High-field Functional Magnetic Resonance Imaging Research Articles

Somatosensory migraine auras evoked by bihemispheric cortical spreading depression events in human parietal cortex.

Cortical spreading depression (CSD) is associated with pronounced alterations in cerebral blood flow. These alterations can be captured using high-field functional magnetic resonance imaging (fMRI). While compelling clinical and experimental data suggest that CSD is involved in the pathogenesis of migraine aura, the mechanistic intricacies remain poorly understood. Here, we use visual stimulus-induced blood oxygen level-dependent (BOLD) fMRI responses to characterize spatiotemporal alterations in cerebral blood flow during spontaneous attacks with migraine aura. Six adult participants diagnosed with migraine with aura underwent BOLD fMRI scans with a visual stimulation paradigm, consisting of flickering checkerboard stimulation. Our results revealed that auras with somatosensory symptoms corresponded with bilateral alterations of stimulus-induced BOLD responses in the somatosensory cortex, exhibiting anterior-to-posterior propagation and absence of antecedent occipital abnormalities. These altered stimulus-induced BOLD responses were bilateral, despite a unilateral manifestation of aura symptoms, and had no relationship with positive or negative aura symptoms. The bilateral abnormalities in stimulus-induced BOLD responses completes our current knowledge on migraine aura.

Frontal Lobe Epilepsy: Bermuda's Triangle.

Despite great progress in imaging, genetics, surgery, and therapeutics, frontal lobe epilepsy (FLE) continues to be a challenge for neurologists and epileptologists. This manuscript summarizes the latest advancements in FLE discussed at the 2023 Epilepsy Specialist Symposium during the American Epilepsy Society Annual meeting. Correlation between stereoelectroencephalography and clinical symptoms has reinvigorated symptomatology literature in FLE, allowing for more precise aura anatomical localization. Neuropsychological assessments permit the identification of different FLE cognitive phenotypes, with language being the most prominent domain-specific impairment. These tests can help develop psychotherapeutic and cognitive support systems for these patients. Genetic and molecular studies have uncovered specific genes associated with FLE susceptibility, offering prospects for targeted therapies. Advanced neuroimaging techniques such as high field magnetic resonance imaging (MRI), functional MRI (fMRI), magnetoencephalography and colocalization of multiple imaging techniques have led to more precise localization of the epileptogenic zone providing insights into the dynamic neural networks underlying frontal lobe seizures. This has facilitated guided therapeutic surgical interventions that can be employed around the world, expanding access of these technologies to multiple populations. Despite many advances, prognosis of FLE remains poor for some patients. The biggest determinant for poor prognosis continues to be nonlesional FLE. Newer technological advancements aim to pass these barriers and offer FLE patients a better quality of life with lower seizure burden and higher cognitive outcomes.

Investigation of layer-specific BOLD signal in the human visual cortex during visual attention

Directing spatial attention towards a particular stimulus location enhances cortical responses at corresponding regions in cortex. How attention modulates the laminar response profile within the attended region remains unclear, however. In this paper, we use high-field (7T) functional magnetic resonance imaging to investigate the effects of attention on laminar activity profiles in areas V1–V3 both when a stimulus was presented to the observer and in the absence of visual stimulation. Replicating previous findings, we find robust increases in the overall BOLD response for attended regions in cortex, both with and without visual stimulation. When analysing the BOLD response across the individual layers in visual cortex, we observed no evidence for laminar-specific differentiation with attention. We offer several potential explanations for these results, including theoretical, methodological and technical reasons. Additionally, we provide all data and pipelines openly in order to promote analytic consistency across layer-specific studies and improve reproducibility.

Degenerative disease of the spine: How to relate clinical symptoms to radiological findings.

