The effect of the MR pulse sequence on the regional corpus callosum morphometry.

BACKGROUND AND PURPOSES: Brain morphometry is an important assessment technique to assess certain morphological brain features of various brain regions, which can be quantified in vivo by using high-resolution structural magnetic resonance (MR) imaging. This study aims to investigate the effect of different types of pulse sequence on regional corpus callosum (CC) morphometry analysis. MATERIALS AND METHODS: Twenty-one healthy volunteers were scanned twice on the same 3T MRI scanner (Magnetom Trio, Siemens, Erlangen, Germany) equipped with an 8-channel head coil. Two different MR pulse sequences were applied to acquire high-resolution 3D T1-weighted images: magnetization-prepared rapid gradient-echo (MP-RAGE) and modified driven equilibrium Fourier transform (MDEFT) pulse sequence. Image quality measurements such as SNR, contrast-to-noise ratio, and relative contrast were calculated for each pulse sequence images independently. The values of corpus callosum volume were calculated based on the vertex of reconstructed surfaces. The paired dependent t test was applied to compare the means of two matched groups. RESULTS: Three sub-regional CC, namely anterior, mid-anterior, and posterior, resulted in an estimated volume difference between MDEFT and MP-RAGE pulse sequences. Central and mid-posterior sub-regional CC volume resulted in not significant difference between the two named pulse sequences. CONCLUSION: The findings of this study demonstrate that combining data from different pulse sequences in a multisite study could make some variations in the results.

Resting-state functional brain networks in adults with a new diagnosis of focal epilepsy.

OBJECTIVES: Newly diagnosed focal epilepsy (NDfE) is rarely studied, particularly using advanced neuroimaging techniques. Many patients with NDfE experience cognitive impairments, particularly with respect to memory, sustained attention, mental flexibility, and executive functioning. Cognitive impairments have been related to alterations in resting-state functional brain networks in patients with neurological disorders. In the present study, we investigated whether patients with NDfE had altered connectivity in large-scale functional networks using resting-state functional MRI. METHODS: We recruited 27 adults with NDfE and 36 age- and sex-matched healthy controls. Resting-state functional MRI was analyzed using the Functional Connectivity Toolbox (CONN). We investigate reproducibly determined large-scale functional networks, including the default mode, salience, fronto-parietal attention, sensorimotor, and language networks using a seed-based approach. Network comparisons between patients and controls were thresholded using a FDR cluster-level correction approach. RESULTS: We found no significant differences in functional connectivity between seeds within the default mode, salience, sensorimotor, and language networks and other regions of the brain between patients and controls. However, patients with NDfE had significantly reduced connectivity between intraparietal seeds within the fronto-parietal attention network and predominantly frontal and temporal cortical regions relative to controls; this finding was demonstrated including and excluding the patients with brain lesions. No common alteration in brain structure was observed in patients using voxel-based morphometry. Findings were not influenced by treatment outcome at 1 year. CONCLUSIONS: Patients with focal epilepsy have brain functional connectivity alterations at diagnosis. Functional brain abnormalities are not necessarily a consequence of the chronicity of epilepsy and are present when seizures first emerge.

Microstructure of the superior temporal gyrus and hallucination proneness - a multi-compartment diffusion imaging study.

Previous studies reported that the volume of the left superior temporal gyrus (STG) is reduced in patients with schizophrenia and negatively correlated with hallucination severity. Moreover, diffusion-tensor imaging studies suggested a relationship between the brain microstructure in the STG of patients and auditory hallucinations. Hallucinations are also experienced in non-patient groups. This study investigated the relationship between hallucination proneness and the brain structure of the STG. Hallucination proneness was assessed by the Launey Slade Hallucination Scale (LSHS) in 25 healthy individuals who varied in their propensity to hear voices. Brain volume and microstructure of the STG was assessed by magnetic resonance imaging (MRI). Microstructure was examined by conventional diffusion-tensor imaging as well as by neurite orientation dispersion and density imaging (NODDI). The latter decomposes diffusion-based MRI into multiple compartments that characterize the brain microstructure by its neurite complexity known as orientation dispersion (ODI) and by its neurite density (NDI). Hallucination proneness was negatively correlated with the volume and microstructure (fractional anisotropy, neurite complexity) of the left but not the right STG. The strongest relationship (r = -0.563) was observed for neurite complexity (ODI). No correlation was observed for neurite density (NDI). These findings suggest that there is a relationship between the volume and the microstructure of the left STG and hallucination proneness. Dendritic complexity (but not neurite density) is inversely related to hallucination proneness. Metrics based on multi-compartment diffusion models seem to be more sensitive for hallucination-related neural processes than conventional MRI-based metrics.

