Clinical Manifestations.

Background: Anxiety is prevalent among cognitively unimpaired older adults and is associated with accelerated amyloid-β-related cognitive decline and incident cognitive impairment. Investigating these mechanisms is challenging due to low pathologic burden, high individual variability, and subsyndromal level of symptoms. Recently, brain networks involved in AD were successfully localized by mapping the brain connectivity of atrophy patterns associated with memory impairment and delusions.

Critically Assessing the Unanswered Questions of How, Where, and When to Induce Plasticity in the Posttraumatic Stress Disorder Network With Transcranial Magnetic Stimulation.

Extinction of traumatic memory, a primary treatment approach (termed exposure therapy) in posttraumatic stress disorder (PTSD), occurs through relearning and may be subserved at the molecular level by long-term potentiation of relevant circuits. In parallel, repetitive transcranial magnetic stimulation (TMS) is thought to work through long-term potentiation-like mechanisms and may provide a novel, safe, and effective treatment for PTSD. In a recent failed randomized controlled trial we emphasized the necessity of correctly identifying cortical targets, the directionality of TMS protocols, and the role of memory activation.

Mechanisms of Action of TMS in the Treatment of Depression.

Transcranial magnetic stimulation (TMS) is entering increasingly widespread use in treating depression. The most common stimulation target, in the dorsolateral prefrontal cortex (DLPFC), emerged from early neuroimaging studies in depression. Recently, more rigorous casual methods have revealed whole-brain target networks and anti-networks based on the effects of focal brain lesions and focal brain stimulation on depression symptoms.

Specific Association of Worry With Amyloid-β But Not Tau in Cognitively Unimpaired Older Adults.

Objective: Anxiety disorders and subsyndromal anxiety symptoms are highly prevalent in late life. Recent studies support that anxiety may be a neuropsychiatric symptom during preclinical Alzheimer's disease (AD) and that higher anxiety is associated with more rapid cognitive decline and progression to cognitive impairment. However, the associations of specific anxiety symptoms with AD pathologies and with co-occurring subjective and objective cognitive changes have not yet been established.

A New Angle on Transcranial Magnetic Stimulation Coil Orientation: A Targeted Narrative Review.

Transcranial magnetic stimulation (TMS) is used to treat several neuropsychiatric disorders including depression, where it is effective in approximately one half of patients for whom pharmacological approaches have failed. Treatment response is related to stimulation parameters such as the stimulation frequency, pattern, intensity, location, total number of pulses and sessions applied, and target brain network engagement. One critical but underexplored component of the stimulation procedure is the orientation or yaw angle of the commonly used figure-of-eight TMS coil, which is known to impact neuronal response to TMS.

A potential neuromodulation target for PTSD in Veterans derived from focal brain lesions.

Neuromodulation trials for PTSD have yielded mixed results, and the optimal neuroanatomical target remains unclear. We analyzed three datasets to study brain circuitry causally linked to PTSD in military Veterans. After penetrating traumatic brain injury (n=193), lesions that reduced probability of PTSD were preferentially connected to a circuit including the medial prefrontal cortex (mPFC), amygdala, and anterolateral temporal lobe (cross-validation p=0.

Older age associated with better antidepressant response to H1-coil transcranial magnetic stimulation in female patients.

Background: TMS is increasingly used to treat depression, but predictors of treatment outcomes remain unclear. We assessed the association between age and TMS response given inconsistent prior reports limited by small sample size, heterogeneity, outdated TMS parameters, lack of assessment of H1-coil TMS, and lack of an a priori hypothesis. We hypothesized that older age would be associated with better treatment response based on trends in recent large exploratory analyses.

Targeting Symptom-Specific Networks With Transcranial Magnetic Stimulation.

Increasing evidence suggests that the clinical effects of transcranial magnetic stimulation are target dependent. Within any given symptom, precise targeting of specific brain circuits may improve clinical outcomes. This principle can also be extended across symptoms-stimulation of different circuits may lead to different symptom-level outcomes.

Multiple sclerosis lesions that impair memory map to a connected memory circuit.

Background: Nearly 1 million Americans are living with multiple sclerosis (MS) and 30-50% will experience memory dysfunction. It remains unclear whether this memory dysfunction is due to overall white matter lesion burden or damage to specific neuroanatomical structures. Here we test if MS memory dysfunction is associated with white matter lesions to a specific brain circuit.

The future of brain circuit-targeted therapeutics.

The principle of targeting brain circuits has drawn increasing attention with the growth of brain stimulation treatments such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and focused ultrasound (FUS). Each of these techniques can effectively treat different neuropsychiatric disorders, but treating any given disorder depends on choosing the right treatment target. Here, we propose a three-phase framework for identifying and modulating these targets.

Precision functional MRI mapping reveals distinct connectivity patterns for depression associated with traumatic brain injury.

Depression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to conventional treatments. Brain connectivity differences between the dorsal attention network (DAN), default mode network (DMN), and subgenual cingulate have been implicated in TBI and MDD. To characterize these distinctions, we applied precision functional mapping of brain network connectivity to resting-state functional magnetic resonance imaging data from five published patient cohorts, four discovery cohorts ( = 93), and one replication cohort ( = 180).

Mapping Lesion-Related Epilepsy to a Human Brain Network.

Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions.

Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and networks.