Primary Auditory Areas Research Articles

Reinterpretando la Dislexia. Propuesta diferenciadora para una neurodidáctica inclusiva

Hasta la aparición de las técnicas de neuroimagen las investigaciones sobre la Dislexia se centraron en el déficit fonológico como uno de los factores causales. Estas técnicas han permitido avanzar en el conocimiento anatómico-funcional de las distintas áreas del cerebro revelando la amplitud y complejidad de la red de lectura del cerebro.
 Con el objetivo de una mayor compresión de este trastorno del neurodesarrollo, se analizan los últimos avances sobre las funciones neuroanatómicas de las distintas áreas del cerebro implicadas en la lectura y las investigaciones sobre la etiología neurológica de la Dislexia. Se concluye con la necesidad de considerar un trastorno del neurodesarrollo sensorial localizado en áreas primarias auditiva y visual que conlleva un deficiente procesamiento de la información viso-espacio-temporal. Se considera la Dislexia, y por tanto también el déficit fonológico, como una consecuencia de este trastorno. Esta diferenciación permite visibilizar otros síntomas menos atendidos por la investigación y la didáctica.
 Se extraen implicaciones cognitivas del déficit del procesamiento espacio-temporal en las etapas de educación infantil y primaria ante tareas típicas del aula a partir de las cuales diseñar una didáctica inclusiva, comprensiva con la naturaleza neurológica del trastorno, que no penalice a los alumnos que padecen este trastorno neurológico.

Predictive entrainment of natural speech through two fronto-motor top-down channels

ABSTRACT Natural communication between interlocutors is enabled by the ability to predict upcoming speech in a given context. Previously we showed that these predictions rely on a fronto-motor top-down control of low-frequency oscillations in auditory-temporal brain areas that track intelligible speech. However, a comprehensive spatio-temporal characterisation of this effect is still missing. Here, we applied transfer entropy to source-localised MEG data during continuous speech perception. First, at low frequencies (1–4 Hz, brain delta phase to speech delta phase), predictive effects start in left fronto-motor regions and progress to right temporal regions. Second, at higher frequencies (14–18 Hz, brain beta power to speech delta phase), predictive patterns show a transition from left inferior frontal gyrus via left precentral gyrus to left primary auditory areas. Our results suggest a progression of prediction processes from higher-order to early sensory areas in at least two different frequency channels.

Active Sound Localization Sharpens Spatial Tuning in Human Primary Auditory Cortex.

Spatial hearing sensitivity in humans is dynamic and task-dependent, but the mechanisms in human auditory cortex that enable dynamic sound location encoding remain unclear. Using functional magnetic resonance imaging (fMRI), we assessed how active behavior affects encoding of sound location (azimuth) in primary auditory cortical areas and planum temporale (PT). According to the hierarchical model of auditory processing and cortical functional specialization, PT is implicated in sound location ("where") processing. Yet, our results show that spatial tuning profiles in primary auditory cortical areas (left primary core and right caudo-medial belt) sharpened during a sound localization ("where") task compared with a sound identification ("what") task. In contrast, spatial tuning in PT was sharp but did not vary with task performance. We further applied a population pattern decoder to the measured fMRI activity patterns, which confirmed the task-dependent effects in the left core: sound location estimates from fMRI patterns measured during active sound localization were most accurate. In PT, decoding accuracy was not modulated by task performance. These results indicate that changes of population activity in human primary auditory areas reflect dynamic and task-dependent processing of sound location. As such, our findings suggest that the hierarchical model of auditory processing may need to be revised to include an interaction between primary and functionally specialized areas depending on behavioral requirements.SIGNIFICANCE STATEMENT According to a purely hierarchical view, cortical auditory processing consists of a series of analysis stages from sensory (acoustic) processing in primary auditory cortex to specialized processing in higher-order areas. Posterior-dorsal cortical auditory areas, planum temporale (PT) in humans, are considered to be functionally specialized for spatial processing. However, this model is based mostly on passive listening studies. Our results provide compelling evidence that active behavior (sound localization) sharpens spatial selectivity in primary auditory cortex, whereas spatial tuning in functionally specialized areas (PT) is narrow but task-invariant. These findings suggest that the hierarchical view of cortical functional specialization needs to be extended: our data indicate that active behavior involves feedback projections from higher-order regions to primary auditory cortex.

