The Prospective Sleeping Brain: Age-Related Differences in Episodic Future Thinking and Frontal Sleep Spindles.

Sleep spindles are a physiological marker of off-line memory consolidation. In young adults, sleep spindles are preferentially responsive to encoded information that is tagged as having future relevance. Older adults, on the other hand, show reduced capacity for future simulation and alterations in sleep physiology. Healthy young adults (n = 38) and older adults (n = 28) completed an adaptation night, followed by two in-laboratory polysomnography nights, in which they mentally simulated future events or remembered past events, recorded via written descriptions. We quantified the degree of future/past thinking using linguistic analysis of time orientation. In young adults, greater future thinking was linked to greater spindle density, even when controlling for gender, age, and word count (rp = .370, p = .028). The opposite was true for older adults, such that greater future thinking was associated with reduced spindle density (rp = -.431, p = .031). These patterns were selective to future thinking (not observed for past thinking). The collective findings implicate an impaired interaction between future relevance tagging and sleep physiology as a mechanism by which aging compromises sleep-dependent cognitive processing.

Bedtime Music, Involuntary Musical Imagery, and Sleep.

Many people listen to music for hours every day, often near bedtime. We investigated whether music listening affects sleep, focusing on a rarely explored mechanism: involuntary musical imagery (earworms). In Study 1 (N = 199, mean age = 35.9 years), individuals who frequently listen to music reported persistent nighttime earworms, which were associated with worse sleep quality. In Study 2 (N = 50, mean age = 21.2 years), we randomly assigned each participant to listen to lyrical or instrumental-only versions of popular songs before bed in a laboratory, discovering that instrumental music increased the incidence of nighttime earworms and worsened polysomnography-measured sleep quality. In both studies, earworms were experienced during awakenings, suggesting that the sleeping brain continues to process musical melodies. Study 3 substantiated this possibility by showing a significant increase in frontal slow oscillation activity, a marker of sleep-dependent memory consolidation. Thus, some types of music can disrupt nighttime sleep by inducing long-lasting earworms that are perpetuated by spontaneous memory-reactivation processes.

Classical music, educational learning, and slow wave sleep: A targeted memory reactivation experiment.

Poor sleep in college students compromises the memory consolidation processes necessary to retain course materials. A solution may lie in targeting reactivation of memories during sleep (TMR). Fifty undergraduate students completed a college-level microeconomics lecture (mathematics-based) while listening to distinctive classical music (Chopin, Beethoven, and Vivaldi). After they fell asleep, we re-played the classical music songs (TMR) or a control noise during slow wave sleep. Relative to the control condition, the TMR condition showed an 18% improvement for knowledge transfer items that measured concept integration (d = 0.63), increasing the probability of "passing" the test with a grade of 70 or above (OR = 4.68, 95%CI: 1.21, 18.04). The benefits of TMR did not extend to a 9-month follow-up test when performance dropped to floor levels, demonstrating that long-term-forgetting curves are largely resistant to experimentally-consolidated memories. Spectral analyses revealed greater frontal theta activity during slow wave sleep in the TMR condition than the control condition (d = 0.87), and greater frontal theta activity across conditions was associated with protection against long-term-forgetting at the next-day and 9-month follow-up tests (rs = 0.42), at least in female students. Thus, students can leverage instrumental music-which they already commonly pair with studying-to help prepare for academic tests, an approach that may promote course success and persistence.

Enhancement of Consonant Recognition in Bimodal and Normal Hearing Listeners.

OBJECTIVES: The present study investigated the effects of 3-dimensional deep search (3DDS) signal processing on the enhancement of consonant perception in bimodal and normal hearing listeners. METHODS: Using an articulation-index gram and 3DDS signal processing, consonant segments that greatly affected performance were identified and intensified with a 6-dB gain. Then consonant recognition was measured unilaterally and bilaterally before and after 3DDS processing both in quiet and noise. RESULTS: The 3DDS signal processing provided a benefit to both groups, with greater benefit occurring in noise than quiet. The benefit rendered by 3DDS was the greatest in binaural listening condition. Ability to integrate acoustic features across ears was also enhanced with 3DDS processing. In listeners with normal hearing, manner and place of articulation were improved in binaural listening condition. In bimodal listeners, voicing and manner and place of articulation were also improved in bimodal and hearing aid ear-alone conditions. CONCLUSIONS: Consonant recognition was improved with 3DDS in both groups. This observed benefit suggests 3DDS can be used as an auditory training tool for improved integration and for bimodal users who receive little or no benefit from their current bimodal hearing.

