Inferior Frontal Activation Research Articles

An fMRI study of the prefrontal activity during the performance of a working memory task in premutation carriers of the fragile X mental retardation 1 gene with and without fragile X-associated tremor/ataxia syndrome (FXTAS)

Premutation alleles of the fragile X mental retardation 1 gene ( FMR1) are associated with the risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder that involves neuropsychiatric problems and executive and memory deficits. Although abnormal elevation of FMR1 mRNA has been proposed to underlie these deficits, it remains unknown which brain regions are affected by the disease process of FXTAS and genetic molecular mechanisms associated with the FMR1 premutation. This study used functional magnetic resonance imaging (fMRI) to identify deficient neural substrates responsible for altered executive and memory functions in some FMR1 premutation individuals. We measured fMRI BOLD signals during the performance of verbal working memory from 15 premutation carriers affected by FXTAS (PFX+), 15 premutation carriers unaffected by FXTAS (PFX−), and 12 matched healthy control individuals (HC). We also examined correlation between brain activation and FMR1 molecular variables (CGG repeat size and mRNA levels) in premutation carriers. Compared with HC, PFX+ and PFX− showed reduced activation in the right ventral inferior frontal cortex and left premotor/dorsal inferior frontal cortex. Reduced activation specific to PFX+ was found in the right premotor/dorsal inferior frontal cortex. Regression analysis combining the two premutation groups demonstrated significant negative correlation between the right ventral inferior frontal cortex activity and the levels of FMR1 mRNA after excluding the effect of disease severity of FXTAS. These results indicate altered prefrontal cortex activity that may underline executive and memory deficits affecting some individuals with FMR1 premutation including FXTAS patients.

Inferior Frontal Gyrus Activation Predicts Individual Differences in Perceptual Learning of Cochlear-Implant Simulations

This study investigated the neural plasticity associated with perceptual learning of a cochlear implant (CI) simulation. Normal-hearing listeners were trained with vocoded and spectrally shifted speech simulating a CI while cortical responses were measured with functional magnetic resonance imaging (fMRI). A condition in which the vocoded speech was spectrally inverted provided a control for learnability and adaptation. Behavioral measures showed considerable individual variability both in the ability to learn to understand the degraded speech, and in phonological working memory capacity. Neurally, left-lateralized regions in superior temporal sulcus and inferior frontal gyrus (IFG) were sensitive to the learnability of the simulations, but only the activity in prefrontal cortex correlated with interindividual variation in intelligibility scores and phonological working memory. A region in left angular gyrus (AG) showed an activation pattern that reflected learning over the course of the experiment, and covariation of activity in AG and IFG was modulated by the learnability of the stimuli. These results suggest that variation in listeners' ability to adjust to vocoded and spectrally shifted speech is partly reflected in differences in the recruitment of higher-level language processes in prefrontal cortex, and that this variability may further depend on functional links between the left inferior frontal gyrus and angular gyrus. Differences in the engagement of left inferior prefrontal cortex, and its covariation with posterior parietal areas, may thus underlie some of the variation in speech perception skills that have been observed in clinical populations of CI users.

Recruitment of Additional Brain Regions to Accomplish Simple Motor Tasks in Chronic Alcohol‐Dependent Patients

