Illustration of brain connections with some pathways disrupted, symbolizing schizophrenia's impact on mental health.

Schizophrenia's Silent Struggle: Unveiling the Brain's Hidden Connections to Negative Symptoms

Rhea Morgan in Health & Wellness July 2025 • 4 min read.

"New research illuminates how disrupted communication between brain regions may explain the motivational and emotional challenges faced by individuals with schizophrenia."

Schizophrenia is a severe mental illness marked by two distinct categories of symptoms: positive and negative. While positive symptoms like hallucinations and delusions are often the focus, negative symptoms – including reduced motivation, social withdrawal, and blunted emotions – significantly impact daily life and long-term well-being. These ‘silent struggles’ are also notoriously resistant to treatment, making them a critical area of research.

One promising avenue for understanding negative symptoms lies in exploring the brain's intricate communication networks. Scientists have long suspected that disruptions in how different brain regions connect and interact play a key role in schizophrenia. In particular, the communication highway between the frontal cortex (responsible for higher-level functions) and the striatum (involved in motivation and reward) has garnered attention.

Now, a new study from researchers at the University of Maryland School of Medicine sheds light on this crucial connection. By examining the resting-state brain activity of individuals with schizophrenia, the study reveals specific disruptions in frontostriatal connectivity that are linked to the severity of negative symptoms. These findings not only deepen our understanding of the neurobiological underpinnings of schizophrenia but also pave the way for more targeted and effective treatments.

Decoding the Disrupted Pathways: How Brain Connectivity Impacts Negative Symptoms

Illustration of brain connections with some pathways disrupted, symbolizing schizophrenia's impact on mental health.

The research team, led by Dr. Dinesh K. Shukla, used resting-state functional connectivity (rsFC) data from 95 participants with schizophrenia and 139 healthy controls. This technique allowed them to examine how different brain regions communicate with each other when the brain is at rest, without the influence of specific tasks. Negative symptoms were carefully assessed using the Brief Negative Symptom Scale (BNSS).

The study focused on the connectivity between nine key regions in the frontal cortex and the striatum. Rather than predefine a specific region of interest, they used a data-driven, voxel-wise approach to reduce potential biases. This comprehensive analysis revealed that individuals with schizophrenia exhibited significantly reduced rsFC between the striatum and several frontal regions, including:

Right medial orbitofrontal cortex (mOFC): Critical for social evaluation, decision-making, and emotional representation.
Right lateral orbitofrontal cortex (lOFC).
Lateral prefrontal cortex (lPFC).
Rostral anterior cingulate cortex.

Importantly, the researchers found a significant correlation between the strength of connectivity between the right mOFC and the striatum, specifically the ventral putamen, and the severity of negative symptoms. The weaker this connection, the more pronounced the negative symptoms. This finding suggests that disrupted communication within this specific circuit may be a key driver of motivational and emotional deficits in schizophrenia.

A New Path Forward: Targeting Brain Circuits for Improved Outcomes

This study provides compelling evidence for the role of disrupted frontostriatal connectivity in the emergence of negative symptoms in schizophrenia. By pinpointing the specific involvement of the right mOFC and ventral striatum, the research offers a more precise target for future interventions.

While the study highlights a significant link, further research is needed to fully understand the direction of causality and the potential influence of medication. However, the findings open doors to exploring novel therapies aimed at strengthening these weakened brain connections. This could involve targeted brain stimulation techniques, cognitive training programs designed to enhance mOFC function, or pharmacological interventions that promote healthy dopamine signaling within the striatum.

Ultimately, by focusing on the underlying neural circuitry of negative symptoms, researchers and clinicians can work towards developing more effective and personalized treatments that address the full spectrum of challenges faced by individuals with schizophrenia, leading to improved quality of life and a greater sense of well-being.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1093/schbul/sby165, Alternate LINK

Title: Aberrant Frontostriatal Connectivity In Negative Symptoms Of Schizophrenia

Subject: Psychiatry and Mental health

Journal: Schizophrenia Bulletin

Publisher: Oxford University Press (OUP)

Authors: Dinesh K Shukla, Joshua John Chiappelli, Hemalatha Sampath, Peter Kochunov, Stephanie M Hare, Krista Wisner, Laura M Rowland, L Elliot Hong

Published: 2018-12-21

Everything You Need To Know

What is schizophrenia, and what are the key differences between positive and negative symptoms?

Schizophrenia is a severe mental illness classified by two main categories of symptoms, positive and negative. Positive symptoms include hallucinations and delusions. Negative symptoms, such as reduced motivation, social withdrawal, and blunted emotions, significantly affect daily life and long-term well-being. Negative symptoms have proven resistant to treatment, which is why research is targeting this area.

What specific brain connections were found to be disrupted in individuals with schizophrenia, and what is the significance of these disruptions?

The study highlights disruptions in the frontostriatal connectivity, particularly between the frontal cortex and the striatum. The communication highway between the frontal cortex, responsible for higher-level functions, and the striatum, involved in motivation and reward, is critical. Researchers found reduced resting-state functional connectivity (rsFC) between the striatum and several frontal regions, including the right medial orbitofrontal cortex (mOFC), right lateral orbitofrontal cortex (lOFC), lateral prefrontal cortex (lPFC), and rostral anterior cingulate cortex. The weaker the connection between the right mOFC and the striatum, specifically the ventral putamen, the more severe the negative symptoms.

What are negative symptoms of schizophrenia, and why are they a focus of research?

Negative symptoms include reduced motivation, social withdrawal, and blunted emotions. They are a critical area of research due to their impact on daily life and long-term well-being. These symptoms are notoriously resistant to treatment, making them a focus of ongoing research. The study revealed that the severity of negative symptoms correlates with disrupted communication within the specific circuit of the right mOFC and ventral striatum, potentially causing motivational and emotional deficits.

What is resting-state functional connectivity (rsFC), and how was it used in the study?

Resting-state functional connectivity (rsFC) is a technique used to examine how different brain regions communicate when the brain is at rest, without the influence of specific tasks. The study used rsFC to examine the communication between nine key regions in the frontal cortex and the striatum. The researchers used a data-driven, voxel-wise approach to reduce potential biases, revealing reduced rsFC between the striatum and several frontal regions in individuals with schizophrenia.

What is the role of the right medial orbitofrontal cortex (mOFC), and why is it significant in the context of this study?

The right medial orbitofrontal cortex (mOFC) is critical for social evaluation, decision-making, and emotional representation. Research found that the weaker the connection between the right mOFC and the striatum, specifically the ventral putamen, the more pronounced the negative symptoms of schizophrenia. This discovery offers a precise target for future interventions, potentially improving outcomes for individuals with schizophrenia by targeting specific brain circuits and functions.