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Music listening provides one of the most significant abstract rewards for humans because hearing music activates the dopaminergic mesolimbic system. Given the strong link between reward, dopamine, and memory, we aimed here to investigate the hypothesis that dopamine-dependent musical reward can drive memory improvements. Twenty-nine healthy participants of both sexes provided reward ratings of unfamiliar musical excerpts that had to be remembered following a consolidation period under three separate conditions: after the ingestion of a dopaminergic antagonist, a dopaminergic precursor, or a placebo. Linear mixed modeling of the intervention data showed that the effect of reward on memory-i.e., the greater the reward experienced while listening to the musical excerpts, the better the memory recollection performance-was modulated by both dopaminergic signaling and individual differences in reward processing. Greater pleasure was consistently associated with better memory outcomes in participants with high sensitivity to musical reward, but this effect was lost when dopaminergic signaling was disrupted in participants with average or low musical hedonia. Our work highlights the flexibility of the human dopaminergic system, which can enhance memory formation not only through explicit and/or primary reinforcers but also via abstract and aesthetic rewards such as music.

Distinguishing between regular and irregular heartbeats, conversing with speakers of different accents, and tuning a guitar-all rely on some form of auditory learning. What drives these experience-dependent changes? A growing body of evidence suggests an important role for non-sensory influences, including reward, task engagement, and social or linguistic context. This review is a collection of contributions that highlight how these non-sensory factors shape auditory plasticity and learning at the molecular, physiological, and behavioral level. We begin by presenting evidence that reward signals from the dopaminergic midbrain act on cortico-subcortical networks to shape sound-evoked responses of auditory cortical neurons, facilitate auditory category learning, and modulate the long-term storage of new words and their meanings. We then discuss the role of task engagement in auditory perceptual learning and suggest that plasticity in top-down cortical networks mediates learning-related improvements in auditory cortical and perceptual sensitivity. Finally, we present data that illustrates how social experience impacts sound-evoked activity in the auditory midbrain and forebrain and how the linguistic environment rapidly shapes speech perception. These findings, which are derived from both human and animal models, suggest that non-sensory influences are important regulators of auditory learning and plasticity and are often implemented by shared neural substrates. Application of these principles could improve clinical training strategies and inform the development of treatments that enhance auditory learning in individuals with communication disorders.

Background and purpose: This study was undertaken to determine and compare lesion patterns and structural dysconnectivity underlying poststroke aprosodia and amusia, using a data-driven multimodal neuroimaging approach. Methods: Thirty-nine patients with right or left hemisphere stroke were enrolled in a cohort study and tested for linguistic and affective prosody perception and musical pitch and rhythm perception at subacute and 3-month poststroke stages. Participants listened to words spoken with different prosodic stress that changed their meaning, and to words spoken with six different emotions, and chose which meaning or emotion was expressed. In the music tasks, participants judged pairs of short melodies as the same or different in terms of pitch or rhythm. Structural magnetic resonance imaging data were acquired at both stages, and machine learning-based lesion-symptom mapping and deterministic tractography were used to identify lesion patterns and damaged white matter pathways giving rise to aprosodia and amusia. Results: Both aprosodia and amusia were behaviorally strongly correlated and associated with similar lesion patterns in right frontoinsular and striatal areas. In multiple regression models, reduced fractional anisotropy and lower tract volume of the right inferior fronto-occipital fasciculus were the strongest predictors for both disorders, over time. Conclusions: These results highlight a common origin of aprosodia and amusia, both arising from damage and disconnection of the right ventral auditory stream integrating rhythmic-melodic acoustic information in prosody and music. Comorbidity of these disabilities may worsen the prognosis and affect rehabilitation success.

In recent years, car manufacturers have consistently upgraded the audio systems of their vehicles, with audio aficionados adding further modifications to them. The acoustics of the vehicle cabin and the sound effects of the audio systems have become one of the most important topics of the Research and Development Departments of manufacturers. For example, the selected vehicle in this experiment has implemented different spatial audio algorithms in its models to achieve a better listening experience. By capitalizing on impulse responses, binaural audio technology provides the opportunity and the flexibility to virtually generate the sound effects of a particular space without the requirement of physically being in that space. We used binaural technology and the vehicle to develop a standardized procedure for the evaluation of car audio systems. A perceptual listening test was integrated into this study to verify the procedure and to further evaluate this specific audio system.