Basal Forebrain Nuclei Display Distinct Projecting Pathways and Functional Circuits to Sensory Primary and Prefrontal Cortices in the Rat.

Recent evidence supports that specific projections between different basal forebrain (BF) nuclei and their cortical targets are necessary to modulate cognitive functions in the cortex. We tested the hypothesis of the existence of specific neuronal populations in the BF linking with specific sensory, motor, and prefrontal cortices in rats. Neuronal tracing techniques were performed using retrograde tracers injected in the primary somatosensory (S1), auditory (A1), and visual (V1) cortical areas, in the medial prefrontal cortex (mPFC) as well as in BF nuclei. Results indicate that the vertical and horizontal diagonal band of Broca (VDB/HDB) nuclei target specific sensory cortical areas and maintains reciprocal projections with the prelimbic/infralimbic (PL/IL) area of the mPFC. The basal magnocellular nucleus (B nucleus) has more widespread targets in the sensory-motor cortex and does not project to the PL/IL cortex. Optogenetic stimulation was used to establish if BF neurons modulate whisker responses recorded in S1 and PL/IL cortices. We drove the expression of high levels of channelrhodopsin-2, tagged with a fluorescent protein (ChR2-eYFP) by injection of a virus in HDB or B nuclei. Blue-light pulses were delivered to the BF through a thin optic fiber to stimulate these neurons. Blue-light stimulation directed toward the HDB facilitated whisker responses in S1 cortex through activation of muscarinic receptors. The same optogenetic stimulation of HDB induced an inhibition of whisker responses in mPFC by activation of nicotinic receptors. Blue-light stimulation directed toward the B nucleus had lower effects than HDB stimulation. Our findings pointed the presence of specific neuronal networks between the BF and the cortex that may play different roles in the control of cortical activity.

Amusia and its electrophysiological correlates in neurofibromatosis type 1.

Auditory processing deficits are common in people with neurofibromatosis type 1 (NF1) and they often report difficulties in musical performance. We investigated whether NF1 could be associated with amusia as well as with some impairment of primary auditory cortex activity. Eighteen people with NF1 and 22 healthy volunteers, matched for age, sex and educational level, were evaluated with the Montreal Battery Evaluation of Amusia - short version. The integrity of cortical primary auditory processing areas was evaluated by evoked potential mismatch negativity. Amusia was correlated with NF1 (p = 0.001, odds ratio = 42.0, confidence interval 4.5-39.6). Patients with NF1 exhibited a greater prevalence of amusia than healthy controls (67% vs. 4.5%) and difficulties in both melodic and temporal music perception. Worse performance on the Montreal Battery Evaluation of Amusia was correlated with a greater mismatch negativity latency in NF1 group. Amusia is a common feature in NF1 and may result from impairment of activity in primary auditory processing areas.

Bilateral Pathways from the Basal Forebrain to Sensory Cortices May Contribute to Synchronous Sensory Processing.

Sensory processing in the cortex should integrate inputs arriving from receptive fields located on both sides of the body. This role could be played by the corpus callosum through precise projections between both hemispheres. However, different studies suggest that cholinergic projections from the basal forebrain (BF) could also contribute to the synchronization and integration of cortical activities. Using tracer injections and optogenetic techniques in transgenic mice, we investigated whether the BF cells project bilaterally to sensory cortical areas, and have provided anatomical evidence to support a modulatory role for the cholinergic projections in sensory integration. Application of the retrograde tracer Fluor-Gold or Fast Blue in both hemispheres of the primary somatosensory (S1), auditory or visual cortical areas showed labeled neurons in the ipsi- and contralateral areas of the diagonal band of Broca and substantia innominata. The nucleus basalis magnocellularis only showed ipsilateral projections to the cortex. Optogenetic stimulation of the horizontal limb of the diagonal band of Broca facilitated whisker responses in the S1 cortex of both hemispheres through activation of muscarinic cholinergic receptors and this effect was diminished by atropine injection. In conclusion, our findings have revealed that specific areas of the BF project bilaterally to sensory cortices and may contribute to the coordination of neuronal activity on both hemispheres.

