High-resolution Functional Magnetic Resonance Research Articles

Effective connectivity in a duration selective cortico-cerebellar network

How the human brain represents millisecond unit of time is far from clear. A recent neuroimaging study revealed the existence in the human premotor cortex of a topographic representation of time i.e., neuronal units selectively responsive to specific durations and topographically organized on the cortical surface. By using high resolution functional Magnetic Resonance Images here, we go beyond this previous work, showing duration preferences across a wide network of cortical and subcortical brain areas: from cerebellum to primary visual, parietal, premotor and prefrontal cortices. Most importantly, we identify the effective connectivity structure between these different brain areas and their duration selective neural units. The results highlight the role of the cerebellum as the network hub and that of medial premotor cortex as the final stage of duration recognition. Interestingly, when a specific duration is presented, only the communication strength between the units selective to that specific duration and to the neighboring durations is affected. These findings link for the first time, duration preferences within single brain region with connectivity dynamics between regions, suggesting a communication mode that is partially duration specific.

Greater occipital nerve block modulates nociceptive signals within the trigeminocervical complex

IntroductionThe pharmacological block of the greater occipital nerve has been proven effective in numerous headache and facial pain syndromes. This clinical effect supports the hypothesis of a strong functional interaction...

Basal ganglia and cerebellum contributions to vocal emotion processing as revealed by high-resolution fMRI

Until recently, brain networks underlying emotional voice prosody decoding and processing were focused on modulations in primary and secondary auditory, ventral frontal and prefrontal cortices, and the amygdala. Growing interest for a specific role of the basal ganglia and cerebellum was recently brought into the spotlight. In the present study, we aimed at characterizing the role of such subcortical brain regions in vocal emotion processing, at the level of both brain activation and functional and effective connectivity, using high resolution functional magnetic resonance imaging. Variance explained by low-level acoustic parameters (fundamental frequency, voice energy) was also modelled. Wholebrain data revealed expected contributions of the temporal and frontal cortices, basal ganglia and cerebellum to vocal emotion processing, while functional connectivity analyses highlighted correlations between basal ganglia and cerebellum, especially for angry voices. Seed-to-seed and seed-to-voxel effective connectivity revealed direct connections within the basal ganglia—especially between the putamen and external globus pallidus—and between the subthalamic nucleus and the cerebellum. Our results speak in favour of crucial contributions of the basal ganglia, especially the putamen, external globus pallidus and subthalamic nucleus, and several cerebellar lobules and nuclei for an efficient decoding of and response to vocal emotions.

Altered somatosensory processing in Parkinson's disease and modulation by dopaminergic medications

BackgroundSomatosensory abnormalities contribute to the pathophysiology of Parkinson's disease (PD). The goal of this study was to identify abnormalities in the tactile-evoked activation of the somatosensory and motor cortices in PD, and in a sensorimotor circuit that traverses both of these cortical loci. The second goal was to investigate the impact of dopaminergic medication on these measures. MethodsIndividuals with PD (n = 10, age 61 ± 8 years) and aged-matched controls (n = 11, age 52.3 ± 10.4 years) were studied. PD subjects were studied on and off dopaminergic medications. Using high-resolution functional magnetic resonance, imaging data was acquired over the primary somatosensory and motor cortices during passively delivered, computer-automated tactile stimulation of digits 2 and 5 of the more affected hand in PD and the analogous hand in controls. Short and long-latency afferent inhibition (SAI, LAI) were assessed via median nerve stimulation followed by transcranial magnetic stimulation over the motor cortical representation of the first dorsal interosseous muscle. ResultsCompared to controls, PD subjects demonstrated diminished activation within the somatosensory cortex, reduced LAI and normal SAI, of which all were insensitive to dopaminergic medications. In addition to improving motor symptoms, dopaminergic medications reduced the hyperactivity observed within primary motor cortex in PD. ConclusionsSomatosensory processing is deficient in PD. Reduction in tactile-evoked activation within primary motor cortex may contribute to improvement in motor symptoms with dopaminergic medications.