Understanding how the brain translates a structured sequence of sounds, such as music, into a pleasant and rewarding experience is a fascinating question which may be crucial to better understand the processing of abstract rewards in humans. Previous neuroimaging findings point to a challenging role of the dopaminergic system in music-evoked pleasure. However, there is a lack of direct evidence showing that dopamine function is causally related to the pleasure we experience from music. We addressed this problem through a double blind within-subject pharmacological design in which we directly manipulated dopaminergic synaptic availability while healthy participants (n = 27) were engaged in music listening. We orally administrated to each participant a dopamine precursor (levodopa), a dopamine antagonist (risperidone), and a placebo (lactose) in three different sessions. We demonstrate that levodopa and risperidone led to opposite effects in measures of musical pleasure and motivation: while the dopamine precursor levodopa, compared with placebo, increased the hedonic experience and music-related motivational responses, risperidone led to a reduction of both. This study shows a causal role of dopamine in musical pleasure and indicates that dopaminergic transmission might play different or additive roles than the ones postulated in affective processing so far, particularly in abstract cognitive activities.

Statistical learning (SL) is the ability to extract regularities from the environment. In the domain of language, this ability is fundamental in the learning of words and structural rules. In lack of reliable online measures, statistical word and rule learning have been primarily investigated using offline (post-familiarization) tests, which gives limited insights into the dynamics of SL and its neural basis. Here, we capitalize on a novel task that tracks the online statistical learning of language rules combined with computational modelling to show that online SL responds to reinforcement learning principles rooted in striatal function. Specifically, we demonstrate - on two different cohorts - that a Temporal Difference model, which relies on prediction errors, accounts for participants’ online learning behavior. We then show that the trial-by-trial development of predictions through learning strongly correlates with activity in both ventral and dorsal striatum. Our results thus provide a detailed mechanistic account of language-related SL and an explanation for the oft-cited implication of the striatum in SL tasks. This work, therefore, bridges the longstanding gap between language learning and reinforcement learning phenomena.

Listening to vocal music has been recently shown to improve language recovery in stroke survivors. The neuroplasticity mechanisms supporting this effect are, however, still unknown. Using data from a three-arm single-blind randomized controlled trial including acute stroke patients (N=38) and a 3-month follow-up, we set out to compare the neuroplasticity effects of daily listening to self-selected vocal music, instrumental music, and audiobooks on both brain activity and structural connectivity of the language network. Using deterministic tractography we show that the 3-month intervention induced an enhancement of the microstructural properties of the left frontal aslant tract (FAT) for the vocal music group as compared to the audiobook group. Importantly, this increase in the strength of the structural connectivity of the left FAT correlated with improved language skills. Analyses of stimulus-specific activation changes showed that the vocal music group exhibited increased activations in the frontal termination points of the left FAT during vocal music listening as compared to the audiobook group from acute to 3-month post-stroke stage. The increased activity correlated with the structural neuroplasticity changes in the left FAT. These results suggest that the beneficial effects of vocal music listening on post-stroke language recovery are underpinned by structural neuroplasticity changes within the language network and extend our understanding of music-based interventions in stroke rehabilitation. Listening to vocal music has been recently shown to improve language recovery in stroke survivors. The neuroplasticity mechanisms supporting this effect are, however, still unknown. Using data from a three-arm, single-blind, randomized controlled trial including acute stroke patients (N = 38) and a 3 month follow-up, we set out to compare the neuroplasticity effects of daily listening to self-selected vocal music, instrumental music, and audiobooks on both brain activity and structural connectivity of the language network. Using deterministic tractography, we show that the 3 month intervention induced an enhancement of the microstructural properties of the left frontal aslant tract (FAT) for the vocal music group compared with the audiobook group. Importantly, this increase in the strength of the structural connectivity of the left FAT correlated with improved language skills. Analyses of stimulus-specific activation changes showed that the vocal music group exhibited increased activations in the frontal termination points of the left FAT during vocal music listening compared with the audiobook group from acute to 3 month poststroke stage. The increased activity correlated with the structural neuroplasticity changes in the left FAT. These results suggest that the beneficial effects of vocal music listening on poststroke language recovery are underpinned by structural neuroplasticity changes within the language network and extend our understanding of music-based interventions in stroke rehabilitation.