Degenerative disease of the spine (DDS) is one of the most common pathological conditions in humans. The clinical presentation of DDS is highly variable, ranging from mild pain to severe neurological symptoms. When more severe clinical symptoms are present, it is necessary to use imaging methods, such as magnetic resonance imaging (MRI), to confirm the diagnosis and establish the extent of the disease in order to determine proper treatment. There are several MRI changes which, based on clinicoradiological studies, are believed to be potential sources of pain and other clinical symptoms in DDS, including compression of the nerve root or spinal cord by disc herniations or osteophytes, recent ("active") disc herniation, Modic type 1 degenerative changes of the vertebral bodies, degenerative changes of the vertebral endplates (erosive intervertebral osteochondrosis), marked degenerative changes of the facet joints and ligamenta flava, degenerative spinal canal stenosis, degenerative spondylolisthesis, and Baastrup's disease. The authors analyzed the relationship of the MRI findings mentioned above with clinical symptoms of DDS, as well as the differentiation between DDS and nondegenerative diseases, which can manifest with similar clinical signs. The role of contrast-enhanced MRI and advanced MR techniques (e.g., high field MRI, functional MRI and MR spectroscopy) was also discussed. To establish an appropriate treatment for DDS, it is important to emphasize in the MRI report specific changes, which might be the cause of the pain and other clinical signs, as well as to rule out nondegenerative lesions, especially neoplasms, infections and rheumatoid disorders.

Distinct representation of ipsilateral hand movements in sensorimotor areas

There is ample evidence that the contralateral sensorimotor areas play an important role in movement generation, with the primary motor cortex and the primary somatosensory cortex showing a detailed spatial organization of the representation of contralateral body parts. Interestingly, there are also indications for a role of the motor cortex in controlling the ipsilateral side of the body. However, the precise function of ipsilateral sensorimotor cortex in unilateral movement control is still unclear. Here, we show hand movement representation in the ipsilateral sensorimotor hand area, in which hand gestures can be distinguished from each other and from contralateral hand gestures. High‐field functional magnetic resonance imaging (fMRI) data acquired during the execution of six left‐ and six right‐hand gestures by healthy volunteers showed ipsilateral activation mainly in the anterior section of precentral gyrus and the posterior section of the postcentral gyrus. Despite the lower activation in ipsilateral areas closer to the central sulcus, activity patterns for the 12 hand gestures could be mutually distinguished in these areas. The existence of a unique representation of ipsilateral hand movements in the human sensorimotor cortex favours the notion of transcallosal integrative processes that support optimal coordination of hand movements.

Investigating the specificity of the neurologic pain signature against breathlessness and finger opposition.

Brain biomarkers of pain, including pain-predictive "signatures" based on brain activity, can provide measures of neurophysiological processes and potential targets for interventions. A central issue relates to the specificity of such measures, and understanding their current limits will both advance their development and explore potentially generalizable properties of pain to other states. Here, we used 2 data sets to test the neurologic pain signature (NPS), an established pain neuromarker. In study 1, brain activity was measured using high-field functional magnetic resonance imaging (7T fMRI, N = 40) during 5 to 25 seconds of experimental breathlessness (induced by inspiratory resistive loading), conditioned breathlessness anticipation, and finger opposition. In study 2, we assessed anticipation and breathlessness perception (3T, N = 19) under blinded saline (placebo) and remifentanil administration. The NPS responded to breathlessness, anticipation, and finger opposition, although no direct comparisons with painful events were possible. Local NPS patterns in anterior or midinsula, S2, and dorsal anterior cingulate responded to breathlessness and finger opposition and were reduced by remifentanil. Local NPS responses in the dorsal posterior insula did not respond to any manipulations. Therefore, significant global NPS activity alone is not specific for pain, and we offer insight into the overlap between NPS responses, breathlessness, and somatomotor demand.

Good taste or gut feeling? A new method in rats shows oro-sensory stimulation and gastric distention generate distinct and overlapping brain activation patterns.

