Comparative meta-analyses of brain structural and functional abnormalities during cognitive control in attention-deficit/hyperactivity disorder and autism spectrum disorder.

BACKGROUND: People with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic networks. It is unclear to what extent these abnormalities are distinctive or shared. This comparative meta-analysis aimed to identify the most consistent disorder-differentiating and shared structural and functional abnormalities. METHODS: Systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies of cognitive control comparing people with ASD or ADHD with typically developing controls. Regional gray matter volume (GMV) and fMRI abnormalities during cognitive control were compared in the overall sample and in age-, sex- and IQ-matched subgroups with seed-based d mapping meta-analytic methods. RESULTS: Eighty-six independent VBM (1533 ADHD and 1295 controls; 1445 ASD and 1477 controls) and 60 fMRI datasets (1001 ADHD and 1004 controls; 335 ASD and 353 controls) were identified. The VBM meta-analyses revealed ADHD-differentiating decreased ventromedial orbitofrontal (z = 2.22, p < 0.0001) but ASD-differentiating increased bilateral temporal and right dorsolateral prefrontal GMV (zs ⩾ 1.64, ps ⩽ 0.002). The fMRI meta-analyses of cognitive control revealed ASD-differentiating medial prefrontal underactivation but overactivation in bilateral ventrolateral prefrontal cortices and precuneus (zs ⩾ 1.04, ps ⩽ 0.003). During motor response inhibition specifically, ADHD relative to ASD showed right inferior fronto-striatal underactivation (zs ⩾ 1.14, ps ⩽ 0.003) but shared right anterior insula underactivation. CONCLUSIONS: People with ADHD and ASD have mostly distinct structural abnormalities, with enlarged fronto-temporal GMV in ASD and reduced orbitofrontal GMV in ADHD; and mostly distinct functional abnormalities, which were more pronounced in ASD.

Altered white matter connectivity in young people exposed to childhood abuse: a tract-based spatial statistics (TBSS) and tractography study

Background: Childhood abuse is associated with structural brain abnormalities. Few studies have investigated white matter tract abnormalities in medication-naive, drug-free individuals who experienced childhood abuse. We examined the association between childhood abuse and abnormalities in white matter tracts in that population, controlling for psychiatric comorbidities. Methods: We collected diffusion tensor imaging data for age- and sex-matched youth with childhood abuse, psychiatric controls (matched for psychiatric diagnoses) and healthy controls. Tract-specific analysis was conducted using tractography. Tract-based spatial statistics (TBSS) was used to assess group differences in fractional anisotropy (FA) at the whole-brain level. Results: We included 20 youth who experienced childhood abuse, 18 psychiatric controls and 25 healthy controls in our analysis. Tractography analysis showed abuse-specific reduced tract volume in the inferior longitudinal fasciculus (ILF) and inferior frontal-occipital fasciculus (IFoF) in the abuse group relative to both healthy and psychiatric controls. Furthermore, abnormalities in the left IFoF were associated with greater abuse severity. The TBSS analysis showed significantly reduced FA in a left-hemispheric cluster comprising the ILF, IFoF and corpus callosum splenium in the abuse group relative to healthy and psychiatric controls. Limitations: It is unclear to what extent pubertal development, malnutrition and prenatal drug exposure may have influenced the findings. Conclusion: Childhood abuse is associated with altered structure of neural pathways connecting the frontal, temporal and occipital cortices that are known to mediate affect and cognitive control. The abuse-specific deficits in the ILF and IFoF suggest that fibre tracts presumably involved in conveying and processing the adverse abusive experience are specifically compromised in this population.

Altered Functional Connectivity of Fronto-Cingulo-Striatal Circuits during Error Monitoring in Adolescents with a History of Childhood Abuse.

