Peter J Fried

Beth Israel Deaconess Medical Center | BIDMC · Berenson-Allen Center for Noninvasive Brain Stimulation

To identify a spoken word (e.g., dog), people must categorize the speech steam onto distinct units (e.g., contrast dog/fog,) and extract their combinatorial structure (e.g., distinguish dog/god). However, the mechanisms that support these two core functions are not fully understood. Here, we explore this question using transcranial magnetic stimula...

Alzheimer’s disease (AD) is associated with neurophysiologic changes, including cortical hyperexcitability and reduced long‐term potentiation (LTP)‐like plasticity, that can be investigated using transcranial magnetic stimulation (TMS). AD is preceded by a preclinical phase of beta‐amyloid accumulation without clinical or cognitive symptoms. Our go...

Prior studies have suggested that oscillatory activity in cortical networks can modulate stimulus-evoked responses through time-varying fluctuations in neural excitation-inhibition dynamics. Studies combining transcranial magnetic stimulation (TMS) with electromyography (EMG) and electroencephalography (EEG) can provide direct measurements to exami...

Background: The sequelae of stoke, including the loss and recovery of function, are strongly linked to the mechanisms of neuroplasticity. Rehabilitation and non-invasive brain stimulation (NIBS) paradigms have shown promise in modulating corticomotor neuroplasticity to promote functional recovery in individuals post-stroke. However, an important l...

Background Many patients with treatment-resistant depression (TRD) respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This study aimed to investigate whether modulation of corticomotor excitability by rTMS predicts response to rTMS treatment for TRD in 10Hz and intermittent theta-burst stimulation (iTBS) protocols. Methods T...

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs), recorded using electroencephalography (EEG), reflect a combination of TMS-induced cortical activity and multi-sensory responses to TMS. The auditory evoked potential (AEP) is a high-amplitude sensory potential—evoked by the “click” sound produced by every TMS pulse—that can dominate...

Theta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation ( plasticity ) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. In this study we tested the reliability of the effects of two well define...

Background: Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs), recorded using electroencephalography (EEG), reflect a combination of TMS-induced cortical activity and multi-sensory responses to TMS. The auditory evoked potential (AEP) is a high-amplitude sensory potential—evoked by the “click” sound produced by every TMS pulse—that c...

Objective This study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability. Methods Authors of previously published studies were contacted and...

Background Over the past decade, the number of experimental and clinical studies using theta-burst-stimulation (TBS) protocols of transcranial magnetic stimulation (TMS) to modulate brain activity has risen substantially. The use of TBS is motivated by the assumption that these protocols can reliably and lastingly modulate cortical excitability des...

Prior studies have reported increased cortical excitability in people with Alzheimer's disease (AD), but findings have been inconsistent, and how excitability relates to dementia severity remains incompletely understood. We tested the association between transcranial magnetic stimulation (TMS) measure of motor cortical excitability and cognition in...

Objective Interindividual variability of single and paired-pulse TMS data has limited the clinical and experimental applicability of these methods. This study brought together over 60 TMS researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of fac...

Transcranial magnetic stimulation (TMS) reveals decreased efficacy of long-term potentiation-like (LTP-like) neuroplastic mechanisms in Alzheimer's disease (AD). However, it is not yet known whether LTP-like plasticity is also impaired in prodromal AD, or how abnormal TMS measures are related to established AD biomarkers. Here, we investigated the...

As the field of noninvasive brain stimulation (NIBS) expands there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three differ...

Alzheimer’s disease (AD) is associated with increased cortical excitability, including a risk of seizures and epileptiform discharges. Transcranial magnetic stimulation (TMS) can be used to index cortical excitability non‐invasively, and previous studies have revealed increased TMS excitability measures in AD. However, it is not yet known if TMS sh...

Background Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. Objective /Hypothesis: This study brought together over 60 TMS researchers to form the ‘Big TMS Data Collaboratio...

Objective To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for treatment of cognitive symptoms in patients with Alzheimer’s disease (AD). A secondary objective was to analyze associations between brain plasticity and cognitive effects of treatment.Methods In this randomized, sham-co...

Neuroimaging studies show that the brain articulatory motor system is activated during speech perception. These results, however, cannot determine whether the motor system is engaged in motor simulation (e.g., lip movement) or in non-motor computations. To gauge the causal role of the articulatory motor system, here we examine the effect of mechani...

Purpose – Spontaneous eye blink rate is the number of involuntary blinks performed during a certain period of time. Assessing blink rate in humans provides valuable physiological and behavioral data for studying neuropathology and emotional states. Cognitive states, including awareness on the part of the subject that his or her blinks are being cou...

Single bouts of aerobic exercise can modulate cortical excitability and executive cognitive function, but less is known about the effect of light intensity exercise, an intensity of exercise more achievable for certain clinical populations. Fourteen healthy adults (aged 22 to 30) completed the following study procedures twice (≥7 days apart) before...

Rhythmic neural activity has been proposed to play a fundamental role in cognition. Both healthy and pathological aging are characterized by frequency-specific changes in oscillatory activity. However, the cognitive relevance of these changes across the spectrum from normal to pathological aging remains unknown. We examined electroencephalography (...

To assess motor cortex neurophysiology, including the mechanisms of neuroplasticity, transcranial magnetic stimulation (TMS) is typically applied to the motor "hotspot"- the optimal site for inducing a twitch in a given target muscle. It is known that the effects of suprathreshold repetitive TMS (rTMS) spread along functional connections beyond the...