Rapid eye movement sleep mediates age-related decline in prospective memory consolidation.

STUDY OBJECTIVES: Prospective memory, or remembering to execute future intentions, accounts for half of everyday forgetting in older adults. Sleep intervals benefit prospective memory consolidation in young adults, but it is unknown whether age-related changes in slow wave activity, sleep spindles, and/or rapid eye movement (REM) sleep mediate hypothesized effects of aging on prospective memory consolidation. METHODS: After an adaptation night, 76 adults aged 18-84 completed two experimental nights of in-laboratory polysomnography recording. In the evening, participants encoded and practiced a prospective memory task and were tested the next morning. On a counterbalanced night, they encoded and practiced a control task, and were tested the following morning. RESULTS: Increasing age predicted worse prospective memory consolidation (r = -.34), even when controlling for encoding, speed, and control-task performance (all ps < .05). Frontal delta power, slow oscillations, and spindle density were not related to prospective memory consolidation. REM sleep duration, however, explained significant variance in prospective memory consolidation when controlling for age (∆R2 = .10). Bootstrapping mediation showed that less REM sleep significantly mediated the aging effect on prospective memory consolidation [b = -.0016, SE = 0.0009 (95% confidence interval [CI] = -0.0042 to -0.0004)]. REM sleep continued to mediate 24.29% of the total effect of age on prospective memory after controlling for numerous demographic, cognitive, mental health, and sleep variables. CONCLUSION: Age-related variance in REM sleep is informative to how prospective memory consolidation changes with increasing age. Future work should consider how both REM sleep and slow wave activity contribute, perhaps in a sequential or dynamic manner, to preserving cognitive functioning with increasing age.

Functional Characterization of the Human Speech Articulation Network.

A number of brain regions have been implicated in articulation, but their precise computations remain debated. Using functional magnetic resonance imaging, we examine the degree of functional specificity of articulation-responsive brain regions to constrain hypotheses about their contributions to speech production. We find that articulation-responsive regions (1) are sensitive to articulatory complexity, but (2) are largely nonoverlapping with nearby domain-general regions that support diverse goal-directed behaviors. Furthermore, premotor articulation regions show selectivity for speech production over some related tasks (respiration control), but not others (nonspeech oral-motor [NSO] movements). This overlap between speech and nonspeech movements concords with electrocorticographic evidence that these regions encode articulators and their states, and with patient evidence whereby articulatory deficits are often accompanied by oral-motor deficits. In contrast, the superior temporal regions show strong selectivity for articulation relative to nonspeech movements, suggesting that these regions play a specific role in speech planning/production. Finally, articulation-responsive portions of posterior inferior frontal gyrus show some selectivity for articulation, in line with the hypothesis that this region prepares an articulatory code that is passed to the premotor cortex. Taken together, these results inform the architecture of the human articulation system.

Brain damage associated with apraxia of speech: evidence from case studies.

The site of crucial damage that causes acquired apraxia of speech (AOS) has been debated in the literature. This study presents five in-depth cases that offer insight into the role of brain areas involved in AOS. Four of the examined participants had a primary impairment of AOS either with (n = 2) or without concomitant mild aphasia (n = 2). The fifth participant presented with a lesion relatively isolated to the left anterior insula (AIns-L), damage that is rarely reported in the literature, but without AOS. Taken together, these cases challenge the role of the AIns-L and implicate the left motor regions in AOS.

Perception drives production across sensory modalities: A network for sensorimotor integration of visual speech.

Sensory information is critical for movement control, both for defining the targets of actions and providing feedback during planning or ongoing movements. This holds for speech motor control as well, where both auditory and somatosensory information have been shown to play a key role. Recent clinical research demonstrates that individuals with severe speech production deficits can show a dramatic improvement in fluency during online mimicking of an audiovisual speech signal suggesting the existence of a visuomotor pathway for speech motor control. Here we used fMRI in healthy individuals to identify this new visuomotor circuit for speech production. Participants were asked to perceive and covertly rehearse nonsense syllable sequences presented auditorily, visually, or audiovisually. The motor act of rehearsal, which is prima facie the same whether or not it is cued with a visible talker, produced different patterns of sensorimotor activation when cued by visual or audiovisual speech (relative to auditory speech). In particular, a network of brain regions including the left posterior middle temporal gyrus and several frontoparietal sensorimotor areas activated more strongly during rehearsal cued by a visible talker versus rehearsal cued by auditory speech alone. Some of these brain regions responded exclusively to rehearsal cued by visual or audiovisual speech. This result has significant implications for models of speech motor control, for the treatment of speech output disorders, and for models of the role of speech gesture imitation in development.

