Mareike Grotheer

Repetition Probability Effects Depend on Prior Experiences

The magnitude of repetition suppression (RS) in the Fusiform Face Area is influenced by the probability of repetitions of faces (Summerfield et al., 2008), implying that perceptual expectations affect repetition-related processes. Surprisingly, however, macaque single-cell (Kaliukhovich and Vogels, 2011) and human fMRI (Kovács et al., 2013) studies have failed to find repetition probability [P(rep)] modulations of RS with nonface stimuli in the occipitotemporal cortex, suggesting that the effect is face specific. One possible explanation of this category selectivity is that the extensive experience humans have with faces affects the neural mechanisms of RS specifically, creating P(rep) modulatory effects. To address this question, we used fMRI to test the P(rep) effects for another well trained stimulus category, upright letters of the roman alphabet as well as for unfamiliar false fonts. We observed significant RS for both stimulus sets in the Letter Form Area as well as in the caudodorsal part of the lateral occipital complex. Interestingly, the influence of P(rep) on RS was dependent on the stimulus: while we observed P(rep) modulations for the roman letters, no such effects were found for the unfamiliar false fonts in either area. Our findings suggest that P(rep) effects on RS are manifest for nonface stimuli as well, but that they depend on the experience of the subjects with the stimulus category. This shows, for the first time, that prior experience affects the influence of contextual predictive information on RS in the human occipitotemporal cortex.

Neuroimaging Evidence of a Bilateral Representation for Visually Presented Numbers

The clustered architecture of the brain for different visual stimulus categories is one of the most fascinating topics in the cognitive neurosciences. Interestingly, recent research suggests the existence of additional regions for newly acquired stimuli such as letters (letter form area; LFA; Thesen et al., 2012) and numbers (visual number form area; NFA; Shum et al., 2013). However, neuroimaging methods thus far have failed to visualize the NFA in healthy participants, likely due to fMRI signal dropout caused by the air/bone interface of the petrous bone (Shum et al., 2013). In the current study, we combined a 64-channel head coil with high spatial resolution, localized shimming, and liberal smoothing, thereby decreasing the signal dropout and increasing the temporal signal-to-noise ratio in the neighborhood of the NFA. We presented subjects with numbers, letters, false numbers, false letters, objects and their Fourier randomized versions. A group analysis showed significant activations in the inferior temporal gyrus at the previously proposed location of the NFA. Crucially, we found the NFA to be present in both hemispheres. Further, we could identify the NFA on the single-subject level in most of our participants. A detailed analysis of the response profile of the NFA in two separate experiments confirmed the whole-brain results since responses to numbers were significantly higher than to any other presented stimulus in both hemispheres. Our results show for the first time the existence and stimulus selectivity of the NFA in the healthy human brain. SIGNIFICANCE STATEMENT This fMRI study shows for the first time a cluster of neurons selective for visually presented numbers in healthy human adults. This visual number form area (NFA) was found in both hemispheres. Crucially, numbers have gained importance for humans too recently for neuronal specialization to be established by evolution. Therefore, investigations of this region will greatly advance our understanding of learning and plasticity in the brain. In addition, these results will aid our knowledge regarding related neurological illnesses (e.g., dyscalculia). To overcome the fMRI signal dropout in the neighborhood of the NFA, we combined high spatial resolution with liberal smoothing. We believe that this approach will be useful to the broad neuroimaging community.

Can predictive coding explain repetition suppression

While in earlier work various local or bottom-up neural mechanisms were proposed to give rise to repetition suppression (RS), current theories suggest that top-down processes play a role in determining the repetition related reduction of the neural responses. In the current review we summarise those results, which support the role of these top-down processes, concentrating on the Bayesian models of predictive coding (PC). Such models assume that RS is related to the statistical probabilities of prior stimulus occurrences and to the future predictability of these stimuli. Here we review the current results that support or argue against this explanation. We point out that the heterogeneity of experimental manipulations that are thought to reflect predictive processes are likely to measure different processing steps, making their direct comparison difficult. In addition we emphasize the importance of identifying these sub-processes and clarifying their role in explaining RS. Finally, we propose a two-stage model for explaining the relationships of repetition and expectation phenomena in the human cortex.

