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Speakers respond automatically and rapidly to compensate for brief perturbations of pitch in their auditory feedback. The specific adjustments in vocal output require integration of brain regions involved in speech-motor-control in order to detect the sensory-feedback error and implement the motor correction. Cortical regions involved in the pitch reflex phenomenon are highly vulnerable targets of network disruption in Alzheimer's disease (AD). We examined the pitch reflex in AD patients (n = 19) compared to an age-matched control group (n = 16). We measured the degree of behavioral compensation (peak compensation) and the extent of the adaptive response (pitch-response persistence). Healthy-controls reached a peak compensation of 18.7 ± 0.8 cents, and demonstrated a sustained compensation at 8.9 ± 0.69 cents. AD patients, in contrast, demonstrated a significantly elevated peak compensation (22.4 ± 1.2 cents, p < 0.05), and a reduced sustained response (pitch-response persistence, 4.5 ± 0.88 cents, p < 0.001). The degree of increased peak compensation predicted executive dysfunction, while the degree of impaired pitch-response persistence predicted memory dysfunction, in AD patients. The current study demonstrates pitch reflex as a sensitive behavioral index of impaired prefrontal modulation of sensorimotor integration, and compromised plasticity mechanisms of memory, in AD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Navigated transcranial magnetic stimulation (nTMS) is a non-invasive technique for pre-surgical motor and language mapping in patients with brain lesions. This study examines the safety and tolerability of nTMS in a large, multi-center cohort of neurosurgical patients., Methods: Functional mapping with monopulse and repetitive nTMS was performed in 733 patients. In this cohort, 57% of patients had left-sided tumors, 50% had frontal tumors, and 50% had seizures secondary to the lesion. Side effects and pain intensity related to the procedure were documented., Results: Patients undergoing monopulse stimulation underwent an average of 490 pulses while those undergoing repetitive stimulation received an average of 2268 pulses. During monopulse stimulation, 5.1% reported discomfort (VAS 1-3), and 0.4% reported pain (VAS>3). During repetitive stimulation, 23.4% reported discomfort and 69.5% reported pain. No seizures or other adverse events were observed., Conclusions: nTMS is safe and well-tolerated in neurosurgical patients. Clinicians should consider expanding nTMS to patients with frequent seizures, but more evaluation is necessary to evaluate this risk fully., Significance: nTMS is safe and well-tolerated, even in neurosurgical patients with persistent occasional seizure secondary to a lesion. It should be considered in any patient with a lesion in a presumed peri-eloquent or eloquent brain region., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Understanding neural network dysfunction in neurodegenerative disease is imperative to effectively develop network-modulating therapies. In Alzheimer's disease (AD), cognitive decline associates with deficits in resting-state functional connectivity of diffuse brain networks. The goal of the current study was to test whether specific cognitive impairments in AD spectrum correlate with reduced functional connectivity of distinct brain regions. We recorded resting-state functional connectivity of alpha-band activity in 27 patients with AD spectrum--22 patients with probable AD (5 logopenic variant primary progressive aphasia, 7 posterior cortical atrophy, and 10 early-onset amnestic/dysexecutive AD) and 5 patients with mild cognitive impairment due to AD. We used magnetoencephalographic imaging (MEGI) to perform an unbiased search for regions where patterns of functional connectivity correlated with disease severity and cognitive performance. Functional connectivity measured the strength of coherence between a given region and the rest of the brain. Decreased neural connectivity of multiple brain regions including the right posterior perisylvian region and left middle frontal cortex correlated with a higher degree of disease severity. Deficits in executive control and episodic memory correlated with reduced functional connectivity of the left frontal cortex, whereas visuospatial impairments correlated with reduced functional connectivity of the left inferior parietal cortex. Our findings indicate that reductions in region-specific alpha-band resting-state functional connectivity are strongly correlated with, and might contribute to, specific cognitive deficits in AD spectrum. In the future, MEGI functional connectivity could be an important biomarker to map and follow defective networks in the early stages of AD.

