Relating Alpha Power and Phase to Population Firing and Hemodynamic Activity Using a Thalamo-cortical Neural Mass Model.

Oscillations are ubiquitous phenomena in the animal and human brain. Among them, the alpha rhythm in human EEG is one of the most prominent examples. However, its precise mechanisms of generation are still poorly understood. It was mainly this lack of knowledge that motivated a number of simultaneous electroencephalography (EEG) - functional magnetic resonance imaging (fMRI) studies. This approach revealed how oscillatory neuronal signatures such as the alpha rhythm are paralleled by changes of the blood oxygenation level dependent (BOLD) signal. Several such studies revealed a negative correlation between the alpha rhythm and the hemodynamic BOLD signal in visual cortex and a positive correlation in the thalamus. In this study we explore the potential generative mechanisms that lead to those observations. We use a bursting capable Stefanescu-Jirsa 3D (SJ3D) neural-mass model that reproduces a wide repertoire of prominent features of local neuronal-population dynamics. We construct a thalamo-cortical network of coupled SJ3D nodes considering excitatory and inhibitory directed connections. The model suggests that an inverse correlation between cortical multi-unit activity, i.e. the firing of neuronal populations, and narrow band local field potential oscillations in the alpha band underlies the empirically observed negative correlation between alpha-rhythm power and fMRI signal in visual cortex. Furthermore the model suggests that the interplay between tonic and bursting mode in thalamus and cortex is critical for this relation. This demonstrates how biophysically meaningful modelling can generate precise and testable hypotheses about the underpinnings of large-scale neuroimaging signals.

Prior expectations evoke stimulus templates in the primary visual cortex.

Sensory processing is strongly influenced by prior expectations. Valid expectations have been shown to lead to improvements in perception as well as in the quality of sensory representations in primary visual cortex. However, very little is known about the neural correlates of the expectations themselves. Previous studies have demonstrated increased activity in sensory cortex following the omission of an expected stimulus, yet it is unclear whether this increased activity constitutes a general surprise signal or rather has representational content. One intriguing possibility is that top-down expectation leads to the formation of a template of the expected stimulus in visual cortex, which can then be compared with subsequent bottom-up input. To test this hypothesis, we used fMRI to noninvasively measure neural activity patterns in early visual cortex of human participants during expected but omitted visual stimuli. Our results show that prior expectation of a specific visual stimulus evokes a feature-specific pattern of activity in the primary visual cortex (V1) similar to that evoked by the corresponding actual stimulus. These results are in line with the notion that prior expectation triggers the formation of specific stimulus templates to efficiently process expected sensory inputs.

There's more than one way to scan a cat: imaging cat auditory cortex with high-field fMRI using continuous or sparse sampling.

When conducting auditory investigations using functional magnetic resonance imaging (fMRI), there are inherent potential confounds that need to be considered. Traditional continuous fMRI acquisition methods produce sounds >90 dB which compete with stimuli or produce neural activation masking evoked activity. Sparse scanning methods insert a period of reduced MRI-related noise, between image acquisitions, in which a stimulus can be presented without competition. In this study, we compared sparse and continuous scanning methods to identify the optimal approach to investigate acoustically evoked cortical, thalamic and midbrain activity in the cat. Using a 7 T magnet, we presented broadband noise, 10 kHz tones, or 0.5 kHz tones in a block design, interleaved with blocks in which no stimulus was presented. Continuous scanning resulted in larger clusters of activation and more peak voxels within the auditory cortex. However, no significant activation was observed within the thalamus. Also, there was no significant difference found, between continuous or sparse scanning, in activations of midbrain structures. Higher magnitude activations were identified in auditory cortex compared to the midbrain using both continuous and sparse scanning. These results indicate that continuous scanning is the preferred method for investigations of auditory cortex in the cat using fMRI. Also, choice of method for future investigations of midbrain activity should be driven by other experimental factors, such as stimulus intensity and task performance during scanning.

Language networks in anophthalmia: maintained hierarchy of processing in 'visual' cortex.