AGE-RELATED NETWORK DYSFUNCTION: CONTRIBUTIONS OF NEURAL ACTIVITY TO RISK FOR LATE-ONSET AD

This presentation will focus on an age-related shift in neural activity in key circuits that could contribute to boosting progression of Alzheimer's pathology and illuminate the risk conferred by aging in late onset sporadic AD. Neural hyperactivity in aging is associated with memory impairment in outbred rats and non-human primates. Hyperactive hippocampal neurons in those species are similarly localized to increased activation detected by high resolution functional magnetic resonance imaging (fMRI) in elderly humans, a condition that is further augmented in patients with mild cognitive impairment. In addition to the effects of aging on hippocampal circuits, reciprocally connected cortical networks demonstrate alterations in both aging and in prodromal AD. In particular, posterior regions of the default mode network (DMN) that are sites of early amyloid deposition show impaired task-related deactivation in older adults. Studies of the homologous connectional anatomy across species could provide information about the condition of such networks in aging, independent AD pathology. Activation of neural activity was monitored by expression of the immediate early gene cFos to map heightened excitability in behaviorally characterized aged rats. Induction of neural activity was assessed by cFos mRNA expression using quantitative in situ hybridization. Consistent with neurophysiological recording data, greater cFos induction was localized in the hippocampus of aged memory impaired rats compared to unimpaired aged cohorts and young adults. Similar increased cFos was observed in a network of cortical sites, including retrosplenial and parietal regions of the posterior DMN. Pharmacological treatment that reduced excess cFos induction in the hippocampus also normalized cFos induction in posterior DMN. Reduction of neural activity reduces amyloid deposition and preserves synaptic function in AD mouse models. In tau mouse models, manipulation of neural activity also controls tau propagation and pathology in the medial temporal lobe/hippocampus. Heightened neural activity as a condition associated with aging may contribute to the risk conferred by aging in driving the pathophysiology of late-onset sporadic AD. A demonstrated translation for the efficacy of targeting hippocampal hyperactivity in clinical investigations may extend to the additional cortical components of an AD vulnerable network in patients.

RETRACTED ARTICLE: Neural auditory intensity discrimination during naturalistic listening: a brain decoding study.

Neural discrimination of auditory intensity is one of the fundamental questions in human auditory perception. Human neuroimaging studies have demonstrated specific neural activations during intensity discrimination tasks. The detailed functional anatomy, however, remains elusive. Most of the existing studies examined the entire auditory cortex as a whole, neglecting the potential functional differentiation within the auditory cortex. Moreover, these previous results based on controlled auditory stimuli might not necessarily extend to the neural mechanism of natural auditory processing. In this study, we propose a novel brain decoding method to examine neural encoding of intensity discrimination during naturalistic auditory experience. Here, we used publically available dataset (http://studyforrest.org) in which high resolution functional magnetic resonance imaging (fMRI) was acquired when the participants freely listened to the audio-version of the movie “Forrest Gump”. We found the sensitivity and accuracy of intensity discrimination in the auditory cortex critically depend on the divergences in intensity levels, yielding a sigmoidal relationship. Furthermore, anatomical subdivisions of auditory cortex revealed great functional diversity and lateralization in intensity discrimination. While bilateral activations were observed in primary auditory cortex, enhanced left-lateralization effects were shown in inferior frontal gyrus, anterior middle temporal gyrus and temporal-occipital junction. Our findings underscore the value of naturalistic paradigms in mapping auditory processing in the brain: naturalistic paradigm contains enriched and complex natural sounds, which not only improve the ecological validity but also alleviate the discrepancies caused by the differences in stimulus types and task designs in previous studies. The multidisciplinary methodology we developed here provides an analytical framework for studying neural encoding of complex auditory stimuli.

