Spatiotemporally-specific cortical-subthalamic coupling differentiates aspects of speech performance.

Speech provides a rich context for exploring human cortical-basal ganglia circuit function, but direct intracranial recordings are rare. We recorded electrocorticographic signals in the cortex synchronously with single units in the subthalamic nucleus (STN), a basal ganglia node that receives direct input from widespread cortical regions, while participants performed a syllable repetition task during deep brain stimulation (DBS) surgery. We discovered that STN neurons exhibited spike-phase coupling (SPC) events with distinct combinations of frequency, location, and timing that indexed specific aspects of speech. The strength of SPC to posterior perisylvian cortex predicted phoneme production accuracy, while that of SPC to perirolandic cortex predicted time taken for articulation Thus, STN-cortical interactions are coordinated via transient bursts of behavior-specific synchronization that involves multiple neuronal populations and timescales. These results both suggest mechanisms that support auditory-sensorimotor integration during speech and explain why firing-rate based models are insufficient for explaining basal ganglia circuit behavior.

Orthographic learning in adults through overt and covert reading.

Fluent reading and writing rely on well-developed orthographic representations stored in memory. According to the self-teaching hypothesis (Share, D. L. (1995). Phonological recoding and self-teaching: Sine qua non of reading acquisition. Cognition, 55(2), 151-218), children acquire orthographic representations through phonological decoding. However, it is not clear to what extent phonological decoding facilitates orthographic learning in adult readers. Across two experiments, we manipulated access to phonology during overt (aloud) and covert (silent) reading of monosyllabic and multisyllabic pseudowords by English-speaking undergraduate students. Additionally, Experiment 2 tested whether concurrent articulation during covert reading leads to poorer learning due to the suppression of subvocalization. The amount of incidental orthographic learning through reading exposure was measured a week later with a choice task, a spelling task, and a naming task. Overt reading, which leveraged phonological decoding, led to better recognition and recall of pseudowords compared to when readers read silently. Unlike in previous reports of child orthographic learning, concurrent articulation during covert reading did not reduce learning outcomes in adults, suggesting that adult readers may rely upon other processing strategies during covert reading, e.g., direct orthographic processing or lexicalized phonological decoding. This is consistent with claims that with increasing orthographic knowledge reading mechanisms shift from being more phonologically-based to more visually-based.

Lexicality-Modulated Influence of Auditory Cortex on Subthalamic Nucleus During Motor Planning for Speech.

Speech requires successful information transfer within cortical-basal ganglia loop circuits to produce the desired acoustic output. For this reason, up to 90% of Parkinson's disease patients experience impairments of speech articulation. Deep brain stimulation (DBS) is highly effective in controlling the symptoms of Parkinson's disease, sometimes alongside speech improvement, but subthalamic nucleus (STN) DBS can also lead to decreases in semantic and phonological fluency. This paradox demands better understanding of the interactions between the cortical speech network and the STN, which can be investigated with intracranial EEG recordings collected during DBS implantation surgery. We analyzed the propagation of high-gamma activity between STN, superior temporal gyrus (STG), and ventral sensorimotor cortices during reading aloud via event-related causality, a method that estimates strengths and directionalities of neural activity propagation. We employed a newly developed bivariate smoothing model based on a two-dimensional moving average, which is optimal for reducing random noise while retaining a sharp step response, to ensure precise embedding of statistical significance in the time-frequency space. Sustained and reciprocal neural interactions between STN and ventral sensorimotor cortex were observed. Moreover, high-gamma activity propagated from the STG to the STN prior to speech onset. The strength of this influence was affected by the lexical status of the utterance, with increased activity propagation during word versus pseudoword reading. These unique data suggest a potential role for the STN in the feedforward control of speech.

Brain connectivity under light sedation with midazolam and ketamine during task performance and the periodic experience of pain: Examining concordance between different approaches for seed-based connectivity analysis.