Disrupted modular organization of primary sensory brain areas in schizophrenia.

Abnormal brain resting-state functional connectivity has been consistently observed in patients affected by schizophrenia (SCZ) using functional MRI and other neuroimaging techniques. Graph theoretical methods provide a framework to investigate these defective functional interactions and their effects on the organization of brain connectivity networks. A few studies have shown altered distribution of connectivity within and between functional modules in SCZ patients, an indication of imbalanced functional segregation ad integration. However, no major alterations of modular organization have been reported in patients, and unambiguous identification of the neural substrates affected remains elusive. Recently, it has been demonstrated that current modularity analysis methods suffer from a fundamental and severe resolution limit, as they fail to detect features that are smaller than a scale determined by the size of the entire connectivity network. This resolution limit is likely to have hampered the ability to resolve differences between patients and controls in previous studies. Here, we apply Surprise, a novel resolution limit-free approach, to study the modular organization of resting state functional connectivity networks in a large cohort of SCZ patients and in matched healthy controls. Leveraging these important methodological advances we find new evidence of substantial fragmentation and reorganization involving primary sensory, auditory and visual areas in SCZ patients. Conversely, frontal and prefrontal areas, typically associated with higher cognitive functions, appear to be largely unaffected, with changes selectively involving language and speech processing areas. Our findings support the hypothesis that cognitive dysfunction in SCZ may involve deficits occurring already at early stages of sensory processing.

Parasympathetic activation enhanced by slow respiration modulates early auditory sensory gating.

Sensory gating is a preattentional mechanism to filter irrelevant information from the environment. It is typically reflected as a suppression of the event-related P50 component for successive sounds in the auditory modality. Although stress-induced sympathetic activation has been reported to disrupt P50 suppression, little is known about the modulatory effect of parasympathetic activation on early auditory sensory gating. We determined the parasympathetic effect on the magnetic P50 (P50m) suppression by controlling the respiratory rhythm and recording data simultaneously with magnetoencephalography and electrocardiography, using three successive click sounds as stimulus and ten normal individuals as study participants. The respiratory rhythm was guided by visual cues and set at 0.3, 0.25, or 0.2 Hz for distinct auditory stimulus sequence blocks. Heart rate variability analysis showed that slow respiration leads to significantly large high-frequency power, which is known as the parasympathetic index, whereas low-frequency/high-frequency ratio, known as the sympathetic index, did not differ with the respiratory rhythm. Although P50m suppression was observed in the left and right primary auditory areas for every respiratory condition, the left P50m intensity for the first sound was significantly decreased in the case of slow respiration, thereby indicating disruption of the left P50m suppression. Since background alpha oscillatory power, reflecting the arousal level, was similar for every respiratory rhythm, it is concluded that parasympathetic activation enhanced by slow respiration modulates P50m gating by reducing the initial neural sensitivity for an auditory input. Not only sympathetic but also parasympathetic effects should be considered in the evaluation of P50/P50m biomarkers.

Delayed Mismatch Field Latencies in Autism Spectrum Disorder with Abnormal Auditory Sensitivity: A Magnetoencephalographic Study.

Although abnormal auditory sensitivity is the most common sensory impairment associated with autism spectrum disorder (ASD), the neurophysiological mechanisms remain unknown. In previous studies, we reported that this abnormal sensitivity in patients with ASD is associated with delayed and prolonged responses in the auditory cortex. In the present study, we investigated alterations in residual M100 and MMFs in children with ASD who experience abnormal auditory sensitivity. We used magnetoencephalography (MEG) to measure MMF elicited by an auditory oddball paradigm (standard tones: 300 Hz, deviant tones: 700 Hz) in 20 boys with ASD (11 with abnormal auditory sensitivity: mean age, 9.62 ± 1.82 years, 9 without: mean age, 9.07 ± 1.31 years) and 13 typically developing boys (mean age, 9.45 ± 1.51 years). We found that temporal and frontal residual M100/MMF latencies were significantly longer only in children with ASD who have abnormal auditory sensitivity. In addition, prolonged residual M100/MMF latencies were correlated with the severity of abnormal auditory sensitivity in temporal and frontal areas of both hemispheres. Therefore, our findings suggest that children with ASD and abnormal auditory sensitivity may have atypical neural networks in the primary auditory area, as well as in brain areas associated with attention switching and inhibitory control processing. This is the first report of an MEG study demonstrating altered MMFs to an auditory oddball paradigm in patients with ASD and abnormal auditory sensitivity. These findings contribute to knowledge of the mechanisms for abnormal auditory sensitivity in ASD, and may therefore facilitate development of novel clinical interventions.