Satiation is influenced by a variety of signals including gastric distention and oro‐sensory stimulation. Here we developed a high‐field (9.4 T) functional magnetic resonance imaging (fMRI) protocol to test how oro‐sensory stimulation and gastric distention, as induced with a block‐design paradigm, affect brain activation under different states of energy balance in rats. Repeated tasting of sucrose induced positive and negative fMRI responses in the ventral tegmental area and septum, respectively, and gradual neural activation in the anterior insula and the brain stem nucleus of the solitary tract (NTS), as revealed using a two‐level generalized linear model‐based analysis. These unique findings align with comparable human experiments, and are now for the first time identified in rats, thereby allowing for comparison between species. Gastric distention induced more extensive brain activation, involving the insular cortex and NTS. Our findings are largely in line with human studies that have shown that the NTS is involved in processing both visceral information and taste, and anterior insula in processing sweet taste oro‐sensory signals. Gastric distention and sucrose tasting induced responses in mesolimbic areas, to our knowledge not previously detected in humans, which may reflect the rewarding effects of a full stomach and sweet taste, thereby giving more insight into the processing of sensory signals leading to satiation. The similarities of these data to human neuroimaging data demonstrate the translational value of the approach and offer a new avenue to deepen our understanding of the process of satiation in healthy people and those with eating disorders.

Spatially and Temporally Distinct Encoding of Muscle and Kinematic Information in Rostral and Caudal Primary Motor Cortex.

The organizing principle of human motor cortex does not follow an anatomical body map, but rather a distributed representational structure in which motor primitives are combined to produce motor outputs. Electrophysiological recordings in primates and human imaging data suggest that M1 encodes kinematic features of movements, such as joint position and velocity. However, M1 exhibits well-documented sensory responses to cutaneous and proprioceptive stimuli, raising questions regarding the origins of kinematic motor representations: are they relevant in top-down motor control, or are they an epiphenomenon of bottom-up sensory feedback during movement? Here we provide evidence for spatially and temporally distinct encoding of kinematic and muscle information in human M1 during the production of a wide variety of naturalistic hand movements. Using a powerful combination of high-field functional magnetic resonance imaging and magnetoencephalography, a spatial and temporal multivariate representational similarity analysis revealed encoding of kinematic information in more caudal regions of M1, over 200 ms before movement onset. In contrast, patterns of muscle activity were encoded in more rostral motor regions much later after movements began. We provide compelling evidence that top-down control of dexterous movement engages kinematic representations in caudal regions of M1 prior to movement production.

Increased cognitive complexity reveals abnormal brain network activity in individuals with corpus callosum dysgenesis

Cognitive reasoning is thought to require functional interactions between whole-brain networks. Such networks rely on both cerebral hemispheres, with the corpus callosum providing cross-hemispheric communication. Here we used high-field functional magnetic resonance imaging (7 T fMRI), a well validated cognitive task, and brain network analyses to investigate the functional networks underlying cognitive reasoning in individuals with corpus callosum dysgenesis (CCD), an anatomical abnormality that affects the corpus callosum. Participants with CCD were asked to solve cognitive reasoning problems while their brain activity was measured using fMRI. The complexity of these problems was parametrically varied by changing the complexity of relations that needed to be established between shapes within each problem matrix. Behaviorally, participants showed a typical reduction in task performance as problem complexity increased. Task-evoked neural activity was observed in brain regions known to constitute two key cognitive control systems: the fronto-parietal and cingulo-opercular networks. Under low complexity demands, network topology and the patterns of local neural activity in the CCD group closely resembled those observed in neurotypical controls. By contrast, when asked to solve more complex problems, participants with CCD showed a reduction in neural activity and connectivity within the fronto-parietal network. These complexity-induced, as opposed to resting-state, differences in functional network activity help resolve the apparent paradox between preserved network architecture found at rest in CCD individuals, and the heterogeneous deficits they display in response to cognitive task demands [preprint: https://doi.org/10.1101/312629].

Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation.