This work focused on functional connectivity changes under midazolam and ketamine sedation during performance of a memory task, with the periodic experience of pain. To maximize ability to compare to previous and future work, we performed secondary region of interest (ROI)-to-ROI functional connectivity analyses on these data, using two granularities of scale for ROIs. These findings are compared to the results of a previous seed-to-voxel analysis methodology, employed in the primary analysis. Healthy adult volunteers participated in this randomized crossover 3 T functional MRI study under no drug, followed by subanesthetic doses of midazolam or ketamine achieving minimal sedation. Periodic painful stimulation was delivered while subjects repeatedly performed a memory-encoding task. Atlas-based and network-level ROIs were used from within Conn Toolbox (ver 18). Timing of experimental task events was regressed from the data to assess drug-induced changes in background connectivity, using ROI-to-ROI methodology. Compared to saline, ROI-to-ROI connectivity changes under ketamine did not survive correction for multiple comparisons, thus data presented is from 16 subjects in a paired analysis between saline and midazolam. In both ROI-to-ROI analyses, the predominant direction of change was towards increased connectivity under midazolam, compared to saline. These connectivity increases occurred between functionally-distinct brain areas, with a posterior-predominant spatial distribution that included many long-range connectivity changes. During performance of an experimental task that involved periodic painful stimulation, compared to saline, low-dose midazolam was associated with robust increases in functional connectivity. This finding was concordant across different seed-based analyses for midazolam, but not ketamine. The neuroimaging drug trial from which this data was drawn was pre-registered (NCT-02515890) prior to enrollment of the first subject.

Comparing the Reliability of Virtual and In-Person Post-Stroke Neuropsychological Assessment with Language Tasks.

OBJECTIVE: Neuropsychological testing is essential for both clinical and basic stroke research; however, the in-person nature of this testing is a limitation. Virtual testing overcomes the hurdles of geographic location, mobility issues and permits social distancing, yet its validity has received relatively little investigation, particularly in comparison with in-person testing. METHOD: We expand on our prior findings of virtual testing feasibility by assessing virtual versus in-person administration of language and communication tasks with 48 left-hemisphere stroke patients (21 F, 27 M; mean age = 63.4 ± 12; mean years of education = 15.3 ± 3.5) in a quasi-test-retest paradigm. Each participant completed two testing sessions: one in their home and one in the research lab. Participants were assigned to one of the eight groups, with the testing condition (fully in-person, partially virtual), order of home session (first, second) and technology (iPad, Windows tablet) varied across groups. RESULTS: Across six speech-language tasks that utilized varying response modalities and interfaces, we found no significant difference in performance between virtual and in-person testing. However, our results reveal key considerations for successful virtual administration of neuropsychological tests, including technology complications and disparities in internet access. CONCLUSIONS: Virtual administration of neuropsychological assessments demonstrates comparable reliability with in-person data collection involving stroke survivors, though technology issues must be taken into account.

Representations within the Intraparietal Sulcus Distinguish Numerical Tasks and Formats.

How does our brain understand the number five when it is written as an Arabic numeral, and when presented as five fingers held up? Four facets have been implicated in adult numerical processing: semantic, visual, manual, and phonological/verbal. Here, we ask how the brain represents each, using a combination of tasks and stimuli. We collected fMRI data from adult participants while they completed our novel "four number code" paradigm. In this paradigm, participants viewed one of two stimulus types to tap into the visual and manual number codes, respectively. Concurrently, they completed one of two tasks to tap into the semantic and phonological/verbal number codes, respectively. Classification analyses revealed that neural codes representing distinctions between the number comparison and phonological tasks were generalizable across format (e.g., Arabic numerals to hands) within intraparietal sulcus (IPS), angular gyrus, and precentral gyrus. Neural codes representing distinctions between formats were generalizable across tasks within visual areas such as fusiform gyrus and calcarine sulcus, as well as within IPS. Our results identify the neural facets of numerical processing within a single paradigm and suggest that IPS is sensitive to distinctions between semantic and phonological/verbal, as well as visual and manual, facets of number representations.

Neutral auditory words immediately followed by painful electric shock may show reduced next-day recollection.

In this study, we investigated the effect of experimentally delivered acute pain on memory. Twenty-five participants participated in experimental sessions on consecutive days. The first session involved a categorization task to encourage memory encoding. There were two conditions, presented in randomized order, in which participants listened to a series of words, which were repeated three times. In one condition, one-third of the word items were immediately followed by a painful electrical shock. This word-shock pairing was consistent across repetition and the pain-paired items were presented unpredictably. In the other condition, all word items were not associated with pain. Response times over these repeated presentations were assessed for differences. Explicit memory was tested the following day, employing a Remember-Know assessment of word recognition, with no shocks employed. We found evidence that recollection may be reduced for pain-paired words, as the proportion of correct Remember responses (out of total correct responses) was significantly lower. There were no significant reductions in memory for non-pain items that followed painful stimulation after a period of several seconds. Consistent with the experience of pain consuming working memory resources, we theorize that painful shocks interrupt memory encoding for the immediately preceding experimental items, due to a shift in attention away from the word item.

