulates neural activity in functionally defined regions, that is, in task-related prefrontal cortical areas that are selectively and distinctively recruited in young and older subjects.     

Hemispheric differences in neural systems for face working memory: A PET-rCBF study

Neural systems that participate in working memory for faces were investigated in an experiment designed to distinguish face perception areas from working memory areas. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) while subjects performed a sensorimotor control task, a face perception control task, and five working memory tasks with parametrically varied retention intervals, ranging from 1 to 21 sec. Striate and ventral occipitotemporal extrastriate areas demonstrated a simple negative correlation between rCBF and retention delay, indicating that these areas participate principally in perceptual operations performed during visual stimulation. By contrast, right and left frontal areas demonstrated rCBF increases that were significantly more sustained across delays than were increases in ventral extrastriate areas, but the relation between rCBF and retention interval differed significantly by hemisphere. Whereas right frontal rCBF showed a nonsignificant tendency to diminish at longer delays, left inferior frontal, middle frontal, and anterior cingulate cortex, as well as left parietal and inferior temporal cortex, demonstrated their largest rCBF increases at the longest delays. These results indicate that right frontal and left frontal, parietal, and temporal areas all participate in face working memory, but that left hemisphere areas are associated with a more durable working memory representation or strategy that subjects rely on increasingly with longer retention intervals. One possible explanation for this hemispheric difference is that left hemisphere activity is associated with a face representation that embodies the result of more analysis and elaboration, whereas right frontal activity is associated with a simpler, icon-like image of a face that is harder to maintain in working memory. © 1995 Wiley-Liss, Inc.     

Preparation for reaching: a PET study of the participating structures in the human brain.

The regional cerebral blood flow (rCBF) was measured as an indicator of regional metabolic activity with positron emission tomography (PET) in eight subjects who, after seeing a screen with seven targets prepared themselves with their eyes closed to reach these targets. The preparation phase was associated with increases of rCBF in the prefrontal cortex, several remote visual association areas in the parietal lobe, the supramarginal gyrus, the ventrolateral thalamus and the cerebellar vermis. During the course of learning the activations in the parietal visual areas, the supramarginal gyrus and the prefrontal cortex prevailed as a sign of the visual spatial information; its transformation being kept in working memory. The other activations vanished. No activations were seen in the motor cortices, indicating that reaching is a task which does not require substantial preparatory activity of motor cortices prior to the go signal.     

Frontal and parietal components of a cerebral network mediating voluntary attention to novel events

Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating one's internal model of the environment to take into account a novel event.     

Individual differences in PET activation of object perception and attention systems predict face matching accuracy.

We sought to investigate how individual differences in the regional patterns of cerebral blood flow (rCBF) relate to task performance during the perceptual matching of faces. We analyzed rCBF data obtained by PET and H2150 from nine young healthy, right-handed, adult males (mean age 29i3 years) using a statistical model of regional covariance, the Scaled Subprofile Model (SSM). SSM analysis performed on a voxel-basis for scan subtractions comparing face-matching and control tasks extracted two patterns whose subject expression in a multiple regression analysis was highly predictive of task accuracy (R2 = 0.87, p < 0.002). The pattern reflecting this linear combination was principally characterized by higher rCBF in regions of bilateral occipital and occipitotemporal cortex, right orbitofrontal cortex, left thalamus, basal ganglia, midbrain, and cerebellum with relatively lower rCBF in anterior cingulate, regions in bilateral prefrontal and temporal cortex, right thalamus, and right inferior parietal cortex. The results indicate that individual subject differences in face matching performance are specifically associated with the functional interaction of cortical and subcortical brain regions previously implicated in aspects of object perception and visual attentional processing.     