The COVID-19 pandemic has deeply affected mental health. We assessed which of many leisure activities had positive psychological effects, with particular attention to music, which has been reported anecdotally to be important. Questionnaire data from over a thousand individuals primarily from Italy, Spain, and the USA during spring 2020 show that people picked music most often as the best activity to cope with psychological distress. Hours of engagement in music and food-related activities during the pandemic were associated with decreased depression symptoms. The benefits of music were mediated by individual differences in sensitivity to reward, whereas the positive effects of food-related activities were related to emotion regulation. Our results demonstrate that music is an important means of improving well-being, and suggest that the underlying mechanism is related to reward, consistent with neuroscience findings. Our data have practical significance in pointing to effective strategies to cope with mental health issues.

The ability to extract regularities from the environment is arguably an adaptive characteristic of intelligent systems. In the context of speech, statistical learning is thought to be an important mechanism for language acquisition. By considering individual differences in speech auditory-motor synchronization, an independent component analysis of fMRI data revealed that the neural substrates of statistical word form learning are not fully shared across individuals. While a network of auditory and superior pre/motor regions is universally activated in the process of learning, a fronto-parietal network is instead additionally and selectively engaged by some individuals, boosting their performance. Furthermore, interfering with the use of this network via articulatory suppression (producing irrelevant speech during learning) normalizes performance across the entire sample. Our work provides novel insights on language-related statistical learning and reconciles previous contrasting findings, while highlighting the need to factor in fundamental individual differences for a precise characterization of cognitive phenomena.

Previously, we provided causal evidence for a dopamine-dependent effect of intrinsic reward on memory during self-regulated learning (Ripollés et al., 2016; Ripollés et al., 2018). Here, we further investigated the dopamine-dependent link between reward and memory by focusing on one of the most iconic abstract rewards in humans: music. Twenty-nine healthy participants listened to unfamiliar excerpts—which had to be remembered following a consolidation period—after the intake of a dopaminergic antagonist, a dopaminergic precursor, and a placebo across three separated sessions. The intervention modulated the pleasantness experienced during music-listening and memory recognition of the presented songs (i.e., lower with the antagonist, higher with the precursor) in individuals with higher sensitivity to musical reward. Our work highlights the flexibility of the human dopaminergic system, which is able to enhance memory formation not only through explicit and/or primary reinforcers but also via intrinsic, abstract, or aesthetic rewards of different natures.

Objective: Previous studies suggest that daily music listening can aid stroke recovery, but little is known about the stimulus-dependent and neural mechanisms driving this effect. Building on neuroimaging evidence that vocal music engages extensive and bilateral networks in the brain, we sought to determine if it would be more effective for enhancing cognitive and language recovery and neuroplasticity than instrumental music or speech after stroke. Methods: Using data pooled from two single-blind randomized controlled trials in stroke patients (N = 83), we compared the effects of daily listening to self-selected vocal music, instrumental music, and audiobooks during the first 3 poststroke months. Outcome measures comprised neuropsychological tests of verbal memory (primary outcome), language, and attention and a mood questionnaire performed at acute, 3-month, and 6-month stages and structural and functional MRI at acute and 6-month stages. Results: Listening to vocal music enhanced verbal memory recovery more than instrumental music or audiobooks and language recovery more than audiobooks, especially in aphasic patients. Voxel-based morphometry and resting-state and task-based fMRI results showed that vocal music listening selectively increased gray matter volume in left temporal areas and functional connectivity in the default mode network. Interpretation: Vocal music listening is an effective and easily applicable tool to support cognitive recovery after stroke as well as to enhance early language recovery in aphasia. The rehabilitative effects of vocal music are driven by both structural and functional plasticity changes in temporoparietal networks crucial for emotional processing, language, and memory.