Neuroprosthetics research in amputee patients aims at developing new prostheses that move and feel like real limbs. Targeted muscle and sensory reinnervation (TMSR) is such an approach and consists of rerouting motor and sensory nerves from the residual limb towards intact muscles and skin regions. Movement of the myoelectric prosthesis is enabled via decoded electromyography activity from reinnervated muscles and touch sensation on the missing limb is enabled by stimulation of the reinnervated skin areas. Here we ask whether and how motor control and redirected somatosensory stimulation provided via TMSR affected the maps of the upper limb in primary motor (M1) and primary somatosensory (S1) cortex, as well as their functional connections. To this aim, we tested three TMSR patients and investigated the extent, strength, and topographical organization of the missing limb and several control body regions in M1 and S1 at ultra high-field (7 T) functional magnetic resonance imaging. Additionally, we analysed the functional connectivity between M1 and S1 and of both these regions with fronto-parietal regions, known to be important for multisensory upper limb processing. These data were compared with those of control amputee patients (n = 6) and healthy controls (n = 12). We found that M1 maps of the amputated limb in TMSR patients were similar in terms of extent, strength, and topography to healthy controls and different from non-TMSR patients. S1 maps of TMSR patients were also more similar to normal conditions in terms of topographical organization and extent, as compared to non-targeted muscle and sensory reinnervation patients, but weaker in activation strength compared to healthy controls. Functional connectivity in TMSR patients between upper limb maps in M1 and S1 was comparable with healthy controls, while being reduced in non-TMSR patients. However, connectivity was reduced between S1 and fronto-parietal regions, in both the TMSR and non-TMSR patients with respect to healthy controls. This was associated with the absence of a well-established multisensory effect (visual enhancement of touch) in TMSR patients. Collectively, these results show how M1 and S1 process signals related to movement and touch are enabled by targeted muscle and sensory reinnervation. Moreover, they suggest that TMSR may counteract maladaptive cortical plasticity typically found after limb loss, in M1, partially in S1, and in their mutual connectivity. The lack of multisensory interaction in the present data suggests that further engineering advances are necessary (e.g. the integration of somatosensory feedback into current prostheses) to enable prostheses that move and feel as real limbs.

High-Field Functional Imaging of Pitch Processing in Auditory Cortex of the Cat.

The perception of pitch is a widely studied and hotly debated topic in human hearing. Many of these studies combine functional imaging techniques with stimuli designed to disambiguate the percept of pitch from frequency information present in the stimulus. While useful in identifying potential “pitch centres” in cortex, the existence of truly pitch-responsive neurons requires single neuron-level measures that can only be undertaken in animal models. While a number of animals have been shown to be sensitive to pitch, few studies have addressed the location of cortical generators of pitch percepts in non-human models. The current study uses high-field functional magnetic resonance imaging (fMRI) of the feline brain in an attempt to identify regions of cortex that show increased activity in response to pitch-evoking stimuli. Cats were presented with iterated rippled noise (IRN) stimuli, narrowband noise stimuli with the same spectral profile but no perceivable pitch, and a processed IRN stimulus in which phase components were randomized to preserve slowly changing modulations in the absence of pitch (IRNo). Pitch-related activity was not observed to occur in either primary auditory cortex (A1) or the anterior auditory field (AAF) which comprise the core auditory cortex in cats. Rather, cortical areas surrounding the posterior ectosylvian sulcus responded preferentially to the IRN stimulus when compared to narrowband noise, with group analyses revealing bilateral activity centred in the posterior auditory field (PAF). This study demonstrates that fMRI is useful for identifying pitch-related processing in cat cortex, and identifies cortical areas that warrant further investigation. Moreover, we have taken the first steps in identifying a useful animal model for the study of pitch perception.

High-resolution 7-Tesla fMRI data on the perception of musical genres – an extension to the studyforrest dataset

Here we present an extension to the studyforrest dataset – a versatile resource for studying the behavior of the human brain in situations of real-life complexity (http://studyforrest.org). This release adds more high-resolution, ultra high-field (7 Tesla) functional magnetic resonance imaging (fMRI) data from the same individuals. The twenty participants were repeatedly stimulated with a total of 25 music clips, with and without speech content, from five different genres using a slow event-related paradigm. The data release includes raw fMRI data, as well as precomputed structural alignments for within-subject and group analysis. In addition to fMRI, simultaneously recorded cardiac and respiratory traces, as well the complete implementation of the stimulation paradigm, including stimuli, are provided. An initial quality control analysis reveals distinguishable patterns of response to individual genres throughout a large expanse of areas known to be involved in auditory and speech processing. The present data can be used to, for example, generate encoding models for music perception that can be validated against the previously released fMRI data from stimulation with the “Forrest Gump” audio-movie and its rich musical content. In order to facilitate replicative and derived works, only free and open-source software was utilized.