A voxel-based asymmetry study of the relationship between hemispheric asymmetry and language dominance in Wada tested patients.

Determining the anatomical basis of hemispheric language dominance (HLD) remains an important scientific endeavor. The Wada test remains the gold standard test for HLD and provides a unique opportunity to determine the relationship between HLD and hemispheric structural asymmetries on MRI. In this study, we applied a whole-brain voxel-based asymmetry (VBA) approach to determine the relationship between interhemispheric structural asymmetries and HLD in a large consecutive sample of Wada tested patients. Of 135 patients, 114 (84.4%) had left HLD, 10 (7.4%) right HLD, and 11 (8.2%) bilateral language representation. Fifty-four controls were also studied. Right-handed controls and right-handed patients with left HLD had comparable structural brain asymmetries in cortical, subcortical, and cerebellar regions that have previously been documented in healthy people. However, these patients and controls differed in structural asymmetry of the mesial temporal lobe and a circumscribed region in the superior temporal gyrus, suggesting that only asymmetries of these regions were due to brain alterations caused by epilepsy. Additional comparisons between patients with left and right HLD, matched for type and location of epilepsy, revealed that structural asymmetries of insula, pars triangularis, inferior temporal gyrus, orbitofrontal cortex, ventral temporo-occipital cortex, mesial somatosensory cortex, and mesial cerebellum were significantly associated with the side of HLD. Patients with right HLD and bilateral language representation were significantly less right-handed. These results suggest that structural asymmetries of an insular-fronto-temporal network may be related to HLD.

Agency performance modulates resting-state variation in prefrontal brain regions.

Distinguishing the effects of own from others' actions is a prerequisite for effective interpersonal functioning. Individuals differ in their ability to do this. For example, difficulties in self-other attribution have been linked to positive symptoms of schizophrenia such as hallucinations, with causally ambiguous situations proving a universal challenge. The goal of the present study was to examine relationships between individual differences in resting-state functional connectivity and self-other attribution performance. Fifty-five healthy adults completed a resting-state fMRI scan and an attribution task that involved tapping at irregular intervals while listening to a tone sequence. The likelihood that tones in the sequence corresponded to the participant's taps was systematically varied. Using group independent component analysis (ICA) and dual regression, we found that connectivity between prefrontal networks associated with self-referential processing and regions sensitive to externally-generated stimuli was modulated by participants' ability to accurately assess the proportion of tones belonging to self versus other. These findings shed additional light on the neural mechanisms of agency, emphasising that connectivity with prefrontal networks play an important role in self-other differentiation.

Neural response to modulating the probability that actions of self or other result in auditory tones: A parametric fMRI study into causal ambiguity.

In normal circumstances we can easily distinguish between changes to the external world brought about by our own actions from those with external causes. However, in certain contexts our sense of ownership and agency over acts is not so clear. Neuroimaging studies have implicated a number of regions in the sense of agency, some of which have been shown to vary continuously with action-outcome discordance. However, little is known about dynamic, ambiguous contexts characterised by a lack of information for self-other differentiation, yet such ambiguous states are important in relation to symptoms and levels of consciousness that characterise certain mental health conditions. With a block-design fMRI paradigm, we investigated neural responses to changes in the probability that a participant's irregular finger taps over 12s would result in auditory tones as opposed to tones generated by 'another's finger taps'. The main findings were that misattribution increased in ambiguous conditions where the probability of a tone belonging to self and other was equal. Task-sensitive brain regions, previously identified in self-agency, motor cognition, and ambiguity processing, showed a quadratic response to our self-to-other manipulation, with particular sensitivity to self-control. Task performance (low error and bias) was related to attenuated response in ambiguous conditions while increased response in regions associated with the default mode network was associated with greater overall error and bias towards other. These findings suggest that causal ambiguity as it occurs over time is a prominent feature in sense of agency, one that may eventually contribute to a more comprehensive understanding of positive symptoms of psychosis.

Ambiguity between self and other: Individual differences in action attribution.