Childhood maltreatment is associated with error hypersensitivity. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA) interaction on functional brain connectivity during error processing in medication/drug-free adolescents. Functional connectivity was compared, using generalized psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 22 age- and gender-matched medication-naïve and substance abuse-free adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed an individually adjusted tracking stop-signal task, designed to elicit 50% inhibition failures. During inhibition failures, abused participants relative to healthy controls exhibited reduced connectivity between right and left putamen, bilateral caudate and anterior cingulate cortex (ACC), and between right supplementary motor area (SMA) and right inferior and dorsolateral prefrontal cortex. Abuse-related connectivity abnormalities were associated with longer abuse duration. No group differences in connectivity were observed for successful inhibition. The findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-cingulo-striatal networks during error processing. Furthermore that the severity of connectivity abnormalities increases with abuse duration. Reduced connectivity of error detection networks in maltreated individuals may be linked to constant monitoring of errors in order to avoid mistakes which, in abusive contexts, are often associated with harsh punishment.

Reduced functional connectivity of fronto-parietal sustained attention networks in severe childhood abuse.

Childhood maltreatment is associated with attention deficits. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA, FKBP5) interaction on functional brain connectivity during sustained attention in medication/drug-free adolescents. Functional connectivity was compared, using generalised psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 21 age-and gender-matched adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed a parametrically modulated vigilance task requiring target detection with a progressively increasing load of sustained attention. Behaviourally, participants exposed to childhood abuse had increased omission errors compared to healthy controls. During the most challenging attention condition abused participants relative to controls exhibited reduced connectivity, with a left-hemispheric bias, in typical fronto-parietal attention networks, including dorsolateral, rostromedial and inferior prefrontal and inferior parietal regions. Abuse-related connectivity abnormalities were exacerbated in individuals homozygous for the risky C-allele of the single nucleotide polymorphism rs3800373 of the FK506 Binding Protein 5 (FKBP5) gene. Findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-parietal attention networks and that the FKBP5 genotype moderates neurobiological vulnerability to abuse. These findings represent a first step towards the delineation of abuse-related neurofunctional connectivity abnormalities, which hopefully will facilitate the development of specific treatment strategies for victims of childhood maltreatment.

Neurofunctional Abnormalities during Sustained Attention in Severe Childhood Abuse.

Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naïve, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse.

Structural and Functional Brain Abnormalities in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder: A Comparative Meta-analysis.

IMPORTANCE: Patients with attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) share impaired inhibitory control. However, it is unknown whether impairments are mediated by shared or disorder-specific neurostructural and neurofunctional abnormalities. OBJECTIVE: To establish shared and disorder-specific structural, functional, and overlapping multimodal abnormalities in these 2 disorders through a voxel-based meta-analytic comparison of whole-brain gray matter volume (GMV) and functional magnetic resonance imaging (fMRI) studies of inhibition in patients with ADHD and OCD. DATA SOURCES: Literature search using PubMed, ScienceDirect, Web of Knowledge, and Scopus up to September 30, 2015. STUDY SELECTION: Whole-brain voxel-based morphometry (VBM) or fMRI studies during inhibitory control comparing children and adults with ADHD or OCD with controls. DATA EXTRACTION AND SYNTHESIS: Voxel-wise meta-analyses of GMV or fMRI differences were performed using Seed-based d-Mapping. Regional structure and function abnormalities were assessed within each patient group and then a quantitative comparison was performed of abnormalities (relative to controls) between ADHD and OCD. MAIN OUTCOMES AND MEASURES: Meta-analytic disorder-specific and shared abnormalities in GMV, in inhibitory fMRI, and in multimodal functional and structural measures. RESULTS: The search revealed 27 ADHD VBM data sets (including 931 patients with ADHD and 822 controls), 30 OCD VBM data sets (928 patients with OCD and 942 controls), 33 ADHD fMRI data sets (489 patients with ADHD and 591 controls), and 18 OCD fMRI data sets (287 patients with OCD and 284 controls). Patients with ADHD showed disorder-contrasting multimodal structural (left z = 1.904, P < .001; right z = 1.738, P < .001) and functional (left z = 1.447, P < .001; right z = 1.229, P < .001) abnormalities in bilateral basal ganglia/insula, which were decreased in GMV and function in patients with ADHD relative to those with OCD (and controls). In OCD patients, they were enhanced relative to controls. Patients with OCD showed disorder-specific reduced function and structure in rostral and dorsal anterior cingulate/medial prefrontal cortex (fMRI z = 2.113, P < .001; VBM z = 1.622, P < .001), whereas patients with ADHD showed disorder-specific underactivation predominantly in the right ventrolateral prefrontal cortex (z = 1.229, P < .001). Ventromedial prefrontal GMV reduction was shared in both disorders relative to controls. CONCLUSIONS AND RELEVANCE: Shared impairments in inhibitory control, rather than representing a transdiagnostic endophenotype in ADHD and OCD, were associated with disorder-differential functional and structural abnormalities. Patients with ADHD showed smaller and underfunctioning ventrolateral prefrontal/insular-striatal regions whereas patients with OCD showed larger and hyperfunctioning insular-striatal regions that may be poorly controlled by smaller and underfunctioning rostro/dorsal medial prefrontal regions.