Contains fulltext : 219449.pdf (Publisher’s version ) (Closed access) The human hippocampus is believed to be a crucial node in the neural network supporting autobiographical memory retrieval. Structural mesial temporal damage associated with temporal lobe epilepsy (TLE) provides an opportunity to systematically investigate and better understand the local and distal functional consequences of mesial temporal damage in the engagement of the autobiographical memory network. We examined 19 TLE patients (49.21 ± 11.55 years; 12 females) with unilateral mesial TLE (MTLE; 12 with anterior temporal lobe resection: 6 right MTLE, 6 left MTLE) or bilateral mesial TLE (7 BMTLE) and 18 matched healthy subjects. We used functional MRI (fMRI) with an adapted autobiographical memory paradigm and a specific neuropsychological test (Autobiographical Memory Interview, AMI). While engaged in the fMRI autobiographical memory paradigm, all groups activated a large fronto-temporo-parietal network. However, while this network was left lateralized for healthy participants and right MTLE patients, left MTLE and patients with BMTLE also showed strong activation in right temporal and frontal regions. Moreover, BMTLE and left MTLE patients also showed significant mild deficits in episodic autobiographical memory performance measured with the AMI test. The right temporal and extra-temporal fMRI activation, along with the impairment in autobiographical memory retrieval found in left MTLE and BMTLE patients suggest that alternate brain areas - other than the hippocampus - may also support this process, possibly due to neuroplastic effects. 15 p.

A crucial aspect when learning a language is discovering the rules that govern how words are combined in order to convey meanings. Because rules are characterized by sequential co-occurrences between elements (e.g., “These cupcakes are unbelievable”), tracking the statistical relationships between these elements is fundamental. However, purely bottom-up statistical learning alone cannot fully account for the ability to create abstract rule representations that can be generalized, a paramount requirement of linguistic rules. Here, we provide evidence that, after the statistical relations between words have been extracted, the engagement of goal-directed attention is key to enable rule generalization. Incidental learning performance during a rule-learning task on an artificial language revealed a progressive shift from statistical learning to goal-directed attention. In addition, and consistent with the recruitment of attention, functional MRI (fMRI) analyses of late learning stages showed left parietal activity within a broad bilateral dorsal frontoparietal network. Critically, repetitive transcranial magnetic stimulation (rTMS) on participants’ peak of activation within the left parietal cortex impaired their ability to generalize learned rules to a structurally analogous new language. No stimulation or rTMS on a nonrelevant brain region did not have the same interfering effect on generalization. Performance on an additional attentional task showed that this rTMS on the parietal site hindered participants’ ability to integrate “what” (stimulus identity) and “when” (stimulus timing) information about an expected target. The present findings suggest that learning rules from speech is a two-stage process: following statistical learning, goal-directed attention—involving left parietal regions—integrates “what” and “when” stimulus information to facilitate rapid rule generalization., European Research Council (ERC), Spanish Ministerio de Ciencia e Innovacio PRIME RdD-B, European Research Council (ERC) 727595, Juan de la Cierva Post-Doctorate Fellowship JCI-2012-12335, Ministerio de Economia y Competividad

Research in reversal learning has mainly focused on the functional role of dopamine and striatal structures in driving behavior on the basis of classic reinforcement learning mechanisms. However, recent evidence indicates that, beyond classic reinforcement learning adaptations, individuals may also learn the inherent task structure and anticipate the occurrence of reversals. A candidate structure to support such task representation is the hippocampus, which might create a flexible representation of the environment that can be adaptively applied to goal-directed behavior. To investigate the functional role of the hippocampus in the implementation of anticipatory strategies in reversal learning, we first studied, in 20 healthy individuals (11 women), whether the gray matter anatomy and volume of the hippocampus were related to anticipatory strategies in a reversal learning task. Second, we tested 20 refractory temporal lobe epileptic patients (11 women) with unilateral hippocampal sclerosis, who served as a hippocampal lesion model. Our results indicate that healthy participants were able to learn the task structure and use it to guide their behavior and optimize their performance. Participants' ability to adopt anticipatory strategies correlated with the gray matter volume of the hippocampus. In contrast, hippocampal patients were unable to grasp the higher-order structure of the task with the same success than controls. Present results indicate that the hippocampus is necessary to respond in an appropriately flexible manner to high-order environments, and disruptions in this structure can render behavior habitual and inflexible. SIGNIFICANCE STATEMENT Understanding the neural substrates involved in reversal learning has provoked a great deal of interest in the last years. Studies with nonhuman primates have shown that, through repetition, individuals are able to anticipate the occurrence of reversals and, thus, adjust their behavior accordingly. The present investigation is devoted to know the role of the hippocampus in such strategies. Importantly, our findings evidence that the hippocampus is necessary to anticipate the occurrence of reversals, and disruptions in this structure can render behavior habitual and inflexible.