Individuals differ in their ability to attribute actions to self or other. This variance is thought to explain, in part, the experience of voice-hearing. Misattribution can also be context-driven. For example, causal ambiguity can arise when the actions of two or more individuals are coordinated and produce similar effects (e.g., music-making). Experience in such challenging contexts may refine skills of action attribution. Forty participants completed a novel finger-tapping task which parametrically manipulated the proportion of control that 'self' versus 'other' possessed over resulting auditory tones. Results showed that action misattribution peaked in the middle of the self-to-other continuum and was biased towards other. This pattern was related to both high hallucination-proneness and to low musical-experience. Findings suggest not only that causal ambiguity plays a key role in agency but also that action attribution abilities may improve with practice, potentially providing an avenue for remediation of the positive symptoms of schizophrenia.

Diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predicts patient outcomes.

BACKGROUND: Diffusion-weighted MRI (DWI) has been used in neurosurgical practice mainly to distinguish cerebral metastases from abscess and glioma. There is evidence from other solid organ cancers and metastases that DWI may be used as a biomarker of prognosis and treatment response. We therefore investigated DWI characteristics of cerebral metastases and their peritumoral region recorded pre-operatively and related these to patient outcomes. METHODS: Retrospective analysis of 76 cases operated upon at a single institution with DWI performed pre-operatively at 1.5T. Maps of apparent diffusion coefficient (ADC) were generated using standard protocols. Readings were taken from the tumor, peritumoral region and across the brain-tumor interface. Patient outcomes were overall survival and time to local recurrence. RESULTS: A minimum ADC greater than 919.4 × 10(-6) mm(2)/s within a metastasis predicted longer overall survival regardless of adjuvant therapies. This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer. The change in diffusion across the tumor border and into peritumoral brain was measured by the "ADC transition coefficient" or ATC and this was more strongly predictive than ADC readings alone. Metastases with a sharp change in diffusion across their border (ATC >0.279) showed shorter overall survival compared to those with a more diffuse edge. The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 - 0.97, p = 0.04). CONCLUSIONS: DWI demonstrates changes in the tumor, across the tumor edge and in the peritumoral region which may not be visible on conventional MRI and this may be useful in predicting patient outcomes for operated cerebral metastases.

Specific brain morphometric changes in spinal cord injury with and without neuropathic pain.

Why only certain patients develop debilitating pain after spinal chord injury and whether structural brain changes are implicated remain unknown. The aim of this study was to determine if patients with chronic, neuropathic below-level pain have specific cerebral changes compared to those who remain pain-free. Voxel-based morphometry of high resolution, T1-weighted images was performed on three subject groups comprising patients with pain (SCI-P, n = 18), patients without pain (SCI-N, n = 12) and age- and sex-matched controls (n = 18). The SCI-P group was first compared directly with the SCI-N group and then subsequently with controls. Overall, grey and white matter changes dependent on the presence of pain were revealed. Significant changes were found within the somatosensory cortex and also in corticospinal tracts and visual-processing areas. When the SCI-P group was directly compared with the SCI-N group, reduced grey matter volume was found in the deafferented leg area of the somatosensory cortex bilaterally. This region negatively correlated with pain intensity. Relative to controls, grey matter in this paracentral primary sensory cortex was decreased in SCI-P but conversely increased in SCI-N. When compared with controls, discrepant corticospinal tract white matter reductions were found in SCI-P and in SCI-N. In the visual cortex, SCI-N showed increased grey matter, whilst the SCI-N showed reduced white matter. In conclusion, structural changes in SCI are related to the presence and degree of below-level pain and involve but are not limited to the sensorimotor cortices. Pain-related structural plasticity may hold clinical implications for the prevention and management of refractory neuropathic pain.

Different association between intentionality competence and prefrontal volume in left- and right-handers.