Neural Correlates of Error Processing in Young People With a History of Severe Childhood Abuse: An fMRI Study.

OBJECTIVE: Childhood maltreatment is associated with various cognitive deficits, including inhibitory deficits and hypersensitivity to negative feedback. The authors used a stop-signal task to investigate the association between severe childhood abuse and inhibitory and error processing brain activation in medication-naive, drug-free young people with and without severe childhood abuse, controlling for psychiatric comorbidities by including a psychiatric control group. METHOD: Using functional MRI, the authors compared brain activation in 22 age- and gender-matched young people exposed to severe childhood abuse, 17 psychiatric comparison subjects matched for psychiatric diagnoses with the abused group, and 27 healthy comparison subjects during an individually adjusted tracking stop-signal task designed to elicit 50% inhibition failures. RESULTS: During failed inhibition, the childhood abuse group showed increased brain activation relative to the healthy comparison group in typical error processing regions of the dorsomedial frontal cortex, including the left and right presupplementary and supplementary motor area and anterior cingulate cortex. The increased activation in a smaller cluster in the supplementary motor area survived comparison with the psychiatric comparison group. No group differences in activation were observed for successful inhibition. CONCLUSIONS: The findings suggest that severe childhood abuse is associated with abnormally increased activation in classical dorsomedial frontal error-processing regions; furthermore, the increased activation in the supplementary motor area was abuse specific. However, childhood abuse was not associated with inhibitory dysfunction. Increased sensitivity of error-detection networks in participants in the childhood abuse group may be due to the constant need to monitor their own actions in order to avoid painful mistakes, which are often associated with harsh punishment in abusive settings.

Predictive neurofunctional markers of attention-deficit/hyperactivity disorder based on pattern classification of temporal processing.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is currently diagnosed on the basis of subjective measures, despite evidence for multi-systemic structural and neurofunctional deficits. A consistently observed neurofunctional deficit is in fine-temporal discrimination (TD). The aim of this proof-of-concept study was to examine the feasibility of distinguishing patients with ADHD from controls using multivariate pattern recognition analyses of functional magnetic resonance imaging (fMRI) data of TD. METHOD: A total of 20 medication-naive adolescent male patients with ADHD and 20 age-matched healthy controls underwent fMRI while performing a TD task. The fMRI data were analyzed with Gaussian process classifiers to predict individual ADHD diagnosis based on brain activation patterns. RESULTS: The pattern of brain activation correctly classified up to 80% of patients and 70% of controls, achieving an overall classification accuracy of 75%. The distributed activation networks with the highest delineation between patients and controls corresponded to a distributed network of brain regions involved in TD and typically compromised in ADHD, including inferior and dorsolateral prefrontal, insula, and parietal cortices, and the basal ganglia, anterior cingulate, and cerebellum. These regions overlapped with areas of reduced activation in patients with ADHD relative to controls in a univariate analysis, suggesting that these are dysfunctional regions. CONCLUSIONS: We show evidence that pattern recognition analyses combined with fMRI using a disorder-sensitive task such as timing have potential in providing objective diagnostic neuroimaging biomarkers of ADHD.