Chronic alcohol-dependent patients (ALC) exhibit neurocognitive impairments attributed to alcohol-induced fronto-cerebellar damage. Deficits are typically found in complex task performance, whereas simple tasks may not be significantly compromised, perhaps because of little understood compensatory changes. We compared finger tapping with either hand at externally paced (EP) or maximal self-paced (SP) rates and concomitant brain activation in ten pairs of right-hand dominant, age-, and gender-matched, severe, uncomplicated ALC and normal controls (NC) using functional magnetic resonance imaging (fMRI). Mean tapping rates were not significantly different in ALC and NC for either task, but SP tapping variances were greater in ALC for both hands. SP tapping was more rapid with dominant hand (DH) than non-dominant hand (NDH) for both groups. EP and SP tapping with the non-dominant hand demonstrated significantly more activation in ALC than NC in the pre and postcentral gyri, inferior frontal gyrus, inferior parietal lobule, and the middle temporal gyrus. Areas activated only by ALC (not at all by NC) during NDH tapping included the inferior frontal gyrus, middle temporal gyrus, and postcentral gyrus. There were no significant group activation differences with DH tapping. No brain regions activated more in NC than ALC. SP tapping in contrast to EP activated fronto-cerebellar networks in NC, including postcentral gyrus, anterior cingulate, and the anterior lobe and vermis of the cerebellum, but only parietal precuneus in ALC. These findings with NDH finger tapping support previous reports of neurocognitive inefficiencies in ALC. Inferior frontal activation with EP in ALC, but not in NC, suggests engagement of regions needed for planning, organization, and impulse regulation; greater contralateral parietal lobe activation with SP in ALC may reflect right hemispheric impairments in visuospatial performance. Contrasting brain activation during SP and EP suggests that ALC may not have enlisted a fronto-cerebellar network as did NC but rather employed a higher order planning mode by recruiting parietal lobe functions to attain normal mean finger tapping rates. Elucidation of the compensatory neural mechanisms that allow near normal performance by ALC on simple tasks can inform functional rehabilitation of patients in recovery.

Effects of aging on hemispheric asymmetry in inferior frontal cortex activity during belief–bias syllogistic reasoning: A near-infrared spectroscopy study

The belief–bias effect in syllogistic reasoning refers to the tendency for subjects to be erroneously biased when logical conclusions are incongruent with beliefs about the world. This study examined age-related differences in inferior frontal cortex (IFC) activity associated with belief–bias reasoning using near-infrared spectroscopy (NIRS). The subjects were 32 older (mean age, 68.53 years) and 32 young adult volunteers (mean age, 21.50 years). They performed belief-congruent and incongruent reasoning trials while right and left IFC activities were being measured by NIRS. Behavioral analysis found that older adults exhibited a larger belief–bias than young adults. NIRS analysis showed that the right IFC was more activated than the left IFC in young adults, while there was no significant hemispheric difference in older adults. On correlation analysis, there was a significant positive correlation between reasoning accuracy and IFC activation in both hemispheres for older adults, while in young adults, the correlation was significant only in the right hemisphere. These correlation patterns suggest that the right IFC is critical for resolving conflicting reasoning in young adults, but that older adults may further recruit the left IFC to compensate for the age-related decline in the inhibitory control functions. Thus, we demonstrate, for the first time, age-related differences in neural activity associated with belief–bias reasoning.

Hierarchical organization of scripts: converging evidence from FMRI and frontotemporal degeneration.

The present study examined the organization of complex familiar activities, known as "scripts" (e.g., "going fishing"). We assessed whether events in a script are processed in a linear-sequential manner or clustered-hierarchical manner, and we evaluated the neural basis for this processing capacity. Converging evidence was obtained from functional neuroimaging in healthy young adults and from behavioral and structural magnetic resonance imaging (MRI) data in patients with focal neurodegenerative disease. In both studies, participants judged the order of consecutive event pairs taken from a script. Event pairs either were clustered together within a script or were from different clusters within the script. Controls judged events more accurately and quickly if taken from the same cluster within a script compared with different clusters, even though all event pairs were consecutive, consistent with the hierarchical organization of a script. Functional magnetic resonance imaging associated this with bilateral inferior frontal activation. Patients with progressive nonfluent aphasia or behavior-variant frontotemporal dementia did not distinguish between event pairs from the same cluster or from different clusters within a script. Structural MRI associated this deficit with significant frontal cortical atrophy. Our findings suggest that frontal cortex contributes to clustering events during script comprehension, underlining the role of frontal cortex in the hierarchical organization of a script.