We introduce a deceptively simple behavioral task that robustly identifies two qualitatively different groups within the general population. When presented with an isochronous train of random syllables, some listeners are compelled to align their own concurrent syllable production with the perceived rate, whereas others remain impervious to the external rhythm. Using both neurophysiological and structural imaging approaches, we show group differences with clear consequences for speech processing and language learning. When listening passively to speech, high synchronizers show increased brain-to-stimulus synchronization over frontal areas, and this localized pattern correlates with precise microstructural differences in the white matter pathways connecting frontal to auditory regions. Finally, the data expose a mechanism that underpins performance on an ecologically relevant word-learning task. We suggest that this task will help to better understand and characterize individual performance in speech processing and language learning. A simple behavioral task identifies two qualitatively different groups within the general population, according to their speech-to-speech synchronization abilities. Group pertinence predicts brain function and anatomy, as well as word-learning performance.

Contains fulltext : 207577.pdf (Publisher’s version ) (Open Access) Brain imaging methods have contributed to shed light on the mechanisms of recovery after early brain insult. The assumption that the unaffected right hemisphere can take over language functions after left perinatal stroke is still under debate. Here, we report how patterns of brain structural and functional reorganization were associated with language outcomes in a group of four-year-old children with left perinatal arterial ischemic stroke (PAIS). Specifically, we gathered specific fine-grained developmental measures of receptive and productive aspects of language as well as standardized measures of cognitive development. We also collected structural neuroimaging data as well as functional activations during a passive listening story-telling fMRI task and a resting state session (rs-fMRI). Children with a left perinatal stroke showed larger lateralization indices of both structural and functional connectivity of the dorsal language pathway towards the right hemisphere that, in turn, were associated with better language outcomes. Importantly, the pattern of structural asymmetry was significantly more right-lateralized in children with a left perinatal brain insult than in a group of matched healthy controls. These results strongly suggest that early lesions of the left dorsal pathway and the associated perisylvian regions can induce the interhemispheric transfer of language functions to right homolog regions. This study provides combined evidence of structural and functional brain reorganization of language networks after early stroke with strong implications for neurobiological models of language development. 18 p.

In the last decade, several studies have investigated the neuroplastic changes induced by long-term musical training. Here we investigated structural brain differences in expert pianists compared to non-musician controls, as well as the effect of the age of onset (AoO) of piano playing. Differences with non-musicians and the effect of sensitive periods in musicians have been studied previously, but importantly, this is the first time in which the age of onset of music-training was assessed in a group of musicians playing the same instrument, while controlling for the amount of practice. We recruited a homogeneous group of expert pianists who differed in their AoO but not in their lifetime or present amount of training, and compared them to an age-matched group of non-musicians. A subset of the pianists also completed a scale-playing task in order to control for performance skill level differences. Voxel-based morphometry analysis was used to examine gray-matter differences at the whole-brain level. Pianists showed greater gray matter (GM) volume in bilateral putamen (extending also to hippocampus and amygdala), right thalamus, bilateral lingual gyri and left superior temporal gyrus, but a GM volume shrinkage in the right supramarginal, right superior temporal and right postcentral gyri, when compared to non-musician controls. These results reveal a complex pattern of plastic effects due to sustained musical training: a network involved in reinforcement learning showed increased GM volume, while areas related to sensorimotor control, auditory processing and score-reading presented a reduction in the volume of GM. Behaviorally, early-onset pianists showed higher temporal precision in their piano performance than late-onset pianists, especially in the left hand. Furthermore, early onset of piano playing was associated with smaller GM volume in the right putamen and better piano performance (mainly in the left hand). Our results, therefore, reveal for the first time in a single large dataset of healthy pianists the link between onset of musical practice, behavioral performance, and putaminal gray matter structure. In summary, skill-related plastic adaptations may include decreases and increases in GM volume, dependent on an optimization of the system caused by an early start of musical training. We believe our findings enrich the plasticity discourse and shed light on the neural basis of expert skill acquisition.

Novel rehabilitation interventions have improved motor recovery by induction of neural plasticity in individuals with stroke. Of these, Music-supported therapy (MST) is based on music training designed to restore motor deficits. Music training requires multimodal processing, involving the integration and co-operation of visual, motor, auditory, affective and cognitive systems. The main objective of this study was to assess, in a group of 20 individuals suffering from chronic stroke, the motor, cognitive, emotional and neuroplastic effects of MST. Using functional magnetic resonance imaging (fMRI) we observed a clear restitution of both activity and connectivity among auditory-motor regions of the affected hemisphere. Importantly, no differences were observed in this functional network in a healthy control group, ruling out possible confounds such as repeated imaging testing. Moreover, this increase in activity and connectivity between auditory and motor regions was accompanied by a functional improvement of the paretic hand. The present results confirm MST as a viable intervention to improve motor function in chronic stroke individuals.