Pattern classification of response inhibition in ADHD: toward the development of neurobiological markers for ADHD.

The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern classification to task-based functional magnetic resonance imaging (fMRI) of inhibition, to accurately predict the diagnostic status of ADHD. Thirty adolescent ADHD and thirty age-matched healthy boys underwent fMRI while performing a Stop task. fMRI data were analyzed with Gaussian process classifiers (GPC), a machine learning approach, to predict individual ADHD diagnosis based on task-based activation patterns. Traditional univariate case-control analyses were also performed to replicate previous findings in a relatively large dataset. The pattern of brain activation correctly classified up to 90% of patients and 63% of controls, achieving an overall classification accuracy of 77%. The regions of the discriminative network most predictive of controls included later developing lateral prefrontal, striatal, and temporo-parietal areas that mediate inhibition, while regions most predictive of ADHD were in earlier developing ventromedial fronto-limbic regions, which furthermore correlated with symptom severity. Univariate analysis showed reduced activation in ADHD in bilateral ventrolateral prefrontal, striatal, and temporo-parietal regions that overlapped with areas predictive of controls, suggesting the latter are dysfunctional areas in ADHD. We show that significant individual classification of ADHD patients of 77% can be achieved using whole brain pattern analysis of task-based fMRI inhibition data, suggesting that multivariate pattern recognition analyses of inhibition networks can provide objective diagnostic neuroimaging biomarkers of ADHD.

Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects.

CONTEXT Functional magnetic resonance imaging studies in attention-deficit/hyperactivity disorder (ADHD) revealed fronto-striato-parietal dysfunctions during tasks of inhibition and attention. However, it is unclear whether task-dissociated dysfunctions exist and to what extent they may be influenced by age and by long-term stimulant medication use. OBJECTIVE To conduct a meta-analysis of functional magnetic resonance imaging studies in ADHD during inhibition and attention tasks, exploring age and long-term stimulant medication use effects. DATA SOURCES PubMed, ScienceDirect, Web of Knowledge, Google Scholar, and Scopus databases were searched up to May 2012 for meta-analyses. Meta-regression methods explored age and long-term stimulant medication use effects. STUDY SELECTION Twenty-one data sets were included for inhibition (287 patients with ADHD and 320 control subjects), and 13 data sets were included for attention (171 patients with ADHD and 178 control subjects). DATA EXTRACTION Peak coordinates of clusters of significant group differences, as well as demographic, clinical, and methodological variables, were extracted for each study or were obtained from the authors. DATA SYNTHESIS Patients with ADHD relative to controls showed reduced activation for inhibition in the right inferior frontal cortex, supplementary motor area, and anterior cingulate cortex, as well as striato-thalamic areas, and showed reduced activation for attention in the right dorsolateral prefrontal cortex, posterior basal ganglia, and thalamic and parietal regions. Furthermore, the meta-regression analysis for the attention domain showed that long-term stimulant medication use was associated with more similar right caudate activation relative to controls. Age effects could be analyzed only for the inhibition meta-analysis, showing that the supplementary motor area and basal ganglia were underactivated solely in children with ADHD relative to controls, while the inferior frontal cortex and thalamus were underactivated solely in adults with ADHD relative to controls. CONCLUSIONS Patients with ADHD have consistent functional abnormalities in 2 distinct domain-dissociated right hemispheric fronto-basal ganglia networks, including the inferior frontal cortex, supplementary motor area, and anterior cingulate cortex for inhibition and dorsolateral prefrontal cortex, parietal, and cerebellar areas for attention. Furthermore, preliminary evidence suggests that long-term stimulant medication use may be associated with more normal activation in right caudate during the attention domain.

Meta-analysis of fMRI studies of timing in attention-deficit hyperactivity disorder (ADHD).