Olfactory fMRI in Patients with Parkinson's Disease

Hyposmia is one of the early signs in idiopathic Parkinson's disease (PD). Olfactory stimuli were applied during fMRI scanning to show disease-related modulation of central nervous system structures and to advance our understanding of olfactory dysfunction in PD patients. All participants received either unpleasant stimuli that smelled like rotten eggs or pleasant ones that smelled like roses. Using a block design at a 1.5 T scanner we investigated a total of 8 PD patients (mean age 60 ± 10.9 years) and 13 age matched controls (mean age 58 ± 9.6 years). PD duration ranged from 1 to 9 years (mean 6.63 years); patients had an average “Unified Parkinson's Disease Rating Scale III” score of 23.25 (range, 6–46). Olfactory function was established using the “Sniffin’ Sticks” test battery. Patients tended to rate the stimuli presented during fMRI scans as less intense, but also as more pleasant than controls. fMRI results revealed differences between PD patients and controls which depended on the type of stimulation. While both pleasant and unpleasant stimulation was associated with lower activation in the amygdalo–hippocampal complex in patients compared to controls, increased activity in response to pleasant stimuli was observed in the striatum and the left inferior frontal gyrus. In contrast, unpleasant stimulation led to hypoactivation of the ventral striatum in patients (but not in controls) and did not enhance left inferior frontal activity. These results may partly reflect differences between PD patients and healthy controls in the processing of primary dimensions of odors, intensity, and valence.

“It’s not what you say, but how you say it”: a reciprocal temporo-frontal network for affective prosody

Humans communicate emotion vocally by modulating acoustic cues such as pitch, intensity and voice quality. Research has documented how the relative presence or absence of such cues alters the likelihood of perceiving an emotion, but the neural underpinnings of acoustic cue-dependent emotion perception remain obscure. Using functional magnetic resonance imaging in 20 subjects we examined a reciprocal circuit consisting of superior temporal cortex, amygdala and inferior frontal gyrus that may underlie affective prosodic comprehension. Results showed that increased saliency of emotion-specific acoustic cues was associated with increased activation in superior temporal cortex [planum temporale (PT), posterior superior temporal gyrus (pSTG), and posterior superior middle gyrus (pMTG)] and amygdala, whereas decreased saliency of acoustic cues was associated with increased inferior frontal activity and temporo-frontal connectivity. These results suggest that sensory-integrative processing is facilitated when the acoustic signal is rich in affective information, yielding increased activation in temporal cortex and amygdala. Conversely, when the acoustic signal is ambiguous, greater evaluative processes are recruited, increasing activation in inferior frontal gyrus (IFG) and IFG STG connectivity. Auditory regions may thus integrate acoustic information with amygdala input to form emotion-specific representations, which are evaluated within inferior frontal regions.

Development of audiovisual integration of print and speech in normal and poor readers: An ERP and fMRI study