Intentionality is the ability to explain and predict the behaviour of others by attributing to them mental states, and is thus important for social cognition. Prefrontal cortex (PFC) including orbital and dorsal regions is implicated in a range of social and metacognitive executive functions (EFs). We investigate, for the first time, in 39 left-handers and 43 right-handers the effect of handedness on the relationship between intentionality and (i) PFC volume using stereology and (ii) grey matter (GM) volume within six a priori regions of interest using voxel-based morphometry (VBM). Although no association was found between degree of handedness and intentionality competence (p = .17), handedness groups differ significantly in the relationship between intentionality and PFC volume. Right-handers with handedness score =+75 (based on a range from -100 to +100) show a significant positive correlation between intentionality and orbital PFC volume (p = .01), while no significant correlation is observed for dorsal PFC volume (p = .82); and left-handers with handedness score =-75 show a significant positive correlation between intentionality and dorsal PFC volume (p = .02) while no significant correlation is observed for orbital PFC volume (p = .44). VBM results showed significantly greater GM volume correlated with intentionality in right-handers compared to left-handers (family-wise error - FWE, p < .05) in right temporo-parietal junction and superior temporal sulcus. Correlations between GM volume and intentionality were found across all subjects (FWE, p < .05) in bilateral middle frontal gyrus, superior temporal sulcus and right inferior frontal gyrus, superior frontal gyrus and precuneus. Overall, the findings suggest that the neuroanatomy underlying intentionality competence is influenced by handedness and that different methodological approaches can and should be considered in conjunction when investigating neuroanatomical correlates of psychological functioning.

Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings in the TIPIT study.

BACKGROUND: In order to assess relationships between thyroid hormone status and findings on brain MRI, a subset of babies was recruited to a multi-centre randomised, placebo-controlled trial of levothyroxine (LT4) supplementation for babies born before 28 weeks' gestation (known as the TIPIT study, for Thyroxine supplementation In Preterm InfanTs). These infants were imaged at term-equivalence. MATERIALS AND METHODS: Forty-five TIPIT participants had brain MRI using diffusion tensor imaging (DTI) to estimate white matter development by apparent diffusion coefficient (ADC), fractional anisotropy (FA) and tractography metrics of number and length of streamlines. We made comparisons between babies with the lowest and highest plasma FT4 concentrations during the initial 4 weeks after birth. RESULTS: There were no differences in DTI metrics between babies who had received LT4 supplementation and those who had received a placebo. Among recipients of a placebo, babies in the lowest quartile of plasma-free thyroxine (FT4) concentrations had significantly higher apparent diffusion coefficient measurements in the posterior corpus callosum and streamlines that were shorter and less numerous in the right internal capsule. Among LT4-supplemented babies, those who had plasma FT4 concentrations in the highest quartile had significantly lower apparent diffusion coefficient values in the left occipital lobe, higher fractional anisotropy in the anterior corpus callosum and longer and more numerous streamlines in the anterior corpus callosum. CONCLUSION: DTI variables were not associated with allocation of placebo or thyroid supplementation. Markers of poorly organised brain microstructure were associated with low plasma FT4 concentrations after birth. The findings suggest that plasma FT4 concentrations affect brain development in very immature infants and that the effect of LT4 supplementation for immature babies with low FT4 plasma concentrations warrants further study.

Structural alterations in brainstem of fibromyalgia syndrome patients correlate with sensitivity to mechanical pressure.

Fibromyalgia syndrome is a chronic pain disorder characterised by widespread pain and tenderness in muscles and deep tissues. Current theories regarding the pathophysiological origins of fibromyalgia syndrome point towards central sensitisation and a decreased capacity of descending nociceptive controls. Morphological alterations to subcortical brain regions may contribute to such pathophysiological mechanisms, and to pain and other symptoms seen in fibromyalgia. Therefore, we evaluated geometric differences in subcortical structures in fibromyalgia patients relative to healthy people using a novel method of shape analysis. Sixteen female fibromyalgia patients and 15 age and sex matched, healthy control subjects underwent high-resolution T1-weighted magnetic resonance image scanning. Data was analysed using shape analysis of 15 subcortical regions and standard voxel-based morphometry analysis. Fibromyalgia syndrome patients, relative to healthy control participants, exhibited alterations to the shape of the left lateral aspect of the lower brainstem (medulla). The mean total volume of the brainstem was also found to be significantly reduced in the patient group compared to healthy control subjects, and this brainstem volume reduction in patient group significantly correlated with clinical manual tender point scale scores. Voxel-based morphometry analysis revealed that patients also demonstrated decreased local grey matter volumes in the brainstem (pons) and left precuneus, and increased grey matter volumes in bilateral primary somatosensory cortices. Results suggest that the volume reduction and associated geometric shape alterations seen in the brainstem of the patient group may contribute to sensitivity to pressure pain in fibromyalgia syndrome. This finding may be due to structure-related deficiencies in regions subserving descending nociceptive control.

Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging.