Repetition probability effects for inverted faces

It has been shown, that the repetition related reduction of the blood-oxygen level dependent (BOLD) signal is modulated by the probability of repetitions (P(rep)) for faces (Summerfield et al., 2008), providing support for the predictive coding (PC) model of visual perception (Rao and Ballard, 1999). However, the stage of face processing where repetition suppression (RS) is modulated by P(rep) is still unclear. Face inversion is known to interrupt higher level configural/holistic face processing steps and if modulation of RS by P(rep) takes place at these stages of face processing, P(rep) effects are expected to be reduced for inverted when compared to upright faces. Therefore, here we aimed at investigating whether P(rep) effects on RS observed for face stimuli originate at the higher-level configural/holistic stages of face processing by comparing these effects for upright and inverted faces. Similarly to previous studies, we manipulated P(rep) for pairs of stimuli in individual blocks of fMRI recordings. This manipulation significantly influenced repetition suppression in the posterior FFA, the OFA and the LO, independently of stimulus orientation. Our results thus reveal that RS in the ventral visual stream is modulated by P(rep) even in the case of face inversion and hence strongly compromised configural/holistic face processing. An additional whole-brain analysis could not identify any areas where the modulatory effect of probability was orientation specific either. These findings imply that P(rep) effects on RS might originate from the earlier stages of face processing.

Causal evidence of the involvement of the number form area in the visual detection of numbers and letters

Recent research suggests the existence of a visual area selectively processing numbers in the human inferior temporal cortex (number form area (NFA); Abboud et al., 2015; Grotheer et al., 2016; Shum et al., 2013). The NFA is thought to be involved in the preferential encoding of numbers over false characters, letters and non-number words (Grotheer et al., 2016; Shum et al., 2013), independently of the sensory modality (Abboud et al., 2015). However, it is not yet clear if this area is mandatory for normal number processing. The present study exploited the fact that high-resolution fMRI can be applied to identify the NFA individually (Grotheer et al., 2016) and tested if transcranial magnetic stimulation (TMS) of this area interferes with stimulus processing in a selective manner. Double-pulse TMS targeted at the right NFA significantly impaired the detection of briefly presented and masked Arabic numbers in comparison to vertex stimulation. This suggests the NFA to be necessary for fluent number processing. Surprisingly, TMS of the NFA also impaired the detection of Roman letters. On the other hand, stimulation of the lateral occipital complex (LO) had neither an effect on the detection of numbers nor on letters. Our results show, for the first time, that the NFA is causally involved in the early visual processing of numbers as well as of letters.

The relationship between stimulus repetitions and fulfilled expectations

Several neuroimaging studies showed that fulfilled expectations increase the magnitude of repetition suppression (RS) in the face-selective visual cortex. However, previous fMRI studies did not allow a distinction between the reductions of the response due to stimulus repetitions and fulfilled expectations (expectation suppression, ES). In most prior studies repetitions and expectations were not independent from each other as repetitions occurred more often when they were expected and less often when they were not expected, thereby confounding RS with ES. To overcome this confound, we presented pairs of female and male faces that were either repeating or alternating with an overall probability of 50-50%. Orthogonally to this, the gender of the first face in each pair signaled with 75% accuracy whether repetitions or alternations were more likely to occur. We found significant RS in the FFA, the OFA and the LO. In addition, these areas showed a reduction of the response for expected when compared to surprising trials. Moreover, the effects of RS and ES were always additive rather than interactive in our ROIs. This implies that stimulus repetition and fulfilled expectations can be dissociated from one another in terms of their effects on the neural responses.

The contribution of surprise to the prediction based modulation of fMRI responses

In recent years, several functional magnetic resonance imaging (fMRI) studies showed that correct stimulus predictions reduce the neural responses when compared to surprising events (Egner et al., 2010). Further, it has been shown that such fulfilled expectations enhance the magnitude of repetition suppression (RS, i.e. a decreased neuronal response after the repetition of a given stimulus) in face selective visual cortex as well (Summerfield et al., 2008). Current MEG and neuroimaging studies suggest that the underlying mechanisms of expectation effects are independent from these of RS (Grotheer and Kovács, 2015; Todorovic and Lange, 2012). However, it is not clear as of today how perceptual expectations modulate the neural responses: is the difference between correctly predicted and surprising stimuli due to a genuine response reduction for correctly predicted stimuli or is it due to an increased response for surprising stimuli? Therefore, here we used a modified version of the paradigm of Grotheer and Kovács (2015) to induce predictions independently from repetition probability by presenting pairs of faces (female, male or infant) that were either repeated or alternating. Orthogonally to this, predictions were manipulated by the gender of the first face within each pair so that it signaled high, low or equal probability of repetitions. An unpredicted, neutral condition with equal probabilities for alternating and repeated trials was used to identify the role of surprising and enhancing modulations. Similarly, to Grotheer and Kovács (2015), we found significant RS and significant expectation effect in the FFA. Importantly, we observed larger response for surprising events in comparison to the neutral and correctly predicted conditions for alternating trials. Altogether, these results emphasize the role of surprise in prediction effects.