Event Abstract Back to Event Development of audiovisual integration of print and speech in normal and poor readers: An ERP and fMRI study Silvia Brem1, 2*, Ulla Richardson1, Silvia Bach1, 2, Christoph Hofstetter2, Ernst Martin3, 4 and Daniel Brandeis2, 4, 5 1 University of Jyväskylä, Agora Center, Finland 2 University of Zurich, Department of Child and Adolescent Psychiatry, Switzerland 3 University Childrens Hospital Zurich, MR-Center, Switzerland 4 University of Zurich, Center for Integrative Human Physiology, Switzerland 5 Central Institute of Mental Health, Department of Child and Adolescent Psychiatry, Germany The integration of multisensory information from speech and print is highly automatized in good readers but remains deficient in poor readers (Blau et al. 2009). Recent studies consistently point to the crucial involvement of the superior temporal sulcus (STS) in integration (van Atteveldt et al. 2004) and conceptual matching (Hocking and Price 2008) of incoming audiovisual information starting around 380ms (Raij et al. 2000) after presentation. In this study we aimed to track emergence and development of audiovisual integration from kindergarten to adulthood in normal and poor readers with functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs). Non-reading kindergartners (n=14, 5.7-7.1y), normal (n=31, 7.8-9.2y) and poor reading (n=15, 7.8-8.9y) 2nd graders as well as normal reading adults (n=15, 21.9-34.5y) were examined with fMRI and ERPs. Conceptual matching effects determined by the statistical difference between incongruous and congruous audiovisual conditions are reported for each age group and for the differences between groups. While kindergarten children did not show conceptual matching effects, normal reading 2nd graders and adults activated inferior frontal and superior temporal brain regions more to incongruous than congruous items. The inferior frontal activation of the 2nd graders was furthermore correlated with reading performance. ERPs pointed to a mismatch effect in the form of a pronounced centro-parietal negativity starting at around 380ms in adults, which was delayed in normal reading 2nd graders. In contrast to adults, 2nd graders showed an additional earlier condition difference around 140-220ms. In summary our results show that incongruous presentation of speech and print evokes a conceptual mismatch effect in fMRI and ERPs as soon as children’s basic reading skills allow matching written to spoken information. The modulation of the matching effect by children’s reading skills points to deficient integration of audiovisual information in poor readers. Conference: EARLI SIG22 - Neuroscience and Education, Zurich, Switzerland, 3 Jun - 5 Jun, 2010. Presentation Type: Poster Presentation Topic: Language and reading Citation: Brem S, Richardson U, Bach S, Hofstetter C, Martin E and Brandeis D (2010). Development of audiovisual integration of print and speech in normal and poor readers: An ERP and fMRI study. Front. Neurosci. Conference Abstract: EARLI SIG22 - Neuroscience and Education. doi: 10.3389/conf.fnins.2010.11.00010 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 May 2010; Published Online: 28 May 2010. * Correspondence: Silvia Brem, University of Jyväskylä, Agora Center, Jyväskylä, Finland, sbrem@kjpd.uzh.ch Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Silvia Brem Ulla Richardson Silvia Bach Christoph Hofstetter Ernst Martin Daniel Brandeis Google Silvia Brem Ulla Richardson Silvia Bach Christoph Hofstetter Ernst Martin Daniel Brandeis Google Scholar Silvia Brem Ulla Richardson Silvia Bach Christoph Hofstetter Ernst Martin Daniel Brandeis PubMed Silvia Brem Ulla Richardson Silvia Bach Christoph Hofstetter Ernst Martin Daniel Brandeis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis

Schizophrenia is characterized by altered prefrontal activity and elevated striatal dopaminergic function. To investigate the relationship between these abnormalities in the prodromal phase of the illness, we combined functional Magnetic Resonance Imaging and (18)F-Dopa Positron Emission Tomography. When performing a verbal fluency task, subjects with an At-Risk Mental State showed greater activation in the inferior frontal cortex than controls. Striatal dopamine function was greater in the At-Risk group than in controls. Within the At-Risk group, but not the control group, there was a direct correlation between the degree of left inferior frontal activation and the level of striatal dopamine function. Altered prefrontal activation in subjects with an At-Risk Mental State for psychosis is related to elevated striatal dopamine function. These changes reflect an increased vulnerability to psychosis and predate the first episode of frank psychosis.

Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-d-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3±3, post 6±3; p<0.001) but not when subjects were instructed to inhibit craving (pre 3±2, post 3±3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p<0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p<0.005), which was associated with right inferior frontal activation (r=−0.62, p<0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

Anterior temporal lobe connectivity correlates with functional outcome after aphasic stroke

Focal brain lesions are assumed to produce language deficits by two basic mechanisms: local cortical dysfunction at the lesion site, and remote cortical dysfunction due to disruption of the transfer and integration of information between connected brain regions. However, functional imaging studies investigating language outcome after aphasic stroke have tended to focus only on the role of local cortical function. In this positron emission tomography functional imaging study, we explored relationships between language comprehension performance after aphasic stroke and the functional connectivity of a key speech-processing region in left anterolateral superior temporal cortex. We compared the organization of left anterolateral superior temporal cortex functional connections during narrative speech comprehension in normal subjects with left anterolateral superior temporal cortex connectivity in a group of chronic aphasic stroke patients. We then evaluated the language deficits associated with altered left anterolateral superior temporal cortex connectivity in aphasic stroke. During normal narrative speech comprehension, left anterolateral superior temporal cortex displayed positive functional connections with left anterior basal temporal cortex, left inferior frontal gyrus and homotopic cortex in right anterolateral superior temporal cortex. As a group, aphasic patients demonstrated a selective disruption of the normal functional connection between left and right anterolateral superior temporal cortices. We observed that deficits in auditory single word and sentence comprehension correlated both with the degree of disruption of left-right anterolateral superior temporal cortical connectivity and with local activation in the anterolateral superior temporal cortex. Subgroup analysis revealed that aphasic patients with preserved positive intertemporal connectivity displayed better receptive language function; these patients also showed greater than normal left inferior frontal gyrus activity, suggesting a possible ‘top-down’ compensatory mechanism. These results demonstrate that functional connectivity between anterolateral superior temporal cortex and right anterior superior temporal cortex is a marker of receptive language outcome after aphasic stroke, and illustrate that language system organization after focal brain lesions may be marked by complex signatures of altered local and pathway-level function.