High-field functional magnetic resonance imaging of vocalization processing in marmosets.

Vocalizations are behaviorally critical sounds, and this behavioral importance is reflected in the ascending auditory system, where conspecific vocalizations are increasingly over-represented at higher processing stages. Recent evidence suggests that, in macaques, this increasing selectivity for vocalizations might culminate in a cortical region that is densely populated by vocalization-preferring neurons. Such a region might be a critical node in the representation of vocal communication sounds, underlying the recognition of vocalization type, caller and social context. These results raise the questions of whether cortical specializations for vocalization processing exist in other species, their cortical location, and their relationship to the auditory processing hierarchy. To explore cortical specializations for vocalizations in another species, we performed high-field fMRI of the auditory cortex of a vocal New World primate, the common marmoset (Callithrix jacchus). Using a sparse imaging paradigm, we discovered a caudal-rostral gradient for the processing of conspecific vocalizations in marmoset auditory cortex, with regions of the anterior temporal lobe close to the temporal pole exhibiting the highest preference for vocalizations. These results demonstrate similar cortical specializations for vocalization processing in macaques and marmosets, suggesting that cortical specializations for vocal processing might have evolved before the lineages of these species diverged.

Functional topography of the human entorhinal cortex.

Despite extensive research on the role of the rodent medial and lateral entorhinal cortex (MEC/LEC) in spatial navigation, memory and related disease, their human homologues remain elusive. Here, we combine high-field functional magnetic resonance imaging at 7 T with novel data-driven and model-based analyses to identify corresponding subregions in humans based on the well-known global connectivity fingerprints in rodents and sensitivity to spatial and non-spatial information. We provide evidence for a functional division primarily along the anteroposterior axis. Localising the human homologue of the rodent MEC and LEC has important implications for translating studies on the hippocampo-entorhinal memory system from rodents to humans.

Direct in vivo assessment of human stem cell graft–host neural circuits

Despite the potential of stem cell-derived neural transplants for treating intractable neurological diseases, the global effects of a transplant's electrical activity on host circuitry have never been measured directly, preventing the systematic optimization of such therapies. Here, we overcome this problem by combining optogenetics, stem cell biology, and neuroimaging to directly map stem cell-driven neural circuit formation in vivo. We engineered human induced pluripotent stem cells (iPSCs) to express channelrhodopsin-2 and transplanted resulting neurons to striatum of rats. To non-invasively visualize the function of newly formed circuits, we performed high-field functional magnetic resonance imaging (fMRI) during selective stimulation of transplanted cells. fMRI successfully detected local and remote neural activity, enabling the global graft–host neural circuit function to be assessed. These results demonstrate the potential of a novel neuroimaging-based platform that can be used to identify how a graft's electrical activity influences the brain network in vivo.

High-field fMRI reveals tonotopically-organized and core auditory cortex in the cat

As frequency is one of the most basic elements of sound, it is not surprising that the earliest stages of auditory cortical processing are tonotopically organized. In cats, there are four known tonotopically organized cortical areas: the anterior (AAF), posterior (PAF), and ventral posterior (VPAF) auditory fields and primary auditory cortex (A1). Electrophysiological and anatomical evidence have suggested that AAF and A1 form core auditory cortex. The purpose of this investigation was to determine if high-field functional magnetic resonance imaging (fMRI) could be used to define the borders of all four tonotopically organized areas, identify core auditory cortex, and demonstrate tonotopy similar to that found using more invasive techniques. Five adult cats were examined. Eight different pure tones or one broad-band noise (BBN) stimuli were presented in a block paradigm during continuous fMRI scanning. Analysis was performed on each animal individually using conservative familywise error thresholds. Group analysis was performed by extracting data from fMRI analysis software and performing a battery of statistical tests. In auditory cortex, a reversal of the tonotopic gradient is known to occur at the borders between tonotopically organized areas. Therefore, high and low tones were used to delineate these borders. Activations in response to BBN as opposed to tonal stimulation demonstrated that core auditory cortex consists of both A1 and AAF. Finally, tonotopy was identified in each of the four known tonotopically organized areas. Therefore, we conclude that fMRI is effective at defining all four tonotopically organized cortical areas and delineating core auditory cortex.