Listening to white noise may facilitate cognitive performance, including new word learning, for some individuals. This study investigated whether auditory white noise facilitates the learning of novel written words from context in healthy young adults. Sixty-nine participants were required to determine the meaning of novel words placed within sentence contexts during a silent reading task. Learning was performed either with or without white noise, and recognition of novel word meanings was tested immediately after learning and after a short delay. Immediate recognition accuracy for learned novel word meanings was higher in the noise group relative to the no noise group, however this effect was no longer evident at the delayed recognition test. These findings suggest that white noise has the capacity to facilitate meaning acquisition from context, however further research is needed to clarify its capacity to improve longer-term retention of meaning.

We recently provided evidence that an intrinsic reward-related signal—triggered by successful learning in absence of any external feedback—modulated the entrance of new information into long-term memory via the activation of the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop; Ripollés et al., 2016). Here, we used a double-blind, within-subject randomized pharmacological intervention to test whether this learning process is indeed dopamine-dependent. A group of healthy individuals completed three behavioral sessions of a language-learning task after the intake of different pharmacological treatments: a dopaminergic precursor, a dopamine receptor antagonist or a placebo. Results show that the pharmacological intervention modulated behavioral measures of both learning and pleasantness, inducing memory benefits after 24 hr only for those participants with a high sensitivity to reward. These results provide causal evidence for a dopamine-dependent mechanism instrumental in intrinsically regulated learning and further suggest that subject-specific reward sensitivity drastically alters learning success.

We recently provided evidence that an intrinsic reward-related signal—triggered by successful learning in absence of any external feedback—modulated the entrance of new information into long-term memory via the activation of the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop; Ripollés et al., 2016). Here, we used a double-blind, within-subject randomized pharmacological intervention to test whether this learning process is indeed dopamine-dependent. A group of healthy individuals completed three behavioural sessions of our learning task after the intake of different pharmacological treatments: a dopaminergic precursor, a dopamine receptor antagonist or a placebo. Results show that the pharmacological intervention bidirectionally modulated behavioral measures of both learning and pleasantness, inducing memory benefits after 24 hours only for those participants with a high sensitivity to reward. These results provide causal evidence for a dopamine-dependent mechanism instrumental in intrinsically regulated learning, and further suggest that subject-specific dopamine sensitivity drastically alters learning success.

Learning the associations between words and meanings is a fundamental human ability. Although the language network is cortically well defined, the role of the white matter pathways supporting novel word-to-meaning mappings remains unclear. Here, by using contextual and cross-situational word learning, we tested whether learning the meaning of a new word is related to the integrity of the language-related white matter pathways in 40 adults (18 women). The arcuate, uncinate, inferior-fronto-occipital and inferior-longitudinal fasciculi were virtually dissected using manual and automatic deterministic fiber tracking. Critically, the automatic method allowed assessing the white matter microstructure along the tract. Results demonstrate that the microstructural properties of the left inferior-longitudinal fasciculus predict contextual learning, whereas the left uncinate was associated with cross-situational learning. In addition, we identified regions of special importance within these pathways: the posterior middle temporal gyrus, thought to serve as a lexical interface and specifically related to contextual learning; the anterior temporal lobe, known to be an amodal hub for semantic processing and related to cross-situational learning; and the white matter near the hippocampus, a structure fundamental for the initial stages of new-word learning and, remarkably, related to both types of word learning. No significant associations were found for the inferior-fronto-occipital fasciculus or the arcuate. While previous results suggest that learning new phonological word forms is mediated by the arcuate fasciculus, these findings show that the temporal pathways are the crucial neural substrate supporting one of the most striking human abilities: our capacity to identify correct associations between words and meanings under referential indeterminacy.SIGNIFICANCE STATEMENTThe language-processing network is cortically (i.e., gray matter) well defined. However, the role of the white matter pathways that support novel word learning within this network remains unclear. In this work, we dissected language-related (arcuate, uncinate, inferior-fronto-occipital, and inferior-longitudinal) fasciculi using manual and automatic tracking. We found the left inferior-longitudinal fasciculus to be predictive of word-learning success in two word-to-meaning tasks: contextual and cross-situational learning paradigms. The left uncinate was predictive of cross-situational word learning. No significant correlations were found for the arcuate or the inferior-fronto-occipital fasciculus. While previous results showed that learning new phonological word forms is supported by the arcuate fasciculus, these findings demonstrate that learning new word-to-meaning associations is mainly dependent on temporal white matter pathways.