Neural Correlates of Value, Risk, and Risk Aversion Contributing to Decision Making under Risk

Decision making under risk is central to human behavior. Economic decision theory suggests that value, risk, and risk aversion influence choice behavior. Although previous studies identified neural correlates of decision parameters, the contribution of these correlates to actual choices is unknown. In two different experiments, participants chose between risky and safe options. We identified discrete blood oxygen level-dependent (BOLD) correlates of value and risk in the ventral striatum and anterior cingulate, respectively. Notably, increasing inferior frontal gyrus activity to low risk and safe options correlated with higher risk aversion. Importantly, the combination of these BOLD responses effectively decoded the behavioral choice. Striatal value and cingulate risk responses increased the probability of a risky choice, whereas inferior frontal gyrus responses showed the inverse relationship. These findings suggest that the BOLD correlates of decision factors are appropriate for an ideal observer to detect behavioral choices. More generally, these biological data contribute to the validity of the theoretical decision parameters for actual decisions under risk.

Neural Signatures of Semantic and Phonemic Fluency in Young and Old Adults

As we age, our ability to select and to produce words changes, yet we know little about the underlying neural substrate of word-finding difficulties in old adults. This study was designed to elucidate changes in specific frontally mediated retrieval processes involved in word-finding difficulties associated with advanced age. We implemented two overt verbal (semantic and phonemic) fluency tasks during fMRI and compared brain activity patterns of old and young adults. Performance during the phonemic task was comparable for both age groups and mirrored by strongly left-lateralized (frontal) activity patterns. On the other hand, a significant drop of performance during the semantic task in the older group was accompanied by additional right (inferior and middle) frontal activity, which was negatively correlated with performance. Moreover, the younger group recruited different subportions of the left inferior frontal gyrus for both fluency tasks, whereas the older participants failed to show this distinction. Thus, functional integrity and efficient recruitment of left frontal language areas seems to be critical for successful word retrieval in old age.

The Left Ventral Occipito-Temporal Response to Words Depends on Language Lateralization but Not on Visual Familiarity

The sensitivity of the left ventral occipito-temporal (vOT) cortex to visual word processing has triggered a considerable debate about the role of this region in reading. One popular view is that the left vOT underlies the perceptual expertise needed for rapid skilled reading. Because skilled reading breaks down when words are presented in a visually unfamiliar format, we tested this hypothesis by analyzing vOT responses to horizontally presented words (familiar format) and vertically presented words (unfamiliar format). In addition, we compared the activity in participants with left and right cerebral dominance for language generation. Our results revealed 1) that the vOT activity during reading is lateralized to the same side as the inferior frontal activity during word generation, 2) that vertically and horizontally presented words triggered the same amount of activity in the vOT of the dominant hemisphere, but 3) that there was significantly more activity for vertically presented words in the vOT of the nondominant hemisphere. We suggest that the reading-related activity in vOT reflects the integration of general perceptual processes with language processing in the anterior brain regions and is not limited to skilled reading in the familiar horizontal format.