Lateralized and Region-Specific Thalamic Processing of Lexical Status during Reading Aloud.

To explore whether the thalamus participates in lexical status (word vs nonword) processing during spoken word production, we recorded local field potentials from the ventral lateral thalamus in 11 essential tremor patients (three females) undergoing thalamic deep-brain stimulation lead implantation during a visually cued word and nonword reading-aloud task. We observed task-related beta (12-30 Hz) activity decreases that were preferentially time locked to stimulus presentation, and broadband gamma (70-150 Hz) activity increases, which are thought to index increased multiunit spiking activity, occurring shortly before and predominantly time locked to speech onset. We further found that thalamic beta activity decreases bilaterally were greater when nonwords were read, demonstrating bilateral sensitivity to lexical status that likely reflects the tracking of task effort; in contrast, greater nonword-related increases in broadband gamma activity were observed only on the left, demonstrating lateralization of thalamic broadband gamma selectivity for lexical status. In addition, this lateralized lexicality effect on broadband gamma activity was strongest in more anterior thalamic locations, regions which are more likely to receive basal ganglia than cerebellar afferents and have extensive connections with prefrontal cortex including Brodmann's areas 44 and 45, regions consistently associated with grapheme-to-phoneme conversions. These results demonstrate active thalamic participation in reading aloud and provide direct evidence from intracranial thalamic recordings for the lateralization and topography of subcortical lexical status processing.SIGNIFICANCE STATEMENT Despite the corticocentric focus of most experimental work and accompanying models, there is increasing recognition of the role of subcortical structures in speech and language. Using local field potential recordings in neurosurgical patients, we demonstrated that the thalamus participates in lexical status (word vs nonword) processing during spoken word production, in a lateralized and region-specific manner. These results provide direct evidence from intracranial thalamic recordings for the lateralization and topography of subcortical lexical status processing.

Numerical estrangement and integration between symbolic and non-symbolic numerical information: Task-dependence and its link to math abilities in adults.

Most adults have access to two different number systems to represent numerical information: an exact number system, which relies on different forms of number symbols to represent exact numerical information, and an approximate number system, which allows for approximate estimates of numerical quantities. Here we investigate the integration between the symbolic and non-symbolic numerical information (i.e., "numerical integration"), and how numerical integration relates to adults' formal math abilities. We administered two tasks to measure numerical integration. For a number comparison task with non-symbolic dot arrays and Arabic numerals, participants indicated the larger of two sequentially presented stimuli that were same-format (dot-dot or numeral-numeral), or mixed-format (dot-numeral or numeral-dot). For a number-letter discrimination task, participants identified Arabic numerals or letter pairs that co-occurred with dot arrays (matching or mismatching the quantity represented by the numeral). In the number comparison task, participants were significantly slower when comparing mixed-format stimuli, especially when Arabic numerals were presented first and dot arrays second, suggesting estrangement between symbolic and non-symbolic numerical information and an asymmetry depending on the order in which the numerical information is presented. In contrast, in the number-letter discrimination task, participants were significantly faster in number-letter discrimination for matching dot arrays and numerals, suggesting integration between symbolic and non-symbolic numerical information. Surprisingly, some measures of numerical estrangement derived from the number comparison task significantly correlated with adults' performance on a standardized math assessment. Thus, we conclude that numerical integration or estrangement is task-dependent, and adults with greater levels of symbolic estrangement tend to have higher math skills.

Comprehension of Morse Code Predicted by Item Recall From Short-Term Memory.

Purpose Morse code as a form of communication became widely used for telegraphy, radio and maritime communication, and military operations, and remains popular with ham radio operators. Some skilled users of Morse code are able to comprehend a full sentence as they listen to it, while others must first transcribe the sentence into its written letter sequence. Morse thus provides an interesting opportunity to examine comprehension differences in the context of skilled acoustic perception. Measures of comprehension and short-term memory show a strong correlation across multiple forms of communication. This study tests whether this relationship holds for Morse and investigates its underlying basis. Our analyses examine Morse and speech immediate serial recall, focusing on established markers of echoic storage, phonological-articulatory coding, and lexical-semantic support. We show a relationship between Morse short-term memory and Morse comprehension that is not explained by Morse perceptual fluency. In addition, we find that poorer serial recall for Morse compared to speech is primarily due to poorer item memory for Morse, indicating differences in lexical-semantic support. Interestingly, individual differences in speech item memory are also predictive of individual differences in Morse comprehension. Conclusions We point to a psycholinguistic framework to account for these results, concluding that Morse functions like "reading for the ears" (Maier et al., 2004) and that underlying differences in the integration of phonological and lexical-semantic knowledge impact both short-term memory and comprehension. The results provide insight into individual differences in the comprehension of degraded speech and strategies that build comprehension through listening experience. Supplemental Material https://doi.org/10.23641/asha.16451868.