Imaging studies in blind subjects have consistently shown that sensory and cognitive tasks evoke activity in the occipital cortex, which is normally visual. The precise areas involved and degree of activation are dependent upon the cause and age of onset of blindness. Here, we investigated the cortical language network at rest and during an auditory covert naming task in five bilaterally anophthalmic subjects, who have never received visual input. When listening to auditory definitions and covertly retrieving words, these subjects activated lateral occipital cortex bilaterally in addition to the language areas activated in sighted controls. This activity was significantly greater than that present in a control condition of listening to reversed speech. The lateral occipital cortex was also recruited into a left-lateralized resting-state network that usually comprises anterior and posterior language areas. Levels of activation to the auditory naming and reversed speech conditions did not differ in the calcarine (striate) cortex. This primary 'visual' cortex was not recruited to the left-lateralized resting-state network and showed high interhemispheric correlation of activity at rest, as is typically seen in unimodal cortical areas. In contrast, the interhemispheric correlation of resting activity in extrastriate areas was reduced in anophthalmia to the level of cortical areas that are heteromodal, such as the inferior frontal gyrus. Previous imaging studies in the congenitally blind show that primary visual cortex is activated in higher-order tasks, such as language and memory to a greater extent than during more basic sensory processing, resulting in a reversal of the normal hierarchy of functional organization across 'visual' areas. Our data do not support such a pattern of organization in anophthalmia. Instead, the patterns of activity during task and the functional connectivity at rest are consistent with the known hierarchy of processing in these areas normally seen for vision. The differences in cortical organization between bilateral anophthalmia and other forms of congenital blindness are considered to be due to the total absence of stimulation in 'visual' cortex by light or retinal activity in the former condition, and suggests development of subcortical auditory input to the geniculo-striate pathway.

Diminished top-down control underlies a visual imagery deficit in normal aging.

Mental imagery is involved in a wide variety of cognitive abilities, including reasoning, spatial navigation, and memory. Cognitive aging is associated with impairments in these abilities, suggesting that diminished fidelity of mental images in older adults may be related to diverse cognitive deficits. However, an age-related deficit in mental imagery and its role in memory impairment is still a matter of debate. Previous human fMRI studies demonstrated that visual imagery activates representations in category-selective visual cortex via top-down control mechanisms. Here, we use fMRI to show that normal aging is associated with diminished selectivity of visual cortex activation during visual imagery, with a corresponding reduction in the selectivity of functional connections between prefrontal cortex and visual cortices. Moreover, a relationship between reduced imagery selectivity and visual memory in older adults was established. These results reveal that aging disrupts neural networks that subserve mental imagery and offers evidence of this as a factor in age-related memory decline.

Top-down modulation of human early visual cortex after stimulus offset supports successful postcued report.

Modulations of sensory processing in early visual areas are thought to play an important role in conscious perception. To date, most empirical studies focused on effects occurring before or during visual presentation. By contrast, several emerging theories postulate that sensory processing and conscious visual perception may also crucially depend on late top-down influences, potentially arising after a visual display. To provide a direct test of this, we performed an fMRI study using a postcued report procedure. The ability to report a target at a specific spatial location in a visual display can be enhanced behaviorally by symbolic auditory postcues presented shortly after that display. Here we showed that such auditory postcues can enhance target-specific signals in early human visual cortex (V1 and V2). For postcues presented 200 msec after stimulus termination, this target-specific enhancement in visual cortex was specifically associated with correct conscious report. The strength of this modulation predicted individual levels of performance in behavior. By contrast, although later postcues presented 1000 msec after stimulus termination had some impact on activity in early visual cortex, this modulation no longer related to conscious report. These results demonstrate that within a critical time window of a few hundred milliseconds after a visual stimulus has disappeared, successful conscious report of that stimulus still relates to the strength of top-down modulation in early visual cortex. We suggest that, within this critical time window, sensory representation of a visual stimulus is still under construction and so can still be flexibly influenced by top-down modulatory processes.

Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal.

Creatine monohydrate is an organic acid that plays a key role in ATP re-synthesis. Creatine levels in the human brain vary considerably and dietary supplementation has been found to enhance cognitive performance in healthy individuals. To explore the possibility that the fMRI Blood Oxygen Level Dependent (BOLD) response is influenced by creatine levels, BOLD responses to visual stimuli were measured in visual cortex before and after a week of creatine administration in healthy human volunteers. The magnitude of the BOLD response decreased by 16% following creatine supplementation of a similar dose to that previously shown to increase cerebral levels of phosphocreatine. We also confirmed that cognitive performance (memory span) is increased. These changes were not found in a placebo group. Possible mechanisms of BOLD change are considered. The results offer potential for insight into the coupling between neural activity and the BOLD response and the more immediate possibility of accounting for an important source of variability during fMRI analysis in clinical studies and other investigations where between-subjects variance is an issue.

Auditory selective attention to speech modulates activity in the visual word form area.

Selective attention to speech versus nonspeech signals in complex auditory input could produce top-down modulation of cortical regions previously linked to perception of spoken, and even visual, words. To isolate such top-down attentional effects, we contrasted 2 equally challenging active listening tasks, performed on the same complex auditory stimuli (words overlaid with a series of 3 tones). Instructions required selectively attending to either the speech signals (in service of rhyme judgment) or the melodic signals (tone-triplet matching). Selective attention to speech, relative to attention to melody, was associated with blood oxygenation level-dependent (BOLD) increases during functional magnetic resonance imaging (fMRI) in left inferior frontal gyrus, temporal regions, and the visual word form area (VWFA). Further investigation of the activity in visual regions revealed overall deactivation relative to baseline rest for both attention conditions. Topographic analysis demonstrated that while attending to melody drove deactivation equivalently across all fusiform regions of interest examined, attending to speech produced a regionally specific modulation: deactivation of all fusiform regions, except the VWFA. Results indicate that selective attention to speech can topographically tune extrastriate cortex, leading to increased activity in VWFA relative to surrounding regions, in line with the well-established connectivity between areas related to spoken and visual word perception in skilled readers.

Category-specific organization in the human brain does not require visual experience.

Distinct regions within the ventral visual pathway show neural specialization for nonliving and living stimuli (e.g., tools, houses versus animals, faces). The causes of these category preferences are widely debated. Using functional magnetic resonance imaging, we find that the same regions of the ventral stream that show category preferences for nonliving stimuli and animals in sighted adults show the same category preferences in adults who are blind since birth. Both blind and sighted participants had larger blood oxygen-level dependent (BOLD) responses in the medial fusiform gyrus for nonliving stimuli compared to animal stimuli and differential BOLD responses in lateral occipital cortex for animal stimuli compared to nonliving stimuli. These findings demonstrate that the medial-to-lateral bias by conceptual domain in the ventral visual pathway does not require visual experience in order to develop and suggest the operation of innately determined domain-specific constraints on the organization of object knowledge.

Combined functional MRI and diffusion tensor imaging analysis of visual motion pathways.

BACKGROUND: Motion perception may be preserved after damage to striate cortex (primary visual cortex, area V1). Awareness and normal discrimination of fast-moving stimuli have been observed even in the complete absence of V1. These facts suggest that motion-sensitive cortex (the V5/MT complex or V5/MT+) may be activated by direct thalamic or collicular inputs that bypass V1. Such projections have been identified previously in monkeys but have not been shown in humans using neuroimaging techniques. METHODS: We used diffusion tensor imaging (DTI) tractography to visualize white matter fiber tracts connecting with V5/MT+ in 10 healthy volunteers. V5/MT+ was localized for each subject using functional MRI (fMRI). Functional activity maps were overlaid on high-resolution anatomical images and registered with the diffusion-weighted images to define V5/MT+ as the region of interest (ROI) for DTI tractography analysis. Fibers connecting to V1 were excluded from the analysis. RESULTS: Using conservative tractography parameters, we found connections between the V5/MT+ region and the posterior thalamus and/or superior colliculus in 4 of 10 subjects. CONCLUSIONS: Connections between the V5/MT+ region and the posterior thalamus and/or superior colliculus may explain visual motion awareness in the absence of a functioning V1.

