Electrophysiological signatures of phonological and semantic maintenance in sentence repetition.

Verbal short-term memory comprises resources for phonological rehearsal, which have been characterized anatomically, and for maintenance of semantic information, which are less understood. Sentence repetition tasks tap both processes interactively. To distinguish brain activity involved in phonological vs. semantic maintenance, we recorded magnetoencephalography during a sentence repetition task, incorporating three manipulations emphasizing one mechanism over the other. Participants heard sentences or word lists and attempted to repeat them verbatim after a 5-second delay. After MEG, participants completed a cued recall task testing how much they remembered of each sentence. Greater semantic engagement relative to phonological rehearsal was hypothesized for 1) sentences vs. word lists, 2) concrete vs. abstract sentences, and 3) well recalled vs. poorly recalled sentences. During auditory perception and the memory delay period, we found highly left-lateralized activation in the form of 8-30 Hz event-related desynchronization. Compared to abstract sentences, concrete sentences recruited posterior temporal cortex bilaterally, demonstrating a neural signature for the engagement of visual imagery in sentence maintenance. Maintenance of arbitrary word lists recruited right hemisphere dorsal regions, reflecting increased demands on phonological rehearsal. Sentences that were ultimately poorly recalled in the post-test also elicited extra right hemisphere activation when they were held in short-term memory, suggesting increased demands on phonological resources. Frontal midline theta oscillations also reflected phonological rather than semantic demand, being increased for word lists and poorly recalled sentences. These findings highlight distinct neural resources for phonological and semantic maintenance, with phonological maintenance associated with stronger oscillatory modulations.

Semantic and phonological contributions to short-term repetition and long-term cued sentence recall.

The function of verbal short-term memory is supported not only by the phonological loop, but also by semantic resources that may operate on both short and long time scales. Elucidation of the neural underpinnings of these mechanisms requires effective behavioral manipulations that can selectively engage them. We developed a novel cued sentence recall paradigm to assess the effects of two factors on sentence recall accuracy at short-term and long-term stages. Participants initially repeated auditory sentences immediately following a 14-s retention period. After this task was complete, long-term memory for each sentence was probed by a two-word recall cue. The sentences were either concrete (high imageability) or abstract (low imageability), and the initial 14-s retention period was filled with either an undemanding finger-tapping task or a more engaging articulatory suppression task (Exp. 1, counting backward by threes; Exp. 2, repeating a four-syllable nonword). Recall was always better for the concrete sentences. Articulatory suppression reduced accuracy in short-term recall, especially for abstract sentences, but the sentences initially recalled following articulatory suppression were retained better at the subsequent cued-recall test, suggesting that the engagement of semantic mechanisms for short-term retention promoted encoding of the sentence meaning into long-term memory. These results provide a basis for using sentence imageability and subsequent memory performance as probes of semantic engagement in short-term memory for sentences.

Localization of electrophysiological responses to semantic and syntactic anomalies in language comprehension with MEG.

Syntactically and semantically anomalous words encountered during sentence comprehension are known to elicit dissociable electrophysiological responses, which are thought to reflect distinct aspects of language processing. However, the sources of these responses have not been well characterized. We used beamforming analysis of magnetoencephalography (MEG) data to map generators of electrophysiological responses to linguistic anomalies. Anomalous words occurred in the context of a sentence acceptability judgement task conducted in both visual and auditory modalities. Time-frequency analysis revealed that both kinds of violations elicited event-related synchronization (ERS) in the delta-theta frequency range (1-5 Hz), and desynchronization (ERD) in the alpha-beta range (8-30 Hz). In addition, these responses were differentially modulated by violation type and presentation modality. 1-5 Hz responses were consistently localized within medial prefrontal cortex and did not vary significantly across violation types, but were stronger for visual presentation. In contrast, 8-30 Hz ERD occurred in different regions for different violation types. For semantic violations the distribution was predominantly in the bilateral occipital cortex and left temporal and inferior frontal regions, and these effects did not differ for visual and auditory presentation. In contrast, syntactic responses were strongly affected by presentation modality. Under visual presentation, syntactic violations elicited bilateral 8-30 Hz ERD extending into dorsal parietal and frontal regions, whereas effects were much weaker and mostly statistically insignificant in the auditory modality. These results suggest that delta-theta ERS reflects generalized increases in working memory demands related to linguistic anomaly detection, while alpha-beta ERD reflects specific activation of cortical regions involved in distinct aspects of linguistic processing, such as semantic vs. phonological short-term memory. Beamforming analysis of time-domain average signals (ERFs) revealed an N400m effect for semantic anomalies in both modalities, localized to left superior temporal and posterior frontal regions, and a later P600-like effect for syntactic anomalies in both modalities, widespread over bilateral frontal, posterior temporal, and parietal regions. These results indicate that time-domain averaged responses and induced oscillatory responses have distinct properties, including localization and modality dependence, and likely reflect dissociable and complementary aspects of neural activity related to language comprehension and additional task-related processes.