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. The most frequent pathologic finding in this condition is hippocampal sclerosis (HS). In addition, in a small proportion (14-23%) of refractory TLE patients, the presence of HS is bilateral. TLE involves grey matter (GM) and white matter (WM) abnormalities in a wide cortico-subcortical network. However, the impact of neuronal loss on specific WM fiber pathways and associated functional systems as well as seizure propagation pathways remains unclear. There is still much controversy regarding the role of the commissures (corpus callosum, hippocampal commissure and anterior commissure) in interhemispheric seizure propagation. This study aimed to investigate the integrity of WM interhemispheric connectivity in a singular sample of patients with TLE and bilateral HS using structural magnetic resonance imaging (MRI). We performed multimodal structural MRI [high resolution T1-weighted and diffusion tensor imaging (DTI)] analyses of seven patients with medically refractory TLE with bilateral HS, fourteen unilateral left TLE patients and fifteen matched healthy individuals. Whole-brain voxel-wise analysis techniques were used. These patients evidenced WM derangement [reduced fractional anisotropy (FA), increased mean diffusivity (MD) or reduced WM volume] in temporal and extratemporal tracks, but also in commissural pathways, compared to the unilateral left TLE patients and the control group. Presence of reduced FA or increased MD in the fornix, cingulum and uncinate fasciculus in addition to reduced WM volume in the fornix was also encountered. Neuropsychological assessment was performed without significant correlations with structural data. The current results support the idea that commissural pathways play a contributory role in interhemispheric TLE seizure propagation in bilateral HS and offer new perspectives about the long-term effects on interhemispheric connectivity associated with seizure propagation patterns in TLE patients.

Introduction No study has examined structural brain changes specifically associated with chemotherapy in a lung cancer population. The aim of this cross-sectional study was to assess differences in brain structure between small-cell lung cancer patients (C+) following chemotherapy, non–small-cell lung cancer patients (C−) before chemotherapy and healthy controls (HC). Methods Twenty-eight small-cell lung cancer patients underwent a neuropsychological assessment and a structural magnetic resonance imaging, including T1-weighted and diffusion tensor imaging to examine gray matter density and white matter (WM) integrity, respectively, 1 month following completion of platinum-based chemotherapy. This group was compared with 20 age and education-matched non–small-cell lung cancer patients before receiving chemotherapy and 20 HC. Results Both C+ and C− groups exhibited cognitive impairment compared with the HC group. The C+ group performed significantly worse than HC in verbal fluency and visuospatial subtests; C− performed significantly worse than both C+ and HC in verbal memory. Voxel-based morphometry analysis revealed lower gray matter density in the insula and parahippocampal gyrus bilaterally, and left anterior cingulate cortex in C+ compared with HC. Diffusion tensor imaging indices showed focal decreased WM integrity in left cingulum and bilateral inferior longitudinal fasciculus in the C+ group and more widespread decreased integrity in the C− group compared with the HC group. Conclusion This study demonstrates that lung cancer patients exhibit cognitive impairment before and after chemotherapy. Before the treatment, C− showed verbal memory deficits as well as a widespread WM damage. Following treatment, the C+ group performed exhibited lower visuospatial and verbal fluency abilities, together with structural gray matter and WM differences in bilateral regions integrating the paralimbic system.