Multiple adjoining word- and face-selective regions in ventral temporal cortex exhibit distinct dynamics.

The map of category-selectivity in human ventral temporal cortex (VTC) provides organizational constraints to models of object recognition. One important principle is lateral-medial response biases to stimuli that are typically viewed in the center or periphery of the visual field. However, little is known about the relative temporal dynamics and location of regions that respond preferentially to stimulus classes that are centrally viewed, like the face- and word-processing networks. Here, word- and face-selective regions within VTC were mapped using intracranial recordings from 36 patients. Partially overlapping, but also anatomically dissociable patches of face- and word-selectivity were found in VTC. In addition to canonical word-selective regions along the left posterior occipitotemporal sulcus, selectivity was also located medial and anterior to face-selective regions on the fusiform gyrus at the group level and within individual male and female subjects. These regions were replicated using 7 Tesla fMRI in healthy subjects. Left hemisphere word-selective regions preceded right hemisphere responses by 125 ms, potentially reflecting the left hemisphere bias for language; with no hemispheric difference in face-selective response latency. Word-selective regions along the posterior fusiform responded first, then spread medially and laterally, then anteriorally. Face-selective responses were first seen in posterior fusiform regions bilaterally, then proceeded anteriorally from there. For both words and faces, the relative delay between regions was longer than would be predicted by purely feedforward models of visual processing. The distinct time-courses of responses across these regions, and between hemispheres, suggest a complex and dynamic functional circuit supports face and word perception.SIGNIFICANCE STATEMENT:Representations of visual objects in the human brain have been shown to be organized by several principles, including whether those objects tend to be viewed centrally or peripherally in the visual field. However, it remains unclear how regions that process objects that are viewed centrally, like words and faces, are organized relative to one another. Here, invasive and non-invasive neuroimaging suggests there is a mosaic of regions in ventral temporal cortex that respond selectively to either words or faces. These regions display differences in the strength and timing of their responses, both within and between brain hemispheres, suggesting they play different roles in perception. These results illuminate extended, bilateral, and dynamic brain pathways that support face perception and reading.

Midazolam and Ketamine Produce Distinct Neural Changes in Memory, Pain, and Fear Networks during Pain.

BACKGROUND: Despite the well-known clinical effects of midazolam and ketamine, including sedation and memory impairment, the neural mechanisms of these distinct drugs in humans are incompletely understood. The authors hypothesized that both drugs would decrease recollection memory, task-related brain activity, and long-range connectivity between components of the brain systems for memory encoding, pain processing, and fear learning. METHODS: In this randomized within-subject crossover study of 26 healthy adults, the authors used behavioral measures and functional magnetic resonance imaging to study these two anesthetics, at sedative doses, in an experimental memory paradigm using periodic pain. The primary outcome, recollection memory performance, was quantified with d' (a difference of z scores between successful recognition versus false identifications). Secondary outcomes were familiarity memory performance, serial task response times, task-related brain responses, and underlying brain connectivity from 17 preselected anatomical seed regions. All measures were determined under saline and steady-state concentrations of the drugs. RESULTS: Recollection memory was reduced under midazolam (median [95% CI], d' = 0.73 [0.43 to 1.02]) compared with saline (d' = 1.78 [1.61 to 1.96]) and ketamine (d' = 1.55 [1.12 to 1.97]; P < 0.0001). Task-related brain activity was detected under saline in areas involved in memory, pain, and fear, particularly the hippocampus, insula, and amygdala. Compared with saline, midazolam increased functional connectivity to 20 brain areas and decreased to 8, from seed regions in the precuneus, posterior cingulate, and left insula. Compared with saline, ketamine decreased connectivity to 17 brain areas and increased to 2, from 8 seed regions including the hippocampus, parahippocampus, amygdala, and anterior and primary somatosensory cortex. CONCLUSIONS: Painful stimulation during light sedation with midazolam, but not ketamine, can be accompanied by increased coherence in brain connectivity, even though details are less likely to be recollected as explicit memories.

Unmasking individual differences in adult reading procedures by disrupting holistic orthographic perception.