Heidelberg Neuro-Music Therapy Enhances Task-Negative Activity in Tinnitus Patients.

Background: Suffering from tinnitus causes mental distress in most patients. Recent findings point toward a diminished activity of the brain's default-mode network (DMN) in subjects with mental disorders including depression or anxiety and also recently in subjects with tinnitus-related distress. We recently developed a therapeutic intervention, namely the Heidelberg Neuro-Music Therapy (HNMT), which shows an effective reduction of tinnitus-related distress following a 1-week short-term treatment. This approach offers the possibility to evaluate the neural changes associated with the improvements in tinnitus distress. We previously reported gray matter (GM) reorganization in DMN regions and in primary auditory areas following HNMT in cases of recent-onset tinnitus. Here we evaluate on the same patient group, using functional MRI (fMRI), the activity of the DMN following the improvements tinnitus-related distress related to the HNMT intervention.Methods: The DMN activity was estimated by the task-negative activation (TNA) during long inter-trial intervals in a word recognition task. The level of TNA was evaluated twice, before and after the 1-week study period, in 18 treated tinnitus patients (“treatment group,” TG), 21 passive tinnitus controls (PTC), and 22 active healthy controls (AC). During the study, the participants in TG and AC groups were treated with HNMT, whereas PTC patients did not receive any tinnitus-specific treatment. Therapy-related effects on DMN activity were assessed by comparing the pairs of fMRI records from the TG and PTC groups.Results: Treatment of the TG group with HNMT resulted in an augmented DMN activity in the PCC by 2.5% whereas no change was found in AC and PTC groups. This enhancement of PCC activity correlated with a reduction in tinnitus distress (Spearman Rho: −0.5; p < 0.005).Conclusion: Our findings show that an increased DMN activity, especially in the PCC, underlies the improvements in tinnitus-related distress triggered by HNMT and identify the DMN as an important network involved in therapeutic improvements.

The Hierarchical Cortical Organization of Human Speech Processing.

Speech comprehension requires that the brain extract semantic meaning from the spectral features represented at the cochlea. To investigate this process, we performed an fMRI experiment in which five men and two women passively listened to several hours of natural narrative speech. We then used voxelwise modeling to predict BOLD responses based on three different feature spaces that represent the spectral, articulatory, and semantic properties of speech. The amount of variance explained by each feature space was then assessed using a separate validation dataset. Because some responses might be explained equally well by more than one feature space, we used a variance partitioning analysis to determine the fraction of the variance that was uniquely explained by each feature space. Consistent with previous studies, we found that speech comprehension involves hierarchical representations starting in primary auditory areas and moving laterally on the temporal lobe: spectral features are found in the core of A1, mixtures of spectral and articulatory in STG, mixtures of articulatory and semantic in STS, and semantic in STS and beyond. Our data also show that both hemispheres are equally and actively involved in speech perception and interpretation. Further, responses as early in the auditory hierarchy as in STS are more correlated with semantic than spectral representations. These results illustrate the importance of using natural speech in neurolinguistic research. Our methodology also provides an efficient way to simultaneously test multiple specific hypotheses about the representations of speech without using block designs and segmented or synthetic speech.SIGNIFICANCE STATEMENT To investigate the processing steps performed by the human brain to transform natural speech sound into meaningful language, we used models based on a hierarchical set of speech features to predict BOLD responses of individual voxels recorded in an fMRI experiment while subjects listened to natural speech. Both cerebral hemispheres were actively involved in speech processing in large and equal amounts. Also, the transformation from spectral features to semantic elements occurs early in the cortical speech-processing stream. Our experimental and analytical approaches are important alternatives and complements to standard approaches that use segmented speech and block designs, which report more laterality in speech processing and associated semantic processing to higher levels of cortex than reported here.