Attention-deficit hyperactivity disorder (ADHD) is associated with deficits in timing functions with, however, inconclusive findings on the underlying neurofunctional deficits. We therefore conducted a meta-analysis of 11 functional magnetic resonance imaging (fMRI) studies of timing in ADHD, comprising 150 patients and 145 healthy controls. Peak coordinates were extracted from significant case-control activation differences as well as demographic, clinical, and methodological variables. In addition, meta-regression analyses were used to explore medication effects. The most consistent deficits in ADHD patients relative to controls were reduced activation in typical areas of timing such as left inferior prefrontal cortex (IFC)/insula, cerebellum, and left inferior parietal lobe. The findings of left fronto-parieto-cerebellar deficits during timing functions contrast with well documented right fronto-striatal dysfunctions for inhibitory and attention functions, suggesting cognitive domain-specific neurofunctional deficits in ADHD. The meta-regression analysis showed that right dorsolateral prefrontal cortex (DLPFC) activation was reduced in medication-naïve patients but normal in long-term stimulant medicated patients relative to controls, suggesting potential normalization effects on the function of this prefrontal region with long-term psychostimulant treatment.

Neuroimaging of child abuse: a critical review.

Childhood maltreatment is a stressor that can lead to the development of behavior problems and affect brain structure and function. This review summarizes the current evidence for the effects of childhood maltreatment on behavior, cognition and the brain in adults and children. Neuropsychological studies suggest an association between child abuse and deficits in IQ, memory, working memory, attention, response inhibition and emotion discrimination. Structural neuroimaging studies provide evidence for deficits in brain volume, gray and white matter of several regions, most prominently the dorsolateral and ventromedial prefrontal cortex but also hippocampus, amygdala, and corpus callosum (CC). Diffusion tensor imaging (DTI) studies show evidence for deficits in structural interregional connectivity between these areas, suggesting neural network abnormalities. Functional imaging studies support this evidence by reporting atypical activation in the same brain regions during response inhibition, working memory, and emotion processing. There are, however, several limitations of the abuse research literature which are discussed, most prominently the lack of control for co-morbid psychiatric disorders, which make it difficult to disentangle which of the above effects are due to maltreatment, the associated psychiatric conditions or a combination or interaction between both. Overall, the better controlled studies that show a direct correlation between childhood abuse and brain measures suggest that the most prominent deficits associated with early childhood abuse are in the function and structure of lateral and ventromedial fronto-limbic brain areas and networks that mediate behavioral and affect control. Future, large scale multimodal neuroimaging studies in medication-naïve subjects, however, are needed that control for psychiatric co-morbidities in order to elucidate the structural and functional brain sequelae that are associated with early environmental adversity, independently of secondary co-morbid conditions.

Different areas of human non-primary auditory cortex are activated by sounds with spatial and nonspatial properties.

In humans, neuroimaging studies have identified the planum temporale to be particularly responsive to both spatial and nonspatial attributes of sound. However, a functional segregation of the planum temporale along these acoustic dimensions has not been firmly established. We evaluated this scheme in a factorial design using modulated sounds that generated a percept of motion (spatial) or frequency modulation (nonspatial). In addition, these sounds were presented in the context of a motion detection and a frequency-modulation detection task to investigate the cortical effects of directing attention to different perceptual attributes of the sound. Motion produced stronger activation in the medial part of the planum temporale and frequency-modulation produced stronger activation in the lateral part of the planum temporale, as well as an additional non-primary area lateral to Heschl's gyrus. These separate subregions are consistent with the notion of divergent processing streams for spatial and nonspatial auditory information. Activation in the superior parietal cortex, putatively involved in the spatial pathway, was dependent on the task of motion detection and not simply on the presence of acoustic cues for motion. This finding suggests that the listening task is an important determinant of how the processing stream is engaged.

Amplitude and frequency-modulated stimuli activate common regions of human auditory cortex.