The ability to learn to use new words is thought to depend on the integrity of the left dorsal temporo-frontal speech processing pathway. We tested this assumption in a chronic aphasic individual (AA) with an extensive left temporal lesion using a new-word learning paradigm. She exhibited severe phonological problems and Magnetic Resonance Imaging (MRI) suggested a complete disconnection of this left-sided white-matter pathway comprising the arcuate fasciculus (AF). Diffusion imaging tractography confirmed the disconnection of the direct segment and the posterior indirect segment of her left AF, essential components of the left dorsal speech processing pathway. Despite her left-hemispheric damage and moderate aphasia, AA learned to name and maintain the novel words in her active vocabulary on par with healthy controls up to 6 months after learning. This exceeds previous demonstrations of word learning ability in aphasia. Interestingly, AA's preserved word learning ability was modality-specific as it was observed exclusively for written words. Functional magnetic resonance imaging (fMRI) revealed that in contrast to normals, AA showed a significantly right-lateralized activation pattern in the temporal and parietal regions when engaged in reading. Moreover, learning of visually presented novel word–picture pairs also activated the right temporal lobe in AA. Both AA and the controls showed increased activation during learning of novel versus familiar word–picture pairs in the hippocampus, an area critical for associative learning. AA's structural and functional imaging results suggest that in a literate person, a right-hemispheric network can provide an effective alternative route for learning of novel active vocabulary. Importantly, AA's previously undetected word learning ability translated directly into therapy, as she could use written input also to successfully re-learn and maintain familiar words that she had lost due to her left hemisphere lesion.

The aim of this study was to use diffusion tensor imaging measures to determine the existence of white matter microstructural differences in the preclinical phases of Alzheimer's disease, assessing cognitively normal older individuals with positive amyloid β protein (Aβ42) levels (CN_Aβ42+) on the basis of normal cognition and cerebrospinal fluid Aβ42 levels below 500 pg/mL. Nineteen CN_Aβ42+ and 19 subjects with Aβ42 levels above 500 pg/mL (CN_Aβ42-) were included. We encountered increases in axial diffusivity (AxD) in CN_Aβ42+ relative to CN_Aβ42- in the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus bilaterally, and also in the left fornix, left uncinate fasciculus, and left inferior fronto-occipital fasciculus. However, no differences were found in other diffusion tensor imaging indexes. Cognitive reserve scores were positively associated with AxD exclusively in the CN_Aβ42+ group. The finding of AxD alteration together with preserved fractional anisotropy, mean diffusivity, and radial diffusivity indexes in the CN_Aβ42+ group may indicate that, subtle axonal changes may be happening in the preclinical phases of Alzheimer's disease, whereas white matter integrity is still widely preserved.

Brain damage causing acquired amusia disrupts the functional music processing system, creating a unique opportunity to investigate the critical neural architectures of musical processing in the brain. In this longitudinal fMRI study of stroke patients (N = 41) with a 6-month follow-up, we used natural vocal music (sung with lyrics) and instrumental music stimuli to uncover brain activation and functional network connectivity changes associated with acquired amusia and its recovery. In the acute stage, amusic patients exhibited decreased activation in right superior temporal areas compared to non-amusic patients during instrumental music listening. During the follow-up, the activation deficits expanded to comprise a wide-spread bilateral frontal, temporal, and parietal network. The amusics showed less activation deficits to vocal music, suggesting preserved processing of singing in the amusic brain. Compared to non-recovered amusics, recovered amusics showed increased activation to instrumental music in bilateral frontoparietal areas at 3 months and in right middle and inferior frontal areas at 6 months. Amusia recovery was also associated with increased functional connectivity in right and left frontoparietal attention networks to instrumental music. Overall, our findings reveal the dynamic nature of deficient activation and connectivity patterns in acquired amusia and highlight the role of dorsal networks in amusia recovery.

Background and purpose The main aim of this study was to identify which patients with glioblastoma multiforme (GBM) have a higher risk of presenting seizures during follow-up. Methods Patients with newly diagnosed GBM were reviewed (n = 306) and classified as patients with (Group 1) and without (Group 2) seizures at onset. Group 2 was split into patients with seizures during follow-up (Group 2A) and patients who never had seizures (Group 2B). The anatomical location of GBM was identified and compared by voxel-based lesion symptom mapping (discovery set). Seizure-susceptible brain regions obtained were assessed visually and automatically in external GBM validation series (n = 85). Results In patients with GBM who had no seizures at onset, an increased risk of presenting seizures during follow-up was identified in the superior frontal and inferior occipital lobe, as well as in inferoposterior regions of the temporal lobe. Conversely, those patients with GBM located in medial and inferoanterior temporal areas had a significantly lower risk of suffering from seizures during follow-up. Additionally, the seizure-susceptible brain region maps obtained classified patients in the validation set with high positive and negative predictive values. Conclusions Tumor location is a useful marker to identify patients with GBM who are at risk of suffering from seizures during follow-up. These results may help to support the use of antiepileptic prophylaxis in a selected GBM population and to improve stratification in antiepileptic clinical trials.