Jerzy Bodurka

Matching categorical object representations in inferior temporal cortex of man and monkey.

Inferior temporal (IT) object representations have been intensively studied in monkeys and humans, but representations of the same particular objects have never been compared between the species. Moreover, ITs role in categorization is not well understood. Here, we presented monkeys and humans with the same images of real-world objects and measured the IT response pattern elicited by each image. In order to relate the representations between the species and to computational models, we compare response-pattern dissimilarity matrices. IT response patterns form category clusters, which match between man and monkey. The clusters correspond to animate and inanimate objects; within the animate objects, faces and bodies form subclusters. Within each category, IT distinguishes individual exemplars, and the within-category exemplar similarities also match between the species. Our findings suggest that primate IT across species may host a common code, which combines a categorical and a continuous representation of objects.

Unraveling multisensory integration: patchy organization within human STS multisensory cortex

Although early sensory cortex is organized along dimensions encoded by receptor organs, little is known about the organization of higher areas in which different modalities are integrated. We investigated multisensory integration in human superior temporal sulcus using recent advances in parallel imaging to perform functional magnetic resonance imaging (fMRI) at very high resolution. These studies suggest a functional architecture in which information from different modalities is brought into close proximity via a patchy distribution of inputs, followed by integration in the intervening cortex.

How long to scan? The relationship between fMRI temporal signal to noise ratio and necessary scan duration.

Recent advances in MRI receiver and coil technologies have significantly improved image signal-to-noise ratios (SNR) and thus temporal SNR (TSNR). These gains in SNR and TSNR have allowed the detection of fMRI signal changes at higher spatial resolution and therefore have increased the potential to localize small brain structures such as cortical layers and columns. The majority of current fMRI processing strategies employ multi-subject averaging and therefore require spatial smoothing and normalization, effectively negating these gains in spatial resolution higher than about 10 mm3. Reliable detection of activation in single subjects at high resolution is becoming a more common desire among fMRI researchers who are interested in comparing individuals rather than populations. Since TSNR decreases with voxel volume, detection of activation at higher resolutions requires longer scan durations. The relationship between TSNR, voxel volume and detectability is highly non-linear. In this study, the relationship between TSNR and the necessary fMRI scan duration required to obtain significant results at varying P values is determined both experimentally and theoretically. The results demonstrate that, with a TSNR of 50, detection of activation of above 2% requires at most 350 scan volumes (when steps are taken to remove the influence of physiological noise from the data). Importantly, these results also demonstrate that, for activation magnitude on the order of 1%, the scan duration required is more sensitive to the TSNR level than at 2%. This study showed that with voxel volumes of approximately 10 mm3 at 3 T, and a corresponding TSNR of approximately 50, the required number of time points that guarantees detection of signal changes of 1% is about 860, but if TSNR increases by only 20%, the time for detection decreases by more than 30%. More than just being an exercise in numbers, these results imply that imaging of columnar resolution (effect size=1% and assuming a TR of 1 s) at 3 T will require either 10 min for a TSNR of 60 or 40 min for a TSNR of 30. The implication is that at these resolutions, TSNR is likely to be critical for determining success or failure of an experiment.

Toward direct mapping of neuronal activity: MRI detection of ultraweak, transient magnetic field changes

A novel method based on selective detection of rapidly changing ΔB0 magnetic fields and suppression of slowly changing ΔB0 fields is presented. The ultimate goal of this work is to present a method that may allow detection of transient and subtle changes in B0 in cortical tissue associated with electrical currents produced by neuronal activity. The method involves the detection of NMR phase changes that occur during a single‐shot spin‐echo (SE) echo‐planar sequence (EPI) echo time. SE EPI effectively rephases all changes in B0 that occur on a time scale longer than the echo time (TE) and amplifies all ΔB0 changes that occur during TE/2. The method was tested on a phantom that contains wires in which current can be modulated. The sensitivity and flexibility of the technique was demonstrated by modulation of the temporal position and duration of the stimuli‐evoked transient magnetic field relative to the 180 RF pulse in the imaging sequence—requiring precise stimulus timing. Currently, with this method magnetic field changes as small as 2 × 10−10 T (200 pT) and lasting for 40 msec can be detected. Implications for direct mapping of brain neuronal activity with MRI are discussed. Magn Reson Med 47:1052–1058, 2002. Published 2002 Wiley‐Liss, Inc.