Improvement of Clinical Language Localization with an Overt Semantic and Syntactic Language Functional MR Imaging Paradigm

Functional MR imaging (fMRI) is a promising but, in some aspects, still debated noninvasive tool for functional language mapping. We developed a clinical fMRI overt language design at the sentential level to optimize sensitivity for language-related areas of the brain. To evaluate applicability and sensitivity, we investigated a consecutive series of presurgical patients with epilepsy with minimal morphologic brain abnormalities. Thirty right-handed patients with temporal lobe epilepsy (TLE) and a control group of 23 right-handed healthy subjects participated in the study. The language design included semantic and syntactic error-detection tasks and was constructed to represent the most relevant aspects of everyday language demands. It was applied during block-designed fMRI runs. We performed image preprocessing and statistical analysis with SPM5 at a group level, applying widely used statistical criteria. The study was approved by the local ethics committee, and all participants gave written informed consent. Given the strict statistical criteria, the sensitivity for inferior frontal and posterior temporal activations (comprising Broca and Wernicke regions) was improved relative to previous findings in the literature. For both language areas, we found 100% sensitivity in healthy subjects (Brodmann areas, BA22 and BA44) and 97% sensitivity in patients (when including BA47). Lateralization results demonstrated the capability to detect atypical language lateralizations in patients, which were more frequent in than those in healthy subjects. We developed a clinical language fMRI design that integrates various relevant aspects of everyday language demands and provides robust localization of core language areas.

Neural mechanisms of empathy in adolescents with autism spectrum disorder and their fathers

A deficit in empathy has been repeatedly described in individuals with autism spectrum disorder (ASD) and also, albeit less markedly, in their unaffected relatives. Here, we aimed to investigate the neural mechanisms of empathy in ASD, and to explore familial contributions to empathy correlates. Using functional magnetic resonance imaging, 15 boys with ASD, 11 fathers of adolescents with ASD, and two control groups comparable for age and IQ (n=15 typically developing boys and their fathers (n=9)) were investigated during an empathy task. Emotional faces were presented and participants were either asked to infer the emotional state from the face (other-task) or to judge their own emotional response to the face (self-task). When attributing emotions to self and other, the ASD group showed diminished fusiform gyrus activation compared to controls. Neural activity in the fusiform gyrus was inversely related to social deficits in ASD subjects. Moreover, when ASD subjects inferred their own emotional response to faces, they showed less congruent reactions and inferior frontal gyrus activity was decreased. Although fathers of ASD children scored higher on a self-rating scale for autistic symptoms compared to control fathers, their task performance was unimpaired. However, neurally, fathers of affected children also showed reduced fusiform gyrus activation when inferring others' emotions. Shared abnormalities in fusiform gyrus activation in affected adolescents and first-degree relatives suggest that this dysfunction constitutes a fundamental deviation in ASD. Moreover, the findings provide evidence that both aberrant neural face and mirroring mechanisms are implicated in empathy impairments in ASD.

Brain activation for reading and listening comprehension: An fMRI study of modality effects and individual differences in language comprehension.

The study compared the brain activation patterns associated with the comprehension of written and spoken Portuguese sentences. An fMRI study measured brain activity while participants read and listened to sentences about general world knowledge. Participants had to decide if the sentences were true or false. To mirror the transient nature of spoken sentences, visual input was presented in rapid serial visual presentation format. The results showed a common core of amodal left inferior frontal and middle temporal gyri activation, as well as modality specific brain activation associated with listening and reading comprehension. Reading comprehension was associated with more left-lateralized activation and with left inferior occipital cortex (including fusiform gyrus) activation. Listening comprehension was associated with extensive bilateral temporal cortex activation and more overall activation of the whole cortex. Results also showed individual differences in brain activation for reading comprehension. Readers with lower working memory capacity showed more activation of right-hemisphere areas (spillover of activation) and more activation in the prefrontal cortex, potentially associated with more demand placed on executive control processes. Readers with higher working memory capacity showed more activation in a frontal-posterior network of areas (left angular and precentral gyri, and right inferior frontal gyrus). The activation of this network may be associated with phonological rehearsal of linguistic information when reading text presented in rapid serial visual format. The study demonstrates the modality fingerprints for language comprehension and indicates how low- and high working memory capacity readers deal with reading text presented in serial format.

Increased inferior frontal activation during word generation: A marker of genetic risk for schizophrenia but not bipolar disorder?