Comparison of visual cortical activations induced by electro-acupuncture at vision and nonvision-related acupoints.

In the current study, we investigated whether or not stimulation at vision and nonvision-related acupoints was able to induce similarity in the time domain, although stimulation at different acupoints could produce similar spatial distributions. This phenomenon still remains uncertain and contradictory. We introduced a novel experimental paradigm using a modified non-repeated event-related (NRER) design, and utilized the methods of independent component analysis (ICA) combined with seed correlated functional connectivity analysis to locate visual cortical activations and to study their temporal characteristics during electro-acupuncture (EAS) at vision-related acupoint GB 37 and nonvision-related acupoint KI 8. Results showed that strong activations were present in the visual cortical areas (BA 17/18/19) at both acupoints, but temporal correlation analysis indicated that they were modulated in opposite directions during the resting state after acupuncture. Our results revealed that acupuncture at vision and nonvision-related acupoints can induce similar activations in spatial distribution but different modulation effects temporally.

Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity.

Haemodynamic signals underlying functional brain imaging (for example, functional magnetic resonance imaging (fMRI)) are assumed to reflect metabolic demand generated by local neuronal activity, with equal increases in haemodynamic signal implying equal increases in the underlying neuronal activity. Few studies have compared neuronal and haemodynamic signals in alert animals to test for this assumed correspondence. Here we present evidence that brings this assumption into question. Using a dual-wavelength optical imaging technique that independently measures cerebral blood volume and oxygenation, continuously, in alert behaving monkeys, we find two distinct components to the haemodynamic signal in the alert animals' primary visual cortex (V1). One component is reliably predictable from neuronal responses generated by visual input. The other component-of almost comparable strength-is a hitherto unknown signal that entrains to task structure independently of visual input or of standard neural predictors of haemodynamics. This latter component shows predictive timing, with increases of cerebral blood volume in anticipation of trial onsets even in darkness. This trial-locked haemodynamic signal could be due to an accompanying V1 arterial pumping mechanism, closely matched in time, with peaks of arterial dilation entrained to predicted trial onsets. These findings (tested in two animals) challenge the current understanding of the link between brain haemodynamics and local neuronal activity. They also suggest the existence of a novel preparatory mechanism in the brain that brings additional arterial blood to cortex in anticipation of expected tasks.

The role of spectral and durational properties on hemispheric asymmetries in vowel perception.

The aim of the current study is to investigate potential hemispheric asymmetries in the perception of vowels and the influence of different time scales on such asymmetries. Activation patterns for naturally produced vowels were examined at three durations encompassing a short (75 ms), medium (150 ms), and long (300 ms) integration time window in a discrimination task. A set of 5 corresponding non-speech sine wave tones were created with frequencies matching the second formant of each vowel. Consistent with earlier hypotheses, there was a right hemisphere preference in the superior temporal gyrus for the processing of spectral information for both vowel and tone stimuli. However, observed laterality differences for vowels and tones were a function of heightened right hemisphere sensitivity to long integration windows, whereas the left hemisphere showed sensitivity to both long and short integration windows. Although there were a number of similarities in the processing of vowels and tones, differences also emerged suggesting that even fairly early in the processing stream at the level of the STG, different mechanisms are recruited for processing vowels and tones.

Independent components in stimulus-related BOLD signals and estimation of the underlying neural responses.