Automated lesion detection on MRI scans using combined unsupervised and supervised methods.

BACKGROUND: Accurate and precise detection of brain lesions on MR images (MRI) is paramount for accurately relating lesion location to impaired behavior. In this paper, we present a novel method to automatically detect brain lesions from a T1-weighted 3D MRI. The proposed method combines the advantages of both unsupervised and supervised methods. METHODS: First, unsupervised methods perform a unified segmentation normalization to warp images from the native space into a standard space and to generate probability maps for different tissue types, e.g., gray matter, white matter and fluid. This allows us to construct an initial lesion probability map by comparing the normalized MRI to healthy control subjects. Then, we perform non-rigid and reversible atlas-based registration to refine the probability maps of gray matter, white matter, external CSF, ventricle, and lesions. These probability maps are combined with the normalized MRI to construct three types of features, with which we use supervised methods to train three support vector machine (SVM) classifiers for a combined classifier. Finally, the combined classifier is used to accomplish lesion detection. RESULTS: We tested this method using T1-weighted MRIs from 60 in-house stroke patients. Using leave-one-out cross validation, the proposed method can achieve an average Dice coefficient of 73.1% when compared to lesion maps hand-delineated by trained neurologists. Furthermore, we tested the proposed method on the T1-weighted MRIs in the MICCAI BRATS 2012 dataset. The proposed method can achieve an average Dice coefficient of 66.5% in comparison to the expert annotated tumor maps provided in MICCAI BRATS 2012 dataset. In addition, on these two test datasets, the proposed method shows competitive performance to three state-of-the-art methods, including Stamatakis et al., Seghier et al., and Sanjuan et al. CONCLUSIONS: In this paper, we introduced a novel automated procedure for lesion detection from T1-weighted MRIs by combining both an unsupervised and a supervised component. In the unsupervised component, we proposed a method to identify lesioned hemisphere to help normalize the patient MRI with lesions and initialize/refine a lesion probability map. In the supervised component, we extracted three different-order statistical features from both the tissue/lesion probability maps obtained from the unsupervised component and the original MRI intensity. Three support vector machine classifiers are then trained for the three features respectively and combined for final voxel-based lesion classification.

Stereotaxic Magnetic Resonance Imaging Brain Atlases for Infants from 3 to 12 Months.

BACKGROUND: Accurate labeling of brain structures within an individual or group is a key issue in neuroimaging. Methods for labeling infant brains have depended on the labels done on adult brains or average magnetic resonance imaging (MRI) templates based on adult brains. However, the features of adult brains differ in several ways from infant brains, so the creation of a labeled stereotaxic atlas based on infants would be helpful. The current work builds on the recent creation of age-appropriate average MRI templates during the first year (3, 4.5, 6, 7.5, 9, and 12 months) by creating anatomical label sets for each template. METHODS: We created stereotaxic atlases for the age-specific average MRI templates. Manual delineation of cortical and subcortical areas was done on the average templates based on infants during the first year. We also applied a procedure for automatic computation of macroanatomical atlases for individual infant participants using two manually segmented adult atlases (Hammers, LONI Probabilistic Brain Atlas-LPBA40). To evaluate our methods, we did manual delineation of several cortical areas on selected individuals from each age. Linear and nonlinear registration of the individual and average template was used to transform the average atlas into the individual participant's space, and the average-transformed atlas was compared to the individual manually delineated brain areas. We also applied these methods to an external data set - not used in the atlas creation - to test generalizability of the atlases. RESULTS: Age-appropriate manual atlases were the best fit to the individual manually delineated regions, with more error seen at greater age discrepancy. There was a close fit between the manually delineated and the automatically labeled regions for individual participants and for the age-appropriate template-based atlas transformed into participant space. There was close correspondence between automatic labeling of individual brain regions and those from the age-appropriate template. These relationships held even when tested on an external set of images. CONCLUSION: We have created age-appropriate labeled templates for use in the study of infant development at 6 ages (3, 4.5, 6, 7.5, 9, and 12 months). Comparison with manual methods was quite good. We developed three stereotaxic atlases (one manual, two automatic) for each infant age, which should allow more fine-grained analysis of brain structure for these populations than was previously possible with existing tools. The template-based atlases constructed in the current study are available online (http://jerlab.psych.sc.edu/NeurodevelopmentalMRIDatabase).