During verbal-fluency tasks, impairments in performance and functional abnormalities in the inferior frontal cortex have been observed in both schizophrenia patients and their unaffected relatives. We sought to examine whether such functional abnormalities are a specific marker of genetic vulnerability to schizophrenia. We studied a sample of 132 subjects, comprising 39 patients with schizophrenia, 10 unaffected monozygotic (MZ) cotwins of schizophrenia probands, 28 patients with bipolar disorder, 7 unaffected MZ cotwins of bipolar disorder probands and 48 healthy controls. Blood oxygen level-dependent response was measured using functional magnetic resonance imaging during the performance of an overt verbal-fluency task with two levels of task difficulty, in a cytoarchitectonic region of interest encompassing Brodmann areas 44 and 45 bilaterally. Patients with schizophrenia and the unaffected MZ cotwins of schizophrenia probands showed increased activation in the inferior frontal cortex relative to healthy controls and bipolar patients. Increased engagement of the inferior frontal cortex during verbal-fluency may thus be a marker of genetic vulnerability to schizophrenia.

Enhanced activation of the left inferior frontal gyrus in deaf and dyslexic adults during rhyming.

Hearing developmental dyslexics and profoundly deaf individuals both have difficulties processing the internal structure of words (phonological processing) and learning to read. In hearing non-impaired readers, the development of phonological representations depends on audition. In hearing dyslexics, many argue, auditory processes may be impaired. In congenitally profoundly deaf individuals, auditory speech processing is essentially absent. Two separate literatures have previously reported enhanced activation in the left inferior frontal gyrus in both deaf and dyslexic adults when contrasted with hearing non-dyslexics during reading or phonological tasks. Here, we used a rhyme judgement task to compare adults from these two special populations to a hearing non-dyslexic control group. All groups were matched on non-verbal intelligence quotient, reading age and rhyme performance. Picture stimuli were used since this requires participants to generate their own phonological representations, rather than have them partially provided via text. By testing well-matched groups of participants on the same task, we aimed to establish whether previous literatures reporting differences between individuals with and without phonological processing difficulties have identified the same regions of differential activation in these two distinct populations. The data indicate greater activation in the deaf and dyslexic groups than in the hearing non-dyslexic group across a large portion of the left inferior frontal gyrus. This includes the pars triangularis, extending superiorly into the middle frontal gyrus and posteriorly to include the pars opercularis, and the junction with the ventral precentral gyrus. Within the left inferior frontal gyrus, there was variability between the two groups with phonological processing difficulties. The superior posterior tip of the left pars opercularis, extending into the precentral gyrus, was activated to a greater extent by deaf than dyslexic participants, whereas the superior posterior portion of the pars triangularis extending into the ventral pars opercularis, was activated to a greater extent by dyslexic than deaf participants. Whether these regions play differing roles in compensating for poor phonological processing is not clear. However, we argue that our main finding of greater inferior frontal gyrus activation in both groups with phonological processing difficulties in contrast to controls suggests greater reliance on the articulatory component of speech during phonological processing when auditory processes are absent (deaf group) or impaired (dyslexic group). Thus, the brain appears to develop a similar solution to a processing problem that has different antecedents in these two populations.

Atomoxetine Modulates Right Inferior Frontal Activation During Inhibitory Control: A Pharmacological Functional Magnetic Resonance Imaging Study

Atomoxetine, a selective noradrenaline reuptake inhibitor (SNRI) licensed for the treatment of attention-deficit/hyperactivity disorder (ADHD), has been shown to improve response inhibition in animals, healthy volunteers, and adult patients. However, the mechanisms by which atomoxetine improves inhibitory control have yet to be determined. The effects of atomoxetine (40 mg) were measured with a stop-signal functional magnetic resonance imaging (fMRI) paradigm in 19 healthy volunteers, in a within-subject, double-blind, placebo-controlled design. Atomoxetine improved inhibitory control and increased activation in the right inferior frontal gyrus when volunteers attempted to inhibit their responses (irrespective of success). Plasma levels of drug correlated significantly with right inferior frontal gyrus activation only during successful inhibition. These results show that atomoxetine exerts its beneficial effects on inhibitory control via modulation of right inferior frontal function, with implications for understanding and treating inhibitory dysfunction of ADHD and other disorders.