Multi-Regional Adaptation in Human Auditory Association Cortex.

In auditory cortex, neural responses decrease with stimulus repetition, known as adaptation. Adaptation is thought to facilitate detection of novel sounds and improve perception in noisy environments. Although it is well established that adaptation occurs in primary auditory cortex, it is not known whether adaptation also occurs in higher auditory areas involved in processing complex sounds, such as speech. Resolving this issue is important for understanding the neural bases of adaptation and to avoid potential post-operative deficits after temporal lobe surgery for treatment of focal epilepsy. Intracranial electrocorticographic recordings were acquired simultaneously from electrodes implanted in primary and association auditory areas of the right (non-dominant) temporal lobe in a patient with complex partial seizures originating from the inferior parietal lobe. Simple and complex sounds were presented in a passive oddball paradigm. We measured changes in single-trial high-gamma power (70–150 Hz) and in regional and inter-regional network-level activity indexed by cross-frequency coupling. Repetitive tones elicited the greatest adaptation and corresponding increases in cross-frequency coupling in primary auditory cortex. Conversely, auditory association cortex showed stronger adaptation for complex sounds, including speech. This first report of multi-regional adaptation in human auditory cortex highlights the role of the non-dominant temporal lobe in suppressing neural responses to repetitive background sounds (noise). These results underscore the clinical utility of functional mapping to avoid potential post-operative deficits including increased listening difficulties in noisy, real-world environments.

Auditory bubbles: An application of relative weights to explore perceptual and neural representations of continuous speech

Several labs have recently developed relative weights procedures for estimating crucial time-frequency regions of the speech spectrogram. Due to the large degree of acoustic variability in natural speech, these spectrogram-based methods work best with rather limited sets of brief (e.g., syllable-length) utterances. We have developed a procedure that measures relative weights on the modulation power spectrum (MPS), which is obtained from the 2D Fourier transform of the speech spectrogram. Modulation patterns are relatively stable across utterances, which allows measurement of relative weights in the MPS domain using more ecologically-valid sets of continuous utterances (e.g., sentences). Our procedure works by applying randomly-shaped filters to the MPS over many trials and relating the filter patterns to an outcome measure using reverse correlation. Here, we estimate relative weights in the MPS domain for two outcome measures: keyword recognition/intelligibility (perceptual weights) and physiological activity measured with blood-oxygen-level-dependent fMRI (neural weights). Perceptual weights indicate that a circumscribed region of the MPS supports intelligible speech perception. Patterns of neural weights differ across regions of the auditory cortex—namely, primary auditory areas encode a broad range of the MPS while downstream regions converge toward a circumscribed representation that strongly resembles the pattern observed in perceptual weights.

Twist and turn into chronic disorders ofconsciousness: Potential role oftheauditory stapedial reflex.

Patients suffering from chronic disorders of consciousness (DOC), including minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS), typically show an awareness impairment paralleled by a significant reflex hyper-excitability, which depend on the cortical deafferentation following brain-damage-induced thalamocortical system deterioration. Nonetheless, recent studies have shown a residual preservation of cortico-subcortical pathways that may sustain residual fragments of awareness in some DOC patients. The aim of our study was to assess whether the cortical modulation of auditory stapedial reflex (ASR) could be a marker of a higher degree of brain network connectivity, which is a fundamental prerequisite for awareness generation and maintenance. We applied a repetitive transcranial magnetic stimulation (rTMS) protocol over the primary auditory area and measured the neuromodulation effects on ASR threshold (ASRt) in a DOC sample and a healthy control group (HC). We observed an ASRt reduction in all the HC and MCS individuals, in parallel to a better sound-induced motor responsiveness in MCS sample, while all the UWS patients, but two, did not show any significant ASRt modulation. We hypothesize that our conditioning protocol may have entrained and potentiated some spared cortico-subcortical networks that sustained the clinical and electrophysiological amelioration we found. Our data electrophysiologically demonstrate for the first time that primary the auditory area can influence ASR elicitation, and such finding may support the DOC differential diagnosis.