Effects of right-hemisphere cortical infarction and muscarinic acetylcholine receptor blockade on spatial visual attention performance in rats

The syndrome of hemispatial neglect is defined as an inability to report, respond or orient to stimuli contralateral to a cerebral lesion despite intact elementary sensory or motor function. This syndrome is typically observed after lesions of the right cerebral cortex, and has been associated with impairment of attention. We studied whether visual attention performance is impaired after right-hemisphere infarction in rats. Using a behavioural paradigm measuring spatial visual attention, we tested the effects of photothrombotic infarction to either the frontal cortex or the parietal cortex on attention performance. Since the cholinergic system is known to modulate attention performance, we additionally evaluated the role of cholinergic receptor blockade with scopolamine in our task paradigm. Our results show a transient response bias immediately after cortical infarction, with a decrease in contralesional responses and an increase in contralesional omissions after frontal infarction. Parietal infarction and systemic administration of scopolamine also resulted in a decrease in correct responses and an increase in omissions, but without a difference in side responding. In conclusion, right frontal infarction induces a transient impairment in contralesional spatial visual attention that we explain as left-sided neglect. Right parietal infarction and cholinergic blockade shows non-lateralized deficits in spatial visual attention, suggestive of global attentional impairment. We postulate that both effects of cortical infarction on attention performance may be related to cholinergic dysfunction. Our study confirms the role of frontal and parietal cortices in attention performance in rats, and corroborates the theory that attention performance is impaired in hemispatial neglect in human stroke patients.     

Decreases in regional cerebral blood flow with normal aging

Positron emission tomographic (PET) images of regional cerebral blood flow (rCBF) from 30 normal, resting volunteers aged 30 to 85 years were analysed to identify areas where rCBF fell with age. Images were anatomically normalised, and a pixel-by-pixel linear regression was performed to remove differences in global CBF between subjects. Pixels at which rCBF then showed a significant (p less than 0.01) negative correlation with age were identified. They were displayed as a statistical parametric map (SPM) of correlations. We demonstrate an age-related decrease in adjusted rCBF in the cingulate, parahippocampal, superior temporal, medial frontal, and posterior parietal cortices bilaterally, and in the left insular and left posterior prefrontal cortices (omnibus significance, chi 2 = 2,291, p less than 0.0001, df = 1). Decreases in rCBF suggest a regionally specific loss of cerebral function with age. The affected areas were all limbic, or association, cortices. Therefore, these decreases may constitute the cerebral substrate of the cognitive changes that occur during normal aging.     

Neuroanatomical correlates of intellectual ability across the life span

Attempts to correlate measures of intellectual ability with localized anatomical imaging features of the brain have yielded variable findings distributed across frontal, parietal, and temporal lobes. To better define the gray and white matter correlates of intellectual ability and the effects of sex and age, we analyzed the brains of 105 healthy individuals, ages 7-57 years, who had a Full Scale Intelligence Quotient (FSIQ) of 70 or higher. We examined associations of FSIQ with cortical thickness and with white matter volume throughout the cerebrum. Thinning of left ventromedial and right dorsolateral prefrontal cortices correlated significantly with FSIQ. Sex modified correlations of cortical thickness with FSIQ in the left inferior frontal, left cingulate, and right dorsomedial prefrontal cortices. Correlations of local white matter volumes with FSIQ varied by age, with adults showing inverse correlations of white matter volume with FSIQ in a large territory of right frontal white matter likely corresponding to fiber tracts of the superior corona radiata and superior longitudinal fasciculus. These findings corroborate the role of frontal and parietal association cortices and long association white matter fibers in higher intelligence and suggest ways in which the neuroanatomical correlates of higher intelligence may vary by sex and age.     

Selective and divided visual attention: Age-related changes in regional cerebral blood flow measured by H215O PET

Regional cerebral blood flow (rCBF) was measured using H₂¹⁵O and positron emission tomography (PET) to test the hypothesis that age-related changes in the pattern of rCBF activation would be greater under divided attention conditions than under selective attention conditions. Subjects were 24 right-handed men: 12 young adults (age 21–28 years), and 12 older adults (age 60–77 years). Measurement of rCBF was obtained during performance of three visual search task conditions, each of which involved viewing a series of nine-letter displays and making a two-choice button press response to each display. Analyses of subjects' mean reaction time and error rate confirmed that older adults' search performance was disproportionately impaired when it was necessary to divide attention among the display positions. The rCBF data indicated that attending selectively to a target letter in a known (central) location was not associated with cortical activation for either age group. The requirement to divide attention among the display positions led to rCBF activation in occipitotemporal, occipitoparietal, and prefrontal cortical regions. In the divided-attention condition, rCBF activation in the occipitotemporal pathway was relatively greater for young adults; activation in prefrontal regions was relatively greater for older adults. These differences in rCBF activation were related to search reaction time and suggest that, when attention was divided, young adults' performance relied primarily on letter identification processes, whereas older adults required the recruitment of additional forms of task control. Hum. Brain Mapping 5:389–409, 1997. © 1997 Wiley-Liss, Inc.     

