Background

In electroencephalogram (EEG) studies of auditory steady-state responses (ASSRs), patients with schizophrenia show a deficit in power and/or phase-locking, particularly at the 40 Hz frequency where these responses resonate. In addition, studies of the transient gamma-band response (GBR) elicited by single tones have revealed deficits in gamma power and phase-locking in schizophrenia. We examined the degree to which the 40 Hz ASSR and the transient GBR to single tones are correlated and whether they assess overlapping or distinct gamma-band abnormalities in schizophrenia.

Methods

EEG was recorded during 40 Hz ASSR and auditory oddball paradigms from 28 patients with schizophrenia or schizoaffective disorder (SZ) and 25 age- and gender-matched healthy controls (HC). The ASSR was elicited by 500 ms click trains, and the transient GBR was elicited by the standard tones from the oddball paradigm. Gamma phase and magnitude values, calculated using Morlet wavelet transformations, were used to derive total power and phase-locking measures.

Results

Relative to HC, SZ patients had significant deficits in total gamma power and phase-locking for both ASSR- and GBR-based measures. Within both groups, the 40 Hz ASSR and GBR phase-locking measures were significantly correlated, with a similar trend evident for the total power measures. Moreover, co-varying for GBR substantially reduced 40 Hz ASSR power and phase-locking differences between the groups.

Conclusions

40 Hz ASSR and transient GBR measures provide very similar information about auditory gamma abnormalities in schizophrenia, despite the overall enhancement of 40 Hz ASSR total power and phase-locking values relative to the corresponding GBR values.

Background

Obsessive-compulsive disorder (OCD) is associated with an abnormally large error-related negativity (ERN), an electrophysiological measure of error monitoring in response to performance errors, but it is unclear if hoarding disorder (HD) also shows this abnormality. This study aimed to determine whether the neurophysiological mechanisms underlying error monitoring are similarly compromised in HD and OCD.

Method

We used a visual flanker task to assess ERN in response to performance errors in 14 individuals with HD, 27 with OCD, 10 with HD+OCD, and 45 healthy controls (HC). Age-corrected performance and ERN amplitudes were examined using analyses of variance and planned pairwise group comparisons.

Results

A main effect of hoarding on ERN (p = 0.031) was observed, indicating ERN amplitudes were attenuated in HD relative to non-HD subjects. A group × age interaction effect on ERN was also evident. In HD-positive subjects, ERN amplitude deficits were significantly greater in younger individuals (r = -0.479, p = 0.018), whereas there were no significant ERN changes with increasing age in OCD and HC participants.

Conclusions

The reduced ERN in HD relative to OCD and HC provides evidence that HD is neurobiologically distinct from OCD, and suggests that deficient error monitoring may be a core pathophysiological feature of HD. This effect was particularly prominent in younger HD participants, further suggesting that deficient error monitoring manifests most strongly early in the illness course and/or in individuals with a relatively early illness onset.

As we talk, we unconsciously adjust our speech to ensure it sounds the way we intend it to sound. However, because speech production involves complex motor planning and execution, no two utterances of the same sound will be exactly the same. Here, we show

Background: The default mode network (DMN) is a set of brain regions typically activated at rest and suppressed during extrinsic cognition. Schizophrenia has been associated with deficient DMN suppression, though the extent to which DMN dysfunction predate

Background: N-methyl-d-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia and its associated neurocognitive impairments. The high rate of cigarette smoking in schizophrenia raises questions about how nicotine

Background

Precise targeting of brain functional networks is believed critical for treatment efficacy of rTMS (repetitive pulse transcranial magnetic stimulation) in treatment resistant major depression.

Objective

To use imaging data from a "failed" clinical trial of rTMS in Veterans to test whether treatment response was associated with rTMS coil location in active but not sham stimulation, and compare fMRI functional connectivity between those stimulation locations.

Methods

An imaging substudy of 49 Veterans (mean age, 56 years; range, 27-78 years; 39 male) from a randomized, sham-controlled, double-blinded clinical trial of rTMS treatment, grouping participants by clinical response, followed by group comparisons of treatment locations identified by individualized fiducial markers on structural MRI and resting state fMRI derived networks.

Results

The average stimulation location for responders versus nonresponders differed in the active but not in the sham condition (P = .02). The average responder location derived from the active condition showed significant negative functional connectivity with the subgenual cingulate (P < .001) while the nonresponder location did not (P = .17), a finding replicated in independent cohorts of 84 depressed and 35 neurotypical participants. The responder and nonresponder stimulation locations evoked different seed based networks (FDR corrected clusters, all P < .03), revealing additional brain regions related to rTMS treatment outcome.

Conclusion

These results provide evidence from a randomized controlled trial that clinical response to rTMS is related to accuracy in targeting the region within DLPFC that is negatively correlated with subgenual cingulate. These results support the validity of a neuro-functionally informed rTMS therapy target in Veterans.

Background

The efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression may vary depending on the subregion stimulated within the dorsolateral prefrontal cortex (DLPFC). Clinical TMS typically uses scalp-based landmarks for DLPFC targeting, rather than individualized MRI guidance.

Objective

In rTMS patients, determine the brain systems targeted by multiple DLPFC stimulation rules by computing several surrogate measures: underlying brain targets labeled with connectivity-based atlases, subgenual cingulate anticorrelation strength, and functionally connected networks.

Methods

Forty-nine patients in a randomized controlled trial of rTMS therapy for treatment resistant major depression underwent structural and functional MRI. DLPFC rules were applied virtually using MR-image guidance. Underlying cortical regions were labeled, and connectivity with the subgenual cingulate and whole-brain computed.

Results

Scalp-targeting rules applied post hoc to these MRIs that adjusted for head size, including Beam F3, were comparably precise, successful in directly targeting classical DLPFC and frontal networks, and anticorrelated with the subgenual cingulate. In contrast, all rules involving fixed distances introduced variability in regions and networks targeted. The 5 cm rule targeted a transitional DLPFC region with a different connectivity profile from the adjusted rules. Seed-based connectivity analyses identified multiple regions, such as posterior cingulate and inferior parietal lobe, that warrant further study in order to understand their potential contribution to clinical response.

Conclusion

EEG-based rules consistently targeted DLPFC brain regions with resting-state fMRI features known to be associated with depression response. These results provide a bridge from lab to clinic by enabling clinicians to relate scalp-targeting rules to functionally connected brain systems.