A preference for mathematical processing outweighs the selectivity for Arabic numbers in the inferior temporal gyrus

&NA; A region in the posterior inferior temporal gyrus (ITG), referred to as the number form area (NFA, here ITG‐numbers) has been implicated in the visual processing of Arabic numbers. However, it is unknown if this region is specifically involved in the visual encoding of Arabic numbers per se or in mathematical processing more broadly. Using functional magnetic resonance imaging (fMRI) during experiments that systematically vary tasks and stimuli, we find that mathematical processing, not preference to Arabic numbers, consistently drives both mean and distributed responses in the posterior ITG. While we replicated findings of higher responses in ITG‐numbers to numbers than other visual stimuli during a 1‐back task, this preference to numbers was abolished when participants engaged in mathematical processing. In contrast, an ITG region (ITG‐math) that showed higher responses during an adding task vs. other tasks maintained this preference for mathematical processing across a wide range of stimuli including numbers, number/letter morphs, hands, and dice. Analysis of distributed responses across an anatomically‐defined posterior ITG expanse further revealed that mathematical task but not Arabic number form can be successfully and consistently decoded from these distributed responses. Together, our findings suggest that the function of neuronal regions in the posterior ITG goes beyond the specific visual processing of Arabic numbers. We hypothesize that they ascribe numerical content to the visual input, irrespective of the format of the stimulus. HighlightsITG shows preference for math task not Arabic numbers, across stimuli and experiments.Math task not number stimulus can be reliably decoded from distributed ITG responses.Results suggest a rethinking of the ITG function and its key role in math processing.

The relationship between repetition suppression and face perception

Repetition of identical face stimuli leads to fMRI response attenuation (fMRI adaptation, fMRIa) in the core face-selective occipito-temporal visual cortical network, involving the bilateral fusiform face area (FFA) and the occipital face area (OFA). However, the functional relevance of fMRIa observed in these regions is unclear as of today. Therefore, here we aimed at investigating the relationship between fMRIa and face perception ability by measuring in the same human participants both the repetition-induced reduction of fMRI responses and identity discrimination performance outside the scanner for upright and inverted face stimuli. In the correlation analysis, the behavioral and fMRI results for the inverted faces were used as covariates to control for the individual differences in overall object perception ability and basic visual feature adaptation processes, respectively. The results revealed a significant positive correlation between the participants’ identity discrimination performance and the strength of fMRIa in the core face processing network, but not in the extrastriate body area (EBA). Furthermore, we found a strong correlation of the fMRIa between OFA and FFA and also between OFA and EBA, but not between FFA and EBA. These findings suggest that there is a face-selective component of the repetition-induced reduction of fMRI responses within the core face processing network, which reflects functionally relevant adaptation processes involved in face identity perception.

Separate lanes for math and reading in the white matter highways of the human brain

Math and reading involve distributed brain networks and learning disabilities associated with these skills have a high rate of co-occurrence. However, it is unknown what are shared vs. dissociated white matter substrates of math and reading networks. Here we address this question using an innovative, multimodal approach applying functional MRI, diffusion MRI, and quantitative MRI to define these networks and evaluate structural properties of their fascicles. Results reveal that the superior longitudinal (SLF) and arcuate (AF) fascicles are shared between math and reading networks. Strikingly, within these fascicles, reading- and math-related tracts are segregated into parallel sub-bundles and show structural differences related to myelination. These novel findings: (i) open a new avenue of research enabling linkage of sub-bundles within fascicles to behavior and (ii) may explain both isolated and comorbid cases of math and reading disabilities, which may be associated with white matter abnormalities within sub-bundles or entire fascicles, respectively.