EP 32. Automated high resolution fMRI mapping of the cortical sensory fingertip somatotopy in group examinations

Objective The increasing spatial precision in functional brain mapping is a methodological key issue driving the progress in brain research. Mapping of previously invisible fine scale details permits the discovery of unknown functional brain properties. Currently, the available resolution of fMRI examinations is increasing rapidly. However, data analysis techniques lag behind this development, and achieve an effective resolution which is smaller as the maximum possible spatial precision. We present a data analysis technique with maximum spatial precision in group analyses of high resolution functional magnetic resonance imaging (fMRI) data. Methods The contralateral fingertip representations of thumb, index and middle finger were investigated in a group of 18 participants, for right and left hand. A block design was applied (absolute duration of 200 s) including long counting pulses as a temporal identification task for attention monitoring ( Fig. 1 ). Imaging was carried out with a 3 Tesla MRI-scanner (Verio, Siemens, Germany). FreeSurfer recommendations for the anatomy scans were followed (standard MPRAGE sequence). A standard gradient-echo EPI sequence was used for fMRI (resolution 1.5 × 1.5 × 2 mm 3 , 17 slices, field of view = 191 × 179 mm 2 , TE/TR = 3.6 ms/21 ms). Data analysis was performed with an automated protocol ( Pfannmoller et al., 2015 ), including vessel artefact removal. Cortical positions of the fingertips were computed on individual and MNI brains, using volume-based linear or surface-based non-linear normalization. An assessment of cortical distance measures, for mapping of functional properties, was carried out including straight-line distances, using the 3-D Euclidean measure, and shortest connections within the cortical surface, either with the Dijkstra or LOS-Floyd algorithms. Results In BA3b a distinct somatotopy was found for both hands. The maximum spatial fingertip spread in BA3b after linear normalization was at least two times larger than for the non-linear normalization. All properties of the BA3b fingertip somatotopy were left-right symmetric. Since the representation in BA1 did not exhibit any of those features it was neglected. The LOS-Floyd algorithm achieved an error free result for the distances within measurement accuracy. In contrast, Euclidean distances did not account for the relevant cortical properties. Dijkstra distances were sufficiently precise in the individual brains, but excessively overestimated the left-hand distances after non-linear normalization. Discussion & conclusion Since the representations in BA1 and BA3b are entirely different, the cytoarchitectonic divisions need to be accounted for. The convergence of the BA3b fingertip positions after non-linear normalization implies a removal of the anatomical variability, leaving exclusively functional variability. In the distance mapping, application of the LOS-Floyd algorithm was mandatory in the group template. The Dijkstra algorithm represents a fast alternative for distance mapping in individual brains, while the precision of Euclidean distances did not suffice for our purposes. In conclusion, our methodology improves the spatial precision of somatotopic mapping at 3 T. At larger field strengths improvements to even higher resolutions are anticipated.

Decoding power-spectral profiles from FMRI brain activities during naturalistic auditory experience.

Recent studies have demonstrateda close relationship between computational acoustic features and neural brain activities, and have largely advanced our understanding of auditory information processing in the human brain. Along this line, we proposed a multidisciplinary study to examine whether power spectral density (PSD) profiles can be decoded from brain activities during naturalistic auditory experience. The study was performed on a high resolution functional magnetic resonance imaging (fMRI) dataset acquired when participants freely listened to the audio-description of the movie "Forrest Gump". Representative PSD profiles existing in the audio-movie were identified by clustering the audio samples according to their PSD descriptors. Support vector machine (SVM) classifiers were trained to differentiate the representative PSD profiles using corresponding fMRI brain activities. Based on PSD profile decoding, we explored how the neural decodability correlated to power intensity and frequency deviants. Our experimental results demonstrated that PSD profiles can be reliably decoded from brain activities. We also suggested a sigmoidal relationship between the neural decodability and power intensity deviants of PSD profiles. Our study in addition substantiates the feasibility and advantage of naturalistic paradigm for studying neural encoding of complex auditory information.