Word identification is undeniably important for skilled reading and ultimately reading comprehension. Interestingly, both lexical and sublexical procedures can support word identification. Recent cross-linguistic comparisons have demonstrated that there are biases in orthographic coding (e.g., holistic vs. analytic) linked with differences in writing systems, such that holistic orthographic coding is correlated with lexical-level reading procedures and vice versa. The current study uses a measure of holistic visual processing used in the face processing literature, orientation sensitivity, to test individual differences in word identification within a native English population. Results revealed that greater orientation sensitivity (i.e., greater holistic processing) was associated with a reading profile that relies less on sublexical phonological measures and more on lexical-level characteristics within the skilled English readers. Parallels to Chinese procedures of reading and a proposed alternative route to skilled reading are discussed.

Abstract inference of unchosen option values.

Reinforcement learning research has pursued a persistent question: Does reward feedback prompt inferences that transcend simple associations? Reversal learning data suggest an affirmative answer: When the positive stimulus (S+) becomes the negative stimulus (S-), trained humans rapidly switch to choosing the former S-. The operations supporting such inferences remain ambiguous. Do participants identify transitions between stimulus-specific contexts (i.e., A+B- and A-B+), or deduce values by learning the abstract contingency structure? Across two experiments, we probed humans' use of abstract rules to infer the values of unchosen alternatives. In Experiment 1, 37 participants attempted a task that originally demonstrated monkeys' difficulty with this form of inference. We presented modified discrimination problems in which the initially chosen stimulus (abstract inference group) or unchosen stimulus (control group) was replaced with a novel stimulus of identical status on Trial 2. In the abstract inference condition, accurate performance can be achieved by applying the consistent contingency structure (but not memory of stimulus-specific reward associations) to infer to the unchosen stimulus' value. The abstract inference group learned to make accurate choices, but only after committing substantially more errors than were observed among control participants-suggesting that unchosen value inferences are infrequently drawn in standard discrimination scenarios. In Experiment 2, 17 participants completed abstract inference problems that had been modified to be suitable for fMRI investigations. Behavioral results both corroborated the Experiment 1 trends and further revealed marked individual differences in explicit awareness of the novel stimulus values.

Memory for non-painful auditory items is influenced by whether they are experienced in a context involving painful electrical stimulation.

In this study, we sought to examine the effect of experimentally induced somatic pain on memory. Subjects heard a series of words and made categorization decisions in two different conditions. One condition included painful shocks administered just after presentation of some of the words; the other condition involved no shocks. For the condition that included painful stimulations, every other word was followed by a shock, and subjects were informed to expect this pattern. Word lists were repeated three times within each condition in randomized order, with different category judgments but consistent pain-word pairings. After a brief delay, recognition memory was assessed. Non-pain words from the pain condition were less strongly encoded than non-pain words from the completely pain-free condition. Recognition of pain-paired words was not significantly different than either subgroup of non-pain words. An important accompanying finding is that response times to repeated experimental items were slower for non-pain words from the pain condition, compared to non-pain words from the completely pain-free condition. This demonstrates that the effect of pain on memory may generalize to non-pain items experienced in the same experimental context.

Word inversion sensitivity as a marker of visual word form area lateralization: An application of a novel multivariate measure of laterality.

An area within the ventral occipitotemporal cortex (vOTC), the "visual word form area" (VWFA), typically exhibits a strongly left-lateralized response to orthographic stimuli in skilled readers. While individual variation in VWFA lateralization has been observed, the behavioral significance of laterality differences remains unclear. Here, we test the hypothesis that differences in VWFA lateralization reflect differing preferences for holistic orthographic analysis. To examine this hypothesis, we implemented a new multivariate method that uses machine learning to assess functional lateralization, along with a traditional univariate lateralization method. We related these neural metrics to behavioral indices of holistic orthographic analysis (inversion sensitivity). The multivariate measure successfully detected the lateralization of orthographic processing in the VWFA, and as hypothesized, predicted behavioral differences in holistic orthographic analysis. An exploratory whole brain analysis identified further regions with a relationship between inversion sensitivity and lateralization: one near the junction of the inferior frontal and precentral sulci, and another along the superior temporal gyrus. We conclude that proficient native readers of English exhibit differences in cortical lateralization of the VWFA that have significant implications for reading behavior.

Subthalamic Nucleus and Sensorimotor Cortex Activity During Speech Production.