Anesthesia and brain sensory processing: impact on neuronal responses in a female songbird.

Whether anesthesia impacts brain sensory processing is a highly debated and important issue. There is a general agreement that anesthesia tends to diminish neuronal activity, but its potential impact on neuronal “tuning” is still an open question. Here we show, based on electrophysiological recordings in the primary auditory area of a female songbird, that anesthesia induces neuronal responses towards biologically irrelevant sounds and prevents the seasonal neuronal tuning towards functionally relevant species-specific song elements.

PET-CT observations of cortical activity in pre-lingually deaf adolescent and adult patients with cochlear implantation

Conclusions: The present study yielded useful information concerning pre-lingually deaf adolescents and adults who try or manage to understand languages. PET-CT can provide insights into brain plasticity and elucidate which mode of communication is the most effective for education of such patients.Objectives: To study the cortical activity in pre-lingually deaf adolescent and adult cochlear implants (CI) users who have been trained in auditory-verbal/oral communication since childhood.Methods: Using positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG), brain activities in six pre-lingually and two post-lingually deaf CI users (mean age at CI surgery = , 20.3 years; three males, five females) were compared with those of 10 normal age-matched controls (mean age = 27.1 years). Regional cerebral blood flow changes were measured during an acoustic presentation of a story.Results: In compliant CI users, the number of hypermetabolic auditory-related areas was greater in those who had a CI in their 20s than in those who did so in their adolescence. In poor and non-compliant users, hypermetabolism was not seen in the auditory association area, but in the primary auditory areas (BA41) and the Broca’s area (BA45). In post-lingually deaf CI users, no increase in the number of hypermetabolic areas was found in auditory-related regions.

Reorganization of neural systems mediating peripheral visual selective attention in the deaf: An optical imaging study

Theories of brain plasticity propose that, in the absence of input from the preferred sensory modality, some specialized brain areas may be recruited when processing information from other modalities, which may result in improved performance. The Useful Field of View task has previously been used to demonstrate that early deafness positively impacts peripheral visual attention. The current study sought to determine the neural changes associated with those deafness-related enhancements in visual performance. Based on previous findings, we hypothesized that recruitment of posterior portions of Brodmann area 22, a brain region most commonly associated with auditory processing, would be correlated with peripheral selective attention as measured using the Useful Field of View task. We report data from severe to profoundly deaf adults and normal-hearing controls who performed the Useful Field of View task while cortical activity was recorded using the event-related optical signal. Behavioral performance, obtained in a separate session, showed that deaf subjects had lower thresholds (i.e., better performance) on the Useful Field of View task. The event-related optical data indicated greater activity for the deaf adults than for the normal-hearing controls during the task in the posterior portion of Brodmann area 22 in the right hemisphere. Furthermore, the behavioral thresholds correlated significantly with this neural activity. This work provides further support for the hypothesis that cross-modal plasticity in deaf individuals appears in higher-order auditory cortices, whereas no similar evidence was obtained for primary auditory areas. It is also the only neuroimaging study to date that has linked deaf-related changes in the right temporal lobe to visual task performance outside of the imaging environment. The event-related optical signal is a valuable technique for studying cross-modal plasticity in deaf humans. The non-invasive and relatively quiet characteristics of this technique have great potential utility in research with clinical populations such as deaf children and adults who have received cochlear or auditory brainstem implants.

Study of tonotopic brain changes with functional MRI and FDG-PET in a patient with unilateral objective cochlear tinnitus

We studied possible brain changes with functional MRI (fMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a rare, high-intensity “objective tinnitus” (high-level SOAEs) in the left ear of 10 years duration, with no associated hearing loss. This is the first case of objective cochlear tinnitus to be investigated with functional neuroimaging.The objective cochlear tinnitus was measured by Spontaneous Otoacoustic Emissions (SOAE) equipment (frequency 9689 Hz, intensity 57 dB SPL) and is clearly audible to anyone standing near the patient. Functional modifications in primary auditory areas and other brain regions were evaluated using 3T and 7T fMRI and FDG-PET.In the fMRI evaluations, a saturation of the auditory cortex at the tinnitus frequency was observed, but the global cortical tonotopic organization remained intact when compared to the results of fMRI of healthy subjects. The FDG-PET showed no evidence of an increase or decrease of activity in the auditory cortices or in the limbic system as compared to normal subjects.In this patient with high-intensity objective cochlear tinnitus, fMRI and FDG-PET showed no significant brain reorganization in auditory areas and/or in the limbic system, as reported in the literature in patients with chronic subjective tinnitus.