What We Have Learned about Human Primary Visual Cortex from High Resolution Functional Magnetic Resonance Imaging.

This article reviews our exploration of structures and functions of the human visual cortex using high resolution (submillimeter) functional magnetic resonance imaging (fMRI). It discusses factors that restrict the spatial resolution of blood oxygenation-level dependent (BOLD) fMRI-the point-spread function of the BOLD signal, limited by both imaging techniques to be used and neurovascular units to be studied, and the signal-to-noise ratio. I offer personal thoughts regarding optimal solutions for dealing with these issues, summarize techniques we have developed over the years for using high resolution fMRI to visualize functional architectures and explore physiological properties in the primary visual cortex of humans, including choices of imaging hardware and pulse sequences, experimental procedures, and stimulation paradigms, and finally offer my personal opinions regarding the future of high resolution fMRI.

Errors on interrupter tasks presented during spatial and verbal working memory performance are linearly linked to large-scale functional network connectivity in high temporal resolution resting state fMRI.

The brain is organized into networks composed of spatially separated anatomical regions exhibiting coherent functional activity over time. Two of these networks (the default mode network, DMN, and the task positive network, TPN) have been implicated in the performance of a number of cognitive tasks. To directly examine the stable relationship between network connectivity and behavioral performance, high temporal resolution functional magnetic resonance imaging (fMRI) data were collected during the resting state, and behavioral data were collected from 15 subjects on different days, exploring verbal working memory, spatial working memory, and fluid intelligence. Sustained attention performance was also evaluated in a task interleaved between resting state scans. Functional connectivity within and between the DMN and TPN was related to performance on these tasks. Decreased TPN resting state connectivity was found to significantly correlate with fewer errors on an interrupter task presented during a spatial working memory paradigm and decreased DMN/TPN anti-correlation was significantly correlated with fewer errors on an interrupter task presented during a verbal working memory paradigm. A trend for increased DMN resting state connectivity to correlate to measures of fluid intelligence was also observed. These results provide additional evidence of the relationship between resting state networks and behavioral performance, and show that such results can be observed with high temporal resolution fMRI. Because cognitive scores and functional connectivity were collected on nonconsecutive days, these results highlight the stability of functional connectivity/cognitive performance coupling.

Optimized protocol for high resolution functional magnetic resonance imaging at 3T using single-shot echo planar imaging.

To translate highly accelerated EPI-fMRI protocols as commonly used at ultra-high field strengths to clinical 3T settings. EPI protocols with increasing matrix sizes and parallel imaging (PI) factors were tested in two separate fMRI studies, a simple motor-task and a complex motivation-task experiment with focus on the sensorimotor cortex (SMC) and the nucleus accumbens (NAcc), respectively. By increasing the matrix size and the PI-factor simultaneously, BOLD-sensitivity in terms of maximal t-values and numbers of activated clusters was uncompromised in single individuals in both fMRI experiments. In the SMC, the multi-subject analysis revealed an increase of 66% of the maximal t-value whereby the number of activated clusters was increased by a factor of 3.3 when the matrix size (PI-factor) was increased from 96×96 (R=2) to 192×192 (R=4). In the NAcc, the number of activated clusters increased from 5 to 7 whereby the maximal t-value remained unaffected when the matrix size (PI-factor) was increased from 96×96 (R=2) to 160×160 (R=3). Using the proposed high-resolution EPI protocol, spatial blurring was clearly reduced. Further, BOLD sensitivity was clearly improved in multi-subject analyses and remained unaffected in single individuals compared to using the standard protocols. Conventionally used matrix sizes (PI-factors) might be non-optimal for some applications sacrificing BOLD spatial specificity. We recommend using the proposed high-resolution protocols applicable in detecting robust BOLD activation in fMRI.