Signal-to-noise ratio and parallel imaging performance of a 16-channel receive-only brain coil array at 3.0 Tesla†

The performance of a 16‐channel receive‐only RF coil for brain imaging at 3.0 Tesla was investigated using a custom‐built 16‐channel receiver. Both the image signal‐to‐noise ratio (SNR) and the noise amplification (g‐factor) in sensitivity‐encoding (SENSE) parallel imaging applications were quantitatively evaluated. Furthermore, the performance was compared with that of hypothetical coils with one, two, four, and eight elements (n) by combining channels in software during image reconstruction. As expected, both the g‐factor and SNR improved substantially with n. Compared to an equivalent (simulated) single‐element coil, the 16‐channel coil showed a 1.87‐fold average increase in brain SNR. This was mainly due to an increase in SNR in the peripheral brain (an up to threefold SNR increase), whereas the SNR increase in the center of the brain was 4%. The incremental SNR gains became relatively small at large n, with a 9% gain observed when n was increased from 8 to 16. Compared to the (larger) product birdcage head coil, SNR increased by close to a factor of 2 in the center, and by up to a factor of 6 in the periphery of the brain. For low SENSE acceleration (rate‐2), g‐factors leveled off for n > 4, and improved only slightly (1.4% averaged over brain) going from n = 8 to n = 16. Improvements in g for n > 8 were larger for higher acceleration rates, with the improvement for rate‐3 averaging 12.0%. Magn Reson Med 51:22–26, 2004. Published 2003 Wiley‐Liss, Inc.

Self-Regulation of Amygdala Activation Using Real-Time fMRI Neurofeedback

Real-time functional magnetic resonance imaging (rtfMRI) with neurofeedback allows investigation of human brain neuroplastic changes that arise as subjects learn to modulate neurophysiological function using real-time feedback regarding their own hemodynamic responses to stimuli. We investigated the feasibility of training healthy humans to self-regulate the hemodynamic activity of the amygdala, which plays major roles in emotional processing. Participants in the experimental group were provided with ongoing information about the blood oxygen level dependent (BOLD) activity in the left amygdala (LA) and were instructed to raise the BOLD rtfMRI signal by contemplating positive autobiographical memories. A control group was assigned the same task but was instead provided with sham feedback from the left horizontal segment of the intraparietal sulcus (HIPS) region. In the LA, we found a significant BOLD signal increase due to rtfMRI neurofeedback training in the experimental group versus the control group. This effect persisted during the Transfer run without neurofeedback. For the individual subjects in the experimental group the training effect on the LA BOLD activity correlated inversely with scores on the Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale. The whole brain data analysis revealed significant differences for Happy Memories versus Rest condition between the experimental and control groups. Functional connectivity analysis of the amygdala network revealed significant widespread correlations in a fronto-temporo-limbic network. Additionally, we identified six regions — right medial frontal polar cortex, bilateral dorsomedial prefrontal cortex, left anterior cingulate cortex, and bilateral superior frontal gyrus — where the functional connectivity with the LA increased significantly across the rtfMRI neurofeedback runs and the Transfer run. The findings demonstrate that healthy subjects can learn to regulate their amygdala activation using rtfMRI neurofeedback, suggesting possible applications of rtfMRI neurofeedback training in the treatment of patients with neuropsychiatric disorders.

Phasic and sustained fear in humans elicits distinct patterns of brain activity.

Aversive events are typically more debilitating when they occur unpredictably than predictably. Studies in humans and animals indicate that predictable and unpredictable aversive events can induce phasic and sustained fear, respectively. Research in rodents suggests that anatomically related but distinct neural circuits may mediate phasic and sustained fear. We explored this issue in humans by examining threat predictability in three virtual reality contexts, one in which electric shocks were predictably signaled by a cue, a second in which shocks occurred unpredictably but never paired with a cue, and a third in which no shocks were delivered. Evidence of threat-induced phasic and sustained fear was presented using fear ratings and skin conductance. Utilizing recent advances in functional magnetic resonance imaging (fMRI), we were able to conduct whole-brain fMRI at relatively high spatial resolution and still have enough sensitivity to detect transient and sustained signal changes in the basal forebrain. We found that both predictable and unpredictable threat evoked transient activity in the dorsal amygdala, but that only unpredictable threat produced sustained activity in a forebrain region corresponding to the bed nucleus of the stria terminalis complex. Consistent with animal models hypothesizing a role for the cortex in generating sustained fear, sustained signal increases to unpredictable threat were also found in anterior insula and a frontoparietal cortical network associated with hypervigilance. In addition, unpredictable threat led to transient activity in the ventral amygdala-hippocampal area and pregenual anterior cingulate cortex, as well as transient activation and subsequent deactivation of subgenual anterior cingulate cortex, limbic structures that have been implicated in the regulation of emotional behavior and stress responses. In line with basic findings in rodents, these results provide evidence that phasic and sustained fear in humans may manifest similar signs of distress, but appear to be associated with different patterns of neural activity in the human basal forebrain.