Predictive coding for motion stimuli in human early visual cortex.

The current study investigates if early visual cortical areas, V1, V2 and V3, use predictive coding to process motion information. Previous studies have reported biased visual motion responses at locations where novel visual information was presented (i.e., the motion trailing edge), which is plausibly linked to the predictability of visual input. Using high-field functional magnetic resonance imaging (fMRI), we measured brain activation during predictable versus unpreceded motion-induced contrast changes during several motion stimuli. We found that unpreceded moving dots appearing at the trailing edge gave rise to enhanced BOLD responses, whereas predictable moving dots at the leading edge resulted in suppressed BOLD responses. Furthermore, we excluded biases in directional sensitivity, shifts in cortical stimulus representation, visuo-spatial attention and classical receptive field effects as viable alternative explanations. The results clearly indicate the presence of predictive coding mechanisms in early visual cortex for visual motion processing, underlying the construction of stable percepts out of highly dynamic visual input.

Functional MRI and neural responses in a rat model of Alzheimer's disease

Based on the hypothesis that brain plaques and tangles can affect cortical function in Alzheimer's disease (AD), we investigated functional responses in an AD rat model (called the Samaritan Alzheimer's rat achieved by ventricular infusion of amyloid peptide) and age-matched healthy control. High-field functional magnetic resonance imaging (fMRI) and extracellular neural activity measurements were applied to characterize sensory-evoked responses. Electrical stimulation of the forepaw led to BOLD and neural responses in the contralateral somatosensory cortex and thalamus. In AD brain we noted much smaller BOLD activation patterns in the somatosensory cortex (i.e., about 50% less activated voxels compared to normal brain). While magnitudes of BOLD and neural responses in the cerebral cortex were markedly attenuated in AD rats compared to normal rats (by about 50%), the dynamic coupling between the BOLD and neural responses in the cerebral cortex, as assessed by transfer function analysis, remained unaltered between the groups. However thalamic BOLD and neural responses were unaltered in AD brain compared to controls. Thus cortical responses in the AD model were indeed diminished compared to controls, but the thalamic responses in the AD and control rats were quite similar. Therefore these results suggest that Alzheimer's disease may affect cortical function more than subcortical function, which may have implications for interpreting altered human brain functional responses in fMRI studies of Alzheimer's disease.

Correlations of prefrontal cortical activation and cognitive performance with therapeutic cholinesterase inhibitor treatment: A high-field functional magnetic resonance imaging study

Correlations of prefrontal cortical activation and cognitive performance with therapeutic cholinesterase inhibitor treatment: A high-field functional magnetic resonance imaging study

Gender differences in the neural correlates of humor processing: Implications for different processing modes

Humor is a complex phenomenon of human social cognition with large inter-individual variability. Gender differences in emotion processing are a common finding in functional neuroimaging studies, and have been documented in behavioral studies of humor, but have received limited attention in functional neuroimaging studies on humor. Using blood oxygenation level dependent (BOLD) contrasts with high-field (3T) functional magnetic resonance imaging (fMR) we investigated 29 healthy subjects (14 female, 15 male) during the processing of humorous cartoons. In women, the ventral system implicated ín detection and appraisal of emotion was activated, including amygdala, insula, and Anterior Cingulate Cortex (ACC). Men showed activation in both the ventral and dorsal processing systems. The results indicate that women process humor though limbic reactivity, involving appraisal of its emotional features, while men apply more evaluative, executive resources to humor processing.