Monocular signals in human lateral geniculate nucleus reflect the Craik-Cornsweet-O'Brien effect

The human visual system has a remarkable ability to accurately estimate the relative brightness of adjacent objects despite large variations in illumination. However, the lightness of two identical equiluminant gray regions can appear quite different when a light-dark luminance transition falls between them. This illusory brightness "filling-in" phenomenon, the Craik-Cornsweet-O'Brien (CCOB) illusion, exposes fundamental assumptions made by the visual system in estimating lightness, but its neural basis remains unclear. While the responses of high-level visual cortex can be correlated with perception of the CCOB, simple computational models suggest that the effect may originate from a much lower level, possibly subcortical. Here, we used high spatial resolution functional magnetic resonance imaging to show that the CCOB illusion is strongly correlated with signals recorded from the human lateral geniculate nucleus. Moreover, presenting the light and dark luminance transitions that induce the CCOB effect separately to each eye abolishes the illusion, suggesting that it depends on eye-specific signals. Our observations suggest that the CCOB effect arises from signals in populations of monocular neurons very early in the human geniculostriate visual pathway.

Somatotopic organisation of the human insula to painful heat studied with high resolution functional imaging

Pain perception is a multidimensional phenomenon, derived from sensory, affective, cognitive–evaluative and homeostatic information. Neuroimaging studies of pain perception have investigated the role of primary somatosensory cortex (SI); however, they have typically failed to demonstrate the expected somatotopy. An alternative network for the sensory component of pain has been proposed, involving a temperature and pain-specific nucleus of the thalamus (VMpo) and its projections to dorsal posterior insula (dpIns). According to this hypothesis, projections to the insula should be arranged somatotopically. In order to test for the presence of somatotopy in the operculo-insular brain region, we delivered moderately painful thermal stimuli to the right face, hand and foot in 14 healthy subjects and recorded brain responses using high resolution functional magnetic resonance imaging at 3 T. For each subject, the thermode temperature was adjusted to produce pain ratings of 5 to 6 out of 10, which corresponded to average temperatures for the face, hand and foot of 49.6, 48.5 and 48.5°C, respectively. Examination of mixed effects group activation maps suggested a pain-related somatotopy in the contralateral posterior insula and putamen. Construction of frequency maps revealed that face activation within the posterior insula was anterior to both hand and foot, whilst foot activation was located medially in the circular sulcus. Single subject analysis demonstrated that only coordinates for dpIns activation were significantly dependent on stimulus location (Hotelling's Trace, P = 0.012). Coordinates for face (paired t test, P = 0.004) and hand ( P < 0.001) activity were more lateral than those for foot, whilst face activation was anterior to the foot ( P = 0.037). Based on single subject analyses, the average standard space (MNI) coordinates for face, hand and foot activity were (−40,−16,11), (−40,−19,14) and (−35,−21,11) respectively.

FMRI Priors for the Linear Inverse Estimation of EEG Cortical Sources

In this paper, advanced methods for the modeling of human cortical activity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are reviewed. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from magnetic resonance images, multidipole source model, and regularized linear inverse source estimate based on boundary element mathematics. Furthermore, determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) and event-related (coupling of activated voxels) fMRI. Linear inverse source estimates of cortical activity were regularized by taking into account the covariance of background EEG sensor noise. As an example, these methods were applied to EEG (128 electrodes) and fMRI data, which were recorded in separate sessions while normal subjects executed voluntary right one-digit movements.

Multimodal integration of high resolution EEG and functional magnetic resonance: a simulation study

Multimodal integration of high resolution EEG and functional magnetic resonance: a simulation study

Electrical Nerve Stimulation Can Be Used as a Tool in fMRI Studies of Pain- and Tingling-Evoked Activations