Age-specific MRI brain and head templates for healthy adults from 20 through 89 years of age.

This study created and tested a database of adult, age-specific MRI brain and head templates. The participants included healthy adults from 20 through 89 years of age. The templates were done in five-year, 10-year, and multi-year intervals from 20 through 89 years, and consist of average T1W for the head and brain, and segmenting priors for gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). It was found that age-appropriate templates provided less biased tissue classification estimates than age-inappropriate reference data and reference data based on young adult templates. This database is available for use by other investigators and clinicians for their MRI studies, as well as other types of neuroimaging and electrophysiological research.

The superior precentral gyrus of the insula does not appear to be functionally specialized for articulation.

Broca (Broca P. Bull Soc Anat Paris 36: 330-357, 1861) influentially argued that posterior left inferior frontal gyrus supports speech articulation. According to an alternative proposal (e.g., Dronkers NF. Nature 384: 159-161, 1996; Wise RJ, Greene J, Buchel C, Scott SK. Lancet 353: 1057-1061, 1999; Baldo JV, Wilkins DP, Ogar J, Willock S, Dronkers NF. Cortex 47: 800-807, 2011), a region in the anterior insula [specifically, the superior precentral gyrus of the insula (SPGI)] is the seat of articulatory abilities. Moreover, Dronkers and colleagues have argued that the SPGI is functionally specialized for (complex) speech articulation. Here, we evaluate this claim using individual-subject functional MRI (fMRI) analyses (e.g., Fedorenko E, Hsieh PJ, Nieto-Castanon A, Whitfield-Gabrieli S, Kanwisher N. J Neurophysiol 104: 1177-1194, 2010). We find that the SPGI responds weakly, if at all, during articulation (parts of Broca's area respond 3-4 times more strongly) and does not show a stronger response to higher articulatory demands. This holds regardless of whether the SPGI is defined functionally (by selecting the most articulation-responsive voxels in the vicinity of the SPGI in each subject individually) or anatomically (by using masks drawn on each individual subject's anatomy). Critically, nonspeech oral movements activate the SPGI more strongly than articulation, especially under the anatomical definition of the SPGI. In line with Hillis et al. (Hillis AE, Work M, Barker PB, Jacobs MA, Breese EL, Maurer K. Brain 127: 1479-1487, 2004; also Trupe L, Varma DD, Gomez Y, Race D, Leigh R, Hillis AE, Gottesman RF. Stroke 44: 740-744, 2013), we argue that previous links between the SPGI, and perhaps anterior insula more generally, and articulation may be due to its high base rate of ischemic damage (and activation in fMRI; Yarkoni T, Poldrack RA, Nichols TE, Van Essen DC, Wager TD. Nat Methods 8: 665-670, 2011), combined with its proximity to regions that more directly support speech articulation, such as the precentral gyrus or the posterior aspects of the inferior frontal gyrus (Richardson JD, Fillmore P, Rorden C, Lapointe LL, Fridriksson J. Brain Lang 123: 125-130, 2012), and thus susceptibility to joint damage.

Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas.

Despite being perhaps the most studied form of aphasia, the critical lesion location for Broca's aphasia has long been debated, and in chronic patients, cortical damage often extends far beyond Broca's area. In a group of 70 patients, we examined brain damage associated with Broca's aphasia using voxel-wise lesion-symptom mapping (VLSM). We found that damage to the posterior portion of Broca's area, the pars opercularis, is associated with Broca's aphasia. However, several individuals with other aphasic patterns had considerable damage to pars opercularis, suggesting that involvement of this region is not sufficient to cause Broca's aphasia. When examining only individuals with pars opercularis damage, we found that patients with Broca's aphasia had greater damage in the left superior temporal gyrus (STG; roughly Wernicke's area) than those with other aphasia types. Using discriminant function analysis and logistic regression, based on proportional damage to the pars opercularis and Wernicke's area, to predict whether individuals had Broca's or another types of aphasia, over 95% were classified correctly. Our findings suggest that persons with Broca's aphasia have damage to both Broca's and Wernicke's areas, a conclusion that is incongruent with classical neuropsychology, which has rarely considered the effects of damage to both areas.

Regional white matter damage predicts speech fluency in chronic post-stroke aphasia.