Changes to saccade behaviors in Parkinson's disease following dancing and observation of dancing.

BACKGROUND: The traditional view of Parkinson's disease (PD) as a motor disorder only treated by dopaminergic medications is now shifting to include non-pharmacologic interventions. We have noticed that patients with PD obtain an immediate, short-lasting benefit to mobility by the end of a dance class, suggesting some mechanism by which dancing reduces bradykinetic symptoms. We have also found that patients with PD are unimpaired at initiating highly automatic eye movements to visual stimuli (pro-saccades) but are impaired at generating willful eye movements away from visual stimuli (anti-saccades). We hypothesized that the mechanisms by which a dance class improves movement initiation may generalize to the brain networks impacted in PD (frontal lobe and basal ganglia, BG), and thus could be assessed objectively by measuring eye movements, which rely on the same neural circuitry. METHODS: Participants with PD performed pro- and anti-saccades before, and after, a dance class. "Before" and "after" saccade performance measurements were compared. These measurements were then contrasted with a control condition (observing a dance class in a video), and with older and younger adult populations, who rested for an hour between measurements. RESULTS: We found an improvement in anti-saccade performance following the observation of dance (but not following dancing), but we found a detriment in pro-saccade performance following dancing. CONCLUSION: We suggest that observation of dance induced plasticity changes in frontal-BG networks that are important for executive control. Dancing, in contrast, increased voluntary movement signals that benefited mobility, but interfered with the automaticity of efficient pro-saccade execution.

A case of apathy due to frontotemporal dementia responsive to memantine.

OBJECTIVE: To study the effect of memantine on apathy, a common symptom of behavioral variant frontotemporal dementia (bvFTD). DESIGN: The patient underwent an off-label trial of memantine with behavioral inventories and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans performed at baseline, 7 weeks and 6 months. SUBJECT: The patient was a 66-year-old male whose main manifestation of bvFTD was affective, behavioral and cognitive apathy. INTERVENTION: The patient began memantine at an oral dose of 5 mg per morning and titrated up by 5 mg per week to the maintenance dose of 10 mg PO bid. RESULTS: Informants reported reduction of the apathy. The insula and cerebellum, both involved in the salience network, showed improved metabolism. CONCLUSION: Further study to correlate the effects of memantine on apathy and the salience network in bvFTD are warranted.

Cholinergic pathways and cognition in patients with schizophrenia: a pilot study.

BACKGROUND: Cognitive deficits are core features in schizophrenia. Disruption in cholinergic neurotransmission has been associated with executive dysfunction in animals and humans. The objective of this study was to evaluate the impact of compromised cholinergic pathways on executive versus non-executive cognitive functions of patients with schizophrenia. METHODS: 62 patients with schizophrenia and 62 age- and sex-matched non-psychiatric control subjects ("controls") were assessed and compared using: clinical measures, cognitive measures of global cognition, executive function, and memory; and an MRI-based visual rating scale that assesses damage strategically localized within the cholinergic pathways. RESULTS: 11 of the 62 patients with schizophrenia (17.7%) and 6 of the 62 controls (9.7%) had compromised cholinergic pathways. These proportions were not statistically significant. Patients and controls with compromised cholinergic pathways were more impaired on measures related to executive function than patients or controls without compromised pathways. CONCLUSIONS: Patients with schizophrenia have worse executive function than controls. Compromised cholinergic pathways appear to worsen the executive dysfunction observed in schizophrenia. If these preliminary findings are replicated, they could lead to the identification of a subgroup of patients with schizophrenia who could specifically benefit from interventions enhancing cholinergic neurotransmission.

Apathy is not associated with basal ganglia atrophy in frontotemporal dementia.

OBJECTIVE: To determine whether basal ganglia atrophy, known to be associated with apathy in nondementia populations, was associated with presence of apathy in patients with frontotemporal dementia (FTD). METHODS: A cross-sectional case study was conducted at two tertiary dementia care clinics in Toronto, Ontario, Canada. Striatal and thalamic gray matter volumes and apathy measures were collected from 21 subjects with FTD, 6 of whom did not show apathy on the Neuropsychiatric Inventory. RESULTS: No significant differences in gray matter volumes were found between apathetic and nonapathetic groups for the striatum or the thalamus. CONCLUSIONS: Our findings imply that the etiology of apathy seen in patients with FTD differs from that of patients with apathy after acquired injuries to the basal ganglia. Further study is needed to determine whether posterior thalamic atrophy correlates with apathy in FTD or functional imaging techniques might successfully find a relationship between basal ganglia dysfunction and apathy.