Convergent and divergent intranetwork and internetwork connectivity patterns in patients with remitted late-life depression and amnestic mild cognitive impairment

IntroductionBoth remitted late-life depression (rLLD) and amnesiac mild cognitive impairment (aMCI) alter brain functions in specific regions of the brain. They are also disconnection syndromes that are associated with a high risk of developing Alzheimer's disease (AD). ObjectivesResting-state functional connectivity magnetic resonance imaging (rs-fcMRI) was performed to define the shared and distinct aberrant patterns in intranetwork and internetwork connectivity between rLLD and aMCI and to determine how knowledge of these differences might contribute to our essential understanding of the altered sequences involved in functional systems both inside and outside of resting-state networks. MethodsWe used rs-fcMRI to investigate in five functionally well-defined brain networks in two large cohorts of subjects at high risk for AD (55 rLLD and 87 aMCI) and 114 healthy controls (HC). ResultsA reduced degree of functional connectivity was observed in the bilateral inferior temporal cortex and supplemental motor area, and reduced correlations were observed within the sensory-motor network (SMN) and in the default mode network (DMN)–control network (CON) pair in the rLLD group than the HC group. The aMCI group showed only focal functional changes in regions of interest pairs, a trend toward increased correlations within the salience network and SMN, and a trend toward a reduced correlation in the DMN–CON pair. Furthermore, the rLLD group exhibited more severely altered functional connectivity than the aMCI group. Interestingly, these altered connectivities were associated with specific multi-domain cognitive and behavioral functions in both rLLD and aMCI. The degree of functional connectivity in the right primary auditory areas was negatively correlated with Hamilton Depression Scale scores in rLLD. Notably, altered connectivity between the right middle temporal cortex and the posterior cerebellum was negatively correlated with Mattis Dementia Rating Scale scores in both rLLD and aMCI. ConclusionsThese results demonstrate that rLLD and aMCI may share convergent and divergent aberrant intranetwork and internetwork connectivity patterns as a potential continuous spectrum of the same disease. They further suggest that dysfunctions in the right specific temporal-cerebellum neural circuit may contribute to the similarities observed in rLLD and aMCI conversion to AD.

Altered Topology in Information Processing of a Narrated Story in Older Adults with Mild Cognitive Impairment.

The ability to store, integrate, and manipulate information declines with aging. These changes occur earlier, faster, and to a greater degree as a result of neurodegeneration. One of the most common and early characteristics of cognitive decline is difficulty with comprehension of information. The neural mechanisms underlying this breakdown of information processing are poorly understood. Using functional MRI and natural stimuli (e.g., stories), we mapped the neural mechanisms by which the human brain accumulates and processes information with increasing duration and complexity in participants with amnestic mild cognitive impairment (aMCI) and healthy older adults. To explore the mechanisms of information processing, we measured the reliability of brain responses elicited by listening to different versions of a narrated story created by segmenting the story into words, sentences, and paragraphs and then scrambling the segments. Comparing healthy older adults and participants with aMCI revealed that in both groups, all types of stimuli similarly recruited primary auditory areas. However, prominent differences between groups were found at the level of processing long and complex stimuli. In healthy older adults, parietal and frontal regions demonstrated highly synchronized responses in both the paragraph and full story conditions, as has been previously reported in young adults. Participants with aMCI, however, exhibited a robust functional shift of long time scale processing to the pre- and post-central sulci. Our results suggest that participants with aMCI experienced a functional shift of higher order auditory information processing, possibly reflecting a functional response to concurrent or impending neuronal or synaptic loss. This observation might assist in understanding mechanisms of cognitive decline in aMCI.