Hall et al. (Hall et al., 2002, Cerebral Cortex 12:140-149) recently showed that pulsed frequency-modulated tones generate considerably higher activation than their unmodulated counterparts in non-primary auditory regions immediately posterior and lateral to Heschl's gyrus (HG). Here, we use fMRI to explore the type of modulation necessary to evoke such differential activation. Carrier signals were a single tone and a harmonic-complex tone, with a 300 Hz fundamental, that were modulated at a rate of 5 Hz either in frequency, or in amplitude, to create six stimulus conditions (unmodulated, FM, AM). Relative to the silent baseline, the modulated tones, in particular, activated widespread regions of the auditory cortex bilaterally along the supra-temporal plane. When compared with the unmodulated tones, both AM and FM tones generated significantly greater activation in lateral HG and the planum temporale, replicating the previous findings. These activation patterns were largely overlapping, indicating a common sensitivity to both AM and FM. Direct comparisons between AM and FM revealed a higher magnitude of activation in response to the variation in amplitude than in frequency, plus a small part of the posterolateral region in the right hemisphere whose response was specifically AM-, and not FM-, dependent. The dominant pattern of activation was that of co-localized activation by AM and FM, which is consistent with a common neural code for AM and FM within these brain regions.

The sound-level-dependent growth in the extent of fMRI activation in Heschl's gyrus is different for low- and high-frequency tones.

fMRI (functional magnetic resonance imaging) was used to investigate whether the growth in activation of the human auditory cortex, with increasing sound level, is discernibly different for high- and low-frequency tones. Ten volunteers were scanned whilst listening to sequences of low-frequency (0.30-kHz) tones at sound levels between 42 and 96 dB sound pressure level (SPL), and 10 whilst listening to high-frequency (4.75-kHz) tones at the same sound levels. Activation was measured in Heschl's gyrus (including primary auditory cortex) which has been shown to be most sensitive to changes in sound level. For the 0.30-kHz tone, the extent of activation was flat up to 66 dB and then showed a rapid growth which continued up to the highest level studied (96 dB SPL). In contrast, increasing the level of 4.75-kHz tones produced a steady growth in the extent of activation across the range of levels studied. These results are consistent with physiological evidence suggesting that recruitment of primary auditory cortical neurones may be different at high and low frequencies.

Relationships between human auditory cortical structure and function.

The human auditory cortex comprises multiple areas, largely distributed across the supratemporal plane, but the precise number and configuration of auditory areas and their functional significance have not yet been clearly established. In this paper, we discuss recent research concerning architectonic and functional organisation within the human auditory cortex, as well as architectonic and neurophysiological studies in non-human species, which can provide a broad conceptual framework for interpreting functional specialisation in humans. We review the pattern in human auditory cortex of the functional responses to various acoustic cues, such as frequency, pitch, sound level, temporal variation, motion and spatial location, and we discuss their correspondence to what is known about the organisation of the auditory cortex in other primates. There is some neuroimaging evidence of multiple tonotopically organised fields in humans and of functional specialisations of the fields in the processing of different sound features. It is thought that the primary area, on Heschl's gyrus, may have a larger involvement in processing basic sound features, such as frequency and level, and that posterior non-primary areas on the planum temporale may play a larger role in processing more spectrotemporally complex sounds. Ways in which current knowledge of auditory cortical organisation and different data analysis approaches may benefit future functional neuroimaging studies which seek to link auditory cortical structure and function are discussed.

Heschl's gyrus is more sensitive to tone level than non-primary auditory cortex.

Previous neuroimaging studies generally demonstrate a growth in the cortical response with an increase in sound level. However, the details of the shape and topographic location of such growth remain largely unknown. One limiting methodological factor has been the relatively sparse sampling of sound intensities. Additionally, most studies have either analysed the entire auditory cortex without differentiating primary and non-primary regions or have limited their analyses to Heschl's gyrus (HG). Here, we characterise the pattern of responses to a 300-Hz tone presented in 6-dB steps from 42 to 96 dB sound pressure level as a function of its sound level, within three anatomically defined auditory areas; the primary area, on HG, and two non-primary areas, consisting of a small area lateral to the axis of HG (the anterior lateral area, ALA) and the posterior part of auditory cortex (the planum temporale, PT). Extent and magnitude of auditory activation increased non-linearly with sound level. In HG, the extent and magnitude were more sensitive to increasing level than in ALA and PT. Thus, HG appears to have a larger involvement in sound-level processing than does ALA or PT.