Attentional control: temporal relationships within the fronto-parietal network

Selective attention to particular aspects of incoming sensory information is enabled by a network of neural areas that includes frontal cortex, posterior parietal cortex, and, in the visual domain, visual sensory regions. Although progress has been made in understanding the relative contribution of these different regions to the process of visual attentional selection, primarily through studies using neuroimaging, rather little is known about the temporal relationships between these disparate regions. To examine this, participants viewed two rapid serial visual presentation (RSVP) streams of letters positioned to the left and right of fixation point. Before each run, attention was directed to either the left or the right stream. Occasionally, a digit appeared within the attended stream indicating whether attention was to be maintained within the same stream ('hold' condition) or to be shifted to the previously ignored stream ('shift' condition). By titrating the temporal parameters of the time taken to shift attention for each participant using a fine-grained psychophysics paradigm, we measured event-related potentials time-locked to the initiation of spatial shifts of attention. The results revealed that shifts of attention were evident earlier in the response recorded over frontal than over parietal electrodes and, importantly, that the early activity over frontal electrodes was associated with a successful shift of attention. We conclude that frontal areas are engaged early for the purpose of executing an attentional shift, likely triggering a cascade through the fronto-parietal network ultimately, resulting in the attentional modulation of sensory events in posterior cortices.     

ERPs and PET analysis of time perception: spatial and temporal brain mapping during visual discrimination tasks

ERPs were recorded from 12 subjects performing duration and intensity visual discrimination tasks which have been previously used in a PET study. PET data showed that the same network was activated in both tasks [P. Maquet et al., NeuroImage 3:119-126, 1996]. Different ERP waveforms were observed for the late latency components depending on the dimension of the stimulus to be processed: frontal negativity (CNV) for the duration task and parieto-occipital positivity (P300) for the intensity task. Using BESA software, the sources were first modelled with a "PET dipolar model" (right prefrontal, right parietal, anterior cingulate, left and right fusiforms). To obtain a better fit for ERPs recorded in each task, two sources (cuneus, left prefrontal area) had to be added. Consistently with PET findings, dipole modelling indicates that duration and intensity dimensions of a visual stimulus are processed in the same areas. However, ERPs also reveal prominent differences between the time course of the dipole activations for each task, particularly for sources contributing to the late latency ERP components. In the intensity task, dipoles located in the cuneus, the anterior cingulate, and the left prefrontal area yield largest activity within the P300 interval, then activity diminishes rapidly as the stimulus ends, whereas in the duration task, the cuneus and anterior cingulate are still active several hundred milliseconds following stimulus offset. Moreover, in the duration task, the activity of the right frontal dipole parallels the CNV waveform, whereas in the intensity task, this dipole is largely inactive. We assume that the right frontal area plays a specific role in the formation of temporal judgments.     

Retrosplenial cortical activation in the fibromyalgia syndrome

To study the CNS in chronic muscular pain typical of fibromyalgia we compared PET measures of regional cerebral blood flow (rCBF) in eight fibromyalgic patients and controls at rest. Higher rCBF for patients than controls was found bilaterally in the retrosplenial cortex. Lower rCBF for patients than controls were seen in the left frontal, temporal, parietal, and occipital cortices. The higher retroplenial rCBF in patients than controls may reflect increased attention towards sub-noxious somatosensory signaling, and agrees with the notion that fibromyalgic pain reflects secondary hyperalgesia. The brain regions with lower rCBF in fibromyalgic patients than controls participate in the normal cognitive processing of pain, which may be dysfunctional in fibromyalgia.