Keeping the body in mind: Insula functional organization and functional connectivity integrate interoceptive, exteroceptive, and emotional awareness

Relatively discrete experimental literatures have grown to support the insulas role in the domains of interoception, focal exteroceptive attention and cognitive control, and the experience of anxiety, even as theoretical accounts have asserted that the insula is a critical zone for integrating across these domains. Here we provide the first experimental demonstration that there exists a functional topography across the insula, with distinct regions in the same participants responding in a highly selective fashion for interoceptive, exteroceptive, and affective processing. Although each insular region is associated with areas of differential resting state functional connectivity relative to the other regions, overall their functional connectivity profiles are quite similar, thereby providing a map of how interoceptive, exteroceptive, and emotional awareness are integrated within the insular cortex. Hum Brain Mapp 34:2944–2958, 2013.

Major depressive disorder is associated with abnormal interoceptive activity and functional connectivity in the insula.

BACKGROUND Somatic complaints and altered interoceptive awareness are common features in the clinical presentation of major depressive disorder (MDD). Recently, neurobiological evidence has accumulated demonstrating that the insula is one of the primary cortical structures underlying interoceptive awareness. Abnormal interoceptive representation within the insula may thus contribute to the pathophysiology and symptomatology of MDD. METHODS We compared functional magnetic resonance imaging blood oxygenation level-dependent responses between 20 unmedicated adults with MDD and 20 healthy control participants during a task requiring attention to visceral interoceptive sensations and also assessed the relationship of this blood oxygenation level-dependent response to depression severity, as rated using the Hamilton Depression Rating Scale. Additionally, we examined between-group differences in insula resting-state functional connectivity and its relationship to Hamilton Depression Rating Scale ratings of depression severity. RESULTS Relative to the healthy control subjects, unmedicated MDD subjects exhibited decreased activity bilaterally in the dorsal mid-insula cortex (dmIC) during interoception. Activity within the insula during the interoceptive attention task was negatively correlated with both depression severity and somatic symptom severity in depressed subjects. Major depressive disorder also was associated with greater resting-state functional connectivity between the dmIC and limbic brain regions implicated previously in MDD, including the amygdala, subgenual prefrontal cortex, and orbitofrontal cortex. Moreover, functional connectivity between these regions and the dmIC was positively correlated with depression severity. CONCLUSIONS Major depressive disorder and the somatic symptoms of depression are associated with abnormal interoceptive representation within the insula.

Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder.

Background Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD), and normalize with remission. Real-time functional MRI neurofeedback (rtfMRI-nf) offers a non-invasive method to modulate this regional activity. We examined whether depressed participants can use rtfMRI-nf to enhance amygdala responses to positive autobiographical memories, and whether this ability alters symptom severity. Methods Unmedicated MDD subjects were assigned to receive rtfMRI-nf from either left amygdala (LA; experimental group, n = 14) or the horizontal segment of the intraparietal sulcus (HIPS; control group, n = 7) and instructed to contemplate happy autobiographical memories (AMs) to raise the level of a bar representing the hemodynamic signal from the target region to a target level. This 40s Happy condition alternated with 40s blocks of rest and counting backwards. A final Transfer run without neurofeedback information was included. Results Participants in the experimental group upregulated their amygdala responses during positive AM recall. Significant pre-post scan decreases in anxiety ratings and increases in happiness ratings were evident in the experimental versus control group. A whole brain analysis showed that during the transfer run, participants in the experimental group had increased activity compared to the control group in left superior temporal gyrus and temporal polar cortex, and right thalamus. Conclusions Using rtfMRI-nf from the left amygdala during recall of positive AMs, depressed subjects were able to self-regulate their amygdala response, resulting in improved mood. Results from this proof-of-concept study suggest that rtfMRI-nf training with positive AM recall holds potential as a novel therapeutic approach in the treatment of depression.