RECENTLY, TWO DIFFERENT WHITE MATTER REGIONS THAT SUPPORT SPEECH FLUENCY HAVE BEEN IDENTIFIED: the aslant tract and the anterior segment of the arcuate fasciculus (ASAF). The role of the ASAF was demonstrated in patients with post-stroke aphasia, while the role of the aslant tract shown in primary progressive aphasia. Regional white matter integrity appears to be crucial for speech production; however, the degree that each region exerts an independent influence on speech fluency is unclear. Furthermore, it is not yet defined if damage to both white matter regions influences speech in the context of the same neural mechanism (stroke-induced aphasia). This study assessed the relationship between speech fluency and quantitative integrity of the aslant region and the ASAF. It also explored the relationship between speech fluency and other white matter regions underlying classic cortical language areas such as the uncinate fasciculus and the inferior longitudinal fasciculus (ILF). Damage to these regions, except the ILF, was associated with speech fluency, suggesting synergistic association of these regions with speech fluency in post-stroke aphasia. These observations support the theory that speech fluency requires the complex, orchestrated activity between a network of pre-motor, secondary, and tertiary associative cortices, supported in turn by regional white matter integrity.

Mapping remote subcortical ramifications of injury after ischemic strokes.

BACKGROUND: The extent of brain damage in chronic stroke patients is traditionally defined as the necrotic tissue observed on magnetic resonance image (MRI). However, patients often exhibit symptoms suggesting that functional impairment may affect areas beyond the cortical necrotic lesion, for example, when cortical symptoms ensue after subcortical damage. This observation suggests that disconnection or diaschisis can lead to remote cortical dysfunction that can be functionally equivalent to direct cortical lesions. Objective. To directly measure subcortical disconnection after stroke. METHODS: We describe a principled approach utilizing the whole brain connectome reconstructed from diffusion MRI to evaluate the reduction of apparent white matter fiber density in the hemisphere affected by the stroke compared with the spared hemisphere. RESULTS: In eight chronic stroke patients, we observed subcortical disconnection extending beyond the location of tissue necrosis and affecting major white matter pathways underlying the necrotic area. CONCLUSIONS: We suggest that it is possible to detect and quantify previously unappreciated areas of subcortical and cortical disconnection. Specifically, this method can be used to evaluate the relationship between lesion location and symptoms, with emphasis on a connectivity-based approach.

Damage to the anterior arcuate fasciculus predicts non-fluent speech production in aphasia.

Non-fluent aphasia implies a relatively straightforward neurological condition characterized by limited speech output. However, it is an umbrella term for different underlying impairments affecting speech production. Several studies have sought the critical lesion location that gives rise to non-fluent aphasia. The results have been mixed but typically implicate anterior cortical regions such as Broca's area, the left anterior insula, and deep white matter regions. To provide a clearer picture of cortical damage in non-fluent aphasia, the current study examined brain damage that negatively influences speech fluency in patients with aphasia. It controlled for some basic speech and language comprehension factors in order to better isolate the contribution of different mechanisms to fluency, or its lack. Cortical damage was related to overall speech fluency, as estimated by clinical judgements using the Western Aphasia Battery speech fluency scale, diadochokinetic rate, rudimentary auditory language comprehension, and executive functioning (scores on a matrix reasoning test) in 64 patients with chronic left hemisphere stroke. A region of interest analysis that included brain regions typically implicated in speech and language processing revealed that non-fluency in aphasia is primarily predicted by damage to the anterior segment of the left arcuate fasciculus. An improved prediction model also included the left uncinate fasciculus, a white matter tract connecting the middle and anterior temporal lobe with frontal lobe regions, including the pars triangularis. Models that controlled for diadochokinetic rate, picture-word recognition, or executive functioning also revealed a strong relationship between anterior segment involvement and speech fluency. Whole brain analyses corroborated the findings from the region of interest analyses. An additional exploratory analysis revealed that involvement of the uncinate fasciculus adjudicated between Broca's and global aphasia, the two most common kinds of non-fluent aphasia. In summary, the current results suggest that the anterior segment of the left arcuate fasciculus, a white matter tract that lies deep to posterior portions of Broca's area and the sensory-motor cortex, is a robust predictor of impaired speech fluency in aphasic patients, even when motor speech, lexical processing, and executive functioning are included as co-factors. Simply put, damage to those regions results in non-fluent aphasic speech; when they are undamaged, fluent aphasias result.

Re-establishing Broca's initial findings.