We measured blood oxygen level dependent (BOLD) responses to the onset of dynamic noise stimulation in defined regions of the primary retinotopic projection (V1) in visual cortex. The response waveforms showed a remarkable diversity across stimulus types, violating the basic assumption of a unitary general linear model of a uniform BOLD response function convolved with each stimulus sequence. We used independent component analysis (ICA) to analyze the component mechanisms contributing to these responses. The underlying neural responses for the components were estimated by nonlinear optimization through the Friston-Buxton hemodynamic model of the BOLD response. Our analysis suggests that one of the identified components reflected a sustained neural response to the stimulus and that another reflected an extremely slow neural response. A third component exhibited nonlinear change-specific transient responses. The first two components showed stable spatial structure in the V1 region of interest with respect to the eccentricity of the noise stimulus.

Independence of anticipatory signals for spatial attention from number of nontarget stimuli in the visual field.

Covertly attending to a location modulates the activity of visual areas even in the absence of visual stimulation. These effects are widespread, being found in the cortical representations of both attended and unattended portions of the visual field. It is not clear, however, whether preparatory modulations depend on subjects' expectation regarding the presence of additional nontarget stimuli in the visual field. Here, we asked subjects to endogenously direct attention to a peripheral location in the upper visual field, to identify the orientation of a low-contrast target stimulus, and we manipulated the number and behavioral relevance of other low-contrast nontarget stimuli in the visual field. Anticipatory (i.e., prestimulus) blood oxygenation level-dependent (BOLD) signal increments in visual cortex were strongest at the contralateral attended location, whereas signal decrements were strongest at the unattended mirror-opposite ipsilateral location/region of visual cortex. Importantly, these strong anticipatory decrements were not related to the presence/absence of nontarget low-contrast stimuli and did not correlate with either weaker target-evoked responses or worse performance. Second, the presence of other low-contrast stimuli in the visual field, even when potential targets, did not modify the anticipatory signal modulation either at target or nontarget locations. We conclude that the topography of spatial attention-related anticipatory BOLD signal modulation across visual cortex, specifically decrements at unattended locations, is mainly determined by processes at the cued location and not by the number or behavioral relevance of distant low-contrast nontarget stimuli elsewhere in the visual field.

Phonological processing of ignored distractor pictures, an fMRI investigation.

BACKGROUND: Neuroimaging studies of attention often focus on interactions between stimulus representations and top-down selection mechanisms in visual cortex. Less is known about the neural representation of distractor stimuli beyond visual areas, and the interactions between stimuli in linguistic processing areas. In the present study, participants viewed simultaneously presented line drawings at peripheral locations, while in the MRI scanner. The names of the objects depicted in these pictures were either phonologically related (i.e. shared the same consonant-vowel onset construction), or unrelated. Attention was directed either at the linguistic properties of one of these pictures, or at the fixation point (i.e. away from the pictures). RESULTS: Phonological representations of unattended pictures could be detected in the posterior superior temporal gyrus, the inferior frontal gyrus, and the insula. CONCLUSION: Under some circumstances, the name of ignored distractor pictures is retrieved by linguistic areas. This implies that selective attention to a specific location does not completely filter out the representations of distractor stimuli at early perceptual stages.

Asymmetry of anticipatory activity in visual cortex predicts the locus of attention and perception.

Humans can use advance information to direct spatial attention before stimulus presentation and respond more accurately to stimuli at the attended location compared with unattended locations. Likewise, spatially directed attention is associated with anticipatory activity in the portion of visual cortex representing the attended location. It is unknown, however, whether and how anticipatory signals predict the locus of spatial attention and perception. Here, we show that prestimulus, preparatory activity is highly correlated across regions representing attended and unattended locations. Comparing activity representing attended versus unattended locations, rather than measuring activity for only one location, dramatically improves the accuracy with which preparatory signals predict the locus of attention, largely by removing this positive correlation common across locations. In V3A, moreover, only the difference in activity between attended and unattended locations predicts whether upcoming visual stimuli will be accurately perceived. These results suggest that the locus of attention is coded in visual cortex by an asymmetry of anticipatory activity between attended and unattended locations and that this asymmetry predicts the accuracy of perception. This coding strategy may bias activity in downstream brain regions to represent the stimulus at the attended location.

Atypical [corrected] participation of visual cortex during word processing in autism: an fMRI study of semantic decision.