The sensorimotor cortex is somatotopically organized to represent the vocal tract articulators such as lips, tongue, larynx, and jaw. How speech and articulatory features are encoded at the subcortical level, however, remains largely unknown. We analyzed LFP recordings from the subthalamic nucleus (STN) and simultaneous electrocorticography recordings from the sensorimotor cortex of 11 human subjects (1 female) with Parkinson's disease during implantation of deep-brain stimulation (DBS) electrodes while they read aloud three-phoneme words. The initial phonemes involved either articulation primarily with the tongue (coronal consonants) or the lips (labial consonants). We observed significant increases in high-gamma (60-150 Hz) power in both the STN and the sensorimotor cortex that began before speech onset and persisted for the duration of speech articulation. As expected from previous reports, in the sensorimotor cortex, the primary articulators involved in the production of the initial consonants were topographically represented by high-gamma activity. We found that STN high-gamma activity also demonstrated specificity for the primary articulator, although no clear topography was observed. In general, subthalamic high-gamma activity varied along the ventral-dorsal trajectory of the electrodes, with greater high-gamma power recorded in the dorsal locations of the STN. Interestingly, the majority of significant articulator-discriminative activity in the STN occurred before that in sensorimotor cortex. These results demonstrate that articulator-specific speech information is contained within high-gamma activity of the STN, but with different spatial and temporal organization compared with similar information encoded in the sensorimotor cortex.SIGNIFICANCE STATEMENT Clinical and electrophysiological evidence suggest that the subthalamic nucleus (STN) is involved in speech; however, this important basal ganglia node is ignored in current models of speech production. We previously showed that STN neurons differentially encode early and late aspects of speech production, but no previous studies have examined subthalamic functional organization for speech articulators. Using simultaneous LFP recordings from the sensorimotor cortex and the STN in patients with Parkinson's disease undergoing deep-brain stimulation surgery, we discovered that STN high-gamma activity tracks speech production at the level of vocal tract articulators before the onset of vocalization and often before related cortical encoding.

Role of the striatum in incidental learning of sound categories.

Humans are born as "universal listeners" without a bias toward any particular language. However, over the first year of life, infants' perception is shaped by learning native speech categories. Acoustically different sounds-such as the same word produced by different speakers-come to be treated as functionally equivalent. In natural environments, these categories often emerge incidentally without overt categorization or explicit feedback. However, the neural substrates of category learning have been investigated almost exclusively using overt categorization tasks with explicit feedback about categorization decisions. Here, we examined whether the striatum, previously implicated in category learning, contributes to incidental acquisition of sound categories. In the fMRI scanner, participants played a videogame in which sound category exemplars aligned with game actions and events, allowing sound categories to incidentally support successful game play. An experimental group heard nonspeech sound exemplars drawn from coherent category spaces, whereas a control group heard acoustically similar sounds drawn from a less structured space. Although the groups exhibited similar in-game performance, generalization of sound category learning and activation of the posterior striatum were significantly greater in the experimental than control group. Moreover, the experimental group showed brain-behavior relationships related to the generalization of all categories, while in the control group these relationships were restricted to the categories with structured sound distributions. Together, these results demonstrate that the striatum, through its interactions with the left superior temporal sulcus, contributes to incidental acquisition of sound category representations emerging from naturalistic learning environments.

The VWFA Is the Home of Orthographic Learning When Houses Are Used as Letters.

Learning to read specializes a portion of the left mid-fusiform cortex for printed word recognition, the putative visual word form area (VWFA). This study examined whether a VWFA specialized for English is sufficiently malleable to support learning a perceptually atypical second writing system. The study utilized an artificial orthography, HouseFont, in which house images represent English phonemes. House images elicit category-biased activation in a spatially distinct brain region, the so-called parahippocampal place area (PPA). Using house images as letters made it possible to test whether the capacity for learning a second writing system involves neural territory that supports reading in the first writing system, or neural territory tuned for the visual features of the new orthography. Twelve human adults completed two weeks of training to establish basic HouseFont reading proficiency and underwent functional neuroimaging pre and post-training. Analysis of three functionally defined regions of interest (ROIs), the VWFA, and left and right PPA, found significant pre-training versus post-training increases in response to HouseFont words only in the VWFA. Analysis of the relationship between the behavioral and neural data found that activation changes from pre-training to post-training within the VWFA predicted HouseFont reading speed. These results demonstrate that learning a new orthography utilizes neural territory previously specialized by the acquisition of a native writing system. Further, they suggest VWFA engagement is driven by orthographic functionality and not the visual characteristics of graphemes, which informs the broader debate about the nature of category-specialized areas in visual association cortex.