The importance of the left inferior pre-frontal cortex (LIPC) for speech production was first popularized by Paul Broca, providing a cornerstone of behavioral neurology and laying the foundation for future research examining brain-behavior relationships. Although Broca's findings were rigorously challenged, comprehensive contradictory evidence was not published until 130years later. This evidence suggested that damage to left anterior insula was actually the best predictor of motor speech impairment. Using high-resolution structural magnetic resonance imaging (MRI) in patients with chronic stroke, we reveal that LIPC involvement more accurately predicts acquired motor speech impairment than insula damage. Perfusion-weighted MRI provides complementary evidence, highlighting how damage to left inferior pre-frontal gyrus often includes insula involvement, and vice versa. Our findings suggest that Broca's initial conclusions associating acquired motor speech impairment with LIPC damage remain valid nearly 150years after his initial report on this issue.

FM-selective networks in human auditory cortex revealed using fMRI and multivariate pattern classification.

Frequency modulation (FM) is an acoustic feature of nearly all complex sounds. Directional FM sweeps are especially pervasive in speech, music, animal vocalizations, and other natural sounds. Although the existence of FM-selective cells in the auditory cortex of animals has been documented, evidence in humans remains equivocal. Here we used multivariate pattern analysis to identify cortical selectivity for direction of a multitone FM sweep. This method distinguishes one pattern of neural activity from another within the same ROI, even when overall level of activity is similar, allowing for direct identification of FM-specialized networks. Standard contrast analysis showed that despite robust activity in auditory cortex, no clusters of activity were associated with up versus down sweeps. Multivariate pattern analysis classification, however, identified two brain regions as selective for FM direction, the right primary auditory cortex on the supratemporal plane and the left anterior region of the superior temporal gyrus. These findings are the first to directly demonstrate existence of FM direction selectivity in the human auditory cortex.

Allocentric neglect strongly associated with egocentric neglect.

Following brain injury, many patients experience egocentric spatial neglect, where they fail to respond to stimuli on the contralesional side of their body. On the other hand, allocentric, object-based neglect refers to the symptom of ignoring the contralesional side of objects, regardless of the objects' egocentric position. There is an established tradition for considering these two phenomena as both behaviorally and anatomically dissociable. However, several studies and some theoretical work have suggested that these rather reflect two aspects of a unitary underlying disorder. Furthermore, in a recent large study Yue et al. [Archives of Physical Medicine and Rehabilitation 93 (2012) 156] reported that acute allocentric neglect is only observed in cases where substantial egocentric neglect is also present. In a new sample of right hemisphere stroke patients, we attempted to control for potential confounds by using a novel continuous measure for allocentric neglect (in addition to a recently developed continuous measure for egocentric neglect). Our findings suggest a strong association between egocentric and allocentric neglect. Consistent with the work of Yue et al. (2012), we found allocentric behavioral deficits only in conjunction with egocentric deficits as well as a large corresponding overlap for the anatomical regions associated with egocentric and with allocentric neglect. We discuss how different anatomical and behavioral findings can be explained in a unified physiologically plausible framework, whereby allocentric and egocentric effects interact.

Left hemisphere plasticity and aphasia recovery.

A recent study by our group revealed a strong relationship between functional brain changes in the left hemisphere and anomia treatment outcome in chronic stroke patients (N=26) with aphasia (Fridriksson, 2010). The current research represents a continuation of this work in which we have refined our methods and added data from four more patients (for a total sample size of 30) to assess where in the left hemisphere treatment-related brain changes occur. Unlike Fridriksson (2010) which only focused on changes in correct naming as a marker of treatment outcome, the current study examined the relationship between changes in left hemisphere activity and changes in correct naming, semantic paraphasias, and phonemic paraphasias following treatment. We also expanded on the work by Fridriksson by examining whether neurophysiological measures taken at baseline (defined henceforth as the time-point before the start of anomia treatment) predict treatment outcome. Our analyses revealed that changes in activation in perilesional areas predicted treatment-related increases in correct naming in individuals with chronic aphasia. This relationship was most easily observed in the left frontal lobe. A decrease in the number of semantic and phonemic paraphasias was predicted by an activation change in the temporal lobe involving cortical areas that were shown to be active during picture naming in 14 normal subjects. In contrast, a far less certain relationship was found between baseline neurophysiological measures and anomia treatment outcome. Our findings suggest that improved naming associated with behavioral anomia treatment in aphasia is associated with modulation of the left frontal lobe whereas a reduction in naming errors is mediated by left posterior regions that classically are thought to be involved in language processing.