OBJECTIVES/HYPOTHESES: To determine whether transcutaneous electrical nerve stimulation (TENS) provides adequate, inexpensive and simple means to image innocuous and pain-related activations in the thalamus and cortex.SUBJECTS AND METHODS: High resolution functional magnetic resonance imaging (fMRI) was used to obtain functional data sets on a 1.5T General Electric echospeed scanner (General Electric, Milwaukee) from six axial slices during interleaved periods of rest and TENS at either nonpainful tingling or painful intensities. The volume of brain imaged allowed inspection of stimulation-related activations in the thalamus, insula and second somatosensory cortex (S2).RESULTS: Tingling TENS activations were identified primarily in the contralateral posterolateral thalamus. Painful TENS activations were found in the contralateral posterolateral thalamus, medial and/or anterior thalamus. The insula and S2 were activated in four of the subjects with tingling TENS and in all subjects with painful TENS. Tingling TENS activations were located in the posterior insula, whereas pain-related activations were located in the anterior insula. Painful TENS activations found in S2 overlapped with tingling TENS activations.CONCLUSIONS: These findings demonstrate that TENS is a simple mode of stimulation that produces fairly consistent cortical activations, especially at painful levels, and thus may be useful in carefully designed and controlled clinical fMRI studies of pain and touch.

A functional magnetic resonance imaging study of listening comprehension of languages in human at 3 tesla-comprehension level and activation of the language areas

Passive listening comprehension of native and non-native language was investigated using high resolution functional magnetic resonance imaging (fMRI) at a static magnetic field strength of 3 tesla. Wernicke's area was activated by comprehensive and non-comprehensive languages indicating that this area is associated with common phonological processing of language. The task with comprehensive but non-native language activated Broca's area and angular gyrus most frequently. The activations in these areas may be related to demand in semantic and syntactic processing in listening comprehension. Supplementary motor area and pre-motor area were activated by comprehensive languages but not by non-comprehensive language. These motor controlling areas may be involved in semantic processing. Listening to comprehensive but non-native language seems to demand more networked co-processing.

Ocular dominance in human V1 demonstrated by functional magnetic resonance imaging.

Very high resolution functional magnetic resonance imaging (fMRI) at a 4 Tesla (T) magnetic field was used to map ocular dominance regions in the human visual cortical layers using the blood oxygen level dependent (BOLD) contrast mechanism. The fMRI response from primary visual cortex (V1) exhibited a distribution of ocular dominance reminiscent of the single-cell recordings of Hubel and Wiesel. Pixels could be grouped into seven categories varying from left-only response to binocular-only response to right-only responses. Nonspecific responses were found in the MRI-visible draining veins as well as in the parenchyma. Although large vessel BOLD signals are easily detectable, regardless of field strength, they demonstrate a fMRI response to photic input that could not be used to distinguish ocular dominance. The difference in BOLD response between a region activated by one eye and that activated by the other is only 2.9% on average. This necessitates the use of a difference paradigm to visualize the regions of ocular dominance accurately. The data show that BOLD-based fMRI is sensitive to neuronal activity in cortical columns when using differential techniques, opening up the possibility of mapping specialized populations of neurons in humans that are not accessible to electrophysiological or other methods of invasive mapping.

FMRI of the prefrontal cortex during overt verbal fluency.

Verbal fluency is known to be associated with activity in the left prefrontal cortex. Recent positron emission tomography (PET) results confirmed this finding. In the present study, high resolution functional magnetic resonance imaging (fMRI) was used to further localize activity in the prefrontal cortex related to verbal fluency. Activation was observed in three behavioral tasks: (1) Repeat-subjects repeated words, (2) Opposite-subjects produced the antonym of words, and (3) Generate-subjects generated words beginning with a given letter. When comparing Generate with both Repeat and Opposite, we observed small areas of activation in the left inferior frontal gyrus and anterior cingulate, similar to the centers of mass reported using PET. We also found additional activation around the superior frontal sulcus.

Parceling of mesial frontal motor areas during ideation and movement using functional magnetic resonance imaging at 1.5 tesla.

Finger movement-related responses were identified in three discrete sites of mesial frontal cortex in 7 normal subjects using high resolution functional magnetic resonance imaging. During imagination of the same movements there was a differential response with rostral areas more active than caudal areas. Humans have multiple motor areas in mesial frontal cortex that subserve different functions in motor planning and execution.