INTRODUCTION: Tinnitus is a poorly understood auditory perception of sound in the absence of external stimuli. Convergent evidence proposes that tinnitus perception involves brain structural alterations as part of its pathophysiology. The aim of this study is to investigate the structural brain changes that might be associated with tinnitus-related stress and negative emotions. METHODS: Using high-resolution magnetic resonance imaging and diffusion tensor imaging, we investigated grey matter and white matter (WM) alterations by estimating cortical thickness measures, fractional anisotropy and mean diffusivity in 14 tinnitus subjects and 14 age- and sex-matched non-tinnitus subjects. RESULTS: Significant cortical thickness reductions were found in the prefrontal cortex (PFC), temporal lobe and limbic system in tinnitus subjects compared to non-tinnitus subjects. Tinnitus sufferers were found to have disrupted WM integrity in tracts involving connectivity of the PFC, temporal lobe, thalamus and limbic system. CONCLUSION: Our results suggest that such neural changes may represent neural origins for tinnitus or consequences of tinnitus and its associations.

Regional brain responses to pleasant and unpleasant IAPS pictures: different networks.

PURPOSE: The purpose of this study was to investigate the brain circuitry involved in the processing of both positive and negative emotions in normal healthy subjects. METHOD: we have recruited 15 healthy volunteers (9 males and 6 females, age range 30-60). In this block-design fMRI study, we compared the blood oxygen level dependant (BOLD) signal change as response to pleasant and unpleasant IAPS pictures, each compared to a neutral condition. RESULTS: Pleasant pictures versus neutral condition contrast demonstrated significant activation (p(FDRcorrected) <0.05) in bilateral pre-frontal cortex (PFC), anterior and posterior cingulate gyri and temporal lobe. Unpleasant pictures relative to neutral condition exhibit significant activation (p(FDRcorrected) <0.05) in amygdala, hippocampus, parahippocampal gyri, temporal lobe, visual cortex, fusiform gyri, PFC and anterior cingulate gyrus. CONCLUSION: Amygdala is mainly involved in the processing of negative emotions. Although an overlap in regions involved in the processing of pleasant and unpleasant IAPS pictures exists, the neural network for each is unique.

Calibrated fMRI during a cognitive Stroop task reveals reduced metabolic response with increasing age.

fMRI studies of aging have revealed increased blood oxygenation level dependent (BOLD) response to tasks of executive function with advancing age, which is generally interpreted as increased neural activity. However, changes in the cerebrovascular system with age can alter the BOLD signal, complicating this interpretation. Arterial spin labeling (ASL) allows simultaneous acquisition of BOLD and cerebral blood flow (CBF) information and can be used to quantify the component parts of the BOLD signal. We used this calibrated BOLD approach in 58 healthy participants over an age range of 18-71 years to determine the relative vascular and neuronal contributions to the age-related BOLD changes in response to a Stroop task. The percentage BOLD response increased significantly with increasing age but the percentage CBF response did not alter, such that the BOLD increase is attributed to a significant reduction in the oxygen metabolism response with increasing age. Hence, in this study, the BOLD increase with age should be interpreted as a reduction in neural activity. The greatest percentage BOLD increases with age were found in the left and right medial frontal gyri and the primary motor cortex and were again linked to a reduction in oxygen metabolism. On separating the participants into three groups (young, old high performers and old low performers), age-related differences in percentage BOLD response and oxygen metabolism response could be attributed to the low performing old group. This study demonstrates the need to take into account alterations in vascular-metabolic coupling and resting blood volume when interpreting changes in the BOLD response with aging.

Plasticity of the superior and middle cerebellar peduncles in musicians revealed by quantitative analysis of volume and number of streamlines based on diffusion tensor tractography.

This work was conducted to study the plasticity of superior (SCP) and middle (MCP) cerebellar peduncles in musicians. The cerebellum is well known to support several musically relevant motor, sensory and cognitive functions. Previous studies reported increased cerebellar volume and grey matter (GM) density in musicians. Here, we report on plasticity of white matter (WM) of the cerebellum. Our cohort included 10/10 gender and handedness-matched musicians and controls. Using diffusion tensor imaging, fibre tractography of SCP and MCP was performed. The fractional anisotropy (FA), number of streamlines and volume of streamlines of SCP/MCP were compared between groups. Automatic measurements of GM and WM volumes of the right/left cerebellar hemispheres were also compared. Musicians have significantly increased right SCP volume (p = 0.02) and number of streamlines (p = 0.001), right MCP volume (p = 0.004) and total WM volume of the right cerebellum (p = 0.003). There were no significant differences in right MCP number of streamlines, left SCP/MCP volume and number of streamlines, SCP/MCP FA values, GM volume of the right cerebellum and GM/WM volumes of the left cerebellum. We propose that increased volume and number of streamlines of the right cerebellar peduncles represent use-dependent structural adaptation to increased sensorimotor and cognitive functional demands on the musician's cerebellum.