Background: Schizophrenia (SZ) is associated with functional decoupling between cortical regions, but we do not know whether and where this occurs in low-frequency electromagnetic oscillations. The goal of this study was to use magnetoencephalography (MEG) to identify brain regions that exhibit abnormal resting-state connectivity in the alpha frequency range in patients with schizophrenia and investigate associations between functional connectivity and clinical symptoms in stable outpatient participants., Methods: Thirty patients with SZ and 15 healthy comparison participants were scanned in resting-state MEG (eyes closed). Functional connectivity MEG source data were reconstructed globally in the alpha range, quantified by the mean imaginary coherence between a voxel and the rest of the brain., Results: In patients, decreased connectivity was observed in left prefrontal cortex (PFC) and right superior temporal cortex, whereas increased connectivity was observed in left extrastriate cortex and the right inferior PFC. Functional connectivity of left inferior parietal cortex was negatively related to positive symptoms. Low left PFC connectivity was associated with negative symptoms. Functional connectivity of midline PFC was negatively correlated with depressed symptoms. Functional connectivity of right PFC was associated with other (cognitive) symptoms., Conclusions: This study demonstrates direct functional disconnection in SZ between specific cortical fields within low-frequency resting-state oscillations. Impaired alpha coupling in frontal, parietal, and temporal regions is associated with clinical symptoms in these stable outpatients. Our findings indicate that this level of functional disconnection between cortical regions is an important treatment target in SZ., (2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear., Methods: In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from 13 patients and matched controls., Results: Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength., Conclusions: There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD., Significance: Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning-based sensorimotor interventions., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Successful linguistic processing requires efficient encoding of successively-occurring auditory input in a time-constrained manner, especially under noisy conditions. In this study we examined the early neural response dynamics to rapidly-presented successive syllables in schizophrenia participants and healthy comparison subjects, and investigated the effects of noise on these responses. We used magnetoencephalography (MEG) to reveal the time-course of stimulus-locked activity over bilateral auditory cortices during discrimination of syllable pairs that differed either in voice onset time (VOT) or place of articulation (POA), in the presence or absence of noise. We also examined the association of these early neural response patterns to higher-order cognitive functions. The M100 response, arising from auditory cortex and its immediate environs, showed less attenuation to the second syllable in patients with schizophrenia than healthy comparison subjects during VOT-based discrimination in noise. M100 response amplitudes were similar between groups for the first syllable during all three discrimination conditions, and for the second syllable during VOT-based discrimination in quiet and POA-based discrimination in noise. Across subjects, the lack of M100 attenuation to the second syllable during VOT-based discrimination in noise was associated with poorer task accuracy, lower education and IQ, and lower scores on measures of Verbal Learning and Memory and Global Cognition. Because the neural response to the first syllable was not significantly different between groups, nor was a schizophrenia-related difference obtained in all discrimination tasks, early linguistic processing dysfunction in schizophrenia does not appear to be due to general sensory input problems. Rather, data suggest that faulty temporal integration occurs during successive syllable processing when the signal-to-noise ratio is low. Further, the neural mechanism by which the second syllable is suppressed during noise-challenged VOT discrimination appears to be important for higher-order cognition and provides a promising target for neuroscience-guided cognitive training approaches to schizophrenia., (Published by Elsevier B.V.)

Unlabelled: An fMRI study examining lexical access and lexical generation in nine non-stuttering and seven stuttering speakers is presented. Lexical access was examined during a word description task that was presented auditorily while subjects "silently" thought of the target words. Participants alternated between four 30-s rest blocks and four 30-s "active" blocks. Activation patterns were assessed utilizing a standard subtraction paradigm, where the activation during the rest blocks was subtracted from the activation during the active blocks. High levels of variability characterized activation patterns within both speaker groups. Group comparisons using random effects statistical analyses did not identify significant differences between the groups when corrected for multiple comparisons. Analyses were subsequently conducted by comparing the trends in the group activation patterns between the speaker groups using fixed (corrected) and random effects (uncorrected) analyses. Non-stuttering control speakers activated primarily left hemisphere cortical speech and language areas while the stuttering speakers appeared to produce more bilateral activation. Discussion of these results focuses on the specific within- and between-hemispheric activation patterns and possible interpretations of these patterns., Educational Objectives: The reader will learn about: (1) issues related to interpreting brain activation findings in stuttering speakers; (2) the role and neurological substrates of lexical access during speech production in non-stuttering and stuttering speakers; (3) the basics of functional MRI; and (4) the brain activation areas involved during a silent lexical retrieval task in non-stuttering and stuttering speakers.