Language delay and impairment are salient features of autism. More specifically, there is evidence of atypical semantic organization in autism, but the functional brain correlates are not well understood. The current study used functional MRI to examine activation associated with semantic category decision. Ten high-functioning men with autism spectrum disorder and 10 healthy control subjects matched for gender, handedness, age, and nonverbal IQ were studied. Participants indicated via button press response whether visually presented words belonged to a target category (tools, colors, feelings). The control condition required target letter detection in unpronounceable letter strings. Significant activation for semantic decision in the left inferior frontal gyrus (Brodmann areas 44 and 45) was found in the control group. Corresponding activation in the autism group was more limited, with smaller clusters in left inferior frontal areas 45 and 47. Autistic participants, however, showed significantly greater activation compared to controls in extrastriate visual cortex bilaterally (areas 18 and 19), which correlated with greater number of errors on the semantic task. Our findings suggest an important role of perceptual components (possibly visual imagery) during semantic decision, consistent with previous evidence of atypical lexicosemantic performance in autism. In the context of similar findings from younger typically developing children, our results suggest an immature pattern associated with inefficient processing, presumably due to atypical experiential embedding of word acquisition in autism.

Hemodynamic responses in human multisensory and auditory association cortex to purely visual stimulation.

BACKGROUND: Recent findings of a tight coupling between visual and auditory association cortices during multisensory perception in monkeys and humans raise the question whether consistent paired presentation of simple visual and auditory stimuli prompts conditioned responses in unimodal auditory regions or multimodal association cortex once visual stimuli are presented in isolation in a post-conditioning run. To address this issue fifteen healthy participants partook in a "silent" sparse temporal event-related fMRI study. In the first (visual control) habituation phase they were presented with briefly red flashing visual stimuli. In the second (auditory control) habituation phase they heard brief telephone ringing. In the third (conditioning) phase we coincidently presented the visual stimulus (CS) paired with the auditory stimulus (UCS). In the fourth phase participants either viewed flashes paired with the auditory stimulus (maintenance, CS-) or viewed the visual stimulus in isolation (extinction, CS+) according to a 5:10 partial reinforcement schedule. The participants had no other task than attending to the stimuli and indicating the end of each trial by pressing a button. RESULTS: During unpaired visual presentations (preceding and following the paired presentation) we observed significant brain responses beyond primary visual cortex in the bilateral posterior auditory association cortex (planum temporale, planum parietale) and in the right superior temporal sulcus whereas the primary auditory regions were not involved. By contrast, the activity in auditory core regions was markedly larger when participants were presented with auditory stimuli. CONCLUSION: These results demonstrate involvement of multisensory and auditory association areas in perception of unimodal visual stimulation which may reflect the instantaneous forming of multisensory associations and cannot be attributed to sensation of an auditory event. More importantly, we are able to show that brain responses in multisensory cortices do not necessarily emerge from associative learning but even occur spontaneously to simple visual stimulation.

Multisensory interactions within human primary cortices revealed by BOLD dynamics.

Whether signals from different sensory modalities converge and interact within primary cortices in humans is unresolved, despite emerging evidence in animals. This is partially because of debates concerning the appropriate analyses of functional magnetic resonance imaging (fMRI) data in response to multisensory phenomena. Using event-related fMRI, we observed that simple auditory stimuli (noise bursts) activated primary visual cortices and that simple visual stimuli (checkerboards) activated primary auditory cortices, indicative of multisensory convergence. Moreover, analyses of blood oxygen level-dependent response dynamics revealed facilitation of hemodynamic response peak latencies and slopes for multisensory auditory-visual stimuli versus either unisensory condition, indicative of multisensory interactions within primary sensory cortices. Neural processing at the lowest cortical levels can be modulated by interactions between the senses. Temporal information in fMRI data can reveal these modulations and overcome analytic and interpretational challenges of more traditional procedures. In addition to providing an essential translational link with animal models, these results suggest that longstanding notions of cortical organization need to be revised to include multisensory interactions as an inherent component of functional brain organization.