Objectives: In older adults, type-2 diabetes mellitus (T2DM) impacts cognition and increases dementia risk. Prior studies suggest that impaired neuroplasticity may contribute to the cognitive decline in T2DM, but the underlying mechanisms of altered neuroplasticity are unclear. We investigated the relationship of the concentration of glutamatergic...

Objectives: The utility of continuous theta-burst stimulation (cTBS) as index of cortical plasticity is limited by inadequate characterization of its test-retest reliability. Thus, we evaluated the reliability of cTBS aftereffects, and explored the roles of age, and brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) polymorphisms....

Purpose of review: Alzheimer's disease is a progressive neurodegenerative disease without effective pharmacological treatment. Noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), are increasingly being investigated for their potential to ameliora...

Transcranial magnetic stimulation (TMS) is a safe and noninvasive means of electrically stimulating the brain by electromagnetic induction. TMS is capable of probing intracortical circuits and modulating cortical activity in humans; as such it has been instrumental to studying the neurophysiology and functional neuroanatomy of the frontal lobes. Fo...

Comforts in modern society have generally been associated with longer survival rates, enabling individuals to reach advanced age as never before in history. With the increase in longevity, however, the incidence of neurodegenerative diseases, especially Alzheimer's disease, has also doubled. Nevertheless, most of the observed variance, in terms of...

The pulse waveform and current direction of transcranial magnetic stimulation (TMS) influence its interactions with the neural substrate; however, their role in the efficacy and reliability of single- and paired-pulse TMS measures is not fully understood. We investigated how pulse waveform and current direction affect the efficacy and test-retest r...

Background: Alzheimer's disease (AD) and type 2 diabetes (T2DM) are common causes of cognitive decline among older adults and share strong epidemiological links. Distinct patterns of cortical atrophy are observed in with AD and T2DM, but robust comparisons between structure-function relationships across these two disease states are lacking. Objec...

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conve...

Spatial working memory strategy Controls mTBI 30-minutes of aerobic exercise: q increased LTP-like plasticity in individuals with mTBI (B). q Increased ICF in healthy young adults, but not in individuals with mTBI (C). q Improved spatial working memory pre/post in individuals with mTBI but not in healthy adults (D,E). Timeline of the 2*2 quasi-rand...

Objective: We studied the correlation between motor evoked potentials (MEPs) and early TMS-evoked EEG potentials (TEPs) from single-pulse TMS before and after intermittent Theta Burst Stimulation (iTBS) to the left primary motor cortex (M1) in 17 healthy older participants. Methods: TMS was targeted to the hand region of M1 using a MRI-guided na...

Background: Transcranial magnetic stimulation (TMS) can be used to assess neurophysiology and the mechanisms of cortical brain plasticity in humans in vivo. As the use of these measures in specific populations (e.g., Alzheimer’s disease; AD) increases, it is critical to understand their reproducibility (i.e., test–retest reliability) in the populat...

Scientists and clinicians have traditionally targeted single brain regions with stimulation to modulate brain function and disease. However, brain regions do not operate in isolation, but interact with other regions through networks. As such, stimulation of one region may impact and be impacted by other regions in its network. Here we test whether...

Alzheimer’s disease (AD) is a looming public health crisis that currently lacks an effective treatment. Noninvasive Brain Stimulation (NBS), particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), offers a promising alternative approach to pharmacological interventions for an increasing number of neu...

Background: Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer's disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the...

Objective: Identify the optimal number of pulses necessary to achieve reliable measures of motor evoked potentials (MEPs) in transcranial magnetic stimulation (TMS) studies. Methods: Retrospective data was obtained from 54 healthy volunteers (30 men, mean age 61.7±13.1years) who as part of prior studies had completed three blocks of 30 consecuti...

The dorsolateral prefrontal cortex (DLPFC) is a common target for repetitive transcranial magnetic stimulation (rTMS) in major depression, but the conventional "5 cm rule" misses DLPFC in >1/3 cases. Another heuristic, BeamF3, locates the F3 EEG site from scalp measurements. MRI-guided neuronavigation is more onerous, but can target a specific DLPF...

Tactile stimuli produce afferent signals that activate specific regions of the cerebral cortex. Noninvasive transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. We therefore hypothesized that a single session of tDCS targeting the sensory cortices would alter the cortical response to tactile stimuli. This hypo...

The human dorsolateral prefrontal cortex (dlPFC) is crucial for monitoring and manipulating information in working memory, but whether such contributions are domain-specific remains unsettled. Neuroimaging studies have shown bilateral dlPFC activity associated with working memory independent of the stimulus domain, but the causality of this relatio...

Phosphenes are commonly evoked by transcranial magnetic stimulation (TMS) to study the functional organization, connectivity, and excitability of the human visual brain. For years, phosphenes have been documented only from stimulating early visual areas (V1-V3) and a handful of specialized visual regions (V4, V5/MT+) in occipital cortex. Recently,...

The stimulation of the occipital cortex induces transient visual percepts, known as phosphenes. The characterization and analysis of the features of these visual qualia can provide a window into the physiology and neuroanatomy of cerebral visual networks of humans. Phosphenes can be reliably elicited in humans by a variety of invasive and non-invas...

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical stimulation of the occipital cortex, but also by non-invasive Transcranial Magnetic Stimulation (TMS)(1) of the same cortical regions. The intensity at which a phosphene is induced (phosphene threshold...

Recent emerging biochemical data indicate that several important neuroregulatory genes and proteins may be involved in the etiology of schizophrenia and bipolar disorder. Additionally, the same genes appear to be targets of several psychotropic medications that are used to treat these disorders. Recent DNA microarray studies show that genes involve...