Increased gray matter volume of left pars opercularis in male orchestral musicians correlate positively with years of musical performance.

PURPOSE: To compare manual volumetry of gray matter (GM) / white matter (WM) of Broca's area subparts: pars opercularis (POP) and pars triangularis (PTR) in both hemispheres between musicians and nonmusician, as it has been shown that these regions are crucial for musical abilities. A previous voxel-based morphometric (VBM) study conducted in our laboratory reported increased GM density in Broca's area of left hemisphere in male orchestral musicians. Functional segregation of POP/PTR justified separate volumetric analysis of these parts. MATERIALS AND METHODS: We used the same cohort for the VBM study. Manual morphometry (stereology) was used to compare volumes between 26/26 right-handed orchestral musicians/nonmusicians. RESULTS: As expected, musicians showed significantly increased GM volume in the Broca's area, specifically in the left POP. No significant results were detected in right POP, left/right PTR GM volumes, and WM volumes for all regions. Results were positively correlated with years of musical performance (r = 0.7, P = 0.0001). CONCLUSION: This result corroborates the VBM study and is in line with the hypothesis of critical involvement of POP in hearing-action integration being an integral component of frontoparietotemporal mirror neuron network. We hypothesize that increased size of musicians' left POP represent use-dependent structural adaptation in response to intensive audiomotor skill acquisition.

Regional corpus callosum morphometry: effect of field strength and pulse sequence.

PURPOSE: To investigate whether scanning at different field strengths and pulse sequences would influence reproducibility of corpus callosum (CC) morphometric measurements as variations in scanning parameters may result in differences in contrast properties between resulting images that are independent of the underlying tissue but rather reflect the physics of the imaging process. MATERIALS AND METHODS: Ten subjects were scanned twice at 3T using magnetization-prepared rapid gradient-echo imaging (MPRAGE) and modified driven equilibrium Fourier transform (MDEFT) sequences and once at 1.5T using MPRAGE. Cross-sectional area measurements of four callosal regions were performed on midsagittal magnetic resonance imaging (MRI) sections. RESULTS: Repeated measures analysis of variance with four regions as dependent variables and three scanning protocols (1.5T MPRAGE, 3T MPRAGE and 3T MDEFT) as independent variables revealed no significant region by protocol interaction: F(6,54) = 0.69, P = 0.52. Reliability measures for (3T MPRAGE/3T MDEFT) and (1.5T MPRAGE/3T MPRAGE; 1.5T MPRAGE/3T MDEFT) comparisons were high, ranging between 0.90 and 0.97. CONCLUSION: Based on our results, combining and comparing CC morphometric data obtained at different field strengths and/or with different pulse sequences appears possible.

Heschl gyrus and its included primary auditory cortex: structural MRI studies in healthy and diseased subjects.

Despite the fact that the Heschl gyrus (HG) is a crucial brain structure as it contains the primary auditory cortex (PAC), relatively few structural MRI studies have concentrated upon it. We propose that this may be attributed in part to the considerable variability of this structure and, most importantly, to the lack of unified criteria for defining the extent of the PAC along the MRI-determined landmarks of the HG, which ultimately affects the reliability and reproducibility of these studies. This review highlights three aspects: first, the standard and variant anatomy of the HG and PAC with particular focus on MRI definition of these regions; second, the importance of studying the HG and PAC in health and disease using structural MRI; and, third, the problem of MRI localization of the PAC. The scientific community should be aware that the HG and its included PAC are not synonyms. Additionally, owing to the great complexity and variability of these regions, future MRI studies should be cautious when using single brain-based atlas or maps generated by simply averaging across individuals to localize these regions. Instead, and while waiting for future in vivo microstructural localization of the PAC, the use of probabilistic and functional maps is advantageous but not without shortcomings.